Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study.

Kamlesh Khunti1,2⇑, Melanie Davies1,2, Azeem Majeed3, Brian Larsen Thorsted4, Michael Lyng Wolden4 and Sanjoy K. Paul5

OBJECTIVE Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes (T1D) or type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This retrospective cohort study used data from the Clinical Practice Research Datalink database, and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes. RESULTS In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with T1D were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with T2D, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with T1D were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with T2D, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with T1D and T2D. CONCLUSIONS Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.

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