Rate of Hypoglycemia in Insulin-Treated Patients with Type 2 Diabetes Can Be Predicted from Glycemic Variability Data

Background: We set out to study the relationship between different measures of glycemic variability and the rate of hypoglycemia in patients with type 2 diabetes. Subjects and Methods: Data were pooled from three 24-week insulin trials including patients on twice-daily (BID) insulin lispro mix 75/25 (75% insulin lispro protamine suspension, 25% insulin lispro) (n = 805), daily (QD) insulin glargine (n = 1,019), insulin lispro protamine suspension (n = 353) (QD or BID), and insulin detemir (n = 166) (QD or BID), all with continuation of prestudy oral antihyperglycemic medications. Glycemic variability measures were derived from seven-point self-monitored blood glucose profiles. Results: At baseline, mean (+/- SD) age was 56.9 +/- 9.7 years, duration of type 2 diabetes was 9.5 +/- 6.1 years, hemoglobin A1c (HbA1c) was 8.9 +/- 1.1%, and 51.9% were male. Intra-day glucose coefficient of variation (CV), fasting blood glucose, intra-day minimum glucose and inter-day glucose CV at 24 weeks, and intra-day glucose CV at baseline were significantly correlated with the rate of hypoglycemia events between Weeks 12 to 24 (P < 0.05 for all measures). Conclusions: Intra-day and inter-day glycemic variability is significantly associated with the risk of hypoglycemia in insulin-treated patients with type 2 diabetes, even after adjusting for mean glucose and HbA1c. The intra-day glycemic variability before starting insulin is significantly associated with the risk of hypoglycemia during insulin treatment, which points at treatment-and patient-related factors mediating this relationship.