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Symptomatic hypoglycemia increases risk of cardiovascular events, death in type 2 diabetes

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Symptomatic hypoglycemic episodes, regardless of their severity, in patients with type 2 diabetes is associated with excess cardiovascular risk and all-cause mortality, according to Taiwanese researchers. They published their findings in the April issue of Diabetes Care (2013;36:894-900).

The present study investigated the correlation between hypoglycemic events and cardiovascular events using data from 77,611 patients with newly diagnosed type 2 diabetes in the Taiwan National Health Insurance Research Database during 1998 to 2009. Unlike most previous studies, which used glucose levels to identify hypoglycemia, this study identified hypoglycemia based on symptoms or a physician’s diagnosis, and recruited patients from real-world outpatient clinical practice. From the database, 1,844 hypoglycemic events were identified—500 in inpatients and 1,344 in outpatients. The incidence of hypoglycemia was 2.38%. Cardiovascular outcomes and total mortality were compared between randomly selected patients with hypoglycemia and matched patients with type 2 diabetes without hypoglycemia.

The percentage of insulin and sulfonylureas use, and good compliance with diabetes medications were higher in both mild and severe hypoglycemia cases.

The percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease was greater for both mild (outpatient) and severe (inpatient) hypoglycemic cases versus the controls.

During follow-up, 1,187 diabetic patients had a stroke, 1,164 developed coronary heart disease (CHD), 3,515 had cardiovascular events, and 773 died before the end of the study.

Patients with hypoglycemia had a significantly higher risk of cardiovascular events during the clinical treatment periods than those without hypoglycemia.

Compared with patients without hypoglycemia, those with hypoglycemia (both inpatient and outpatients) had a higher hospitalization rate for stroke, CHD, and cardiovascular disease (CVD), and a higher rate for total mortality. Both inpatients and outpatients with hypoglycemia had a more than two-fold higher relative risk of stroke (hazard ratio [HR]: 2.55) and CHD events (HR: 2.35), and more than triple the relative risk of CVD (HR: 3.19) and total mortality (HR: 3.49).

In multivariate models adjusting for other important comorbidities, both mild and severe hypoglycemic events showed increased HRs for stroke, CHD, and all cardiovascular events.

Hypoglycemia was significantly and positively correlated with cardiovascular events and mortality for patients receiving sulfonylureas. The HRs for mild and severe hypoglycemia were as follows: 1.82 and 1.32, respectively, for stroke; 1.88 and 1.35, respectively, for CHD; 2.32 and 1.96, respectively, for CVD; and 2.97 and 2.24, respectively, for total mortality.

In propensity-matched analysis, patients with mild or severe hypoglycemia were at significantly increased risk for cardiovascular events (HR: 2.09), all-cause hospitalization (HR: 2.51), and total mortality (HR: 2.48).

The authors write, “…our results suggest that clinically driven hypoglycemia in diabetes may increase adverse cardiovascular outcomes and hospitalization from any cause by approximately two-fold. Even after propensity score–adjusted analysis, hypoglycemia still has [approximately] 2.0-times to 2.5- times the risk for CVD events, all-cause hospitalization, and all-cause mortality.”

“Clinically, more attention may be needed for diabetic patients with hypoglycemic episodes,” they conclude.

Last modified: August 30, 2021