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How to cite this article: Noyola-García ME, Díaz-Romero A, Arce-Quiñones M, Chong-Martínez BA, Anda-Garay JC. [Vitamin D deficiency associated with insulin resistance in medical residents]. Rev Med Inst Mex Seguro Soc. 2016;54 Suppl 2:S202-9.
ORIGINAL CONTRIBUTIONS
Received: November 2nd 2015
Judged: May 2nd 2015
Vitamin D deficiency associated with insulin resistance in medical residents
Maura Estela Noyola-García,a Alberto Díaz-Romero,b Mariana Arce-Quiñones,c Blanca Alicia Chong-Martínez,a Juan Carlos Anda-Garaya
aDepartamento de Medicina Interna, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México
bHospital General de Zona 1-A, Ciudad de México
cHospital General de Zona 51, Gómez Palacio, Durango
Instituto Mexicano del Seguro Social, México
Communication with: Maura Estela Noyola García
Telephone: (55) 5627 6909
Email: mnoyola.g@gmail.com
Background: Several studies have reported a correlation between vitamin D deficiency and insulin resistance; however, other clinical trials show that vitamin D supplementation do not normalize glucose and insulin levels. We designed a study to show if there is a correlation between serum vitamin D and the homeostatic model assessment 2 (HOMA 2).
Methods: it was designed a cross-sectional, descriptive, and analytical study, which included medical residents. They answered a questionnaire to record the time of sun exposure. We took anthropometric measurements, such as weight, height, and waist circumference, as well as some serum levels: serum vitamin D, serum insulin, fasting blood glucose, triglycerides and high-density lipoprotein-cholesterol. The correlation between serum vitamin D and HOMA 2 was determined by the correlation of Pearson; it was considered significant a p < 0.05.
Results: The decreased serum vitamin D levels did not correlate with high concentrations of HOMA 2 (r = −0.11, p = 0.34). A negative correlation between vitamin D levels and index size waist was observed (r = −0.27, p = 0.025). HOMA 2 was positively correlated with waist size index (r = 0.23, p = 0.05) and triglycerides (r = 0.61, p = 0.01) and negatively with high density lipoprotein-cholesterol (r = −0.26, p = 0.02).
Conclusions: We couldn’t show the correlation between vitamin D deficiency and insulin resistance.
Keywords: Insulin resistance; Vitamin D deficiency
Vitamin D deficiency is a public health problem that has gained importance in recent decades, due to the current knowledge of its involvement in multiple physiological functions of the body, as well as the wide variability of serum concentrations and the difficulty of defining the deficiency. Several factors have been identified that influence the concentration, such as age, gender, genetic factors, obesity, intake of foods containing vitamin D, the use of dietary supplements, taking multivitamins, and sun exposure.1,2 Interest in this issue has also increased, as a high prevalence of vitamin D deficiency has been found, especially in overweight subjects with different degrees of obesity.3-5 One risk factor for vitamin D deficiency is poor exposure to sunlight. Therefore, these factors have been studied in health workers and medical residents, who have been found to have increased risk of developing vitamin D deficiency.6
The effects of vitamin D on glucose metabolism have been studied extensively.5,7,8 In peripheral tissues, vitamin D can directly improve insulin sensitivity by receptor expression or by peroxisome proliferator-activated receptor (PPAR-delta), a transcription factor involved in the regulation of both fatty acid metabolism in skeletal muscle and adipose tissue, and the regulation of the extracellular calcium concentration across membranes. Vitamin D can also affect insulin resistance indirectly through the renin-angiotensin system. It is thought that angiotensin II contributes to the development of insulin resistance by inhibiting the action of insulin in the vascular tissue and adipose tissue, contributing to worsening glucose reuptake. It has been described that vitamin D deficiency is a risk factor for the development of diabetes and insulin resistance. In vitro and in vivo, vitamin D deficiency decreases glucose-mediated insulin secretion in the pancreatic cells, whereas supplementation restores insulin secretion. Likewise, vitamin D can have a direct effect on pancreatic cell function by activating the vitamin D receptor expressed by cells in the form 1,25 (OH) 2D.6,7 An indirect effect of vitamin D in the beta cell can be mediated via regulation of the concentration and flux of extracellular calcium. Vitamin D also regulates calbindin, a cytosolic calcium carrier protein found in multiple tissues, including pancreatic cells; it has also been held that vitamin D regulates immune cells.9-11
The diagnosis of insulin resistance requires specialized tests, such as hyperinsulinemic-euglycemic clamp, fasting glucose/insulin ratio, the minimal model, or insulin tolerance.12,13 Validation of different techniques is done by comparison to the hyperinsulinemic-euglycemic clamp (or euglycemic clamp), which is the gold standard for the study of insulin resistance; thus, a technique is considered better, the closer its results correlate with the clamp.14 HOMA 2 (homeostasis model assessment 2) was developed by Turner’s group in the first half of the 80s. Their results have a good correlation with the clamp, both in patients with normal tolerance and in type 2 diabetics of different ages and degrees of obesity. It has also shown predictive ability for the future development of glucose intolerance and type 2 diabetes in prospective studies. All this makes it a good method for large epidemiological studies.12-14
Experimental studies have shown that disordered glucose metabolism mediated by insulin secretion could be normalized by treatment with vitamin D.15-18 Some other studies show that vitamin D has a protective effect against cytokine production induced by pancreatic B-cell dysfunction; it has also been suggested that vitamin D may have effects on the growth and differentiation of beta cells.4,11,19 The study by Haney et al., which analyzed a group of medical residents in the Internal Medicine specialty (n = 35) of the University of Portland in Oregon (USA), found a significant variation in levels of 25 (OH) D in a seasonal period considered high-risk, and they determined a 51.4% prevalence of deficiency of this vitamin, without finding a correlation with levels of PTH or performing analyses with other metabolic variables, due to a limitation in the N of the study.20 Similarly, in 2013 Victoria Mendoza et al. in Mexico City made a study of medical residents in training, which were virtually considered a risk group for vitamin D deficiency; the authors found that despite maintaining significantly lower 25 (OH) D levels than the control group, the levels of parathyroid hormone and the different metabolic indices showed no significant changes, the main limitation of the findings being a small group of resident doctors (n = 20).21 There is controversy in some studies on the improvement in fasting glucose levels, HbA1c, insulin resistance, carbohydrate intolerance, and the risk of developing diabetes mellitus type 1 and 2 with vitamin D supplementation.16,22-25 There is also controversy about whether low vitamin D levels correlate with insulin resistance in residents of medical specialties that are a risk group for developing both disorders, and, if so, it would be necessary to take vitamin D supplements. Therefore, the main objective of this study is to determine the frequency of insulin resistance and vitamin D deficiency in medical residents, and to demonstrate whether there is a correlation between low levels of vitamin D and insulin resistance measured by HOMA 2, in residents of medical specialties.
Methods
A transversal and descriptive study, in which medical specialties residents at the Hospital de Especialidades of the Centro Médico Nacional Siglo XXI were invited to participate; the protocol was approved by the Local Research and Health Ethics Committee number 3601, with registration number R-2014-3601-67. All participants were asked to sign the letter of informed consent before study initiation. The recruitment period was between the months of December 2013 and February 2014. It included subjects older than 18 years with body mass index (BMI) between 18.5 and 26.9, without comorbidities. Subjects with comorbidities of any kind, such as diabetes mellitus, hypertension, heart disease, liver disease, kidney disease, presence of chronic diarrhea or diagnosis of intestinal malabsorption, a history of bowel resection, history of thyroid disease, parathyroid, and known metabolic bone disease were excluded, as were those under supplementation with any form of vitamin D.
A questionnaire was applied to collect data including lifestyle, diet, sun exposure, sunscreen use, skin color, and use of food supplements or drugs. All participants were asked for anthropometric measurements: weight, height, waist circumference, waist-hip ratio, waist-height ratio, and body mass index. Laboratory studies were taken during the morning, with a minimum of eight hours of fasting. HOMA 2 measurement was made with the software provided by Oxford University, Diabetes Trial Unit, which can be accessed at the web address https://www.dtu.ox.ac.uk/homacalculator. Measurement of vitamin D was made by chemiluminescence immunoassay to check the levels of 25-hydroxyvitamin D (LIAISON®25 OH Vitamin D TOTAL Assay) in the laboratory of the unit. Deficiency was defined with values of 0-10 ng/dL, insufficiency with 10-30 ng/dL, and sufficiency with 30-100 ng/dL. Serum parathyroid hormone concentration was determined by immunoassay; values below the detection limit were indicated as < 10 pg/mL, and values above were indicated as > 65 pg/mL.
For the statistical analysis, the overall frequency of vitamin D deficiency, the insulin resistance measured by HOMA 2, and the parathyroid hormone levels were measured, as was the impact of vitamin D deficiency and insulin resistance adjusted by age and gender. The association between serum levels of 25 (OH) D and HOMA 2 levels was calculated using the Pearson correlation coefficient. The correlation between HOMA 2 and the different clinical and biochemical variables, and the correlation between vitamin D levels and clinical and biochemical variables were also analyzed, including parathyroid hormone; a p-value < 0.05 was considered significant.
Results
The study population was 70 subjects who met the inclusion criteria. 54% (32) were women; the rest men. 74.3% of the subjects reported a history of diabetes mellitus and hypertension in relatives. 71.4% did not exercise. 77.1% (54) reported that they were exposed to solar radiation less than 30 minutes per day, and only 22.9% (16) reported having more than 30 minutes of sun exposure per day, with inconstant and variable body surface exposed, but generally less than 10% of total body surface. The average age for women was 27.69 ± 1.4 and 28.13 ± 1.96 in men. The average weight for women was 58.72 ± 5.4 and 71.15 ± 9.2 in men. BMI had an average of 22.8 ± 1.84 in men, and 23.68 ± 2.14 in women. It was found that 7.1% (5) presented blood pressure figures above 130/85 mmHg. As for the measurement of waist circumference, 26.8% of men and 56.3% of women had a length indicating metabolic syndrome (MS) (Table I).
| Table I General characteristics of participants divided by gender (n = 70) | ||||
| Women (n = 32) |
Men (n = 38) |
|||
| Mean ± SD | Mean ± SD | |||
| Age (in years) | 27.69 ± 1.49 | 28.13 ± 1.96 | ||
| Weight (in kg) | 58 72 ± 5.48 | 71.15 ± 9.12 | ||
| Height (in m) | 1.60 ± 0.62 | 1.73 ± 0.71 | ||
| BMI (in kg/m2) | 22.87 ± 1.84 | 23.68 ± 2.14 | ||
| n | % | n | % | |
| 18.0-20.9 | 4 | 12.5 | 5 | 13.2 |
| 21.0-22.9 | 13 | 40.6 | 6 | 15.8 |
| 23.0-24.9 | 15 | 46.9 | 27 | 71.1 |
| Hereditary family history | ||||
| No | 7 | 21.9 | 11 | 28.9 |
| Yes | 25 | 78.1 | 27 | 71.1 |
| Physical activity | ||||
| No | 26 | 81.3 | 24 | 63.2 |
| Yes | 6 | 18.8 | 14 | 36.8 |
| Diet | ||||
| Good | 4 | 12.5 | 4 | 10.5 |
| Average | 22 | 68.8 | 23 | 60.5 |
| Bad | 6 | 18.8 | 11 | 28.9 |
| Sun exposure | ||||
| < 30 min day | 25 | 78.1 | 29 | 76.3 |
| > 30 min day | 7 | 21.9 | 9 | 23.7 |
| Sunscreen use | ||||
| No | 26 | 81.3 | 37 | 97.4 |
| Yes | 6 | 18.8 | 1 | 2.6 |
| SD = standard deviation; BMI = body mass index | ||||
Insulin resistance determined by HOMA 2 greater than 1.0 was found in 58.6% of participants (22 women and 19 men) (Table II). Vitamin D deficiency was found in 32.9%, insufficiency in 65.7%, and only one participant (1.4%) had normal serum levels of vitamin D (Table III). Although more than half of the population had insulin resistance measured by HOMA 2, only 5.7% (4) had metabolic syndrome according to the International Diabetes Federation criteria. The presence of two criteria of metabolic syndrome was observed in 21.4% of participants. The most common metabolic disorders were hypertriglyceridemia above 150 mg/dL in 17.1%, followed by low levels of high-density cholesterol less than 50 mg/dL in women and less than 40 mg/dL in men at 8.5% of subjects, and fasting glucose greater than 100mg/dL in 5.7%.
| Table II Components of metabolic syndrome and their distribution by gender | ||||||
| Anthropometric variables | General population (n = 70) |
Women (n = 32) |
Men (n = 38) |
|||
| Waist circumference (in cm)* | 84.43 ± 6.0 | 81.59 ± 5.4 | 86.8 ± 5.5 | |||
| n | % | n | % | |||
| > 90† | 14 | 26.8 | ||||
| < 90† | 24 | 63.2 | ||||
| > 80† | 18 | 56.3 | ||||
| < 80† | 14 | 43.8 | ||||
| Waist-hip ratio* | 0.91 ± 0.037 | 0.89 ± 0.03 | 0.92 ± 0.03 | |||
| > 0.90† | 1 | 2.6 | ||||
| < 0.90† | 37 | 97.4 | ||||
| > 0.85† | 29 | 90.6 | ||||
| < 0.85† | 3 | 9.4 | ||||
| Waist-height ratio* | 0.51 ± 0.03 | 0.50 ± 0.03 | ||||
| > 0.5† | 15 | 46.9 | 20 | 52.6 | ||
| < 0.5† | 17 | 53.1 | 18 | 47.4 | ||
| Metabolic variables | ||||||
| Glucose (in mg/dL) * | 86.36 ± 8.5 | 84 97 ± 9.0 | 87.53 ± 7.9 | |||
| > 100† | 2 | 6.3 | 2 | 5.3 | ||
| < 100† | 30 | 93.8 | 36 | 94.7 | ||
| Triglycerides (mg/dL) * | 110 63.89 ±.00 | 88.06 43 ±.8 | 130.11 ± 70.4 | |||
| > 150† | 3 | 9.4 | 12 | 31.6 | ||
| < 150† | 29 | 90.6 | 26 | 68.4 | ||
| HDL (mg/dL) * | 56.99 ± 13.78 | 61.94 ± 10.5 | 52.8 ± 14.8 | |||
| > 40† | 32 | 84.2 | ||||
| < 40† | 6 | 15.8 | ||||
| > 50† | 29 | 90.6 | ||||
| < 50† | 3 | 9.4 | ||||
| HOMA 2‡ | 1.05 | 0.40-6.1 | 1.15 | 0.40-2.4 | 0.95 | 0.40-6.1 |
| > 1.0† | 41 | 58.6 | 22 | 68.8 | 19 | 50 |
| < 1.0† | 29 | 41.4 | 10 | 31.3 | 19 | 50 |
| *Average with standard deviation †Frequency of participants (n/%) ‡ Median with interquartile range |
||||||
| Table III Frequency of vitamin D deficiency and levels of parathormone (PTH) | ||||||
| Metabolic variables | General population (n = 70) |
Women (n = 32) |
Men (n = 38) |
|||
| Vitamin D (ng/dL)* | 13.28 ± 5.3 | 13.82 ± 5.2 | 12.8 ± 5.5 | |||
| n | % | n | % | n | % | |
| 0-10: deficiency† | 23 | 32.9 | 9 | 28.1 | 14 | 36.8 |
| 10-30: insufficiency† | 46 | 65.7 | 22 | 68.8 | 24 | 63.2 |
| 30-100: sufficiency† | 1 | 1.4 | 1 | 3.1 | 0 | --- |
| PTH (pg/mL) * | 42.83 ± 15.21 | 37.46 ± 12.7 | 47.46 ± 15.8 | |||
| < 65† | 64 | 91.4 | 30 | 93.8 | 34 | 89.5 |
| > 65† | 6 | 8.6 | 2 | 6.3 | 4 | 10.5 |
| *Average with standard deviation †Frequency of participants (n/%) |
||||||
Correlation of vitamin D and HOMA 2 with clinical and biochemical variables of MS
This correlation was not statistically significant, since a negative Pearson correlation coefficient was obtained with an r of -0.11 with a p-value = 0.34. We analyzed the correlation between vitamin D levels and anthropometric variables, and found a negative correlation with waist circumference (r = -0.54) and BMI (r = -1.94); however, these were not statistically significant. The same did not happen with our findings for waist-height ratio, which obtained a negative correlation (r = -0.27) and was statistically significant because p = 0.025, suggesting that the lower the concentration of vitamin D, the higher the waist-height ratio presented by the study subjects. Parathyroid hormone levels were not statistically significantly correlated with low levels of vitamin D, because a Pearson correlation coefficient r -0.05 was obtained with a p-value = 0.96, without being statistically significant (Table IV).
| Table IV Pearson correlation coefficient analysis among vitamin D and HOMA 2 in clinical and biochemical parameters | ||
| Variable | partial r | p |
| Waist circumference | −0.54 | 0.658 |
| Body mass index | −1.94 | 0.108 |
| Waist-height ratio | −0.27 | 0.025 |
| Insulin resistance (HOMA 2) | −0.11 | 0.34 |
| Insulin | −0.10 | 0.38 |
| Glucose | −0.002 | 0.98 |
| Triglycerides | −0.16 | 0.17 |
| HDL | −0.02 | 0.86 |
| Hemoglobin A1c | 0.07 | 0.56 |
| A p–value < 0.05 was statistically significant HDL = high density lipoprotein |
||
Correlation between HOMA 2 and clinical and biochemical variables of MS
In analyzing the correlation between HOMA 2 and the variables of metabolic syndrome, we found that associating the HOMA 2 index with clinical and laboratory variables has a positive correlation coefficient, since the waist-height ratio presents r = 0.23 and p = 0.05; likewise with serum triglyceride levels, a correlation coefficient was obtained with r = 0.61 with a p-value = 0.01; both were statistically significant. Likewise, HOMA 2 was negatively correlated with high density cholesterol levels with r = -0.26 and a p-value < 0.01, so one can assume that the higher the HOMA 2, the lower the concentration of high-density cholesterol (Table V).
| Table V Pearson correlation coefficient analysis of HOMA-2 and clinical and biochemical variables | ||
| Correlated variable | partial r | p |
| Waist circumference | 0.19 | 0.09 |
| Waist-hip ratio | −0.04 | 0.72 |
| Body mass index | 0.19 | 0.09 |
| Waist-height ratio | 0.23 | 0.05 |
| HDL | −0.26 | 0.02 |
| Triglycerides | 0.61 | 0.01 |
| A p–value < 0.05 was statistically significant HDL = high density lipoprotein |
||
Discussion
The characteristics of the study population are young subjects with BMI in normal and overweight ranges, in which, although there are risk factors for metabolic syndrome, the high prevalence of vitamin D deficiency and insufficiency is notable. It was shown that although it was considered a healthy population, more than a third had some criteria for metabolic syndrome; of these criteria, increased waist circumference is the most frequent disorder. Hypertriglyceridemia proved the most common laboratory abnormality of metabolic syndrome. Significantly, it is relevant to this study that 58.6% of the population had insulin resistance according to the HOMA 2 index, which is higher than that reported in a previous study.21 Vitamin D deficiency in the study group is mainly caused by long working hours in the hospital, which results in a poor exposure to sunlight, as well as the difficulty of obtaining or preparing adequate food. The degree of exposure and different skin tones were not considered as factors of bias in this study, since most of the participants had the same degree of skin pigmentation, and the latitude of Mexico City gives constant solar radiation without major changes throughout the seasons.
It is noteworthy that the vitamin D and parathyroid hormone levels did not show the expected correlation as reported by other studies, which find hyperparathyroidism as the primary response to vitamin D deficiency, a condition that was only found in 8.6% of participants.
Similarly, according to our data there is a negative but not significant correlation between 25-hydroxyvitamin D deficit with increased insulin resistance; again we are faced with this controversy in clinical studies, with which we cannot assume the deleterious effects caused by low levels of vitamin D on glucose metabolism from biochemical parameters. We believe that the inability to properly correlate 25-hydroxyvitamin D levels with metabolic syndrome, insulin resistance, and alterations in bone mineral metabolism had to do with the fact that over 90% of the subjects studied had deficient and insufficient vitamin D, which did not allow this study to compare with subjects with normal levels of vitamin D (n = 1); this leaves room to question whether the determination used for vitamin D deficiency in this unit is adequate, or if the cutoff point in which parathyroid hormone changes is correct.
The study is limited by the relatively small sample size; despite this, the number of participants is larger than several studies of the same nature. The study is also limited because it was done in a single institution and with no control group.
Conclusion
Low levels of 25-hydroxyvitamin D do not correlate with high levels of HOMA 2, or alterations in bone metabolism determined by the levels of parathyroid hormone, so this finding requires further study for vitamin D to be taken as a valid measurement for proper correlation with metabolic and bone disorders.
Acknowledgments
We thank the staff of the Clinical Laboratory of the Hospital de Especialidades of the Centro Médico Nacional Siglo XXI.References
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Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.
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