Daily consumption of vitamin D or vitamin D + calciumfortied yogurt

drink improved glycemic control in patients with type 2 diabetes:

a randomized clinical trial
13
Bahareh Nikooyeh, Tirang R Neyestani, Maryamosadat Farvid, Hamid Alavi-Majd, Anahita Houshiarrad, Ali Kalayi,
Nastaran Shariatzadeh, Aazam Gharavi, Soudabeh Heravifard, Nima Tayebinejad, Shabnam Salekzamani,
and Malihe Zahedirad
ABSTRACT
Background: Low serum concentrations of 25-hydroxyvitamin D
[25(OH)D] have been associated with impaired glucose tolerance
and diabetes.
Objective: This study aimed to compare the effects of daily intake
of vitamin D or vitamin D
3
+ calciumfortied yogurt drink on
glycemic status in subjects with type 2 diabetes (T2D).
Design: Ninety diabetic subjects were randomly allocated to 3
groups to consume plain yogurt drink (PY; containing no vitamin
D and 150 mg Ca/250 mL), vitamin Dfortied yogurt drink (DY;
containing 500 IU vitamin D
3
and 150 mg Ca/250 mL), or vitamin
D + calciumfortied yogurt drink (DCY; containing 500 IU vita-
min D
3
and 250 mg Ca/250 mL) twice per day for 12 wk. Fasting
serum glucose (FSG), glycated hemoglobin (Hb A
1c
), homeostasis
model assessment of insulin resistance (HOMA-IR), serum lipid
prole, and percentage fat mass (FM) were assessed before (base-
line) and after the intervention.
Results: In both the DY and DCY groups, mean serum 25(OH)D
3
improved (+32.8 6 28.4 and +28.8 6 16.1 nmol/L, respectively;
P ,0.001 for both), but FSG [212.9 633.7 mg/dL (P = 0.015) and
29.6 6 46.9 mg/dL (P = 0.035)], Hb A
1c
[20.4 6 1.2% (P ,
0.001) and 20.4 6 1.9% (P , 0.001)], HOMA-IR [20.6 6 1.4
(P = 0.001) and 20.6 6 3.2 (P , 0.001)], waist circumference
(23.6 6 2.7 and 22.9 6 3.3; P , 0.001 for both), and body mass
index [in kg/m
2
; 20.9 6 0.6 (P , 0.001) and 20.4 6 0.7 (P =
0.005)] decreased signicantly more than in the PY group. An in-
verse correlation was observed between changes in serum 25(OH)
D
3
and FSG (r = 20.208, P = 0.049), FM (r = 20.219, P = 0.038),
and HOMA-IR (r = 20.219, P = 0.005).
Conclusion: Daily intake of a vitamin Dfortied yogurt drink,
either with or without added calcium, improved glycemic status
in T2D patients. This trial was registered at clinicaltrials.gov as
NCT01229891. Am J Clin Nutr 2011;93:76471.
INTRODUCTION
Vitamin D deciency is still a global health care concern. A
growing number of studies have reported widespread vitamin D
deciency and insufciency in both apparently healthy pop-
ulations and patients with various pathologies (1). It has been
estimated that 1 billion people worldwide are affected by various
degrees of vitamin D deciency (2).
Diabetes is the most prevalent endocrinologic disorder in the
world. The total number of people with diabetes worldwide is
estimated to increase from 171 million in 2000 to .366 million
by 2030 (3). Type 2 diabetes (T2D) is associated with increased
morbidity and mortality and hence with accelerated health care
costs. It can result in many long-term micro- and macrovascular
complications clinically presented as blindness, kidney disease,
heart disease, and neuropathy, among others. Persons with di-
abetes are 4 times as likely to have heart disease as are those
without diabetes (4).
Since the rst report on the inuence of vitamin D on insulin
secretion (5), which was further supported by animal studies (6,
7), evidence has proposed a role for vitamin D in both the oc-
currence (8, 9) and treatment (10, 11) of T2D. There is now
convincing evidence that vitamin D has some role in both
pancreatic insulin secretion (11, 12) and insulin sensitivity (10)
and thereby affects the pathogenesis of the disease.
The role of calcium in the development of T2D has been
indirectly suggested by cross-sectional studies in which a high
calcium intake has been found to be inversely associated with
body weight and adiposity (13). Note that adequate calcium
intake could indirectly lead to an improvement in vitamin D
status because there would be less need for conversion of 25-
hydroxyvitamin D [25(OH)D] to 1,25-dihydroxyvitamin D (14).
Accordingly, cohort studies have documented associations of
dietary calcium and vitamin D intake with a reduced risk of
subsequent diabetes (15). These observations have led to the idea
that amelioration of glycemic status could be achieved by an
1
From the Laboratory of Nutrition Research, National Research Institute
and Faculty of Nutrition and Food Technology, Shahid Beheshti University
of Medical Sciences, Tehran, Iran (BN, TRN, MF, HA-M, AH, AK, NS, AG,
SH, NT, SS, and MZ), and the Department of Biostatistics, Shahid Beheshti
University of Medical Sciences, Tehran, Iran (HA-M).
2
Supported by the National Nutrition and Food Technology Research
Institute. The yogurt drinks were produced and donated by the Dairy In-
dustries of Iran (Pegah Company).
3
Address correspondence to TR Neyestani, Laboratory of Nutrition Re-
search, National Research Institute and Faculty of Nutrition and Food Tech-
nology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
E-mail: t.neyestani@nnftri.ac.ir or neytr@yahoo.com.
Received October 29, 2010. Accepted for publication December 28, 2010.
First published online February 2, 2011; doi: 10.3945/ajcn.110.007336.
764 Am J Clin Nutr 2011;93:76471. Printed in USA. 2011 American Society for Nutrition

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improvement in vitamin D and calcium status in patients with
T2D.
The high prevalence of vitamin D deciency (1618), the
metabolic syndrome (18), and T2D (19) in Iran warrants an
immediate population-based intervention. Some studies in Iran
have shown a high occurrence of vitamin D deciency in both
patients with diabetes and nonpatients with diabetes (20) and in
overweight and obese women with and without the metabolic
syndrome (TR Neyestani et al, unpublished observations, 2010);
no signicant difference in serum 25(OH)D
3
concentrations was
observed between the patients and the healthy control subjects.
The available human data are limited because most, if not all,
observational studies have been cross-sectional, whereas prospective
studies have not measured circulating vitamin D concentration and
there is a paucity of randomized controlled trials with vitamin Dand/
or calcium supplementation specically designed for outcomes
related to T2D (21). Therefore, a clinical trial was conducted in
subjects with T2D to evaluate the possible metabolic effects of
regular intake of calcium and/or vitamin Dfortied dairy product.
In this study, a native popular yogurt drink (Persian name: doogh)
was used for fortication with calcium and/or vitamin D.
SUBJECTS AND METHODS
Study design
The project was conducted during the fall and winter of the
year 20092010 and started in late October and concluded in
early March, during which cutaneous vitamin D
3
synthesis is
minimal (22).
Diabetic subjects registered at the Iranian Diabetes Society
were recruited via phone call. Using data from a previous study
on the vitamin D status of Iranian diabetic patients (20), we
calculated that a sample of 30 subjects in each group would have
90% power to detect a change in means of 25(OH)D of 1 SD
(assuming an effect size of 1).
The inclusion criteria were age 3060 y and a fasting blood
glucose concentration 126 mg/dL at the rst visit. The exclusion
criteria included 1) an inability or unwillingness to participate 2);
intake of vitamin D, calcium, or omega-3 (n23) supplements
within the past 3 mo 3); use of medications that could potentially
inuence vitamin D metabolism (notably estrogens and calcito-
nin) within the past 3 mo 4); any other concomitant clinical
disease that could inuence vitamin D metabolism (eg, renal,
hepatic, other endocrinologic disorders, and malignancies); and 5)
use of insulin or any change in the type or dosage of current
hypoglycemic medications during the intervention period.
After a 2-wk run-in period, the subjects were randomly assigned
to 1 of 3 groups: 1) plain yogurt drink (PY; containing 150 mg Ca/
250 mL and no detectable vitamin D
3
) 2); vitamin Dfortied
yogurt drink (DY; containing 500 IU vitamin D
3
and 150 mg Ca/
250 mL); or 3) vitamin D + calciumfortied yogurt drink (DCY;
containing 500 IU vitamin D
3
and 250 mg Ca/250 mL). The
concentrations of calcium and vitamin D
3
in the yogurt drinks
were determined by a specialized laboratory accredited by the
Deputy of Food and Drug of the Iranian Ministry of Health. Pa-
tients were instructed to consume one serving of the yogurt drink
with both lunch and dinner (ie, 2 servings/d) for 12 wk.
On the rst visit, the objectives and the protocol of the study
were fully described to the subjects before they signed an in-
formed written consent form. Then, a general questionnaire on
demographic data, history of illness, and medication use was
completed. In addition, information on duration of sun exposure
was also gathered. Participants were asked to recall the number of
minutes/hour that they have spent in daylight (23). The subjects
were then asked not to change their lifestyle during the run-in
period or during the study. All of the subjects were visited at
approximately biweekly intervals to both assess their compliance
and to deliver the yogurt drinks for the next 2 wk.
All of the participants were also given a consumption in-
struction manual including a yogurt drink consumption table
that consisted of 28 empty boxes for each week. The patients
were instructed to mount the table where it was readily observed
(eg, on the fridge) and to tick each box after consumption of
a yogurt drink with each meal. They were also asked to keep the
empty bottles and to bring them back on their next visit.
Compliance was assessed by checking the consumption tables,
counting the empty bottles, and making weekly phone calls.
Dietary (24-h recall), anthropometric, and laboratory assessments
were done for all of the participants before (baseline) and after the
intervention period (Figure 1). The study was approved by the
Ethical Committee of the National Nutrition and Food Tech-
nology Research Institute.
Diet
The participants were instructed to followa weight-maintenance
diabetic diet for 2 wk (run-in period) according to American
Diabetes Association (ADA) guidelines (24), after which
FIGURE 1. Summary of the study design. vit, vitamin; Ca-D, calcium +
vitamin D.
VITAMIN D AND GLYCEMIC CONTROL IN DIABETES 765

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equivalent amounts of dairy products in the diet were replaced by
2 servings of the yogurt drink by a dietitian. Dietary intake was
assessed at the beginning and at the end of the intervention
period by using a validated 24-h recall questionnaire (25) for 2 d
(including a weekend).
Anthropometric measures and blood pressure
Weight was measured by using a digital scale to the nearest of
0.1 kg (Seca 808; Seca, Hamburg, Germany) while the partic-
ipants were wearing light clothing and no shoes. Height was
determined with a stadiometer to the nearest of 0.1 cm (Seca).
BMI was calculated as weight (kg)/height
2
(m). WC was mea-
sured at the midpoint between the lower rib and iliac crest at the
end of expiration by using a measuring tape to the nearest of 0.1
cm. Percentage body fat mass (FM) was estimated by using
a bioelectrical impedance analysis (BIA) system (Quadscan
4000; BodyStat, Douglas, United Kingdom). Blood pressure was
measured with a digital system (BC 08; Beurer, Ulm, Germany),
whereas the subject was seated for 10 min. The average of
duplicate measurements was considered for blood pressure. All
measurements were done between 0800 and 1000, whereas the
subjects were fasting and not allowed to smoke.
Laboratory investigations
After 1214 h of fasting, venous blood samples were collected
and kept at room temperature for 3060 min in the dark. The
samples were then centrifuged at 2000 g at room temperature.
Sera recovered and transferred to fresh microtubes in aliquots
were kept at 280C until the day of analysis. Fasting serum
glucose (FSG) and lipid proles were determined by using en-
zymatic methods (Pars-Azmoon, Tehran, Iran) and an auto-an-
alyzer (Selecta E; Vitalab, Holliston, Netherlands) on the same
day of bleeding.
Serum 25(OH)D
3
was assayed by HPLC, as described earlier
(26). In this study, vitamin D status was dened on the basis of
serum concentrations of 25(OH)D
3
as sufcient (50 nmol/L),
insufcient (27.5 to ,50 nmol/L), and decient (,27.5 nmol/L)
(27).
Fasting serum insulin was assayed by immunoradiometric assay
(IRMA) (Biosource, Dorest, Belgium) and a gamma-counter system
(Gamma I; Genesys). Insulin resistance was evaluated by homeostasis
model assessment of insulin resistance (HOMA-IR), which was
calculated by using the following formula: HOMA-IR = [fasting
insulin (mU/L) FSG (mmol/L)]/22.5 (28). Glycated hemoglobin
(Hb A
1c
) was measured by a colorometric method after an initial
separation by ion exchange chromatography (Biosystem, Barcelona,
Spain).
Statistical analyses
Data are expressed as means 6 SDs. The normality of data
distribution was assessed by using the Kolmogorov-Smirnov
goodness-of-t test. Two-factor repeated-measures analysis of
variance (ANOVA) was used to test time group interactions,
with time and treatment as factors. In case of a signicant time
group interaction, a between group comparison of changes at 12
mo was done by using ANOVA followed by Tukeys post hoc
analysis. When the time effect was signicant, the within-group
comparison of values was performed by paired-samples t test
with Bonferroni correction. Differences in proportions were
evaluated by using a chi-square test. Correlations between var-
iables were evaluated by using either Pearson (r) (for data with
normal distribution) or Spearman (r
s
) (for data with nonnormal
distribution) correlations. All statistical analyses were done by
using the Statistical Package for Social Sciences (SPSS version
16; SPSS Inc, Chicago, IL). P , 0.05 was considered signi-
cant.
RESULTS
The subjects included 55 women and 35 men aged 50.7 6
6.1 y. Their mean (6SD) ages (PY: 50.8 6 6.6 y; DY: 51.4 6
5.4 y; and DCY: 49.9 6 6.2 y), durations of disease (PY: 9.5 6
7.1 y; DY: 8.9 6 5.9 y; and DCY: 8.8 6 5.4 y), and sex ratios
were not signicantly different between the groups. All partic-
ipants completed the study, and overall compliance by the
subjects was estimated as being 100%. Categories of vitamin D
status improved overall in the 2 groups (Table 1), which was
accompanied by a signicant increase in serum 25(OH)D
3
concentrations in both the DY and DCY groups (Table 2). In
contrast, serum 25(OH)D
3
in the PY group did not change
signicantly (Table 2).
Suboptimal vitamin Dstatus observed in 70%of the subjects at
baseline in both the DYand DCY groups decreased dramatically
to only 10% and 20% (overall 15%) of the subjects, respectively,
at the end of the intervention. In the PY group, however, the
percentage of the suboptimal vitamin D status did not change
TABLE 1
Comparison of vitamin D status based on serum concentrations of 25-hydroxyvitamin D
3
between the 3 groups
1
Before intervention After intervention
P value
2
Deciency Insufciency Sufciency P value
2
Deciency Insufciency Sufciency
PY [n (%)] 14 (46.7) 10 (33.3) 6 (20) 0.065 18 (60) 7 (23.3) 5 (16.7) ,0.001
DY [n (%)] 6 (20) 15 (50) 9 (30) 0 (0) 3 (10) 27 (90)
DCY [n (%)] 15 (50) 6 (20) 9 (30) 1 (3.3) 5 (16.7) 24 (80)
Total [n (%)] 35 (38.9) 31 (34.4) 24 (26.7) 19 (21.1) 15 (16.7) 56 (62.2)
1
PY, plain yogurt; DY, vitamin Dfortied yogurt drink; DCY, calcium + vitamin Dfortied yogurt drink. Deciency
is dened as ,27.5 nmol/L, insufciency as 27.5 to ,50 nmol/L, and sufciency as 50 nmol/L.
2
Denotes the signicance of differences in the distribution of vitamin D categories between the 3 groups (chi-square
test).
766 NIKOOYEH ET AL

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g
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(
2
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.
VITAMIN D AND GLYCEMIC CONTROL IN DIABETES 767

b
y

g
u
e
s
t

o
n

A
p
r
i
l

1
9
,

2
0
1
3
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n
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t
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w
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l
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a
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d

f
r
o
m

signicantly from the beginning (80%) to the end of the study
(83.3%) (Table 1).
The time effects were statistically signicant on weight, BMI,
WC, and waist-to-hip ratio (all P , 0.001). The time group
interaction effects on weight, BMI, WC (all P , 0.001), FM
(P = 0.001), FSG (P = 0.010), insulin, HOMA-IR, and Hb A
1c
(all
P , 0.001) were signicant.
Both the DYand DCY groups had signicantly lower weight,
BMI, and WCat the end of the intervention than did the PYgroup
and compared with baseline values. FSG (P = 0.024), insulin
(P , 0.001), HOMA-IR (P , 0.001), and Hb A
1c
(P , 0.001)
all increased signicantly after 12 wk in the PY group; however,
these variables did not change remarkably in the DCY group and
only in the DY group were the decrements in serum glucose (P =
0.04) and HOMA-IR (P = 0.032) signicant. However, ANOVA
of changes within groups showed a signicant decrease in serum
glucose, insulin, HOMA-IR, and Hb A
1c
in both the DY and
DCY groups compared with the PY group (Table 2). The serum
lipid prole, except for serum triglycerides, did not change
signicantly, either within or between groups. Note that only 8
subjects were taking statins (n = 3, 3, and 2 in groups 1, 2, and 3,
respectively). No adjustments were made for this for 2 reasons.
First, the distribution of statin consumers was comparable
between groups; second, no signicant change in serum cho-
lesterol was observed with supplementation nor was a correla-
tion between serum 25(OH)D
3
and cholesterol concentrations
observed before or after supplementation.
No signicant within- or between-group differences in intakes
of energy, macronutrients, calcium, or vitamin D were observed
at baseline or after the intervention period, except for the extra
calcium (only in group 3) and vitamin D (in groups 2 and 3)
intakes provided by the fortied yogurt drink (Table 3).
Overall, a signicant inverse association was found between
changes in serum 25(OH)D
3
and changes in weight (r = 20.331,
P = 0.001), BMI (r = 2358, P = 0.001), FM (r = 20.219, P =
0.038), FSG (r = 20.208, P = 0.049), serum insulin (r = 20.308,
P = 0.003), HOMA-IR (r
s
= 20.219, P = 0.005), and Hb A
1c
(r = 20.215, P = 0.042).
DISCUSSION
The present investigation showed that improvement in the
vitamin D status of T2D patients is benecial for glycemic
optimization and weight control. Fortication of a yogurt drink
with calcium did not confer further improvement. We found
a high occurrence of subclinical vitamin D deciency (73.3%)
and a considerable proportion of severe deciency (38.9%) in our
diabetic subjects. To date, there is no consensus on the optimal
concentration of serum 25(OH)D
3
. However, a wide range be-
tween 50 and 100 nmol/L has been proposed as optimal (2). The
daily intake of cholecalciferol needed to reach this concentration
is likely to be much higher than the recommended 400600 IU/
d for adults (29). In this study, 1000 IU/d in 2 divided doses was
used, which is, on the basis of current knowledge, believed to be
safe (30). This dose was effective at achieving a serum 25(OH)
D
3
concentration .50 nmol/L in most subjectsa concentration
considered optimal by many experts (31, 32). Because of its
high popularity in Iran, a yogurt drink seemed to be a good
dairy product for vitamin D fortication and an appropriate re-
placement for milk, when not consumed for any reason. No T
A
B
L
E
3
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+
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(
k
c
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/
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)
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differences in calcium and vitamin D intakes or in the duration
of sun exposure were observed between the 3 groups; therefore,
the improvement in vitamin D status was due to the intervention.
Anthropometric measures
Our nding on the effect of the daily intake of a vitamin D
fortied yogurt drink (with or without added calcium) on body
weight, FM, and WC is noteworthy. Few previous studies have
reported the effect of vitamin D supplementation on weight, and
the results are contradictory (33, 34). However, several clinical
studies have reported the preventive effect of increasing calcium
intake against the risk of overweight (35). On the other hand,
vitamin D supplementation had a small effect on the prevention
of weight gain (36). The weight-lowering effect of vitamin D
could be indirectly due to its suppressing effect on parathyroid
hormone, which is known to promote fat accumulation by in-
creasing intracellular calcium concentrations (36). Previous
cross-sectional studies have shown that 25(OH)D concentrations
are associated with body-composition variables, especially body
fat (37). In agreement with this, our ndings showed a strong
inverse association between serum 25(OH)D
3
concentrations and
FM or WC. The excess fat, by sequestering vitamin D, makes it
less available for use by the body (38). On the other hand, vi-
tamin D supplementation had a small effect on the prevention of
weight gain (39). The possible effects of vitamin D on adipocyte
and weight gain remain to be claried.
Lipid prole
Despite a relatively healthy lipid prole in our subjects, a slight
nonsignicant improvement in serum concentrations of choles-
terol and a signicant reduction in serum triglycerides were seen
at 12 wk in the DCY group compared with the PY group. It is
hypothesized that an increase in calcium intake can reduce serum
triglycerides by decreasing hepatic triglyceride formation and/or
secretion via an effect on hepatocellular calcium (40). The effect
of vitamin D and calcium intake on lipid prole in dyslipidemic
subjects needs to be investigated further.
Glycemic status
The rationale for vitamin D treatment in patients with T2D is
based on studies that suggest that vitamin D may have some role
in insulin secretion and/or sensitivity (41). Data from several
studies have shown that hypovitaminosis D might play an im-
portant role in the pathogenesis of T2D (42). In cross-sectional
studies, lower serum 25(OH)D concentrations have been asso-
ciated with an increased risk of developing T2D (9, 15, 43), and
serum 25(OH)D
3
concentrations have been correlated negatively
with glucose and insulin concentrations and also with insulin
resistance (9, 10). Interventional studies investigating vitamin D
supplementation alone or in combination with calcium for the
prevention or treatment of T2D have shown minimal effects, and
the results of these studies in humans have been inconsistent (11,
21, 44, 45).
A large 20-y observational study reported a decreased in-
cidence of T2D in women taking vitamin D and calcium sup-
plements (15). However, a randomized placebo-controlled trial
did not show a reduction in the development of T2D with vitamin
D and calcium supplementation (43). However, despite a similar
calcium dosage in both studies, the dosage of vitamin D in the
clinical trial (400 IU) was much lower than that in the obser-
vational study (800 IU).
The results of the longest and largest vitamin D treatment
studies were reported by Pittas et al (44). A post hoc analysis of
a 3-y trial designed to assess the effects of vitamin Dplus calcium
in 314 elderly persons without diabetes found that the increase in
fasting blood glucose concentrations during the study was lower
with vitamin D therapy than with placebo, but only in the group
that had impaired fasting glucose at baseline. Insulin resistance,
as assessed by HOMA-IR, increased in the placebo group, but not
in the vitamin D group (44). It is not possible to determine
whether the observed effect was related to vitamin D therapy,
calcium therapy, or both, because only combination therapy was
given.
Previous studies had many possible limitations, such as a small
sample size (46), inclusion of subjects with or without diabetes
(47), the lack of a control group (48), a short intervention period
(46, 47), the use of a low dose of vitamin D (47), and low
bioavailability from supplements (46, 47). To eliminate the
aforementioned limitations, we enrolled a sufcient number of
subjects to detect changes with adequate power in a double-blind
randomized clinical trial. Our nding of benecial effects of
vitamin D supplementation on glucose homeostasis in T2D are
supported by evidence that calcium and vitamin D improve
factors contributing to the development of T2D (pancreatic b cell
function, insulin sensitivity, and inammation) (21). For in-
stance, glucose-stimulated insulin secretion is impaired in islets
from vitamin Ddecient rats (49). Administration of small
doses of 1,25-dihydroxyvitamin D
3
to vitamin Ddecient rats
led to restoration of insulin secretion (41). The effect of vitamin
D on insulin secretion (21, 50) and action (21, 51, 52) may be
mediated either directly or indirectly.
Our nding of decreased insulin resistance in the DYand DCY
groups indicates an improvement in the glucose-stimulated in-
sulin response (21, 41, 49). Consistent with our ndings, a recent
study reported that vitamin D supplementation can improve
insulin resistance and decrease fasting insulin (53).
Evidence of an association between vitamin D deciency and
insulin resistance is limited, but the reports of the effect of vi-
tamin D supplementation on insulin resistance from short-term,
nonrandomized, uncontrolled human trials are conicting (11,
12, 54). Extrapolation from the observations in the current study
suggests that increasing 25(OH)D
3
from 45 to 76 nmol/L can
improve insulin sensitivity by 13.3%, which is comparable with
the effect of metformin (55). Of particular interest, after ad-
justment for FM and weight, the correlation between changes in
serum 25(OH)D
3
and glycemic markers disappeared. However,
in an analysis of covariance, differences in changes in FSG
(P = 0.015, P = 0.049 respectively), insulin (both P , 0.001),
and HOMA-IR (P ,0.001, P = 0.002, respectively) between the
DY or DCY and PY groups after adjustment for FM remained
signicant. These ndings indicate both the direct and indirect
glycemic optimizing effects of vitamin D in our subjects.
To the best of our knowledge, this is the rst report of
a controlled clinical trial in diabetic patients to evaluate the
effects of daily vitamin D, with or without calcium supple-
mentation, in the form of a fortied yogurt drink, on anthro-
pometric, metabolic, and glycemic status. In conclusion, daily
intake of a yogurt drink fortied with cholecalciferol, either with
VITAMIN D AND GLYCEMIC CONTROL IN DIABETES 769

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or without added calcium, for 12 wk improved the anthropo-
metric and glycemic status in the subjects with T2D. Our ndings
indicated both the direct (on insulin secretion and insulin sen-
sitivity) and indirect (by decreasing weight and FM) glycemic
optimizing effects of vitamin D. Therefore, replenishment of
vitamin D might be taken into consideration as a preventive
nutritional strategy against development and as an adjunct
treatment of diabetes.
However, this study had some limitations. The changes ob-
served after the 12-wk intervention period do not necessarily
reect the long-term outcomes of the daily consumption of
a fortied yogurt drink. Moreover, no practical approach was
used to control intake of the yogurt drinks; intakes were reported
by the subjects. A strength of this study was that the expected
increases in serum 25(OH)D indicated satisfactory compliance
with supplementation by the study subjects.
Our ndings have potentially important public health impli-
cations, because the modest effect of vitamin D intake on an-
thropometric and glycemic status in individual persons translates
to a dramatic effect in the population as a whole because the high
prevalence of hypovitaminosis D carries an attributable risk of
T2D and the metabolic syndrome.
We acknowledge the Iranian Diabetes Society for their cooperation, with
special thanks to its head, Asadollah Rajab. We also appreciate all of the sub-
jects who participated in this study. All of the laboratory bench work was
conducted at the Laboratory of Nutrition Research.
The authors responsibilities were as followsTRN and MF: designed and
supervised the study. TRN, MF, and BN: were involved in all stages of the
research, including all laboratory bench work; HA-M: supervised the estima-
tion of the sample size and the statistical analyses; AK and NS: were involved
in the anthropometric measures and laboratory assays; AG: performed the
HPLC analyses; AH: supervised the dietary assessments; and SH, NT, SS,
and MZ: recruited the subjects, arranged the visits, instructed the patients,
and conducted the follow-up. None of the authors declared a conict of interest.
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