Predictors of Long-term Glycemic Remission After 2-Week Intensive Insulin Treatment in Newly Diagnosed Type 2 Diabetes

Hui Wang; Jian Kuang; Mingtong Xu; Zhengnan Gao; Qifu Li; Shiping Liu; Fan Zhang; Yerong Yu; Zhen Liang; Weigang Zhao; Gangyi Yang; Ling Li; Yang Wang; Guangwei Li

Disclosures

J Clin Endocrinol Metab. 2019;104(6):2153-2162. 

In This Article

Abstract and Introduction

Abstract

Context: Although several studies suggest that improved β-cell function is a key determinant of glycemic remission in type 2 diabetes, other predictors remain unclear.

Objective: The aim of this clamp-based study was to identify predictors of 2-year glycemic remission after short-term intensive insulin treatment.

Design: A 2-year follow-up was planned in 124 drug-naive patients with type 2 diabetes who received continuous subcutaneous insulin infusion (CSII) for 2 weeks. Euglycemic-hyperinsulinemic clamps and IV glucose tolerance tests were performed to assess the insulin sensitivity [glucose infusion rate (GIR)] and acute insulin response (AIR) before and after CSII.

Results: First-phase insulin secretion was restored, and the GIR was significantly improved (P < 0.0001) after the 2-week CSII. Glycemic remission rates were 47.6% and 30.7% after 12 and 24 months of follow-up, respectively. Cox analysis revealed that a higher post-CSII glucose level [hazard ratio (HR), 1.38; 95% CI, 1.15 to 1.66; P = 0.0005] and older age at diabetes diagnosis (HR, 1.34; 95% CI, 1.05 to 1.72; P = 0.02) accounted for an increased risk of hyperglycemic relapse. A 1 SD increase in the AIR (HR, 0.75; 95% CI, 0.57 to 0.99; P = 0.04), GIR (HR, 0.67; 95% CI, 0.48 to 0.93; P = 0.016) after CSII, and baseline GIR (HR, 0.71; 95% CI, 0.51 to 0.99; P = 0.047) was inversely associated with this risk.

Conclusions: Younger age at diabetes diagnosis, higher baseline insulin sensitivity, and lower glucose levels after insulin treatment significantly favored a 2-year glycemic remission. This long-term remission was attributed to both improved insulin sensitivity and enhanced β-cell function after short-term intensive insulin treatment.

Introduction

Several studies have reported that short-term continuous subcutaneous insulin infusion (CSII) can induce long-term glycemic remission in patients with newly diagnosed type 2 diabetes.[1–6] A potential mechanism of remission is that short-term intensive insulin treatment relieves glucose toxicity by normalizing plasma glucose and thereafter preserves or enhances pancreatic β-cell function.[7–14] However, the eligibility of other predictors for glycemic remission, particularly insulin sensitivity, remains unclear. The euglycemic-hyperinsulinemic clamp is considered the "gold standard" to measure insulin sensitivity in vivo. However, the evidence derived from this technique for the early use of short-term intensive insulin treatment in type 2 diabetes mellitus remains limited.[15,16] To the best of our knowledge, the insulin clamp technique has never been employed to identify the predictive effect of insulin sensitivity on long-term glycemic remission. The current study aimed to determine to what extent insulin sensitivity and β-cell function can be improved by 2-week intensive insulin treatment in newly diagnosed patients with type 2 diabetes mellitus with severe hyperglycemia and to identify the major predictors of 2-year, long-term glycemic remission. Among these factors, the role of baseline body mass index (BMI), insulin sensitivity, and β-cell function after insulin treatment were particularly explored.

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