Although rates of atherosclerotic complications in type 2 diabetes have fallen in high-income countries due to better management of traditional risk factors such as lipids, blood pressure, and glycemia levels, the risk of diabetes-related heart failure has not demonstrated similar declines and might even be increasing amongst those who develop the disease at younger ages—according to a review article in Diabetes Care.

According to principal investigator Naveed Sattar, PhD, professor of cardiometabolic medicine at the University of Glasgow, the deposition of ectopic fat is not only a significant contributor to the pathogenesis of type 2 diabetes but also an upstream factor in the formation of the many metabolic/hormonal defects in individuals with the disease. However, recent evidence has shown weight loss plays an important role in mitigating such risks and can lead to remission of type 2 diabetes itself. While it has yet to be shown that sustained diabetes remission lowers cardiovascular disease, associated improvements in glucose levels, blood pressure, weight, and lipids suggest that such risk should decrease.

Genetic research has also linked obesity to cardiovascular risk in people with type 2 diabetes. Specifically, such studies have found that adiposity is likely causal for such adverse events as heart failure, atrial fibrillation, hypertension, and coronary heart disease. Other studies have found that polymorphisms associated with BMI and systolic blood pressure predicted multiple cardiovascular complications among individuals with type 2 diabetes.

Other research has found that excess adiposity is more associated with heart failure and chronic kidney disease than it is for cardiovascular complications in people with type 2 diabetes and that cardiovascular risk factors are uniquely associated with different diabetes comorbidities. One longitudinal Swedish study concluded that higher BMI was almost linearly associated with substantially higher risk for incident heart-failure hospitalization. In another study of people with type 2 diabetes already at increased risk for chronic kidney disease, high BMI was independently associated with even higher risk for the disease.

Nevertheless, research has demonstrated that addressing such traditional cardiovascular risk factors through pharmacologic agents has markedly driven down cardiovascular event rates among people with diabetes. Yet, as these individuals live longer, more people with the disease are developing multiple long-term conditions linked to progressively greater aggregated exposure to excess adiposity, hyperglycemia, or both.

As obesity rates have grown, the number of people with type 2 diabetes under the age of 40 has also increased. Current research suggests individuals who develop diabetes earlier in life will have a greater and longer aggregated exposure to hyperglycemia, excess adiposity, and associated risk factors than their counterparts who develop the disease later in life. This may be partly because younger individuals with type 2 diabetes undergo less aggressive LDL cholesterol and blood pressure management than older people with the disease.

Given the important role that excess adiposity plays in the long-term wellbeing of people with type 2 diabetes, the authors suggested that treatment for these individuals includes more than the three main classes of medications that have traditionally been used in diabetes: metformin, sulfonylureas, and insulin. There is now considerable evidence for cardiovascular protection with newer classes of diabetes medications that favorably affect lipids, blood pressure, and/or other elements of diabetes pathogenesis, as well as associated weight loss. These include SGLT2 inhibitors and GLP-1 receptor agonists.

Given these many findings, the authors noted that earlier targeting of weight loss in type 2 diabetes may be particularly useful in helping to attenuate heart failure and chronic kidney disease complications, as well as multiple other complications of obesity. “In conclusion,” they wrote, “considerable evidence from multiple angles and study types—clinical, epidemiological, trends in complications, genetic, and treatment effects—all suggests the need to aggressively target excess weight (in addition to other established cardiovascular risk factors) to more robustly treat and prevent many type 2 diabetes–associated complications.”

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Disclosures: Authors declared financial ties to drugmakers. See full study for details.

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