Examination Committee of Criteria for 'Obesity Disease' in Japan, Japan Society for the Study of Obesity
New criteria for 'obesity disease' in Japan.
Circ J. 2002 Nov;66(11):987-92. doi: 10.1253/circj.66.987.
Abstract/Text
The present study was designed to establish adequate criteria for categorizing 'obesity disease' in Japan in relation to obesity-related complications. The subjects were 1,193 Japanese subjects (775 men, 418 women; age: 20-84 years old, body mass index (BMI): 14.9-56.4 kg/m(2)) including subjects undergoing a health examination and obese subjects visiting an obesity clinic. Visceral fat area (VFA) and subcutaneous fat area (SFA) were determined by computed tomography (CT) at the umbilical level. Anthropometric parameters, including BMI, waist circumference (W), waist/hip circumference (W/H), ratio and waist circumference/body height (W/BH) ratio, were measured. Hyperglycemia, dyslipidemia, and hypertension were evaluated as obesity-related complications. The relationship between each parameter and the prevalence of the complications was investigated. The number of complications increased in accordance with BMI and the average value was greater than 1.0 at a BMI of 25. The best combination of the sensitivity and specificity for detecting subjects with multiple risk factors was a BMI of 25. BMI showed a close positive correlation with SFA (r=0.82), even for BMI > or =25 (r=0.77), but had a weaker correlation with VFA (r=0.54). The obese subjects with a BMI > or =25 had no correlation between BMI and VFA because of the wide individual variation of VFA. The number of disorders was greater than 1.0 at 100 cm(2) of VFA and the best combination of the sensitivity and specificity for determining subjects with multiple risk factors was 100 cm(2) of VFA. Between the simple anthropometric values and measurement of VFA, it was proven that W had the closest relationship with VFA in both men (r=0.68) and women (r=0.65). The regression line obtained from simple correlation analyses indicated that the W corresponding to 100 cm(2) of VFA was 84.4 cm in men and 92.5 cm in women. These data suggest that obesity is adequately specified as a BMI > or =25 in Japan where the prevalence and degree of obesity remains mild. It is reasonable to establish the cut-off point of VFA at 100 cm(2) as indicative of the risk of obesity-related disorders and a waist circumference of 85 cm in men and 90 cm in women approximates to this visceral fat mass.
メタボリックシンドローム診断基準検討委員会：メタボリックシンドロームの定義と診断基準．日内会誌 2006;94:188-203.
Hiroyasu Iso, Renzhe Cui, Iseki Takamoto, Masahiko Kiyama, Isao Saito, Tomonori Okamura, Yoshihiro Miyamoto, Aya Higashiyama, Yutaka Kiyohara, Toshiharu Ninomiya, Michiko Yamada, Hideaki Nakagawa, Masaru Sakurai, Michio Shimabukuro, Moritake Higa, Kazuaki Shimamoto, Shigeyuki Saito, Makoto Daimon, Takamasa Kayama, Mitsuhiko Noda, Sadayoshi Ito, Koutaro Yokote, Chikako Ito, Kazuwa Nakao, Toshimasa Yamauchi, Takashi Kadowaki
Risk Classification for Metabolic Syndrome and the Incidence of Cardiovascular Disease in Japan With Low Prevalence of Obesity: A Pooled Analysis of 10 Prospective Cohort Studies.
J Am Heart Assoc. 2021 Dec 7;10(23):e020760. doi: 10.1161/JAHA.121.020760. Epub 2021 Nov 19.
Abstract/Text
Background It is uncertain whether risk classification under the nationwide program on screening and lifestyle modification for metabolic syndrome captures well high-risk individuals who could benefit from lifestyle interventions. We examined the validity of risk classification by linking the incidence of cardiovascular disease (CVD). Methods and Results Individual-level data of 29 288 Japanese individuals aged 40 to 74 years without a history of CVD from 10 prospective cohort studies were used. Metabolic syndrome was defined as the presence of high abdominal obesity and/or overweight plus risk factors such as high blood pressure, high triglyceride or low high-density lipoprotein cholesterol levels, and high blood glucose levels. The risk categories for lifestyle intervention were information supply only, motivation-support intervention, and intensive support intervention. Sex- and age-specific hazard ratios and population attributable fractions of CVD, which were also further adjusted to consider non-high density lipoprotein cholesterol levels, were estimated with reference to nonobese/overweight individuals, using Cox proportional hazard regression. Since the reference category included those with risk factors, we set a supernormal group (nonobese/overweight with no risk factor) as another reference. We documented 1023 incident CVD cases (565 men and 458 women). The adjusted CVD risk was 60% to 70% higher in men and women aged 40 to 64 years receiving an intensive support intervention, and 30% higher in women aged 65 to 74 years receiving a motivation-support intervention, compared with nonobese/overweight individuals. The population attributable fractions in men and women aged 40 to 64 years receiving an intensive support intervention were 17.7% and 6.6%, respectively, while that in women aged 65 to 74 years receiving a motivation-support intervention was 9.4%. Compared with the supernormal group, nonobese/overweight individuals with risk factors had similar hazard ratios and population attributable fractions as individuals with metabolic syndrome. Conclusions Similar CVD excess and attributable risks among individuals with metabolic syndrome components in the absence and presence of obesity/overweight imply the need for lifestyle modification in both high-risk groups.
Aki Hiuge-Shimizu, Ken Kishida, Tohru Funahashi, Masaaki Okutsu, Ryosuke Kametani, Hiroshi Kobayashi, Yoichi Nozaki, Akihiro Nomura, Hiroyoshi Yokoi, Tohru Yoshizumi, Tetsuya Ohira, Tadashi Nakamura, Yuji Matsuzawa, Satoru Sumitsuji, Iichiro Shimomura
Coexistence of visceral fat and multiple risk factor accumulations is strongly associated with coronary artery disease in Japanese (the VACATION-J study).
J Atheroscler Thromb. 2012;19(7):657-63. doi: 10.5551/jat.13037. Epub 2012 May 4.
Abstract/Text
AIM: Multiple risk factor syndrome is a target for the prevention of coronary artery disease (CAD). A cluster of multiple risk factors, such as hypertension, glucose intolerance, and/or dyslipidemia, is encountered in Japanese without and with excess visceral fat. The present study investigated the relationship between multiple risk factor accumulation and CAD in Japanese without and with visceral fat accumulation.
METHODS: The study subjects comprised 257 Japanese with suspected CAD (males/females= 153/ 104), who underwent 64-row multislice computed tomography (CT) coronary angiography and visceral fat area (VFA) measurement by CT. Based on the Japanese criteria for visceral fat accumulation, they were divided into those with VFA <100 and ≥10 cm(2).
RESULTS: In subjects with VFA <100 cm(2), the age- and sex-adjusted odds ratios (ORs) for 2 and 3 risk factors were 5.33 (95% confidence intervals; 1.04-27.38, p=0.0449) and 4.07 (0.72-23.15, p=0.1138), respectively, compared with VFA <100 cm(2) and 0 risk factor set at 1.0 (p=0.0569 for trend). In contrast, the respective ORs for subjects with VFA ≥100 cm(2) were much higher [6.46 (1.25-33.44, p=0.0261) and 20.42 (3.60-115.73, p=0.0007)] (p<0.0001 for trend). The multivariate adjusted model demonstrated a significant relative excess CAD risk of 1.08 (p=0.0484) and 5.01 (p<0.0001) for the interactions of 2 risk factors and VFA ≥100 cm(2), and 3 risk factors and VFA ≥100 cm(2), whereas multiple risk factor accumulation was not related with the increase of CAD risk in subjects with VFA <100 cm(2).
CONCLUSIONS: Coexistence of visceral fat and risk factor accumulations is strongly associated with CAD in Japanese.
T Nagaya, H Yoshida, H Takahashi, M Kawai
Increases in body mass index, even within non-obese levels, raise the risk for Type 2 diabetes mellitus: a follow-up study in a Japanese population.
Diabet Med. 2005 Aug;22(8):1107-11. doi: 10.1111/j.1464-5491.2005.01602.x.
Abstract/Text
AIMS: Obesity, the strongest risk factor for Type 2 diabetes mellitus, is less prevalent in Japanese than in other populations. We investigated the effects of body mass index (BMI, kg/m(2)) on the incidence of diabetes mellitus in a Japanese population.
METHODS: A follow-up study in 16 829 men and 8370 women who were apparently healthy at baseline (age 30-59 years, BMI 14.9-43.2 kg/m(2)). Incident diabetes mellitus was identified by 'fasting serum glucose > or = 7.00 mmol/l (126 mg/dl)' and/or 'under medical treatment for diabetes mellitus'. Hazard ratio, as an index for risk ratio, for incident diabetes mellitus according to BMI was estimated using Cox's proportional hazard models. Baseline age, smoking, drinking, exercise and education were computed as confounders.
RESULTS: During mean follow-up periods of 7.4 years for men and 7.1 years for women, 869 men and 224 women had incident diabetes mellitus. Although the subjects were averagely non-obese [mean (sd) BMI 23.1 (2.6) kg/m(2) for men, 22.3 (2.7) kg/m(2) for women], hazard ratio for incident diabetes mellitus increased in parallel with increases in BMI. Multivariate-adjusted hazard ratios (95% confidence intervals) for increases in BMI of 1 kg/m(2) were 1.26 (1.24, 1.29) for men and 1.24 (1.20, 1.29) for women.
CONCLUSION: BMI, even within the non-obese level, is a dose-dependent risk factor for diabetes mellitus in middle-aged Japanese. Increases in BMI of 1 kg/m(2) (= body-weight gain of 2.4-2.9 kg) may raise the risk by about 25%.
Akiko Nanri, Tetsuya Mizoue, Yoshihiko Takahashi, Yumi Matsushita, Mitsuhiko Noda, Manami Inoue, Shoichiro Tsugane, Japan Public Health Center-based Prospective Study Group
Association of weight change in different periods of adulthood with risk of type 2 diabetes in Japanese men and women: the Japan Public Health Center-Based Prospective Study.
J Epidemiol Community Health. 2011 Dec;65(12):1104-10. doi: 10.1136/jech.2009.097964. Epub 2010 Jul 13.
Abstract/Text
BACKGROUND: Few studies have examined the impact of weight change in different periods of lifetime on type 2 diabetes risk, and the association of weight loss with type 2 diabetes is unclear. We prospectively investigated the association of weight change since age 20 y and that during middle-to-late adulthood with the incidence of type 2 diabetes.
METHODS: Subjects were 52,014 men and women aged 45-75 y who participated in the Japan Public Health Center-Based Prospective Study and had no history of diabetes. ORs of self-reported physician-diagnosed type 2 diabetes for weight change between age 20 y and baseline survey (mean age 50.6 y) and during 5 y between baseline and second surveys were estimated using logistic regression analysis.
RESULTS: During the 5-year period following 5-year survey, 989 newly diagnosed cases of type 2 diabetes were self-reported. Weight gain from age 20 y was associated with an increased risk of type 2 diabetes. The multivariate-adjusted OR (95% CI) for a weight gain of ≥5 kg versus a stable weight were 2.61 (2.11 to 3.23) in men and 2.56 (1.95 to 3.35) in women. A weight gain of ≥5 kg over the 5-y following the baseline survey was also associated with an increased risk in women. No association with weight loss was observed for either period.
CONCLUSIONS: These results suggest that long-term weight gain from early adulthood to middle-age increases risk of type 2 diabetes in men and women and that risk is further enhanced by weight gain in later life in women.
Sun Ha Jee, Jae Woong Sull, Jungyong Park, Sang-Yi Lee, Heechoul Ohrr, Eliseo Guallar, Jonathan M Samet
Body-mass index and mortality in Korean men and women.
N Engl J Med. 2006 Aug 24;355(8):779-87. doi: 10.1056/NEJMoa054017. Epub 2006 Aug 22.
Abstract/Text
BACKGROUND: Obesity is associated with diverse health risks, but the role of body weight as a risk factor for death remains controversial.
METHODS: We examined the association between body weight and the risk of death in a 12-year prospective cohort study of 1,213,829 Koreans between the ages of 30 and 95 years. We examined 82,372 deaths from any cause and 48,731 deaths from specific diseases (including 29,123 from cancer, 16,426 from atherosclerotic cardiovascular disease, and 3362 from respiratory disease) in relation to the body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters).
RESULTS: In both sexes, the average baseline BMI was 23.2, and the rate of death from any cause had a J-shaped association with the BMI, regardless of cigarette-smoking history. The risk of death from any cause was lowest among patients with a BMI of 23.0 to 24.9. In all groups, the risk of death from respiratory causes was higher among subjects with a lower BMI, and the risk of death from atherosclerotic cardiovascular disease or cancer was higher among subjects with a higher BMI. The relative risk of death associated with BMI declined with increasing age.
CONCLUSIONS: Underweight, overweight, and obese men and women had higher rates of death than men and women of normal weight. The association of BMI with death varied according to the cause of death and was modified by age, sex, and smoking history.
Copyright 2006 Massachusetts Medical Society.
Wei Nie, Yi Zhang, Sun Ha Jee, Keum Ji Jung, Bing Li, Qingyu Xiu
Obesity survival paradox in pneumonia: a meta-analysis.
BMC Med. 2014 Apr 10;12:61. doi: 10.1186/1741-7015-12-61. Epub 2014 Apr 10.
Abstract/Text
BACKGROUND: It is unclear whether an 'obesity survival paradox' exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk.
METHODS: Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model.
RESULTS: Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I(2) = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2) increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%).
CONCLUSIONS: This meta-analysis suggests that an 'obesity survival paradox' exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.
Dariush Mozaffarian, Tao Hao, Eric B Rimm, Walter C Willett, Frank B Hu
Changes in diet and lifestyle and long-term weight gain in women and men.
N Engl J Med. 2011 Jun 23;364(25):2392-404. doi: 10.1056/NEJMoa1014296.
Abstract/Text
BACKGROUND: Specific dietary and other lifestyle behaviors may affect the success of the straightforward-sounding strategy "eat less and exercise more" for preventing long-term weight gain.
METHODS: We performed prospective investigations involving three separate cohorts that included 120,877 U.S. women and men who were free of chronic diseases and not obese at baseline, with follow-up periods from 1986 to 2006, 1991 to 2003, and 1986 to 2006. The relationships between changes in lifestyle factors and weight change were evaluated at 4-year intervals, with multivariable adjustments made for age, baseline body-mass index for each period, and all lifestyle factors simultaneously. Cohort-specific and sex-specific results were similar and were pooled with the use of an inverse-variance-weighted meta-analysis.
RESULTS: Within each 4-year period, participants gained an average of 3.35 lb (5th to 95th percentile, -4.1 to 12.4). On the basis of increased daily servings of individual dietary components, 4-year weight change was most strongly associated with the intake of potato chips (1.69 lb), potatoes (1.28 lb), sugar-sweetened beverages (1.00 lb), unprocessed red meats (0.95 lb), and processed meats (0.93 lb) and was inversely associated with the intake of vegetables (-0.22 lb), whole grains (-0.37 lb), fruits (-0.49 lb), nuts (-0.57 lb), and yogurt (-0.82 lb) (P≤0.005 for each comparison). Aggregate dietary changes were associated with substantial differences in weight change (3.93 lb across quintiles of dietary change). Other lifestyle factors were also independently associated with weight change (P<0.001), including physical activity (-1.76 lb across quintiles); alcohol use (0.41 lb per drink per day), smoking (new quitters, 5.17 lb; former smokers, 0.14 lb), sleep (more weight gain with <6 or >8 hours of sleep), and television watching (0.31 lb per hour per day).
CONCLUSIONS: Specific dietary and lifestyle factors are independently associated with long-term weight gain, with a substantial aggregate effect and implications for strategies to prevent obesity. (Funded by the National Institutes of Health and others.).
Andrew Reynolds, Jim Mann, John Cummings, Nicola Winter, Evelyn Mete, Lisa Te Morenga
Carbohydrate quality and human health: a series of systematic reviews and meta-analyses.
Lancet. 2019 Feb 2;393(10170):434-445. doi: 10.1016/S0140-6736(18)31809-9. Epub 2019 Jan 10.
Abstract/Text
BACKGROUND: Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre.
METHODS: We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence.
FINDINGS: Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15-30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce.
INTERPRETATION: Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.
FUNDING: Health Research Council of New Zealand, WHO, Riddet Centre of Research Excellence, Healthier Lives National Science Challenge, University of Otago, and the Otago Southland Diabetes Research Trust.
Copyright © 2019 Elsevier Ltd. All rights reserved.
C Sauvaget, J Nagano, N Allen, K Kodama
Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.
Stroke. 2003 Oct;34(10):2355-60. doi: 10.1161/01.STR.0000089293.29739.97. Epub 2003 Sep 18.
Abstract/Text
BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately.
METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered.
RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction.
CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.
Momoko Muto, Osamu Ezaki
High Dietary Saturated Fat is Associated with a Low Risk of Intracerebral Hemorrhage and Ischemic Stroke in Japanese but not in Non-Japanese: A Review and Meta-Analysis of Prospective Cohort Studies.
J Atheroscler Thromb. 2018 May 1;25(5):375-392. doi: 10.5551/jat.41632. Epub 2017 Dec 20.
Abstract/Text
AIM: The associations between dietary saturated fatty acids and the risks of stroke subtypes in cohort studies were examined by a meta-analysis of separate ethnic Japanese and non-Japanese cohorts, and causes of their difference were elucidated.
METHOD: Log hazard ratio (HR) with 95% confidence interval (CI) of the highest versus the lowest saturated fat intake from cohort studies were weighed by an inverse variance method to combine HRs.
RESULTS: Five studies of intracerebral hemorrhage and 11 studies/comparisons of ischemic stroke were selected. A meta-analysis of intracerebral hemorrhage excluding subarachnoid hemorrhage showed a strong inverse association in Japanese (n=3, HR=0.55, 95% CI 0.32-0.94) but not in non-Japanese (n=2, HR=0.98, 95% CI 0.62-1.53). A meta-analysis of ischemic stroke showed a mild inverse association in Japanese (n=4, HR=0.82, 95% CI 0.71-0.93) but not in non-Japanese (n=7, HR= 0.93, 95% CI 0.84-1.03). The effect size of saturated fat in reducing the risk of stroke in Japanese was stronger for intracerebral hemorrhage (45% reduction) than for ischemic stroke (18% reduction).
CONCLUSIONS: In Japanese but not in non-Japanese, a diet high in saturated fat is associated with a low risk of intracerebral hemorrhage and ischemic stroke. This may be due to differences in the range of intake of saturated fat, genetic susceptibility, incidence of lacunar infarction, and/or confounding factors such as dietary proteins. An intervention study targeting Japanese will be required to verify the causality.
Giancarlo Bilancio, Pierpaolo Cavallo, Carolina Ciacci, Massimo Cirillo
Dietary Protein, Kidney Function and Mortality: Review of the Evidence from Epidemiological Studies.
Nutrients. 2019 Jan 18;11(1). doi: 10.3390/nu11010196. Epub 2019 Jan 18.
Abstract/Text
The World Health Organization recommends a minimum requirement of 0.8 g/day protein/kg ideal weight. Low protein diets are used against kidney failure progression. Efficacy and safety of these diets are uncertain. This paper reviews epidemiological studies about associations of protein intake with kidney function decline and mortality. Three studies investigated these associations; two reported data on mortality. Protein intake averaged >60 g/day and 1.2 g/day/kg ideal weight. An association of baseline protein intake with long-term kidney function decline was absent in the general population and/or persons with normal kidney function but was significantly positive in persons with below-normal kidney function. Independent of kidney function and other confounders, a J-curve relationship was found between baseline protein intake and mortality due to ≈35% mortality excess for non-cardiovascular disease in the lowest quintile of protein intake, a quintile where protein intake averaged <0.8 g/day/kg ideal weight. Altogether, epidemiological evidence suggests that, in patients with reduced kidney function, protein intakes of ≈0.8 g/d/kg ideal weight could limit kidney function decline without adding non-renal risks. Long-term lower protein intake could increase mortality. In most patients, an intake of ≈0.8 g/day/kg would represent a substantial reduction of habitual intake considering that average intake is largely higher.
Ania M Jastreboff, Louis J Aronne, Nadia N Ahmad, Sean Wharton, Lisa Connery, Breno Alves, Arihiro Kiyosue, Shuyu Zhang, Bing Liu, Mathijs C Bunck, Adam Stefanski, SURMOUNT-1 Investigators
Tirzepatide Once Weekly for the Treatment of Obesity.
N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4.
Abstract/Text
BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.
METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.
RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.
CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).
Copyright © 2022 Massachusetts Medical Society.
Nobuya Inagaki, Masakazu Takeuchi, Tomonori Oura, Takeshi Imaoka, Yutaka Seino
Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.
Lancet Diabetes Endocrinol. 2022 Sep;10(9):623-633. doi: 10.1016/S2213-8587(22)00188-7. Epub 2022 Jul 30.
Abstract/Text
BACKGROUND: As the disease progresses, many patients with type 2 diabetes have difficulty in reaching treatment goals. We aimed to assess the efficacy and safety of tirzepatide, a novel GIP and GLP-1 receptor agonist, compared with dulaglutide in Japanese patients with type 2 diabetes.
METHODS: This multicentre, randomised, double-blind, parallel, active-controlled, phase 3 trial was conducted in 46 medical research centres and hospitals in Japan. Adults aged 20 years or older with type 2 diabetes who had discontinued oral antihyperglycaemic monotherapy or were treatment-naïve were included. Participants were randomly assigned (1:1:1:1) to receive tirzepatide (5, 10, or 15 mg) or dulaglutide (0·75 mg) once per week using a computer-generated random sequence with an Interactive Web Response System. Participants were stratified based on baseline HbA1c (≤8·5% or >8·5%), baseline BMI (<25 or ≥25 kg/m2), and washout of antidiabetic medication. Participants, investigators, and the sponsor were masked to treatment assignment. The starting dose of tirzepatide was 2·5 mg once per week for 4 weeks, which was then increased to 5 mg in the tirzepatide 5 mg treatment group. For the tirzepatide 10 and 15 mg treatment groups, increases by 2·5 mg occurred once every 4 weeks until the assigned dose was reached. The primary endpoint was mean change in HbA1c from baseline at week 52 measured in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03861052.
FINDINGS: Between May 7, 2019, and March 31, 2021, 821 participants were assessed for study eligibility and 636 were randomly assigned to receive at least one dose of tirzepatide 5 mg (n=159), 10 mg (n=158), or 15 mg (n=160), or dulaglutide 0·75 mg (n=159). 615 (97%) participants completed the study and 21 (3%) discontinued. Participants had a mean age of 56·6 years (SD 10·3) and were mostly male (481 [76%]). At week 52, HbA1c decreased from baseline by a least squares mean of -2·4 (SE 0·1) for tirzepatide 5 mg, -2·6 (0·1) for tirzepatide 10 mg, -2·8 (0·1) for tirzepatide 15 mg, and -1·3 (0·1) for dulaglutide. Estimated mean treatment differences versus dulaglutide were -1·1 (95% CI -1·3 to -0·9) for tirzepatide 5 mg, -1·3 (-1·5 to -1·1) for tirzepatide 10 mg, and -1·5 (-1·71 to -1·4) for tirzepatide 15 mg (all p<0·0001). Tirzepatide was associated with dose-dependent reductions in bodyweight with a least square mean difference of -5·8 kg (SE 0·4; -7·8% reduction) for 5 mg, -8·5 kg (0·4; -11·0% reduction) for 10 mg, and -10·7 kg (0·4; -13·9% reduction) for 15 mg of tirzepatide compared with -0·5 kg (0·4; -0·7% reduction) for dulaglutide. The most common treatment-emergent adverse events were nausea (19 [12%] participants in the 5 mg group vs 31 [20%] in the 10 mg group vs 32 [20%] in the 15 mg group all receiving tirzepatide vs 12 (8%) in the group receiving dulaglutide), constipation (24 [15%] vs 28 [18%] vs 22 [14%] vs 17 [11%]), and nasopharyngitis (29 [18%] vs 25 [16%] vs 22 [14%] vs 26 [16%]). The most frequent adverse events were gastrointestinal (23 [4%] of 636).
INTERPRETATION: Tirzepatide was superior compared with dulaglutide for glycaemic control and reduction in bodyweight. The safety profile of tirzepatide was consistent with that of GLP-1 receptor agonists, indicating a potential therapeutic use in Japanese patients with type 2 diabetes.
FUNDING: Eli Lilly and Company.
TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.
Copyright © 2022 Elsevier Ltd. All rights reserved.
Takashi Kadowaki, Rina Chin, Akichika Ozeki, Takeshi Imaoka, Yoshihiro Ogawa
Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial.
Lancet Diabetes Endocrinol. 2022 Sep;10(9):634-644. doi: 10.1016/S2213-8587(22)00187-5. Epub 2022 Jul 30.
Abstract/Text
BACKGROUND: Due to potential ethnic differences in the pathophysiology of type 2 diabetes, new therapeutics need to be evaluated in Japanese patients. We aimed to assess the safety and glycaemic efficacy of tirzepatide as an add-on treatment in Japanese patients with type 2 diabetes who had inadequate glycaemic control with stable doses of various oral antihyperglycaemic monotherapies.
METHODS: This multicentre, open-label, parallel-group, randomised, phase 3 trial was conducted at 34 medical research centres and hospitals in Japan. Eligible participants were aged 20 years or older with inadequately controlled (HbA1c ≥7·0% to <11·0%) type 2 diabetes and were receiving oral antihyperglycaemic monotherapy (sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinedione, glinides, or SGLT2 inhibitors) for at least 3 months (stable dose for ≥8 weeks before screening), had a BMI of 23 kg/m2 or higher, and stable bodyweight (±5%) for at least 3 months before screening. After a 2-week screening and 2-week lead-in period, all participants were randomly assigned (1:1:1) to receive 5, 10, or 15 mg of tirzepatide, administered once per week subcutaneously for 52 weeks followed by a 4 week safety follow-up period, using a computer-generated random sequence and interactive web response system, stratified by oral antihyperglycaemic medication group. All participants started receiving 2·5 mg tirzepatide and doses were escalated by 2·5 mg every 4 weeks until the assigned dose was reached. The primary endpoint was safety and tolerability during 52 weeks of treatment, assessed as incidence of treatment-emergent adverse events in the modified intention-to-treat (mITT) population. This trial is registered with ClinicalTrials.gov, NCT03861039.
FINDINGS: Between March 30, 2019, and Feb 16, 2021, with recruitment and enrolment continuing until Feb 4, 2020, 484 participants were assessed for eligibility and 443 were randomly assigned to receive at least one dose of tirzepatide (148 [33%] in the 5 mg group, 147 [33%] in the 10 mg group, and 148 [33%] in the 15 mg group). 398 (90%) participants completed the study and treatment. Most participants (343 [77%] of 443) had at least one treatment-emergent adverse event. Treatment-emergent adverse events were more frequent in the tirzepatide 15 mg group (125 [84%] of 148) than the 5 mg (109 [74%] of 148) and 10 mg groups (109 [74%] of 147). The most frequent treatment-emergent adverse events with tirzepatide were mild or moderate nasopharyngitis (75 [17%]), nausea (74 [17%]), constipation (54 [12%]), diarrhoea (51 [12%]), and decreased appetite (44 [10%]). At week 52, mean changes from baseline in bodyweight were -3·8 kg (SE 0·5; -5·1% reduction) in the 5 mg group, -7·5 kg (0·5; -10·1% reduction) in the 10 mg group, and -10·2 kg (0·5; -13·2% reduction) in the 15 mg group. Least squares mean HbA1c at baseline reduced from 8·5% (SE 0·1) to 6·0% (0·1) in the 5 mg tirzepatide group, from 8·6% (0·1) to 5·6% (0·1) in the 10 mg group, and from 8·6% (0·1) to 5·6% (0·1) in the 15 mg group at week 52. No adjudication-confirmed deaths were reported.
INTERPRETATION: Tirzepatide was well tolerated as an add-on to oral antihyperglycaemic monotherapy in Japanese participants with type 2 diabetes and showed improvement in glycaemic control and bodyweight, irrespective of background oral antihyperglycaemic medication. Tirzepatide is a potential new treatment option for Japanese patients with type 2 diabetes that is inadequately controlled with single oral antihyperglycaemic medication.
FUNDING: Eli Lilly and Company.
TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.
Copyright © 2022 Elsevier Ltd. All rights reserved.
Domenica M Rubino, Frank L Greenway, Usman Khalid, Patrick M O'Neil, Julio Rosenstock, Rasmus Sørrig, Thomas A Wadden, Alicja Wizert, W Timothy Garvey, STEP 8 Investigators
Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.
JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.
Abstract/Text
IMPORTANCE: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.
OBJECTIVE: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338).
INTERVENTIONS: Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85).
MAIN OUTCOMES AND MEASURES: The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points.
RESULTS: Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide.
CONCLUSIONS AND RELEVANCE: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04074161.
Maria J Pereira, Jan W Eriksson
Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity.
Drugs. 2019 Feb;79(3):219-230. doi: 10.1007/s40265-019-1057-0.
Abstract/Text
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.
Jarl S Torgerson, Jonathan Hauptman, Mark N Boldrin, Lars Sjöström
XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
Diabetes Care. 2004 Jan;27(1):155-61. doi: 10.2337/diacare.27.1.155.
Abstract/Text
OBJECTIVE: It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients.
RESEARCH DESIGN AND METHODS: In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat.
RESULTS: Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).
CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].
Kohji Shirai, Toru Fujita, Michitaka Tanaka, Yuka Fujii, Masatsugu Shimomasuda, Soichi Sakai, Yoshishige Samukawa
Efficacy and Safety of Lipase Inhibitor Orlistat in Japanese with Excessive Visceral Fat Accumulation: 24-Week, Double-Blind, Randomized, Placebo-Controlled Study.
Adv Ther. 2019 Jan;36(1):86-100. doi: 10.1007/s12325-018-0835-5. Epub 2018 Dec 10.
Abstract/Text
INTRODUCTION: Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat accumulation in Japanese subjects. Therefore, this comparative, placebo-controlled, double-blind, randomized study aimed to evaluate the efficacy and safety of orlistat in Japanese participants with excessive visceral fat accumulation and without dyslipidemia, diabetes mellitus, and hypertension ("metabolic diseases").
METHODS: The study population included Japanese participants with excessive visceral fat accumulation (waist circumference ≥ 85 cm in males and ≥ 90 cm in females, which corresponds to a visceral fat area of 100 cm2) and without metabolic diseases. Following a 12-week observation term, participants were randomized to the orlistat 60 mg group (n = 100) or placebo group (n = 100). Both drugs were administered orally three times daily for 24 weeks. Participants were also counseled to improve their diet and to maintain exercise throughout the study. Visceral fat area, subcutaneous fat area, waist circumference, body weight, body mass index, adverse reactions, laboratory tests, and blood pressure were regularly assessed.
RESULTS: Visceral fat area, waist circumference, and body weight were significantly reduced in the orlistat group (mean ± standard error, - 13.50 ± 1.52%, - 2.51 ± 0.25%, and - 2.79 ± 0.30%, respectively) compared to the placebo group (- 5.45 ± 1.50%, - 1.55 ± 0.26%, and - 1.22 ± 0.28%, respectively) at the last assessment. The main adverse reactions were defecation-related symptoms including oily spotting and flatus with discharge, resulting from the pharmacological effects of orlistat. Most adverse reactions were mild, and none were serious or severe.
CONCLUSION: Orlistat administration reduced visceral fat area, waist circumference, and body weight in Japanese participants with excessive visceral fat and without metabolic diseases. In addition, safety was confirmed with a tolerable profile. Orlistat may be useful to reduce excessive visceral fat accumulation when used in combination with diet and exercise.
TRIAL REGISTRATION: Japan Pharmaceutical Information Center identifier, JapicCTI-184005.
FUNDING: Taisho Pharmaceutical Co., Ltd.
Kohji Shirai, Michitaka Tanaka, Toru Fujita, Yuka Fujii, Masatsugu Shimomasuda, Soichi Sakai, Yoshishige Samukawa
Reduction of Excessive Visceral Fat and Safety with 52-Week Administration of Lipase Inhibitor Orlistat in Japanese: Long-Term Clinical Study.
Adv Ther. 2019 Jan;36(1):217-231. doi: 10.1007/s12325-018-0822-x. Epub 2018 Nov 1.
Abstract/Text
INTRODUCTION: Orlistat is an inhibitor of pancreatic lipase and is used as an anti-obesity drug in many countries. However, there are no data available regarding the effects of orlistat on visceral fat (VF) accumulation in Japanese individuals. Therefore, this study aimed to analyze the efficacy and safety of 52 weeks of orlistat administration in Japanese individuals.
METHODS: Orlistat 60 mg was administered orally three times daily for 52 weeks to Japanese participants with excessive VF accumulation and without dyslipidemia, diabetes mellitus, and hypertension (metabolic diseases). Participants were also counseled to improve their diet and to maintain exercise habits. We defined excessive VF accumulation as a waist circumference (WC) of ≥ 85 cm for males and ≥ 90 cm for females, which corresponds to a VF area of 100 cm2. Adverse reactions, clinical laboratory tests, VF, WC, body weight (BW), etc., were monitored throughout the study period.
RESULTS: VF, WC, and BW were significantly reduced at week 52 from baseline; the mean ± standard error rate of change was - 21.52% ± 1.89%, - 4.89% ± 0.45%, and - 5.36% ± 0.56%, respectively, and continued to reduce throughout the 52 weeks; these significantly reduced at whole term compared with baseline. Most adverse reactions were defecation-related symptoms such as oily spotting and flatus with discharge (flatus with small amounts of stool or oil) due to the pharmacologic effects of the lipase inhibitor. These symptoms were mostly mild, reversible, and recognizable by the participants; none were serious or severe. No participants discontinued by medical judgment about adverse reactions, and the drug could be administered continuously.
CONCLUSION: VF, WC, and BW were reduced from week 4 to week 52, indicating the effect of long-term orlistat administration. Moreover, it was well tolerated with an acceptable safety profile. Long-term administration of orlistat may be efficacious in reducing VF accumulation with safety when used in combination with diet and exercise.
TRIAL REGISTRATION: This study is registered with the Japan Pharmaceutical Information Center (identifier: JapicCTI-184004).
FUNDING: Funding for this study was provided by Taisho Pharmaceutical Co., Ltd.
Ian J Douglas, Julia Langham, Krishnan Bhaskaran, Ruth Brauer, Liam Smeeth
Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink.
BMJ. 2013 Apr 12;346:f1936. doi: 10.1136/bmj.f1936. Epub 2013 Apr 12.
Abstract/Text
OBJECTIVE: To measure the association between orlistat and acute liver injury.
DESIGN: Self controlled case series study.
SETTING: Population based primary care setting, United Kingdom.
PARTICIPANTS: 94,695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011.
MAIN OUTCOME MEASURE: Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage.
RESULTS: Among 94,695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment.
CONCLUSION: The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug.
Marc Morris, Peter Lane, Kwan Lee, Daniel Parks
An integrated analysis of liver safety data from orlistat clinical trials.
Obes Facts. 2012;5(4):485-94. doi: 10.1159/000341589. Epub 2012 Jul 23.
Abstract/Text
OBJECTIVE: Orlistat is an oral gastrointestinal lipase inhibitor and is indicated for treatment of obesity in combination with a hypocaloric diet. Post-marketing reports of adverse reactions revealed hints for possible drug-induced liver injury which has prompted changes to the product information. Orlistat's development program, involving over 30,000 patients, did not indicate a hepatic safety issue.
METHODS: We analyzed liver function test data from randomized clinical trials of orlistat, using i) meta-analysis of published study safety data, ii) time-to-event analysis for individual patients, and iii) a novel and more sensitive method derived from the U.S. Food and Drug Administration's (FDA) evaluation of drug-induced serious hepatotoxicity (eDISH) technique. Over 10,000 subjects were included.
RESULTS: The combined odds ratio from a simple summary-level fixed-effects meta-analysis of treatment-emergent abnormalities in serum alanine aminotransferase (ALT) (defined as greater than the upper level of normal for 2 successive measurements) was 1.09 (95% CI 0.93-1.28), and in total bilirubin 1.24 (95% CI 1.03-1.49). Part of the small apparent effect was due to longer exposure to orlistat than to placebo, on average. A patient-level display, adjusting for regression towards the mean, and Kaplan-Meier analysis of changes in ALT and bilirubin, taking account of different exposure, showed no significant difference between orlistat and placebo. This shows that there is no signal for hepatic damage in clinical studies of orlistat.
CONCLUSION: While idiosyncratic liver injury following exposure to orlistat cannot be excluded, it is likely to be extremely rare.
Kazushi Uneda, Yuki Kawai, Takayuki Yamada, Akira Kaneko, Ryuji Saito, Lin Chen, Tomoaki Ishigami, Takao Namiki, Tadamichi Mitsuma
Japanese traditional Kampo medicine bofutsushosan improves body mass index in participants with obesity: A systematic review and meta-analysis.
PLoS One. 2022;17(4):e0266917. doi: 10.1371/journal.pone.0266917. Epub 2022 Apr 13.
Abstract/Text
BACKGROUND: The number of people with obesity is rapidly increasing worldwide. Since obesity is a critical risk factor for cardiovascular diseases and mortality, the management of obesity is an urgent issue. However, anti-obesity drugs are insufficient in current clinical settings. Bofutsushosan (BTS, Fang-Feng-Tong-Sheng-San in China) is a traditional Japanese Kampo formula for patients with obesity. Recent basic studies have indicated that BTS potentially improves the pathophysiology of obesity. However, it is still unknown whether BTS clinically reduces body mass index (BMI) in patients with obesity.
METHODS: We searched electronic databases, including the Medline, EMBASE, Cochrane Library, and Japanese/Chinese/Korean databases, on June 15, 2021. We conducted a meta-analysis of randomized controlled trials to evaluate the effects of BTS on BMI, waist circumference, glycolipid metabolism, and blood pressure in participants with obesity. The primary outcome was change in BMI.
RESULTS: We included seven studies and 679 participants (351 in the BTS group and 328 in the control group). In participants with obesity, BTS significantly reduced BMI relative to controls (mean difference, MD [95% confidence interval]: -0.52 kg/m2 [-0.86, -0.18], P = 0.003). There was no significant difference in waist circumference, glycolipid parameters, or blood pressure. Sensitivity analyses showed robust outcomes for the primary endpoint, although the heterogeneity was considerable. Moreover, no serious adverse events were observed in the BTS group.
CONCLUSION: BTS showed a potential benefit in safely and tolerably improving BMI in participants with obesity.
Kengo Azushima, Kouichi Tamura, Sona Haku, Hiromichi Wakui, Tomohiko Kanaoka, Masato Ohsawa, Kazushi Uneda, Ryu Kobayashi, Kohji Ohki, Toru Dejima, Akinobu Maeda, Tatsuo Hashimoto, Jin Oshikawa, Yusuke Kobayashi, Koichiro Nomura, Chieko Azushima, Yasuyo Takeshita, Ryota Fujino, Ken Uchida, Ken Shibuya, Daisaku Ando, Yasuo Tokita, Tetsuya Fujikawa, Yoshiyuki Toya, Satoshi Umemura
Effects of the oriental herbal medicine Bofu-tsusho-san in obesity hypertension: a multicenter, randomized, parallel-group controlled trial (ATH-D-14-01021.R2).
Atherosclerosis. 2015 May;240(1):297-304. doi: 10.1016/j.atherosclerosis.2015.01.025. Epub 2015 Mar 25.
Abstract/Text
OBJECTIVE: There is no clinical evidence that supports the benefit of integrative medicine, defined as combination therapy of oriental and western medicine, on obesity-related hypertension. This study evaluates the efficacy of Bofu-tsusho-san (BOF), an oriental herbal medicine, on the ambulatory blood pressure (BP) profile in hypertensive patients with obesity.
METHODS: The study design was a multicenter, randomized, open-label, parallel-group controlled trial in 107 hypertensive patients with obesity. Participants were randomly assigned to receive either the conventional control therapy or BOF add-on therapy. In both groups antihypertensive therapy was aimed at achieving the target clinic BP. The primary outcome was change in the ambulatory BP profile from baseline to 24 weeks after randomization.
RESULTS: Daytime systolic BP variability, an important parameter of ambulatory BP profile, was decreased in the BOF group, and the difference in the changes in daytime systolic BP variability was significant between the BOF and control group (Control vs BOF; the change from baseline in daytime systolic BP variability, 1.0±3.3 vs -1.0±3.3%; p=0.006).
CONCLUSION: The BOF add-on therapy effectively improved the ambulatory BP variability. This is the first report suggesting that an integrative medicine approach may exert favorable effects on obesity-related hypertension compared with conventional pharmaceutical treatment.
CLINICAL TRIAL REGISTRATION: UMIN000003878.
Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Tomoaki Ishida, Kei Kawada, Kohei Jobu, Tetsushi Kawazoe, Naohisa Tamura, Mitsuhiko Miyamura
Analysis of Drug-Induced Liver Injury from Bofutsushosan Administration Using Japanese Adverse Drug Event Report (JADER) Database.
Biol Pharm Bull. 2022;45(4):460-466. doi: 10.1248/bpb.b21-00887.
Abstract/Text
Bofutsushosan is a traditional Japanese Kampo medicine. In recent years, it has been reported to be effective in the treatment of lifestyle-related diseases, and its use is increasing. However, side effects from bofutsushosan administration are common, with drug-induced liver injury being the most frequently reported complication. In this study, we analyzed the Japanese Adverse Drug Event Report (JADER) database regarding the occurrence of liver injury after bofutsushosan administration. The results showed that bofutsushosan presented a significant reporting odds ratio (ROR) signal [crude ROR 14, 95% confidence interval (CI) 12-17; p < 0.001], indicating liver injury. Furthermore, the incidents of adverse events following bofutsushosan administration, as recorded in the JADER database, were higher in women aged between 30 and 59 years. The results of logistic regression analysis in patients taking this agent showed that females in the aforementioned age range had higher odds of developing drug-induced liver injury (adjusted ROR 5.5, 95% CI 2.8-11; p < 0.001). Therefore, although bofutsushosan is a useful drug for lifestyle-related diseases, it may be necessary to refrain from its overuse, and caution should be taken during its occasional use to avoid severe adverse events.
Cara B Ebbeling, Michael M Leidig, Henry A Feldman, Margaret M Lovesky, David S Ludwig
Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial.
JAMA. 2007 May 16;297(19):2092-102. doi: 10.1001/jama.297.19.2092.
Abstract/Text
CONTEXT: The results of clinical trials involving diet in the treatment of obesity have been inconsistent, possibly due to inherent physiological differences among study participants.
OBJECTIVE: To determine whether insulin secretion affects weight loss with 2 popular diets.
DESIGN, SETTING, AND PARTICIPANTS: Randomized trial of obese young adults (aged 18-35 years; n = 73) conducted from September 2004 to December 2006 in Boston, Mass, and consisting of a 6-month intensive intervention period and a 12-month follow-up period. Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12, and 18 months. Missing data were imputed conservatively.
INTERVENTIONS: A low-glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate and 20% fat) diet.
MAIN OUTCOME MEASURES: Body weight, body fat percentage determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk factors.
RESULTS: Change in body weight and body fat percentage did not differ between the diet groups overall. However, insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier (group x time x insulin concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat percentage). For those with insulin concentration at 30 minutes above the median (57.5 microIU/mL; n = 28), the low-glycemic load diet produced a greater decrease in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03) than the low-fat diet at 18 months. There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level (n = 28). Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors. In the full cohort, plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet, whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet.
CONCLUSIONS: Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00130299.
Christopher D Gardner, John F Trepanowski, Liana C Del Gobbo, Michelle E Hauser, Joseph Rigdon, John P A Ioannidis, Manisha Desai, Abby C King
Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial.
JAMA. 2018 Feb 20;319(7):667-679. doi: 10.1001/jama.2018.0245.
Abstract/Text
Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.
Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.
Design, Setting, and Participants: The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.
Interventions: Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.
Main Outcomes and Measures: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.
Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.
Conclusions and Relevance: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.
Trial Registration: clinicaltrials.gov Identifier: NCT01826591.
Karen Rees, Andrea Takeda, Nicole Martin, Leila Ellis, Dilini Wijesekara, Abhinav Vepa, Archik Das, Louise Hartley, Saverio Stranges
Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease.
Cochrane Database Syst Rev. 2019 Mar 13;3:CD009825. doi: 10.1002/14651858.CD009825.pub3. Epub 2019 Mar 13.
Abstract/Text
BACKGROUND: The Seven Countries study in the 1960s showed that populations in the Mediterranean region experienced lower coronary heart disease (CHD) mortality probably as a result of different dietary patterns. Later observational studies have confirmed the benefits of adherence to a Mediterranean dietary pattern on cardiovascular disease (CVD) risk factors but clinical trial evidence is more limited.
OBJECTIVES: To determine the effectiveness of a Mediterranean-style diet for the primary and secondary prevention of CVD.
SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9); MEDLINE (Ovid, 1946 to 25 September 2018); Embase (Ovid, 1980 to 2018 week 39); Web of Science Core Collection (Thomson Reuters, 1900 to 26 September 2018); DARE Issue 2 of 4, 2015 (Cochrane Library); HTA Issue 4 of 4, 2016 (Cochrane Library); NHS EED Issue 2 of 4, 2015 (Cochrane Library). We searched trial registers and applied no language restrictions.
SELECTION CRITERIA: We selected randomised controlled trials (RCTs) in healthy adults and adults at high risk of CVD (primary prevention) and those with established CVD (secondary prevention). Both of the following key components were required to reach our definition of a Mediterranean-style diet: high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant-based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The intervention could be dietary advice, provision of relevant foods, or both. The comparison group received either no intervention, minimal intervention, usual care or another dietary intervention. Outcomes included clinical events and CVD risk factors. We included only studies with follow-up periods of three months or more defined as the intervention period plus post intervention follow-up.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and assessed risk of bias. We conducted four main comparisons:1. Mediterranean dietary intervention versus no intervention or minimal intervention for primary prevention;2. Mediterranean dietary intervention versus another dietary intervention for primary prevention;3. Mediterranean dietary intervention versus usual care for secondary prevention;4. Mediterranean dietary intervention versus another dietary intervention for secondary prevention.
MAIN RESULTS: In this substantive review update, 30 RCTs (49 papers) (12,461 participants randomised) and seven ongoing trials met our inclusion criteria. The majority of trials contributed to primary prevention: comparisons 1 (nine trials) and 2 (13 trials). Secondary prevention trials were included for comparison 3 (two trials) and comparison 4 (four trials plus an additional two trials that were excluded from the main analyses due to published concerns regarding the reliability of the data).Two trials reported on adverse events where these were absent or minor (low- to moderate-quality evidence). No trials reported on costs or health-related quality of life.Primary preventionThe included studies for comparison 1 did not report on clinical endpoints (CVD mortality, total mortality or non-fatal endpoints such as myocardial infarction or stroke). The PREDIMED trial (included in comparison 2) was retracted and re-analysed following concerns regarding randomisation at two of 11 sites. Low-quality evidence shows little or no effect of the PREDIMED (7747 randomised) intervention (advice to follow a Mediterranean diet plus supplemental extra-virgin olive oil or tree nuts) compared to a low-fat diet on CVD mortality (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.50 to 1.32) or total mortality (HR 1.0, 95% CI 0.81 to 1.24) over 4.8 years. There was, however, a reduction in the number of strokes with the PREDIMED intervention (HR 0.60, 95% CI 0.45 to 0.80), a decrease from 24/1000 to 14/1000 (95% CI 11 to 19), moderate-quality evidence). For CVD risk factors for comparison 1 there was low-quality evidence for a possible small reduction in total cholesterol (-0.16 mmol/L, 95% CI -0.32 to 0.00) and moderate-quality evidence for a reduction in systolic (-2.99 mmHg (95% CI -3.45 to -2.53) and diastolic blood pressure (-2.0 mmHg, 95% CI -2.29 to -1.71), with low or very low-quality evidence of little or no effect on LDL or HDL cholesterol or triglycerides. For comparison 2 there was moderate-quality evidence of a possible small reduction in LDL cholesterol (-0.15 mmol/L, 95% CI -0.27 to -0.02) and triglycerides (-0.09 mmol/L, 95% CI -0.16 to -0.01) with moderate or low-quality evidence of little or no effect on total or HDL cholesterol or blood pressure.Secondary preventionFor secondary prevention, the Lyon Diet Heart Study (comparison 3) examined the effect of advice to follow a Mediterranean diet and supplemental canola margarine compared to usual care in 605 CHD patients over 46 months and there was low-quality evidence of a reduction in adjusted estimates for CVD mortality (HR 0.35, 95% CI 0.15 to 0.82) and total mortality (HR 0.44, 95% CI 0.21 to 0.92) with the intervention. Only one small trial (101 participants) provided unadjusted estimates for composite clinical endpoints for comparison 4 (very low-quality evidence of uncertain effect). For comparison 3 there was low-quality evidence of little or no effect of a Mediterranean-style diet on lipid levels and very low-quality evidence for blood pressure. Similarly, for comparison 4 where only two trials contributed to the analyses there was low or very low-quality evidence of little or no effect of the intervention on lipid levels or blood pressure.
AUTHORS' CONCLUSIONS: Despite the relatively large number of studies included in this review, there is still some uncertainty regarding the effects of a Mediterranean-style diet on clinical endpoints and CVD risk factors for both primary and secondary prevention. The quality of evidence for the modest benefits on CVD risk factors in primary prevention is low or moderate, with a small number of studies reporting minimal harms. There is a paucity of evidence for secondary prevention. The ongoing studies may provide more certainty in the future.
Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group.
N Engl J Med. 2001 Jan 4;344(1):3-10.
Abstract/Text
William C Knowler, Elizabeth Barrett-Connor, Sarah E Fowler, Richard F Hamman, John M Lachin, Elizabeth A Walker, David M Nathan, Diabetes Prevention Program Research Group
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
N Engl J Med. 2002 Feb 7;346(6):393-403. doi: 10.1056/NEJMoa012512.
Abstract/Text
BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors--elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle--are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.
METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups.
RESULTS: The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin.
CONCLUSIONS: Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
Look AHEAD Research Group, Rena R Wing, Paula Bolin, Frederick L Brancati, George A Bray, Jeanne M Clark, Mace Coday, Richard S Crow, Jeffrey M Curtis, Caitlin M Egan, Mark A Espeland, Mary Evans, John P Foreyt, Siran Ghazarian, Edward W Gregg, Barbara Harrison, Helen P Hazuda, James O Hill, Edward S Horton, Van S Hubbard, John M Jakicic, Robert W Jeffery, Karen C Johnson, Steven E Kahn, Abbas E Kitabchi, William C Knowler, Cora E Lewis, Barbara J Maschak-Carey, Maria G Montez, Anne Murillo, David M Nathan, Jennifer Patricio, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, David Reboussin, Judith G Regensteiner, Amy D Rickman, Donna H Ryan, Monika Safford, Thomas A Wadden, Lynne E Wagenknecht, Delia S West, David F Williamson, Susan Z Yanovski
Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.
N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24.
Abstract/Text
BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).
CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
W Jack Rejeski, Edward H Ip, Alain G Bertoni, George A Bray, Gina Evans, Edward W Gregg, Qiang Zhang, Look AHEAD Research Group
Lifestyle change and mobility in obese adults with type 2 diabetes.
N Engl J Med. 2012 Mar 29;366(13):1209-17. doi: 10.1056/NEJMoa1110294.
Abstract/Text
BACKGROUND: Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients.
METHODS: We randomly assigned 5145 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle intervention or a diabetes support-and-education program; 5016 participants contributed data. We used hidden Markov models to characterize disability states and mixed-effects ordinal logistic regression to estimate the probability of functional decline. The primary outcome was self-reported limitation in mobility, with annual assessments for 4 years.
RESULTS: At year 4, among 2514 adults in the lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%) had good mobility; the numbers among 2502 participants in the support group were 656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001). Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect (P<0.001 for both variables). Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at year 1.
CONCLUSIONS: Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.).
Suzanne Phelan, Alka M Kanaya, Leslee L Subak, Patricia E Hogan, Mark A Espeland, Rena R Wing, Kathryn L Burgio, Vicki DiLillo, Amy A Gorin, Delia S West, Jeanette S Brown, Look AHEAD Research Group
Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial.
J Urol. 2012 Mar;187(3):939-44. doi: 10.1016/j.juro.2011.10.139. Epub 2012 Jan 20.
Abstract/Text
PURPOSE: We determined the effect of weight loss on the prevalence, incidence and resolution of weekly or more frequent urinary incontinence in overweight/obese women with type 2 diabetes after 1 year of intervention in the Look AHEAD (Action for Health in Diabetes) trial.
MATERIALS AND METHODS: Women in this substudy (2,739, mean ± SD age 57.9 ± 6.8 years, body mass index 36.5 ± 6.1 kg/m(2)) were randomized into an intensive lifestyle weight loss intervention or a diabetes support and education control condition.
RESULTS: At baseline 27% of participants reported urinary incontinence on a validated questionnaire (no significant difference by intensive lifestyle intervention vs diabetes support and education). After 1 year of intervention the intensive lifestyle intervention group in this substudy lost 7.7 ± 7.0 vs 0.7 ± 5.0 kg in the diabetes support and education group. At 1 year fewer women in the intensive lifestyle intervention group reported urinary incontinence (25.3% vs 28.6% in the diabetes support and education group, p = 0.05). Among participants without urinary incontinence at baseline 10.5% of intensive lifestyle intervention and 14.0% of diabetes support and education participants experienced urinary incontinence after 1 year (p = 0.02). There were no significant group differences in the resolution of urinary incontinence (p >0.17). Each kg of weight lost was associated with a 3% reduction in the odds of urinary incontinence developing (p = 0.01), and weight losses of 5% to 10% reduced these odds by 47% (p = 0.002).
CONCLUSIONS: Moderate weight loss reduced the incidence but did not improve the resolution rates of urinary incontinence at 1 year among overweight/obese women with type 2 diabetes. Weight loss interventions should be considered for the prevention of urinary incontinence in overweight/obese women with diabetes.
Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Gary D Foster, Kelley E Borradaile, Mark H Sanders, Richard Millman, Gary Zammit, Anne B Newman, Thomas A Wadden, David Kelley, Rena R Wing, F Xavier Pi-Sunyer, David Reboussin, Samuel T Kuna, Sleep AHEAD Research Group of Look AHEAD Research Group
A randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD study.
Arch Intern Med. 2009 Sep 28;169(17):1619-26. doi: 10.1001/archinternmed.2009.266.
Abstract/Text
BACKGROUND: The belief that weight loss improves obstructive sleep apnea (OSA) has limited empirical support. The purpose of this 4-center study was to assess the effects of weight loss on OSA over a 1-year period.
METHODS: The study included 264 participants with type 2 diabetes and a mean (SD) age of 61.2 (6.5) years, weight of 102.4 (18.3) kg, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 36.7 (5.7), and an apnea-hypopnea index (AHI) of 23.2 (16.5) events per hour. The participants were randomly assigned to either a behavioral weight loss program developed specifically for obese patients with type 2 diabetes (intensive lifestyle intervention [ILI]) or 3 group sessions related to effective diabetes management (diabetes support and education [DSE]).
RESULTS: The ILI participants lost more weight at 1 year than did DSE participants (10.8 kg vs 0.6 kg; P < .001). Relative to the DSE group, the ILI intervention was associated with an adjusted (SE) decrease in AHI of 9.7 (2.0) events per hour (P < .001). At 1 year, more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among ILI participants was half that of the DSE group. Initial AHI and weight loss were the strongest predictors of changes in AHI at 1 year (P < .01). Participants with a weight loss of 10 kg or more had the greatest reductions in AHI.
CONCLUSIONS: Physicians and their patients can expect that weight loss will result in significant and clinically relevant improvements in OSA among obese patients with type 2 diabetes. Trial Registration clinicaltrials.gov Identifier: NCT00194259.
Lucy F Faulconbridge, Thomas A Wadden, Richard R Rubin, Rena R Wing, Michael P Walkup, Anthony N Fabricatore, Mace Coday, Brent Van Dorsten, David L Mount, Linda J Ewing, Look AHEAD Research Group
One-year changes in symptoms of depression and weight in overweight/obese individuals with type 2 diabetes in the Look AHEAD study.
Obesity (Silver Spring). 2012 Apr;20(4):783-93. doi: 10.1038/oby.2011.315. Epub 2011 Oct 20.
Abstract/Text
Depressed individuals are frequently excluded from weight loss trials because of fears that weight reduction may precipitate mood disorders, as well as concerns that depressed participants will not lose weight satisfactorily. The present study examined participants in the Look AHEAD study to determine whether moderate weight loss would be associated with incident symptoms of depression and suicidal ideation, and whether symptoms of depression at baseline would limit weight loss at 1 year. Overweight/obese adults with type 2 diabetes (n = 5,145) were randomly assigned to an Intensive Lifestyle Intervention (ILI) or a usual care group, Diabetes Support and Education (DSE). Of these, 5,129 participants completed the Beck Depression Inventory (BDI) and had their weight measured at baseline and 1 year. Potentially significant symptoms of depression were defined by a BDI score ≥10. Participants in ILI lost 8.6 ± 6.9% of initial weight at 1 year, compared to 0.7 ± 4.8% for DSE (P < 0.001, effect size = 1.33), and had a reduction of 1.4 ± 4.7 points on the BDI, compared to 0.4 ± 4.5 for DSE (P < 0.001, effect size = 0.23). At 1 year, the incidence of potentially significant symptoms of depression was significantly lower in the ILI than DSE group (6.3% vs. 9.6%) (relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.5, 0.8; P < 0.001). In the ILI group, participants with and without symptoms of depression lost 7.8 ± 6.7% and 8.7 ± 6.9%, respectively, a difference not considered clinically meaningful. Intentional weight loss was not associated with the precipitation of symptoms of depression, but instead appeared to protect against this occurrence. Mild (or greater) symptoms of depression at baseline did not prevent overweight/obese individuals with type 2 diabetes from achieving significant weight loss.
Donald A Williamson, Jack Rejeski, Wei Lang, Brent Van Dorsten, Anthony N Fabricatore, Katie Toledo, Look AHEAD Research Group
Impact of a weight management program on health-related quality of life in overweight adults with type 2 diabetes.
Arch Intern Med. 2009 Jan 26;169(2):163-71. doi: 10.1001/archinternmed.2008.544.
Abstract/Text
BACKGROUND: Inconsistent findings have been reported regarding improved health-related quality of life (HRQOL) after weight loss. We tested the efficacy of a weight management program for improving HRQOL in overweight or obese adults diagnosed as having type 2 diabetes mellitus.
METHODS: We conducted a randomized multisite clinical trial at 16 outpatient research centers with 2 treatment arms and blinded measurements at baseline and the end of year 1. A total of 5145 participants (mean [SD] age, 58.7 [6.9] years; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 36.0 [5.9]; 59.5% women; 63.1% white) were randomized to an intensive lifestyle intervention (ILI) or to diabetes support and education (DSE). Main outcome measures included the 36-Item Short-Form Health Survey physical component summary (PCS) and mental health component summary (MCS) scores and Beck Depression Inventory II (BDI-II) scores. Baseline mean (SD) scores were 47.9 (7.9) for PCS, 54.0 (8.1) for MCS, and 5.7 (5.0) for BDI-II.
RESULTS: Improved HRQOL was demonstrated by the PCS and BDI-II scores (P < .001) in the ILI arm compared with the DSE arm. The largest effect was observed for the PCS score (difference, -2.91; 99% confidence interval, -3.44 to -2.37). The greatest HRQOL improvement occurred in participants with the lowest baseline HRQOL levels. Mean (SD) changes in weight (ILI, -8.77 [8.2] kg and DSE, -0.86 [5.0] kg), improved fitness, and improved physical symptoms mediated treatment effects associated with the BDI-II and PCS.
CONCLUSIONS: Overweight adults diagnosed as having type 2 diabetes experienced significant improvement in HRQOL by enrolling in a weight management program that yielded significant weight loss, improved physical fitness, and reduced physical symptoms.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00017953.
Ignacio Jáuregui-Lobera
Iron deficiency and bariatric surgery.
Nutrients. 2013 May 15;5(5):1595-608. doi: 10.3390/nu5051595. Epub 2013 May 15.
Abstract/Text
It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients' outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron), before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented.
Guilherme M Campos, Jad Khoraki, Matthew G Browning, Bernardo M Pessoa, Guilherme S Mazzini, Luke Wolfe
Changes in Utilization of Bariatric Surgery in the United States From 1993 to 2016.
Ann Surg. 2020 Feb;271(2):201-209. doi: 10.1097/SLA.0000000000003554.
Abstract/Text
OBJECTIVE: The aim of this study was to obtain estimates of changes in perioperative outcomes and utilization of bariatric surgery in the United States from 1993 to 2016.
BACKGROUND: Bariatric surgery has evolved over the past 2 decades. Nationally representative information on changes of perioperative outcomes and utilization of surgery in the growing eligible population (class III obesity or class II obesity with comorbidities) is lacking.
METHODS: Adults with obesity diagnosis who underwent primary bariatric surgery in the United States from 1993 to 2016 were identified in the National Inpatient Sample database. Estimates of the yearly number, types and cost of surgeries, patients' and hospital characteristics, complications and mortality rates were obtained. Prevalence of obesity and comorbidities were obtained from the National Health and Nutrition Examination Survey and changes in utilization of surgery were estimated.
RESULTS: An estimated 1,903,273 patients underwent bariatric surgery in the United States between 1993 and 2016. Mean age was 43.9 years (79.9% women, 70.9% white race, 70.7% commercial insurance); these and other characteristics changed over time. Surgeries were exclusively open operations in 1993 (n = 8,631; gastric bypass and vertical banded gastroplasty, 49% each) and 98% laparoscopic (n = 162,969; 69.8% sleeve gastrectomy and 27.8% gastric bypass) in 2016. Complication and mortality rates peaked in 1998 (11.7% and 1%) and progressively decreased to 1.4% and 0.04% in 2016. Utilization increased from 0.07% in 1993 to 0.62% in 2004 and remained low at 0.5% in 2016.
CONCLUSIONS: Perioperative safety of bariatric surgery improved over the last quarter-century. Despite growth in number of surgeries, utilization has only marginally increased. Addressing barriers for utilization may allow for greater access to surgical therapy.
Viktoria L Gloy, Matthias Briel, Deepak L Bhatt, Sangeeta R Kashyap, Philip R Schauer, Geltrude Mingrone, Heiner C Bucher, Alain J Nordmann
Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials.
BMJ. 2013 Oct 22;347:f5934. Epub 2013 Oct 22.
Abstract/Text
OBJECTIVE: To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity.
DESIGN: Systematic review and meta-analysis based on a random effects model.
DATA SOURCES: Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status.
ELIGIBILITY CRITERIA: Eligible studies were randomised controlled trials with ≥ 6 months of follow-up that included individuals with a body mass index ≥ 30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events.
RESULTS: The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference -26 kg (95% confidence interval -31 to -21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference -0.7 mmol/L (-1.0 to -0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%).
CONCLUSIONS: Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).
Ali Aminian, Rickesha Wilson, Abbas Al-Kurd, Chao Tu, Alex Milinovich, Matthew Kroh, Raul J Rosenthal, Stacy A Brethauer, Philip R Schauer, Michael W Kattan, Justin C Brown, Nathan A Berger, Jame Abraham, Steven E Nissen
Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity.
JAMA. 2022 Jun 28;327(24):2423-2433. doi: 10.1001/jama.2022.9009.
Abstract/Text
IMPORTANCE: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk.
OBJECTIVE: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity.
DESIGN, SETTING, AND PARTICIPANTS: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021.
EXPOSURES: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265).
MAIN OUTCOMES AND MEASURES: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality.
RESULTS: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01).
CONCLUSIONS AND RELEVANCE: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.
Antonio E Pontiroli, Alberto Morabito
Long-term prevention of mortality in morbid obesity through bariatric surgery. a systematic review and meta-analysis of trials performed with gastric banding and gastric bypass.
Ann Surg. 2011 Mar;253(3):484-7. doi: 10.1097/SLA.0b013e31820d98cb.
Abstract/Text
BACKGROUND: Bariatric surgery has been reported to reduce long-term mortality in operated participants in comparison with nonoperated participants.
METHODS: We performed a systematic review and meta-analysis of clinical trials published as full articles dealing with cardiovascular (CV) mortality, all-cause mortality (noncardiovascular), and global mortality (sum of CV and all-cause mortality). Pooled-fixed effects of estimates of the risk of mortality in participants undergoing surgery were calculated compared with controls.
RESULTS: Of 44,022 participants from 8 trials (14,052 undergoing surgery and 29,970 controls), death occurred in 3317 participants (400 in surgery, 2917 in controls); when the kind of death was specified, 321 CV deaths (118 in surgery, 203 in controls), and 523 all-cause deaths (218 in surgery, 305 in controls) occurred. Compared with controls, surgery was associated with a reduced risk of global mortality (OR = 0.55, CI, 0.49-0.63), of CV mortality (OR = 0.58, CI, 0.46-0.73), and of all-cause mortality (OR = 0.70, CI, 0.59-0.84).Data of all-cause mortality were not heterogeneous; heterogeneity of data of CV mortality decreased when studies were grouped according to size (large vs small studies). The reduction of risk was smaller in large than in small studies (OR = 0.61 vs 0.21, 0.63 vs 0.16, 0.74 vs 0.35 for global, CV, and all-cause mortality, respectively). The effect of gastric banding and gastric by-pass (3797 vs 10,255 interventions) was similar for global and all-cause mortality (OR = 0.57 vs 0.55, and 0.66 vs 0.70, respectively), different for CV mortality (OR = 0.71 vs 0.48). At meta-regression analysis, a trend for a decrease of global mortality (Log OR) linked to increasing BMI appeared.
CONCLUSION: This meta-analysis indicates that (1) bariatric surgery reduces long-term mortality; (2) risk reduction is smaller in large than in small studies; and (3) both gastric banding and gastric by-pass reduce mortality with a greater effect of the latter on CV mortality.
Atsuhito Saiki, Takashi Yamaguchi, Sho Tanaka, Akira Sasaki, Takeshi Naitoh, Yasuyuki Seto, Hisahiro Matsubara, Koutaro Yokote, Shinichi Okazumi, Satoshi Ugi, Hiroshi Yamamoto, Masayuki Ohta, Yasushi Ishigaki, Kazunori Kasama, Yosuke Seki, Junichiro Irie, Toru Kusakabe, Motoyoshi Tsujino, Hideharu Shimizu, Kohji Shirai, Akira Onozaki, Aya Kitahara, Karin Hayashi, Yasuhiro Miyazaki, Takayuki Masaki, Daiji Nagayama, Shigeo Yamamura, Ichiro Tatsuno, Japanese Survey of Morbid and Treatment‐Resistant Obesity Group (J‐SMART Group)
Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients.
Ann Gastroenterol Surg. 2019 Nov;3(6):638-647. doi: 10.1002/ags3.12285. Epub 2019 Aug 26.
Abstract/Text
AIM: Laparoscopic sleeve gastrectomy (LSG) is becoming popular in Japan, but insufficient weight loss is often observed in patients after LSG. We investigated the effect of LSG on obesity-related comorbidities and identified the background characteristics of Japanese patients with insufficient weight loss after LSG.
METHODS: In this multi-institutional retrospective study at 10 certified bariatric institutions, 322 Japanese patients who underwent LSG with a follow-up period of more than 2 years were analyzed. Anthropometry, obesity-related comorbidities and psychosocial background data were collected. Weight loss was expressed as 2-year percent total weight loss (%TWL).
RESULTS: Mean age, body weight, body mass index (BMI) and glycated hemoglobin were 46.9 years, 119.2 kg, 43.7 kg/m2 and 7.1%, respectively. Prevalence of mental disorders was 26.3%. Mean BMI declined to 30.3 kg/m2 at 2 years and %TWL was 29.9%. Improvements in the markers and prevalence of obesity-related comorbidities were observed. Remission rates of diabetes, dyslipidemia and hypertension were 75.6%, 59.7% and 41.8%, respectively. %TWL at the respective cut-off level of diabetes remission was 20.8%. Lower remission rates of diabetes in patients with %TWL <20%, and less calorie restriction and higher prevalence of mental disorders (46.9%) in patients with %TWL <15% were observed. Frequencies of %TWL <15% and <20% were 6.5% and 18.5%, respectively.
CONCLUSION: %TWL 20% was a candidate cut-off point of insufficient weight loss for diabetes remission after LSG, and mental disorders might be relevant to intractable obesity in Japanese patients.
© 2019 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.
Atsuhito Saiki, Rieko Kanai, Shoko Nakamura, Sho Tanaka, Rena Oka, Yasuhiro Watanabe, Takashi Yamaguchi, Masahiro Ohira, Takashi Oshiro, Karin Hayashi, Ichiro Tatsuno
Impact of Mental Health Background and Nutrition Intake on Medium-Term Weight Loss in Japanese Patients Undergoing Laparoscopic Sleeve Gastrectomy.
Obes Facts. 2020;13(4):371-383. doi: 10.1159/000509342. Epub 2020 Aug 18.
Abstract/Text
OBJECTIVES: Bariatric surgery is the most effective weight loss therapy, and recently laparoscopic sleeve gastrectomy (LSG) is gaining popularity worldwide. On the other hand, patients undergoing bariatric surgery have a high prevalence of mental disorders. A Japanese nationwide survey reported high prevalence of mental disorders in patients with low percent total weight loss (%TWL) and also in those with high %TWL. The aim of this study was to investigate the relationship of 1-year %TWL with background mental health status, 3-year outcomes, and nutrition intake in Japanese patients after LSG.
METHODS: This study was a single-center retrospective database analysis. A total of 89 Japanese patients who underwent LSG and were followed for 3 years were enrolled (mean age 41.9 years, baseline body mass index 44.9, baseline glycosylated hemoglobin, HbA1c, 7.0%). The patients were divided into 3 groups according to 1-year %TWL as follows: ≤19.9% (insufficient group), 20.0-34.9% (average group) and ≥35.0% (excessive group). Psychosocial and nutritional status as well as physical data were collected from all patients.
RESULTS: The prevalence of mental disorders was 51.7%, and 1-year %TWL was 28.1% in all patients. No significant differences were observed in the changes in body weight and HbA1c between patients with and those without mental disorders. The prevalence of mental disorders was particularly high in the insufficient and excessive groups. In the insufficient group, mood disorders and mental retardation/developmental disorders were frequent, and snacking and eating out habits were often observed. In the excessive group, the frequencies of mood disorders and binge eating were high, and a decrease in skeletal muscle mass due to low protein intake was observed. Furthermore, weight regain was shown 12 months after LSG in both groups. In the average group, there were fewer problems in weight loss outcomes, mental health, nutrition intake and body composition.
CONCLUSIONS: Psychosocial and nutritional problems were often found not only in patients with insufficient weight loss, but also in those with seemingly "excellent" weight reduction. To improve long-term weight loss outcome and future health, a multidisciplinary approach focusing on mental health and nutrition is essential for patients undergoing bariatric surgery.
© 2020 The Author(s) Published by S. Karger AG, Basel.
