HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study

Abstract

Objective: We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes.

Research design and methods: Type 2 diabetic patients in a large, integrated healthcare system, who were 30-77 years of age and treated with glucose-lowering therapy, were asked about severe hypoglycemia requiring assistance in the year prior to the Diabetes Study of Northern California survey conducted in 2005-2006 (62% response rate). The main exposure of interest was the last HbA1c level collected in the year preceding the observation period. Poisson regression models adjusted for selected demographic and clinical variables were specified to evaluate the relative risk (RR) of severe hypoglycemia across HbA1c levels. We also tested whether the HbA1c-hypoglycemia association differed across potential effect modifiers (age, diabetes duration, and category of diabetes medication).

Results: Among 9,094 eligible survey respondents (mean age 59.5 ± 9.8 years, mean HbA1c 7.5 ± 1.5%), 985 (10.8%) reported experiencing severe hypoglycemia. Across HbA1c levels, rates of hypoglycemia were 9.3-13.8%. Compared with those with HbA1c of 7-7.9%, the RR of hypoglycemia was 1.25 (95% CI 0.99-1.57), 1.01 (0.87-1.18), 0.99 (0.82-1.20), and 1.16 (0.97-1.38) among those with HbA1c <6, 6-6.9, 8-8.9, and ≥9%, respectively, in a fully adjusted model. Age, diabetes duration, and category of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship.

Conclusions: Severe hypoglycemia was common among patients with type 2 diabetes across all levels of glycemic control. Risk tended to be higher in patients with either near-normal glycemia or very poor glycemic control.

Figure 1

DISTANCE survey respondents selected for study analysis. DM, diabetes mellitus.

Figure 2

Timing of the DISTANCE survey, occurrence of hypoglycemia, and collection of key variables for the study.

Figure 3

RR of hypoglycemia in unadjusted, demographically adjusted, and fully adjusted modified Poisson models (reference: HbA_1c 7–7.9%). The fully adjusted model includes age, sex, race, diabetes duration, comorbidities (including renal function), polypharmacy, prior history of hypoglycemia, and category of diabetes medications. P values for RR of hypoglycemia in HbA_1c categories <6, 6–6.9, 8–8.9, and ≥9% were 0.48, 0.10, 0.39, and 0.003 in the unadjusted model; 0.31, 0.16, 0.38, and 0.005 in the demographically adjusted model; and 0.06, 0.88, 0.94, and 0.10 in the fully adjusted model, respectively.