Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

Abstract

Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). Patients with type 1 diabetes (<i>n</i> = 66, duration ≥50 years) and age-/sex-matched control subjects (<i>n</i> = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m² and <30 mg/day urine albumin) and 22 patients with DN (eGFR ≤60 mL/min/1.73 m² or ≥30 mg/day urine albumin). Intrarenal hemodynamic function (glomerular filtration rate for inulin [GFR_INULIN], effective renal plasma flow for <i>p</i>-aminohippuric acid [ERPF_PAH]) was measured. Afferent arteriolar resistance, efferent arteriolar resistance, renal blood flow, renal vascular resistance [RVR], filtration fraction, and glomerular pressure were derived from the Gomez equations. Fat and lean mass were quantified by DXA. Whereas measures of adiposity did not associate with GFR_INULIN or ERPF_PAH in healthy control subjects, trunk fat mass inversely correlated with GFR_INULIN (<i>r</i> = -0.46, <i>P</i> < 0.0001) and ERPF_PAH (<i>r</i> = -0.31, <i>P</i> = 0.01) and positively correlated with RVR (<i>r</i> = 0.53, <i>P</i> = 0.0003) in type 1 diabetes. In analyses stratified by DN status, greater central adiposity related to lower GFR_INULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPF_PAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function.