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Aims: To examine whether addition of amlodipine (5 mg)/atorvastatin (10 mg) A/A to Therapeutic Lifestyle change intervention (TLC) would beneficially modulate Metabolic Syndrome (MetS) and oxidized low-density lipoprotein (Ox-LDL) levels., Methods: Patients with MetS (n = 53) were randomized to TLC + placebo or TLC + A/A for 12 months. Anthropometric measurements, blood pressure (BP), lipid profile, plasma Ox-LDL, and area under the curve of free fatty acid (AUC FFA ) during oral glucose tolerance test, a marker of adipose tissue health, were assessed before and after the intervention., Results: Twenty-six patients completed the study with an overall improvement of MetS (p = 0.02). TLC + placebo was beneficial in reversing MetS comparable to TLC + A/A (54% vs. 39%; p = 0.08). Both treatments decreased systolic BP (p ≤ 0.01). TLC + A/A also decreased diastolic BP and triglyceride levels. The changes in Ox-LDL levels directly correlated with changes in weight in the TLC-placebo group (r = 0.64; p = 0.04). AUC FFA determined the loss of fat mass (r = 0.472, p = 0.03)., Conclusions: 1) Addition of A/A has the advantage of improving the lipid profile and BP; but TLC alone was comparable to TLC + A/A in improving MetS; 2) weight change determines the TLC-associated change in Ox-LDL levels; and 3) AT metabolic health is a significant predictor of TLC-associated loss of body fat mass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the variability of subcutaneous abdominal adipose tissue (AT) dynamics in obese subjects with a wide range of insulin sensitivity (IS) and the correlation between these two metabolic measures. Ten obese (BMI 30-40 kg/m²) nondiabetic subjects with (n = 6) and without (n = 4) the metabolic syndrome were studied following a 12-wk ²H₂O labeling period. Subcutaneous abdominal AT biopsies were collected. Deuterium incorporation into triglyceride (TG)-glycerol and TG-palmitate were measured by gas chromatography-mass spectrometry for the calculation of fractional TG synthesis (fTG) and fractional de novo lipogenesis (fDNL). Muscle IS and insulin-mediated nonesterified fatty acid (NEFA) suppression (a measure for adipose IS) indexes were derived from the oral glucose tolerance test (OGTT). The ability of subcutaneous abdominal AT to synthesize lipids varied significantly in obese subjects (fTG range 7-28%, fDNL range 1.1-4.6%) with significantly lower values (>35% reduction) for both parameters in obese with the metabolic syndrome. fTG correlated positively with muscle IS (r = 0.64, P = 0.04) and inversely with NEFA suppression during the OGTT (r = -0.69, P = 0.03). These results demonstrate a large variability in subcutaneous abdominal AT lipid turnover in obesity. Moreover, a reduced capacity for subcutaneous abdominal AT fat storage is associated with muscle and adipose tissue insulin resistance as well as with the metabolic syndrome, thus identifying a form of obesity at heightened risk for type 2 diabetes and cardiovascular disease.

Adipose tissue dysfunction rather than excess adipose tissue mass (defined as obesity) is mechanistically related to development of metabolic diseases traditionally linked to obesity: metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of adipose tissue seems to be an important manifestation of adipose tissue dysfunction and closely relates to insulin resistance, the mediator of obesity-related morbidity. However, it is not completely clear whether inflammation in adipose tissue leads to first, local, and then systemic insulin resistance or insulin resistance leads to adipose tissue inflammation, which, in turn, increases insulin resistance. These questions can only be answered by studying models of insulin resistance, independent of obesity. The conceptual shift from adipose tissue mass to adipose tissue function will have significant diagnostic and therapeutic implications. Our efforts in establishing markers to identify "at risk" population and finding newer therapeutic agents must focus on adipose tissue dysfunction and not on obesity alone.

The metabolic syndrome is a constellation of cardiovascular risk factors that include atherogenic dyslipidemia, elevated blood pressure, abdominal/truncal obesity, and glucose intolerance. Current National Cholesterol Education Program (NCEP) recommendations for specific treatment of the metabolic syndrome are centered on therapeutic lifestyle changes. A recent publication from the NCEP Adult Treatment Panel III suggests pharmacologic intervention for parameters of metabolic syndrome, including dyslipidemia, hypertension, and hyperglycemia, to prevent cardiovascular disease, based on risk category. This review looks at the clinical trial evidence to support the use of statins in metabolic syndrome.

Background: Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis., Methods: Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies., Results: For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P= 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001)., Conclusion: We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.

Two cholesterol-raising fatty acids in the diet, saturated fatty acids and trans fatty acids, increase the serum low-density lipoprotein cholesterol concentration. This fact justifies the recommendation of a reduced intake of cholesterol-raising fatty acids. Emerging data suggest that diets higher in unsaturated fatty acids, particularly monounsaturated fatty acids, have several advantages over high-carbohydrate intakes. This advantage appears to hold, particularly for populations having a high prevalence of insulin resistance, such as the US population. If the US public were to modify its eating habits in the direction of better weight control and more exercise, higher intakes of carbohydrate might be better tolerated. At the same time, the experience with the Mediterranean population reveals that in healthier populations, diets relatively high in unsaturated fatty acids are well tolerated and are associated with a low prevalence of both coronary heart disease and type 2 diabetes.