Effects of vitamin D3 supplementation combined with standardized hypoglycemic regimen on islet β cell function and macrovascular complications in newly diagnosed type 2 diabetes mellitus

Objective To observe the effect of oral vitamin A and vitamin D on improvement of the prognosis of type 2 diabetes and tuberculosis patients,and analyze the effect of vitamin A and vitamin D on immune cell function in type 2 diabetic patients of pulmonary tuberculosis. Methods Fifty-eight patients were diagnosed with type 2 diabetes and simultaneously tuberculosis patients were randomly di-vided into vitamin（VA）intervention group,vitamin D（VD）intervention group,vitamin A ＋ vitamin D （combined）intervention group,and control group. One the basis of normal standard treatment,addition-al oral VA was given in VA intervention group,additional VD was given,in joint intervention group,oral vitamin A ＋ vitamin D was given,while in the control group,no vitamin oral drugs were given. After giv-ing hypoglycemic therapy combined with anti-TB drugs,the blood glucose levels and acid-fast bacilli neg-ative rates after chemotherapy were observed. The CD4 ＋ / CD8 ＋ levels after treatment were observed. Results AFB negative rates of VA group,VD group and the combination group were significantly higher than those in control group（P ﹤ 0. 05）. But there was no significant difference in combination of vitamins A,D on tuberculosis negative rate. Alone or in combination with vitamin A,D had no significant effect on reducing fasting blood glucose levels. Compared with the control group and the monotherapy group, the combination of vitamin A and vitamin enhanced the CD4 ＋ / CD8 ＋ levels（P ﹤ 0. 05）. Conclusions Alone or in combination with vitamin A and vitamin D can improve the prognosis of patients with diabetes mellitus type 2 and TB and improve the patients’immune state. Key words: Vitamin A; Vitamin D; Type 2 diabetes mellitus; Pulmonary tuberculosis

Objective To investigate the value of 25-hydroxy vitamin D levels in patients with type 2 diabetic nephropathy. Methods Six hundred type 2 diabetic patients were enrolled in the study. The height, weight and fasting venous blood lipids and 25 hydroxyvitamin D levels were measured, and the urinary albumin excretion rates in one day were calculated, the relationship between diabetic nephropathy and 25 hydroxyvitamin D levels was analyzed. Results There was no significant difference in the gender, age, LDL-C, TC, HbAlc, HDL-C levels, body mass index (BMI), smoking history between the two groups (P<0.05). The TG level, incidences of hypertension, obesity, serum creatinine levels, use of hypoglycemic drugs ratio were higher, the duration of diabetes was longer (P<0.05). The incidence of high blood lipid in macroalbuminuria group was higher than other groups (P<0.05). The vitamin deficiency rates in patients with diabetic nephropathy were significantly higher than those in patients without diabetic nephropathy (P<0.05). The urinary albumin excretion rate in vitamin D deficiency group was significantly higher than that of the other two groups (P<0.05). Women were more likely to have difficiency of vitamin D than men (P<0.05). The decreased HDL-C levels was correlated with lack of vitamin D, and smoking and hyperlipidemia abnormal proportion, HbAlc, duration of diabetes, hypertension were not correlated with vitamin D difficiency. There was a significant negative correlation between UAER and Vitamin D levels (r=-1.792, P<0.01), but the serum creatinine concentration with vitamin D levels was not correlated, and lack of vitamin D could significantly increase the incidence of diabetic nephropathy (P<0.05). Conclusions The patients with type 2 diabetes has low 25-vitamin D levels, and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus increases with the decrease of the level of 25-hydroxy vitamin D. Key words: 25-hydroxy vitamin D; Diabetic nephropathy; Type 2 diabetes mellitus; Urinary albumin excretion rate; Detection value

Objective To explore the association of adiponectin and macrovascular complica-tions in patients with type 2 diabetes mellitus. Methods Eighty - three cases of type 2 diabetes mellitus were divided into two groups (43 cases with macrovascular disease and 40 cases DM without macroangi-opathy), plasma adiponectin, HbAlc, fasting plasma glucose and plasma insulin levels were detected in all cases and were compared with those of 41 healthy people. Results Adiponectin in macroangiopathy group and DM group without macroangiopathy were significantly lower than those of healthy control group (P < 0.01). Adiponectin was also significantly decreased in DM group with macroangiopathy as com-pared with DM group without macroangiopathy (P < 0.01). Conclusions The decreased adiponectin seems to be a risk factor of type 2 diabetes and its macrovascular complication. Key words: Type 2 diabetes mellitus; Macroangiopathy ; Adiponectin

Objective To study the change of vitamin D in newly diagnosed type 2 diabetes mellitus (T2DM), and to explore the relationship between the level of serum vitamin D and islet β cell dysfunction as well as insulin resistance. Methods Fasting serum 25-hydroxyvitamin D3 (25-(OH)D3) concentration was measured by high pressure liquid chromatography (HPLC) in 97 newly diagnosed T2DM patients (men 57, women 40, aged (52±10)years) and 69 healthy controls (men 40, women 29, aged (50±11)years). Oral-glucose-tolerance test was performed, and area under the curve of glucose (AUCG), area under the curve of insulin (AUCI), early-phase insulin secretion index (ΔI30/ΔG30), β cell function index (HOMA-B), insulin resistance index (HOMA-IR) were compared between T2DM with low 25-(OH)D3 ((25-(OH)D3 <37.5 nmol/L, n=61) and those without (n=36). The correlation of serum 25-(OH)D3 with sex, age, body mass index (BMI), waist-hip rate (WHR), blood pressure, lipids, HbA1c, insulin resistance and β cell function was analysed by using Pearson correlation and multiple stepwise regression analysis. Results The level of serum 25-(OH)D3 was much lower in T2DM patients than in controls ((36±19)nmol/L vs (80±26) nmol/L, t=-13.00, P<0.01). The prevelence of hypovitaminosis 25-(OH)D3 in T2DM was 62.9% (61/97). Among T2DM, when compared with those without hypovitaminosis 25-(OH)D3, patients with hypovitaminosis 25-(OH)D3 showed higher HbA1c and AUCG ((10.1±3.0)% vs (7.7±2.6)%, (32±7) h·mmol-1·L-1vs (25±7) h·mmol-1·L-1,t values were 4.44 or 4.45, both P<0.01), although HOMA-B, ΔI30/ΔG30, and AUCI were significantly lower (21±16 vs 75±64, 1.9±1.9 vs 8.3±7.7, (30±21) h·mU-1·L-1vs(104±80) h·mU-1·L-1,t values were -5.68, -6.81, and -7.69; all P<0.01). In multiple stepwise regression analysis, ΔI30/ΔG30 and AUCI had independent positive correlation with 25-(OH)D3 (t values were 2.21 and 4.67, all P<0.01). Conclusion 25-(OH)D3 is lower in newly diagnosed T2DM, and associated with severity of blood glucose disorders. The shortage of vitamin D in T2DM may be correlated with decreased early-phase insulin secretion and whole insulin secretion. Key words: Diabetes mellitus, type 2; Calcifediol; Insulin

Objective To analyze the serum level of 25-hydroxy vitamin D3 and the degree of vitamin D deficiency in the patients with type 2 diabetes mellitus,and the relationships between the degree of vitamin D deficiency,durations of diabetes and glycosylated hemoglobin A1c (HbA1c) levels were also investigated.Methods 140 patients with type 2 diabetes mellitus (60 male and 80 female) were selected from the Department of Endocrinology of The General Hospital of Tianjin Medical University,aged 21 to 89,with an average age of (58.25 ± 13.76) years old.Serum 25-hydroxy vitamin D3 levels between different age groups (＜50,≥ 50 and ＜70,≥70years old group) and tested season groups (winter and spring,summer and autumn group),different duration of diabetes groups (＜ 10,≥ 10 and ＜20,≥ 20 years group) and different HbA l c level groups (＜ 7％,≥7％ and＜ 10％,≥ 10％) were compared.Results (1)The serum 25(OH)D3 levels of these 140 patients were all below normal range,and the average levels was (40.07 ± 16.12) nmol/L.The prevalence of severe vitamin D deficiency,deficiency and sufficiency were 13.57％,67.86％ and 4.29％,respectively.But there was no significant difference between male and female both in the serum 25(OH)D3 levels and the degree of vitamin D deficiency(t =0.803,x2=0.189,both P ＞0.05).(2) The serum 25(OH)D3 levels of patients aged ≥ 50 and＜70 were lower than that of the subjects aged ＜50 in male (F =2.362,P ＜0.05).In female,the serum 25 (OH)D3 levels of patients aged ≥ 50 were lower than that of the subjects aged ＜50 (F =3.928,P ＜ 0.05),and the percentages of vitamin D deficiency were also greater than that in patients younger than 50 years (x2=10.036,P ＜0.01).(3)The serum 25(OH)D3 levels in winter and spring were lower than that in summer and autumn (t =-4.681,P ＜0.01),and the percentage of severe vitamin D deficiency and deficiency were increased as well (x2=18.202,P ＜ 0.01).(4)The serum 25(OH)D3 levels in patients whose durations of diabetes were more than 10 years were lower than that of patients with diabetic duration less than 10 years (F =5.489,P ＜0.05,P ＜0.01),and the percentage of severe vitamin D deficiency in patients whose durations were more than 20 years was higher than that of patients with diabetic duration less than 10 years (x2=7.284,P ＜0.05).(5)The serum 25 (OH)D3 levels in patients whose HbA l c were more than 7％ were lower than those with HbAlc lower than 7％(F =3.963,P ＜0.01),and the percentages of severe vitamin D deficiency and deficiency were higher than that of patients with HbAlc lower than 7％ as well (x2=6.712,P ＜0.05).Conclusion Vitamin D deficiency is common in patients with type 2 diabetes,especially in patient with long durations and continuously poor blood glucose control.The assessment and supplement of vitamin D should be strengthened in patients with diabetes especially in winter. Key words: 25-Hydroxy vitamin D3; Vitamin D deficiency; Vitamin D insufficiency; Diabetes mellitus

Type 1 diabetes mellitus (T1DM) is a chronic disease caused by insulin deficiency resulting from autoimmune destruction of pancreatic beta cells. Increased risk of fractures and osteoporosis in T1DM is associated with reducing osteoblast proliferation, survival, and activity. Osteocalcin (OC) is a marker of late-stage osteoblast differentiation. It might be positively modulated by vitamin D. This study was aimed to investigate the effect of vitamin D3 supplementation on the level of 25(OH)D3, HbA1c, and OC in children with T1DM. A randomized clinical trial was conducted to measures the levels of 25(OH)D3, HbA1c, and OC in children with T1DM supplemented with vitamin D3. Many 26 children with T1DM were equally assigned into two groups: control (standardized insulin treatment) and treatment group (standardized insulin treatment + vitamin D3 2000 IU/day). Subject characteristics showed that the subjects were predominantly female (15/26), well-nourished (19/26), the average age is 12,31 ± 3,069 year, and the dose of insulin average is 1,17 ± 0,233 IU/kg BW/day. Our data demonstrated that vitamin D3 treatment significantly increased the level of 25(OH)D3 and improved glycemic control, represented by a low HbA1c level. However, there was no significant difference in OC level in both groups (independent t-test, p &gt; 0.05). Further analysis showed no significant relationship between the level of 25(OH)D3, HbA1c, and OC. We concluded that vitamin D3 supplementation improves children's glycemic control with T1DM, but no significant alteration on OC levels.Keywords: HbA1c, Osteocalcin, T1DM, Vitamin D

Objective To investigate correlation between vitamin D and glucose metabolism, lipid metabolism, insulin resistance, early secretory function of pancreatic islets in postmenopausal women with type 2 diabetes. Methods 115 postmenopausal women with type 2 diabetes were selected as observation group.115 postmenopausal women without type 2 diabetes were selected in hospital at same period as control group.All patients received detection of vitamin D, glucose metabolism, lipid metabolism, insulin resistance, early secretory function of pancreatic islets.Correlation between vitamin D and glucose metabolism, lipid metabolism, insulin resistance, early secretory function of pancreatic islets were analyzed. Results Fasting blood glucose, postprandial 2h blood glucose, glycosylated hemoglobin, body mass index, total cholesterol, triglyceride, low density lipoprotein cholesterol, insulin resistance index in the observation group were higher than the control group[(8.5±1.2)mmol/L vs (5.1±0.6)mmol/L, (13.4±1.5)mmol/L vs (7.8±0.7)mmol/L, (8.7±1.1)% vs (5.6±0.5)%, (25.7±1.0)kg/m2 vs (22.3±0.4)kg/m2, (5.6±0.7)mmol/L vs (4.5±0.4)mmol/L, (2.3±0.5)mmol/L vs (1.7±0.3)mmol/L, (3.5±0.6)mmol/L vs (2.2±0.4)mmol/L, (3.6±0.5) vs (2.5±0.4), t=9.667, 10.179, 8.535, 4.524, 5.443, 6.529, 8.909, 7.406, all P<0.05]. High density lipoprotein cholesterol, insulin first secretion phase peak factor, pancreatic islet βcell function index, fasting insulin, vitamin D in the observation group were lower than the control group[(1.0±0.2)mmol/L vs (1.2±0.3)mmol/L, (5.2±1.3) vs (8.4±1.6), (135.8±11.7) vs (194.3±19.2), (4.1±0.9)IU/mL vs (10.8±0.6)IU/mL, (10.8±2.1)ng/L vs (27.4±3.8)ng/L, t=5.087, 9.153, 7.370, 10.414, 18.371, all P<0.05]. Vitamin D was significantly negatively correlated with fasting blood glucose, postprandial 2h blood glucose, glycosylated hemoglobin, body mass index, total cholesterol, triglyceride, low density lipoprotein cholesterol, insulin resistance index(r=-0.537, -0.512, -0.469, -0.387, -0.325, -0.316, -0.372, -0.457, all P<0.05). Vitamin D were significantly positively correlated with high density lipoprotein cholesterol, insulin first secretion phase peak factor, pancreatic islet β cell function index, fasting insulin(r=0.351, 0.418, 0.674, 0.316, all P<0.05). Conclusion Vitamin D deficiency in postmenopausal women with type 2 diabetes may be involved in glucose-lipid metabolism and insulin resistance, but also may be one of the reasons leading to decreasing of early secretory function of pancreatic β cells. Key words: Diabetes, type 2; Vitamin D; Glucose-lipid metabolism; Insulin resistance; Early pancreatic secretion function; Correlation

Objective To observe the effect of Danzhi Jiangtang capsule on quality of life in elderly patients with type 2 diabetes mellitus. Methods 60 elderly patients with type 2 diabetes mellitus were randomly divided into control group and observation group, 30 cases in each group. The two groups were given comprehensive treatment measures. The observation group was treated with Danzhi Jiangtang capsule for 3 months. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) were detected before treatment and 3 months after treatment, respectively, and tranditional chinese medcine (TCM) syndrome scores were filled in. The Diabetes Specific Quality of Life Scale (DSQL) was evaluated. Results After treatment, FPG and HbA1c in the two groups decreased significantly, and the treatment group was better than the control group (P<0.05). The curative effect of TCM syndromes in observation group was 93.3%, better than that of the control group (63.6%, P<0.05). The observation group was better than the control group in terms of physiological function, treatment effect on patients and total score (P<0.05). Conclusions Danzhi Jiangtang capsule can significantly improve the quality of life in elderly patients with type 2 diabetes mellitus. Key words: HYPOGLYCEMIC AGENTS (TCD); CAPSULES; Diabetes mellitus, type 2; Quality of life; Aged

Meta-analyses of randomized controlled trials (RCTs) have demonstrated a protective effect of vitamin D3 (cholecalciferol) supplementation against cancer mortality. In the VITAL study, a RCT including 25,871 men ≥ 50 years and women ≥ 55 years, protective effects of vitamin D3 supplementation (2000 IU/day over a median of 5.3 years) with respect to incidence of any cancer and of advanced cancer (metastatic cancer or cancer death) were seen for normal-weight participants but not for overweight or obese participants. We aimed to explore potential reasons for this apparent variation of vitamin D effects by body mass index. We conducted complementary analyses of published data from the VITAL study on the association of body weight with cancer outcomes, stratified by vitamin D3 supplementation. Significantly increased risks of any cancer and of advanced cancer were seen among normal-weight participants compared to obese participants in the control group (relative risk (RR), 1.27; 95% confidence interval (CI), 1.07–1.52, and RR, 1.44; 95% CI, 1.04–1.97, respectively). No such patterns were seen in the intervention group. Among those with incident cancer, vitamin D3 supplementation was associated with a significantly reduced risk of advanced cancer (RR, 0.86; 95% CI, 0.74–0.99). The observed patterns point to pre-diagnostic weight loss of cancer patients and preventive effects of vitamin D3 supplementation from cancer progression as plausible explanations for the body mass index (BMI)—intervention interactions. Further research, including RCTs more comprehensively exploring the potential of adjuvant vitamin D therapy for cancer patients, should be pursued with priority.

Background: Neuropathy is a common diabetic microvascular complication which reduces quality of life; causing pain and irritation in lower limbs and may result in amputation. Several Studies documented that vitamin D deficiency have extra skeletal effects including poor glycemic control and microvascular complications. Objectives: To explore the relationship between levels of vitamin D and diabetic neuropathy in Sudanese patients with type 2 diabetes mellitus. Methods: In this cross-sectional case control and hospital based study conducted at Jabber Abu Eliz Diabetes Centre (JAEDC), from February 2015 to November 2018, Sixty diabetic patients (thirty patients with neuropathy and thirty patients without neuropathy), and sixty healthy subjects were compared in terms of levels of vitamin D, C-peptide, lipid profile, HbA1C, C-reactive protein, and MAU. SPSS software was used for analysis of clinical variables. Results: Vitamin D levels where significantly decreased in diabetic patients and also in those with neuropathy when compared to those without neuropathy (P 0.05). 86.8% of patients with neuropathy had vitamin D deficiency and 6.6% had insufficiency. Vitamin D levels where significantly reduced with increasing severity of neuropathy (P 0.001). Conclusion: Vitamin D levels are significantly decreased in diabetic patients especially in those with neuropathy. Severity of neuropathy is significantly correlated to severity of vitamin D deficiency. Diabetic patients should be screened for vitamin D level and supplementation should be prescribed to correct the deficiency.

Objective To determine vitamin D levels in patients with type 1 diabetes mellitus (T1DM),and to explore the relationship of vitamin D and pancreatic β-cell function in these patients.Methods Sixty-five patients with T1DM,78 controls with normal glucose tolerance (NGT),as well as 87 type 2 diabetes mellitus (T2DM) patients,whose HbA1C,blood glucose levels,and duration of diabetes were matched with those in the T1 DM group,were enrolled from January 2011 to April 2012.The differences in serum 25-hydroxyvitamin D3 [25 (OH) D3] levels among the three groups were compared.Pearson correlation analysis was used for investigating the relationship between fasting C-peptide levels and other variables in T1DM group,all P＜0.05 variables then were included in a stepwise multiple linear regression analysis.Results Serum 25 (OH) D3 levels were significantly lower in T1 DM group than those in NGT and T2DM groups [7.7 (4.8-14.9)vs 13.9 (10.0-17.9),12.5 (9.3-17.4)ng/mg,both P＜0.01].Stepwise multiple linear regression analysis showed that fasting serum C-peptide concentration was independently associated with serum 25 (OH) D3 level in T1 DM group.Conclusions T1DM patients had lower vitamin D levels than NGT and T2DM subjects,vitamin D status showed independently a positive association with β-cell function in T1DM patients.Whether supplement of vitamin D to TIDM patients is a topic worth studying. Key words: Vitamin D; Diabetes mellitus, type 1 ; β-cell function

Objective To investigate the correlation between 25-hydroxyvitamin D [25(OH)D] and indicators of glucose metabolism in inpatients with type 2 diabetes mellitus. Method We retrospectively analyzed the clinical records of 214 inpatients with type 2 diabetes mellitus, including age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, and laboratory test results such as serum parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus, glycosylated hemoglobin A1c (HbA1c), fasting blood glucose, and fasting insulin. Results The prevalence of vitamin D deficiency was high in these patients, with 47.2% of them having a serum 25(OH)D concentration lower than 10 ng/ml. Using 25(OH)D level less than 10 ng/ml as the cut-off point, the patients were divided into vitamin D severe deficiency (Vit-SD) group and vitamin D non-severe deficiency (Vit-NSD) group. Compared with the Vit-NSD group, the Vit-SD group had younger age [(55.27±13.71) years vs. (60.76±12.32) years, P=0.001] and higher HbA1c level [(9.00±2.01)% vs. (8.45±1.86)%, P=0.025]. BMI [ (25.09±4.01)kg/m2vs. (25.39±3.53)kg/m2,P=0.523], fasting blood glucose [(8.91±3.31)mmol/L vs. (8.16±3.02)mmol/L, P=0.063], fasting serum insulin [(21.32±32.50)mIU/L vs. (21.92±26.95)mIU/L, P=0.873] and homeostasis model assessment of insulin resistance index (97.60±8.92 vs. 7.53±9.39, P=0.954) in these two groups were with no statistically significant difference. The association analyses showed that HbA1c was significantly negatively correlated with 25(OH)D (r=-0.190, P=0.003) and not correlated with serum PTH, calcium, or phosphorus, after adjusting for age and creatinine. Multiple linear regression revealed that HbA1c had a significantly negative correlation with age (β=-0.220, P=0.000) and 25(OH)D (β=-0.184, P=0.000). Conclusions There is high prevalence of vitamin D deficiency in inpatients with type 2 diabetes mellitus, which is even higher in relatively young patients. Serum 25 (OH) D may be negatively correlated with HbA1c in these patients independently from age, BMI, fasting serum insulin, and homeostasis model assessment of insulin resistance index. Key words: Diabetes mellitus; 25-hydroxyvitamin D; Parathyroid hormone; Glycosylated hemoglobin; Glucose metabolism

Objective To study the hypoglycemic effect of Liuwei Dihuang pills combined with hypoglycemic drugs and clinical evaluation on reducing the risk of hypoglycemia in the treatment of type 2 diabetes mellitus. Methods A total of 208 patients with type 2 diabetes mellitus were randomly divided into the observation group and the control group. The observation group was treated with Liuwei Dihuang pills combined with metformin, while the control group was treated with metformin. After 16 weeks, FBG, 2hPBG, HbA1C, hypoglycemia and so on were observed. Results There were statistically significant differences in FBG, 2hPBG between the two groups after treatment (t=5.67, 6.32; P<0.01); the overall hypoglycemic effect of the observation group was better than that of the control group (Z=4.187, P<0.05); the incidence of hypoglycemia in the observation group was lower than that in the control group after treatment (χ2=7.61, P<0.05). Conclusion Liuwei Dihuang pills combined with metformin in the treatment of type 2 diabetes mellitus can obtain better clinical efficacy and reduce the risk of hypoglycemia, worthy of clinical application. Key words: Liuwei Dihuang pills; Reducing blood sugar; Hypoglycemia

Objective To investigate the significance of 25 hydroxyvitamin D3 (25 (OH)D3) in patients with type 2 diabetes mellitus by comparing the differences of serum 25-hydroxyvitamin D levels between type 2 diabetes mellitus patients and healthy people.Methods One hundred and forty-seven patients with type 2 diabetes mellitus were selected as the T2DM group,and 135 healthy people were selected as the normal control (NC) group.The level of serum 25 (OH) D3 was detected by ELISA.Clinical data were recorded and biochemical indexes were also detected.Statistical analysis was performed.Results (1) Serum 25 (OH) D3 level in T2DM group was low,but there was no significant difference between two groups((23.10 ± 1.59) μg/L vs.(23.11 ± 1.65) μg/L; t =0.064,P =0.949),as well as between men and women in the 2 populations (T2DM men vs.women(23.22 ± 1.54) μg/L vs.(22.95 ± 1.65) μg/L; t =0.209,P ＞0.05; NC men vs women(23.03 ± 1.73) μg/L vs.(23.18 ± 1.59) μg/L; t =0.436,P ＞0.05) ; (2)The prevalence of vitamin D insufficient and deficiency in T2DM group was high,but it was not statistically significant between two groups (98.0％ vs.94.8 ％ and 2.0％ vs.5.2％ ; x2 =2.034,P =0.154) ; (3) Serum 25 (OH) D3 in T2DM group has a significant negative correlation with triglycerides (r =-0.218,P ＜ 0.01).Conclusion (1) Vitamin D level was low in both the healthy and T2DM populations in the southern region of China,the prevalence of vitamin D insufficient and deficiency was up to 90％.(2)Triglyceride is the only independent risk factor to T2DM population. Key words: Type 2 diabetes mellitus ; 25-dihydroxyvitamin D3 ; Southern region; Triglyceride

Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial. To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study's treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016. Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing. Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs731236) in linkage disequilibrium (D' = 0.98; r2 = 0.6). For rs7968585, among individuals with the AA genotype (26%), vitamin D3 supplementation reduced risk by 64% (RR, 0.36; 95% CI, 0.19-0.69; P = .002; absolute risk decreased from 14.4% to 5.1%). Among individuals with 1 or 2 G alleles (74%), vitamin D3 supplementation increased risk by 41% (RR, 1.41; 95% CI, 0.99-2.00; P = .05; absolute risk increased from 7.7% to 11.1%; P < .001 for interaction). There were no significant interactions of genotypes with calcium supplementation. Our findings suggest that benefits from vitamin D3 supplementation for the prevention of advanced colorectal adenomas may vary according to vitamin D receptor genotype. clinicaltrials.gov Identifier: NCT00153816.