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Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in type 2 diabetes mellitus patients presenting to a functional medicine clinic

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Abstract

This study explores the relationship of 25-hydroxylvitamin D blood levels in 106 randomly selected patient files with diagnosed type 2 Diabetes Mellitus (t2DM) who enrolled in a functional medicine diabetes reversal program from a chiropractic clinic located in Annapolis, Maryland, USA. Using a conservative recommendation for normal serum 25-hydroxyvitamin D concentration of 32 ng/ml, insufficiency level of 20 - 30 ng/ml, and deficiency level < 20 ng/ml, 21% (22/106) of our population were normal, 39% (41/106) were insufficient, and alarmingly, 35% (37/106) were outright deficient. Clinically, 74% (78/ 106) of our entire sample had significantly low vitamin D levels. Ou et al. (2011) determined the optimal concentration of serum 25OHD to be 40 ng/ml in order to optimize insulin sensitivity. In our sample 100/ 106 (94%) had vitamin D levels at or below this optimal cut-off level. BMI was negatively correlated with vitamin D; that is, the greater the BMI of the patient the less their vitamin D level. Both obesity and hypovitaminosis D are each mutually exclusive predictors for t2DM. Obesity and vitamin D deficiency may work synergistically to propel an individual into the diseased state of t2DM. As this study demonstrates that the majority of people with t2DM suffer from inadequate amounts of vitamin D, vitamin D testing should be routine for all people at risk for t2DM, prediabetics and those currently suffering with t2DM in order to elevate levels sufficiently to improve insulin sensitivity and improve long-term outcomes.
J. Biomedical Science and Engineering, 2013, 6, 12-15 JBiSE
http://dx.doi.org/10.4236/jbise.2013.65A003 Published Online May 2013 (http://www.scirp.org/journal/jbise/)
Low serum 25-hydroxyvitamin D [25(OH)D]
concentrations in type 2 diabetes mellitus patients
presenting to a functional medicine clinic
Paul A. Oakley1, Stephanie J. Chaney2, Michael A. Persinger3, Thomas A. Chaney2
1Private Practice, Newmarket, Canada
2Private Practice, Annapolis, USA
3Behavioral Neuroscience Program, Laurentian University, Sudbury, Canada
Email: docoakley.icc@gmail.com
Received 5 March 2013; revised 7 April 2013; accepted 8 May 2013
Copyright © 2013 Paul A. Oakley et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
This study explores the relationship of 25-hydroxyl-
vitamin D blood levels in 106 randomly selected pa-
tient files with diagnosed type 2 Diabetes Mellitus
(t2DM) who enrolled in a functional medicine diabe-
tes reversal program from a chiropractic clinic lo-
cated in Annapolis, Maryland, USA. Using a conser-
vative recommendation for normal serum 25-hy-
droxyvitamin D concentration of 32 ng/ml, insuffi-
ciency level of 20 - 30 ng/ml, and deficiency level < 20
ng/ml, 21% (22/106) of our population were normal,
39% (41/106) were insufficient, and alarmingly, 35%
(37/106) were outright deficient. Clinically, 74% (78/
106) of our entire sample had significantly low vita-
min D levels. Ou et al. (2011) determined the optimal
concentration of serum 25OHD to be 40 ng/ml in or-
der to optimize insulin sensitivity. In our sample 100/
106 (94%) had vitamin D levels at or below this opti-
mal cut-off level. BMI was negatively correlated with
vitamin D; that is, the greater the BMI of the patient
the less their vitamin D level. Both obesity and hy-
povitaminosis D are each mutually exclusive predic-
tors for t2DM. Obesity and vitamin D deficiency may
work synergistically to propel an individual into the
diseased state of t2DM. As this study demonstrates
that the majority of people with t2DM suffer from
inadequate amounts of vitamin D, vitamin D testing
should be routine for all people at risk for t2DM, pre-
diabetics and those currently suffering with t2DM in
order to elevate levels sufficiently to improve insulin
sensitivity and improve long-term outcomes.
Keywords: Diabetes Mellitus; BMI; Vitamin D;
Deficiency; Insufficiency; Functional Medicine
1. INTRODUCTION
Vitamin D was originally misclassified as merely a vita-
min when indeed it is a hormone and involved in a
plethora of physiological processes. Its insufficiency or
outright deficiency is implicated in not only bone frac-
tures and osteoporosis but also numerous serious and
often fatal diseases, including many cancers, infectious
diseases, heart disease, autoimmune and metabolic dis-
eases including type 2 Diabetes Mellitus (t2DM).
Vitamin D status has been verified to be inversely as-
sociated with future risks of t2DM [1]. Vitamin D status
in t2DM patients is associated with glucose and lipid
parameters [2]. This study explores the relationship of
vitamin D blood levels in those with diagnosed t2DM
upon first presentation to a functional medicine diabetes
reversal program.
2. METHODS
2.1. Subjects
106 t2DM patients were randomly selected out of the
files of a functional medicine and chiropractic clinic lo-
cated in Annapolis, Maryland, USA. Sixty of the subjects
were Black, 41 were Caucasian, and 5 were Asian.
The patients had presented to the office for enrolment
into a t2DM reversal program during the years 2011-
2012. All patients had been previously diagnosed with
t2DM by an MD or Endocrinologist and were taking
either oral medication for glucose control or by injecting
insulin.
2.2. Parameters Investigated
Initial consultation and examination involved the routine
assessment of serum 25-hydroxy vitamin D concentra-
OPEN ACCESS
P. A. Oakley et al. / J. Biomedical Science and Engineering 6 (2013) 12-15 13
tion (ng/ml). This was referred out to a local blood lab.
Vitamin D blood levels were investigated for differences
in gender, height, weight, BMI, race and age and also
how these population averages compare to “normal”
(32 ng/ml) [3], “insufficient” (20 - 30 ng/ml) [4] and
“deficient” (<20 ng/ml) [4,5] values.
3. RESULTS
The 106 patient files review consisted of 61 females and
45 males (Table 1). The average age was 58.6 (±9.3)
years, height was 171.2 cm (±9.7), weight was 95.5 kg
(±20.0), and BMI was 32.6 (±6.2). The average serum
25-hydroxy vitamin D concentration was 24.5 ng/ml
(±9.2). Twenty-one percent, 39% and 35% of the sample
fell into categories of normal (32 ng/ml), insufficient
(20 - 30 ng/ml), and deficient (<20 ng/ml), respectively.
Two-way analysis of variance as a function of race
and gender displayed only statistically significant gender
differences. As there were few Asians in our sample (n =
5), only Blacks and Caucasians were considered for ra-
cial difference. There were no statistically significant
differences in vitamin D between race (F = 1.59, p = 0.21)
nor was there a gender by race interaction. In other
words there was no differential gender effect between the
races. When height is covaried; that is, the correlation
between vitamin D levels and height is first removed,
there is still no emergence of racial differences or racial
by sex interactions.
To discern potential hidden variables, partial correla-
tions were completed. Vitamin D levels were signifi-
cantly correlated negatively with BMI (rho = 0.21, p <
0.05) (Figure 1) and positively correlated with height
(rho = 0.25, p < 0.05) (Figure 2).
Since gender was the only primary and persistent sta-
tistically significant effect, one-way analyses were com-
pleted for each variable. Only height and BMI were sig-
nificant statistically, where males were taller (F = 34.9, p
< 0.01) and had a greater BMI (F = 5.9, p < 0.05).
4. DISCUSSION
We explored the relationship of serum 25-hydroxyvita-
Table 1. Mean, standard deviation, minimum, and maximum
values for age (years), height (cm), weight (kg), BMI (kg/m2),
and serum 25-hydroxyvitamin D concentration (d level: ng/ml).
Va ri a b l e Mean Std. Dev. Minimum Maximum
Age (yrs) 58.6 9.3 35.0 80.0
Height (cm) 171.2 9.7 147.3 195.6
Wei g ht ( kg ) 95.5 20.0 58.5 150.6
BMI (kg/m2) 32.6 6.2 21.8 53.6
d level (ng/ml) 24.5 9.2 7.0 45.5
2
Figure 1. Body mass index (kg/m
2) vs serum 25-hydroxyvi-
tamin D concentration (ng/ml) were significantly correlated rho
= 0.21, p < 0.05.
Figure 2. Height (cm) vs serum 25-hydroxyvitamin D concen-
tration (ng/ml) were significantly correlated rho = 0.25, p < 0.05.
min D concentrations in a random sample of 106 t2DM
patients who presented to a functional medicine diabetes
reversal program during the years 2011 and 2012 from a
clinic located in Annapolis, Maryland, USA. All the pa-
tients had been diagnosed with adult onset, type 2 Dia-
betes Mellitus by either their primary medical doctor or
an endocrinologist.
A conservative recommendation for serum 25-hy-
droxyvitamin D concentration is 32 ng/ml [3]. Our sam-
ple average was well below this level, in fact, only 22/
106 (21%) had healthy levels. Thirty nine percent of the
sample (41/106) were “insufficient”, and alarmingly, one
third were outright “deficient” 37/106 (35%). Thus, over-
all 74% (78/106) of our entire sample had clinically sig-
nificantly low vitamin D levels.
Although there may be debate as to an actual single
optimal vitamin D level, if we consider a normal “func-
tional” range between 30 to 74 ng/ml, (suppose an aver-
age of 52 ng/ml; SD = 11), relative to this our population
would be 2.75 Standard deviations below the normal
mean level. These results coincide with the findings of
others finding very low vitamin D levels in groups of
diabetic patients [6-8].
Considering vitamin D deficiency increases the risk of
all-cause and cardiovascular mortality in t2DM patients
Copyright © 2013 SciRes. OPEN ACCESS
P. A. Oakley et al. / J. Biomedical Science and Engineering 6 (2013) 12-15
14
[9], this is very concerning. Further, Annapolis, MD is
located at 38˚ latitude, it is alarming to consider the
blood levels of vitamin D in other t2DM patients living
northward and into Canada as latitude effects on vitamin
D status is a well known phenomenon [10].
Our results and others demonstrate that serum vitamin
D levels in t2DM patients are typically low. Vitamin D
has been shown in research to play an important role in
insulin resistance as well as impaired beta cell function,
the main issues with t2DM [11].
Hypovitaminosis D has long been suspected as a risk
factor for glucose intolerance [12]. Once theorized that
glucose tolerance could adversely affect insulin sensitiv-
ity and beta-cell function [13], this was directly proven
by Chiu et al. [12] in 126 glucose-tolerant subjects.
Therefore, the rationale for supplementation of vita-
min D for t2DM patients is substantiated. Vitamin D
supplementation has been proven to reduce the risk of
developing the disease [14], as well as to reverse the
disease state altogether [15-17].
The mechanisms underlying the improvements in
glucose tolerance are less understood, but are thought to
be due to vitamin D’s effects on both insulin production
and sensitivity [12,18]. More specifically, the mecha-
nisms underlying improved glucose response to vitamin
D may lie in potential relationships with improvements
in lean mass, regulation of insulin release, altered insulin
receptor expression and specific effects on insulin action
[19].
There were no racial differences between the Cauca-
sian and black samples as may be expected [20,21]. This
is undoubtedly due to the fact that our entire sample of
t2DM patients had very low levels of vitamin D (mean
24 ng/ml), and as discussed this very population typically
has low levels despite racial orientation.
It was determined that the taller the patient, the greater
the vitamin D levels in our sample (rho = 0.25, p < 0.05).
Height is not expected to correlate to vitamin D status for
any rationale reason and because of this, we assume that
although statistically significant, this is merely a coinci-
dental finding in our particular sample.
Our sample did not demonstrate any significant age
and vitamin D level association. Age, however would be
expected to negatively correlate with vitamin D status
since older individuals are less efficient at producing
vitamin D in sunlight as opposed to younger individuals
as well as the fact that older individuals kidneys are less
able to convert vitamin D into its active form [22].
BMI was negatively correlated with vitamin D (rho =
0.21, p < 0.05); that is, the greater the BMI of the pa-
tient the less their vitamin D level. Both obesity and hy-
povitaminosis D are each mutually exclusive predictors
for t2DM [23,24]. Further each has an exacerbated ef-
fect on the other. Gonzalez-Molero et al. (2013) [23] for
example, determined that subjects with vitamin D defi-
ciency were significantly associated with developing ob-
esity within the next four years. Alternatively, those who
are obese have greater requirements for vitamin D [24].
Obesity and vitamin D deficiency may work synergis-
tically to propel an individual into the diseased state of
t2DM. The average BMI in our sample was 32.6 (6.2),
which by definition is on average, an obese group (BMI
> 30). The average vitamin D level in our group was 24.5
ng/ml (9.2), very clinically low.
Ou et al. (2011) [24] determined the optimal concen-
tration of serum 25OHD to be 40 ng/ml in order to opti-
mize insulin sensitivity. In our sample 100/106 (94%)
had vitamin D levels at or below this optimal cut-off
level.
Because the overweight and obese with hypovitami-
nosis D may benefit more than normal weight subjects,
the use of vitamin D supplementation as first-line treat-
ment would be logical. In fact, it has been determined
that an increase in vitamin D serum levels from 10 to 30
ng/ml increases insulin sensitivity by 60% [12]. As Chiu
et al. [12] note, a 60% improvement in insulin sensitivity
is more potent than the medications of troglitazone (54%
improvement [25]) and metformin (13% improvement
[25]).
As this study demonstrates that the majority of people
with t2DM suffer from inadequate amounts of vitamin D,
vitamin D testing should be routine for all people at risk
for t2DM, pre-diabetics and those currently suffering
with t2DM in order to elevate levels sufficiently to im-
prove insulin sensitivity and improve long-term out-
comes [15-18,26].
It should be no surprise that those at risk for diabetes
are the same as those at risk for low vitamin D including
the elderly, those living indoors, dressing in a covered-up
style, dark-skinned individuals, and the obese [22,27].
The evidence has become overwhelming for the safe,
cost-effective addition for vitamin D supplementation as
a first line approach in the treatment and management of
type 2 diabetes. Large scale, well-controlled clinical tri-
als assessing the effects of vitamin D treatment in this
disorder are overdue and warranted.
5. CONCLUSION
Type 2 Diabetes Mellitus patients typically have low
vitamin D serum levels that perpetuate and worsen
patient outcomes. Large scale, well-controlled clinical
trials assessing the effects of vitamin D treatment in this
disorder are overdue and warranted.
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... p < 0.05). 20 The inverse relationship between vitamin D and obesity may be multifactorial -genetic, increased metabolic clearance, negative feedback, and reduced production due to relatively lesser exposure to sunlight. 21 ...
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The potential relationship between vitamin D (VitD) status and metabolic control in patients with type 2 diabetes mellitus (T2DM) warrants further study. We aimed to evaluate the relationship between the serum 25-hydroxyvitamin D [25(OH)D] level and various parameters in patients with T2DM. We analyzed retrospectively data from 276 Korean patients with T2DM whose serum 25(OH)D level was measured in our hospital. Nondiabetic healthy subjects who visited the hospital for health screening were selected as the control group (Non-DM, n=160). Compared with control subjects, patients with T2DM had a lower serum 25(OH)D level (15.4±0.5 vs. 12.9±0.4 ng/ml, p<0.01). Eleven percent of T2DM patients were VitD "insufficient" (20-29 ng/ml) and 87% of the patients were VitD "deficient" (<20 ng/ml). The serum 25(OH)D level was significantly related to serum fibrinogen, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ferritin, the urine albumin creatinine ratio, and hemoglobin A(1C) (HbA1C). In a multivariate logistic regression analysis, high levels of HbA1C, TG, and LDL-C were independently associated with VitD deficiency in T2DM patients. The results of the present study show that the majority of Koreans with T2DM are VitD deficient, and the serum 25(OH)D level in patients with T2DM is related to lipid and glucose parameters. Further studies are required of the relationship of VitD with fibrinogen and other related parameters.
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African Americans have lower vitamin D levels and reduced health outcomes compared to white Americans. Vitamin D deficiency may contribute to adverse health outcomes in African Americans. We hypothesized that race would be associated with vitamin D status and testing in African Americans veterans, and that vitamin D status is a major contributor to health care costs in African American veterans compared to white veterans. A retrospective analysis of the medical data in the Veterans Integrated Service Network 9 (southeastern United States) was performed, and 14148 male veterans were identified. Race was designated by the patient and its relationship to vitamin D levels/status and costs was assessed. Vitamin D levels were significantly lower and the percent of patients with vitamin D deficiency was significantly higher in African American veterans. This difference was independent of latitude and seasonality. Vitamin D testing was done significantly more in white veterans compared to African American veterans (5.4 % vs 3.8 %). While follow-up testing was 42% more likely if a patient was found to be vitamin D deficient, white veterans were 34% more likely than African American veterans to have at least 1 follow-up 25-hydroxyvitamin D performed. African American veterans had significantly higher health care costs, which were linked to lower vitamin D levels; however, the cost differential persisted even after adjusting for vitamin D status. Vitamin D deficiency is highly prevalent in African American veterans and needs improved management within the Veteran Administration system. Vitamin D status appears not to be the sole contributor to increased health care costs in African-American veterans.
Article
A cross-sectional survey was carried out in a New Zealand Polynesian and Caucasian workforce of 5677 staff aged 40–64 years to determine whether serum concentrations of 25-hydroxyvitamin D3 are altered in people with newly diagnosed diabetes mellitus and impaired glucose tolerance (IGT). Serum 25-hydroxyvitamin D3 concentration was significantly lower in newly detected cases with diabetes and IGT (n = 238) compared with controls individually matched by sex, age (± 2 years), ethnicity, and date of interview (mean (S.D.): 69 (31) vs. 76 (34) nmol/l; P = 0.0016). Among controls, serum concentrations were significantly lower in Maori (mean (S.E.) = 65 (5) nmol/l; P = 0.0013) and Pacific Islanders (59 (4) nmol/l; P = 0.0001) compared with Europeans (82 (3) nmol/l), after adjusting for age, sex, and time of year. We conclude that diabetes and IGT are associated with low serum concentrations of 25-hydroxyvitamin D3 and that low concentrations of this hormone in New Zealand Polynesians may partly explain their increased prevalence of diabetes/IGT compared with Europeans.
Article
African Americans suffer disproportionately from diabetes and cardiovascular disease and are significantly more likely to have suboptimal concentrations of circulating 25-hydroxyvitamin D [25(OH)D]. The results of epidemiologic and observational studies suggest that there is a link between vitamin D deficiency and the risk of cardiometabolic disorders, which underscores the importance of maintaining healthy concentrations of 25(OH)D. The objective was to investigate whether daily supplementation with 4000 IU vitamin D(3) for 1 y would eliminate any disparities in circulating concentrations of 25(OH)D between African American and white men. Serum concentrations of 25(OH)D were measured every 2 mo in 47 subjects who received a daily oral dose of 4000 IU vitamin D(3) for 1 y. More than 90% of African Americans had serum concentrations of 25(OH)D <32 ng/mL, and approximately two-thirds had serum concentrations <20 ng/mL. Furthermore, there were significant disparities in serum concentrations of 25(OH)D between African American and white men. Supplementation with 4000 IU/d for 1 y eliminated any significant differences in circulating concentrations of 25(OH)D between African American and white men. The results of this clinical study show the feasibility and efficacy of this approach in the elimination of hypovitaminosis D, which is a widespread health disparity among African Americans. This trial was registered at clinicaltrials.gov as NCT01045109.
Article
Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
Article
Combination therapy is logical for patients with non-insulin-dependent (type 2) diabetes mellitus, because they often have poor responses to single-drug therapy. We studied the efficacy and physiologic effects of metformin and troglitazone alone and in combination in patients with type 2 diabetes. We randomly assigned 29 patients to receive either metformin or troglitazone for three months, after which they were given both drugs for another three months. Plasma glucose concentrations during fasting and postprandially and glycosylated hemoglobin values were measured periodically during both treatments. Endogenous glucose production and peripheral glucose disposal were measured at base line and after three and six months. During metformin therapy, fasting and postprandial plasma glucose concentrations decreased by 20 percent (58 mg per deciliter [3.2 mmol per liter], P<0.001) and 25 percent (87 mg per deciliter [4.8 mmol per liter], P<0.001), respectively. The corresponding decreases during troglitazone therapy were 20 percent (54 mg per deciliter [2.9 mmol per liter], P=0.01) and 25 percent (83 mg per deciliter [4.6 mmol per liter], P<0.001). Endogenous glucose production decreased during metformin therapy by a mean of 19 percent (P=0.001), whereas it was unchanged by troglitazone therapy (P=0.04 for the comparison between groups). The mean rate of glucose disposal increased by 54 percent during troglitazone therapy (P=0.006) and 13 percent during metformin therapy (P= 0.03 for the comparison within the group and between groups). In combination, metformin and troglitazone further lowered fasting and postprandial plasma glucose concentrations by 18 percent (41 mg per deciliter [2.3 mmol per liter], P=0.001) and 21 percent (54 mg per deciliter [3.0 mmol per liter], P<0.001), respectively, and the mean glycosylated hemoglobin value decreased 1.2 percentage points. Metformin and troglitazone have equal and additive beneficial effects on glycemic control in patients with type 2 diabetes. Metformin acts primarily by decreasing endogenous glucose production, and troglitazone by increasing the rate of peripheral glucose disposal.
Article
Both obesity and type 2 diabetes are associated with hypovitaminosis D. We investigated the impact of body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin sensitivity. This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) and beta-cell function were assessed by using hyperglycaemic clamps. Serum 25OHD concentration was determined in the fasting samples. The correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 0·5271, P < 0·0001) than in the normal weight group (r = 0·2836, P = 0·002). The correlation remained significant in the overweight group (r = 0·3620, P = 0·002), but not in normal weight group after adjusting for age, gender, BMI, season of study, ethnicity and exercise. Nonlinear regression analysis revealed that when serum 25OHD concentration was > 40 ng mL(-1), the association between serum 25D concentrations and insulin sensitivity plateaued. We observed stronger associations of serum 25OHD with insulin sensitivity in overweight than normal weight subjects, suggesting that overweight subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects. Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL(-1). As more than 60% of the US population is overweight and hypovitaminosis D is highly prevalent in overweight subjects, hypovitaminosis D has a large population attributable risk for type 2 diabetes.