Effects of intravenous glucose load on insulin secretion in patients with ketosis-prone diabetes during near-normoglycemia remission

Aidar R Gosmanov, Dawn Smiley, Gonzalo Robalino, Joselita M Siqueira, Limin Peng, Abbas E Kitabchi, Guillermo E Umpierrez, Aidar R Gosmanov, Dawn Smiley, Gonzalo Robalino, Joselita M Siqueira, Limin Peng, Abbas E Kitabchi, Guillermo E Umpierrez

Abstract

Objective: Most patients with ketosis-prone type 2 diabetes (KPD) discontinue insulin therapy and remain in near-normoglycemic remission. The aim of this study was to determine the effect of glucotoxicity on beta-cell function during remission in obese patients with KPD.

Research design and methods: Age- and BMI-matched obese African Americans with a history of KPD (n = 8), severe hyperglycemia but without ketosis (ketosis-resistant type 2 diabetes, n = 7), and obese control subjects (n = 13) underwent intravenous infusion of 10% dextrose at a rate of 200 mg per m(2)/min for 20 h. beta-Cell function was assessed by changes in insulin and C-peptide concentrations during dextrose infusion and by changes in acute insulin response (AIR) and first-phase insulin release (FPIR) to arginine stimulation before and after dextrose infusion.

Results: The mean +/- SD time to discontinue insulin therapy was 7.1 +/- 1.7 weeks in KPD and 9.6 +/- 2.3 weeks in ketosis-resistant type 2 diabetes (NS). During a 20-h dextrose infusion, changes in insulin, C-peptide, and the C-peptide-to-glucose ratio were similar among diabetic and control groups. During dextrose infusion, subjects with ketosis-resistant type 2 diabetes had greater areas under the curve for blood glucose than subjects with KPD and control subjects (P < 0.05). The AIR and FPIR to arginine stimulation as well as glucose potentiation to arginine assessed before and after dextrose infusion were not different among the study groups.

Conclusions: Near-normoglycemia remission in obese African American patients with KPD and ketosis-resistant type 2 diabetes is associated with a remarkable recovery in basal and stimulated insulin secretion. At near-normoglycemia remission, patients with KPD displayed a pattern of insulin secretion similar to that of patients with ketosis-resistant type 2 diabetes and obese nondiabetic subjects.

Figures

Figure 1
Figure 1
Arginine stimulation tests performed before (A) and after (B) a 20-h dextrose infusion in control subjects, subjects with KPD, and subjects with ketosis-resistant diabetes (DM). A maximally stimulatory dose of 10% arginine (5 g) was injected at baseline plasma glucose and after an infusion of 10% dextrose at 200 mg per m2/min for 45 min. Data are means ± SE. BG, blood glucose in milligrams per deciliter.
Figure 2
Figure 2
Changes in blood glucose (A), insulin (B), and the C-peptide–to–glucose ratio (C) during a 20-h glucose infusion as 10% dextrose at 200 mg per m2/min in control subjects, subjects with KPD, and subjects with ketosis-resistant diabetes (DM) 1 week after achieving near-normoglycemic remission. Data are means ± SE.

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