Presence of Macroalbuminuria Predicts Severe Hypoglycemia in Patients With Type 2 Diabetes

OBJECTIVE We investigated the factors that might influence the development of severe hypoglycemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2000 to December 2002, patients with type 2 diabetes aged 25-75 years without chronic kidney disease (estimated glomerular filtration rate ≥60 mL/min/1.73 m(2)) were consecutively recruited (n = 1,217) and followed-up in January 2011 and May 2012. Severe hypoglycemia (SH) was defined as an event requiring the assistance of another person to actively administer glucose, hospitalization, or medical care in an emergency department. We used Cox proportional hazard regression analysis to test the association between SH episodes and potential explanatory variables. RESULTS After a median 10.4 years of follow-up, 111 (12.6%) patients experienced 140 episodes of SH, and the incidence was 1.55 per 100 patient-years. Mean age and duration of diabetes were 55.3 ± 9.8 and 9.8 ± 6.5 years, respectively. The incidence of SH events was higher in older patients (P < 0.001), in those with a longer duration of diabetes (P < 0.001), in those who used insulin (P < 0.001) and sulfonylurea (P = 0.003), and in those who had macroalbuminuria (P < 0.001) at baseline. Cox hazard regression analysis revealed that SH was associated with longer duration of diabetes and the presence of macroalbuminuria (normoalbuminuria versus macroalbuminuria: hazard ratio, 2.52; 95% CI 1.31-4.84; P = 0.006). CONCLUSIONS The development of SH was independently associated with duration of diabetes and presence of macroalbuminuria, even with normal renal function in patients with type 2 diabetes.