Insulin resistance in uremia.

Abstract

A B S T R A C T Tissue sensitivity to insulin was examined with the euglycemic insulin clamp technique in 17 chronically uremic and 36 control subjects. The plasma insulin concentration was raised by -100 ,uU/ ml and the plasma glucose concentration was maintained at the basal level with a variable glucose infusion. Under these steady-state conditions of euglycemia, the glucose infusion rate is a measure of the amount of glucose taken up by the entire body. In uremic subjects insulin-mediated glucose metabolism was reduced by 47% compared with controls (3.71 +0.20 vs. 7.38+0.26 mg/kg-min; P < 0.001). Basal hepatic glucose production (measured with [3H]-3-glucose) was normal in uremic subjects (2.17+0.04 mg/kg-min) and suppressed normally by 94±+2% following insulin administration. In six uremic and six control subjects, net splanchnic glucose balance was also measured directly by the hepatic venous catheterization technique. In the postabsorptive state splanchnic glucose production was similar in uremics (1.57+0.03 mg/kg.min) and controls (1.79+0.20 mg/ kg min). After 90 min of sustained hyperinsulinemia, splanchnic glucose balance reverted to a net uptake which was similar in uremics (0.42±0.11 mg/kg-min) and controls (0.53+0.12 mg/kg.min). In contrast, glucose uptake by the leg was reduced by 60% in the uremic group (21+1 vs. 52+8 ,umol/min kg of leg wt; P < 0.005) and this decrease closely paralleled the decrease in total glucose metabolism by the entire body. These results indicate that: (a) suppression of hepatic glucose production by physiologic hyperinsulinemia is not impaired by uremia, (b) insulinmediated glucose uptake by the liver is normal in uremic subjects, and (c) tissue insensitivity to insulin is the primary cause of insulin resistance in uremia.

Comparative analysis of lipid and glucose metabolism biomarkers in non-diabetic hemodialysis and peritoneal dialysis patients

“…Insulin resistance, which is also considered a risk factor for CVD, was recently associated with all-cause mortality even in a large cohort of 5511 non-diabetic patients 4 and is commonly found in CKD patients, even during their early stages. 10 Insulin sensitivity was lower in our PD patients in all three indirect methods we performed: HOMA index, QUICKI and triglycerides/HDL-c ratio. The mechanism involved is probably related to the higher glucose load daily offered to PD patients, which leads to a high fasting glucose and a compensatory hyperinsulinemia.…”

“…The progressive decline of renal function intensifies CKD-related risk factors such as mineral metabolism disturbances, fluid overload, anemia, uremic toxicity and worsening of insulin resistance, dislipidemia and increased signs of oxidative stress and inflammation. 10,11 Its known that initiation of dialysis therapy partially revert those disturbances. 12 However, initiation of PD adds potential harm related to the great glucose absorption from PD fluids that lead to worsening of insulin resistance, dyslipidemia and higher levels of HbA1c.…”

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

“…Both Type i diabetes [27,28] and chronic renal failure [29,30] determine an impairment of insulin action. The cause of insulin resistance is multifactorial and has been related to hormonal and metabolic abnormalities [13,[31][32][33][34][35][36][37][38][39][40][41][43][44][45][46][47][48][49][50][51].…”

“…In many reports "pure" insulin dependent diabetic patients [27,41] and "pure" uraemic patients [30], showed no insulin resistance at the liver site with a similar insulin dose. We believe that the delayed suppression of hepatic glucose production (70 min) may be due to the combination of diabetes and uraemia, in this study group (1 a).…”

Postprandial hyperglycemia and hyperinsulinemia associated with renal arterio-arteriolosclerosis in chronic kidney disease

“…1,2 An association between insulin resistance and uremia has long been established, 3 and recent studies have consistently reported that insulin resistance is present early in the course of chronic kidney disease (CKD). 4,5 In addition, glucose metabolism/insulin resistance seems to have a role in the progression of CKD.…”