β- and α-cell dysfunctions in africans with ketosis-prone atypical diabetes during near-normoglycemic remission

Abstract

Objective: Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.

Research design and methods: We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.

Results: Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.

Conclusions: Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.

Figure 1

Distribution of the product glucagon × glucose during OGTT at baseline and at 120 min in KPD patients (gray) and control subjects (white). The horizontal line in the middle of each box indicates the median; the top and bottom borders of the box represent the first and third quartiles of the distribution; and the whiskers represent 1.5 times the interquartile range. *P = 0.03; †P < 0.0001 vs. control subjects.

Figure 2

ISR (A) and glucagon secretion (B) during glucose ramp in KPD patients (continuous lines) and control subjects (dashed lines). Variations of insulin (C) and glucagon (D) levels in response to arginine in KPD patients (continuous lines) and control subjects (dashed lines). Thick dark lines are average model prediction; thin gray lines are 95% CI.