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Vitamin D Deficiency in Type 2 Diabetic Patients with Hypogonadism Giuseppe Bellastella, MD, PhD,* Maria Ida Maiorino, MD,* Laura Olita, MD,* Annalisa Capuano, MD,† Concetta Rafaniello, MD,† Dario Giugliano, MD, PhD,* and Katherine Esposito, MD, PhD‡ *Unit of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; †Department of Experimental Medicine, Second University of Naples, Naples, Italy; ‡Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy DOI: 10.1111/jsm.12384
ABSTRACT
Introduction. Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. Aim. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. Methods. We performed a case–control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Main Outcome Measures. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. Results. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P < 0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (30 ng/mL. A recent metaanalysis [6] of 14 prospective studies shows a 19% reduction in risk of future diabetes for individuals with a baseline vitamin D level in the top third of the population vs. those in the bottom third. Moreover, a nested case–control study with a median 4 years of follow-up reported that below the cutoff of 10 ng/mL 25(OH)D, the risk of developing type 2 diabetes increased dramatically [8]. Vitamin D and calcium may play a role in glucose tolerance through their effects on insulin secretion and insulin sensitivity [4,5,9,11,12], but the human association studies are inconclusive, showing conflicting results. Recent advances highlight the expression of vitamin D receptors and vitamin D metabolizing enzymes in the human male reproductive tract; vitamin D 25-hydroxylase (CYP2R1) is recognized as the most important 25-hydroxylase and shows the highest expression in the testis [13–15]. In a cross-sectional survey of 3,369 communitydwelling men aged 40–79 years in eight European centers [16], vitamin D deficiency (25(OH)D 35 kg/m2), any therapy interfering with bone metabolism, malabsorption syndrome, testosterone replacement therapy, documented hypoparathyroidism, kidney diseases, previous orchiectomy, and fish oil consumption were exclusion criteria. One hundred age-matched men without diabetes and with normal gonadal function served as control group; they were recruited from the medical and paramedical staff of our institution and also from volunteer family members of patients. All patients gave their informed consent to the study, which was approved by the local institutional review board. Diagnosis of hypogonadism was made according to evidence-based criteria [19], specifically a serum morning (between 8 and 10 am) testosterone level less than 11 nmol/L in the presence of symptoms and signs of androgen deficiency. Sense of smell and previous fertility were investigated to exclude the enrollment of patients with congenitally caused hypogonadism. To better define symptoms of hypogonadism, we assessed them with the Italian versions of the Aging Males’ Symptoms Scale and the International Index of Erectile Function-5 (IIEF-5). Height, weight, blood pressure, and waist circumference were recorded, and BMI was calculated. Clinical evaluation also considered facial and body hair, testicular volume, gynecomastia, and muscle mass. The differentiation between hypogonadotropic and hypergonadotropic hypogonadism was based on circulating concentrations of luteinizing hormone (LH), which would be low or normal in the first and elevated in the latter. We used the LH threshold (9.4 IU/L) previously suggested by Lee et al. [16]. Testosterone and LH concentrations were evaluated in two different samples; on the second sample, sex hormone-binding globulin was also assessed for the calculation of free testosterone. Although deficiency and insufficiency cutoff points are still a topic of discussion [20], we followed Endocrine Society clinical guidelines and previously recommended cutoff points [21,22] in diagnosing vitamin D deficiency when serum J Sex Med 2014;11:536–542
538
Bellastella et al.
25(OH)D was
Vitamin D Deficiency in Type 2 Diabetic Patients with Hypogonadism Giuseppe Bellastella, MD, PhD,* Maria Ida Maiorino, MD,* Laura Olita, MD,* Annalisa Capuano, MD,† Concetta Rafaniello, MD,† Dario Giugliano, MD, PhD,* and Katherine Esposito, MD, PhD‡ *Unit of Endocrinology and Metabolic Diseases, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; †Department of Experimental Medicine, Second University of Naples, Naples, Italy; ‡Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy DOI: 10.1111/jsm.12384
ABSTRACT
Introduction. Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. Aim. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. Methods. We performed a case–control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Main Outcome Measures. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. Results. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P < 0.001), with 81% of diabetic patients presenting 25(OH)D deficiency (30 ng/mL. A recent metaanalysis [6] of 14 prospective studies shows a 19% reduction in risk of future diabetes for individuals with a baseline vitamin D level in the top third of the population vs. those in the bottom third. Moreover, a nested case–control study with a median 4 years of follow-up reported that below the cutoff of 10 ng/mL 25(OH)D, the risk of developing type 2 diabetes increased dramatically [8]. Vitamin D and calcium may play a role in glucose tolerance through their effects on insulin secretion and insulin sensitivity [4,5,9,11,12], but the human association studies are inconclusive, showing conflicting results. Recent advances highlight the expression of vitamin D receptors and vitamin D metabolizing enzymes in the human male reproductive tract; vitamin D 25-hydroxylase (CYP2R1) is recognized as the most important 25-hydroxylase and shows the highest expression in the testis [13–15]. In a cross-sectional survey of 3,369 communitydwelling men aged 40–79 years in eight European centers [16], vitamin D deficiency (25(OH)D 35 kg/m2), any therapy interfering with bone metabolism, malabsorption syndrome, testosterone replacement therapy, documented hypoparathyroidism, kidney diseases, previous orchiectomy, and fish oil consumption were exclusion criteria. One hundred age-matched men without diabetes and with normal gonadal function served as control group; they were recruited from the medical and paramedical staff of our institution and also from volunteer family members of patients. All patients gave their informed consent to the study, which was approved by the local institutional review board. Diagnosis of hypogonadism was made according to evidence-based criteria [19], specifically a serum morning (between 8 and 10 am) testosterone level less than 11 nmol/L in the presence of symptoms and signs of androgen deficiency. Sense of smell and previous fertility were investigated to exclude the enrollment of patients with congenitally caused hypogonadism. To better define symptoms of hypogonadism, we assessed them with the Italian versions of the Aging Males’ Symptoms Scale and the International Index of Erectile Function-5 (IIEF-5). Height, weight, blood pressure, and waist circumference were recorded, and BMI was calculated. Clinical evaluation also considered facial and body hair, testicular volume, gynecomastia, and muscle mass. The differentiation between hypogonadotropic and hypergonadotropic hypogonadism was based on circulating concentrations of luteinizing hormone (LH), which would be low or normal in the first and elevated in the latter. We used the LH threshold (9.4 IU/L) previously suggested by Lee et al. [16]. Testosterone and LH concentrations were evaluated in two different samples; on the second sample, sex hormone-binding globulin was also assessed for the calculation of free testosterone. Although deficiency and insufficiency cutoff points are still a topic of discussion [20], we followed Endocrine Society clinical guidelines and previously recommended cutoff points [21,22] in diagnosing vitamin D deficiency when serum J Sex Med 2014;11:536–542
538
Bellastella et al.
25(OH)D was
