Impact of activated vitamin D on insulin resistance in nondiabetic chronic kidney disease patients

Abstract

Background Although vitamin D deficiency has been associated with increased insulin resistance, a causal link has not been established. Interpreting the relationship has been confounded by a close correlation between vitamin D deficiency and obesity. The current clinical approach of assessing endogenous 25-hydroxyvitamin D (25(OH)D) concentrations in patients with Chronic Kidney Disease(CKD), and independently administering activated vitamin D(AD), allows a unique opportunity to clarify cause and effect in the relationship of vitamin D, obesity, and insulin resistance. Methods We assessed how 25(OH)D and body mass index(BMI) related to fasting insulin concentrations in 120 nondiabetic CKD patients. In addition, we described how treatment with AD modified these relationships. Results In the full cohort, fasting insulin concentrations varied inversely with both 25(OH)D (r=−0.22, P=0.02) and BMI (r=−0.36, P<.0001). The administration of AD altered these relationships. In individuals treated with AD, there was no association between 25(OH)D and fasting insulin, and the mean fasting insulin concentrations were significantly lower than in those not receiving AD (40.5 ± 22.0 vs 54.1 ± 30.9 pmol/L, P=0.01). In a multivariate analysis, both AD treatment and BMI were independent predictors of fasting insulin. Furthermore, obese patients treated with AD had insulin concentrations similar to nonobese patients (46.1 ± 24.9 vs 40.2 ± 21.5 pmol/L), whereas untreated obese patients had markedly higher fasting insulin concentrations (74.4 ± 33.4 pmol/L, P=0.003). Conclusion 25(OH)D deficiency is associated with insulin resistance in CKD. Replacement with pharmacologic doses of AD is associated with lower fasting insulin concentrations, especially in obese patients.

Insulin Resistance Is Inversely Associated with the Status of Vitamin D in Both Diabetic and Non-Diabetic Populations

“… Forest plot for non-diabetic subject studies showing the correlation between status of vitamin D and fasting plasma insulin. The random effect model was used for the determination of correlation and 95% CI [ 19 , 20 , 57 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ]. …”

Vitamin D receptor polymorphisms in overweight/obese chronic kidney disease patients undergoing hemodialysis

“…In 1,25(OH)2D deficient animals, intravenous 1.25(OH)2D administration improves glucose intolerance and induces insulin releasing from beta cells of pancreas in response to a glucose challenge (46). In a study involving 120 non-diabetic CKD patients, obese patients treated with 1,25(OH)2D had similar insulin concentrations compared to non-obese patients, whereas untreated obese patients had a higher insulin concentration (47). In our study, obese/overweight patients carrying FokI homozygous mutant TT genotype had higher glucose concentrations compared to those having CC and CT genotypes.…”

Vitamin D in Kidney Disease

“…Some short-term studies with vitamin D supplementation in dialysis patients have shown increased insulin sensitivity and secretion (reviewed in [72]). A cross-sectional study of 120 non-diabetic CKD patients found that insulin levels were decreased in patients treated with activated vitamin D [74]. A cross-sectional study of 120 non-diabetic CKD patients found that insulin levels were decreased in patients treated with activated vitamin D [74].…”