Risk of Severe Hypoglycemia in Type 1 Diabetes Over 30 Years of Follow-up in the DCCT/EDIC Study

Abstract

Objective: During the Diabetes Control and Complications Trial (DCCT), intensive diabetes therapy achieving a mean HbA_1c of ∼7% was associated with a threefold increase in the rate of severe hypoglycemia (defined as requiring assistance) compared with conventional diabetes therapy with a mean HbA_1c of 9% (61.2 vs. 18.7 per 100 patient-years). After ∼30 years of follow-up, we investigated the rates of severe hypoglycemia in the DCCT/Epidemiology of Diabetes Inverventions and Complications (EDIC) cohort.

Research design and methods: Rates of severe hypoglycemia were reported quarterly during DCCT and annually during EDIC (i.e., patient recall of episodes in the preceding 3 months). Risk factors influencing the rate of severe hypoglycemia over time were investigated.

Results: One-half of the DCCT/EDIC cohort reported episodes of severe hypoglycemia. During EDIC, rates of severe hypoglycemia fell in the former DCCT intensive treatment group but rose in the former conventional treatment group, resulting in similar rates (36.6 vs. 40.8 episodes per 100 patient-years, respectively) with a relative risk of 1.12 (95% CI 0.91-1.37). A preceding episode of severe hypoglycemia was the most powerful predictor of subsequent episodes. Entry into the DCCT study as an adolescent was associated with an increased risk of severe hypoglycemia, whereas insulin pump use was associated with a lower risk. Severe hypoglycemia rates increased with lower HbA_1c similarly among participants in both treatment groups.

Conclusions: Rates of severe hypoglycemia have equilibrated over time between the two DCCT/EDIC treatment groups in association with advancing duration of diabetes and similar HbA_1c levels. Severe hypoglycemia persists and remains a challenge for patients with type 1 diabetes across their life span.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Figure 1

Spline-smoothed estimates of SH per 100 patient-years by calendar time during DCCT (left) and EDIC (right). Solid lines represent rates for the intensive treatment group; dashed lines represent rates for the conventional treatment group.

Figure 2

Risk of any SH (first episode) as a function of the HbA_1c values for the intensive treatment group (monthly during DCCT and annually during EDIC) (A) and conventional treatment group (quarterly during DCCT and annually during EDIC) (B). The regression line and its 95% confidence band are provided by the simple exponential Poisson models presented in Supplementary Table 2. Bold lines represent the EDIC period; light lines represent the DCCT period.