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

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).

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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.

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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

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: NCT02098980, 28/03/2014 (www.clinicaltrials.gov).

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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.

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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/v2 ◽

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.

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Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin

Endocrine Journal ◽

10.1507/endocrj.ej17-0325 ◽

2018 ◽

Vol 65 (1) ◽

pp. 13-22 ◽

Cited By ~ 1

Author(s):

Qi Fu ◽

Min Sun ◽

Zhixiao Wang ◽

Wei He ◽

Yu Duan ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Glycosylated Hemoglobin ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

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Association between Genetic Polymorphisms of β-Cell Differentiation Genes and Insulin Resistance (β-Cell Dysfunction) in Childhood Acute Lymphoblastic Leukemia (ALL) Survivors.

Blood ◽

10.1182/blood.v110.11.4281.4281 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4281-4281

Author(s):

Pacharapan Surapolchai ◽

Suradej Hongeng ◽

Samart Pakakasama ◽

Pat Mahachoklertwattana ◽

Angkana Winaichatsak ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Sensitivity Index ◽

Insulin Sensitivity Index ◽

Β Cell ◽

Childhood All ◽

Cell Dysfunction ◽

Β Cell Function

Abstract Background: The purposes of the study were to determine β-cell function and insulin sensitivity after ALL therapy cessation and the association between genetic polymorphisms of β-cell differentiation genes, TCF7L2 and PAX4, with insulin resistance (β-cell dysfunction) in childhood ALL survivors. Methods: Childhood ALL patients diagnosed during 1997–2004 finished the treatment for at least 6 months. The oral glucose tolerance test and lipid screening were performed. Impaired glucose tolerance and diabetes mellitus (DM) were defined according to WHO criteria. β-cell function was estimated by homeostasis model assessment β-cell (HOMA β-cell) and insulinogenic index (IGI) and insulin sensitivity was estimated by whole body insulin sensitivity index (WBISI). The polymorphisms of TCF7L2 (rs12255372 and rs7903146) and PAX4 (A1186C) were genotyped and assessed for the association between these polymorphisms and the β-cell function and the insulin sensitivity. Results: 126 patients were studied (52 females, 74 males and age at the time of study; 4–20 yrs). 116 patients (92%) had normal glucose tolerance (NGT) while the others 10 patients (8%) had impaired glucose tolerance (IGT). Comparing between IGT and NGT groups respectively, we found statistically significant differences in age at the diagnosis (7.5 and 5.2 yrs, p=0.041), age at the study (14 and 10.3 yrs, p=0.001), the duration of post ALL therapy cessation (43 and 26 months, p=0.015), and insulin sensitivity index (WBISI) (5.75 and 9.52, p<0.001). HOMA β-cell and IGI were not different between NGT and IGT group (190.8 and 139.5, p=0.332; 23.6 and 15.8, p=0.310, respectively). Moreover, 32 of 126 patients (25%) had insulin resistance (modified from the criteria of WBISI in obese children and adolescents). These 32 patients who had insulin resistance demonstrated significant pictures of metabolic syndrome i.e. hypertriglyceridemia (116.6 and 85.4 mg/dL, p=0.036), low HDL-C (43.0 and 48.3 mg/dL, p=0.015), obesity (BMI SDS 1.03 and 0.38, p=0.044) and were also older age at the study (12.8 and 9.9 yrs, p<0.001). The genotype frequencies and allele frequencies of polymorphisms of TCF7L2 and PAX4 genes between IGT and NGT groups and between insulin resistance and nonresistance were not difference (p>0.05). Conclusion: The childhood ALL survivors who had IGT were associated with the longer duration of ALL therapy cessation, the older age at diagnosis and at the time of study, and insulin resistance while β-cell function was still relatively preserved. Long-term childhood ALL survivors have potential risks of IGT, insulin resistance and metabolic syndrome. Our findings with such small representatives are not yet applicable to associate TCF7L2 and PAX4 polymorphisms with the insulin resistance (β-cell dysfunction) in the childhood ALL survivors.

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Estimation of β-cell function from the data of the oral glucose tolerance test

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00341.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1575-E1580 ◽

Cited By ~ 9

Author(s):

Shinji Sakaue ◽

Shinji Ishimaru ◽

Daisuke Ikeda ◽

Yoshinori Ohtsuka ◽

Toshiro Honda ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Sensitivity Index ◽

Β Cell ◽

Β Cell Function ◽

The Relationship

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln ( x) ( x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include −1, the relationships between IGI and x were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis.

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Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00506.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. E535-E544 ◽

Cited By ~ 37

Author(s):

Christoffer Martinussen ◽

Kirstine N. Bojsen-Møller ◽

Carsten Dirksen ◽

Siv H. Jacobsen ◽

Nils B. Jørgensen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Glucose Effectiveness ◽

Β Cell Function ◽

First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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Ectopic Fat Storage in the Pancreas, Liver, and Abdominal Fat Depots: Impact on β-Cell Function in Individuals with Impaired Glucose Metabolism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1722 ◽

2011 ◽

Vol 96 (2) ◽

pp. 459-467 ◽

Cited By ~ 104

Author(s):

N. J. van der Zijl ◽

G. H. Goossens ◽

C. C. M. Moors ◽

D. H. van Raalte ◽

M. H. A. Muskiet ◽

...

Keyword(s):

Insulin Sensitivity ◽

Magnetic Resonance ◽

Glucose Tolerance ◽

Cell Function ◽

Ectopic Fat ◽

Β Cell ◽

C Peptide ◽

Pancreatic Fat ◽

Β Cell Function ◽

Peptide Secretion

abstract Context: Pancreatic fat content (PFC) may have deleterious effects on β-cell function. Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to β-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Design, Setting and Participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted. Intervention and Main Outcome Measures: Participants underwent the following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp, with subsequent arginine stimulation to quantify insulin sensitivity and β-cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT) and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity adjusted β-cell function) was assessed. Results: IFG and IFG/IGT were more insulin resistant (P < 0.001) compared with NGT. Individuals with IFG/IGT had the lowest values of glucose- and arginine-stimulated C-peptide secretion (both P < 0.03) and DI (P < 0.001), relative to IFG and NGT. PFC and LFC gradually increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively), whereas VAT and SAT were similar between groups. No direct associations were found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was inversely correlated with PFC, LFC, and VAT (all P < 0.05). Conclusions: PFC was increased in individuals with IFG and/or IGT, without a direct relation with β-cell function.

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