Vitamin D affects insulin sensitivity and β-cell function in obese non-diabetic youths

Objective Vitamin D may potentially play a central role in glucose homeostasis and β-cell function (BCF), although studies are not consistent. Aim of our study was to test the hypotheses of a direct relationship between vitamin D, insulin sensitivity (IS) and BCF in overweight and obese non-diabetic children. Design and methods Cross-sectional study carried out at the Childhood Obesity Outpatient Clinic, University Hospital of Verona. One hundred twenty-two Caucasian overweight and obese children (age: 12.8 ± 0.2 years) were enrolled. Exclusion criteria: genetic or endocrine causes of obesity, chronic diseases or therapies. Patients underwent oral glucose tolerance test. HOMA-IR, Matsuda index and insulinogenic index were calculated. BCF was reconstructed by mathematical modeling and described by Derivative and Proportional Control. Total 25-hydroxyvitamin D and vitamin D-binding protein (VDBP) were measured. Two SNPs (rs4588 and rs7041) in the VDBP gene were studied, and bioavailable vitamin D (BVD) was calculated. Results Hypovitaminosis D was documented in 90% of patients. Forty-seven subjects were homozygous for both SNPs. Total vitamin D was positively correlated with Matsuda index (P = 0.002), VDBP (P = 0.045), and negatively with BMI SDS (P = 0.043), HOMA-IR (P = 0.008), HOMA-B (P = 0.001), IGI (P = 0.007), derivative control (P = 0.036) and proportional control (P = 0.018). Total vitamin D, adjusted for age, gender, BMI SDS, puberty and seasonality of vitamin D measurement, was a predictor of Matsuda index, HOMA-IR, HOMA-B, IGI, proportional control (all P < 0.05). BVD was positively correlated with total vitamin D (P < 0.001) and negatively with BMI SDS (P = 0.041). Conclusions Hypovitaminosis D negatively influences BCF and IS, suggesting that vitamin D levels might be implicated in glucose metabolism impairment in overweight and obese individuals.

Download Full-text

Vitamin D and Parathyroid Hormone Status in Pregnancy: Effect on Insulin Sensitivity, β-cell Function, and Gestational Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2341 ◽

2014 ◽

Vol 99 (12) ◽

pp. 4506-4513 ◽

Cited By ~ 27

Author(s):

Caroline K. Kramer ◽

Balakumar Swaminathan ◽

Anthony J. Hanley ◽

Philip W. Connelly ◽

Mathew Sermer ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Vitamin D Deficiency ◽

Cell Function ◽

Β Cell ◽

Matsuda Index ◽

Β Cell Function ◽

Glucose Tolerance Status ◽

In Pregnancy

Context: Previous studies have yielded conflicting findings on the relationship between vitamin D deficiency/insufficiency and gestational diabetes mellitus (GDM). We hypothesized that PTH may be an underlying factor relevant to this potential association. Objective: This study sought to evaluate the effect of vitamin D and PTH status on insulin sensitivity, β-cell function, and glycemia in pregnancy. Setting and Design: Five-hundred-twenty-four women underwent a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in late second/early third trimester. The GCT/OGTT identified 142 women with GDM, 94 with gestational impaired glucose tolerance, 163 with an abnormal GCT and normal OGTT, and 125 with normal GCT and OGTT. Main Outcomes: Glycemia was assessed by glucose tolerance status and area under the glucose curve (AUCgluc) on the OGTT. Insulin sensitivity and β-cell function were assessed by Matsuda index and Insulin Secretion-Sensitivity Index-2 (ISSI-2), respectively. Results: There were 166 women (31.7%) with vitamin D deficiency (25-OH-D < 50 nmol/L), 178 (34%) with insufficiency (25-OH-D ≥ 50 nmol/L and < 75 nmol/L), and 180 (34.3%) with sufficiency (25-OH-D ≥ 75 nmol/L). Vitamin D status was not associated with Matsuda index, ISSI-2, AUCgluc, or glucose tolerance status. In contrast, ISSI-2 decreased and AUCgluc increased across ascending tertiles of PTH (P = .06 and P = .002, respectively). Indeed, the prevalence of GDM progressively increased from the first (22.6%) to second (25.8%) to third (33.5%) tertile of PTH (P < .001). On logistic regression analyses, the third tertile of PTH was independently associated with GDM (adjusted OR = 1.82; 95% CI, 1.09–3.02; P = .022), whereas vitamin D deficiency and insufficiency were not significant predictors of GDM. Conclusions: Increased PTH, rather than vitamin D deficiency/insufficiency, is independently associated with dysglycemia in pregnancy.

Download Full-text

Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial

Acta Endocrinologica ◽

10.1530/eje-19-0156 ◽

2019 ◽

Vol 181 (3) ◽

pp. 287-299 ◽

Cited By ~ 14

Author(s):

Patricia Lemieux ◽

S John Weisnagel ◽

Annabelle Z Caron ◽

Anne-Sophie Julien ◽

Anne-Sophie Morisset ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Cell Function ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Insulinogenic Index ◽

Newly Diagnosed ◽

Β Cell ◽

Β Cell Function

Objective To determine whether vitamin D3 supplementation improves insulin sensitivity, using the hyperinsulinemic-euglycemic clamp. Design This single-centre, double-blind, placebo-controlled trial randomised 96 participants at high risk of diabetes or with newly diagnosed type 2 diabetes to vitamin D3 5000 IU daily or placebo for 6 months. Methods We assessed at baseline and 6 months: (1) primary aim: peripheral insulin sensitivity (M-value using a 2-h hyperinsulinemic-euglycemic clamp); (2) secondary aims: other insulin sensitivity (HOMA2%S, Matsuda) and insulin secretion (insulinogenic index, C-peptide area under the curve, HOMA2-B) indices using a 2-h oral glucose tolerance test (OGTT); β-cell function (disposition index: M-value × insulinogenic index); fasting and 2-h glucose post OGTT; HbA1c; anthropometry. Results Baseline characteristics were similar between groups (% or mean ± s.d.): women 38.5%; age 58.7 ± 9.4 years; BMI 32.2 ± 4.1 kg/m2; prediabetes 35.8%; diabetes 20.0%; 25-hydroxyvitamin D (25(OH)D) 51.1 ± 14.2 nmol/L. At 6 months, mean 25(OH)D reached 127.6 ± 26.3 nmol/L and 51.8 ± 16.5 nmol/L in the treatment and placebo groups, respectively (P < 0.001). A beneficial effect of vitamin D3 compared with placebo was observed on M-value (mean change (95% CI): 0.92 (0.24–1.59) vs −0.03 (−0.73 to 0.67); P = 0.009) and disposition index (mean change (95% CI): 267.0 (−343.4 to 877.4) vs −55.5 (−696.3 to 585.3); P = 0.039) after 6 months. No effect was seen on other outcomes. Conclusions In individuals at high risk of diabetes or with newly diagnosed type 2 diabetes, vitamin D supplementation for 6 months significantly increased peripheral insulin sensitivity and β-cell function, suggesting that it may slow metabolic deterioration in this population.

Download Full-text

Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children

Annals of Nutrition and Metabolism ◽

10.1159/000496459 ◽

2019 ◽

Vol 74 (2) ◽

pp. 125-131 ◽

Cited By ~ 7

Author(s):

Ting Chen ◽

Fengyun Wang ◽

Zhenyu Chu ◽

Ling Sun ◽

Haitao Lv ◽

...

Keyword(s):

Blood Pressure ◽

Insulin Sensitivity ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Pancreatic Β Cell ◽

Obese Children ◽

Β Cell ◽

Β Cell Function ◽

Obese Subjects

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.

Download Full-text

The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial

BMC Nutrition ◽

10.1186/s40795-019-0311-x ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

Mohammed Al Thani ◽

Eman Sadoun ◽

Angeliki Sofroniou ◽

Amin Jayyousi ◽

Khaled Ahmed Mohamed Baagar ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Plasma Glucose ◽

Cell Function ◽

Vitamin D Supplementation ◽

Β Cell ◽

Baseline Serum ◽

Link Type ◽

Β Cell Function

Abstract Background Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, β-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. Methods One hundred thirty-two participants were randomized to 30,000 IU vitamin D weekly for 6 months. Participants underwent oral glucose tolerance test (OGTT) at 3-month intervals to determine the change in plasma glucose concentration at 2 h after 75 g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), β-cell function (HOMA-β, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. Results A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0 ng/ml and 14.9 ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-β significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in β-cell function in both groups. Additionally, HOMA-β was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. Conclusion Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in β-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. Trial registration NCT02098980, 28/03/2014 (www.clinicaltrials.gov).

Download Full-text

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial

Diabetes Care ◽

10.2337/dc15-1057 ◽

2016 ◽

Vol 39 (3) ◽

pp. 345-352 ◽

Cited By ~ 33

Author(s):

Henrik Wagner ◽

Michael Alvarsson ◽

Buster Mannheimer ◽

Marie Degerblad ◽

Claes-Göran Östenson

Keyword(s):

Clinical Trial ◽

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

High Dose ◽

Abnormal Glucose Tolerance ◽

Β Cell ◽

Β Cell Function ◽

High Dose Vitamin

Download Full-text

The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial.

10.21203/rs.2.11375/v1 ◽

2019 ◽

Author(s):

Mohammed Al Thani ◽

Eman Sadoun ◽

Angeliki Sofroniou ◽

Amin Jayyousi ◽

Khaled Ahmed Mohamed Baagar ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Plasma Glucose ◽

Cell Function ◽

Vitamin D Supplementation ◽

Oral Glucose ◽

Β Cell ◽

Baseline Serum ◽

Β Cell Function

Abstract Background: Vitamin D deficiency is associated with indicators of pre-diabetes including, insulin resistance, β-cell dysfunction and elevated plasma glucose with controversial findings from current trials. This study aims to investigate the long-term effect of vitamin D on glucose metabolism and insulin sensitivity in pre-diabetic and highly vitamin-deficient subjects. Methods: 132 participants were randomized to 30,000 IU vitamin D weekly for 6 months. Participants underwent oral glucose tolerance test (OGTT) at 3-month intervals to determine the change in plasma glucose concentration at 2h after 75g OGTT (2hPCG). Secondary measurements included glycated hemoglobin, fasting plasma glucose and insulin, post-prandial insulin, indices of insulin sensitivity (HOMA-IR, Matsuda Index), β-cell function (HOMA-β, glucose and insulin area under the curve (AUC), disposition and insulinogenic indices), and lipid profile. Results: A total of 57 (vitamin D) and 75 (placebo) subjects completed the study. Mean baseline serum 25(OH) D levels were 17.0 ng/ml and 14.9 ng/ml for placebo and vitamin D group, respectively. No significant differences were observed for 2hPC glucose or insulin sensitivity indices between groups. HOMA-β significantly decreased in the vitamin D group, while area under curve for glucose and insulin showed a significant reduction in β-cell function in both groups. Additionally, HOMA-β was found to be significantly different between control and treatment group and significance persisted after adjusting for confounding factors. Conclusion: Vitamin D supplementation in a pre-diabetic and severely vitamin-deficient population had no effect on glucose tolerance or insulin sensitivity. The observed reduction in β-cell function in both placebo and vitamin D groups could be attributed to factors other than supplementation. Trial registration: The trial was registered at www.clinicaltrials.gov with number: NCT02098980.

Download Full-text

Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial

PLoS ONE ◽

10.1371/journal.pone.0109607 ◽

2014 ◽

Vol 9 (10) ◽

pp. e109607 ◽

Cited By ~ 64

Author(s):

Claudia Gagnon ◽

Robin M. Daly ◽

André Carpentier ◽

Zhong X. Lu ◽

Catherine Shore-Lorenti ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Β Cell ◽

Β Cell Function

Download Full-text

The effect of vitamin D supplementation on the glycemic control of pre-diabetic Qatari patients in a randomized control trial.

10.21203/rs.2.11375/v3 ◽

2019 ◽

Author(s):

Mohammed Al Thani ◽

Eman Sadoun ◽

Angeliki Sofroniou ◽

Amin Jayyousi ◽

Khaled Ahmed Mohamed Baagar ◽

...

Keyword(s):

Vitamin D ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Plasma Glucose ◽

Cell Function ◽

Vitamin D Supplementation ◽

Oral Glucose ◽

Β Cell ◽

Baseline Serum ◽

Β Cell Function

Download Full-text

Association of Baseline Characteristics With Insulin Sensitivity and β-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort

10.2337/figshare.13247033 ◽

2020 ◽

Author(s):

Neda Rasouli ◽

Naji Younes ◽

Kristina M. Utzschneider ◽

Silvio E. Inzucchi ◽

Ashok Balasubramanyam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

African Americans ◽

Cell Function ◽

Insulinogenic Index ◽

Model Assessment ◽

Β Cell ◽

Black African ◽

Β Cell Function

Objective: We investigated sex and racial differences in insulin sensitivity, β-cell function and HbA1c, and the associations with selected phenotypic characteristics. Research Design and Methods: This is a cross-sectional analysis of baseline data from 3,108 GRADE participants. All had type 2 diabetes diagnosed <10 years and were on metformin monotherapy. Insulin sensitivity and β-cell function were evaluated using the homeostasis model assessment of insulin sensitivity (HOMA2-S) and estimates from oral glucose tolerance tests including the Matsuda index, insulinogenic index (IGI), C-peptide index (CPI) and oral disposition index (DI). Results: The cohort was 56.6±10 years of age (mean±SD), 63.8% male, with BMI 34.2±6.7 kg/m2, HbA1c 7.5±0.5% and type 2 diabetes duration 4.0±2.8 years. Women had higher DI than men but similar insulin sensitivity. DI was the highest in Black/African Americans, followed by American Indians/Alaska Natives, Asians and Whites in descending order. Compared to white, American Indian/Alaska Native had significantly higher HbA1c but Black/African Americans and Asians had lower HbA1c. However, when adjusted for glucose levels, Black/African Americans had higher HbA1c than whites. Insulin sensitivity correlated inversely with BMI, waist to hip ratio, triglyceride to HDL cholesterol ratio (TG/HDL- C) and the presence of metabolic syndrome; whereas DI was associated directly with age and inversely with BMI, HbA1c and TG/HDL-C. Conclusion: In the GRADE cohort, β-cell function differed by sex and race and was associated with the concurrent level of HbA1c. HbA1c also differed among the races, but not sex. Age, BMI and TG/HDL-C were associated with multiple measures of β-cell function and insulin sensitivity.

Download Full-text

The Macrophage Activation Marker Soluble CD163 is Longitudinally Associated With Insulin Sensitivity and β-cell Function

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz166 ◽

2019 ◽

Vol 105 (3) ◽

pp. e285-e294 ◽

Cited By ~ 1

Author(s):

Zhila Semnani-Azad ◽

Philip W Connelly ◽

Luke W Johnston ◽

Ravi Retnakaran ◽

Stewart B Harris ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Cell Function ◽

Sensitivity Index ◽

Insulinogenic Index ◽

Β Cell ◽

Soluble Cd163 ◽

Β Cell Function ◽

Longitudinal Associations

Abstract Context Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. Methods Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. Results Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = −7.01; 95% CI, −12.26 to −1.44) and ISI (β = −7.60; 95% CI, −11.09 to −3.97) and β-cell function (ISSI-2 (β = −4.67; 95 %CI, −8.59 to −0.58) and IGI/HOMA-IR (β = −8.75; 95% CI, −15.42 to −1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). Conclusions sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.

Download Full-text