Short-term insulin therapy at the time of diagnosis of Type 2 diabetes leads to better glycemic control and improved beta cell function

Abstract

Background: Impaired insulin secretion and insulin resistance are the underlying pathophysiological defects in Type 2 diabetes (T2DM) that lead to hyperglycaemia. The β-cell defect in T2DM is usually progressive, leading to eventual β-cell exhaustion and dependence on insulin. It is known that glucotoxicity and lipotoxicity contribute to the initial decreased insulin secretion at the time of diagnosis of T2DM. Therefore, an aggressive approach early in the course of the disease to correct these defects could possibly alter the natural history of T2DM. Objectives: Our aim was to study the effect of administration of a short course of insulin therapy at the onset of T2DM on glycaemic parameters and pancreatic β-cell function as assessed by C-peptide estimation. Materials and Methods: Treatment-naive T2DM patients (n = 426) with known duration of diabetes of <3 months were recruited from Dr. Mohan’s Diabetes Specialities Centre at Chennai. All patients were treated initially with short-term insulin therapy (4–6 weeks) along with oral hypoglycaemic agents (OHAs), usually metformin alone or sometimes in combination with sulphonylurea. Subsequently, they were continued on diet, exercise and OHA, wherever required. The baseline characteristics, fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) and glycated haemoglobin (HbA1c), were compared after (an initial) a mean follow-up period of 2.6 months. Patients were then followed up for another 2 years to evaluate their long-term glycaemic control. Fasting and stimulated C-peptide levels were measured in a subset of patients at baseline and at follow-up at 2–3 months, 1 year and 2 years. Results: There was a significant reduction in both FPG and PPG levels. The mean FPG decreased from 214 ± 82 to 111 ± 29mg/dl (P < 0.001), whereas the PPG decreased from 332 ± 120 to 158 ± 54mg/dl (P < 0.001). The HbA1c decreased from 11.8% ± 1.9% to 6.8% ± 1.1% (P < 0.001). There was a significant improvement in the serum C-peptide levels, indicating an improvement in β-cell function. The fasting C-peptide levels improved from a mean of 0.85 ± 0.3 to 1.09 ± 0.4 pmol/ml, whereas the stimulated C-peptide value increased from a mean of 1.63 ± 0.8 to 2.09 ± 1.0 pmol/ml even at the end of 2 years after the insulin was discontinued. There was also a favourable change in lipid profile of the patients. Conclusion: Our study demonstrates that, in newly diagnosed T2DM, a short course of insulin therapy given for 4–6 weeks can lead to long-term good glycaemic control and beneficial effects on pancreatic β-cell function, which is sustained up to 2 years.