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Objective: The use of fasting plasma glucose (FPG) level > or =7.0 mmol/l leads to underdiagnosis of type 2 diabetes compared with the oral glucose tolerance test (OGTT). The OGTT is of limited use for population screening. Most of the increase in cardiovascular risk in relation to increasing blood glucose occurs before the threshold at which the diagnosis of type 2 diabetes is made. The aim of this study was to evaluate the use of HbA(1c) and FPG as predictors of type 2 diabetes and cardiovascular risk and, accordingly, to develop a rational approach to screening for abnormalities of glucose tolerance.Research Design and Methods: OGTT and measurement of HbA(1c) and FPG levels were performed in 505 subjects screened for type 2 diabetes. Anthropomorphic measurements were obtained. A cardiovascular risk factor questionnaire was completed.Results: The subjects were aged 19-88 years (mean 53.8). The incidence of type 2 diabetes was 10.4% based on the OGTT and 4% based on an FPG level > or =7.0 mmol/l. Using high-performance liquid chromatography (HPLC), HbA(1c) of <4.7 and > or =6.2% predicted with certainty the absence or presence of type 2 diabetes as defined by the OGTT. The corresponding cutoffs were <5.0 and > or =6.8% for HbA(1c) (DCA2000 HPLC device; Bayer Diagnostics, Mulgrave, Australia) and <4.7 and > or =6.4 mmol/l for FPG. However, 75-85% of subjects in each case had intermediate values, which were therefore nondiagnostic. Cardiovascular risk increased at least 2.2 times at an HbA(1c) level > or =6.2% (by HPLC), 1.8-2.2 times at an HbA(1c) level of 5.6-6.1% (by HPLC), 2 times at an FPG level > or =6.4 mmol/l, and 1.7-1.9 times at an FPG level of 5.6-6.3 mmol/l.Conclusions: Measurement of FPG and HbA(1c) levels will diagnose or exclude type 2 diabetes with certainty in a minority (15%) of people. There is a continuous relationship between FPG and HbA(1c) and cardiovascular risk. Accordingly, we propose that there is a rational basis for using either FPG and HbA(1c) for purposes of screening and assigning risk. Individuals with an HbA(1c) level of 5.6-6.1% and an FPG level of 5.6-6.3 mmol/l are at greatest risk for cardiovascular disease and should be targeted for further evaluation. An algorithm outlining a cost-effective approach is presented. [ABSTRACT FROM AUTHOR]

Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY(3-36) would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY(3-36) or PP+PYY(3-36) (n=7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg(-1) PP and by 6 nmol kg(-1) PYY(3-36) (P<0.05) but not significantly following 3 nmol kg(-1) PP+3 nmol kg(-1) PYY(3-36). In a higher dose study 30 nmol kg(-1) PP, 30 nmol kg(-1) PYY(3-36) and 30 nmol kg(-1) PP+30 nmol kg(-1) PYY(3-36) all inhibited 1 h food intake compared with saline (P<0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg(-1)min(-1) PP, 0.4 pmol kg(-1)min(-1) PYY(3-36) and 4 pmol kg(-1)min(-1) PP+0.4 pmol kg(-1)min(-1) PYY(3-36). A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP+PYY(3-36) treatment (buffet meal energy intake (KJ): saline 2633+/-204, PP+PYY 2693+/-254, PP 2367+/-199, PYY 2511+/-196). These results suggest that PP and PYY(3-36) do not inhibit feeding additively in rodents or humans. [ABSTRACT FROM AUTHOR]

We have shown that the capacity of 25g whey preloads to slow gastric emptying and reduce postprandial glycaemia persists after 4 weeks regular exposure in patients with diet-controlled type 2 diabetes. This dietary strategy therefore appears feasible for larger clinical trials to evaluate beneficial effects on long-term glycaemic control. Registered with the Australian New Zealand Clinical Trials Registry: ACTRN12614000831684., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background and Aim: Diets where carbohydrate has been partially exchanged for protein have shown beneficial changes in persons with type 2 diabetes but no studies have enrolled people with albuminuria. We aim to determine if a high protein to carbohydrate ratio (HPD) in an energy reduced diet has a beneficial effect on metabolic control and cardiovascular risk factors without negatively affecting renal function., Method and Results: Adult, overweight participants with type 2 diabetes, with albuminuria (30-600 mg/24 h or an albumin-to-creatinine ratio of 3.0-60 mg/mmol), and estimated GFR of >40 ml/min/1.73 m(2) were enrolled. Participants were randomized to an HPD or an SPD. Protein:fat:carbohydrate ratio was 30:30:40% of energy for the HPD and 20:30:50% for the SPD. Main outcomes were renal function, weight loss, blood pressure, serum lipids and glycaemic control. We recruited 76 volunteers and 45 (35 men and 10 women) finished. There were no overall changes in renal function at 12 months and no significant differences in weight loss between groups (9.7 ± 2.9 kg and 6.6 ± 1.4 kg HPD and SPD group respectively; p = 0.32). Fasting blood glucose decreased significantly with no treatment effect. The decrease in HbA1c differed between treatments at 6 months (HPD -0.9 vs. SPD -0.3%; p = 0.039) but not at 12 months. HDL increased significantly with no treatment effects. There were no changes in LDL or blood pressure overall but DBP was lower in the HPD group (p = 0.024) at 12 months., Conclusion: Weight loss improved overall metabolic control in this group of well controlled participants with type 2 diabetes regardless of diet composition., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Higher-protein weight-loss diets (defined as >25% of energy as protein) are not recommended for individuals with type 2 diabetes because of their potential adverse effect on renal function., Objective: We aimed to examine the effect of such diets on renal function over 12 mo in people with type 2 diabetes and early renal disease., Design: Overweight and obese people with type 2 diabetes were screened to identify those with an albumin:creatinine ratio from 3 to 30 mg/mmol. Seventy-six subjects were randomly assigned to either a moderate-protein weight-loss diet or a standard-protein weight-loss diet for 12 mo. The primary endpoint was the change in renal function as assessed by the isotope glomerular filtration rate (GFR), estimated GFR, and cystatin C. Forty-five subjects (moderate protein: n = 21; standard protein: n = 24) completed the study., Results: The mean (±SE) weight loss was not different between diets at 9.7 ± 13.4 kg for the moderate-protein diet and 6.6 ± 7.1 kg for the standard-protein diet. There were no changes in renal function or albuminuria or blood pressure, although glycated hemoglobin was lowered with both diets. Changes in renal function were related to the baseline estimated GFR. Patients with stage 1-3 renal disease (<120 mL · min(-1) · 1.73 m(-2); n = 33) had an improvement in renal function, whereas patients with hyperfiltration (>120 mL · min(-1) · 1.73 m(-2); n = 12) had a decrease in the GFR. After adjustment for weight loss, the baseline GFR remained a significant predictor of outcomes with no effect of dietary treatment. An average difference in protein intake between diets of 19 ± 6 g/d was achieved., Conclusion: Weight loss improved renal function, but differences in dietary protein had no effect. This trial was registered at the Australian and New Zealand Clinical Trial Register as ACTRN12608000045314.

To combat the increasing incidence of obesity, much research has been devoted to devising successful strategies for weight loss, including manipulation of diet and gastric surgery. Obesity itself can be associated with renal dysfunction, and the degree of reversibility of this with weight loss has being studied. However, there are significant limitations and flaws in the methods we have available to measure glomerular filtration rate (GFR) in overweight and obese subjects. Obesity is associated with changes in body composition including lean and fat mass. This has implications for assumptions that underpin creatinine-based measures such as creatinine clearance, estimated GFR and other equations devised for obesity including the Salazar-Corcoran equation. These changes in body composition also affect measures of glomerular filtration such as cystatin C and nuclear medicine isotope scans. This article will review the accuracy of these current measures of renal function in the obese and consider the evidence for adjusting for body surface area or adjusting for lean body mass. Finally, the effect of weight loss itself on serial measurements of renal function in a given individual, independent of a true change in renal function, will be reviewed. Ultimately using the Cockcroft-Gault equation with an adjustment for lean body mass seems to be the best measure for renal function in obesity. No method for measuring renal function in situations of weight loss has been shown to be unequivocally superior.

The efficacy and safety of tadalafil for the treatment of erectile dysfunction (ED) were assessed in a 6-month, randomised, double-blind, placebo-controlled study. Australian men with mild, moderate or severe ED of organic, psychogenic or mixed aetiology were randomised to tadalafil 20 mg as needed (n = 93) or placebo (n = 47). Efficacy assessments included the international index of erectile function (IIEF) and the sexual encounter profile (SEP) diary. Tadalafil significantly improved erectile function compared with placebo (p < 0.001, all measures). At the end of the study, the mean per-patient proportion of successful sexual intercourse attempts (SEP question three) was 73.5% for patients treated with tadalafil and 26.8% for placebo-treated patients. Improved erections were reported by 78% of tadalafil-treated patients compared to 12.8% of placebo-treated patients. The most common treatment-emergent adverse events--headache and dyspepsia--were generally mild or moderate. Tadalafil was effective and well tolerated in Australian men with mild to severe ED.