Rate of hypoglycemia in insulin-treated patients with type 2 diabetes can be predicted from glycemic variability data

Diabetes Technol Ther. 2012 Nov;14(11):1008-12. doi: 10.1089/dia.2012.0099.


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.

Trial registration: ClinicalTrials.gov NCT00279201 NCT00494013 NCT00510952.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Fasting / blood*
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Insulin / administration & dosage
  • Insulin / pharmacology*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Assessment


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT00279201
  • ClinicalTrials.gov/NCT00494013
  • ClinicalTrials.gov/NCT00510952