Abstract
BackgroundAn elevated PI/I ratio is attributable to increased secretory demand on β-cells. However, the effect of postprandial targeting therapy on proinsulin level is unknown. We evaluated the metabolic effect of glinide and sulfonylurea (SU) using the meal tolerance test (MTT).MethodsMTT was applied to previously untreated Type 2 Diabetes Mellitus (T2DM) subjects. Twenty-two participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum proinsulin and C-peptide immunoreactivity (CPR) were measured at 0 and 120 min. Postprandial profile was assessed at baseline and following 3 months treatment with either mitiglinide or glimepiride.ResultsPlasma glucose level at 30, 60, 120, and 180 min was significantly improved by mitiglinide. Whereas, glimepiride showed a significant improve plasma glucose at 0, 180 min. Peak IRI shifted from 120 to 30 min by mitiglinide treatment. The pattern of insulin secretion was not changed by glimepiride treatment. Whereas mitiglinide did not affect the PI/I ratio, glimepiride tended to increase the PI/I ratio. Moreover, although mitiglinide did not affect PI/I ratio as a whole, marked reduction was noted in some patients treated by mitiglinide. PI/I ratio was reduced significantly in the responder group. The responder subgroup exhibited less insulin resistance and higher insulinogenic index at baseline than non-responders. Moreover, the triglyceride level of responders was significantly lower than that of non-responders.ConclusionsMitiglinide improved postprandial insulin secretion pattern and thereby suppressed postprandial glucose spike. In T2DM patients with low insulin resistance and low triglyceride, mitiglinide recovered impaired β-cell function from the viewpoint of the PI/I ratio.Trial registrationUMIN-CTR: UMIN000010467
Highlights
An elevated PI/I ratio is attributable to increased secretory demand on β-cells
In Japan, approximately half of all patients with diabetes have a genetic predisposition to the disease, and insulin secretion is often impaired in lean patients with diabetes mellitus [6,7]
First 15 patients were assigned to the mitiglinide group and 7 patients who were registered thereafter were assigned to the glimepiride group
Summary
The effect of postprandial targeting therapy on proinsulin level is unknown. Type 2 diabetes mellitus is a heterogeneous disease characterized by insulin resistance and defective insulin secretion [1]. Proinsulin level is a predictor of type 2 diabetes mellitus (T2DM), obesity, approximately half of all patients with diabetes have a genetic predisposition to the disease, and insulin secretion is often impaired in lean patients with diabetes mellitus [6,7]. Japanese and Asian patients often show reduced β cell function. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes [8]
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