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Dhaher NF, Brismar K, Pikkemaat M, Shaat N, Nilsson A, Bennet L. Impact of lifestyle intervention on vitamin D, Adiponectin, Insulin-like growth factor 1 and Proneurotensin in overweight individuals from the Middle East. Prim Care Diabetes 2024; 18:676-682. [PMID: 39448331 DOI: 10.1016/j.pcd.2024.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 10/15/2024] [Accepted: 10/19/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Immigrants from the Middle East (ME) have a higher prevalence of type 2 diabetes (T2D) compared to the native-born Swedish population. In individuals free from T2D, ME immigrants are more insulin resistant and have lower levels of adjusted insulin secretion (Disposition index, DIo) compared to Swedish-born individuals. The ethnic differences are not fully explained by traditional risk factors. This has raised the question as to whether hormonal factors other than insulin are involved, contributing to higher T2D risk in ME immigrants. AIMS In ME immigrants at high risk of developing T2D, we aimed to study the effect of a randomized culturally adapted lifestyle intervention on the levels of Vitamin D (25(OH)D), insulin-like growth factor 1 (IGF-1), Pro-neurotensin (Pro-NT) and Adiponectin. Furthermore, we aimed to study if the effect of the intervention was associated to these hormones, or if a direct effect of the intervention remained after accounting for these. METHODS In this culturally adapted randomized controlled trial of four months duration, eligible ME immigrants at high risk of developing T2D identified in the MEDIM cohort were invited to participate. The intervention group (N= 35) received a culturally adapted lifestyle intervention program consisting of seven group sessions and cooking classes. The control group (N= 32) were given treatment as usual with oral and written information to improve their lifestyle habits. Using mixed models' linear regression analysis, the changes in the levels of 25(OH)D, IGF-1, Adiponectin and Pro-NT were assessed by comparing the groups and we further studied the effects of the changes on insulin action and secretion. RESULTS The adjusted levels of 25(OH)D significantly increased in the intervention group compared to the control group (β for the effect of the intervention on 25(OH)D: 0.061, 95 % CI 0.009-0.113, P = 0.023). The increase in insulin sensitivity index (ISI) observed in the intervention compared to the control group was altered after adjusting for 25(OH)D: 0.129, 95 % CI -0.016-0.274, P = 0.078). IGF-1, Adiponectin and Pro-NT did not significantly influence the change over time concerning insulin secretion. CONCLUSION Lifestyle intervention increases the adjusted levels of 25(OH)D. Moreover, the effect of the lifestyle intervention on insulin action and secretion was altered when adjusting for 25(OH)D.
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Affiliation(s)
- Nadine Fadhel Dhaher
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Endocrinology, Skåne University Hospital, Malmö, Sweden.
| | - Kerstin Brismar
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Rolf Luft Research Centre for Diabetes and Endocrinology, Karolinska University Hospital, Stockholm, Sweden
| | - Miriam Pikkemaat
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden
| | - Nael Shaat
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Department of Endocrinology, Skåne University Hospital, Malmö, Sweden
| | - Anton Nilsson
- Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Louise Bennet
- Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden; Clinical Research and Trial Centre, Lund University Hospital, Lund, Sweden
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Abbas Fadlallah AA, Mohamed Hassan MH, Farah S, Mohamed Gaffar SE, Mahgoub Ali AH, Alzahrani HS, Alhadhrami AH, Alqahtani FSM. Evaluating the Effect of Vitamin D Supplementation on Type 2 Diabetes Risk: A Systematic Review. Cureus 2024; 16:e75860. [PMID: 39822434 PMCID: PMC11736670 DOI: 10.7759/cureus.75860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/19/2025] Open
Abstract
Although observational studies have linked vitamin D deficiency to diabetes, it is unknown if taking vitamin D supplements can reduce the chance of developing type 2 diabetes mellitus (T2DM). The purpose of this systematic review is to determine whether vitamin D supplementation lowers the risk of type 2 diabetes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to search for studies based on pre-established inclusion and exclusion criteria. Five different databases (Scopus, Web of Science, PubMed, Google Scholar, and Cochrane Library) were used to search for relevant studies. These databases contained 1,916 relevant research papers that were examined for duplication using the EndNote software. After a careful text analysis, only 13 of these articles were found to be pertinent. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in each included study. Ten of the 13 trials examined how vitamin D supplementation affected the homeostasis model assessment of insulin resistance (HOMA-IR) of the patients. Patients using vitamin D supplements saw a drop in their HOMA-IR in six of these RCTs but an increase in four of them. The vitamin D group had a lower HOMA-IR than the placebo cohort in seven of the 10 trials that examined HOMA-IR. Despite the impact on insulin resistance, there is not enough data to conclude that vitamin D supplement significantly lowers the incidence of T2DM. To impact clinical guidelines about supplementation with vitamin D among people at risk of type 2 diabetes, more studies in this area might be beneficial.
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Affiliation(s)
| | | | - Salma Farah
- Palliative Care Medicine, University Hospital Galway, Galway, IRL
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Park CY, Shin S, Han SN. Multifaceted Roles of Vitamin D for Diabetes: From Immunomodulatory Functions to Metabolic Regulations. Nutrients 2024; 16:3185. [PMID: 39339785 PMCID: PMC11435169 DOI: 10.3390/nu16183185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 09/15/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Numerous studies have established associations between vitamin D and diabetes. The vitamin D receptor is widely distributed throughout the human body, including in pancreatic beta cells (β-cells), hepatocytes, and immune cells. Therefore, vitamin D's effect on the risk, progression, or complications of diabetes may be mediated through various mechanisms. These include the regulation of insulin secretion or sensitivity and modulation of β-cell function and its immunomodulatory and anti-inflammatory effects. This review extensively explores the relationship between vitamin D status and diabetes, as well as the preventive or therapeutic effects of vitamin D supplementation on diabetes from human studies. Additionally, it examines in detail the impact of vitamin D on immune and inflammatory responses in the diabetic milieux and β-cell function to better understand the underlying mechanisms through which vitamin D influences diabetes.
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Affiliation(s)
- Chan Yoon Park
- Department of Food & Nutrition, College of Life Care Science Technology, The University of Suwon, Hwaseong-si 18323, Republic of Korea
| | - Sunhye Shin
- Department of Food and Nutrition, College of Science and Convergence Technology, Seoul Women's University, Seoul 01797, Republic of Korea
| | - Sung Nim Han
- Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
- Research Institute of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea
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Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, Lazaretti-Castro M, Lips P, Mitchell DM, Murad MH, Powers S, Rao SD, Scragg R, Tayek JA, Valent AM, Walsh JME, McCartney CR. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2024; 109:1907-1947. [PMID: 38828931 DOI: 10.1210/clinem/dgae290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.
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Affiliation(s)
- Marie B Demay
- Department of Medicine, Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Anastassios G Pittas
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA
| | - Daniel D Bikle
- Departments of Medicine and Dermatology, University of California San Francisco, San Francisco VA Medical Center, San Francisco, CA 94158, USA
| | - Dima L Diab
- Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, OH 45267, USA
| | - Mairead E Kiely
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences and INFANT Research Centre, University College Cork, Cork, T12 Y337, Ireland
| | - Marise Lazaretti-Castro
- Department of Internal Medicine, Division of Endocrinology, Universidade Federal de Sao Paulo, Sao Paulo 04220-00, Brazil
| | - Paul Lips
- Endocrine Section, Amsterdam University Medical Center, Internal Medicine, 1007 MB Amsterdam, Netherlands
| | - Deborah M Mitchell
- Pediatric Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - M Hassan Murad
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN 55905, USA
| | - Shelley Powers
- Bone Health and Osteoporosis Foundation, Los Gatos, CA 95032, USA
| | - Sudhaker D Rao
- Division of Endocrinology, Diabetes and Bone & Mineral Disorders, Henry Ford Health, Detroit, MI 48202, USA
- College of Human Medicine, Michigan State University, Lansing, MI 48824, USA
| | - Robert Scragg
- School of Population Health, The University of Auckland, Auckland 1142, New Zealand
| | - John A Tayek
- Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, USA
- The Lundquist Institute, Torrance, CA 90502, USA
| | - Amy M Valent
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR 97239, USA
| | - Judith M E Walsh
- Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
| | - Christopher R McCartney
- Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
- Department of Medicine, West Virginia University, Morgantown, WV 26506, USA
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Shah VP, Nayfeh T, Alsawaf Y, Saadi S, Farah M, Zhu Y, Firwana M, Seisa M, Wang Z, Scragg R, Kiely ME, Lips P, Mitchell DM, Demay MB, Pittas AG, Murad MH. A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D. J Clin Endocrinol Metab 2024; 109:1961-1974. [PMID: 38828942 DOI: 10.1210/clinem/dgae312] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Indexed: 06/05/2024]
Abstract
CONTEXT Low vitamin D status is common and is associated with various common medical conditions. OBJECTIVE To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. METHODS We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. RESULTS Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. CONCLUSION The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations.
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Affiliation(s)
| | - Tarek Nayfeh
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Yahya Alsawaf
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Samer Saadi
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Magdoleen Farah
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Ye Zhu
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Mohammed Firwana
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Mohamed Seisa
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Zhen Wang
- Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55905, USA
| | - Robert Scragg
- School of Population Health, University of Auckland, Auckland 1023, New Zealand
| | - Mairead E Kiely
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences and INFANT Research Centre, University College Cork, Cork T12 Y337, Ireland
| | - Paul Lips
- Internal Medicine, Endocrine Section, Amsterdam University Medical Center, Amsterdam 1007 MB, The Netherlands
| | - Deborah M Mitchell
- Pediatric Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Marie B Demay
- Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
| | - Anastassios G Pittas
- Divisions of Endocrinology, Diabetes and Metabolism, Tufts-New England Medical Center, Boston, MA 02116, USA
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Korkmaz HA, Arya VB, Barisik V, Atila D, Coskunol F, Alci S, Cekdemir YE, Torlak D, Özkan B. The Association between Vitamin D Deficiency and Hepatosteatosis in Children and Adolescents with Obesity. Horm Res Paediatr 2023; 97:326-333. [PMID: 37793366 DOI: 10.1159/000533908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 08/25/2023] [Indexed: 10/06/2023] Open
Abstract
INTRODUCTION Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis and investigated the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry. METHODS One hundred thirty-three patients with obesity (body mass index [BMI] >+2 standard deviations [SDs] for their age and gender) and vitamin D deficiency (serum 25(OH)D <12 ng/mL) were recruited. Anthropometric measurements, biochemical parameters (serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations), and ultrasonographic findings of hepatosteatosis were recorded before and 6 months after Vitamin D treatment. χ2, Student's t tests, and multivariate analysis were performed. RESULTS Grade 1, 2, and 3 hepatosteatosis at baseline was present in 51 (38.4%), 43 (32.3%), and 10 (7.5%) subjects, respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/mL) compared with those without hepatosteatosis (9.9 ± 2.4 ng/mL, p < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (p < 0.005), whereas age, sex, weight SD, BMI SD, and homeostasis model of assessment (HOMA)-insulin resistance (IR) were not (p > 0.05). There was no significant difference in BMI SD, HOMA-IR, and liver enzymes between subjects with and without hepatosteatosis (p > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/mL vs. 8.7 ± 2.4 ng/mL; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88). CONCLUSION Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.
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Affiliation(s)
- Hüseyin Anıl Korkmaz
- Division of Pediatric Endocrinology, Department of Pediatrics, Manisa City Hospital, Manisa, Turkey
- Division of Pediatric Endocrinology, Department of Pediatrics, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
| | - Ved Bhushan Arya
- Division of Pediatric Endocrinology, Variety Club Childre's Hospital, King's College Hospital NHS Foundation Trust, London, UK
- Faculty of Medicine and Life Science, King's College London, London, UK
| | - Vatan Barisik
- Department of Internal Medicine, Metropol Medical Center, Izmir, Turkey
| | | | - Fulya Coskunol
- Department of Pediatrics, Manisa City Hospital, Manisa, Turkey
| | - Serra Alci
- Department of Pediatrics, Umraniye Training and Research Hospital, Istanbul, Turkey
| | | | - Derun Torlak
- Department of Pediatrics, Acibadem University Hospital, Istanbul, Turkey
| | - Behzat Özkan
- Division of Pediatric Endocrinology, Department of Pediatrics, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, Izmir, Turkey
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Wu J, Atkins A, Downes M, Wei Z. Vitamin D in Diabetes: Uncovering the Sunshine Hormone's Role in Glucose Metabolism and Beyond. Nutrients 2023; 15:nu15081997. [PMID: 37111216 PMCID: PMC10142687 DOI: 10.3390/nu15081997] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/18/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Over the last decades, epidemiology and functional studies have started to reveal a pivotal role of vitamin D in both type 1 and type 2 diabetes pathogenesis. Acting through the vitamin D receptor (VDR), vitamin D regulates insulin secretion in pancreatic islets and insulin sensitivity in multiple peripheral metabolic organs. In vitro studies and both T1D and T2D animal models showed that vitamin D can improve glucose homeostasis by enhancing insulin secretion, reducing inflammation, reducing autoimmunity, preserving beta cell mass, and sensitizing insulin action. Conversely, vitamin D deficiency has been shown relevant in increasing T1D and T2D incidence. While clinical trials testing the hypothesis that vitamin D improves glycemia in T2D have shown conflicting results, subgroup and meta-analyses support the idea that raising serum vitamin D levels may reduce the progression from prediabetes to T2D. In this review, we summarize current knowledge on the molecular mechanisms of vitamin D in insulin secretion, insulin sensitivity, and immunity, as well as the observational and interventional human studies investigating the use of vitamin D as a treatment for diabetes.
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Affiliation(s)
- Jie Wu
- Department of Physiology and Biomedical Engineering, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
| | - Annette Atkins
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Michael Downes
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
| | - Zong Wei
- Department of Physiology and Biomedical Engineering, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
- Division of Endocrinology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
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Khan Z, Muhammad SA, Carpio J, Yousif Y, Gul A, Hamid S, Gupta A. The Effect of Vitamin D Supplementation on Incidence of Type 2 Diabetes: A Systematic Review. Cureus 2023; 15:e36775. [PMID: 37123701 PMCID: PMC10133782 DOI: 10.7759/cureus.36775] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/27/2023] [Indexed: 03/30/2023] Open
Abstract
With the clinical increase in Type 2 Diabetes worldwide, several interventions to decrease its incidence have been investigated. One such intervention is Vitamin D supplementation, as it affects Insulin secretion from the pancreas and Insulin receptors in the cells of the body. This systematic review addresses whether or not Vitamin D supplementation has a role in reducing the risk of developing Type 2 Diabetes. Systematic searches were conducted on PubMed, and Cochrane Library mainly but also checked Google Scholar. Randomized controlled trials, systematic trials and cohort studies were retrieved that included keywords pertaining to Vitamin D supplementation and the incidence of Type 2 Diabetes. Exclusion criteria included studies that looked at different forms of Diabetes, studies including patients aged less than 18 or more than 85 years of age and studies that were not English language. For all the trials identified, the incidence of Type 2 Diabetes among the cohort receiving vitamin D supplementation was compared to the cohort receiving placebo medication. Additionally, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was analyzed to observe if there was a difference between Insulin resistance among these two cohorts between the start of the trials and the end. Thirteen randomized controlled trials were identified. Seven of these identified incidences of Type 2 Diabetes as a research outcome, out of which six showed no statistically significant impact of vitamin D on the incidence of Type 2 Diabetes. Out of the 13 trials, 10 analyzed the impact of vitamin D supplementation on patients' HOMA-IR. In six of these trials, patients receiving vitamin D supplementation had a decrease in their HOMA-IR, while it increased in 4 trials. In seven of the ten trials that analyzed for HOMA-IR, the HOMA-IR was less in the vitamin D cohort than the placebo cohort. There is insufficient evidence to suggest that vitamin D supplementation significantly reduces the incidence of Type 2 Diabetes despite its effects on insulin resistance. Further research in this area would be helpful in order to influence clinical guidelines on vitamin D supplementation among patients at risk of Type 2 Diabetes.
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Mustafa A, Shekhar C. Association between serum 25-hydroxyvitamin-D and Triglycerides-Glucose index among Indian adolescents. BMC Nutr 2022; 8:69. [PMID: 35879737 PMCID: PMC9310494 DOI: 10.1186/s40795-022-00568-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/19/2022] [Indexed: 12/02/2022] Open
Abstract
Background Vitamin D deficiency has been found to associated with numerous skeletal and non-skeletal diseases including Diabetes Mellitus. Insulin Resistance (IR) is considered as one of the primary reasons of Type-2 Diabetes Mellitus (T2DM). The association between vitamin D deficiency and IR has been extensively explore in previous studies, but none of them focused on Indian adolescents, and none of them used the TyG index as IR marker. Hence, this population-based cross-sectional study investigates the relationship between insulin resistance (IR) assessed using the Triglycerides Glucose Index (TyG index) and vitamin D measured by serum 25-hydroxyvitamin-D (25(OH)D). Methods For this study, we utilized data from the Comprehensive National Nutrition Survey (CNNS, 2016–18). The study is based on a sample size of 10,167 adolescents aged 10–19 years. The TyG index cut-off value of 4.65 was used to classify IR. We examined associations between the TyG index and serum 25(OH)D using multiple linear regression models adjusted for potential confounders. Odds of Insulin Resistance among vitamin D deficient/insufficient adolescents were assessed using multivariable logistic regression. Results A significant negative association was found between serum 25(OH)D and the TyG index, where a 10% increase in serum 25(OH)D was associated with 0.56 (95% CI = -0.67, -0.45) unit decrement in the TyG index. The odds of having IR were 90% higher among vitamin D deficient adolescents (OR: 1.90; 95% CI = 1.62—2.23) compared to adolescents with adequate levels of vitamin D. The association between vitamin D deficiency and IR was independent of sex; in other words, the association between vitamin D and IR was significant in both the sexes. Conclusion Independent of sex, this study found a significant inverse association between vitamin D and insulin resistance in Indian adolescents. The findings of this study highlight the utility of TyG index and the importance of vitamin D in lowering the risk of T2DM in future generations of the country.
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Peng H, Wang M, Pan L, Cao Z, Yao Z, Chen Q, Li Y, Wang Y, Lv W. Associations of serum multivitamin levels with the risk of non-alcoholic fatty liver disease: A population-based cross-sectional study in U.S. adults. Front Nutr 2022; 9:962705. [PMID: 36172527 PMCID: PMC9511103 DOI: 10.3389/fnut.2022.962705] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/22/2022] [Indexed: 11/22/2022] Open
Abstract
Vitamins were closely associated with non-alcoholic fatty liver disease (NAFLD) development, but no study had explored the association of serum multivitamin levels with NAFLD risk. We assessed the association between serum levels of both single-vitamin and multivitamins (VA, VB6, VB9, VB12, VC, VD, and VE) and the risk of NAFLD, using the database of National Health and Nutrition Examination Survey (NHANES) (cycles 2003–2004 and 2005–2006). We employed multivariable logistic regression and weighted quantile sum (WQS) regression models to explore the association of serum multivitamin levels with NAFLD. Among all 2,294 participants, 969 participants with NAFLD were more likely to be male, older, less educated, or have hypertension/high cholesterol/diabetes. After adjustment of covariates, serum VC/VD/VB6/VB9 levels were negatively correlated with NAFLD risk, while serum VA/VE levels were positively correlated with NAFLD risk. In the WQS model, elevated serum VA/VE levels and lowered serum VC/VD/VB6 levels were linearly associated with increased NAFLD risk. There was a non-linear relationship between serum VB9/VB12 levels and NAFLD risk. There were evident associations between serum multivitamin levels and reduced NAFLD risk, which was mainly driven by VD/VB9/VC. In conclusion, our findings suggested that serum multivitamin levels were significantly associated with the risk of NAFLD.
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Affiliation(s)
- Hongye Peng
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Hongye Peng,
| | - Miyuan Wang
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liang Pan
- Phase 1 Clinical Trial Center, Deyang People’s Hospital, Deyang, China
| | - Zhengmin Cao
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ziang Yao
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiuye Chen
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanbo Li
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuhua Wang
- Phase 1 Clinical Trial Center, Deyang People’s Hospital, Deyang, China
| | - Wenliang Lv
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Wenliang Lv,
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11
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Muley A, Fernandez R, Green H, Muley P. Effect of thiamine supplementation on glycaemic outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. BMJ Open 2022; 12:e059834. [PMID: 36008064 PMCID: PMC9422810 DOI: 10.1136/bmjopen-2021-059834] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have been shown to have thiamine deficiency. Dietary supplementation is an economic strategy to control blood glucose. Objective: To evaluate effectiveness of thiamine supplementation on glycaemic outcomes in patients with T2DM. METHODS Eligibility criteria: Studies that assessed effect of thiamine supplementation in adults with T2DM which measured glycaemic outcomes-HbA1c, fasting blood glucose (FBG) and/or postprandial blood glucose (PPG) were included. Information sources: PUBMED, Tripdatabase, the Cochrane Central Register, National Institute of Health Clinical Database and Google Scholar were searched until December 2021 for RCTs. Risk of bias: It was assessed using standardised critical appraisal instruments from the Joanna Briggs Institute for RCTs. Synthesis of results: Where possible, studies were pooled in a meta-analysis. Results were presented in a narrative format if statistical pooling was not possible. RESULTS Included studies: Six trials involving 364 participants. Synthesis of results: No significant beneficial effects were observed on glycaemic outcomes with 100-900 mg/day of thiamine or benfotiamine for up to 3 months (HbA1c: MD, -0.02%, 95% CI: -0.35 to 0.31; FBG: MD,-0.20 mmol/L; 95% CI: -0.69 to 0.29; PPG: MD, - 0.20 mmol/L, 95% CI: -2.05 to 1.65 (mean difference, MD)). There was a significant increase in high-density lipoprotein (HDL) (MD, 0.10; 95% CI: 0.10 to 0.20) at 3-month follow-up. Benfotiamine reduced triglyceride level (MD, -1.10; 95% CI: -1.90 to -0.30) in 120 mg/day dose as compared with placebo 150 mg/day, however this was not demonstrated in higher doses. DISCUSSION Limitations of evidence: Inclusion of single-centre trials published only in English, small sample sizes of included studies, lack of trials investigating outcomes for same comparisons and varying follow-up periods. Interpretation: Thiamine supplementation does not affect glycaemic outcomes, however reduces triglycerides while increasing HDL. Multicentre well-designed RCT with higher doses of thiamine and a follow-up period of 1-2 years will provide better evidence. PROSPERO REGISTRATION NUMBER CRD42020170520.
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Affiliation(s)
- Arti Muley
- Medicine, PIMSR, Parul University, Vadodara, Gujarat, India
| | - Ritin Fernandez
- Nursing, University of Wollongong Faculty of Science Medicine and Health, Wollongong, New South Wales, Australia
| | - Heidi Green
- Nursing, Centre for Research in Nursing and Health, St George Hospital, Sydney, New South Wales, Australia
| | - Prasad Muley
- Pediatrics, PIMSR, Parul University, Vadodara, Gujarat, India
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12
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Norbitt CF, Kimita W, Bharmal SH, Ko J, Petrov MS. Relationship between Habitual Intake of Vitamins and New-Onset Prediabetes/Diabetes after Acute Pancreatitis. Nutrients 2022; 14:nu14071480. [PMID: 35406092 PMCID: PMC9003206 DOI: 10.3390/nu14071480] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/29/2022] [Accepted: 03/29/2022] [Indexed: 02/01/2023] Open
Abstract
Vitamins have many established roles in human health. However, the role of habitual dietary intake of vitamins in glucose homeostasis in individuals after acute pancreatitis (AP) is yet to be elucidated. The aim was to investigate the associations between habitual intake of fat- and water-soluble vitamins/vitamers and markers of glucose metabolism (fasting plasma glucose (FPG), homeostasis model assessment insulin resistance (HOMA-IR) index, and homeostasis model assessment β-cell function (HOMA-β)) in individuals after AP. A total of 106 participants after AP were included in this cross-sectional study and were grouped based on glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Habitual intake of seven fat-soluble vitamins/vitamers and seven water-soluble vitamins were determined by the EPIC-Norfolk food frequency questionnaire. Multiple linear regression analyses were conducted using five statistical models built to adjust for covariates (age, sex, daily energy intake, visceral/subcutaneous fat volume ratio, smoking status, daily alcohol intake, aetiology of AP, number of AP episodes, cholecystectomy, and use of antidiabetic medications). In the NODAP group, three fat-soluble vitamins/vitamers (α-carotene, β-carotene, and total carotene) were significantly associated with HOMA-β. One water-soluble vitamin (vitamin B3) was also significantly associated with HOMA-β in the NODAP group. None of the studied vitamins were significantly associated with FPG or HOMA-IR in the NODAP group. Prospective longitudinal studies and randomised controlled trials are now warranted to investigate if the observed associations between vitamin/vitamer intake and NODAP are causal and to unveil the specific mechanisms underlying their involvement with NODAP.
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13
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Zandieh N, Hemami MR, Darvishi A, Hasheminejad SM, Abdollahi Z, Zarei M, Heshmat R. Economic evaluation of a national vitamin D supplementation program among Iranian adolescents for the prevention of adulthood type 2 diabetes mellitus. BMC Complement Med Ther 2022; 22:1. [PMID: 34980092 PMCID: PMC8722369 DOI: 10.1186/s12906-021-03474-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 12/02/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study aimed to evaluate the cost-effectiveness of vitamin D supplementation in preventing type 2 diabetes mellitus (T2DM) among Iranian adolescents. METHODS This analytical observational study was conducted, using the decision tree model constructed in TreeAge Pro to assess the cost per quality-adjusted life-year (QALY) of monthly intake vitamin D supplements to prevent T2DM compared to no intervention from the viewpoint of Iran's Ministry of Health and through an one-year horizon. In the national program of vitamin D supplementation, 1,185,211 Iranian high-school students received 50,000 IU vitamin D supplements monthly for nine months. The costs-related data were modified to 2018. The average cost and effectiveness were compared based on the Incremental Cost-Effectiveness Ratio (ICER). RESULTS Our analytical analysis estimated the 4071.25 (USD / QALY) cost per AQALY gained of the monthly intake of 50,000 IU vitamin D for nine months among adolescents over a one-year horizon. Based on the ICER threshold of 1032-2666, vitamin D supplementation was cost-effective for adolescents to prevent adulthood T2DM. It means that vitamin D supplementation costs were substantially less than the costs of T2DM treatments than the no intervention. CONCLUSIONS Based on the findings, the national vitamin D supplementation program for Iranian adolescents could be a cost-effective strategy to reduce the risk of diabetes in adulthood. From an economic perspective, vitamin D supplementation, especially in adolescents with vitamin D deficiency, would be administrated.
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Affiliation(s)
- Narges Zandieh
- Faculty of pharmacy, Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | | | - Ali Darvishi
- Department of Management and Health Economics, School of Public Health, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Zahra Abdollahi
- Office of Community Nutrition, Deputy of Health, Iran Ministry of Health and Medical Education, Tehran, Iran
| | - Maryam Zarei
- Office of Community Nutrition, Deputy of Health, Iran Ministry of Health and Medical Education, Tehran, Iran
| | - Ramin Heshmat
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, 1941933111, Iran.
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14
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Effect of Vitamin D Supplementation on Glycemic Control in Prediabetes: A Meta-Analysis. Nutrients 2021; 13:nu13124464. [PMID: 34960022 PMCID: PMC8707376 DOI: 10.3390/nu13124464] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/08/2021] [Accepted: 12/09/2021] [Indexed: 12/25/2022] Open
Abstract
Clinical research results of vitamin D supplementation in the improvement of prediabetes remain controversial. Accordingly, a literature search was conducted of PubMed, Embase (Ovid), and Web of Science prior to 9 November 2021. Randomized controlled studies reported that the following indicators were included: body mass index (BMI), fasting blood glucose (FBG), 2 h oral glucose tolerance test plasma glucose (2h-PG), hemoglobin A1c (HbA1c), insulin resistance by homeostasis model assessment (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), and fasting insulin (FINS). Twenty-nine articles (N = 3792) were included in the present meta-analysis. Intriguingly, vitamin D supplementation resulted in a vast improvement in FBG (standardized mean difference (SMD) = -0.38; 95%CI: -0.59, -0.16), HbA1c (SMD = -0.14; 95%CI: -0.22, -0.06) and FINS (SMD = 0.18; 95%CI: -0.26, -0.09), but not in other outcomes. However, preferred changes were observed in subgroups, as follows: Asia (SMD2h-PG = -0.25, 95%CI: -0.45, -0.04), study duration ≥1 year (SMDHOMA-IR = -0.44, 95%CI: -0.81, -0.06) (SMDHOMA-B = 0.34, 95%CI: 0.01, 0.66), baseline 25(OH)D < 50 nmol/L (SMD2h-PG = -0.23, 95%CI: -0.39, -0.06), and baseline 25(OH)D ≥ 50 nmol/L (SMDHOMA-IR = -0.50, 95%CI: -0.96, -0.03). In conclusion, oral supplementation of vitamin D has shown better effects in improving FBG, HbA1c, and FINS compared with controls among prediabetics; long-term vitamin D supplementation could have additional effects in participants with vitamin D deficiency for 2h-PG, HOMA-IR, and HOMA-B.
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15
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Adebayo FA, Itkonen ST, Öhman T, Kiely M, Cashman KD, Lamberg-Allardt C, on behalf of the ODIN Consortium. Safety of Vitamin D Food Fortification and Supplementation: Evidence from Randomized Controlled Trials and Observational Studies. Foods 2021; 10:foods10123065. [PMID: 34945616 PMCID: PMC8701201 DOI: 10.3390/foods10123065] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/18/2021] [Accepted: 11/29/2021] [Indexed: 12/31/2022] Open
Abstract
The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was <10% when vitamin D supplements were administered, and <0.1% for fortified foods. Elevated serum calcium was observed among <0.5% in both administration types. No ODIN RCT participants exceeded the age-specific ULs. In observational studies (n = 61,082), the prevalence of high 25(OH)D among children/adolescents, adults, and older adults was <0.3%, with no evidence of adverse effects. In conclusion, high S-25(OH)D concentrations >125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.
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Affiliation(s)
- Folasade A. Adebayo
- Calcium Research Unit, Department of Food and Nutrition, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland; (F.A.A.); (S.T.I.); (T.Ö.)
| | - Suvi T. Itkonen
- Calcium Research Unit, Department of Food and Nutrition, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland; (F.A.A.); (S.T.I.); (T.Ö.)
| | - Taina Öhman
- Calcium Research Unit, Department of Food and Nutrition, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland; (F.A.A.); (S.T.I.); (T.Ö.)
| | - Mairead Kiely
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, T12 Y337 Cork, Ireland; (M.K.); (K.D.C.)
| | - Kevin D. Cashman
- Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, University College Cork, T12 Y337 Cork, Ireland; (M.K.); (K.D.C.)
| | - Christel Lamberg-Allardt
- Calcium Research Unit, Department of Food and Nutrition, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland; (F.A.A.); (S.T.I.); (T.Ö.)
- Correspondence:
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16
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Zou Y, Guo B, Yu S, Wang D, Qiu L, Jiang Y. Effect of vitamin D supplementation on glycose homeostasis and islet function in vitamin D deficient or insufficient diabetes and prediabetes: a systematic review and meta-analysis. J Clin Biochem Nutr 2021; 69:229-237. [PMID: 34857984 PMCID: PMC8611361 DOI: 10.3164/jcbn.20-165] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Accepted: 10/25/2020] [Indexed: 11/25/2022] Open
Abstract
Objective of the present study was to evaluate the effect of vitamin D supplementation on glycose homeostasis, islet function, and diabetes progress. Literatures were searched via electronic databases, websites, and previous reviews from the earliest available time to the end of May 2020. Randomized controlled trials initially designed for diabetes and prediabetes with 25-dihydroxyvitamin D [25(OH)D]<30 ng/ml were included. All data were analyzed and presented based on the Cochrane guidelines and PRISMA guidelines. In total, 27 articles (n = 1,932) were enrolled in this study. Vitamin D supplementation significantly improved fasting blood glucose, postprandial blood glucose, and quantitative insulin sensitivity check index in diabetes and prediabetes with baseline 25(OH)D<30 ng/ml. Higher percentages regressing from prediabetes to normal glucose status [1.60 (1.19, 2.17), p = 0.002, n = 564] and lower percentage progressing from prediabetes to diabetes [0.68 (0.36, 1.27), p = 0.23, n = 569] were found in the supplementation group. The positive effects of vitamin D supplementation on body mass index, waist, HDL-C, LDL-C, and CRP were also demonstrated. In conclusion, modest improvements in vitamin D supplementation on short-term glycose homeostasis, insulin sensitivity, and disease development in diabetes and prediabetes with 25(OH)D<30 ng/ml were demonstrated, but more research needs to be conducted in the future to support the clinical application. (Register ID: CRD42020186004)
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Affiliation(s)
- Yutong Zou
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifu Yuan, Dongcheng District, Beijing 100730, China
| | - Bo Guo
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifu Yuan, Dongcheng District, Beijing 100730, China
| | - Songlin Yu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifu Yuan, Dongcheng District, Beijing 100730, China
| | - Danchen Wang
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifu Yuan, Dongcheng District, Beijing 100730, China
| | - Ling Qiu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifu Yuan, Dongcheng District, Beijing 100730, China
| | - Yu Jiang
- Department of Epidemiology and Biostatistics, School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Dongcheng District, Beijing 100730, China
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17
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Vitamin D Deficiency Is Inversely Associated with Homeostatic Model Assessment of Insulin Resistance. Nutrients 2021; 13:nu13124358. [PMID: 34959910 PMCID: PMC8705502 DOI: 10.3390/nu13124358] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/24/2021] [Accepted: 11/25/2021] [Indexed: 01/08/2023] Open
Abstract
The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = -0.217; 95% CI = -0.161 to -0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.
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18
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Lu Q, Wan Z, Guo J, Liu L, Pan A, Liu G. Association Between Serum 25-hydroxyvitamin D Concentrations and Mortality Among Adults With Prediabetes. J Clin Endocrinol Metab 2021; 106:e4039-e4048. [PMID: 34089603 DOI: 10.1210/clinem/dgab402] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Indexed: 01/08/2023]
Abstract
OBJECTIVES To investigate the association of circulating 25-hydroxyvitamin D [25(OH)D] levels with mortality among adults with prediabetes. METHODS This retrospective cohort study included 15,195 adults with prediabetes (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2014. Mortality from all causes, cardiovascular disease (CVD), and cancer was linked to National Death Index mortality data. RESULTS The median (interquartile range) concentration of serum 25(OH)D was 60.5 (45.3, 77.4) nmol/L, and only 23.1% had sufficient vitamin D (≥75 nmol/L). Elevated serum 25(OH)D concentrations were significantly associated with lower levels of insulin, homeostasis model assessment of insulin resistance, triglyceride, and C-reactive protein, and higher levels of high-density lipoprotein at baseline (all Ptrend < 0.05). During a median follow up of 10.7 years, 3765 deaths (including 1080 CVD deaths and 863 cancer deaths) were identified. Compared with participants with 25(OH)D <30 nmol/L, the multivariate-adjusted hazard ratios and 95% confidence intervals for participants with 25(OH)D ≥ 75 nmol/L were 0.66 (0.53, 0.82) for all-cause mortality (Ptrend < 0.001), 0.66 (0.48, 0.89) for CVD mortality (Ptrend = 0.001), and 0.82 (0.49, 1.35) for cancer mortality (Ptrend = 0.32). For per-unit increment in ln-transformed 25(OH)D, there was a 27% lower risk of all-cause mortality and a 34% lower risk of CVD mortality (both P < 0.01). CONCLUSIONS These findings suggested that higher serum 25(OH)D concentrations were associated with lower all-cause and CVD mortality among individuals with prediabetes.
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Affiliation(s)
- Qi Lu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Zhenzhen Wan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Jingyu Guo
- Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - An Pan
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Gang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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19
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Di Luigi L, Antinozzi C, Piantanida E, Sgrò P. Vitamin D, sport and health: a still unresolved clinical issue. J Endocrinol Invest 2020; 43:1689-1702. [PMID: 32632904 DOI: 10.1007/s40618-020-01347-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 06/25/2020] [Indexed: 02/07/2023]
Abstract
Vitamin D metabolites have a pleiotropic role in human physiology, both in static and dynamic conditions, and a lot of vitamin D-related biological effects could influence physical and sport performances in athletes. Probably due to different factors (e.g., drugs, doping, nutrition, ultraviolet B radiation exposure), in athletes a very high prevalence of vitamin D inadequacy (i.e., deficiency or insufficiency) has been observed. Vitamin D inadequacy in athletes could be associated with specific health risks and to alterations of functional capacities, potentially influencing the fine adjustment of physical performances during training and sport competitions. When risk factors for vitamin D inadequacy exist, a preventive vitamin D supplementation is indicated, and if a vitamin D inadequacy is diagnosed, its supplementation is recommended. Unfortunately, on these issues many concerns remain unresolved. Indeed, it is not clear if athletes should be classified as a special population at increased risk for vitamin D inadequacy; moreover, in comparison to the non-athletic population, it is still not clear if athletes should have different reference ranges and different optimal target levels for serum vitamin D, if they have additional health risks, and if they need different type of supplementations (doses) for prevention and/or replacement therapy. Moreover, in athletes also the abuse of vitamin D supplements for ergogenic purposes raise different ethical and safety concerns. In this review, the main physio-pathological, functional and clinical issues that relate vitamin D to the world of athletes are described.
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Affiliation(s)
- L Di Luigi
- Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università Degli Studi Di Roma "Foro Italico", Piazza Lauro de Bosis, 6, 00135, Rome, Italy.
| | - C Antinozzi
- Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università Degli Studi Di Roma "Foro Italico", Piazza Lauro de Bosis, 6, 00135, Rome, Italy
| | - E Piantanida
- Department of Medicine and Surgery, University of Insubria, Via Ravasi 2, 21100, Varese, Italy
| | - P Sgrò
- Unit of Endocrinology, Department of Movement, Human and Health Sciences, Università Degli Studi Di Roma "Foro Italico", Piazza Lauro de Bosis, 6, 00135, Rome, Italy
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Sadeghian M, Asadi M, Rahmani S, Akhavan Zanjani M, Sadeghi O, Hosseini SA, Zare Javid A. Circulating vitamin D and the risk of gestational diabetes: a systematic review and dose-response meta-analysis. Endocrine 2020; 70:36-47. [PMID: 32710437 DOI: 10.1007/s12020-020-02360-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 05/19/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE Several meta-analyses of observational studies revealed a modest increase in the risk of gestational diabetes (GDM) among pregnant women with low levels of serum vitamin D. However, no study examined a dose-response meta-analysis as well as a high versus low analysis in this regard. METHODS We systematically searched PubMed, Embase, ISI Web of Science, and Scopus up to August 2019 to find prospective observational studies investigating the association of serum 25(OH)D with the risk of developing GDM. Using a random-effects model, the reported risk estimates were pooled. RESULTS Nine cohort studies and six nested case-control studies were included in the final analysis (40,788 participants and 1848 cases). Considering linear analysis, each 10 nmol/L increase in circulating 25(OH)D was associated with a 2% lower risk of GDM (effect size (ES): 0.98; 95% CI: 0.98, 0.99; I2 = 85.0%, P < 0.001). highest compared with the lowest category of circulating 25(OH)D was associated with a 29% lower risk of GDM, with low evidence of heterogeneity (I2 = 45.0%, P = 0.079). CONCLUSIONS In conclusion, lower levels of serum 25(OH)D were associated with a higher chance of GDM. Differential results existed between the overall and subgroup analysis, either based on vitamin D detection methods or based on maternal age, although these subgroups partially lowered the heterogeneity.
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Affiliation(s)
- Mehdi Sadeghian
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Asadi
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sepideh Rahmani
- Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohsen Akhavan Zanjani
- Division of Kinesiology, School of Health and Human Performance, Dalhousie University, Halifax, Canada
| | - Omid Sadeghi
- Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Ahmad Hosseini
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ahmad Zare Javid
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Pragya PhD P, Yadav Md RK, Khadgawat Dm R, Pandey PhD RM. Effect of Vitamin D Supplementation on Disposition Index in Non-Diabetic Indians with Obesity: A Double-Blind Randomized Placebo-Controlled Trial. J Diet Suppl 2020; 18:630-645. [PMID: 32996330 DOI: 10.1080/19390211.2020.1827116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This double-blind randomized placebo-controlled trial was designed to investigate the effect of vitamin D3 supplementation on the disposition index in non-diabetic Indian subjects with obesity. Subjects with obesity [n = 120] were randomized to receive a monthly dose of 120,000 IU of vitamin D3 or matching placebo for 6 months. The primary outcome was a change in disposition index (DI) and secondary outcome measures were change in the homeostatic model assessment of insulin resistance and change in body composition. A total of 101 subjects [50 in the vitamin D group (VITD) and 51 in the Placebo group (PL)] completed the study. The mean baseline serum 25-hydroxyvitamin [25(OH) D] concentration was 11.6 ng/ml. There was no significant difference observed between the two groups in any of the primary or secondary outcomes. However, there were a significant increase in median serum 25(OH) D levels in the VITD group than the PL at 6 months of intervention. The results of the present study suggest that supplementation of vitamin D3 has no additional benefit over placebo on pancreatic β-cell functions in non-diabetic Indian subjects with obesity. Further larger studies are required to confirm the results of the study. The trial is registered with the Clinical Trials Registry of India, CTRI/2015/04/005727.
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Affiliation(s)
- Pragati Pragya PhD
- Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - Raj Kumar Yadav Md
- Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Khadgawat Dm
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
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Yau JW, Thor SM, Ramadas A. Nutritional Strategies in Prediabetes: A Scoping Review of Recent Evidence. Nutrients 2020; 12:E2990. [PMID: 33003593 PMCID: PMC7650618 DOI: 10.3390/nu12102990] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 09/25/2020] [Accepted: 09/27/2020] [Indexed: 02/06/2023] Open
Abstract
Nutritional therapy has been conventionally recommended for people with prediabetes as a method to delay or halt progression to type 2 diabetes. However, recommended nutritional strategies evolve over time. Hence, we performed a scoping review on recently reported nutritional interventions for individuals with prediabetes. Ovid MEDLINE, PubMed, Embase, Scopus, CINAHL and PsycINFO databases were searched to identify relevant research articles published within the past 10 years. Ninety-five articles involving a total of 11,211 participants were included in this review. Nutritional strategies were broadly classified into four groups: low calorie diet, low glycemic index diet, specific foods, and a combination of diet and exercise. The most frequently assessed outcomes were plasma glucose, serum insulin, serum lipid profile, body mass index and body weight. More than 50% of reported interventions resulted in significant improvements in these parameters. Nutritional interventions have demonstrated feasibility and practicality as an effective option for prediabetes management. However, the intervention variability demonstrates the challenges of a 'one-size-fits-all' approach. Investigations in genetically diverse populations and objective assessment of progression rate to diabetes are necessary to better comprehend the impact of these nutritional strategies in prediabetes.
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Affiliation(s)
| | | | - Amutha Ramadas
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia; (J.W.Y.); (S.M.T.)
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Bassatne A, Jafari A, Kassem M, Mantzoros C, Rahme M, El-Hajj Fuleihan G. Delta-like 1 (DLK1) is a possible mediator of vitamin D effects on bone and energy metabolism. Bone 2020; 138:115510. [PMID: 32622071 PMCID: PMC11133180 DOI: 10.1016/j.bone.2020.115510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 06/11/2020] [Accepted: 06/25/2020] [Indexed: 10/24/2022]
Abstract
Vitamin D effects on bone and mineral metabolism are well recognized, and its anti-inflammatory actions are gaining particular interest. Delta-like 1 (DLK1) is a protein, expressed by progenitor cells of different tissues, and increases the size of progenitor cell population during the inflammatory phase of tissue regeneration. DLK1 also plays a role in energy metabolism as it antagonizes insulin signaling in bone. In this one-year randomized clinical trial of overweight elderly individuals that received either 600 or 3750 IU daily cholecalciferol we assessed the effect of vitamin D supplementation on pre-specified secondary outcomes: DLK1, leptin, adiponectin, C-Reactive Protein (CRP) and Vascular Cell Adhesion Molecule (VCAM). We also examined correlations between DLK1 and bone (BMD, bone markers), fat (adipokines, body composition), insulin sensitivity and inflammatory markers. Multivariate analyses were conducted to further explore these associations. Overall, there was a significant increase in serum DLK1 and leptin and a decrease in VCAM, but no change in CRP, after 12 months of vitamin D supplementation. DLK1 was negatively correlated with BMD and positively correlated with bone markers, associations that persisted after adjusting for age, gender and BMI. DLK1 was also positively associated with indices of insulin resistance and negatively with indices of insulin sensitivity. Correlations between DLK1 and fat parameters, such as adipokines, and DXA derived fat mass were less consistent. There were no correlations between DLK1 and inflammatory markers. In conclusion, twelve months supplementation of vitamin D3 increased serum DLK1. DLK1 was negatively associated with indices of bone health and fuel metabolism, and with 1,25(OH)2D levels. Similar to the role of DLK1 in animal models, our findings support the hypothesis that DLK1 can be targeted to regulate bone and energy metabolism and develop drugs to improve BMD and insulin sensitivity. However, further studies are needed to explore the role of DLK1 and its relationship to vitamin D metabolites in vivo.
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Affiliation(s)
- Aya Bassatne
- Calcium Metabolism and Osteoporosis Program, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Abbas Jafari
- Molecular Endocrinology and Stem Cell Research Unit (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Cellular and Molecular Medicine, Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark
| | - Moustapha Kassem
- Molecular Endocrinology and Stem Cell Research Unit (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Christos Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Maya Rahme
- Calcium Metabolism and Osteoporosis Program, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ghada El-Hajj Fuleihan
- Calcium Metabolism and Osteoporosis Program, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
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Effect of N-Acetylcysteine on Metabolic Profile in Metabolic Syndrome Patients. Metab Syndr Relat Disord 2020; 18:341-346. [DOI: 10.1089/met.2020.0017] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
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Pramono A, Jocken JWE, Blaak EE, van Baak MA. The Effect of Vitamin D Supplementation on Insulin Sensitivity: A Systematic Review and Meta-analysis. Diabetes Care 2020; 43:1659-1669. [PMID: 33534727 DOI: 10.2337/dc19-2265] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 03/02/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n = 612) with placebo (n = 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference -0.01, 95% CI -0.12, 0.10; P = 0.87, I 2 = 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.
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Affiliation(s)
- Adriyan Pramono
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.,Department of Nutrition, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
| | - Johan W E Jocken
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
| | - Ellen E Blaak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
| | - Marleen A van Baak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands
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27
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Yaribeygi H, Maleki M, Sathyapalan T, Iranpanah H, Orafai HM, Jamialahmadi T, Sahebkar A. The molecular mechanisms by which vitamin D improve glucose homeostasis: A mechanistic review. Life Sci 2020; 244:117305. [DOI: 10.1016/j.lfs.2020.117305] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 01/12/2020] [Indexed: 12/16/2022]
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28
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Effects of vitamin D supplementation on the glycemic control of pre-diabetic individuals: a systematic review. NUTR HOSP 2020; 38:186-193. [PMID: 33319569 DOI: 10.20960/nh.03309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Introduction Introduction: research shows the potential effect of vitamin D supplementation with an improvement in the glycemic profile of pre-diabetic patients. Objective: this study evaluates the effects of vitamin D supplementation on glycemic control markers in pre-diabetic individuals. Methods: we analyzed studies published over the last ten years, and indexed in the Science Direct, PubMed, and LILACS databases. We searched studies using health descriptors related to vitamin D, pre-diabetes, and glycemic control markers. We considered randomized controlled trials eligible for inclusion. All phases of selection, data extraction, and risk of bias assessment were carried out by two independent evaluators. Results: we identified 309 articles, of which 4 met the inclusion criteria. Of these, 3 studies have shown that vitamin D supplementation does not alter glycemic control markers in pre-diabetic individuals. Only one study showed a positive effect after supplementation with 60,000 IU/month of vitamin D3 for 12 months, with a significant reduction in the concentrations of glycated hemoglobin, fasting glucose, and two-hour postprandial glucose. Conclusion: there is insufficient scientific evidence to confirm the beneficial effects of vitamin D supplementation on glycemic control markers in pre-diabetic individuals.
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29
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Wallace HJ, Holmes L, Ennis CN, Cardwell CR, Woodside JV, Young IS, Bell PM, Hunter SJ, McKinley MC. Effect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2019; 110:1138-1147. [PMID: 31559433 DOI: 10.1093/ajcn/nqz171] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/03/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Observational studies have suggested an inverse association between low serum 25-hydroxyvitamin D [25(OH)D] concentrations and development of type 2 diabetes. High-quality trials are required to test the hypothesis that vitamin D is a direct contributor to type 2 diabetes pathogenesis. OBJECTIVE The purpose of this double-blind randomized placebo-controlled trial was to investigate the effect of vitamin D3 supplementation on insulin resistance (IR) and β-cell function in people with prediabetes and suboptimal vitamin D status (<50 nmol/L). METHODS Sixty-six individuals were randomly assigned to receive 3000 IU (75 µg) vitamin D3 or placebo daily for 26 wk. Compliance was monitored by pill count and change in serum 25(OH)D concentration using LC-MS. The primary endpoint was between-group difference in change in IR assessed using a 2-step euglycemic-hyperinsulinemic clamp combined with infusion of tritiated glucose. An oral-glucose-tolerance test was performed pre- and postintervention to calculate indices of β-cell function. Between-group comparisons were made using ANCOVA. RESULTS In total, 64 participants completed the study. Baseline serum 25(OH)D concentrations in the vitamin D3 and placebo group were 30.7 and 30.0 nmol/L, with status increasing by 70.5 nmol/L and 5.3 nmol/L, respectively (between-group difference in vitamin D: 65.8 nmol/L; 95% CI: 54.2, 77.3 nmol/L; P < 0.01), after supplementation. There was no difference between groups in measures of whole-body, peripheral, or hepatic IR or in any measure of glycemic control or β-cell function. CONCLUSION This study employed a robust assessment of IR and β-cell function and targeted a high-risk population with low 25(OH)D status at baseline and found that vitamin D3 supplementation had no effect on insulin action in people with prediabetes.This trial was registered on clinicaltrials.gov as NCT01889810.
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Affiliation(s)
- Helen J Wallace
- Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom.,Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Lauren Holmes
- Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Cieran N Ennis
- Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom.,Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Christopher R Cardwell
- Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Jayne V Woodside
- Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Ian S Young
- Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
| | - Patrick M Bell
- Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom
| | - Steven J Hunter
- Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom
| | - Michelle C McKinley
- Nutrition Group, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Belfast, United Kingdom
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Varshney S, Khadgawat R, Gahlot M, Khandelwal D, Oberoi AK, Yadav RK, Sreenivas V, Gupta N, Tandon N. Effect of High-dose Vitamin D Supplementation on Beta Cell Function in Obese Asian-Indian Children and Adolescents: A Randomized, Double Blind, Active Controlled Study. Indian J Endocrinol Metab 2019; 23:545-551. [PMID: 31803595 PMCID: PMC6873255 DOI: 10.4103/ijem.ijem_159_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE Vitamin D deficiency has been found to be associated with insulin resistance. In an attempt to explore this association, we planned a study to investigate the effects of high-dose vitamin D supplementation on beta cell function in obese children and adolescents. METHODS A randomized, double blind, active-controlled study was carried out to investigate the effects of high dose (120,000 IU once a month) vitamin D supplementation in comparison to recommended daily allowance (12,000 IU/month) for 12 months. Beta cell function was assessed by disposition index. Inflammatory cytokines and cardiovascular risk factors were also assessed before and after supplementation. RESULTS A total of 189 obese children and adolescents were recruited. The mean serum 25OHD level of the study population was 8.36 ± 5.45 ng/ml. At baseline, 94.7% subjects were vitamin D deficient (<20 ng/mL). After 12 months of supplementation, serum 25OHD level in intervention group was 26.89 ± 12.23 ng/mL, while in control group, it was 13.14 ± 4.67 ng/mL (P < 0.001). No significant difference in disposition index as well as other parameters of insulin resistance, sensitivity, inflammatory cytokines, and pulse wave velocity was seen after supplementation. CONCLUSION Vitamin D supplementation in doses of 120,000 IU per month for 12 months in obese Asian-Indian children and adolescents did not affect beta cell function as well as cardiovascular risk factors.
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Affiliation(s)
- Shweta Varshney
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Khadgawat
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Monita Gahlot
- Department of Dietitics, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Khandelwal
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Avneet Kaur Oberoi
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - R. K. Yadav
- Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
| | - V Sreenivas
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Nandita Gupta
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
| | - Nikhil Tandon
- Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India
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Vitamin D Status, Calcium Intake and Risk of Developing Type 2 Diabetes: An Unresolved Issue. Nutrients 2019; 11:nu11030642. [PMID: 30884820 PMCID: PMC6471926 DOI: 10.3390/nu11030642] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/11/2019] [Accepted: 03/12/2019] [Indexed: 12/14/2022] Open
Abstract
The relationship between vitamin D status, calcium intake and the risk of developing type 2 diabetes (T2D) is a topic of growing interest. One of the most interesting non-skeletal functions of vitamin D is its potential role in glucose homeostasis. This possible association is related to the secretion of insulin by pancreatic beta cells, insulin resistance in different tissues and its influence on systemic inflammation. However, despite multiple observational studies and several meta-analyses that have shown a positive association between circulating 25-hydroxyvitamin D concentrations and the risk of T2D, no randomized clinical trials supplementing with different doses of vitamin D have confirmed this hypothesis definitively. An important question is the identification of what 25-hydroxyvitamin D levels are necessary to influence glycemic homeostasis and the risk of developing T2D. These values of vitamin D can be significantly higher than vitamin D levels required for bone health, but the currently available data do not allow us to answer this question adequately. Furthermore, a large number of observational studies show that dairy consumption is linked to a lower risk of T2D, but the components responsible for this relationship are not well established. Therefore, the importance of calcium intake in the risk of developing T2D has not yet been established. Although there is a biological plausibility linking the status of vitamin D and calcium intake with the risk of T2D, well-designed randomized clinical trials are necessary to answer this important question.
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A systematic review and meta-analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe. Eur J Clin Nutr 2019; 73:816-834. [PMID: 30872787 DOI: 10.1038/s41430-019-0417-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 02/10/2019] [Accepted: 02/18/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Optimal doses of vitamin D (VitD) supplement in different populations are unclear. We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [25(OH)D] concentration, to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different populations. SUBJECTS/METHODS Literature search was conducted in Embase, etc. Randomized controlled trials about VitD supplemental intakes and their effect on 25(OH)D concentration were enrolled. The effect on 25(OH)D concentration between different supplementation doses in each population group was compared by meta-analysis. Multivariate meta-regression model is utilized to establish reference intake dosage of VitD. RESULTS A total of 136 articles were included about children (3-17 years), adults (18-64 years), postmenopausal women, the elderly ( >64 years), pregnant, or lactating women. Overall, intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose-response effect between intake dose and 25(OH)D concentration. Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration. To reach sufficient 25(OH)D concentration (75 nmol/L), the recommended VitD supplemental intakes was 1340 and 2250 IU/day for children and pregnant women, 2519 and 797 IU/day for European adults aged 18-64 and 65-85 years, 729, 2026, and 1229 IU/day for adults in North America, Asia and Middle East and Africa, respectively. CONCLUSIONS Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested.
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Bassatne A, Chakhtoura M, Saad R, Fuleihan GEH. Vitamin D supplementation in obesity and during weight loss: A review of randomized controlled trials. Metabolism 2019; 92:193-205. [PMID: 30615949 DOI: 10.1016/j.metabol.2018.12.010] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 12/27/2018] [Accepted: 12/29/2018] [Indexed: 01/06/2023]
Abstract
Vitamin D deficiency is common in obese individuals and during weight loss. The recommended vitamin D doses in this specific population are higher than for healthy adults. We reviewed vitamin D supplementation trials in obesity, and during medical or surgical weight loss, and report the effects on 25-hydroxyvitamin D [25(OH)D] concentrations and other relevant outcomes. We conducted a systematic search in PubMed, Medline, Embase and the Cochrane library for relevant randomized controlled trials (RCTs) of oral vitamin D supplementation for at least 3 months in obese individuals without weight loss (OB), and those on medical weight loss (MWL) (2010-2018), and following bariatric surgery (Bar S) (without time restriction). Two reviewers screened the identified citations in duplicate and independently and performed full text screening. One reviewer completed data extraction. We identified 13 RCTs in OB, 6 in MWL and 7 in Bar S. Mean baseline 25(OH)D concentrations ranged between 7 and 27 ng/ml in OB, 15-29 ng/ml in MWL and 15-24 ng/ml in Bar S. In OB (Total N 2036 participants), vitamin D doses of 1600-4000 IU/d increased mean 25(OH)D concentrations to ≥30 ng/ml. Based on three trials during MWL (Total N 359 participants), vitamin D doses of 1200-4600 IU/d for 12 months increased 25(OH)D concentration to ≥30 ng/ml. In Bar S (Total N 615 participants), doses ≥2000 IU/d were needed to reach 30 ng/ml. The change in 25(OH)D concentration was inversely proportional to the administered dose, and to BMI and baseline level with doses of 600-3000 IU/day. With these doses, the change in 25(OH)D concentration [Δ25(OH)D] per 100 IU/d was 0.5-1.2 ng/ml. Three trials assessed bone mineral density as a primary outcome, but only one of them showed a protective effect of vitamin D against bone loss at all sites post-Bar S. There was no effect of vitamin D on weight loss. Data on extra-skeletal parameters, namely glycemic and vascular indices were mostly identified in OB, and findings were inconsistent. In conclusion, Vitamin D doses ≥1600-2000 IU/d may be needed to reach a 25(OH)D concentration of 30 ng/ml in obese individuals and following bariatric surgery. The optimal concentration in this population is unknown, and whether the above doses protect against weight loss induced bone loss and fractures still needs to be confirmed. There is no clear evidence for a beneficial effect of vitamin D supplementation on cardio-metabolic parameters in obese individuals, and data on such parameters with weight loss are very scarce. Well-designed long term RCTs assessing the effect of vitamin D supplementation during weight loss on patient important outcomes are needed.
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Affiliation(s)
- Aya Bassatne
- Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Marlene Chakhtoura
- Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
| | - Randa Saad
- Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ghada El-Hajj Fuleihan
- Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, Division of Endocrinology and Metabolism, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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Urrunaga-Pastor D, Guarnizo-Poma M, Macollunco-Flores P, Lazaro-Alcantara H, Paico-Palacios S, Pantoja-Torres B, Benites-Zapata VA. Association between vitamin D deficiency and insulin resistance markers in euthyroid non-diabetic individuals. Diabetes Metab Syndr 2019; 13:258-263. [PMID: 30641708 DOI: 10.1016/j.dsx.2018.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 09/07/2018] [Indexed: 01/17/2023]
Abstract
AIM To evaluate the association between vitamin D deficiency and insulin resistance (IR) or hyperinsulinemia after oral glucose tolerance test (OGTT) in euthyroid non-diabetic individuals. MATERIALS AND METHODS We carried out an analytical cross-sectional study in euthyroid non-diabetic adults of both sexes, who attended the outpatient service of a private clinic in Lima-Peru during the 2012-2016 period. Participants were categorized in two groups according to their serum vitamin D levels: normal vitamin D levels (serum vitamin D values ≥ 20 ng/dL) and vitamin D deficiency (serum vitamin D values < 20 ng/dL). IR was defined as a Homeostasis Model Assessment (HOMA-IR) value ≥ 3.8 and hyperinsulinemia after OGTT was defined as a serum insulin value ≥ 80μU/mL after 120 min of 75-g glucose intake. We elaborated crude and adjusted Poisson regression models to assess the association between serum vitamin D levels and IR or hyperinsulinemia after OGTT. The reported association measure was the prevalence ratio (PR) with their respective 95% confidence intervals (95%CI). RESULTS We analyzed 204 participants, the average age was 38.5 ± 10.6 (SD) years, 40 (19.6%) were males and the vitamin D median was 25.0 (IQR: 19.0-33.3) ng/dL. The prevalence of vitamin D deficiency, IR and hyperinsulinemia after OGTT was 29.4% (n = 60), 29.9% (n = 61) and 25.0% (n = 51). In the adjusted Poisson regression models, the prevalence of hyperinsulinemia after OGTT was higher among the vitamin D deficient group (aPR=1.75; 95%CI: 1.06-2.90); however, we did not find statistically significant association between vitamin D deficiency and IR (aPR=0.99; 95%CI: 0.61-1.63). CONCLUSIONS We found an association between vitamin D deficiency and hyperinsulinemia after OGTT in euthyroid people with no T2DM.Our findings are consistent with previous reports; providing evidence that serum vitamin D deficiency could be an IR marker.
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Affiliation(s)
- Diego Urrunaga-Pastor
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru.
| | | | | | | | | | | | - Vicente A Benites-Zapata
- Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru.
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Barreira E, Novo A, Vaz JA, Pereira AMG. Dietary program and physical activity impact on biochemical markers in patients with type 2 diabetes: A systematic review. Aten Primaria 2018; 50:590-610. [PMID: 29061310 PMCID: PMC6836882 DOI: 10.1016/j.aprim.2017.06.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 05/26/2017] [Accepted: 06/13/2017] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Evaluate the effectiveness of the implementation of independently or combined dietary and physical activity programs on the blood glucose values and lipid profile in patients with type 2 diabetes, including participants aged 60 years and over. DESIGN Systematic review. DATA SOURCE PubMed/Medline database, with language restrictions. Papers published between 2010 and 2016 were included. STUDY SELECTION A total of 30 randomised controlled trials were included that focused on physical activity and dietary interventions in patients with type 2 diabetes mellitus and include participants aged 60 years and over. RESULTS The selected articles have shown that the implementation of physical activity programs (aerobic, resistance, flexibility and combined exercises), and programs based on a higher intake of vegetables, grains, legumes, fruits, unsaturated fatty acids, as well as consumption of foods with low glycaemic index, calorie restriction, intake of probiotics, vitamin D supplementation and educational sessions about diabetes improves blood glucose levels, as well as the lipid profile, in patients with type 2 diabetes. CONCLUSIONS Physical activity and dietary programs are fundamental in the treatment and metabolic control of type 2 diabetes mellitus.
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Affiliation(s)
- Eduarda Barreira
- Health School, Polytechnic Institute of Bragança, Bragança, Portugal.
| | - André Novo
- Health School, Polytechnic Institute of Bragança, Bragança, Portugal; CINTESIS-Research Center on Health Technologies and Services, Porto, Portugal
| | - Josiana A Vaz
- Health School, Polytechnic Institute of Bragança, Bragança, Portugal; CIMO-Mountain Research Centre, Polytechnic Institute of Bragança, Campus de Santa Apolónia, Bragança, Portugal
| | - Ana M G Pereira
- Health School, Polytechnic Institute of Bragança, Bragança, Portugal
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Ursem SR, Vervloet MG, Büttler RM, Ackermans MT, Oosterwerff MM, Eekhoff EMV, Lips P, Serlie MJ, la Fleur SE, Heijboer AC. The interrelation between FGF23 and glucose metabolism in humans. J Diabetes Complications 2018; 32:845-850. [PMID: 29996975 DOI: 10.1016/j.jdiacomp.2018.06.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 06/13/2018] [Accepted: 06/19/2018] [Indexed: 12/18/2022]
Abstract
AIMS Different studies point to a link between glucose metabolism and Fibroblast Growth Factor 23 (FGF23), an osteocyte-derived phosphaturic hormone. We aimed to investigate in humans the effect of (I) a glucose load and (II) a hyperinsulinemic-euglycemic clamp on FGF23 concentrations and conversely (III) the effect of a diet-induced increase in FGF23 concentration on glucose and insulin concentrations. METHODS Plasma cFGF23 concentrations were measured during: I. an oral glucose tolerance test in eight adults with impaired glucose tolerance and vitamin D deficiency and II. a hyperinsulinemic-euglycemic clamp in nine healthy adults. III. Serum glucose and insulin concentrations were measured in nine healthy adults receiving a single-day phosphate-enriched or -restricted diet. RESULTS I. A glucose load decreased FGF23 and phosphate concentrations. II. The hyperinsulinemic-euglycemic clamp decreased phosphate concentrations, but did not affect FGF23 concentrations. III. Fasting insulin and glucose concentrations remained unchanged after a diet-induced increase in FGF23 concentration. CONCLUSIONS An oral glucose load in vitamin D deficient patients with impaired glucose metabolism decreased FGF23 concentrations, which cannot be attributed to changes in insulin concentration. Thus, bone may react rapidly after glucose loading by alternating FGF23 secretion. A diet-induced increase in FGF23 concentrations did not affect fasting glucose or insulin levels.
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Affiliation(s)
- Stan R Ursem
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, the Netherlands
| | - Marc G Vervloet
- Department of Nephrology, VU University Medical Center, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences (ACS), VU University Medical Center, Amsterdam, the Netherlands
| | - Rahel M Büttler
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, the Netherlands
| | - Mariëtte T Ackermans
- Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Mirjam M Oosterwerff
- Department of Internal Medicine, Section of Endocrinology, Catharina Hospital, Eindhoven, the Netherlands
| | - Elisabeth M V Eekhoff
- Department of Internal Medicine, Section of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands
| | - Paul Lips
- Department of Internal Medicine, Section of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands
| | - Mireille J Serlie
- Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Susanne E la Fleur
- Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Metabolism and Reward group, Netherlands Institute for Neuroscience, KNAW, Amsterdam, the Netherlands
| | - Annemieke C Heijboer
- Department of Clinical Chemistry, Endocrine Laboratory, VU University Medical Center, Amsterdam, the Netherlands; Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
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Dabbaghmanesh MH, Danafar F, Eshraghian A, Omrani GR. Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial. Diabetes Metab Syndr 2018; 12:513-517. [PMID: 29588137 DOI: 10.1016/j.dsx.2018.03.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 03/15/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Low serum vitamin D has been associated with metabolic syndrome and Non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the impact of vitamin D supplementation in treatment of patients with NAFLD. METHODS In a double blind, randomized, placebo controlled trial patients with NAFLD were randomized to receive one weekly pearl of placebo, 50,000 U vitamin D3 (cholecalciferol) pearl per week and 0.25 mg calcitriol (1,25 dihydroxycholecalciferol) pearl per day for 3 months. RESULTS 106 NAFLD patients were randomized to receive calcitriol, vitamin D3 and placebo pearls for 12 weeks and data for 91 patients were analyzed. After 12 weeks of treatment, serum alkaline phosphatase levels was significantly decreased from baseline levels in vitamin D and calcitriol treated groups (P < 0.05). Serum and gamma glutamyl transferase (GGT) level was also significantly decreased compared to the baseline levels after 12 weeks of treatment with vitamin D. There was no statistically significant difference between placebo, calcitriol, vitamin D groups in terms of serum aminotransferase, alkaline phosphatase, serum GGT and lipid profile (P > 0.05). CONCLUSION While significant reduction of serum alkaline phosphatase and GGT were seen with vitamin D and calcitriol supplementation from baseline levels, no beneficial effects was seen when comparing vitamin D, calcitriol and placebo groups at the end of trial.
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Affiliation(s)
| | - Farideh Danafar
- Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahad Eshraghian
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM. Vitamin D Supplementation, Glycemic Control, and Insulin Resistance in Prediabetics: A Meta-Analysis. J Endocr Soc 2018; 2:687-709. [PMID: 29951596 PMCID: PMC6016617 DOI: 10.1210/js.2017-00472] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 05/22/2018] [Indexed: 12/15/2022] Open
Abstract
Diabetes prevention is a public health priority. Vitamin D supplementation may help prevent the development of diabetes in persons at increased risk. We performed a meta-analysis of controlled clinical trials that assessed glycemic outcome measures among adults at risk for type 2 diabetes, including prediabetes, overweight, or obesity. We searched PUBMED/ MEDLINE, CINAHL, and Google Scholar databases for trials published prior to April 2017. Placebo-controlled clinical trials with random allocation to vitamin D with or without calcium supplementation were selected. Data collection included country, study design, inclusion criteria, sample size, form, and dose of vitamin D, supplementation interval, control group, duration, participant characteristics, comorbidities, baseline and follow-up serum 25-hydroxyvitamin D [25(OH)D] concentration, and available outcome measures [glycosylated hemoglobin (HbA1c), fasting plasma glucose, plasma glucose after 2-hour oral glucose tolerance test, and homeostatic model assessment of insulin resistance (HOMA-IR)]. Data synthesis was conducted using random-effect models (PROSPERO registration no. CRD42017055326). Twenty-eight trials, representing 3848 participants, met the eligibility criteria. Compared with the control group, vitamin D supplementation significantly reduced HbA1c level by -0.48% (95% CI, -0.79 to -0.18), fasting plasma glucose level by -0.46 mmol/L (95% CI, -0.74 to -0.19), and HOMA-IR level by -0.39 (95% CI, -0.68 to -0.11). Subgroup analysis revealed that the effects of vitamin D supplementation on different glycemic measures were influenced by age, calcium coadministration, vitamin D deficiency, serum 25(OH)D level after supplementation, and duration of supplementation. Vitamin D supplementation and improved vitamin D status improved glycemic measures and insulin sensitivity and may be useful as part of a preventive strategy for type 2 diabetes.
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Affiliation(s)
| | - Hassanali Vatanparast
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Mohsen Mazidi
- Key State Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
- Institute of Genetics and Developmental Biology, International College, University of Chinese Academy of Sciences, Beijing, China
| | - Samantha M Kimball
- Pure North S’Energy Foundation, Calgary, Alberta, Canada
- St. Mary’s University, Calgary, Alberta, Canada
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39
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Swart KMA, Lips P, Brouwer IA, Jorde R, Heymans MW, Grimnes G, Grübler MR, Gaksch M, Tomaschitz A, Pilz S, Eiriksdottir G, Gudnason V, Wamberg L, Rejnmark L, Sempos CT, Durazo-Arvizu RA, Dowling KG, Hull G, Škrabáková Z, Kiely M, Cashman KD, van Schoor NM. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. Am J Clin Nutr 2018; 107:1043-1053. [PMID: 29868916 PMCID: PMC6248392 DOI: 10.1093/ajcn/nqy078] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 03/23/2018] [Indexed: 12/19/2022] Open
Abstract
Background Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive. Objective The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs. Design Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n = 2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied. Results Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125 nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified. Conclusions For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.
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Affiliation(s)
| | - Paul Lips
- Department of Internal Medicine, Endocrine Section VU University Medical
Center
| | - Ingeborg A Brouwer
- Department of Health Sciences, Faculty of Earth and Life Sciences, VU
University, Amsterdam Public Health Research Institute, Amsterdam, Netherlands
| | - Rolf Jorde
- Tromsø Endocrine Research Group, Department of Clinical Medicine, University of
Tromsø, Tromsø, Norway
| | | | - Guri Grimnes
- Tromsø Endocrine Research Group, Department of Clinical Medicine, University of
Tromsø, Tromsø, Norway
| | - Martin R Grübler
- Department of Internal Medicine, Division of Endocrinology and Diabetology,
Medical University of Graz, Graz, Austria
- Swiss Cardiovascular Center Bern, Department of Cardiology, Bern University
Hospital, University of Bern, Bern, Switzerland
| | - Martin Gaksch
- Department of Laboratory Medicine, Paracelsus Medical University, Salzburg,
Austria
| | - Andreas Tomaschitz
- Department of Internal Medicine, Division of Endocrinology and Diabetology,
Medical University of Graz, Graz, Austria
| | - Stefan Pilz
- Department of Internal Medicine, Division of Endocrinology and Diabetology,
Medical University of Graz, Graz, Austria
| | | | | | - Louise Wamberg
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital,
Aarhus, Denmark
| | - Lars Rejnmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital,
Aarhus, Denmark
| | | | - Ramón A Durazo-Arvizu
- Department of Preventive Medicine and Epidemiology, Loyola University Medical
Center, Maywood, IL
| | - Kirsten G Dowling
- Cork Center for Vitamin D and Nutrition Research, School of Food and
Nutritional Sciences
| | - George Hull
- Cork Center for Vitamin D and Nutrition Research, School of Food and
Nutritional Sciences
| | - Zuzana Škrabáková
- Cork Center for Vitamin D and Nutrition Research, School of Food and
Nutritional Sciences
| | - Mairead Kiely
- Cork Center for Vitamin D and Nutrition Research, School of Food and
Nutritional Sciences
- Irish Center for Fetal and Neonatal Translational Research (INFANT)
| | - Kevin D Cashman
- Cork Center for Vitamin D and Nutrition Research, School of Food and
Nutritional Sciences
- Department of Medicine, University College Cork, Cork, Ireland
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He S, Yu S, Zhou Z, Wang C, Wu Y, Li W. Effect of vitamin D supplementation on fasting plasma glucose, insulin resistance and prevention of type 2 diabetes mellitus in non-diabetics: A systematic review and meta-analysis. Biomed Rep 2018; 8:475-484. [PMID: 29725526 PMCID: PMC5920274 DOI: 10.3892/br.2018.1074] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 02/06/2018] [Indexed: 12/29/2022] Open
Abstract
Increasing epidemiological studies suggest that there is an association between vitamin D deficiency and risk of type 2 diabetes mellitus (T2DM). Therefore, randomized clinical trials (RCTs) have been performed to observe the effect of vitamin D supplementation on preventing T2DM, decreasing fasting plasma glucose (FPG) and improving insulin resistance to confirm the association between vitamin D and T2DM. However, the results of RCTs on controlling FPG level, improving insulin resistance and preventing T2DM in non-diabetics are inconsistent. In the present study, a systematic meta-analysis considering individual variation and intervention strategy was conducted to establish an objective and definitive conclusion. The results suggested that vitamin D supplementation had no significant effect on controlling FPG level, improving insulin resistance or preventing T2DM in non-diabetics in a pooled meta-analysis of 23 articles (containing 28 RCTs). However, stratified analysis indicated that supplementation of vitamin D had differential effects on FPG control, insulin sensitivity improvement and T2DM prevention in individuals with different baseline states: FPG was decreased for those with BMI <25 (P=0.048) or 20≤ 25(OH)D <30 ng/ml (P=0.002); insulin resistance was improved for those with 25(OH)D ≥30 ng/ml (P=0.021); and risk of T2DM was lower for pre-diabetic individuals (P=0.047) or for those with 25≤ BMI <30 (P=0.032). Additionally, the effect on T2DM prevention was improved when the supplement dose was >2,000 IU/day (P=0.047) and with intervention without calcium (P=0.047). Thus, further trials should focus on individual baselines and the supplementation strategy of vitamin D in the prevention of T2DM.
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Affiliation(s)
- Sitian He
- Department of Sanitary Chemistry, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Songcheng Yu
- Department of Sanitary Chemistry, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Zonglei Zhou
- Department of Sanitary Chemistry, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Chongjian Wang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Yongjun Wu
- Department of Sanitary Chemistry, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
| | - Wenjie Li
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
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41
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El Hajj C, Chardigny JM, Boirie Y, Yammine K, Helou M, Walrand S. Effect of Vitamin D Treatment on Glucose Homeostasis and Metabolism in Lebanese Older Adults: A Randomized Controlled Trial. J Nutr Health Aging 2018; 22:1128-1132. [PMID: 30379314 DOI: 10.1007/s12603-018-1083-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND A low serum 25-hydroxyvitamin D [(25(OH) D)] concentration was shown to correlate with higher fasting blood glucose (FBG) and insulin levels. Since age affect insulin sensitivity and the metabolism, we aimed in this randomized controlled trial to investigate the effect of vitamin D supplementation on glucose homeostasis and index of insulin resistance in elderly subjects living in Beirut, Lebanon. METHODS Participants (n= 115) deficient in vitamin D were randomly divided into two groups, a group receiving 30,000 IU cholecalciferol/week for a period of 6 months, and a placebo group. The index of insulin resistance HOMA (homeostasis model assessment) was the primary outcome. Glucose homeostasis and metabolic markers were also measured at start of treatment and at 6 months. RESULTS Vitamin D supplementation led to significant improvements in blood levels of [25(OH) D] (P< 0.0001), and a significant decreased of HOMA, PTH and FBG concentrations (P< 0.0001) in the intervention group compared to placebo. No significant changes were observed in HbA1c levels for both groups. Total cholesterol and LDL cholesterol concentrations have also decreased significantly in the intervention group (P< 0.0001). CONCLUSION Short-term supplementation with cholecalciferol improved vitamin D status, and markers of insulin resistance in healthy elder population. This trial was registered at ClinicalTrials.gov; Identifier number#:NCT03478475.
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Affiliation(s)
- C El Hajj
- Cynthia El Hajj, Département de Diététique et de Nutrition, Hôpital Saint-Charles, Beirut, Lebanon, , Tel: +9613409590
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Jamilian M, Foroozanfard F, Rahmani E, Talebi M, Bahmani F, Asemi Z. Effect of Two Different Doses of Vitamin D Supplementation on Metabolic Profiles of Insulin-Resistant Patients with Polycystic Ovary Syndrome. Nutrients 2017; 9:E1280. [PMID: 29186759 PMCID: PMC5748731 DOI: 10.3390/nu9121280] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/06/2017] [Accepted: 11/07/2017] [Indexed: 12/20/2022] Open
Abstract
This study was carried out to evaluate the effects of vitamin D supplementation on the metabolic profiles of insulin-resistant subjects with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was conducted on 90 insulin-resistant women with PCOS. Participants were randomly assigned to three groups to intake either 4000 IU of vitamin D or 1000 IU of vitamin D or placebo (n = 30 each group) daily for 12 weeks. Vitamin D supplementation (4000 IU), compared with vitamin D (1000 IU) and placebo, led to significant reductions in total testosterone (-0.2 ± 0.2 vs. -0.1 ± 0.6 and +0.1 ± 0.2 ng/mL, respectively, p = 0.02), free androgen index (FAI) (-0.06 ± 0.12 vs. -0.02 ± 0.12 and +0.004 ± 0.04, respectively, p = 0.04), hirsutism (-1.1 ± 1.1 vs. -0.8 ± 1.2 and -0.1 ± 0.4, respectively, p = 0.001) and high-sensitivity C-reactive protein (hs-CRP) (-0.7 ± 1.4 vs. -0.5 ± 0.9 and +0.5 ± 2.4 mg/L, respectively, p = 0.01). In addition, we found significant elevations in mean change of sex hormone-binding globulin (SHBG) (+19.1 ± 23.0 vs. +4.5 ± 11.0 and +0.7 ± 10.4 nmol/L, respectively, p < 0.001) and total antioxidant capacity (TAC) (+130 ± 144 vs. +33 ± 126 and -36 ± 104 mmol/L, respectively, p < 0.001) in the high-dose vitamin D group compared with low-dose vitamin D and placebo groups. Overall, high-dose vitamin D administration for 12 weeks to insulin-resistant women with PCOS had beneficial effects on total testosterone, SHBG, FAI, serum hs-CRP and plasma TAC levels compared with low-dose vitamin D and placebo groups.
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Affiliation(s)
- Mehri Jamilian
- Endocrinology and Metabolism Research Center, Arak University of Medical Sciences, Arak 6618634683, Iran;
| | - Fatemeh Foroozanfard
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan 8715988141, Iran; (F.F.); (M.T.)
| | - Elham Rahmani
- Department of Gynecology and Obstetrics, School of Medicine, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran;
| | - Maesoomeh Talebi
- Department of Gynecology and Obstetrics, School of Medicine, Kashan University of Medical Sciences, Kashan 8715988141, Iran; (F.F.); (M.T.)
| | - Fereshteh Bahmani
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan 8715988141, Iran;
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan 8715988141, Iran;
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Lee JH, Kim S, Kim MK, Yun BH, Cho S, Choi YS, Lee BS, Seo SK. Relationships between 25(OH)D concentration, sarcopenia and HOMA-IR in postmenopausal Korean women. Climacteric 2017; 21:40-46. [DOI: 10.1080/13697137.2017.1395410] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- J. H. Lee
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - S. Kim
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - M. K. Kim
- CHA University, Fertility Center of Gangnam CHA Hospital, Seoul, Republic of Korea
| | - B. H. Yun
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - S. Cho
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Y. S. Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - B. S. Lee
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - S. K. Seo
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
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Lips P, Eekhoff M, van Schoor N, Oosterwerff M, de Jongh R, Krul-Poel Y, Simsek S. Vitamin D and type 2 diabetes. J Steroid Biochem Mol Biol 2017; 173:280-285. [PMID: 27932304 DOI: 10.1016/j.jsbmb.2016.11.021] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 11/21/2016] [Accepted: 11/30/2016] [Indexed: 01/14/2023]
Abstract
Vitamin D deficiency is associated with a decreased insulin release, insulin resistance and type 2 diabetes in experimental and epidemiological studies. Animal studies show that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) stimulates the pancreatic β-cell to secrete insulin. The relationship between vitamin D deficiency and insulin resistance could develop through inflammation, as vitamin D deficiency is associated with increased inflammatory markers. In addition, genetic polymorphisms of vitamin D -related genes may predispose to impaired glycemic control and type 2 diabetes. Epidemiologic studies showed an association between low serum 25-hydroxyvitamin D3 (25(OH)D3) concentration and an increased risk for the metabolic syndrome and type 2 diabetes. This may be partly explained by an increased fat mass. A possible causal relationship between vitamin D deficiency and type 2 diabetes should be proven by randomized clinical trials showing that either type 2 diabetes can be prevented or insulin release and insulin sensitivity can be improved by vitamin D supplements. The results of randomized clinical trials on the effect of vitamin D versus placebo, sometimes combined with calcium, in patients with impaired glucose tolerance ("prediabetes") or type 2 diabetes are inconsistent. Some studies showed a slight decrease of fasting plasma glucose or improvement of insulin resistance, but often only in posthoc analyses. These effects are mainly visible in patients with vitamin D deficiency and impaired glucose tolerance at baseline. Meta-analyses of randomized clinical trials in general did not show significant effects of vitamin D supplementation on glycemic control. Currently, several large scale randomized clinical trials with vitamin D supplementation in doses of 1600-4000IU/d are ongoing with glycemic control or incidence of diabetes mellitus as outcome. Vitamin D deficiency needs to be prevented or cured, but until the results of these trials are published, high-dose vitamin D supplementation cannot be recommended for prevention or amelioration of type 2 diabetes.
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Affiliation(s)
- Paul Lips
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
| | - Marelise Eekhoff
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
| | - Natasja van Schoor
- Department of Epidemiology and Biostatistics, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
| | - Mirjam Oosterwerff
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Department of Internal Medicine, Catharina Hospital, 5623 EJ Eindhoven, The Netherlands
| | - Renate de Jongh
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
| | - Yvonne Krul-Poel
- Department of Internal Medicine, Medical Center Alkmaar, 1800 AM Alkmaar, The Netherlands
| | - Suat Simsek
- Department of Internal Medicine, Endocrine Section, VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Department of Internal Medicine, Medical Center Alkmaar, 1800 AM Alkmaar, The Netherlands
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Dasarathy J, Varghese R, Feldman A, Khiyami A, McCullough AJ, Dasarathy S. Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation. J Nutr 2017; 147:1938-1946. [PMID: 28814531 PMCID: PMC5610550 DOI: 10.3945/jn.117.254292] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 06/06/2017] [Accepted: 07/17/2017] [Indexed: 01/10/2023] Open
Abstract
Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D3) supplementation are conflicting.Objective: The objective of this study was to determine if standard vitamin D3 supplementation is effective in NAFLD with hypovitaminosis D.Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] <30 ng/mL). An observational study was performed in NAFLD patients with hypovitaminosis D treated with 2000 IU cholecalciferol (vitamin D3) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed.Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D <30 ng/mL. Significantly fewer (P < 0.01) patients with NASH were responders (4 of 26, 15.4%) than those with hepatic steatosis (12 of 16, 75%). Baseline fasting serum alanine aminotransferase, plasma glucose, and HOMA-IR were similar in the responders and nonresponders, but the NASH score on the liver biopsy was lower (16.5%) in the responders (P < 0.001). Nonresponders had a higher fat mass (10.5%) and lower fat-free mass (10.4%) than responders did. End-of-treatment alanine aminotransferase and HOMA-IR improved only in responders. The baseline HOMA-IR and histological NASH score were independent predictors of nonresponse to cholecalciferol supplementation.Conclusions: Daily supplementation with 2000 IU cholecalciferol for 6 mo did not correct hypovitaminosis D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153.
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Affiliation(s)
| | | | | | - Amer Khiyami
- Pathology, Metro Health Medical Center, Cleveland, OH; and
| | - Arthur J McCullough
- Department of Gastroenterology and Hepatology, Pathobiology, Cleveland Clinic, Cleveland, OH
| | - Srinivasan Dasarathy
- Department of Gastroenterology and Hepatology, Pathobiology, Cleveland Clinic, Cleveland, OH
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Angellotti E, Pittas AG. The Role of Vitamin D in the Prevention of Type 2 Diabetes: To D or Not to D? Endocrinology 2017; 158:2013-2021. [PMID: 28486616 PMCID: PMC5505219 DOI: 10.1210/en.2017-00265] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Accepted: 05/03/2017] [Indexed: 01/08/2023]
Abstract
Evidence on biological plausibility from mechanistic studies and highly consistent data from observational studies raise the possibility that optimizing vitamin D status may reduce the risk of type 2 diabetes. However, the observational nature of cohort studies precludes a definitive assessment of cause and effect because residual confounding or reverse causation cannot be excluded. Confounding is especially problematic with studies of vitamin D because blood 25-hydoxyvitamin D concentration is not only an excellent biomarker of vitamin D status, reflecting intake or biosynthesis, but also an excellent marker of good overall health. Results from underpowered trials and post hoc analyses of trials designed for nondiabetic outcomes do not support a role of vitamin D supplementation for prevention of type 2 diabetes among people with normal glucose tolerance. Whether vitamin D supplementation may have a role in the prevention of diabetes in high-risk populations remains to be seen. Adequately powered, randomized trials in well-defined populations (e.g., prediabetes) are ongoing and expected to establish whether vitamin D supplementation lowers risk of diabetes.
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Affiliation(s)
- Edith Angellotti
- Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111
- Department of Medical, Surgical, Neurologic, Metabolic and Aging Sciences, University of Campania Luigi Vanvitelli, Naples 80128, Italy
| | - Anastassios G. Pittas
- Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111
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Lee CJ, Iyer G, Liu Y, Kalyani RR, Bamba N, Ligon CB, Varma S, Mathioudakis N. The effect of vitamin D supplementation on glucose metabolism in type 2 diabetes mellitus: A systematic review and meta-analysis of intervention studies. J Diabetes Complications 2017; 31:1115-1126. [PMID: 28483335 PMCID: PMC6016376 DOI: 10.1016/j.jdiacomp.2017.04.019] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Revised: 04/13/2017] [Accepted: 04/17/2017] [Indexed: 10/19/2022]
Abstract
AIMS We aimed to assess whether vitamin D supplementation improves glucose metabolism in adults with type 2 diabetes. METHODS PubMed and Cochrane database were searched up to July 1st 2016 for randomized controlled trials that assessed the relationship between vitamin D supplementation and glucose metabolism (change in hemoglobin A1C (HbA1C) and fasting blood glucose (FBG)) among adults with type 2 diabetes. RESULTS Twenty nine trials (3324 participants) were included in the systematic review. Among 22 studies included in the meta-analysis, 19 reported HbA1C, 16 reported FBG outcomes and 15 were deemed poor quality. There was a modest reduction in HbA1C (-0.32% [-0.53 to -0.10], I2=91.9%) compared to placebo after vitamin D supplementation but no effect on FBG (-2.33mg/dl [-6.62 to 1.95], I2=59.2%). In studies achieving repletion of vitamin D deficiency (n=7), there were greater mean reductions in HbA1C (-0.45%, [-1.09 to 0.20]) and FBG (-7.64mg/dl [-16.25 to 0.97]) although not significant. CONCLUSIONS We found a modest reduction of HbA1C after vitamin D treatment in adults with type 2 diabetes albeit with substantial heterogeneity between studies and no difference in FBG. Larger studies are needed to further evaluate the glycemic effects of vitamin D treatment especially in patients with vitamin D deficiency.
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Affiliation(s)
- Clare J Lee
- Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University, Baltimore, MD, USA.
| | - Geetha Iyer
- The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Yang Liu
- The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Rita R Kalyani
- Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University, Baltimore, MD, USA
| | - N'Dama Bamba
- The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of Infectious Diseases, The Johns Hopkins University, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Colin B Ligon
- Division of Rheumatology, The Johns Hopkins University, Baltimore, MD, USA
| | - Sanskriti Varma
- The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nestoras Mathioudakis
- Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University, Baltimore, MD, USA
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Grammatiki M, Rapti E, Karras S, Ajjan RA, Kotsa K. Vitamin D and diabetes mellitus: Causal or casual association? Rev Endocr Metab Disord 2017; 18:227-241. [PMID: 28062940 DOI: 10.1007/s11154-016-9403-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The incidence of both type 2 and type 1 diabetes mellitus has been increasing worldwide. Vitamin D deficiency, or the awareness of its prevalence, has also been increasing. Vitamin D may have a role in the pathogenic mechanisms predisposing to type 2 diabetes by modulating insulin resistance and/or pancreatic β-cell function. Vitamin D status or elements involved in its activation or transport may also be involved in the development of type 1 diabetes mellitus through immunomodulatory role . Based on these observations a potential association between vitamin D and diabetes has been hypothesized. In this review we discuss up to date evidence linking vitamin D with the development of diabetes. Moreover, the role of vitamin D supplementation in the prevention of both types of diabetes is analysed together with its role in improving glycemic control in diabetic patients. We also address the potential role of vitamin D deficiency in the development of macro- and microvascular complications in diabetes. Finally, we provide recommendation for Vitamin D therapy in diabetes in view of current evidence and highlight areas for potential future research in this area.
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Affiliation(s)
- M Grammatiki
- Department of Endocrinology and Metabolism - Diabetes Center, 1st Clinic of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
| | - E Rapti
- Department of Endocrinology and Metabolism - Diabetes Center, 1st Clinic of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
| | - S Karras
- Department of Endocrinology and Metabolism - Diabetes Center, 1st Clinic of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece
| | - R A Ajjan
- Division of Cardiovascular and Diabetes Research, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds Ringgold Standard Institution, Leeds, UK
| | - Kalliopi Kotsa
- Department of Endocrinology and Metabolism - Diabetes Center, 1st Clinic of Internal Medicine, AHEPA University Hospital, Thessaloniki, Greece.
- Aristotle University, Thessaloniki, Greece.
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Sergeev IN. Vitamin D-Cellular Ca 2+ link to obesity and diabetes. J Steroid Biochem Mol Biol 2016; 164:326-330. [PMID: 26592177 DOI: 10.1016/j.jsbmb.2015.11.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 11/09/2015] [Accepted: 11/11/2015] [Indexed: 12/13/2022]
Abstract
The vitamin D hormone 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-induced cellular Ca2+ signals regulate apoptosis in adipocytes and insulin secretion from pancreatic β-cells, and low vitamin D status is considered a risk factor for obesity and type 2 diabetes. The anti-obesity effects of 1,25(OH)2D3 in mature adipocytes are determined by its activity to generate, via multiple Ca2+ signaling pathways, a sustained increase in intracellular Ca2+ followed by activation of the Ca2+-dependent initiators and effectors of apoptosis. In pancreatic β-cells, 1,25(OH)2D3 induces synchronous Ca2+ oscillations, which pattern pulsatile insulin secretion from these cells. An increased intake of vitamin D3 in a high fat diet-induced obesity mouse model is associated with a decreased weight of white adipose tissue due to induction of apoptosis and the improved blood markers related to adiposity, diabetes, and vitamin D status (plasma concentrations of glucose, insulin, adiponectin, 25-hydroxyvitamin D, and 1,25(OH)2D3). High vitamin D3 intake is also effective in increasing the mineral content of growing bone in obese mice via regulatory effects mediated by 1,25(OH)2D3-parathyroid hormone axis. The 1,25(OH)2D3-dependent cellular Ca2+ signaling can be important for maintaining the normal levels of apoptosis in adipose tissue and insulin secretion from pancreatic β-cells. An increased intake of vitamin D may contribute to the prevention of obesity, type 2 diabetes, and bone disorders associated with these diseases.
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Affiliation(s)
- Igor N Sergeev
- Department of Health and Nutritional Sciences, South Dakota State University, Brookings, SD 57007, USA.
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Vitamin D supplementation reduces insulin resistance in Japanese adults: a secondary analysis of a double-blind, randomized, placebo-controlled trial. Nutr Res 2016; 36:1121-1129. [DOI: 10.1016/j.nutres.2016.07.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 07/21/2016] [Accepted: 07/26/2016] [Indexed: 10/21/2022]
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