clinicaltrials.gov Identifier: NCT00195858.

People with diabetes should receive nutrition counselling by a registered dietitian. Nutrition therapy can reduce glycated hemoglobin (A1C) by 1.0% to 2.0% and, when used with other components of diabetes care, can further improve clinical and metabolic outcomes. Reduced caloric intake to achieve and maintain a healthier body weight should be a treatment goal for people with diabetes who are overweight or obese. The macronutrient distribution is flexible within recommended ranges and will depend on individual treatment goals and preferences. Replacing high glycemic index carbohydrates with low glycemic index carbohydrates in mixed meals has a clinically significant benefit for glycemic control in people with type 1 and type 2 diabetes. Intensive lifestyle interventions in people with type 2 diabetes can produce improvements in weight management, fitness, glycemic control and cardiovascular risk factors. A variety of dietary patterns and specific foods have been shown to be of benefit in people with type 2 diabetes. Consistency in carbohydrate intake and in spacing and regularity in meal consumption may help control blood glucose and weight. Energy As an estimated 80% to 90% of people with type 2 diabetes are overweight or obese, strategies that include energy restriction to achieve weight loss are a primary consideration (26). A modest weight loss of 5% to 10% of initial body weight can substantially improve insulin sensitivity, glycemic control, hypertension and Contents lists available at SciVerse ScienceDirect Canadian Journal of Diabetes j o u r n a l h o m e p a g e : w w w. c a n a d ia n j o u r n a l o f d i a b e t e s. c o m

Resistance training, alone or in combination with aerobic training, may provide psychological benefits in adolescents with overweight or obesity, and therefore could be an alternative to aerobic training for some individuals in the biological and psychological management of adolescent obesity.

OBJECTIVE-We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it. RESEARCH DESIGN AND METHODS-Hyperinsulinemic(ϳ570 pmol/l), euglycemic (5.5 mmol/l), and isoaminoacidemic (kept at postabsorptive concentrations) clamps were performed in 17 hyperglycemic type 2 diabetic subjects and 23 subjects without diabetes matched for age and body composition, after 7 days on a inpatient, protein-controlled, isoenergetic diet. Glucose and leucine kinetics were determined using tracers.RESULTS-In type 2 diabetes, postabsorptive (baseline) glycemia was 8 -9 mmol/l, glucose production (R a ) and disposal (R d ) were elevated, and once clamped, endogenous glucose R a remained greater and R d was less (P Ͻ 0.05) than in control subjects. Baseline leucine kinetics did not differ despite higher insulin levels. The latter was an independent predictor of leucine flux within each sex. With clamp, total flux increased less (P ϭ 0.016) in type 2 diabetic men, although protein breakdown decreased equally (ϳ20%) in male groups but less in female groups. Whereas protein synthesis increased in male control subjects and in both female groups, it did not in male subjects with type 2 diabetes. In men, homeostasis model assessment of insulin resistance predicted 44%, and, in women, waist-to-hip ratio predicted 40% of the change in synthesis. T here is clear evidence for altered protein metabolism in type 1 diabetes (1-5), but in type 2 diabetes, results have been inconsistent. That protein metabolism in type 2 diabetes has been reported to be both unaffected and altered may stem from differences in study design: tracer method, adiposity, and sex of subjects; prevailing glycemia; normalization of data; and types of statistical analyses. We reported accelerated integrated fed-fasted kinetics of whole-body protein metabolism (using [ 15 N]glycine) in obese type 2 diabetic subjects with hyperglycemia (6 -9) compared with obese control subjects (6,7). Such studies required adjusting data for fat-free mass (FFM), sex, and age (6,8,9) and had precise control of protein and energy intake. When glycemic control was normalized with insulin (7), improved with oral antihyperglycemic agents (6), or normalized with oral agents and energy restriction (6), protein turnover was either improved or not different from that of obese control subjects. CONCLUSIONS-DuringMost reports showing no alterations in type 2 diabetes (10 -14) assessed postabsorptive and postinsulin states using amino acid tracers. However, one reported elevated postabsorptive catabolism in hyperglycemic type 2 diabetic patients, not corrected by prior insulin treatment (15). Another showed elevated rates of leucine transamination that decreased with better glycemic control, without altering leucine oxidation (16)....

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover Abstract Aims/hypothesis: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. Materials and methods: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N G -monomethyl-L-arginine (NMMA), lipids and body composition were measured. Results: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75× in obese men and by 1.27× in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). Conclusions/ interpretation: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

BACKGROUND: Predictive equations have been reported to overestimate resting energy expenditure (REE) for obese persons. The presence of hyperglycemia results in elevated REE in obese persons with type 2 diabetes, and its effect on the validity of these equations is unknown. OBJECTIVE: We tested whether (1) indicators of diabetes control were independent associates of REE in type 2 diabetes and (2) their inclusion would improve predictive equations. DESIGN: A cross-sectional study of 65 (25 men, 40 women) obese type 2 diabetic subjects. Variables measured were: REE by ventilated-hood indirect calorimetry, body composition by bioimpedance analysis, body circumferences, fasting plasma glucose (FPG) and hemoglobin A 1c . Data were analyzed using stepwise multiple linear regression. RESULTS: REE, corrected for weight, fat-free mass, age and gender, was significantly greater with FPG > 10 mmol=l (P ¼ 0.017) and correlated with FPG (P ¼ 0.013) and hemoglobin A 1c as percentage upper limit of normal (P ¼ 0.02). Weight was the main determinant of REE. Together with hip circumference and FPG, it explained 81% of the variation. FPG improved the predictability of the equation by > 3%. With poor glycemic control, it can represent an increase in REE of up to 8%. CONCLUSION: Our data indicate that in a population of obese subjects with type 2 diabetes mellitus, REE is better predicted when fasting plasma glucose is included as a variable.

ObjectiveWe performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program.Research Design and MethodsPotential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts.ResultsAmong the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children.ConclusionsAmong women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.

Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNG PEP (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2 H nuclear magnetic resonance spectroscopy of plasma glucose. Whole-body 13 C-leucine and 3 Hglucose kinetics were measured in the postabsorptive state and during a hyperinsulinemic-euglycemic-isoaminoacidemic clamp in 19 (10 men and 9 women) lean and 16 (7 men and 9 women) obese nondiabetic subjects. Endogenous glucose production was not different between groups. Postabsorptive %GNG PEP and GNG PEP flux were higher in obese subjects, and glycogenolysis contributed less to glucose production than in lean subjects. GNG PEP flux correlated with all indexes of adiposity and with postabsorptive leucine rate of appearance (R a ) (protein catabolism). GNG PEP was negatively related to the clamp glucose rate of disposal (R d ) and to the protein anabolic response to hyperinsulinemia. In conclusion, the increased contribution of GNG to glucose production in obesity is linked to increased postabsorptive protein catabolism and insulin resistance of both glucose and protein metabolism. Due to increased protein turnover rates, greater supply of gluconeogenic amino acids to the liver may trigger their preferential use over glycogen for glucose production. Diabetes 55:675-681, 2006 T he increased fractional contribution of gluconeogenesis (GNG) to postaborptive endogenous glucose production (EGP) in type 2 diabetes is well established (1), but its role in obesity is less clear. Elevated GNG has also been reported in obesity but is associated with a smaller contribution of glycogenolysis (GLY), and hence with no increase in EGP, and therefore euglycemia (2-4). Thus, since hepatic autoregulation (5) is apparently intact in obese subjects, it is not immediately clear what mechanism is responsible for increased GNG. Such autoregulation does not appear to be intact in type 2 diabetes (2,3,6), but it remains uncertain whether it causes increased EGP as hyperglycemia increases (1)(2)(3)7,8). Insulin resistance is a hallmark of both type 2 diabetes and obesity, affecting not only glucose and lipid metabolism (9) but protein as well. We have shown that whole-body protein catabolism is increased in hyperglycemic type 2 diabetic people but improves when normoglycemia is achieved with insulin and oral antihyperglycemic agents and with hypoenergetic feeding (10,11). Recently, we reported that postabsorptive rates of endogenous leucine rate of appearance (R a ) (index of protein catabolism) are increased in obese compared with lean women (12). Further, it is well known that when the portal vein glucagon/insulin relationship favors GNG, its rate can be controlled by the supply of substrate from the periphery (9,13). Taken together, these data led us to hypothesize that elevated protein catabolism in obesity contributes to higher GNG via incr...