Changes in Weight and Glucose Can Protect Against Progression in Early Diabetes Independent of Improvements in ß-Cell Function.

CONTEXT: Evidence-based strategies to prevent progression of dysglycemia in newly diagnosed type 2 diabetes are needed. OBJECTIVE: To undertake a secondary analysis of the Early Diabetes Intervention Program (EDIP) in order to understand the features that were protective against worsening glycemia. DESIGN: EDIP was a randomized, placebo-controlled trial. SETTING: Two university diabetes centers. PATIENTS: A total of 219 overweight individuals with fasting glucose < 7.8 mmol/L and 2-hour oral glucose tolerance test (OGTT) glucose > 11.1 mmol/L. INTERVENTIONS: Acarbose versus placebo, on a background of dietary recommendations, with quarterly visits to assess glycemia and intervention adherence for up to 5 years. MAIN OUTCOME MEASURES: Progression of fasting glucose ≥ 7.8 mmol/L on two consecutive quarterly visits. Cox proportional hazards modeling and ANOVA were performed to evaluate determinants of progression. RESULTS: Progression-free status was associated with reductions in weight, fasting glucose, 2-hour OGTT glucose, and increases in the high-density lipoprotein/triglyceride ratio. The reduction in fasting glucose was the only effect that remained significantly associated with progression-free status in multivariable Cox modeling. The reduction in fasting glucose was in turn primarily associated with reductions in weight and in 2-hour OGTT glucose. Acarbose treatment did not explain these changes. CONCLUSIONS: In early diabetes, reductions in glucose, driven by reductions in weight, can delay progressive metabolic worsening. These observations underscore the importance of lifestyle management including weight loss as a tool to mitigate worsening of glycemia in newly diagnosed diabetes.

Depressive symptoms are associated with fasting insulin resistance in obese youth.

BACKGROUND: In adults, depressive symptoms are positively associated with insulin resistance. OBJECTIVE: To determine whether an association exists between depressive symptoms and markers of insulin resistance in youth. METHODS: This study used a retrospective review of data from an obesity clinic. We evaluated the association between depressive symptoms (Children's Depression Inventory, CDI) and fasting insulin and homeostatic model assessment-insulin resistance (HOMA-IR) in obese youth (n = 207, age 10-18 years). Individuals with lower vs. higher CDI T-scores (<65 vs. ≥65) were compared; this cut-point is accepted as indicating the possibility of clinical depression. Multiple linear regression was used to evaluate relationships between CDI T-scores and insulin resistance. RESULTS: Fasting insulin and HOMA-IR values were 40% higher in patients with higher CDI T-scores (P = 0.04). After accounting for gender, race, age and body mass index, CDI T-score remained associated with HOMA-IR, although the strength of the association was small (b = 0.007, P = 0.049). CONCLUSIONS: Relationships between depressive symptoms and insulin resistance should be considered when evaluating obese youth.

Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In paediatric patients, obstructive sleep apnoea is associated with adiposity, especially visceral adiposity. In adults, obstructive sleep apnoea is also associated with a higher prevalence of cardiovascular disease and type 2 diabetes. There are limited and conflicting paediatric studies examining the association between obstructive sleep apnoea and biomarkers of risk for cardiovascular disease and type 2 diabetes in youth. WHAT THIS STUDY ADDS: Obstructive sleep apnoea is linked with greater cardiometabolic risk markers in obese adolescents. Fasting insulin and homeostasis model assessment-insulin resistance may be especially linked with obstructive sleep apnoea among obese male Hispanic adolescents. The relationship between obstructive sleep apnoea and cardiometabolic abnormalities in obese adolescents should be considered when evaluating patients found to have obstructive sleep apnoea. BACKGROUND: Paediatric studies examining the association between obstructive sleep apnoea (OSA) and insulin sensitivity/cardiometabolic risk are limited and conflicting. OBJECTIVE: This study aims to determine if cardiometabolic risk markers are increased among obese youth with obstructive sleep apnoea as compared with their equally obese peers without OSA. METHODS: We performed a retrospective analysis of 96 patients (age 14.2 ± 1.4 years) who underwent polysomnography for suspected OSA. Fasting lipids, glucose, insulin and haemoglobin A1 c (HbA1 c) were performed as part of routine clinical evaluation. Patients were categorized into two groups by degree of OSA as measured by the apnoea-hypopnoea index (AHI): none or mild OSA (AHI < 5) and moderate or severe OSA (AHI ≥ 5). RESULTS: Despite the similar degrees of obesity, patients with moderate or severe OSA had higher fasting insulin (P = 0.037) and homeostasis model assessment-insulin resistance (HOMA-IR [P = 0.0497]) as compared with those with mild or no OSA. After controlling for body mass index, there was a positive association between the AHI and log HOMA-IR (P = 0.005). There was a positive relationship between arousals plus awakenings during the polysomnography and fasting triglycerides. CONCLUSIONS: OSA is linked with greater cardiometabolic risk markers in obese youth.

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

BACKGROUND: The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. METHODS: The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. RESULTS: Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. CONCLUSIONS: Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects.

Magnesium deficiency enhances basal glucose disposal in the rat.

To investigate the contribution of hepatic and peripheral tissues to the enhanced glucose disposal rate (Kg) observed in magnesium (Mg)-deficient rats, euglycemic-hyperinsulinemic clamps were performed with continuous infusion of [3-3H]glucose and three insulin infusion rates, 1, 8, and 16 microU.kg-1.min-1. Moderately Mg-deficient (Mg-, 4.2 microM Mg/g diet) and Mg-adequate (Mg+, 16.7 microM Mg/g diet) Sprague-Dawley rats were studied after 3 wk of dietary treatment. Growth, fasting glucose, and insulin concentrations were not affected by dietary treatment. Basal hepatic glucose output (HGO) and glucose disposal (Rd) were increased by 24% in Mg- rats (P < 0.001). After 1 microU insulin.kg-1.min-1 infusion, Rd and the glucose infusion rate that maintained euglycemia were significantly increased in Mg- rats by 24 and 46%, respectively. However, when the increase in Rd above baseline was examined, no significant differences were observed. Therefore, the increased basal glucose disposal observed in Mg- rats may be mediated by noninsulin-dependent mechanisms. Insulin suppression of HGO during 1 microU insulin.kg-1.min-1 infusion was greater in Mg- rats (43%) compared with Mg+ rats (27%, P < 0.05). In conclusion, the increased Kg observed in Mg- rats is likely to be caused by an increase in noninsulin-mediated glucose uptake and an enhancement of hepatic insulin sensitivity.