Diabetes : GIP and GLP-1 enhance insulin secretion in carriers of sulfonylureas inducing mutations in hepatocellular nuclear factor 1a

Background: Nuclear factor 1a (HNF1A) diabetes mellitus is a single-gene subtype of diabetes, also known as type 3 adolescent mature diabetes mellitus (MODY

Other limitations are the problem of recurrent hypoglycemia in the use of SUs in some patients, and SUs can also lead to weight gain, as observed in patients with type 2 diabetes

Objective: In this study, the infusion rates of GLP-1 and GIP were selected to mimic the postprandial plasma levels

Methods: 10 HNF1A mutation carriers and 10 control subjects without diabetes mellitus were enrolled for double-blind, placebo-controlled, cross-over studies, including 6-day randomized sequence experiments involving 2-hour normal blood glucose-hyperglycemia clamping, co-administration: 1) SU (glimepiride 1 mg) or placebo, combined with 2) GIP (1.

Results: In HNF1A mutation carriers, we observed: 1) hypoinsulinemia, insulinotropic effects of GIP and GLP-1, 3) superimpotent effects on insulin secretion when combined with SU1GIP and SU1GLP-1, respectively, and 4) increased

Table 1 Overview of HNF1A mutations, treatment, and diabetic status

Figure 1- GIP, GLP-1, plasma glucose, and glucose infusions

Table 2 Glucose, C-peptide, C-peptide/glucose and glucagon

Figure 2—C-peptide and C-peptide/glucose

Figure 3 - Insulin and glucagon

Figure 4-SU and incretin interaction.

Conclusions: Our study suggests that combination therapy with SU and incretin-based insulin may be effective

Christensen AS, Hædersdal S, Storgaard H, et al.