ARTEMIS: Stop Progression to Diabetes to Avoid CV Events

Miriam E. Tucker

May 24, 2019

For people with prediabetes who receive treatment for coronary artery disease (CAD), the risk for adverse cardiovascular outcomes may not differ from that of persons with normal glucose levels and is substantially lower than for those with type 2 diabetes, new research suggests.

Results from the prospective, observational Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection Study (ARTEMIS) were published online May 10 in Diabetes Care. The study was conducted by Antti M. Kiviniemi, PhD, of the Research Unit of Internal Medicine, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Finland, and colleagues.

The study involved 834 patients with type 2 diabetes, 314 with impaired glucose tolerance (IGT), 103 with impaired fasting glucose (IFG), and 695 with normal blood glucose levels. All had CAD and had undergone revascularization (79%), had received optimal medical therapy, or both.

During about 6 years of follow-up, the risk for cardiac events did not differ between those with IGT/IFG (ie, prediabetes) and those with normal glycemia. For both groups, the risk was significantly lower than for individuals with type 2 diabetes.

"We were able to demonstrate for the first time that prediabetes does not increase the risk of cardiac death and adverse cardiac events among patients with coronary artery disease," said Kiviniemi in a press release issued by the University of Oulu.

"The results are promising and encourage both good care of coronary artery disease and prevention of diabetes," she said.

Reassuring Results: Work to Prevent Progression to Diabetes

Earlier studies that focused on the normal population found that myocardial infarctions and cardiac deaths are more common among people with prediabetes, explain Kiviniemi and colleagues.

But research on the significance of prediabetes for the prognosis of CAD has been limited, they note.

In their study, conducted in Finland, cardiac mortality — the primary endpoint — was 8.2% for those with type 2 diabetes, 3.8% for the IGT group, 2.9% for the IFG group, and 2.6% for those with normal glucose tolerance.

After adjustments for age, sex, body mass index, blood pressure, and other factors, the risk for cardiac death was significantly lower for patients with IFG (hazard ratio [HR], 0.45) compared to those with normoglycemia and was significantly higher for patients with type 2 diabetes (HR, 2.21). There was no significant difference in risk for patients with IGT (HR, 1.12).

Risks for major adverse cardiac events (MACE) and for all-cause death were significantly elevated only for those with type 2 diabetes (HR, 1.39 and 2.04, respectively).

When the IFG and IGT groups were pooled (ie, the prediabetes group), the adjusted risks for cardiac death, MACE, and all-cause mortality did not differ between the prediabetes group and the normoglycemia group.

Compared to patients with type 2 diabetes, the prediabetes group had significantly lower adjusted risks for cardiac death (HR, 0.44; P = .021), MACE (HR, 0.63; P = .003), and all-cause mortality (HR, 0.57; P = .008). No differences were seen by sex.

Hence, "Prediabetes does not increase the risks for cardiac death and major cardiac morbidities in the current treatment era," say the authors.

They note, however, that this study was conducted before widespread use of newer type 2 diabetes drugs, such as SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists.

The results are "reassuring," they emphasize, because increasing numbers of patients with CAD also have prediabetes, and these data suggest that prediabetes in patients with established CAD "is not associated with increased risk for cardiac events and does not have a predictive value similar to that of type 2 diabetes in patients with CAD."

New-Onset Type 2 Diabetes Higher Among Those With Prediabetes

Not surprisingly, the incidence of new-onset type 2 diabetes was higher in the IGT and IFG groups than in the patients with normal glycemia (P < .001 for both) and did not differ between the two.

Those with new onset of type 2 diabetes during follow-up had a 2.4-fold higher risk for acute coronary syndrome (P = .003), a 4.6-fold higher risk for congestive heart failure (P = .007), and a 2.2-fold higher risk for MACE (P = .003) compared to those who did not develop type 2 diabetes.

Patients with new-onset type 2 diabetes also had a 2.9-fold higher risk for all-cause mortality compared to those who did not develop type 2 diabetes (P = .054), but they did not have a greater risk for cardiac mortality (HR, 1.9; P = .548).

This indicates that "preventive efforts should be made to impede the progression of prediabetes to type 2 diabetes. Exercise and dietary interventions after a diagnosis of CAD are potentially relevant," the authors conclude.

The study was funded by the Finnish Technology Development Center (Tekes), Helsinki, Finland; the Academy of Finland (Research Council for Health), Helsinki; the Finnish Foundation for Cardiovascular Research, Helsinki; and the Paulo Foundation, Espoo, Finland. The study received financial support from the ARTEMIS consortium partners (Polar Electro, Kempele, Finland; and Hur Oy, Kokkola, Finland). One author is supported in part by the American Heart Association Chair in Cardiovascular Research at the University of Miami.

Diabetes Care. Published online May 10, 2019. Abstract

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