Severe obesity increases the prevalence of the metabolic syndrome, and moderate acute weight loss with a very low-calorie diet in obese subjects with the metabolic syndrome leads to significant metabolic benefits. Adiponectin has been implicated in both the pathogenesis of obesity-related insulin resistance and increased inflammation. We analyzed the relationship of the adipocyte-derived hormone adiponectin with indices of inflammation, adiposity, and insulin resistance in obese subjects with (MS+, n = 40) and without (MS-, n = 40) the metabolic syndrome and examined the acute effects of rapid weight loss. MS+ subjects had significantly lower adiponectin (7.6 +/- 0.6 vs. 10.4 +/- 0.6 microg/ml; P = 0.003) and significantly higher TNF-alpha (3.3 +/- 0.2 vs. 2.8 +/- 0.3 pg/ml; P = 0.004) levels compared with MS- subjects matched for age and body mass index. Plasma adiponectin and TNF-alpha levels were inversely related to the number of metabolic syndrome factors in a stepwise manner. After 4-6 wk of weight loss, there was marked improvement in glucose, insulin, leptin, and triglycerides, whereas adiponectin and TNF-alpha concentrations did not change. Thus, increases in plasma levels of adiponectin or reductions in TNF-alpha are not required for marked improvements in glucose/insulin and lipid metabolism with acute weight loss.
OBJECTIVEThis multicenter, double-blind, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in adults with type 2 diabetes receiving basal insulin and oral antidiabetic agents.
RESEARCH DESIGN AND METHODSThe primary end point was HbA 1c change from baseline after 26 weeks' treatment. After an 8-week run-in to optimize basal insulin, subjects were randomized (1:1) to mealtime faster aspart (n = 345) or IAsp (n = 344), titrated using a simple daily patientdriven algorithm, plus insulin glargine U100 and metformin.
RESULTS
HbA
CONCLUSIONSFaster aspart and IAsp were confirmed noninferior in a basal-bolus regimen regarding change from baseline in HbA 1c . Faster aspart improved 1-h PPG with no differences in 224-h PPG versus IAsp. Overall hypoglycemia rates were similar except for an increase in 022-h postmeal hypoglycemia with faster aspart.Basal insulins are one of the recommended steps in type 2 diabetes treatment intensification when oral antidiabetic drugs (OADs) no longer provide sufficient glycemic control (1). As b-cell function decreases further, maintaining target HbA 1c levels becomes challenging, even when target fasting plasma glucose (FPG) levels have been achieved (2), and further therapeutic intensification may be required (3). The aim of
The MS is prevalent in two-thirds of obese individuals enrolling in a structured weight loss programme. Moderate weight loss with a VLCD markedly improved all aspects of the MS.
Of the large number of Americans with the metabolic syndrome, ATP III recommends drug therapy for only a minority, because LDL-C typically is not substantially elevated. Instead, high triglycerides and low HDL-C are more common; clinical trial data are needed to determine whether optimal therapy should focus on reductions in LDL-C or on comprehensive improvements to the lipid profile.
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