Diabetes In Obese Adolescents Research Articles

The rs7903146 Variant in the TCF7L2 Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing beta-Cell Function and Hepatic Insulin Sensitivity

The rs7903146 Variant in the TCF7L2 Gene Increases the Risk of Prediabetes/Type 2 Diabetes in Obese Adolescents by Impairing beta-Cell Function and Hepatic Insulin Sensitivity

Homeostatic model assessment of insulin resistance as a predictor of metabolic syndrome: Consequences of obesity in children and adolescents

BackgroundObesity and/or insulin resistance have gained increasing attention as the core manifestations of metabolic syndrome. ObjectiveTo evaluate insulin resistance according to homeostasis model assessment of insulin resistance index HOMA-IR in obese children and adolescents with or without metabolic syndrome at risk of type 2 diabetes mellitus. Design and subjects60 obese children and adolescents were recruited, metabolic syndrome was diagnosed according to the modified WHO criteria adapted for children and adolescents. Insulin resistance was calculated using the HOMA-IR. ResultsMetabolic syndrome (MS) was found in 42 subjects (70%), using modified WHO guidelines for diagnosing MS. On comparing MS-related parameters between the groups with (MS+) and without metabolic syndrome (MS−), median body mass index, waist circumference, waist/height ratio, and blood pressure, total cholesterol and triglyceride were significantly higher in the MS+group. Basal insulin level as well as HOMA-IR was also significantly different between MS+ and MS-groups. The presence of insulin resistance according to HOMA-IR was identified in 53% of obese children and adolescents. This HOMA-IR age and sex limit was exceeded by 70% children in the MS+group, but only by 43% children in the MS-group (p<0.001). HOMA-IR was positively correlated with the majority of anthropometric and biochemical parameters. The correlation was strongest with body mass index, waist circumference and diastolic blood pressure. ConclusionsHOMA-IR might be a reliable surrogate measure of insulin resistance and a strong predictor of type 2 diabetes in obese adolescents allowing the development of preventive measures and treatment when needed.

Oxidized Fatty Acids: A Potential Pathogenic Link Between Fatty Liver and Type 2 Diabetes in Obese Adolescents?

In this study, we sought to investigate the putative association of the oxidized metabolites derived from linoleic acid (OXFAs) with pediatric nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We studied 80 obese adolescents (age 13.3 ± 3.31 years; body mass index 33.0 ± 6.79 kg/m(2)), who underwent an oral glucose tolerance test, a magnetic resonance imaging (MRI) to measure the hepatic fat content, and the measurement of OXFAs and caspase-cleaved Citokeratin18 fragment (CK-18), a robust biomarker of liver injury. In this study, we show that only in subjects with hepatic steatosis, the OXFAs are associated with the CK-18 and that this association is modulated by the PNPLA3 rs738409 variant. We also show that most of the OXFAs are associated with a lower insulin secretion and that adolescents with T2D have higher levels of OXFAs than subjects with impaired or normal glucose tolerance. These observations lead to the hypothesis that the OXFAs may be the pathogenic link between liver injury and T2D and that the novel therapeutic opportunities targeting the OXFAs are possible in adolescents with early-onset NAFLD and T2D.

Depressive symptoms and metabolic markers of risk for type 2 diabetes in obese adolescents

Although higher rates of depression are found among individuals with type 2 diabetes, it remains unknown if the presence of depressive symptoms is associated with heightened metabolic risk for the development of type 2 diabetes among youth. The objective of this study was to evaluate whether depressive symptoms in obese adolescents are associated with impaired β-cell function relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia or prediabetes, predictors of type 2 diabetes development. Fasting and oral glucose tolerance test (OGTT)-derived indices of glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in obese youth (n = 56, age 15.0 ± 1.6 yr, 68% female). The Children's Depression Inventory was utilized to determine depressive symptomatology. Despite no association between depressive symptoms and measures of adiposity, youth with higher depressive symptoms had (i) significantly higher fasting and stimulated glucose levels (13% higher glucose area under the OGTT curve), (ii) ∼50% lower oDI, and (iii) a 50% frequency of prediabetes. These data point to an important relationship between depressive symptoms and a heightened metabolic risk for type 2 diabetes in obese adolescents, including prediabetes and impairment in β-cell function relative to insulin sensitivity. While the directionality of these relationships is unknown, it should be determined if treating one disorder improves the other or vice versa.

METABOLIC IMPACT OF OBESITY IN CHILDHOOD

Childhood and adolescent obesity have become the most prevalent nutritional diseases in the United States. The results of a number of studies demonstrate that the metabolic alterations caused by excess body fat are expressed early in the natural history of obesity. Such alterations seem clinically important even in children, as evidenced by the recent increase in type 2 diabetes in obese adolescents. These observations underscore the need for research efforts directed at the development of effective interventions to stem the tide of the childhood obesity epidemic.