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

Authors: KIM, JOON - Syracuse University; TFAYLI, HALA - American University Of Beirut; BACHA, FIDA - Children'S Nutrition Research Center (CNRC); ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2021
Publication Date: 6/1/2021
Citation: Kim, J.Y., Tfayli, H., Bacha, F., Arslanian, S. 2021. 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. Journal of Obesity. https://doi.org/10.7570/jomes20088.
DOI: https://doi.org/10.7570/jomes20088

Interpretive Summary: The patter of the elevation of blood sugars after the oral glucose tolerance test (OGTT) can be classified based on the glucose response curves (GRCs) as incessant increase, monophasic, and biphasic. These patterns indicate the degree of impairment of beta cell function, being worse in the incessant increase and superior in the biphasic response. We examined if the OGTT-GRC pattern is worse in youth with obesity clinically diagnosed with type 2 diabetes, who have markers of autoimmunity vs. those who do not have markers of autoimmunity. Forty-seven obese youth, 15 with autoimmune markers and 32 without autoimmune markers were evaluated. Insulin sensitivity, and beta cell function were compared among three groups according to their glucose response curve. We found that incessant increase OGTT-GRC is the most frequent curve type in those with positive autoimmune markers. These youth also had up to 40% lower insulin secretion in the incessant increase group vs. the other two groups (monophasic and biphasic). In those without autoimmune markers, beta-cell function was less impaired than in those with autoimmunity. We conclude that severe insulin deficiency is related to higher prevalence of incessant increase in glucose in youth with a clinical diagnosis of type 2 diabetes who have evidence of autoimmune markers (characteristic of type 1 diabetes).

Technical Abstract: The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and B-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 [IA2])-positive (Ab+) vs. –negative (Ab–) youth clinically diagnosed with type 2 diabetes (CDX-T2D). 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 B-cell function was compared. 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–, while first- and second-phase insulin secretion was significantly lower in the incessant increase vs. the other two groups combined, overall B-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. 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.