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Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD
Ian H de Boer1, Leila Zelnick2, Maryam Afkarian2
1Division of Nephrology and Kidney Research Institute and Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and deboer@u.washington.edu.
Insights
Moderate to severe chronic kidney disease (CKD) reduces insulin sensitivity and clearance, partly due to lifestyle and body composition. This leads to a high prevalence of impaired glucose tolerance in CKD patients.
Area of Science:
- Nephrology
- Endocrinology
- Metabolic Science
Background:
- Chronic kidney disease (CKD) significantly impacts glucose and insulin metabolism.
- The precise mechanisms underlying these metabolic disturbances in moderate-severe CKD are not fully understood.
Purpose of the Study:
- To investigate insulin sensitivity, clearance, secretion, and glucose tolerance in individuals with moderate-severe non-diabetic CKD compared to healthy controls.
- To explore the relationship between estimated glomerular filtration rate (eGFR) and these metabolic parameters in CKD patients.
Main Methods:
- Cross-sectional study involving 59 participants with non-diabetic CKD and 39 healthy controls.
- Utilized hyperinsulinemic-euglycemic clamp and intravenous/oral glucose tolerance tests to assess insulin sensitivity, clearance, secretion, and glucose tolerance.
- Adjusted analyses considered demographics, smoking, physical activity, diet, fat mass, and fat-free mass.
Main Results:
- Participants with CKD exhibited significantly lower insulin sensitivity and insulin clearance compared to controls.
- Insulin clearance was positively correlated with insulin sensitivity.
- While insulin secretion and glucose tolerance did not significantly differ between groups, 65% of CKD participants had impaired glucose tolerance.
- eGFR did not significantly correlate with insulin sensitivity or clearance within the CKD group.
Conclusions:
- Moderate-severe CKD is associated with reduced insulin sensitivity and clearance, partially explained by lifestyle and body composition factors.
- No CKD-specific deficit in insulin secretion was observed, but insulin resistance combined with insufficient insulin secretion augmentation contributes to high rates of impaired glucose tolerance.
- These findings highlight the complex interplay between kidney function, metabolic health, and lifestyle in CKD.
Abstract:
Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m(2)) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, -0.7; 95% confidence interval, -1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, -85; 95% confidence interval, -160 to -10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.
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