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Original Article

Victoria Mendoza, MD1; María T. Villanueva, MD2; Guadalupe Vargas, MD1; Baldomero González, MD1,2; José Halabe, MD2; Jesús Simón, MD2; Moisés Mercado, MD1,2
ABSTRACT Objective: To evaluate different elements of the calciotropic system in a group of house staff physicians, comparing them with age, gender, and body mass index (BMI) matched controls. Methods: We measured vitamin D, calcium, phosphorus, parathyroid hormone (PTH), glucose, insulin (estimating the insulin resistance index by the homeostatic model [HOMA]), and lipid levels in 20 medical residents and 20 age-, gender-, and BMI-matched controls. We looked for correlations between elements of the calciotropic system and metabolic indices. Results: Medical residents and controls were similar in regard to gender distribution, weight, height, BMI, abdominal circumference, as well as systolic and diastolic blood pressure. No differences were found between the two groups in regard to low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, plasma insulin levels, and HOMA-IR. Vitamin D and calcium levels were significantly lower among the medical residents (P = .001 and P = .003, respectively), whereas PTH concentrations tended to be higher. We found an inverse correlation between triglyceride concentrations and vitamin D (r = −0.31, P = .04). Conclusion: Vitamin D deficiency among resident physicians is frequent and could have metabolic effects. Our findings highlight the consequences of the lack of sun exposure due to occupational reasons. We recommend a higher intake of vitamin D during this period. (Endocr Pract. 2013;19:59-63) Abbreviations: BMI = body mass index; CV = coefficient of variation; HOMA-IR = homeostasis model of assessment-insulin resistance; HDL-C = high density lipoprotein cholesterol; IR = interquartile range; LDL-C = low density lipoprotein cholesterol; PTH = parathyroid hormone; UVB = ultraviolet light; 25(OH)D = 25-hydroxyvitamin D or cholecalciferol; 1, 25 (OH)2D = 1, 25-dihydroxyvitamin D or calcitriol INTRODUCTION Vitamin D deficiency is increasingly being diagnosed in the World and although its prevalence varies widely; it usually ranges between 20 and 40%, depending on the population (1). Vitamin D is in fact a hormone synthesized in the skin upon sun exposure, whereby ultraviolet light (UVB) converts 7-dehydrocholesterol into previtamin D. Small amounts of vitamin D are ingested with food (ergochalciferol [vitamin D2] from vegetable sources and cholecalciferol [vitamin D3] from animal sources) (2). Further processing of previtamin D takes place first in the liver, where it is hydroxylated into 25-hydroxyvitamin D (25[OH]D), the most chemically stable and abundant vitamin D metabolite in the circulation. The 25(OH)D is later-on hydroxylated again in the kidney, thereby generating 1,25-dihydroxyvitamin D (1,25[OH]2D), an essential player in calcium homeostasis and bone mineralization, which also has putative effects as a metabolic and immunological regulator (2-5).

Submitted for publication July 4, 2012 Accepted for publication August 28, 2012 From the 1Endocrinology Service, Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social 11560 Mexico City, Mexico; and 2Departments of Medicine and Clinical Pathology, The American British Cowdray Medical Center, Mexico City, Mexico. Address correspondence to Dr. Moisés Mercado, Aristóteles 68, Polanco 11560, Mexico City, Mexico. E-mail: mmercadoa@yahoo.com. Published as a Rapid Electronic Article in Press at http://www.endocrine practice.org on November 27, 2012. DOI:10.4158/EP12185.OR To purchase reprints of this article, please visit: www.aace.com/reprints. Copyright © 2013 AACE.

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and intra-assay coefficients of variation (CV) of 2. We used a specific chemoluminescent assay to measure PTH intact molecule (DiaSorin Inc. this goes on for an average of 4 years for medical specialties and up to 7 or 8 years for some surgical disciplines. and no one used skin solar blockers. Minnesota) with a sensitivity of ≤4 ng/mL and inter. gender-. are only beginning to be unraveled (9). Stillwater. as well as in other biological systems. both surgical and medical trainees start working very early in the morning. Medical residents and controls were similar in regard to gender distribution. BMI. Blood sampling was carried out after a 12-hour fast.1%. total cholesterol. respectively. A clinical and nutritional evaluation was carried out prior to blood sampling. Although schedules vary depending on particular programs. and body mass index (BMI)-matched nonmedical individuals were included in this cross-sectional study. and the calculated HOMA-IR (Table 2). by virtue of being less exposed to sunlight because of a myriad of social. The likelihood that the data were normally distributed was ascertained using the ShapiroWilk test. Insulin was determined using a micro particle enzyme immunoassay on an automated Axsym System (Abbott Diagnostics.1% and 4. even when not on call. and hypertension was considered to be present if the systolic reading was above 130 mm Hg or the diastolic above 85 mm Hg. as well as hip and waist circumference. high-density lipoprotein (HDL)-cholesterol. The statistical power. the cutoffs to define sufficiency.05. height. respectively. antiretroviral. fasting glucose and triglyceride levels were below 100 mg/dL and 150 mg/dL. respectively. The evaluation confirmed the health status of the subjects and verified that they all ate a non-vegetarian diet with adequate daily vitamin D and calcium requirements according to international standards (for vitamin D 600 IU and for calcium 800 mg). deficiency. as well as lipid and glucose concentrations. phosphorus. respectively. and was completed within 1 week in all subjects.2. and economic reasons. We thus hypothesized that healthy house staff working at a university hospital should have lower vitamin D levels as compared to age. or ketoconazol therapy. Abbott Park. yet. Blood pressure was measured in the sitting position.3% and 3. was calculated using the means and SD of the 25(OH)D concentrations in the 2 groups and assuming an α error of 0. sometimes before sunrise and. when Ho is false. .and gender-matched.and intra-assay CVs of 5. HDL-cholesterol. Part of the controversy derives from the fact that modern urban populations. geographical.05. Illinois). Stillwater. RESULTS Basic clinical characteristics of both the medical residents and the control groups are shown in Table 1.7). Mean glucose levels were lower and triglyceride concentrations higher among the medical residents (Table 2). weight. neither clinical nor laboratory evidence of hepatic or renal insufficiency or intestinal malabsorption was found in any of them. Serum was separated from blood cells and stored at −20°C until assayed. anticonvulsant.11). between 8:00 AM and 9:00 AM. healthy nonmedical controls. and Canada but also in Latin America and Europe (10. Serum 25(OH)D was measured in plasma by means of a chemoluminiscent assay (DiaSorin Inc. in all studied subjects. none of them was receiving glucocorticoid. plasma insulin levels. usually show variably low concentrations of 25(OH)D (8). Female subjects were required to have a negative pregnancy test and all had regular menstrual cycles. All subjects signed informed consent forms. respectively. Statistical Analysis Quantitative data is presented as means ± SD when normally distributed and as medians with interquartile ranges when not. Residency training is well known for the long hours spent indoors. Glucose. defined as 1 . and systolic and diastolic blood pressure (Table 1). All subjects were healthy.6%.S. leave the hospital usually after sunset.1% and 8. and insufficiency are a matter of active controversy (6. occupational.5%. The consequences of this relative and variable deficiency of vitamin D in both calcium and bone physiology. The study took place during the summer of 2011 and was approved by our Ethics and Scientific Committees.60 Although it is well established that the serum 25(OH) D level reflects the actual reserves of the hormone.β or the chance of rejecting the null hypothesis (Ho: 25[OH]D in residents = 25[OH]D in nonresidents). and parathyroid hormone (PTH) levels. Illinois) with a sensitivity of 1 µU/mL and inter.and intra-assay CVs of 5. No differences were found between the 2 groups in regard to LDLcholesterol. unpaired Student’s t test and the Wilcoxon signed rank test. triglycerides total calcium and phosphorus were measured on an Architect ci8200 automated analyzer (Abbott Diagnostics. We also sought correlations between vitamin D and calcium. lowdensity lipoprotein (LDL)-cholesterol. PATIENTS AND METHODS Twenty medical and surgical residents working at a university hospital in Mexico City and a group of 20 age-. abdominal circumference. and is rather constant not only in the U. Data were analyzed using the statistical package STATA 11. Statistical significance was defined when the P value was <. Abbott Park. Differences in quantitative variables between the 2 groups were analyzed by means of the two-tailed. Anthropometric measurements included weight and height (with BMI calculation). The insulin resistance index was calculated using the homeostasis model (HOMA-IR) formula: fasting insulin (µIU/mL) × fasting glucose (mg/dL)/405. Minnesota) with a sensitivity of 1 pg/mL and inter. Spearman’s and Pearson’s correlations were sought in the case of nonparametric and parametric variables.

28 .5 ± 7.43 . P = .0 71.05.7 to 81.55 ± 4. respectively. In this latter context. Median intact PTH tended to be slightly higher among medical residents.. An increasing number of reports appear in the literature highlighting the rising prevalence of vitamin D deficiency in the relatively young and healthy (14).55 ± 0. which allows us to reject the null hypothesis (i. mean ± SD Weight (kg).13). by virtue of its long hours spent indoors.1 ± 10. respectively.6].04).13. Undoubtedly both physicians and the lay public are more aware of the problem. nonmedical residents r = 0.49 ± 2. mean ± SD Size (m).03. P = .09 88 (82-95. Phosphorus: 3. median (IR) Abbreviations: BMI = body mass index. respectively.26 ± 0. Looking for the impact of vitamin D deficiency on the calciotropic and metabolic systems.e.90 . Mean plasma 25(OH)D levels were significantly lower in the medical residents group than in the control group (16.1 ng/mL. Vitamin D levels were inversely related to the triglyceride concentration when both groups were analyzed together (r = −0.4 mg/dL. median (IR) Diastolic BP (mm Hg). P = .68 ± 0. matched-control study we have shown that residency training.07 24.18 . 25[OH]D in residents and nonresidents is not different) with reasonable confidence. 1). median (IR) Systolic BP (mm Hg).47 1.16).001) (Fig. P = . this inverse correlation persisted only in the medical residents group (medical residents r = −0.7 ± 0.6 ± 2.3 versus 9. but also for BMI.70 Variable Male. Calcium and phosphorus levels were significantly lower in medical residents with vitamin D deficiency (Calcium: 9.61 Table 1 Basic Clinical Characteristics in the Medical Residents and the Control Groups Medical residents n = 20 11 (55) 29.3 mg/dL.61 88. without reaching statistical significance (68.48 . a significantly higher proportion of residents had 25(OH)D blood levels below the threshold that defines deficiency. vitamin D deficiency stems from the fact that urban populations live more indoors than ever before and thus are less exposed to sunlight. respectively. Both groups were matched not only for age and gender.50). These young physicians had significantly lower levels of 25(OH)D than their matched controls.50 ± 0. mean ± SD BMI (kg/m2).62 ± 16. P = . the estimated statistical power is not at all negligible. The major strength of the study is its matched-control design. Vitamin D deficiency (defined as 25(OH) D levels <20 ng/mL) was more frequently found among the medical residents than in the nonmedical resident controls (15 [75%] versus 9 [45%].3 versus 9.5) 110 (100-115) 60 (60-70) P value . mean ± SD Waist (cm).50) (Table 2).79 . and from the low food content of both ergocalciferol and cholecalciferol (15.9 ± 3. BP = blood pressure.31. respectively.1 versus 21.08 24. respectively. The focus of the controversy has moved from frail and aging groups with well-established bone fracture risks to younger and healthier populations with potential cardiometabolic hazards due to global sociodemographic reasons (12. Furthermore. n (%) Age (y). P<. Mean serum calcium was also lower among the medical residents than among the controls (9.01) (Table 2). The calculated statistical power was 65%. whereas the median serum phosphorus level was similar between the 2 groups (Table 2). No other significant correlations were found between vitamin D levels and the metabolic and calciotropic variables. P =. P = .2] versus 62.9 ± 5. when analyzed separately. and our nutrition survey made sure that subjects in both groups ate an adequate amount of vitamin . Although our sample size is small. we stratified both groups using a cutoff value of 20 ng/mL.3 versus 4.5 (85-92) 110 (100-120) 65 (60-70) Non-medical residents n = 20 11 (55) 28. P = .3 mg/dL. constitutes in fact a risk for vitamin D deficiency.5 pg/mL [interquartile range 59. In the present cross-sectional.003).43. whereas such a difference was not found among vitamin D-sufficient individuals regardless of whether they were medical residents or not.05 ± 0.3 pg/mL [interquartile range 51 to 82.49 1.28 ± 0. IR = interquartile range.70 ± 0. DISCUSSION Over the past decade vitamin D deficiency in the general population has become a controversial public health issue.19 69.80 . and therefore the measurement of 25(OH)D levels has almost become a routine blood test (17).04).

1% of adolescents and in 29. HOMA = homeostasis model of assessment. As expected. mean ± SD Triglycerides (mg/dL). median (IR) HOMA. D with their diet.49 . such as fasting blood glucose.4-13.6) 21. Physicians in general are notorious for working long hours in artificially lit places.85 (3.62 Table 2 Comparison Between Variables in the Medical Residents and the Control Groups Metabolic variables Glucose (mg/dL).85 Abbreviations: 25(OH)D = 25-hydroxy-vitamin D or cholecalciferol. cholesterol. We did not find significant associations between 25(OH)D and clinical variables.12 .5-147) 44 (37-56) 108.7 ± 8. It is also noteworthy that blood sampling took place at the same time and was completed in all subjects within 1 week. median (IR) PTHi (ng/mL).7-81.65 . We also did not find significant correlations with metabolic indices. Although sunlight in Mexico is basically the same throughout the year. but to the best of our knowledge.55 ± 0.2) 16.15 (5. cross-sectional studies have found an association between low 25(OH)D levels and an unfavorable lipid profile.3 (51-82.99 . insulin. Our results are similar to those of Maeda et al. Although we realize that this correlation does not necessarily imply causation. yet performing clamp studies was precluded by its higher cost and more invasive nature. this is the first study using a design based on a carefully matched control group (20-23).005a .23) Nonmedical residents 93. PTHi = intact parathyroid hormone.26 97 (75. controls were young professionals working standard office hours. BP = blood pressure.9% of adults. or the HOMA-IR. the study took place in the middle of the summer.15 ± 34. median (IR) LDL-C (mg/dL). LDL-C = low-density lipoprotein cholesterol.3 3.32 4. vitamin D deficiency was present in 31. correspondingly. This reiterates the effect that behavioral and occupational factors can have in vitamin D physiology (19). Interestingly. or BMI. particularly with high triglycerides and low HDL-cholesterol levels (24-26). a trend towards higher intact PTH levels.01a Medical residents 86.26 ± 0.4) 62. a state of relative secondary hyperparathyroidism. IR = interquartile range. Some studies have looked at vitamin D status and its consequences in physicians. whereas it remained in the group of physicians when analyzed separately. The prevalence of vitamin D deficiency in the medical residents group found in our study is considerably above the recently reported official national figures obtained from open populations (18).5-128) 47 (37.50 .29-3. who also found significantly lower mean 25(OH)D levels and higher PTH concentrations among resident physicians than among a group of indoor workers (20). . In this report. median (IR) HDL-C (mg/dL). However.6-4) 68. mean ± SD Phosphorus (mg/dL). HDL-C = highdensity lipoprotein cholesterol. median (IR) 25(OH)D (ng/mL).05a . the HOMA-IR is not the ideal method for the determination of insulin sensitivity.08 . clinical trials looking at the influence of vitamin D supplementation on lipid levels do not seem to show a consistent positive effect in terms of decreasing triglycerides and increasing HDL-cholesterol (27-28). a Unpaired Student’s t test. Accordingly.98 ± 5.15 (5.12 8.18 ± 30.98 134 (100.55 ± 7. phosphatemia was similar between the 2 groups. median (IR) Calciotropic system Calcium (mg/dL).57 (1.65-4.19 (1. mean ± SD 9.35 ± 6.05 (3. The most apparent physiological consequence of chronic vitamin D deficiency is a reduction in intestinal calcium absorption and hence. such as blood pressure.5-63) 104.9) 2.18 9.5 (59.003a .13) P value . this association was lost in the nonresidents group. waist circumference. both residents and nonresidents came from a similar socioeconomic level. In addition. Vitamin D concentrations did correlate with the triglyceride level when both groups were analyzed together.55) 1. previous large scale. BMI = body mass index. Admittedly.49 10. we found statistically significant lower serum calcium concentrations in the residents than in the nonresidents and.2-3.8-13. mean ± SD Insulin (µU/mL).

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