The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth
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American Diabetes Association Inc.
Abstract
OBJECTIVE: The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clampmeasured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes. RESEARCH DESIGN AND METHODS: A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemiceuglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity. RESULTS: Despite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired β-cell function relative to insulin sensitivity. CONCLUSIONS: In obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer β-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth. © 2016 by the American Diabetes Association.
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Adiposity, Adolescent, Biomarkers, Blood glucose, Body composition, Body mass index, C-peptide, Cross-sectional studies, Diabetes mellitus, type 2, Female, Gastric inhibitory polypeptide, Glucagon, Glucagon-like peptide 1, Glucose tolerance test, Hemoglobin a, glycosylated, Humans, Incretins, Insulin, Male, Pediatric obesity, Risk factors, Adiponectin, C peptide, Cholesterol, Fatty acid, Glucagon like peptide 1, Glucose, Hemoglobin a1c, High density lipoprotein, Incretin, Low density lipoprotein, Pancreas hormone, Pancreas polypeptide, Triacylglycerol, Very low density lipoprotein, Biological marker, Glucose blood level, Glycosylated hemoglobin, Abdominal fat, Area under the curve, Article, B lymphocyte, Body fat, Body mass, Cholesterol blood level, Controlled study, Fatty acid blood level, Glucagon blood level, Glucose response curve, Hemoglobin blood level, Hormone blood level, Human, Hyperglycemic clamp technique, Hyperinsulinemic-euglycemic clamp technique, In vivo study, Insulin blood level, Insulin release, Insulin sensitivity, Lipoprotein blood level, Lymphocyte function, Major clinical study, Non insulin dependent diabetes mellitus, Obesity, Oral glucose tolerance test, Plots and curves, Protein blood level, Triacylglycerol blood level, Blood, Childhood obesity, Cross-sectional study, Metabolism, Risk factor, Secretion (process)