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Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.

ABSTRACT: Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testosterone on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM), 2659 participants from the Henan Rural Cohort were included in the case-control study. Generalized linear models were utilized to estimate associations of vitamin D with IFG or T2DM and interactive effects of vitamin D and testosterone on IFG or T2DM. Principal component analysis (PCA) and mediation analysis were used to estimate whether the lipid profile mediated the association of vitamin D with IFG or T2DM. Serum 25(OH)D₃, 25(OH)D₂, and total 25(OH)D levels were negatively correlated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 0.99 (0.97, 1.00), 0.85 (0.82, 0.88), and 0.97 (0.96, 0.98), respectively). Similarity results for associations between serum 25(OH)D₂ and total 25(OH)D with T2DM (ORs (95%CIs): 0.84 (0.81, 0.88) and 0.97 (0.96, 0.99)) were observed, whereas serum 25(OH)D₃ was negatively correlated to T2DM only in the quartile 2 (Q2) and Q3 groups (both p < 0.05). The lipid profile, mainly TC and TG, partly mediated the relationship between 25(OH)D₂ or total 25(OH)D and IFG or T2DM and the proportion explained was from 2.74 to 17.46%. Furthermore, interactive effects of serum 25(OH)D₂, total 25(OH)D, and testosterone on T2DM were observed in females (both p for interactive <0.05), implying that the positive association between serum testosterone and T2DM was vanished when 25(OH)D₂ was higher than 10.04 ng/mL or total 25(OH)D was higher than 40.04 ng/mL. Therefore, ensuring adequate vitamin D levels could reduce the prevalence of IFG and T2DM, especially in females with high levels of testosterone.

SUBMITTER: Wang L

PROVIDER: S-EPMC7823697 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.

Wang Lulu L Liu Xue X Hou Jian J Wei Dandan D Liu Pengling P Fan Keliang K Zhang Li L Nie Luting L Li Xing X Huo Wenqian W Jing Tao T Li Wenjie W Wang Chongjian C Mao Zhenxing Z

Nutrients 20201230 1

Numerous studies have investigated the associations between serum vitamin D or testosterone and diabetes; however, inconsistencies are observed. Whether there is an interaction between vitamin D and testosterone and whether the lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)) mediates the association between vitamin D and diabetes is unclear. To investigate the effect of vitamin D and testoste ...[more]

PMID: 33396618

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Project description:IntroductionLow serum testosterone is related to increased mortality in male dialysis patients. An association of vitamin D status with serum androgen levels with concordant seasonal variation has been described, but it is undecided whether vitamin D supplementation improves testosterone levels.MethodsIn a randomized, placebo-controlled, and double-blind manner, we investigated the effects of an oral vitamin D supplementation in healthy subjects and hemodialysis patients on testosterone levels. One hundred three healthy individuals received cholecalciferol 800 IE/day (n = 52) or placebo (n = 51) for 12 weeks. Thirty-three hemodialysis patients received cholecalciferol adapted to their serum levels following current guidelines (n = 15) or placebo (n = 18) for 12 weeks.ResultsIn healthy individuals, 25(OH)D3 levels rose significantly in the verum group (38.1 ± 13.7 vs. 72.5 ± 15.4 nmol/L, p < 0.001), whereas in the placebo group, levels dropped (37.7 ± 14.7 vs. 31.9 ± 13.1, p < 0.001). Testosterone levels did not change significantly (verum, males: 20.9 ± 6.6 vs. 20.5 ± 7.9 nmol/L, p = 0.6; verum, females: 0.9 ± 0.5 vs. 0.92 ± 0.5, p = 0.4; placebo, males: 18.5 ± 10.2 vs. 21.8 ± 16.5, p = 0.07, placebo, females: 1.6 ± 4.2 vs. 1.6 ± 4.9, p = 0.6). In dialysis patients, the mean cholecalciferol level was only 32.3 ± 17.8 nmol/L, with only 2% of the values being within the normal range. Cholecalciferol levels normalized in the verum group (29.4 ± 11.2 vs. 87.8 ± 22.3, p < 0.001), whereas levels dropped further in the placebo group (33.6 ± 16.6 vs. 24.6 ± 8.0 nmol/L, p < 0.001). Testosterone levels did not change significantly (verum, males: 8.0 ± 3.7 vs. 7.8 ± 3.8, p = 0.8; verum, females: 1.3 ± 1.0 vs. 1.2 ± 1.0 nmol/L, p = 0.5; placebo, males: 11.9 ± 5.0 vs. 11.6 ± 4.0 nmol/L, p = 0.6; placebo, females: 0.8 ± 0.5 vs. 0.7 ± 0.4 nmol/L, p = 0.8).ConclusionSerum testosterone levels in hemodialysis patients and healthy individuals are independent from vitamin D status and cannot be significantly increased by cholecalciferol supplementation.

Project description:BackgroundDyslipidemia is a major risk factor for cardiovascular disease, and diabetes impacts the lipid metabolism through multiple pathways. In addition to the standard lipid measurements, apolipoprotein concentrations provide added awareness of the burden of circulating lipoproteins. While common genetic variants modestly affect the serum lipid concentrations, rare genetic mutations can cause monogenic forms of hypercholesterolemia and other genetic disorders of lipid metabolism. We aimed to identify low-frequency protein-altering variants (PAVs) affecting lipoprotein and lipid traits.MethodsWe analyzed whole-exome (WES) and whole-genome sequencing (WGS) data of 481 and 474 individuals with type 1 diabetes, respectively. The phenotypic data consisted of 79 serum lipid and apolipoprotein phenotypes obtained with clinical laboratory measurements and nuclear magnetic resonance spectroscopy.ResultsThe single-variant analysis identified an association between the LIPC p.Thr405Met (rs113298164) and serum apolipoprotein A1 concentrations (p=7.8×10-8). The burden of PAVs was significantly associated with lipid phenotypes in LIPC, RBM47, TRMT5, GTF3C5, MARCHF10, and RYR3 (p<2.9×10-6). The RBM47 gene is required for apolipoprotein B post-translational modifications, and in our data, the association between RBM47 and apolipoprotein C-III concentrations was due to a rare 21 base pair p.Ala496-Ala502 deletion; in replication, the burden of rare deleterious variants in RBM47 was associated with lower triglyceride concentrations in WES of >170,000 individuals from multiple ancestries (p=0.0013). Two PAVs in GTF3C5 were highly enriched in the Finnish population and associated with cardiovascular phenotypes in the general population. In the previously known APOB gene, we identified novel associations at two protein-truncating variants resulting in lower serum non-HDL cholesterol (p=4.8×10-4), apolipoprotein B (p=5.6×10-4), and LDL cholesterol (p=9.5×10-4) concentrations.ConclusionsWe identified lipid and apolipoprotein-associated variants in the previously known LIPC and APOB genes, as well as PAVs in GTF3C5 associated with LDLC, and in RBM47 associated with apolipoprotein C-III concentrations, implicated as an independent CVD risk factor. Identification of rare loss-of-function variants has previously revealed genes that can be targeted to prevent CVD, such as the LDL cholesterol-lowering loss-of-function variants in the PCSK9 gene. Thus, this study suggests novel putative therapeutic targets for the prevention of CVD.

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Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.

Publications

Serum Vitamin D Affected Type 2 Diabetes though Altering Lipid Profile and Modified the Effects of Testosterone on Diabetes Status.

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