Normal Glucose Tolerance (NGT) in Obese African-Americans (AA) with Ketosis-Prone Diabetes (KPDM)

Abstract

KPDM is characterized by new-onset DKA and near-normoglycemia remission (HbA1c <7%, fasting blood glucose [BG] <130 mg/dl, and maintain glycemic control for at least one week off insulin) with intensive insulin treatment. Glycemic status at insulin remission varies from NGT, prediabetes or diabetes on OGTT. We hypothesized that patients with NGT at near-normoglycemia remission will have higher insulin sensitivity (Si) and secretion and longer hyperglycemia relapse-free survival. Obese AA who presented with DKA (n=33) and severe hyperglycemia (n=42) (BG >400 mg/dl with no DKA) underwent 2 hour 75-gm OGTT a week after insulin remission. NGT, prediabetes and diabetes were defined as per ADA criteria. At near-normoglycemia remission, Si was calculated using the OGTT minimal model analysis. Insulin secretion was calculated as incremental area under the curve of insulin (IncreAUCi) with insulin levels from OGTT. Disposition index (DI) was calculated as Si x IncreAUCi. Hyperglycemia relapse was defined as fasting BG ≥ 130 mg/dl, HbA1c >7% or 2 random BG ≥ 180 mg/dl. There were no differences in baseline characteristics among patients with NGT (12%), prediabetes (45%) and diabetes (43%). DI was higher in patients with NGT vs. prediabetes vs. diabetes (1.88±1.63 vs. 1.05±1.14 vs. 0.35±0.92, p<0.001). The difference in DI was explained by higher Si than IncreAUCi in NGT compared to prediabetes and diabetes (Si:4.2±4.4 vs. 2.4±3.5 vs. 1.2±2.5 10-4.(mU/l)-1.min-1, p<0.001; IncreAUCi: 6571±3451 vs. 6585±4947 vs. 4450±3051, p=0.14 mU/ml2). Multivariate Cox regression showed that age, sex, DKA presentation, OGTT status, and DI were not associated with long-term relapse-free survival. There were no differences in any variables between patients presenting with DKA or severe hyperglycemia. NGT at near-normoglycemia remission is characterized by higher insulin sensitivity than higher insulin secretion. However, none of these markers were associated with long-term hyperglycemia-free survival. Disclosure P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. D. Stefanovski: None. V. Narwani: None. I. Anzola: None. L. Peng: None. D. Smiley-Byrd: Speaker's Bureau; Self; Sanofi, Merck & Co., Inc., Novo Nordisk Inc. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..