Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes

Abstract

OBJECTIVEHypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown.RESEARCH DESIGN AND METHODSThe study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.RESULTSThere were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]).CONCLUSIONSSymptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.

Incidence and care‐related costs of severe hypoglycaemia requiring emergency treatment in Andalusia (Spain): the PAUEPAD project

“…Diabetes‐associated mortality doubled between 1990 and 2010, and after adjusting the years to reflect disability, the number of healthy years of life that were lost to this disease increased by 70% 2, 3. One of the known causes of death in patients with diabetes is hypoglycaemia 4, 5.…”

Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

“…We screened 1273 citations and included 17 studies with a total of 1498358 participants in the meta-analysis (Bonds et al, 2010, Chiba et al, 2015, Duckworth et al, 2011, Hsu et al, 2013, Origin Trial Investigators et al, 2013, Johnston et al, 2012, Johnston et al, 2011, Khunti et al, 2015, Majumdar et al, 2013, McCoy et al, 2012, Rajpathak et al, 2015, Rathmann et al, 2013, Signorovitch et al, 2013, Zhao et al, 2012, Zoungas et al, 2010. The flow chart of the study selection in shown in the supplementary eFigure.…”

“…All studies attempted to address confounding through the use of multiple logistic regression models, and in addition three studies used Propensity Scores (Hsu et al, 2013) (Origin Trial Investigators et al, 2013, Zhao et al, 2012 .…”

“…Association between hypoglycaemia and vascular disease (Figure 1) We included eight studies in the meta-analysis for macrovascular complications (Duckworth et al, 2011, Hsu et al, 2013 , Johnston et al, 2011, Khunti et al, 2015, Rathmann et al, 2013, Zhao et al, 2012, Zoungas et al, 2010 There are two studies in the meta-analysis which reported on the association between hypoglycaemia and microvascular complications (Zhao et al, 2012, Zoungas et al, 2010. The pooled odds ratio was 1.77 (95% Confidence Interval 1.49, 2.10) with no evidence of heterogeneity (chi-squared p= 0.90, I 2 =0%).…”

“…There are eight studies reporting on overall mortality with a pooled odds ratio of 2.04 (95% Confidence Interval 1.68, 2.47) with substantial heterogeneity (chisquared p< 0.001, I 2 =82%) (Bonds et al, 2010, Hsu et al, 2013, Origin Trial…”