High protein weight loss diets in obese subjects with type 2 diabetes mellitus.

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.

Interpreting different measures of glomerular filtration rate in obesity and weight loss: pitfalls for the clinician.

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.

No evidence of an additive inhibitory feeding effect following PP and PYY 3-36 administration.

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.

Relationship between serum 25-hydroxyvitamin D and bone resorption markers in vitamin D insufficiency.

It is known that nursing-home patients with vitamin D insufficiency have elevated serum parathyroid hormone (PTH) as well as raised serum alkaline phosphatase (ALP). Although it is well known that vitamin D insufficiency and secondary hyperparathyroidism are common among the elderly in western countries, there is continuing controversy over the level of serum 25-hydroxyvitamin D [25(OH)D] necessary for bone health. We approached this issue by examining the relationships between serum 25(OH)D, ionized calcium, PTH, and ALP and the urinary bone resorption markers hydroxyproline, pyridinoline, and deoxypyridinoline, corrected for creatinine (OHPr/Cr, Pyd/Cr, and Dpd/Cr, respectively), in 486 postmenopausal women of mean age 63 (SD 9.5) years, who were referred to our osteoporosis and menopause clinics for investigation. When the patients were divided into two groups with 25(OH)D above and below 20 nmol/L, 30 nmol/L, 40 nmol/L, 50 nmol/L, 60 nmol/L, or 70 nmol/L, the most significant differences between the two groups thus derived was found at a serum 25(OH)D level of 60 nmol/L (P < 0.001 for all markers). The most significant difference between groups for serum PTH was found when the patients were divided at a serum 25(OH)D of 50 nmol/L. PTH, OHPr/Cr, Pyd/Cr, and ALP were inversely related to serum 25(OH)D. PTH was inversely related to serum ionized calcium. There was a trend for ionized calcium to be positively related to 25(OH)D, but this did not reach statistical significance. We conclude that rises in three bone resorption markers and ALP can be detected in postmenopausal women when the serum 25(OH)D level falls below 60 nmol/L. Levels above this may be required for optimal bone health.

A 6-month study of the efficacy and safety of tadalafil in the treatment of erectile dysfunction: a randomised, double-blind, parallel-group, placebo-controlled study in Australian men.

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.