Insulin resistance and impaired myocardial fatty acid metabolism in dialysis patients with normal coronary arteries

Abstract

We investigated whether insulin resistance is associated with impaired cardiac fatty acid metabolism in maintenance hemodialysis patients without coronary artery disease. We studied 55 nondiabetic (63+/-11 years old) and 51 diabetic (61+/-10 years old) hemodialysis patients with normal coronary arteries, using single-photon emission computed tomography (SPECT) with an iodinated fatty acid analogue, iodine-123-beta-methyl iodophenyl-pentadecanoic acid ((123)I-BMIPP), to evaluate cardiac fatty acid metabolism. SPECT imaging was graded regionally from 0 (normal) to 4 (absence of tracer) to calculate a summed score for 17 left ventricular segments. Insulin resistance was determined using the homeostasis model assessment index of insulin resistance (HOMA-IR). HOMA-IR correlated with summed BMIPP score in nondiabetic and diabetic patients. Stepwise multiple regression analysis showed that HOMA-IR was independently associated with BMIPP summed score in nondiabetic (beta=0.774, t=9.218, P=0.0001) and diabetic patients (beta=0.792, t=9.079, P=0.0001). Left ventricular ejection fraction was lower in nondiabetic subjects with BMIPP summed score of at least 6 plus HOMA-IR of at least 4 than in others with lower values for both assessments (53.1+/-13.8%, n=20 vs 67.7+/-9.1%, n=23, P=0.0002); this was also true in diabetic subjects (50.9+/-15.2%, n=24 vs 71.0+/-13.6%, n=11, P=0.0007). Association between insulin resistance and impaired cardiac fatty acid metabolism may contribute to left ventricular dysfunction in patients with maintenance hemodialysis without coronary diseases.

Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia

“…Dyslipidemia is also a common complication of CKD (5,6,24). We observed abnormally elevated plasma lipids and cholesterol in uremic rats, with parallel increases in lipogenic gene and protein expression.…”

“…Dyslipidemia manifested by raised serum levels of triglycerides, free fatty acids, and cholesterol is observed in CKD patients and rodent models of uremia (5,6,24). Dyslipidemia can cause insulin resistance (25,26).…”

“…Although diabetic patients with CKD sometimes develop recurrent hypoglycemia, possibly due to reduced renal catabolism of insulin, it is increasingly recognized that insulin resistance and associated hyperinsulinemia are common complications in patients with CKD (2, 3) with an insulin resistancelike syndrome occurring even at the earliest stage of renal dysfunction (4). CKD-induced insulin resistance is positively and independently associated with increased cardiovascular mortality (5,6). Furthermore, mortality among patients treated with hemodialysis is higher in those with more severe insulin resistance (7).…”

Visfatin and endogenous secretory receptor for advanced glycation end-products in diabetic type 2 and non-diabetic patients undergoing intermittent hemodialysis

“…HOMA-IR closely mirrors the clamp technique in the assessment of insulin sensitivity in subjects with various degrees of glucose tolerance and insulin sensitivity, also in type 2 diabetic patients treated with hypoglycemic agents [30,31]. HOMA-IR has also been applied to nondiabetic patients: with end-stage renal disease [32,33], treated with IHD [33][34][35][36][37][38][39][40][41][42] or peritoneal dialysis [42][43][44][45][46]. Shoji et al [47] demonstrated the usefulness of HOMA-IR to assess insulin resistance in renal failure patients; they also included insulin users into the study.…”

Pre-Clinical Myocardial Metabolic Alterations in Chronic Kidney Disease

“…The price of this switch in metabolism is a less efficient ATP production, even though less oxygen is required for its synthesis. Investigators have used single-photon emission computed tomography with the fatty acid analogue iodine-123-β-methyl iodophenyl-pentadecanoic acid to demonstrate alterations in myocardial fatty acid utilization in end-stage renal disease patients (without coronary artery disease), which was strongly correlated with systemic glucose intolerance and systolic left ventricular dysfunction [31]. In another study, impaired myocardial fatty acid metabolism in asymptomatic patients with end-stage renal disease was able to identify the subgroup of patients who were at high risk for cardiac death [15].…”