The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth

• DOI: 10.2337/dc16-0352
• Publication Date: 2016-06-13T00:07:48Z
• Authors: Joon Young Kim; Sara F. Michaliszyn; Alexis Nasr; SoJung Lee; Hala Tfayli; Tamara Hannon; Kara S. Hughan; Fida Bacha; Silva Arslanian
• Keywords: Blood Glucose; Glycated Hemoglobin; Male; 2. Zero hunger; Adolescent; C-Peptide; Gastric Inhibitory Polypeptide; Glucose Tolerance Test; Glucagon; Incretins; Body Mass Index; 3. Good health; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Insulin Secretion; Body Composition; Humans; Insulin; Female; Biomarkers; Adiposity

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 clamp-measured 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 hyperinsulinemic-euglycemic 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.