ABSTRACT
AIMS/HYPOTHESIS: The prevalence of altered glucose metabolism in obese children and adolescents is growing at a significant rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds differ in their adaptive mechanisms to obesity-related insulin resistance. The aim of this study was to evaluate the early insulin response and insulin clearance in response to an oral glucose load in obese children and adolescents. METHODS: Seven hundred and nine obese children and adolescents underwent an OGTT. Indices of the early insulin response and insulin clearance were compared in participants of White European, African American and Hispanic origin. RESULTS: Participants of the three ethnic groups demonstrated similar mechanisms of adaptation to increasing insulin resistance, but with different magnitudes. African American subjects had a greater early insulin response and decreased insulin clearance than their White European and Hispanic counterparts. This happened regardless of whether the cohort was divided by glucose tolerance level or by level of insulin sensitivity. IGT across ethnic groups was characterised by a marked decline in the acute insulin response in the context of severe insulin resistance and very low insulin clearance. CONCLUSIONS/INTERPRETATION: In obese children and adolescents, mechanisms of adaptation to obesity related to insulin resistance are similar across ethnic groups. The greater early insulin response needed to maintain glucose tolerance in young people of ethnic minorities may partially explain their greater tendency to develop type 2 diabetes.
Subject(s)
Adaptation, Physiological , Insulin Resistance/ethnology , Insulin Resistance/physiology , Insulin-Secreting Cells/metabolism , Obesity/ethnology , Obesity/metabolism , Adolescent , Anthropometry , Child , Cohort Studies , Female , Glucose Tolerance Test , Humans , Insulin/metabolism , Insulin Secretion , Male , Sensitivity and SpecificityABSTRACT
BACKGROUND: Microalbuminuria (MA) has emerged as a strong predictor of cardiovascular (CV) events, even in nondiabetic adults. While the mechanisms behind this association remain to be established, most studies suggest that MA is the result of increased vascular leakage denoting endothelial dysfunction associated with early vasculopathy. OBJECTIVE: To examine if a urine albumin creatinine ratio (UACR) in the microalbuminuric range is related to metabolic markers of CV risk in obese and pre-diabetic youth recruited from an obesity clinic. METHODS: MA was defined as a UACR between 2.0 and 20 mg/mmol. Subjects with gross proteinuria (UACR>20 mg/mmol) were excluded from the study. Analyses were performed to assess the relationship of MA and markers of CV risk, including body mass index (BMI), % body fat, blood pressure (BP), lipid profile, inflammatory markers, insulin sensitivity indexes and degrees of oral glucose tolerance. MA was also correlated with risk factor constellations unique to the metabolic syndrome, a distinct CV risk entity. RESULTS: Postchallenge alterations in glucose metabolism and overall loss in insulin sensitivity were strongly and positively correlated with the presence of MA (P = 0.002 and 0.01, respectively). Neither the metabolic syndrome nor any of the individual CV risk factors examined were associated with MA. CONCLUSIONS: These data suggest that early glucose toxicity, as reflected by postchallenge elevations in plasma glucose even below the diagnostic cutoff for diabetes mellitus may contribute to the presence of MA. Whether MA is equally as predictive of CV disease in youth, as in adulthood, remains to be investigated.
