Weight Change and Risk of Developing Type 2 Diabetes

Objective: To examine the association between weight change and risk of type 2 diabetes and whether initial weight modifies the association. Research Methods and Procedures: This is a prospective cohort study of 20, 187 alumni from Harvard University and the University of Pennsylvania. At baseline in 1962 or 1966, men (mean age, 45.9 years) reported their weight, height, and other risk factors. They also had had their weight and height measured at university entry (mean age, 18.5 years). Participants were followed from baseline to 1998 for type 2 diabetes. Results: During follow‐up, 1223 men developed type 2 diabetes. Weight gain significantly increased the risk of this disease. The multivariate relative risks associated with BMI change from university entry to baseline of <?0.5, ±0.5, >0.5 to 1.0, >1.0 to 1.5, >1.5 to 2.0, >2.0 to 3.0, and >3.0 kg/m² per decade were 0.88, 1.00 (referent), 1.29, 2.09, 2.69, 4.67, and 7.02, respectively (p for trend < 0.0001). Even among men with a low initial BMI < 21 kg/m², weight gain significantly increased risk; the corresponding relative risks were (no cases), 1.00 (referent), 1.00, 1.93, 2.47, 4.82, and 7.68, respectively (p for trend < 0.0001). Discussion: A low initial BMI does not ameliorate the increase in risk of type 2 diabetes with weight gain. Avoidance of weight gain, even among lean individuals, is important to reduce the risk of this disease.     

Decreased Glucagon‐like Peptide 1 Release after Weight Loss in Overweight/Obese Subjects

Objective: Postprandial glucagon‐like peptide 1 (GLP‐1) release seems to be attenuated in obese subjects. Results on whether weight loss improves GLP‐1 release are contradictory. The aim of this study was to further investigate the effect of weight loss on basal and postprandial GLP‐1 release in overweight/obese subjects. Research Methods and Procedures: Thirty‐two overweight/obese subjects participated in a repeated measurement design before (BMI, 30.3 ± 2.8 kg/m²; waist circumference, 92.6 ± 7.8 cm; hip circumference, 111.1 ± 7.4 cm) and after a weight loss period of 6 weeks (BMI, 28.2 ± 2.7 kg/m²; waist circumference, 85.5 ± 8.5 cm; hip circumference, 102.1 ± 9.2 cm). During weight loss, subjects received a very‐low‐calorie diet (Optifast) to replace three meals per day. Subjects came to the laboratory fasted, and after a baseline blood sample, received a standard breakfast (1.9 MJ). Postprandially, blood samples were taken every one‐half hour relative to intake for 120 minutes to determine GLP‐1, insulin, glucose, and free fatty acids from plasma. Appetite ratings were obtained with visual analog scales. Results: After weight loss, postprandial GLP‐1 concentrations at 30 and 60 minutes were significantly lower than before weight loss (p < 0.05). Glucose concentrations were also lower, and free fatty acids were higher compared with before weight loss. Ratings of satiety were increased, and hunger scores were decreased after weight loss (p < 0.05). Discussion: In overweight/obese subjects, GLP‐1 concentrations after weight loss were decreased compared with before weight loss, and nutrient‐related stimulation was abolished. This might be a response to a proceeding negative energy balance. Satiety and GLP‐1 seem to be unrelated in the long term.     

Short‐Term Effects of Weight Loss on the Cardiovascular Risk Factors in Morbidly Obese Patients

Objective: To analyze the short‐term effects of weight loss on the cardiovascular risk factors in morbidly obese patients. Research Methods and Procedures: Five metabolic cardiovascular risk factors (blood glucose, blood pressure, total cholesterol, high‐density lipoprotein (HDL)‐cholesterol, and triglycerides) were determined before and 15.3 ± 2.1 months after laparoscopic gastric banding in 650 morbidly obese patients. Global cardiovascular risk was calculated according to the Prospective Cardiovascular Münster (PROCAM) scoring system. Results: Mean weight loss was 22.7 ± 20.4 kg. Normalization of the metabolic alteration was observed in 67.3% of patients with diabetes, 38.3% of patients with hypercholesterolemia, 72.5% of patients with low HDL‐cholesterol, 72.3% of patients with hypertriglyceridemia, and 46.7% of patients with hypertension. PROCAM score fell from 31.4 ± 11.6 to 28.0 ± 12.0 points (p < 0.001). The modifications of total cholesterol and blood pressure were unrelated to percentage weight loss. Percentage weight loss was significantly related to the reductions of fasting blood glucose, triglyceride level, and the PROCAM score and to the increase of HDL‐cholesterol concentrations observed after surgery. However, the strength of these four relationships was generally low. The variations of HDL‐cholesterol concentrations and blood pressure levels were more influenced by actual energy balance than by the extent of weight loss. Discussion: Weight loss observed in the first 12 to 18 months after gastric banding was associated with a significant improvement of single cardiovascular risk factors and global risk. On the other hand, the extent of weight loss was poorly related to the magnitude of improvement in cardiovascular risk.     

Combined Dietary and Pharmacological Weight Management in Obese Hypopituitary Patients

Objective: The high prevalence of obesity and cardiovascular risk factors in hypopituitarism affirms the need for effective weight loss intervention. In this study, we investigated the combined effect of sibutramine, diet, and exercise in obese hypopituitary patients (HPs). Research Methods and Procedures: In an open‐label prospective intervention trial, 14 obese well‐substituted nondiabetic HPs and 14 matched simple obese controls were allocated to 11‐month treatment with sibutramine (10 to 15 mg), diet (600 kcal/d deficit), and exercise. Anthropometric indices and body composition (obtained from DXA scan) were assessed monthly for the first 5 months and thereafter every second month for the next 6 months. Results: Mean (±SD) weight loss at 11 months was 11.3 ± 4.8 kg in patients vs. 10.7 ± 4.7 kg in controls. The HPs exhibited the same improvements in body composition, waist circumference, blood lipids, and fasting glucose as the simple obese. In a multivariate model, baseline weight, duration of growth hormone replacement therapy, and duration of pituitary disease explained 79% (p = 0.001) of the variation in weight loss at 4 months in the HPs. Only baseline weight and waist circumference could predict weight loss at 11 months. Discussion: HPs are not resistant to weight loss therapy. Almost all will achieve at least 5% weight loss, and 60% can lose >10% weight within 11 months. However, the long‐term effect on risk factors associated with type 2 diabetes and cardiovascular disease as well as on mortality needs to be established.     

Predictors of Weight Change in Middle‐aged and Old Men

Objective: Studies on weight change and mortality have yielded inconclusive results. This 10‐year prospective study was undertaken to improve understanding of factors affecting weight change. Research Methods and Procedures: The subjects were 1143 men, aged 36 to 88 years (mean, 53.3 years) at entry. A questionnaire was filled in at entry and at the end of the follow‐up with queries on weight, height, weight at the age of 20, physician‐diagnosed diseases, smoking, alcohol use, dietary habits, leisure physical activity, occupation, present occupational activity, living conditions (living alone or cohabiting), and former athletic status. Further information on morbidity was obtained from selected national registers. Factors predicting weight change during the study were identified by stepwise linear multiple regression analysis. Results: The mean 10‐year weight change was 0.8 (range, ?29 to +24) kg. Age at entry (β‐coefficient, ?0.17, SE 0.02), weight at entry (β, ?0.03, SE 0.01), diabetes at entry (β, ?3.55, SE 1.02), diabetes diagnosed after entry (β, ?3.94, SE 0.96), malignant cancer (β, ?1.60, SE 0.70), being a smoker (β, ?1.59, SE 0.48), and increased physical activity (β, ?1.27, SE 0.54) were significantly (p < 0.05) associated with weight loss in the final model. The model explained 13% of the variance of weight change. Discussion: The results emphasize the complexity of weight change. Some factors associated with weight change are apparently negatively, and some positively, associated with health. This could explain the equivocal findings on weight change and mortality in the literature.     

Metabolic and Weight Loss Effects of Long‐Term Dietary Intervention in Obese Patients: Four‐Year Results

Objective: To investigate the contribution of meal and snack replacements for long‐term weight maintenance and risk factor reduction in obese patients. Research Methods and Procedures: Prospective, randomized, two‐arm, parallel intervention for 12 weeks followed by a prospective single‐arm 4‐year trial in a University Hospital clinic. One hundred patients, >18 years old and with a body mass index > 25 and ≤ 40 kg/m², were prescribed a 1200 to 1500 kcal/d control diet (Group A) or an isoenergetic diet, including two meal and snack replacements (vitamin‐ and mineral‐fortified shakes, soups, and bars) and one meal high in fruits and vegetables (Group B). Following a 3 months of weight loss, all patients were prescribed the same energy‐restricted diet (1200 to 1500 kcal) with one meal and one snack replacement for an additional 4 years. Results: All 100 patients were evaluated at 12 weeks. Mean percentage weight loss was 1.5 ± 0.4% and 7.8 ± 0.5% (mean ± SEM) for Groups A and B, respectively. At 12 weeks systolic blood pressure, plasma triacylglycerol, glucose, and insulin concentrations were significantly reduced in Group B, whereas no changes occurred in Group A. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.2 ± 0.8% for Group A and 8.4 ± 0.8% (mean ± SEM) for Group B. Both groups showed significant improvement in blood glucose and insulin (p < 0.001), but only Group B showed significant improvement in triacylglycerol and systolic blood pressure compared to baseline values (p < 0.001). Discussion: Providing a structured meal plan via vitamin‐ and mineral‐fortified liquid meal replacements is a safe and effective dietary strategy for obese patients. Long‐term maintenance of weight loss with meal replacements can improve certain biomarkers of disease risk.     

Weight Loss and Leptin Changes in Individuals with Type 2 Diabetes

WILLIAMS, KATHERINE V., MONICA MULLEN, WE1 LANG, ROBERT V. CONSIDINE, AND RENA R. WING. Weight loss and leptin changes in individuals with type 2 diabetes. Obes Res. Objective To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss. Research Methods and Procedures Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped ≥2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point. Results Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7±2.0 kg (p<0.001), and had significant decreases in leptin (5.2±7.0 ng/mL, p<0.001), fasting plasma glucose (1.8±1.8 mmol/L, p<0.001), and insulin (23±60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3±4.4 kg (P<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9±9.0 ng/mL, p<0.05) and insulin levels (+23±65 pmol/L, p<0.05), despite significant overall weight loss (-7.4±4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight. Discussion Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonyl-urea therapy were associated with increases in leptin levels despite weight loss.     

Effect of Energy‐Reduced Diets High in Dairy Products and Fiber on Weight Loss in Obese Adults

Objective: Studies suggest that high‐dairy and high‐fiber/low‐glycemic index diets may facilitate weight loss, but data are conflicting. The effects on weight loss and body fat of a high‐dairy diet and a diet high in dairy and fiber and low in glycemic index were compared with a standard diet. Research Methods and Procedures: Ninety obese subjects were recruited into a randomized trial of three diets designed to provide a calorie deficit of 500 calories/d over a 48‐week period. The study compared a moderate (not low)‐calcium diet with a high‐calcium diet. Results: Seventy‐two subjects completed the study. Significant weight and fat loss occurred with all three diets. A diet with 1400 mg of calcium did not result in greater weight (11.8 ± 6.1 kg) or fat (9.0 ± 6.0 kg) loss than a diet with 800 mg of calcium (10.0 ± 6.8 and 7.5 ± 6.6 kg, respectively). A diet with 1400 mg of calcium, increased fiber content, and fewer high‐glycemic index foods did not result in greater weight (10.6 ± 6.8 kg) or fat (8.5 ± 7.8 kg) loss than the standard diet with 800 mg of calcium. Lipid profile, high‐sensitivity C‐reactive protein, leptin, fasting glucose, and insulin improved significantly, but there were no significant differences between the experimental diets and the control diet. Discussion: We found no evidence that diets higher than 800 mg of calcium in dairy products or higher in fiber and lower in glycemic index enhance weight reduction beyond what is seen with calorie restriction alone.     

Exenatide Therapy in Obese Patients With Type 2 Diabetes Mellitus Treated with Insulin

ObjectiveTo evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.MethodsIn this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A_1c (HbA_1c), high-sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed.ResultsMean body weight (± standard error of the mean) decreased by 6.46 ± 0.8 kg (P < .001) in Group A and increased by 2.4 ± 0.6 kg in Group B (P < .001). In Group A, mean HbA_1c decreased by 0.6 ± 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P < .02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 ± 3.3% (P = .03), triglycerides by 26 ± 7.6% (P = .01), systolic blood pressure by 9.2 ± 3.3 mm Hg (P = .02), and high-sensitivity CRP by 34 ± 14.3% (P = .05). These indices did not change in Group B.ConclusionExenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA_lc, systolic blood pressure, triglycerides, and high-sensitivity CRP. (Endocr Pract 2007;13:444-450)     

Bupropion for Weight Loss: An Investigation of Efficacy and Tolerability in Overweight and Obese Women

Objective: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. Research Methods and Procedures: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m²) women were included. The core component of the study was a randomized, double‐blind, placebo‐controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double‐blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single‐blind follow‐up treatment for a total of 2 years. Results: Subjects receiving bupropion achieved greater mean weight loss (last‐observation‐carried‐forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% ± 3.4% (n = 25) for bupropion treatment compared with 1.3% ± 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% ± 3.1% (n = 18) vs. 1.6% ± 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% ± 5.6% with fat accounting for 73.5% ± 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well‐tolerated in this sample. Discussion: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

Weight Loss Expectations in Patients with Binge‐Eating Disorder

Objective: To study weight loss expectations in patients with binge‐eating disorder and to examine whether expectations differed by sex and motivation for treatment. Research Methods and Procedures: One hundred and thirty patients (104 women and 26 men), aged 23 to 61 (mean age, 43.0 years), with BED completed a measure of desired weights that included their dream weight, happy weight, acceptable weight, and disappointed weight. In a structured interview, participants were asked their primary motivation for seeking treatment (appearance or health) and their lowest adult weight (LAW). Results: The BED participants reported weight loss expectations that far exceeded expert and governmental guidelines. In this sample, desired dream body mass index (BMI), happy BMI, and acceptable BMI averaged reductions in current weight of 36%, 29%, and 23%, respectively. Even the “disappointed” BMI was an average 14% reduction in current weight, and was 1.5 to 3 times greater than the expert recommendation (5% to 10%). Comparisons of desired weights were significantly different for women and men, whereas percent reductions from current weight were not. Although weight goal expectations were significantly lower for those motivated by appearance, compared with those motivated by health, percent reductions for current weight were not. Desired dream weight correlated with reported LAW, and the mean difference between these weights was not significant. Discussion: These findings suggest that patients with BED have weight loss expectations that far exceed expert and governmental guidelines and that these expectations do not differ by sex or motivation for seeking treatment. One possible explanation for these unrealistic desired weights may be the patients’ recollections of their LAWs.     

Pramlintide as an Adjunct to Basal Insulin: Effects on Glycemic Control and Weight in Patients with Type 2 Diabetes Mellitus

Background: Pramlintide is a synthetic analogue of the β-cell hormone amylin. When used as an adjunct to mealtime insulin, it reduces postprandial glucose concentrations, glycosylated hemoglobin (AIC) values, and weight. Due to its effects on postprandial glucose, pramlintide may also provide similar benefits when used as an adjunct to basal insulin in the absence of mealtime insulin in patients with type 2 diabetes mellitus (DM).Objective: The current post hoc analyses examined the efficacy and tolerability of pramlintide as an adjunct to basal insulin in a subset of patients with type 2 DM in 2 clinical trials.Methods: Post hoc analyses of 2 subgroups of patients with type 2 DM treated with pramlintide and basal insulin (with or without oral agents) with no mealtime insulin are reported. One subgroup of patents was from a 52-week, randomized, double-blind, placebo-controlled study; a second subgroup of patients was from an uncontrolled, open-label study. Mean (SE) changes from baseline in A1C, postprandial glucose, weight, and insulin dose are reported. Tolerability was also assessed.Results: Baseline characteristics (mean [SD]) of the placebo-controlled study were as follows: pramlintide—n = 18; age, 59 (11) years; A1C, 9.4% (1.3%); weight, 88.4 (16.5) kg; body mass index (BMI), 31.8 (6.1) kg/m²; placebo—n = 11; age, 56 (9) years; A1C, 9.4% (1.6%); weight, 92.0 (13.4) kg; and BMI, 31.2 (5.1) kg/m². Baseline characteristics (mean [SD]) of the patients from the open-label study were as follows: N = 10; age, 60 (12) years; A1C, 8.1% (1.3%); weight, 109.2 (26.6) kg; and BMI, 35.7 (8.1) kg/m². In the placebo-controlled study, pramlintide treatment (120 μg BID) as an adjunct to basal insulin (neutral protamine Hagedorn, lente, or ultralente) resulted in mean (SE) reductions in A1C (pramlintide, -1.16% [0.22%]; placebo, -0.48% [0.18%]; P < 0.05) and weight (pramlintide, -2.3 [1.0] kg; placebo, -0.9 [1.0] kg) compared with placebo. Similarly, in the open-label study, pramlintide treatment (120 μg before major meals) as an adjunct to insulin glargine resulted in mean (SE) reductions from baseline in AIC (-0.81% [0.26%]; 95% CI, -1.40 to -0.22) and weight (-2.8 [1.0] kg; 95% CI, -5.12 to -0.47). In addition, mean postprandial glucose excursions, ascertained by self-monitoring of blood glucose readings, were reduced after each meal. In both subgroups, pramlintide was generally well tolerated, and there were no episodes of severe hypoglycemia.Conclusion: The improvements in glycemic control and weight in these post hoc analyses warrant further clinical investigation into the use of pramlintide as a potential next therapeutic step in patients with type 2 DM treated with basal insulin.     

Cardiometabolic Risk Profiles Associated with Chronic Complications in Overweight and Obese Type 2 Diabetes Patients in South China

Background

Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated.

Methods

We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m² who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted.

Results

Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88).

Conclusions

Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.     

Impact of Weight‐Cycling History on Bone Density in Obese Women

Objective: The purpose of this study was to examine the effect of weight cycling (as defined by the frequency and magnitude of intentional weight loss) on bone mineral density and bone mineral content in obese sedentary women. Research Methods and Procedures: Bone mineral content and density measured by DXA, submaximal physical fitness assessment, nutrient intake, oral contraceptive use, and weight‐cycling history were assessed in 195 healthy, overweight sedentary women (age, 21 to 45 years; body mass index, 27 to 40 kg/m²) before beginning a behavioral weight‐loss intervention. Results: After controlling for body weight, multivitamin use, oral contraceptive/estrogen use, and calcium and magnesium intake, women who had a history of weight cycling did not have significantly lower total‐body bone mineral content or density or total femur bone mineral density. In addition, 99% of subjects were above or within one SD of age and gender normative data for total femur bone mineral density. Discussion: It does not seem that a history of weight cycling has an adverse affect on total femur and total‐body bone mineral density in overweight sedentary premenopausal women.     

Prevention of Weight Gain in Adult Patients With Type 2 Diabetes Treated With Pioglitazone

Pioglitazone, a thiazolidinedione (TZD) commonly used to treat type 2 diabetes, is associated with weight gain. Our study was designed to examine the effectiveness of three lifestyle‐treatment programs of varying intensity on prevention of pioglitazone‐induced weight gain and to measure the composition of the change in body weight. Thirty‐nine adult overweight and obese subjects with type 2 diabetes mellitus were all treated with pioglitazone and prospectively randomized to one of three lifestyle‐treatment programs with increasing level of intensity for 24 weeks. Body composition was measured by dual‐energy X‐ray absorptiometry (DXA), computed tomography, and multifrequency bioimpedance analysis both before and after therapy. Subjects demonstrated a “dose‐response” effectiveness to three levels of lifestyle intervention to mitigate pioglitazone‐induced weight gain. Mean (s.d.) weight change (kg) for the usual, standard, and intensive lifestyle groups were 4.9 ± 4.9 (P = 0.005), 1.8 ± 3.4 (P = 0.02), and ?0.2 ± 4.4 (NS) respectively. Total body fat increased 2.6 ± 3.4 kg (P = 0.04) for the usual group and decreased for the intensive group ?0.4 ± 3.5 (NS). Change in abdominal subcutaneous and visceral adipose tissue (VAT) did not differ between groups, although ratio of visceral/subcutaneous fat decreased for the standard and intensive groups (NS). Both usual (P < 0.05) and standard care (NS) groups gained total body water. This is the first prospective, randomized study that demonstrates the beneficial effect of participation in a comprehensive lifestyle‐weight‐management program on lessening of weight gain associated with pioglitazone.     

Topiramate: Long‐Term Maintenance of Weight Loss Induced by a Low‐Calorie Diet in Obese Subjects

Objective: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low‐calorie diet. Research Methods and Procedures: Obese subjects (30 ≤ BMI < 50 kg/m²) 18 to 75 years old received a low‐calorie diet for 8 weeks. Those who lost ≥8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled‐release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. Results: Of the 701 subjects enrolled, 80% lost ≥8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run‐in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. Discussion: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low‐calorie diet—and produced additional clinically significant weight loss beyond that achieved by a low‐calorie diet.     

Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes: A Population-Based Cohort Study

Objective

This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25kg/m²) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients.

Methods

This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989–92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers.

Results

Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97–1.50, P = 0.10), 1.26 (0.93–1.72, P = 0.14), and 1.06 (0.79–1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight.

Conclusions

In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years.     

Obesity‐related Comorbidities in Obese African Americans in an Outpatient Weight Loss Program

Objective: To identify, among obese African‐American enrollees in an outpatient weight loss program, differences between those with and without obesity‐related comorbidities (ORCMs). Research Methods and Procedures: Data were from 237 obese African Americans (BMI, 30 to 50 kg/m²; 90% women) who enrolled in a 10‐week lifestyle weight loss program. Analyses compared subgroups defined by ORCM status (from medical history) on baseline characteristics, program attendance, and postprogram weight change. Results: Most participants (76%) had one or more ORCMs. Those with versus without ORCMs, respectively, were older (mean age, 45.6 vs. 37.1 years; p < 0.001), were less educated (59.2% vs. 76.6% with >12 years; p = 0.031), were more likely to perceive a physical limitation affecting activity (22.2% vs. 1.8%; p < 0.001), and had higher waist circumference (mean, 113.7 vs. 106.9 cm; p < 0.001) but not BMI (38.3 vs. 37.0 kg/m²; p = 0.095). Logistic regression analyses confirmed the independence of these associations. Having ORCMs was not associated with class attendance or return for data collection after the 10‐week program. Postprogram weight change (n = 134) was unrelated to ORCMs, but better weight loss was seen among those without perceived physical limitations (1.9 vs. 0.4 kg in those without versus with limitations; p = 0.069). Conclusion: Data from this clinical sample of obese African Americans suggest that waist circumference is relevant to ORCM status at BMI levels up to 50 kg/m². Clear indications for tailoring of treatment based on ORCM status were not identified, although the possible influence of ORCM‐related activity limitations warrants further study.     

Effect of Glucose Tolerance Status on PAI‐1 Plasma Levels in Overweight and Obese Subjects

Objective: The aim of our study was to examine whether plasminogen activator inhibitor‐1 (PAI‐1) plasma levels varied as a function of differences in glucose tolerance status independently of body fatness, body‐fat distribution, and insulin sensitivity. Research Methods and Procedures: Plasma PAI‐1 antigen levels, along with insulin resistance [measured by homeostatic model assessment (HOMA_IR)], central fat accumulation, body composition, blood pressure, and fasting concentrations of glucose, insulin, and lipids, were measured in 229 overweight and obese [body mass index (BMI) ≥25 kg/m²) subjects with normal glucose tolerance (NGT) and in 44 age‐ and BMI‐matched subjects with impaired glucose tolerance (IGT). Results: Plasma PAI‐1 antigen levels were significantly higher in IGT than in NGT subjects. Log PAI‐1 was positively correlated with BMI, HOMA_IR, and log insulin, and inversely associated with high‐density lipoprotein‐cholesterol both in IGT and in NGT individuals. On the other hand, log PAI‐1 was positively correlated with waist circumference, fat mass (FM), fat‐free mass, systolic and diastolic blood pressure, and log triglycerides only in the NGT group. After multivariate analyses, the strongest determinants of PAI‐1 levels were BMI, FM, waist circumference, and high‐density lipoprotein cholesterol in the NGT group and only HOMA_IR in the IGT cohort. Discussion: This study demonstrates that PAI‐1 concentrations are higher in IGT than in NGT subjects. Furthermore, we suggest that the influences of total adiposity, central fat, and insulin resistance, main determinants of PAI‐1 concentrations, are different according to the degree of glucose tolerance.