Original investigations
Pathogenesis and treatment of kidney disease and hypertension
Insulin resistance in patients with chronic kidney disease

https://doi.org/10.1053/j.ajkd.2004.09.034Get rights and content

Background: It has been reported that insulin resistance appears at an earlier stage of chronic kidney disease (CKD). However, few data are available concerning what factors of metabolic abnormalities, such as apolipoprotein (Apo) profile or acidosis, might be associated with insulin resistance in patients with CKD. Methods: We used the hyperinsulinemic euglycemic glucose clamp technique to examine insulin sensitivity in patients without diabetes (n = 29) with different stages of renal function. Results were compared with those in healthy subjects (n = 10) and related to various affecting variables. Results: In healthy subjects, the glucose disposal rate (GDR) was 9.93 ± 1.33 mg/kg/min. The GDR of patients with CKD (6.91 ± 2.46 mg/kg/min) was significantly less than that of healthy subjects (P < 0.01), which shows diminished insulin sensitivity in patients with CKD. There was a negative correlation between GDR and serum creatinine level (r = −0.449; P < 0.05) and positive correlations between GDR and creatinine clearance (r = 0.549; P < 0.01) and Apo A-1/B levels (r = 0.396; P < 0.05). Of particular relevance is the observed close correlation between GDR and bicarbonate level, with an extremely high predictive value for degree of acidosis (r = 0.611; P < 0.0005). Stepwise multivariate regression analysis selected bicarbonate (F = 13.28) and Apo A-1/B levels (F = 6.58) as independent contributing variables. Conclusion We found that insulin resistance correlated linearly with decline in renal function. Independent variables related to insulin resistance were bicarbonate and Apo A-1/B levels in patients with CKD.

Section snippets

Methods

Twenty-nine Japanese patients with CKD aged 29 to 78 years were examined; 16 patients had biopsy-confirmed chronic glomerulonephritis, and the remaining 13 patients had nephrosclerosis. No patient had diabetes mellitus or autosomal dominant polycystic kidney disease. Other exclusion criteria were liver disease, malignant tumors, previous history of stroke or ischemic heart disease, or such systemic disorders as rheumatoid arthritis or systemic lupus erythematosus. CKD is defined as evident

Results

Steady-state plasma glucose concentrations during the last 30 minutes of the glucose clamp study were 98.1 ± 1.5 mg/dL (5.4 ± 0.1 mmol/L) for patients and 98.3 ± 1.6 mg/dL (5.5 ± 0.1 mmol/L) for controls. Mean plasma insulin values determined at 120 minutes during the glucose clamp study were 64.8 ± 10.8 μU/mL (465 ± 77 pmol/L) in healthy subjects and 72.7 ± 9.8 μU/mL (522 ± 70 pmol/L) in patients.

In healthy subjects, GDR was 9.93 ± 1.33 mg/kg/min. GDR of patients with CKD was 6.91 ± 2.46

Discussion

It recently was reported that insulin resistance is present early in the course of renal disease.9, 10, 11, 12 In the present study, contributing factors related to insulin resistance in addition to traditional atherosclerotic cardiovascular risk factors were determined. Among lipid profiles, we found that Apo A-1/B and TG levels are both associated with GDR. Regarding TG level, data are in good agreement with observations of Fliser et al.11 However, we first report that Apo A-1/B ratio is

References (25)

  • J. Howard et al.

    Insulin sensitivity and atherosclerosis

    Circulation

    (1996)
  • J.F. Moorhead et al.

    The role of abnormalities of lipid metabolism in the progression of renal disease

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    Originally published online as doi:10.1053/j.ajkd.2004.09.034 on December 22, 2004.

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