Aims/hypothesis Short-term dietary studies suggest that high-protein diets can enhance weight loss and improve glycaemic control in people with type 2 diabetes. However, the long-term effects of such diets are unknown. The aim of this study was to determine whether high-protein diets are superior to high-carbohydrate diets for improving glycaemic control in individuals with type 2 diabetes. Methods Overweight/obese individuals (BMI 27-40 kg/m 2 ) with type 2 diabetes (HbA 1c 6.5-10%) were recruited for a 12 month, parallel design, dietary intervention trial conducted at a diabetes specialist clinic (Melbourne, VIC, Australia). Of the 108 initially randomised, 99 received advice to follow low-fat (30% total energy) diets that were either high in protein (30% total energy, n=53) or high in carbohydrate (55% total energy, n=46). Dietary assignment was done by a third party using computer-generated random numbers. The primary endpoint was change in HbA 1c . Secondary endpoints included changes in weight, lipids, blood pressure, renal function and calcium loss. Study endpoints were assessed blinded to the diet group, but the statistical analysis was performed unblinded. This study used an intention-to-treat model for all participants who received dietary advice. Follow-up visits were encouraged regardless of dietary adherence and last measurements were carried forward for study non-completers. Results Ninety-nine individuals were included in the analysis (53 in high protein group, 46 in high carbohydrate group). HbA 1c decreased in both groups over time, with no significant difference between groups (mean difference of the change at 12 months; 0.04 [95% CI −0.37, 0.46]; p=0.44). Both groups also demonstrated decreases over time in weight, serum triacylglycerol and total cholesterol, and increases in HDL-cholesterol. No differences in blood pressure, renal function or calcium loss were seen. Conclusions/interpretation These results suggest that there is no superior long-term metabolic benefit of a high-protein diet over a high-carbohydrate in the management of type 2 diabetes.

Objective: Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action. Research Methods and Procedures: Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/⌬I) was determined by hyperinsulinemic-euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long-chain acyl-CoA esters (LCAC). Results: Significant inverse relationships were observed between LCAC and M/⌬I (R 2 ϭ 0.34, p ϭ 0.01) and between CF and M/⌬I (R 2 ϭ 0.38, p ϭ 0.006), but not between CF and LCAC (R 2 ϭ 0.0005, p ϭ 0.93). In a multiple regression model (R 2 ϭ 0.71, p Ͻ 0.0001), both CF (p ϭ 0.0006) and LCAC (p ϭ 0.0009) were independent statistical predictors of M/⌬I. Leptin levels correlated inversely with M/⌬I (R 2 ϭ 0.60, p ϭ 0.0002) and positively with central (R 2 ϭ 0.41, p ϭ 0.006) and total body fat (R 2 ϭ 0.63, p ϭ 0.0001). Discussion:The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.

OBJECTIVE:To investigate whether normal glucose-tolerant and type II diabetic overweight adults differ in response to weight regain with regard to substrate oxidation and metabolic parameters. METHODS: A total of 15 overweight-obese subjects: seven normal glucose tolerant (NGT) and eight with type II diabetes (DM) were restudied 5 y after significant weight loss. Prediet, after 28 days calorie restriction and at 5 y, subjects were characterised for weight, height, waist-to-hip ratio (WHR) and body composition by dual-energy X-ray absorptiometry. Fasting glucose, insulin, leptin and lipid levels were measured and subjects underwent euglycaemic-hyperinsulinaemic clamp (insulin 0.25 U/kg/h for 150 min). Indirect calorimetry was performed resting and in the final 30 min of the clamp. Dietary assessment was by 4-day dietdiary. RESULTS: Both NGT and DM groups regained weight at 5 y and were not different to prediet. Total body fat (%) and WHR were higher at 5 y compared to prediet in both groups. Fasting glucose was increased in NGT subjects at 5 y, and fasting insulin was higher in both groups at 5 y compared to prediet. Insulin sensitivity (GIR) was similar at 5 y compared to prediet, but at 5 y DM subjects were more insulin resistant than NGT subjects. At 5 y, both DM and NGT groups had significantly reduced basal fat oxidation and no significant suppression of fat oxidation with insulin. Clamp respiratory quotient levels at 5 y were significantly higher in NGT compared to DM subjects. CONCLUSION: Reduced basal fat oxidation, and reduced variation in substrate oxidation in response to insulin develop with fat regain and fasting hyperinsulinaemia in both NGT and DM obese adults.

By design, the HFMs were not isocaloric but the presence of carbohydrate in a HFM invoked an insulin response that significantly reduced the 4 h postprandial triglyceride response even in healthy, normolipidaemic subjects. This phenomenon may have clinical implications, particularly in relation to insulin sensitivity.