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Objective: Obesity and type 2 diabetes mellitus (T2DM) have been associated with increased levels of circulating branched-chain amino acids (BCAAs) that may be involved in the pathogenesis of insulin resistance. However, weight loss has not been consistently associated with the reduction of BCAA levels., Research Design and Methods: We included 30 obese normal glucose-tolerant (NGT) subjects, 32 obese subjects with T2DM, and 12 lean female subjects. Obese subjects underwent either a restrictive procedure (gastric banding [GB], a very low-calorie diet [VLCD]), or a restrictive/bypass procedure (Roux-en-Y gastric bypass [RYGB] surgery). Fasting blood samples were taken for the determination of amine group containing metabolites 4 weeks before, as well as 3 weeks and 3 months after the intervention., Results: BCAA levels were higher in T2DM subjects, but not in NGT subjects, compared with lean subjects. Principal component (PC) analysis revealed a concise PC consisting of all BCAAs, which showed a correlation with measures of insulin sensitivity and glucose tolerance. Only after the RYGB procedure, and at both 3 weeks and 3 months, were circulating BCAA levels reduced., Conclusions: Our data confirm an association between deregulation of BCAA metabolism in plasma and insulin resistance and glucose intolerance. Three weeks after undergoing RYGB surgery, a significant decrease in BCAAs in both NGT as well as T2DM subjects was observed. After 3 months, despite inducing significant weight loss, neither GB nor VLCD induced a reduction in BCAA levels. Our results indicate that the bypass procedure of RYGB surgery, independent of weight loss or the presence of T2DM, reduces BCAA levels in obese subjects., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes., Research Design and Methods: A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and -11377) were examined in these subjects., Results: After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype., Conclusions: ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.

Objective: We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S(I)), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference., Research Design and Methods: Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S(I) and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S(I) with AIR. Multiple linear regression modeling was employed., Results: No association was observed between glycemic index and S(I), fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S(I), insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S(I) and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR., Conclusion: Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.

Objective: To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT)., Research Design and Methods: This study compared the effects of an American Heart Association (AHA) step 2 diet (<30% of total calories as fat, <7% saturated fat, 55% carbohydrate, and < 200 mg cholesterol daily) plus endurance exercise for 1 h three times a week (treatment group) with an AHA step 1 diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and <300 mg cholesterol) plus stretching exercise three times a week (control group) on BMI, body composition (% fat), and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT, 58 of whom completed the study., Results: At 6 months, the treatment group showed significantly greater reduction in percent, body fat (-1.4 +/- 0.4 vs. -0.3 +/- 0.3%); BMI (-1.1 +/- 0.2 vs. -0.4 +/- 0.1 kg/m(2)); subcutaneous fat by computed tomography at the abdomen (-29.3 +/- 4.2 vs. -5.7 +/- 5.9 cm(2)), thigh (-13.2 +/- 3.6 vs. -3.6 +/- 3.0 cm(2)), and thorax (-19.6 +/- 3.6 vs. -8.9 +/- 2.6 cm(2)); and skinfold thickness at the bicep (-2.0 +/- 0.6 vs. 1.1 +/- 0.6 mm) and tricep (-3.7 +/- 0.8 vs. -0.9 +/- 0.6 mm), which continued despite moving to home-based exercise for the last 18 months., Conclusions: Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT.

Objective: To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance., Research Design and Methods: A 5-year Follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0-11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = l04), 3 years (n = 99), and 5 years (n = 103)., Results: Compared with the control group, weight decreased in the reduced-fat-diet group (P < 0.0001); the greatest difference was noted at 1 year (-3.3 kg), diminished at subsequent follow-up (-3.2 kg at 2 years and -1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P < 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026 respectively) compared with control subjects., Conclusions: The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake

Objective: The effects of altering meal frequency on measures of glucose and lipid metabolism in type 2 diabetes were examined by comparing isocaloric dietary regimens in which daily food intake was provided by three or nine meals each day., Research Design and Methods: A total of 13 free-living men and women with type 2 diabetes or persistently impaired glucose tolerance participated in a randomized crossover study in which three- and nine-meal regimes were followed for 4-week periods. Fasting plasma lipid and lipoprotein, glucose and insulin concentrations were measured at weekly intervals and glucose, insulin, and triglyceride responses following a 75-g glucose load at weeks 2 and 4 of each diet period. Dietary intake was also recorded during these weeks., Results: Nutrient intakes and all measures of carbohydrate and lipid metabolism were similar on the three- and nine-meal regimes., Conclusions: This longer-term study could not confirm the potential benefits of increased meal frequency suggested by comparable 4-week studies in type 2 diabetic individuals and acute experiments in individuals with diabetes. However, as there were no adverse effects of consuming nine meals per day, it would seem appropriate that meal frequency in those with type 2 diabetes should be left to personal choice, provided that energy balance is maintained.

Objective: Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications., Research Design and Methods: In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment., Results: The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or > or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively., Conclusions: Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

Objective: To emphasis the need for timely diagnosis of Alström syndrome., Case: We report a case of late-detected Alström syndrome in a boy 15 1/2 years of age who was admitted because of poor wound healing and hyperglycemia., Results: Diagnosis was made and the patient's impaired glucose tolerance improved by diet., Conclusions: Regular follow-ups are needed to recognize and possibly prevent late-appearing complications.

Objective: To determine whether a 2-year lifestyle intervention program improves glucose tolerance and lipid levels in people with persistent impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM)., Research Design and Methods: Screening for IGT and NIDDM was carried out in 1,752 people. Subjects with persistent IGT or NIDDM completed three 2-h oral glucose tolerance tests (OGTTs) before the start of the study and after 2 years. A single OGTT was carried out every 3 months. A 4-day food diary and a 7-day exercise diary were completed, and weight, blood pressure, glycated hemoglobin (HbA1), plasma lipids, and fasting and 2-h serum insulin were measured at baseline and every 3 months. Subjects were encouraged to make dietary changes and increase exercise., Results: Thirty-two subjects with persistent IGT and 20 subjects with NIDDM were recruited. Women reported significant decreases in total and saturated fat and an increase in carbohydrate, but few subjects reached the recommended intakes. Men achieved smaller dietary changes. There were significant decreases in body mass index, fasting and 2-h plasma glucose, HbA1, total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels in both the IGT and NIDDM groups during the study., Conclusions: Results suggest that a diet and exercise program can result in significant improvements in a range of clinical and metabolic variables in some people with IGT or NIDDM, although the absence of a control group precludes firm conclusions. Screening for IGT in those at high risk for developing NIDDM and offering those with persistent IGT a lifestyle intervention program could help reduce the progression of IGT to NIDDM.