Adverse LV Remodeling and Dysfunction Affected by Diabetes and Insulin Resistance

The group who developed diabetes earlier had less favorable left ventricular ejection fraction, 4-chamber longitudinal peak strain, and circumferential peak strain.

Higher insulin resistance or cumulative exposure to diabetes in early adulthood has negative effects on left ventricular (LV) remodeling and function at middle age, according to an analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study.

CARDIA is a 25-year multicenter prospective study that enrolled >5000 African-American and white men and women aged 18 to 30 years from 4 US centers between 1985 and 1986.

João A.C. Lima, MD of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues evaluated 3179 patients for whom glucose metabolism data were available.  They hypothesized that exposure to glycemic abnormalities and insulin resistance over a long duration would be associated with adverse LV remodeling and worse function.

Dr Lima and colleagues also investigated whether the association of glucose control among patients with diabetes would be associated with LV remodeling and dysfunction at middle age, and whether trajectory patterns of insulin resistance are related to remodeling and dysfunction independent of obesity.

Patients were divided into 4 subgroups: normal glucose tolerance; impaired glucose tolerance or impaired fasting glucose; late diabetes (diagnosed at year 15 or later); and early diabetes (diagnosed between years 0 and 15).

The group who developed diabetes earlier had less favorable left ventricular ejection fraction (LVEF; coefficient: -2.72%; P<.05); 4-chamber longitudinal peak strain (coefficient: 1.53%; P<.001), and circumferential peak strain (coefficient: 1.12%; P<.05) compared with the normal glucose tolerance group.

Normal glucose tolerance was maintained by 1495 patients, diabetes developed in 453 patients, and the rest developed borderline dysglycemia. At the 25-year examination, 244 out of the 453 patients with diabetes were on treatment (64 on insulin).

Hypertension, use of anti-hypertensive medications, current smoking, and low education levels were observed more often in the late-onset diabetes group. These patients also had higher BMIs, waist circumferences, fasting insulin levels, C-reactive protein and HOMA-IR levels, and worse LV diastolic indices. The late-onset group, however, had the lowest LV function echocardiographic profiles.

Despite having lower blood pressure and BMI levels than the late-onset diabetes group, the early-onset group had the highest left ventricular mass indices (LVMI) and LVM/LV end-diastolic volumes (EDV) ratios (LVMI coefficient: 11.04 g/m2; P<.001; LVEDV ratio coefficient: 0.21; P<.005).

“While those with early-onset diabetes group had higher LVMI, for both early and late diabetes groups, there was no difference in LVMI between high HbA1C and low HbA1C groups,” the authors wrote. However, having high HbA1C and being in the early-onset diabetes group was independently associated with greater odds of having systolic dysfunction (odds ratio: 5.44; P<.005) compared to the normal glucose tolerance group.

A couple of potential study limitations were noted. The euglycemic insulin clamp glucose disposal rate, which the authors stated “more accurately characterizes insulin resistance” was not used, and “the relation of diabetic complications to altered LV structure and function” was not taken into account.

“Cumulative exposure to diabetes and higher insulin resistance from early adulthood to middle age are risk factors for adverse LV remodeling and subclinical LV dysfunction later in life,” Dr Lima and colleagues concluded. “LV remodeling and worse myocardial deformation are important determinants of lifetime risk for developing future cardiovascular morbidity and mortality, including clinical heart failure with both depressed and preserved LVEF.”


Kishi S, Gidding SS, Reis JP, et al. Association of insulin resistance and glycemic metabolic abnormalities with left ventricular structure and function in middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. JACC Cardiovasc Imag. 2016. doi:10.1016/j.jcmg.2016.02.033.