Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic chronic kidney disease patients: a randomized controlled study

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Abstract

Purpose

The purpose of the study is to observe the effects of active vitamin D supplementation on insulin resistance and islet β-cell function (HOMA-β) in patients with non-diabetic chronic kidney disease (NDCKD).

Methods

A total of 134 patients with NDCKD who met the inclusion criteria were enrolled in the prospective controlled study and categorized as such: 60 patients in the non-dialysis (ND) group; 36, hemodialysis (HD) group; and 38, peritoneal dialysis (PD) group. Each group was divided into two equal-numbered subgroups for vitamin D supplementation. Those in the experimental subgroups received calcitriol 0.5 ug/day orally, and were followed-up for 6 months. A total of 117 patients were followed-up, including 57 patients in the ND group; 29, HD group; and 31, PD group. Changes in the insulin resistance index (HOMA-IR) and HOMA-β index were calculated and compared at the time of enrollment and after 1, 3, and 6 months of intervention.

Results

(1) Mean HOMA-IR value: In the ND group, mean HOMA-IR value of the experimental group significantly decreased compared with that of the control group after 3 months of intervention ( P = 0.02). In the HD and PD groups, there was no statistical difference between the experimental and control groups ( P > 0.05). (2) Mean HOMA-β index: In the ND group, mean HOMA-β index of the experimental group was higher than that of the control group after 1 month of active vitamin D treatment ( P = 0.03), and, with an extended intervention time, the index gradually increased ( P < 0.001). In the HD group, mean HOMA-β index of the experimental group was higher than that of the control group after 3 months of active vitamin D treatment ( P = 0.01). Among PD patients, mean HOMA-β index of the patients in the experimental group was higher than that of the control group after 6 months of active vitamin D treatment ( P = 0.02).

Conclusions

Active vitamin D supplementation improved insulin resistance and HOMA-β after 6 months in ND patients, but only improved HOMA-β in the dialysis patients, with no significant effect on insulin resistance.

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Most cited references 26

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Vitamin D Switches BAF Complexes to Protect β Cells

Michael Downes, Ronald Evans, Ruth T Yu … (2018)

A primary cause of disease progression in type 2 diabetes (T2D) is β cell dysfunction due to inflammatory stress and insulin resistance. However, preventing β cell exhaustion under diabetic conditions is a major therapeutic challenge. Here, we identify the vitamin D receptor (VDR) as a key modulator of inflammation and β cell survival. Alternative recognition of an acetylated lysine in VDR by bromodomain proteins BRD7 and BRD9 directs association to PBAF and BAF chromatin remodeling complexes, respectively. Mechanistically, ligand promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response. Importantly, pharmacological inhibition of BRD9 promotes PBAF-VDR association to restore β cell function and ameliorate hyperglycemia in murine T2D models. These studies reveal an unrecognized VDR-dependent transcriptional program underpinning β cell survival and identifies the VDR:PBAF/BAF association as a potential therapeutic target for T2D.

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Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease.

R Prager, A. Kautzky-Willer, E. Franek … (1998)

In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addition, healthy age-matched subjects. Insulin sensitivity and other variables of glucose metabolism were assessed using a frequent sampling intravenous glucose tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was assessed in renal patients using the inulin-clearance technique. Mean insulin sensitivity index (SI), that is, insulin sensitivity, was significantly lower (P < 0.001) in all patients combined than in matched healthy subjects (N = 16; 14 males, mean age 42 +/- 3 years; mean SI 8.6 +/- 0.8 min-1 uU/ml). The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intact PTH (r = -0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82). Consequently, the mean SI was similar in renal patients with GFR within the normal range (N = 19; 17 males, mean age 41 +/- 2 years; mean GFR 119 +/- 5 ml/min/1.73 m2; 5.1 +/- 0.7 min-1 uU/ml), in patients with mild to moderate renal failure (N = 16; 15 males, 46 +/- 3 years; 67 +/- 4 ml/min/1.73 m2; 5.1 +/- 0.7 min-1 microU/ml) and in patients with advanced renal failure (N = 15; 13 males, 46 +/- 3 years; 25 +/- 2 ml/min/1.73 m2; 4.7 +/- 0.6 min-1 uU/ml). Mean fasted plasma insulin concentration, the area under the curve for plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patients than in healthy subjects, reflecting hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration (r = -0.32, P < 0.009), AUC (r = -0.62, P < 0.0001) and TID (r = -0.34, P < 0.004) in patients were significantly correlated with insulin sensitivity (SI). The present data document that insulin resistance and concomitant hyperinsulinemia are present early in the course of renal disease, that is, even in patients with GFR within the normal range, irrespective of the type of renal disease. This observation may have potential implications with respect to the high cardiovascular morbidity and mortality in patients with renal disease.

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The regulation of parathyroid hormone secretion and synthesis.

Rajiv Kumar, James R Thompson (2011)

Secondary hyperparathyroidism classically appears during the course of chronic renal failure and sometimes after renal transplantation. Understanding the mechanisms by which parathyroid hormone (PTH) synthesis and secretion are normally regulated is important in devising methods to regulate overactivity and hyperplasia of the parathyroid gland after the onset of renal insufficiency. Rapid regulation of PTH secretion in response to variations in serum calcium is mediated by G-protein coupled, calcium-sensing receptors on parathyroid cells, whereas alterations in the stability of mRNA-encoding PTH by mRNA-binding proteins occur in response to prolonged changes in serum calcium. Independent of changes in intestinal calcium absorption and serum calcium, 1α,25-dihydroxyvitamin D also represses the transcription of PTH by associating with the vitamin D receptor, which heterodimerizes with retinoic acid X receptors to bind vitamin D-response elements within the PTH gene. 1α,25-Dihydroxyvitamin D additionally regulates the expression of calcium-sensing receptors to indirectly alter PTH secretion. In 2°HPT seen in renal failure, reduced concentrations of calcium-sensing and vitamin D receptors, and altered mRNA-binding protein activities within the parathyroid cell, increase PTH secretion in addition to the more widely recognized changes in serum calcium, phosphorus, and 1α,25-dihydroxyvitamin D. The treatment of secondary hyperparathyroidism by correction of serum calcium and phosphorus concentrations and the administration of vitamin D analogs and calcimimetic agents may be augmented in the future by agents that alter the stability of mRNA-encoding PTH.

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Author and article information

Contributors

Zongwu Tong: tongzongwud@126.com

Journal

Journal ID (nlm-ta): Int Urol Nephrol

Journal ID (iso-abbrev): Int Urol Nephrol

Title: International Urology and Nephrology

Publisher: Springer Netherlands (Dordrecht )

ISSN (Print): 0301-1623

ISSN (Electronic): 1573-2584

Publication date (Electronic): 22 November 2021

Publication date PMC-release: 22 November 2021

Publication date (Print): 2022

Volume: 54

Issue: 7

Pages: 1725-1732

Affiliations

[1 ]GRID grid.459918.8, Department of Nephrology, , People’s Hospital of Yuxi City, The Sixth Affiliated Hospital of Kunming Medical University, ; Yuxi City, 653100 Yunnan Province China

[2 ]Department of Internal Medicine, Beicheng Health Center, Hongta District, Yuxi City, 653100 Yunnan Province China

Author information

Yongxin Lu http://orcid.org/0000-0002-0414-375X

Article

Publisher ID: 2968

DOI: 10.1007/s11255-021-02968-7

PMC ID: 9184423

PubMed ID: 34807347

SO-VID: 49073cc0-3fbe-4fa0-8feb-e26598ccf5a3

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 22 March 2021

Date accepted : 25 July 2021

Funding

Funded by: medical reserve talents training program of yunnan provincial health commission of china

Award ID: H-2018053

Award Recipient : Yongxin Lu

Funded by: Applied Basic Research of Yunnan Province, China (Joint Special Project of Kunming Medical University)

Award ID: 2017FE468 (-229)

Award Recipient : Yongxin Lu

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ScienceOpen disciplines: Nephrology

Keywords: active vitamin d,non-diabetic chronic kidney disease,insulin resistance,islet β-cell function

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ScienceOpen disciplines: Nephrology

Keywords: active vitamin d, non-diabetic chronic kidney disease, insulin resistance, islet β-cell function

Effects of active vitamin D on insulin resistance and islet β-cell function in non-diabetic chronic kidney disease patients: a randomized controlled study

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Karger: Nephrology

Most cited references 26

Vitamin D Switches BAF Complexes to Protect β Cells

Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease.

The regulation of parathyroid hormone secretion and synthesis.

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