Association Between Severe Hypoglycemia and Cardiovascular Disease Risk in Japanese Patients With Type 2 Diabetes

Atsushi Goto, Maki Goto, Yasuo Terauchi, Naohito Yamaguchi, Mitsuhiko Noda, Atsushi Goto, Maki Goto, Yasuo Terauchi, Naohito Yamaguchi, Mitsuhiko Noda

Abstract

Background: It remains unclear whether severe hypoglycemia is associated with cardiovascular disease (CVD) in Asian populations with type 2 diabetes (T2D). Furthermore, no study in Japan, where the prescription patterns differ from those in other countries, has examined this association.

Methods and results: We retrospectively included 58 223 patients (18-74 years old) with T2D. First, we examined the potential predictors of severe hypoglycemia. Then, we investigated the association between severe hypoglycemia and CVD risk. Finally, we performed an updated systematic review and meta-analysis to incorporate our findings and recently published studies into the previous systematic review and meta-analysis. During 134 597 person-years from cumulative observation periods, 128 persons experienced severe hypoglycemia and 550 developed CVD events. In a multivariate Cox proportional hazard model, severe hypoglycemia was strongly and positively associated with the risk of CVD (multivariate-adjusted adjusted hazard ratio, 3.39; 95% CI, 1.25-9.18). In a propensity score-matched cohort that had similar baseline characteristics for patients with severe hypoglycemia and those without, severe hypoglycemia was more strongly associated with the risk of CVD. An updated systematic review and meta-analysis that included 10 studies found that severe hypoglycemia was associated with an ≈2-fold increased risk of CVD (pooled relative risk, 1.91; 95% CI, 1.69-2.15).

Conclusions: Our results suggest that severe hypoglycemia is strongly associated with an increased risk of CVD in Japanese patients with T2D, further supporting the notion that avoiding severe hypoglycemia may be important in preventing CVD in this patient population.

Keywords: cardiovascular disease; cohort study; epidemiology; meta‐analysis; type 2 diabetes mellitus.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Random‐effects meta‐analysis. ADVANCE indicates Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ORIGIN, Outcomes Reduction with an Initial Glargine Intervention; VADT, Veterans Affairs Diabetes Trial. Khunti 1 denotes the estimates for patients with a history of cardiovascular disease; Khunti 2 denotes the estimates for patients without a history of cardiovascular disease. Dots indicate the relative risks for severe hypoglycemia and cardiovascular risk in patients with type 2 diabetes. Horizontal lines indicate 95% CIs for relative risks. Diamond markers represent the pooled relative risk estimates with 95% CIs.

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