Insulin resistance in chronic kidney disease: a systematic review

Abstract

Insulin resistance (IR) is an early metabolic alteration in chronic kidney disease (CKD) patients, being apparent when the glomerular filtration rate is still within the normal range and becoming almost universal in those who reach the end stage of kidney failure. The skeletal muscle represents the primary site of IR in CKD, and alterations at sites beyond the insulin receptor are recognized as the main defect underlying IR in this condition. Estimates of IR based on fasting insulin concentration are easier and faster but may not be adequate in patients with CKD because renal insufficiency reduces insulin catabolism. The hyperinsulinemic euglycemic clamp is the gold standard for the assessment of insulin sensitivity because this technique allows a direct measure of skeletal muscle sensitivity to insulin. The etiology of IR in CKD is multifactorial in nature and may be secondary to disturbances that are prominent in renal diseases, including physical inactivity, chronic inflammation, oxidative stress, vitamin D deficiency, metabolic acidosis, anemia, adipokine derangement, and altered gut microbiome. IR contributes to the progression of renal disease by worsening renal hemodynamics by various mechanisms, including activation of the sympathetic nervous system, sodium retention, and downregulation of the natriuretic peptide system. IR has been solidly associated with intermediate mechanisms leading to cardiovascular (CV) disease in CKD including left ventricular hypertrophy, vascular dysfunction, and atherosclerosis. However, it remains unclear whether IR is an independent predictor of mortality and CV complications in CKD. Because IR is a modifiable risk factor and its reduction may lower CV morbidity and mortality, unveiling the molecular mechanisms responsible for the pathogenesis of CKD-related insulin resistance is of importance for the identification of novel therapeutic targets aimed at reducing the high CV risk of this condition.

Glucocorticoid activation by 11β‐hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: A cross‐sectional study

“…15,16 Insulin resistance manifests from the early stages of renal impairment, and diabetes mellitus co-exists in one third of people with CKD. 15,16 Insulin resistance manifests from the early stages of renal impairment, and diabetes mellitus co-exists in one third of people with CKD.…”

Coronary heart disease risk associated with the dyslipidaemia of chronic kidney disease

“…A potential unifying explanation for the observed dyslipidaemic pattern of CKD is that of insulin resistance which has been shown to be an early metabolic alteration in CKD and independent of diabetes and obesity in this population 25. More research is, however, needed to further the understanding of the likely complex relationship between kidney function, insulin resistance and lipoprotein metabolism.…”

The relationship between chronic kidney function and homeostasis model assessment of insulin resistance and beta cell function in Korean adults with or without type 2 diabetes mellitus

“…In the measurements of IR and beta cell function, the "gold-standard" method (e.g., hyperinsulinemic-euglycemic clamp and the hyperglycemic clamp test) is known to more accurate than HOMA indices. Some studies suggested that HOMA-IR is imperfect to estimate insulin resistance in CKD due to its several limitations [45,46]. Therefore, in future studies, it is necessary to study the relationship between CKD and IR and beta cell function using the "gold-standard" method.…”