Original Paper Med Princ Pract 2014;23:229–233 DOI: 10.1159/000360540
Received: July 14, 2013 Accepted: February 11, 2014 Published online: March 18, 2014
Relationship between 25-Hydroxyvitamin D and Newly Diagnosed Type 2 Diabetes Mellitus in Postmenopausal Women with Osteoporosis Snezana Vujosevic Sanja Borozan Nemanja Radojevic Svetlana Aligrudic Dragica Bozovic Clinical Centre of Montenegro, Department of Endocrinology, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Abstract Objective: The aim of the study was to determine a correlation between the level of 25-hydroxivitamin D (25-OHD) and the incidence of diabetes. Subjects and Methods: In this prospective observational study, 97 (out of an initial 100) Caucasian women with osteoporosis (OS) were monitored for 2 years for the incidence of diabetes. Logistic regression analysis was used to establish an association with and prognostic value of vitamin D for the onset of type 2 diabetes mellitus, as well as insulin resistance, body mass index (BMI), total cholesterol and triglyceride levels in the development of diabetes. The serum level of 25-OHD was measured using immunochemiluminescence in March and April 2011. Results: Of the 97 patients (mean age 51.64 ± 5.86 years, range 36.0– 73.0), 21 (21.65%) were diagnosed with diabetes during the observational period. The study showed that the 22 patients with low levels of vitamin D were more susceptible to diabetes (odds ratio = 0.958). The cut-off value of vitamin D using a receiver operating characteristic curve was 62.36 nmol/l with a sensitivity of 39.5% and a specificity of 90.5%. With an increase in BMI and triglyceride levels, women were, respec-
© 2014 S. Karger AG, Basel 1011–7571/14/0233–0229$39.50/0 E-Mail [email protected] www.karger.com/mpp
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
tively, 1,591 and 2,821 times more likely to get diabetes than those without an increase. Conclusion: This study showed that the patients with postmenopausal OS and hypovitaminosis D, besides a high BMI, elevated triglyceride levels and insulin resistance, had an increased risk of developing type 2 diabetes. © 2014 S. Karger AG, Basel
Introduction
According to the International Diabetes Federation, the estimated prevalence of diabetes mellitus (DM) in adults worldwide is 8.3% [1]. The majority of patients (85–95%) suffer from type 2 diabetes mellitus (T2DM) which is a metabolic disorder characterized by hyperglycemia and caused by insulin resistance (IR) and relative insulin deficiency, either or both of which may be present at the time diabetes is diagnosed [1]. Although therapies for T2DM and its complications have improved over the last few decades, the increasing burden of T2DM highlights the need for innovative approaches for the management and prevention of the disease [2]. Vitamin D is a steroid prohormone synthesized in the skin following UV exposure or else acquired by supplemental or dietary intake [3]. Originally, it was described Nemanja Radojevic, MD Clinical Centre of Montenegro Faculty of Medicine, University of Montenegro Ljubljanska 1, ME–20000 Podgorica (Montenegro) E-Mail com_nr @ yahoo.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 10:28:36 PM
Key Words Osteoporosis · 25-Hydroxyvitamin D · Type 2 diabetes mellitus
Subjects and Methods The study included 100 postmenopausal Caucasian women diagnosed with OS and hypovitaminosis D (serum level 0.05)]. Finally, the correlation coefficients between HOMAIR and 25-OHD for both groups were very low (–0.135 for the first group and 0.128 for the second), since no significant difference existed between them (p > 0.05).
Discussion
Besides IR, a high BMI and elevated TG levels, all wellknown positive predictors for developing T2DM, patients with lower 25-OHD levels also had a significantly greater chance of being diagnosed with T2DM (p = 0.0256) with an OR of 0.958. Thus, in the case of 25OHD for the obtained OR of 0.958, the chances for someMed Princ Pract 2014;23:229–233 DOI: 10.1159/000360540
231
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groups of patients, the one with T2DM and the other without T2DM were homogeneous according to age and menopause age; this permitted the analysis of correlations between variables. The results of descriptive statistics for both groups are given in table 1. The comorbidities were as follows: all the patients (100%) had hypovitaminosis D, 19 (19.69%) were obese, 84 (86.6%) had elevated total-C levels, 71 (73.2%) had elevated TG levels and 37 (38.14%) had IR. In the logistic regression analysis, the occurrence (presence) of T2DM was the criterion or dependent variable (dependent/response variable) and the predictors or independent variables (independent/explanatory variables) were: 25-OHD, BMI, total-C and TG. HOMA-IR was highly correlated with the presence of T2DM (a nearly collinear relationship [1]), with this predictor being analyzed independently of other predictors. Increased amounts of 25-OHD significantly reduced the probability of T2DM occurrence (p < 0.05). With the increase in BMI, the probability of diabetes also increases; this finding was also statistically significant (p < 0.01). Total-C levels were not significantly associated with the occurrence of diabetes (p > 0.05). By increasing the TG parameter, the probability of an incidence of T2DM significantly increased (p < 0.05). The odds ratio (OR) displays chances for each of the predictor variables. For 25-OHD, OR is 1.200 mg calcium and >800 IU vitamin D was associated with a 33% lower risk of T2DM over 20 years. Our study, on the other hand, followed postmenopausal women taking calcium 1,000 mg and 800 IU of 25-OHD as daily supplementation over 2 years, but we still registered a lower probability of T2DM in those with higher serum levels of vitamin D. Pittas et al. [17] later published a meta-analysis which concluded that combined supplementation of vitamin D and calcium may play a role in the prevention of T2DM [17]. However, the evidence from current studies is insufficient to be able recommend vitamin D supplementation for the prevention of T2DM [18]. Further prospective studies are needed to establish whether achieving a sufficient 25-OHD level would indeed reduce the risk of DM, the severity of the disease or any of its complications. Apart from the relation of a low serum level of 25OHD to greater bone turnover, bone loss and OS, it is in
References
Vitamin D and Diabetes in Postmenopausal Women
8 Boucher BJ: Is vitamin D status relevant to metabolic syndrome? Dermatoendocrinol 2012;4:212–224. 9 De Paula FJ, Horowitz MC, Rosen CJ: Novel insights into relationship between diabetes and osteoporosis. Diabetes Metab Res Rev 2010;26:622–630. 10 Boucher BJ: Vitamin D deficiency and diabetes risk. Curr Drug Targets 2011;12:61–87. 11 Michael FH, Tai CC: Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87:1080S–1086S. 12 Kanis JA: Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359: 1929–1936. 13 International Diabetes Federation, 2012: Global Guideline for Type 2 Diabetes (accessed September 19, 2013). http://www.idf. org. 14 Balkau B, Charles MA: Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999; 16: 442– 443. 15 Lee S, Clark SA, Gill RK, et al: 1.25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression and insulin secretion. Endocrinology 1994;134:1602–1610.
16 Pittas AG, Dawson-Hughes B, Li T, et al: Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006; 29: 650–656. 17 Pittas AG, Lau J, Hu FB, et al: The role of vitamin D and calcium in type 2 diabetes mellitus. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007;92:2017–2029. 18 Pilz S, Kienreich K, Rutters F, et al: Role of vitamin D in the development of insulin resistance and type 2 diabetes. Curr Diab Rep 2013;13:261–270. 19 MacDonald HM, Mavroedi A, Barr RJ, et al: Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. Bone 2008; 42: 996– 1003. 20 Brazdilova K, Dlesk A, Koller T, et al: Vitamin D deficiency – a possible link between osteoporosis and metabolic syndrome. Bratisl Lek Listy 2012;113:412–416. 21 McGill AT, Stewart JM, Lithander FE, et al: Relationship of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 2008;7:4. 22 Wortsman J, Matsuoka LY, Chen TC, et al: Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690–693.
Med Princ Pract 2014;23:229–233 DOI: 10.1159/000360540
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1 International Diabetes Federation, 2012: The Global Burden (accessed September 27, 2013). http://www.idf.org/diabetesatlas/5e/ the-global-burden. 2 Pittas AG, Dawson-Hughes B: The role of vitamin D in type 2 diabetes and hypertension; in Feldman D, Pike JW, Adams J (eds): Vitamin D, ed 3. Philadelphia, Elsevier, 2011, p 1907. 3 Brock KE, Huang WY, Fraser DR, et al: Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1.25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Br J Nutr 2011; 106: 339–344. 4 Afzal S, Bojesen SE, Nordestgaard BG: Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem 2013;59:381–391. 5 Perez-Lopez FR: Vitamin D and its implications for musculoskeletal health in women: an update. Maturitas 2007;58:117–137. 6 Norman AW, Frankel JB, Heldt AM, et al: Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 1980;209:823–825. 7 Li L, Wu B, Liu JY, et al: Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Arch Med Res 2013; 44: 235– 241.
Received: July 14, 2013 Accepted: February 11, 2014 Published online: March 18, 2014
Relationship between 25-Hydroxyvitamin D and Newly Diagnosed Type 2 Diabetes Mellitus in Postmenopausal Women with Osteoporosis Snezana Vujosevic Sanja Borozan Nemanja Radojevic Svetlana Aligrudic Dragica Bozovic Clinical Centre of Montenegro, Department of Endocrinology, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Abstract Objective: The aim of the study was to determine a correlation between the level of 25-hydroxivitamin D (25-OHD) and the incidence of diabetes. Subjects and Methods: In this prospective observational study, 97 (out of an initial 100) Caucasian women with osteoporosis (OS) were monitored for 2 years for the incidence of diabetes. Logistic regression analysis was used to establish an association with and prognostic value of vitamin D for the onset of type 2 diabetes mellitus, as well as insulin resistance, body mass index (BMI), total cholesterol and triglyceride levels in the development of diabetes. The serum level of 25-OHD was measured using immunochemiluminescence in March and April 2011. Results: Of the 97 patients (mean age 51.64 ± 5.86 years, range 36.0– 73.0), 21 (21.65%) were diagnosed with diabetes during the observational period. The study showed that the 22 patients with low levels of vitamin D were more susceptible to diabetes (odds ratio = 0.958). The cut-off value of vitamin D using a receiver operating characteristic curve was 62.36 nmol/l with a sensitivity of 39.5% and a specificity of 90.5%. With an increase in BMI and triglyceride levels, women were, respec-
© 2014 S. Karger AG, Basel 1011–7571/14/0233–0229$39.50/0 E-Mail [email protected] www.karger.com/mpp
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
tively, 1,591 and 2,821 times more likely to get diabetes than those without an increase. Conclusion: This study showed that the patients with postmenopausal OS and hypovitaminosis D, besides a high BMI, elevated triglyceride levels and insulin resistance, had an increased risk of developing type 2 diabetes. © 2014 S. Karger AG, Basel
Introduction
According to the International Diabetes Federation, the estimated prevalence of diabetes mellitus (DM) in adults worldwide is 8.3% [1]. The majority of patients (85–95%) suffer from type 2 diabetes mellitus (T2DM) which is a metabolic disorder characterized by hyperglycemia and caused by insulin resistance (IR) and relative insulin deficiency, either or both of which may be present at the time diabetes is diagnosed [1]. Although therapies for T2DM and its complications have improved over the last few decades, the increasing burden of T2DM highlights the need for innovative approaches for the management and prevention of the disease [2]. Vitamin D is a steroid prohormone synthesized in the skin following UV exposure or else acquired by supplemental or dietary intake [3]. Originally, it was described Nemanja Radojevic, MD Clinical Centre of Montenegro Faculty of Medicine, University of Montenegro Ljubljanska 1, ME–20000 Podgorica (Montenegro) E-Mail com_nr @ yahoo.com
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 10:28:36 PM
Key Words Osteoporosis · 25-Hydroxyvitamin D · Type 2 diabetes mellitus
Subjects and Methods The study included 100 postmenopausal Caucasian women diagnosed with OS and hypovitaminosis D (serum level 0.05)]. Finally, the correlation coefficients between HOMAIR and 25-OHD for both groups were very low (–0.135 for the first group and 0.128 for the second), since no significant difference existed between them (p > 0.05).
Discussion
Besides IR, a high BMI and elevated TG levels, all wellknown positive predictors for developing T2DM, patients with lower 25-OHD levels also had a significantly greater chance of being diagnosed with T2DM (p = 0.0256) with an OR of 0.958. Thus, in the case of 25OHD for the obtained OR of 0.958, the chances for someMed Princ Pract 2014;23:229–233 DOI: 10.1159/000360540
231
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 10:28:36 PM
groups of patients, the one with T2DM and the other without T2DM were homogeneous according to age and menopause age; this permitted the analysis of correlations between variables. The results of descriptive statistics for both groups are given in table 1. The comorbidities were as follows: all the patients (100%) had hypovitaminosis D, 19 (19.69%) were obese, 84 (86.6%) had elevated total-C levels, 71 (73.2%) had elevated TG levels and 37 (38.14%) had IR. In the logistic regression analysis, the occurrence (presence) of T2DM was the criterion or dependent variable (dependent/response variable) and the predictors or independent variables (independent/explanatory variables) were: 25-OHD, BMI, total-C and TG. HOMA-IR was highly correlated with the presence of T2DM (a nearly collinear relationship [1]), with this predictor being analyzed independently of other predictors. Increased amounts of 25-OHD significantly reduced the probability of T2DM occurrence (p < 0.05). With the increase in BMI, the probability of diabetes also increases; this finding was also statistically significant (p < 0.01). Total-C levels were not significantly associated with the occurrence of diabetes (p > 0.05). By increasing the TG parameter, the probability of an incidence of T2DM significantly increased (p < 0.05). The odds ratio (OR) displays chances for each of the predictor variables. For 25-OHD, OR is 1.200 mg calcium and >800 IU vitamin D was associated with a 33% lower risk of T2DM over 20 years. Our study, on the other hand, followed postmenopausal women taking calcium 1,000 mg and 800 IU of 25-OHD as daily supplementation over 2 years, but we still registered a lower probability of T2DM in those with higher serum levels of vitamin D. Pittas et al. [17] later published a meta-analysis which concluded that combined supplementation of vitamin D and calcium may play a role in the prevention of T2DM [17]. However, the evidence from current studies is insufficient to be able recommend vitamin D supplementation for the prevention of T2DM [18]. Further prospective studies are needed to establish whether achieving a sufficient 25-OHD level would indeed reduce the risk of DM, the severity of the disease or any of its complications. Apart from the relation of a low serum level of 25OHD to greater bone turnover, bone loss and OS, it is in
References
Vitamin D and Diabetes in Postmenopausal Women
8 Boucher BJ: Is vitamin D status relevant to metabolic syndrome? Dermatoendocrinol 2012;4:212–224. 9 De Paula FJ, Horowitz MC, Rosen CJ: Novel insights into relationship between diabetes and osteoporosis. Diabetes Metab Res Rev 2010;26:622–630. 10 Boucher BJ: Vitamin D deficiency and diabetes risk. Curr Drug Targets 2011;12:61–87. 11 Michael FH, Tai CC: Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87:1080S–1086S. 12 Kanis JA: Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359: 1929–1936. 13 International Diabetes Federation, 2012: Global Guideline for Type 2 Diabetes (accessed September 19, 2013). http://www.idf. org. 14 Balkau B, Charles MA: Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999; 16: 442– 443. 15 Lee S, Clark SA, Gill RK, et al: 1.25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression and insulin secretion. Endocrinology 1994;134:1602–1610.
16 Pittas AG, Dawson-Hughes B, Li T, et al: Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 2006; 29: 650–656. 17 Pittas AG, Lau J, Hu FB, et al: The role of vitamin D and calcium in type 2 diabetes mellitus. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007;92:2017–2029. 18 Pilz S, Kienreich K, Rutters F, et al: Role of vitamin D in the development of insulin resistance and type 2 diabetes. Curr Diab Rep 2013;13:261–270. 19 MacDonald HM, Mavroedi A, Barr RJ, et al: Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. Bone 2008; 42: 996– 1003. 20 Brazdilova K, Dlesk A, Koller T, et al: Vitamin D deficiency – a possible link between osteoporosis and metabolic syndrome. Bratisl Lek Listy 2012;113:412–416. 21 McGill AT, Stewart JM, Lithander FE, et al: Relationship of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J 2008;7:4. 22 Wortsman J, Matsuoka LY, Chen TC, et al: Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690–693.
Med Princ Pract 2014;23:229–233 DOI: 10.1159/000360540
233
Downloaded by: NYU Medical Center Library 128.122.253.212 - 5/20/2015 10:28:36 PM
1 International Diabetes Federation, 2012: The Global Burden (accessed September 27, 2013). http://www.idf.org/diabetesatlas/5e/ the-global-burden. 2 Pittas AG, Dawson-Hughes B: The role of vitamin D in type 2 diabetes and hypertension; in Feldman D, Pike JW, Adams J (eds): Vitamin D, ed 3. Philadelphia, Elsevier, 2011, p 1907. 3 Brock KE, Huang WY, Fraser DR, et al: Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1.25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Br J Nutr 2011; 106: 339–344. 4 Afzal S, Bojesen SE, Nordestgaard BG: Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem 2013;59:381–391. 5 Perez-Lopez FR: Vitamin D and its implications for musculoskeletal health in women: an update. Maturitas 2007;58:117–137. 6 Norman AW, Frankel JB, Heldt AM, et al: Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 1980;209:823–825. 7 Li L, Wu B, Liu JY, et al: Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Arch Med Res 2013; 44: 235– 241.
