Admission Proinsulin Is Associated With Mortality in Patients With Admission Hyperglycemia During Acute Coronary Syndrome: Results From a Pilot Observational Study

Study Questions:

What is the relation between acute hyperglycemia and hyperproinsulinemia in identifying patients with acute coronary syndrome (ACS) with worse outcomes?

Methods:

A total of 308 consecutive ACS patients who underwent percutaneous coronary intervention (PCI) were included. Patients were separated into three groups: patients with proven diabetes mellitus (DM group; n = 55), nondiabetic patients with a normal admission glucose (NAG group; n = 175), and nondiabetic patients with acute hyerglycemia at presentation (AHG group; n = 78). Blood samples for glucose, insulin, and proinsulin measurements were obtained at admission. The primary endpoint was all-cause mortality. The mean follow-up was 19 months (interquartile range, 12-28 months).

Results:

Patients in the AHG and DM groups had significantly (p = 0.048) higher all-cause mortality compared with the NAG group. Proinsulin concentration was significantly associated with all-cause mortality for all patients (hazard ratio, 1.013; 95% confidence interval, 1.00-1.024; p = 0.02). AHG patients with increased proinsulin concentrations showed a mortality rate similar to that of DM patients, but had a significantly higher mortality rate than patients with AHG and a low proinsulin concentration (χ2 = 7.57; p = 0.006) and patients with NAG (with or without increased proinsulin [χ2 = 7.66; p = 0.006] and 13.98 [p < 0.001], respectively). Concentrations of glucose and proinsulin at admission were independent significant (p = 0.002) predictors of all-cause mortality.

Conclusions:

An increased proinsulin concentration may be a marker for mortality in ACS patients with hyperglycemia at admission and without known diabetes. Further studies are needed to evaluate the role of metabolic parameters such as proinsulin.

Perspective:

These data suggest that in patients with ACS, the presence of either diabetes or acute hyperglycemia on presentation is associated with higher levels of proinsulin and an adverse prognosis. These data further the developing consensus about the detrimental effects of insulin resistance, which was a better predictor than the glucose levels. Specifically, those with acute hyperglycemia and low proinsulin levels had mortalities similar to the control group without hyperglycemia, whereas those with acute hyperglycemia and elevated proinsulin levels had event rates similar to the diabetic group. These data have important implications for the prognosis and perhaps eventually for the treatment of patients with hyperglycemia with or without diabetes.

Keywords: Incidence, Prognosis, Acute Coronary Syndrome, Hyperglycemia, Follow-Up Studies, Biomarkers, Blood Glucose, Insulin Resistance, Diabetes Mellitus, Percutaneous Coronary Intervention


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