The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan‐induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Adult Male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 μg/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

BackgroundMC4R genotype has been related to adiposity, glucose metabolism and risk of GDM. We aimed to test whether MC4R genotype modify postpartum weight retention on glucose metabolism biomarkers at postpartum among women with history of gestational diabetes mellitus (GDM).Methods and materialsWe analyzed glucose metabolism biomarkers (HOMA‐IR, fasting glucose, 2 hours glucose and HbA1c) at 1‐5 years after delivery in 1208 Chinese women with prior GDM. Postpartum retention weight was calculated by weight change from pre‐pregnancy to postpartum 1‐5 years. We genotyped GWAS‐identified MC4R rs6567160.ResultsThe mean of weight retention was 2.8kg (95% CI: 2.4; 3.1kg). The frequency of adiposity‐increasing allele (C) of SNP rs6567160 was 23%, and it was significantly associated with a 0.09% higher postpartum HbA1c (p=0.014) after adjustment for age and BMI. In addition, we found significant interactions between MC4R genotype and weight retention on 2 hours glucose levels (β=0.023 p=0.003) and HOMA‐IR (β=‐0.055 p=0.035) after adjustment for age, BMI and follow‐up year.ConclusionOur data indicate that MC4R genotype is related to glucose metabolism, and interact with postpartum weight retention in women with history of GDM.

Background: The progression of cardio-metabolic disease is believed to be driven by increasing Insulin resistance (IR). While increased physical activity (PA) is often encouraged among individuals with metabolic syndrome to improve their IR, there is limited information on its impact among individuals without metabolic syndrome (MS) or obesity. We aimed to ascertain the effect of PA on IR across a spectrum of metabolic conditions. Methods: We evaluated 5,795 healthy Brazilian subjects (43±10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. We defined IR using Triglyceride: High Density Lipoprotein-Cholesterol ratio (TG: HDL) > 3.0. PA was assessed using the International Physical Activity Questionnaire (IPAQ) scale and MS was classified with the IDF criteria. Obesity was defined as having a BMI ≥ 30. Results: The prevalence of IR was 39% (n=2,233), 1,316 (23%) were obese and 1,161 (20%) had metabolic syndrome. IR was significantly higher among individuals with the metabolic syndrome (84%) vs. individuals with no metabolic syndrome (27%), p<0.001. Overall 1,308 (23%) were sedentary, 2,008 (35%) minimally active and 2,473(42%) very active. There were significant reduction in IR prevalence with increasing physical activity (sed: 48%, minimally active: 43%, active= 31%, p<0.001). As shown in table below, after adjusting for confounding variables, higher activity levels was 20-56% less likely associated with IR. The benefits appeared to extend to individuals with and without MS or Obesity. Conclusions: PA presents a dose response association with insulin resistance independent of the MS or Obesity. Staying active has tremendous benefits in reducing insulin resistance across populations regardless of their metabolic profile.