Is severe obesity a cardiovascular health concern in the Inuit population?

OBJECTIVES: Obesity is rising globally and severe obesity (SO) [body mass index (BMI) = 40 kg/m(2) or = 35 kg/m(2) with co-morbidity] is growing at a much faster rate. Amongst the Inuit, evolution of SO remains unknown. We investigated whether the level of SO changed and whether the cardio-metabolic profile improved or deteriorated in Nunavik Inuit between 1992 and 2004. METHODS: SO subjects were selected from two comparable population-based studies. These studies were undertaken in Nunavik (Quebec, Canada), and were performed in two different time frames, separated by 12 years. Physiological (lipid profile, fasting insulin, fasting glucose, and blood pressure) as well as anthropometric data (BMI, waist circumference, and waist to hip ratio) were collected in both studies. RESUTLS: There was approximately a fourfold increase in the prevalence of SO in comparable age groups. This increase affected both genders between 1992 and 2004. Smoking rates in SO populations have significantly decreased during this period, from 85% to 41% (P < 0.0001). Overall, there were no statistically significant differences in the cardio-metabolic profile (insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, systolic and diastolic blood pressures, BMI, and waist to hip ratio). There was, however, a significant increase in waist circumference (P < 0.001), especially in women (P < 0.01). Type 2 diabetes remained stable, at around 40% in this population. CONCLUSION: Although the prevalence of SO increased, the cardio-metabolic profile remained stable. Nevertheless, regular monitoring of chronic disease in this population remains crucial.

Acute hyperaminoacidemia does not suppress insulin-mediated glucose turnover in healthy young men.

Elevated circulating amino acids (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed 2-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels. During the clamp stage, insulin was raised to postprandial levels, glycemia clamped at 5.5 mmol/L by glucose infusion, and branched-chain AA (BCAA) maintained at either postabsorptive (Hyper1; n = 8) or postprandial (Hyper2; n = 7) by AA infusion. Glucose turnover was measured by d-3-[3H]glucose dilution. Octreotide suppressed C-peptide; glucagon, growth hormone, and glycemia were maintained at postabsorptive levels throughout. Insulin did not differ at postabsorptive (72 ± 5 vs. 60 ± 5 pmol/L; Hyper1 vs. Hyper2) and increased to similar concentrations at basal (108 ± 11 vs. 106 ± 14) and clamp stages (551 ± 23 vs. 540 ± 25). Postabsorptive BCAA were maintained during Hyper1 and increased >2-fold (830 ± 26 µmol/L) during Hyper2. Endogenous glucose production was similarly suppressed (0.95 ± 0.16 vs. 1.37 ± 0.23 mg/kg lean body mass/min; Hyper1 vs. Hyper2) and basal glucose disposal (3.44 ± 0.12 vs. 3.67 ± 0.14) increased to similar levels (10.89 ± 0.56 vs. 11.11 ± 1.00) during the clamp. Thus, acute physiological elevation of AA for 3 h did not cause IR in healthy men. Novelty: A 2-step pancreatic clamp was used to quantify the effect of AA on insulin sensitivity in humans. Acute physiological elevation of circulating AA to postprandial levels does not cause IR in healthy men.

Treatment options for low high-density lipoproteins.

PURPOSE OF REVIEW: To examine the current and future therapeutic option of HDL-based therapies. RECENT FINDINGS: The inverse association between plasma level of high-density lipoprotein cholesterol (HDL-C) is strong and coherent across the population studied. In-vitro and in-vivo studies show the strong biological plausibility for HDL as a therapeutic target. Mendelian randomization does not support HDL-C as a causal (protective) cardiovascular risk factor, and clinical data does not support the concept that raising HDL-cholesterol mass alters the outcomes. Better biomarkers of HDL function are being examined in the clinical trials. These include cellular cholesterol efflux, antioxidant and anti-inflammatory effects, effects on vascular endothelial cells (inflammation and nitric oxide release) and endothelial progenitor cells. Novel therapeutic agents that alter HDL function are in advanced phase 3 trials and in early preclinical trials. These include inhibitors of cholesteryl ester transfer protein, reconstituted proteoliposomes, apolipoprotein A-I and HDL mimetic peptides and small molecules that increase apo A-I production rate. SUMMARY: Targeting HDL-C has, to date, not led to changes in the cardiovascular outcomes. Novel therapeutic advances target the HDL function. In keeping with the recent 2013 American College of Cardiology/American Heart Association Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults, the major focus of prevention lies with LDL-cholesterol reduction.