Obese Non-diabetic Adults Research Articles

In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes

We recently reported that rs361072, a promoter C/T variant of p110β, the catalytic subunit of PI3-kinase, was associated with a protection from insulin resistance (IR) in Caucasian adolescents in proportion of their body mass. We tested if this cis-regulatory QTL is associated with IR and type 2 diabetes in 7885 middle-aged obese and non-obese adults of European ancestry. We genotyped rs361072 in 1139 non-diabetic obese (NDO) European adults, in whom IR was estimated by the HOMA-IR index. We also studied 427 type 2 diabetic obese adults (DO) and 424 diabetic non-obese (DNO) adults to test whether their disease status was associated with a decreased prevalence of the protective variant. The prevalence of rs361072 and association with IR was also examined in 5895 non-obese non-diabetic adults (NDNO). rs361072 was associated with HOMA-IR ( p = 4 · 10 −4) in NDO, so that C/C patients had a 17% decrease of this index ( p = 0.002). A statistical trend ( p = 1.1 · 10 −2) for the same genotypic differences was also observed in NDNO adults, but of insignificant magnitude (4.2%). The distribution of rs361072 genotype was comparable in NDO, DO, DNO and NDNO individuals. Allele C of rs361072 is associated with a protection from IR in obese and non-obese adults, but has no significant effect, however, on diabetes risk in obese or non-obese Europeans.

The Effect of Metformin on the Incidence of Type 2 Diabetes Mellitus and Cardiovascular Disease Risk Factors in Overweight and Obese Subjects – The Carmos Study

We investigated whether the addition of metformin to the treatment of overweight and obese individuals further reduces the incidence of type 2 diabetes mellitus (T (2)DM), prediabetes and metabolic syndrome (MetS) and improves cardiovascular disease (CVD) risk factors (RFs). We studied 366 adults (mean age 53.0+/-0.5 SE years, and mean BMI 32.3+/-0.2 SE Kg/m (2)) without CVD. All subjects received lifestyle recommendations and drug management of CVD-RFs, whilst 95 of them were additionally given metformin. The follow-up period lasted 12 months. At the end of the study the frequency of T (2)DM in the metformin and non-metformin group was 1.1 and 8.1%, respectively (risk difference=-7% with 95% CI from -12.7% to -1.4%, p=0.012). Participants with prediabetes displayed a greater reduction in the incidence of T (2)DM after taking metformin compared to those who had not received this drug (risk difference=-18.5% with 95%CI from -33.1% to -3.9%, p=0.010). Metformin had a similar beneficial impact on subjects with MetS (risk difference=-12.9% with 95% from -25% to -0.7%, p=0.040) and this was attributed to the greater increase in HDL-C (p=0.046) and decrease in fasting plasma glucose levels (p=0.024). Metformin also achieved a greater reduction in total cholesterol and LDL-C levels (metformin vs. non-metformin treated subjects: -31.9 vs. -17.3 mg/dl, p=0.001, and -26.2 vs. -15.9 mg/dl, p=0.006, respectively). Metformin reduces the occurrence of T (2)DM in overweight and obese non-diabetic adults and decreases the rate of MetS by improving the CVD risk factor profile.

Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults

Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes. In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo. Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 17% (P < 0.0003). Although insulin levels were unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared with placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05). This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention.

Abstract #43: Prevalence of Comorbid Metabolic Abnormalities in Non-Diabetic Overweight or Obese Adults

Abstract #43: Prevalence of Comorbid Metabolic Abnormalities in Non-Diabetic Overweight or Obese Adults

Effects of caloric restriction and exercise of insulin receptors in obesity: Association with changes in membrane lipids

We have studied the effects of supervised caloric restriction and exercise on mononuclear leukocyte lipid composition, membrane fluidity, and insulin receptors in ten nondiabetic obese adults, (175 ± 9.3% of ideal body weight) and ten normal adult subjects. In a second study, we examined the effects of caloric restriction alone using a very low calorie liquid diet in the treatment of another ten obese adults. In both groups of obese adults, fasting insulin levels were elevated and fell to normal levels following treatment. Insulin binding to monocytes, which was reduced in obese subjects, increased toward normal after short-term treatment; this was due to the restoration of total insulin binding capacity to levels one half of that seen in the normal adult group. Obese subjects undergoing either treatment had elevated membrane cholesterol/phospholipid ratios prior to treatment (0.499 ± 0.050 and 0.446 ± 0.011 v 0.400 ± 0.025 mol/mol in normal adults P < 0.005 by ANOVA). Prior to treatment, for all subjects there was a significant inverse correlation between insulin tracer binding and membrane cholesterol/phospholipid ratios ( r = .484, n = 34, P < 0.005). This relationship did not change significantly in obese subjects in either treatment group. Cell membrane microviscosity was determined by fluorescence polarization (FP) using DPH (2 × 10 −6 mol/L). Prior to weight loss, obese subjects had significantly higher FP values than controls (0.304 ± 0.006 and 0.319 v 0.259 ± 0.009, P < 0.005, by ANOVA) indicating greater microviscosity. After caloric restriction and exercise (study 1), membrane microviscosity fell to normal (0.269 ± 0.006, P < 0.005) whereas, in the group treated with caloric restriction alone (study 2), FP measurements increased (0.322 ± 0.005 v 0.331 ± 0.005, P < 0.02, paired t-test). Obese subjects in both treatment groups showed significant reductions in membrane phospholipid/protein ratios (0.132 ± 0.008 v 0.105 ± 0.009 μg/ μg, P < 0.01 and 0.156 ± 0.019 v 0.130 ± 0.005, P < 0.02). The improvement in membrane fluidity following exercise could not be explained on the basis of any lipid changes determined in the present study. A significant inverse relationship was observed between insulin tracer binding and cell microviscosity measurement for these subjects ( r = .546, P < 0.02). We have shown previously that reduction of membrane phospholipid/protein ratios and increased microviscosity in states of caloric restriction or immaturity are associated with increased detection of the insulin receptor on plasma membranes. In this study, the increase in insulin receptor number and affinity seen with short-term weight loss in obese subjects may be mediated by the fall in membrane phospholipid/protein ratios. However, the role that changes in membrane microviscosity plays in these effects, especially in exercising subjects, remains to be determined.