Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

Abstract

OBJECTIVE Increased glycemic variability has been reported to be associated with the risk of hypoglycemia and possibly diabetes complications and is believed to be due to β-cell dysfunction. However, it is not known whether improvement in β-cell function can reduce glycemic variability. Because short-term intensive insulin therapy (IIT) can improve β-cell function in early type 2 diabetes (T2DM), our objective was to determine whether the β-cell functional recovery induced by this therapy is associated with decreased glycemic variability. RESEARCH DESIGN AND METHODS Sixty-one patients with T2DM of 3.0 years mean duration underwent 4 weeks of IIT, which consisted of basal insulin detemir and premeal insulin aspart. Glucose variability was assessed in both the first and the last week by the coefficient of variation of capillary glucose on daily 6-point self-monitoring profiles. β-Cell function before and after IIT was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTS Between the first and the last week on IIT, 55.7% of patients had a reduction in glucose variability. Change in glucose variability was negatively correlated with the change in β-cell function (ISSI-2) (r = −0.34, P = 0.008). On multiple linear regression analyses, percentage change in ISSI-2 emerged as the only factor independently associated with the change in glucose variability (standardized β = −0.42, P = 0.03). Moreover, patients with an increase in ISSI-2 ≥25% experienced a reduction in glucose variability compared with their peers who had almost no change (−0.041 ± 0.06 vs. −0.0002 ± 0.04, respectively; P = 0.006). CONCLUSIONS In early T2DM, glycemic variability is a modifiable parameter that can be reduced by improving β-cell function with short-term IIT.