Study Details Prediabetes, MACE Link

Patients with prediabetes are at significantly higher risk of major cardiovascular events than those who have never had high blood sugar.

Study findings show prediabetes, rather than a benign condition to be monitored with a watchful eye, is a dangerous one to be prevented.

Patients with prediabetes were significantly more likely to suffer a heart attack, stroke, or other major cardiovascular event than those with normal blood sugar levels, according to research presented in May at the American College of Cardiology’s 70th Annual Scientific Session. Even patients with prediabetes who lowered their blood sugar levels to a normal range were still at higher risk.

The incidence of major adverse cardiovascular events (MACE) in the prediabetes group (17.97%; 95% confidence interval [CI], 17.3-18.63%) was significantly higher than the incidence observed in the control group (11.01%; 95% CI, 10.48-11.55%) (P<.0001), according to the study, published in the Journal of the American College of Cardiology. MACE is defined as any cerebrovascular accident, myocardial infarction, unstable angina, or acute coronary syndrome.

Furthermore, MACE occurred in 10.5% of patients with prediabetes whose blood sugar levels returned to normal, compared with 6% of those with no diabetes or prediabetes.

“In general, we tend to treat prediabetes as no big deal. But we found that prediabetes itself can significantly boost someone's chance of having a major cardiovascular event, even if they never progress to having diabetes,” said lead author Adrian Michel, MD, an internal medicine resident at Beaumont Hospital-Royal Oak, Michigan. “Instead of preventing diabetes, we need to shift focus and prevent prediabetes.”

The CDC estimates that in 2018, 34 million Americans, or just over 1 in 10, had diabetes, and another 88 million, or 1 in 3, had prediabetes.

Researchers reviewed the charts of 25,829 patients at Beaumont Health System and split them into a prediabetes group and a control group. Data were collected from 2006 to 2020. Follow-up of patients was conducted over a 14-year period.

The relationship between higher blood sugar levels and MACE remained significant even after considering other potentially contributing factors including age, gender, body mass index, blood pressure, cholesterol, sleep apnea, smoking, and peripheral artery disease.

Overall, the relationship was strongest among males, Black individuals, and those with a family history of cardiovascular disease or personal risk factors for heart disease. Among all patients, those who were overweight had the highest incidence of MACE.

The authors also called for further research.

“Based on our data, having prediabetes nearly doubled the chance of a major adverse cardiovascular event, which accounts for 1 out of 4 deaths in the United States,” Michel said. “As clinicians, we need to spend more time educating our patients about the risk of elevated blood sugar levels and what it means for their heart health and consider starting medication much earlier or more aggressively, and advising on risk factor modification, including advice on exercise and adopting a healthy diet.”

Prediabetes is thought to play a role in heart health because elevated glucose levels in the blood can damage and cause inflammation within the vessels. This can lead to vessel injuries in the body and may narrow the vessels and ultimately cause cardiovascular injury, Michel said.

Prediabetes is suspected when a patient has a glycated hemoglobin level between 5.7 and 6.4%, fasting blood sugar of 100-125 mg/dl, or an oral glucose tolerance test of 140-199 mg/dl, according to the American Diabetes Association.


Michel A, Mando R, Waheed MA, Halalau A, and Karabon P. Prediabetes associated with an increase in major adverse cardiovascular events. J Am Coll Cardiol. Published online May 16, 2021. doi: 10.1016/S0735-1097%2821%2901357-7 

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