Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises

• Type of Material: Article
• Authors: Priyathama Vellanki, Emory University; Darko Stefanovski, University of Pennsylvania; Isabel I. Anzola, Emory University; Dawn Smiley-Byrd, Emory University; Limin Peng, Emory University; Guillermo Umpierrez, Emory University
• Language: English
• Date: 2020-01-01
• Publisher: BMJ Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2020.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/bmjdrc-2019-001062
• Title of Journal or Parent Work: BMJ Open Diabetes Research & Care
• Volume: 8
• Issue: 1
• Grant/Funding Information: PV is supported in part by K12HD085850 and K23DK113241-01A1.; GEU is partly supported by research grants from the NIH/NATS UL1 TR002378 from the Clinical and Translational Science Award program, and 1P30DK111024-01 from NIH and National Center for Research Resources.; This work was funded by K08DK0830361 (DDS) and was supported by the National Center for Advancing Translational Sciences Award number (UL1TR002378) and 1P30DK111024-01 from the National Institutes of Health and National Research Resources.
• Keywords: Science & Technology; NIDDM; ketoacidosis; Near normoglycemic remission; insulin secretion; Endocrinology & Metabolism; Life Sciences & Biomedicine; Diabetic ketoacidosis; antidiabetic drugs; insulin action
• Research Categories: Biology, Biostatistics; Biology, Bioinformatics; Health Sciences, Medicine and Surgery; Health Sciences, Public Health

Abstract

Introduction Many African-Americans (AA) with obesity with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) discontinue insulin therapy and achieve near-normoglycemia remission (hemoglobin A1c (HbA1c) <7%, fasting blood glucose (FBG) <130 mg/dL) and able to be managed on oral antidiabetic agents (OAD) during follow-up. Using combined data from two randomized controlled trials, we assessed long-term carbohydrate tolerance and changes in insulin sensitivity and insulin secretion. Research design and methods Seventy-five participants with DKA (n=33) and SH (n=42) underwent 2-hour 75 g oral glucose tolerance test (OGTT) after insulin discontinuation and every 6 months until hyperglycemia relapse (FBG ≥130 mg/dL, HbA1c >7% or two random BG ≥180 mg/dL) while treated with OAD (metformin, sitagliptin or pioglitazone) or placebo. Glucose tolerance status was defined as per the American Diabetes Association. Sensitivity index (Si) was calculated by oral minimal model, insulin secretion as the incremental area under the curve of insulin (IncreAUCi) and disposition index (DI) as Si×IncreAUCi. Results During remission, OGTT showed normal glucose tolerance (NGT) (n=9 (12%)), prediabetes (n=34 (45%)) and diabetes (n=32 (43%)). DI and Si were higher in patients with NGT versus prediabetes versus diabetes (p<0.001), while IncreAUCi was not significantly different among NGT, prediabetes and diabetes (p=0.14). Achieving NGT status did not prolong near-normoglycemia remission. OAD treatment significantly prolonged hyperglycemia relapse-free survival (log-rank p=0.0012) compared with placebo and was associated with lower hyperglycemia relapse (HR: 0.45, 95% CI: (0.21 to 0.96), p=0.04). Conclusions In AA patients with obesity with history of DKA and SH, near-normoglycemia remission is associated with improved insulin secretion and action with half of patients achieving NGT or prediabetes, and only half having diabetes on OGTT. NGT and prediabetes on OGTT were not associated with prolonged hyperglycemia relapse-free survival.