Of the 37 million Americans with type II diabetes, a substantial proportion have a normal body mass index (BMI). These populations suffer a disproportionately high burden of mortality; the development of diabetic cardiomyopathy (DCM) is likely a contributor. Myocardial steatosis, a known consequence of diabetes, is a significant part of DCM's pathogenesis; unfortunately, there is no feasible way to screen patients for steatosis. Exosomal microRNAs (miRNAs) are a promising biomarker for this purpose. However, no study has evaluated miRNA signatures in normal-weight patients with diabetes. Serum samples of obese/overweight and normal-weight diabetic subjects were obtained via IMPACT and STRONG-D clinical trial protocols respectively. Exosomes were extracted using the ExoTIC (exosome total isolation chip) platform. MiRNA-1 levels from extracellular vesicles were quantified using RT-qPCR and compared via unpaired student's two-tailed t-test. A total of 8 samples (4 normal-weight and 4 overweight/obese) were analyzed. Overall, the obese cohort had a mean age of 63.7 vs. 57.2 for the normal-weight cohort. The obese cohort had a mean BMI of 29.7 vs. 23.1 for the normal weight cohort. Both cohorts were composed of 75% men and 25% women. The obese cohort had a mean hemoglobin A1c of 7.2% vs. 8.0% in the normal-weight cohort. Serum miRNA-1 levels were significantly higher in normal-weight diabetic subjects (p = 0.0004). In this pilot study, patients with diabetes of a normal weight had significantly higher levels of serum miRNA-1, implying that they may have more myocardial steatosis and possibly, more cardiac dysfunction. This pathophysiologic difference could help explain the significant morbidity and mortality that diabetic patients of a normal weight suffer. Further directions for our study include the complete quantification of both miRNA-1 and miRNA-133a among our entire cohort, as well as assessment of echocardiographic parameters.

Disclosure

S.Palanisamy: None. U.Parlatan: None. M.Ozen: None. A.H.Karim: None. D.Akin: None. U.Demirci: None. L.Palaniappan: None.

Funding

National Institutes of Health (1R18DK096394-01A1, 2R01DK081371-06A1)

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