The Shape of the Oral Glucose Tolerance Test-Glucose Response Curve in Islet Cell Antibody-Positive vs. -Negative Obese Youth Clinically Diagnosed with Type 2 Diabetes

Background: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA-2])-positive (Ab+) vs. -negative (Ab-) youth clinically diagnosed with type 2 diabetes (CDX-T2D).

Methods: Forty-seven obese youth, 15 Ab+ and 32 Ab-, were divided into three OGTT-GRC groups: incessant increase, monophasic, and biphasic. The prevalence of OGTT-GRC, clamp-measured insulin sensitivity, and β-cell function was compared.

Results: Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab+ vs. Ab- youth CDX-T2D. In Ab+ youth, there was up to 40% lower second-phase insulin secretion in the incessant increase group vs. the other two groups combined (monophasic and biphasic). In Ab- youth, while first- and second-phase insulin secretion was significantly lower in the incessant increase vs. the other two groups combined, overall β-cell function was less impaired than in Ab+ youth. In neither Ab- or Ab+ youth was OGTT-GRC related to hepatic or peripheral insulin sensitivity.

Conclusion: Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab+ vs. Ab- obese youth.