Practice Update: DIABETES

CARDIOVASCULAR COMPLICATIONS 19

Effect of fasting glucose levels on cardiovascular disease and all-cause mortality Metabolism – Clinical and Experimental Take-home message

COMMENT By Silvio E Inzucchi MD T his study from the Women’s Health Initiative sought to deter- mine whether low fasting glucose levels are associated with cardiovas- cular events and/or mortality. The researchers actually found a neutral effect, whereas in most circumstances hyperglycemia increased the risk. This is in contrast to reports from some larger surveys where lower glucose levels appear to be associated with all-cause mortality. Some feel that, in diabetic cohorts, this reflects the dele- terious effects of hypoglycemia on the cardiovascular system. In nondiabetic cohorts, it likely reflects malnutrition, renal or liver disease, or other condi- tions that may increase the risk of death. In the Mongraw-Chaffin paper, the only event that appeared to be associated with hypoglycemia was heart failure, not an intuitively obvious link. The study, although provocative, is marred by very low numbers of patients at the extremes of blood glucose concentrations, mak- ing any conclusions impossible.

• In this prospective study, the authors investigated the risk of cardiovascular disease and all-cause mortality in postmenopausal women with low fasting glucose levels. In all, 17,287 women from the Women’s Health Initiative were separated into four groups based on fasting glucose levels: low, normal, impaired, and diabetic. Median follow-up was 15 years. Impaired and diabetic fasting glucose were positively associated with all outcomes. Low fasting glucose was significantly and inversely associated with coronary heart disease. The association was null or inverse and not significant with stroke, combined cardiovascular disease, and all-cause mortality. There was a positive but not significant association with heart failure. • Higher levels of fasting glucose were significantly associated with cardiovascular disease and all-cause mortality.

Dr Inzucchi is Professor of Medicine at Yale University School of Medicine, and Clinical Chief of the Section of Endocrinology, Program Director of the Endocrinology and

Abstract BACKGROUND While there is increasing recogni- tion of the risks associated with hypoglycemia in patients with diabetes, few studies have inves- tigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population. OBJECTIVE We hypothesized that low fasting glu- cose would be associated with cardiovascular disease risk and all-cause mortality in postmen- opausal women. METHODS To test our hypothesis, we used both continuous incidence rates and Cox propor- tional hazards models in 17,287 participants from the Women’s Health Initiative with fasting glu- cose measured at baseline. Participants were separated into groups based on fasting glu- cose level: low (<80mg/dL), normal/reference (80–99mg/dL), impaired (100–125mg/dL), and diabetic (≥126mg/dL). RESULTS Participants were free of cardiovas- cular disease at enrollment, had mean age of

Metabolism Fellowship, and Director of the Yale Diabetes Center, Connecticut.

62years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15years. Graphs of continuous incidence rates compared to fasting glucose dis- tribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fast- ing glucose were positively associated with all The study, although provocative, is marred by very low numbers of patients at the extremes of blood glucose concentrations, making any conclusions impossible.

outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. CONCLUSIONS Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality. A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women’s Health Initiative. Metab Clin Exp 2017 May 01;70(xx)116-124, M Mon- graw-Chaffin, AZ LaCroix, DD Sears, et al.

VOL. 1 • NO. 1 • 2017