The association between clinical symptomatic hypoglycemia with cardiovascular events in type 2 diabetes: A nested case control study in nation-wide representative population

[[abstract]]Background: Hypoglycemia was already known to be associated with serious health outcomes. Previous evidences were all derived from clinical trials or inpatient database with other specific admission cause. How is the consequence of those clinically treated type 2 diabetes patients who had hypoglycemia episode experiences is unknown? Methods: The study population was comprised of 76,987 type 2 diabetic mellitus patients identified from the “National Health Insurance Research Database” released by the Taiwan National Health Research Institutes during 2000-2009. We designed a nested case control cohort, which was consistent of hypoglycemic type 2 diabetes patients with randomly selected and matched type 2 diabetes patients without hypoglycemia. We investigated the relationship between hypoglycemia and cardiovascular events including stroke, coronary heart disease, cardiovascular events, and all cause of hospitalization. Results: There were total 2,641 hypoglycemic events (589 defined by inpatient and 2,052 defined by outpatient) from 76,986 type 2 diabetes mellitus patients. The incidence risk of hypoglycemia was 3.43% (2,641/76,986). Women had higher risk of hypoglycemia than men (1.98% vs. 1.45%). Both in the mild and severe hypoglycemia cases have higher percentage of co morbidity, including hypertension, renal diseases, cancer, stroke and heart disease. Hypertension (HR = 1.74; 95%confidence intervals: 1.58-1.92), renal disease (2.96; 2.57-3.40), cancer (2.37; 1.94-2.91), stroke (2.79; 2.35-3.29), and coronary heart disease (1.81; 1.52-2.15) were independently associated with hypoglycemia. Those diabetes patients with hypoglycemia had significantly higher risk of cardiovascular events in clinical treatment periods in multivariate models. Even after propensity score adjusted model,mild and severe hypoglycemia still have around 1.94 (1.71-2.19), 2.23 (2.00-2.49) higher relative risk for CVD and all cause hospitalization respectively. Around 70%of hypoglycemic subjects experienced admission of any cause in the following first year. Conclusion: Symptomatic hypoglycemia, both clinically mild and severe, were associated with an increased risk for cardiovascular and all causes events for hospitalization. The adverse events after hypoglycemia are most frequently occurred in the following first year. Clinically, we should aggressively treat those hypoglycemic episode accompanied type 2 diabetes patients and prevent their immediate and further clinical adverse events