The case for a ketogenic diet in the management of kidney disease.

Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease.

Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes.

OBJECTIVE: Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels. RESEARCH DESIGN AND METHODS: Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-controlled study. RESULTS: In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered. CONCLUSIONS: We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin's associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin.

Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet.

OBJECTIVE: Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified. METHODS: In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months. RESULTS: Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups. CONCLUSIONS: Leptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans.

To elucidate whether the role of leptin in regulating neuroendocrine and immune function during short-term starvation in healthy humans is permissive, i.e., occurs only when circulating leptin levels are below a critical threshold level, we studied seven normal-weight women during a normoleptinemic-fed state and two states of relative hypoleptinemia induced by 72-h fasting during which we administered either placebo or recombinant methionyl human leptin (r-metHuLeptin) in replacement doses. Fasting for 72 h decreased leptin levels by approximately = 80% from a midphysiologic (14.7 +/- 2.6 ng/ml) to a low-physiologic (2.8 +/- 0.3 ng/ml) level. Administration of r-metHuLeptin during fasting fully restored leptin to physiologic levels (28.8 +/- 2.0 ng/ml) and reversed the fasting-associated decrease in overnight luteinizing hormone pulse frequency but had no effect on fasting-induced changes in thyroid-stimulating hormone pulsatility, thyroid and IGF-1 hormone levels, hypothalamic-pituitary-adrenal and renin-aldosterone activity. FSH and sex steroid levels were not altered. Short-term reduction of leptin levels decreased the number of circulating cells of the adaptive immune response, but r-metHuLeptin did not have major effects on their number or in vitro function. Thus, changes of leptin levels within the physiologic range have no major physiologic effects in leptin-replete humans. Studies involving more severe and/or chronic leptin deficiency are needed to precisely define the lower limit of normal leptin levels for each of leptin's physiologic targets.