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1420
Effect of Vitamin D
Supplementation on Glycemic
Control in Patients With Type 2
Diabetes (SUNNY Trial): A
Randomized Placebo-Controlled
Trial
OBJECTIVE
Low vitamin D status has been associated with impaired glycemic control in
patients with type 2 diabetes. The purpose of our study was to evaluate the effect of vitamin D supplementation on glycemic control in patients with type 2
diabetes.
RESEARCH DESIGN AND METHODS
1
Department of Internal Medicine, Medical Center Alkmaar, Alkmaar, the Netherlands
2
Department of Clinical Chemistry, Medical Center Alkmaar, Alkmaar, the Netherlands
3
Amsterdam Rheumatology and Immunology
Center, VU University Medical Center, Amsterdam,
the Netherlands
4
Department of Epidemiology and Biostatistics,
EMGO Institute for Health and Care Research,
VU University Medical Center, Amsterdam, the
Netherlands
5
Department of General Practice, DIAZON,
Alkmaar, the Netherlands
6
Department of Internal Medicine/Endocrinology,
VU University Medical Center, Amsterdam, the
Netherlands
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All participants were randomized according to either an oral dose of cholecalciferol 50,000 IU once a month or an
identically looking placebo 50,000 IU
once a month for 6 months (Meander
Medical Center, Amersfoort, the Netherlands). The patients were randomized
1:1 according to the method of block
randomization with a block size of 10.
No stratication was used. The randomization procedure was performed by the
pharmacist. The participants and the research team remained blinded till the
end of the study.
Outcome Measures
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Statistical Analysis
Figure 1Participant owchart. *Most patients did not meet the inclusion criteria because of
insulin therapy; criteria for premature termination of the trial: increase of HbA1c (n = 5), change in
antidiabetic medication (n = 10), or serum 25(OH)D ,15 or .150 nmol/L (n = 2). ITT, intent to treat.
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Demographic parameters
Male, n (%)
Age (years)
Diabetes duration (years)
White skin color, n (%)
Antidiabetic treatment, n (%)
Lifestyle adjustments
Metformin
SU derivatives
Metformin + SU derivatives
Microvascular complications $1, n (%)*
Cardiovascular disease, n (%)
Current smoker, n (%)
Alcohol use #2 units/day, n (%)
Dairy intake $2 units/day, n (%)
Fish intake .1 servings/week, n (%)
Vitamin D supplements, n (%)
Exposure to sun, n (%)
,5 h/week
510 h/week
.10 h/week
Physical activity, n (%)
,2 h/week
25 h/week
.5 h/week
Season of blood collection, n (%)
Spring
Summer
Autumn
Winter
Clinical characteristics
BMI (kg/m2)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Waist circumference (cm), median (IQR)
Fasting glucose (mmol/L)
Fasting insulin (mU/L)
HbA1c (%/mmol/mol)
HOMA-IR, median (IQR)
QUICKI
HOMA-B, median (IQR)
Cholesterol (mmol/L)
HDL cholesterol (mmol/L), median (IQR)
Triglycerides (mmol/L), median (IQR)
LDL cholesterol (mmol/L)
Total cholesterol-to-HDL ratio (mmol/L)
Serum 25(OH)D (nmol/L)
Serum creatinine (mmol/L)
Serum calcium (mmol/L), median (IQR)
Serum PTH (pmol/L)
Vitamin D group
(n = 129)
Placebo group
(n = 132)
88 (68)
67 6 8
664
122 (95)
82 (62)
67 6 9
665
122 (93)
4 (3)
91 (71)
3 (2)
31 (24)
35 (27)
35 (27)
18 (14)
114 (88)
85 (66)
45 (35)
18 (14)
7 (5)
75 (57)
5 (4)
45 (34)
16 (12)
48 (36)
19 (14)
114 (86)
100 (76)
56 (42)
12 (9)
50 (39)
57 (44)
22 (17)
52 (39)
59 (45)
21 (16)
40 (31)
56 (43)
33 (26)
38 (29)
67 (51)
27 (20)
15 (12)
31 (24)
63 (49)
20 (15)
12 (9)
32 (24)
64 (45)
24 (18)
28.7 6 4.6
146 6 18
81 6 10
105 (97111)
7.7 6 1.1
15.6 6 9.9
6.8 6 0.5/51 6 6
4.63 (2.616.78)
0.31 6 0.03
64.8 (43.3102.6)
4.4 6 1.0
1.1 (1.01.3)
1.5 (1.12.0)
2.5 6 0.9
3.88 6 1.06
60.6 6 23.3
83 6 18
2.32 (2.282.38)
5.4 6 2.2
28.5 6 4.5
146 6 18
81 6 9
103 (95109)
7.6 6 1.1
16.6 6 10.1
6.8 6 0.5/51 6 5
4.59 (3.17.0)
0.31 6 0.03
66.7 (46.9122.9)
4.4 6 1.0
1.1 (1.01.3)
1.4 (1.02.1)
2.5 6 0.9
3.92 6 1.28
59.1 6 23.2
81 6 18
2.33 (2.282.40)
5.6 6 2.1
Data are presented as mean 6 SD, unless indicated otherwise. *Including nephropathy,
neuropathy, and retinopathy. Maximum dose of 400 IU vitamin D supplement daily before start
of the trial.
association was found between baseline BMI and the change in serum
25(OH)D.
CONCLUSIONS
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Table 2Comparison of characteristics before and after treatment in both groups in A: the entire study population, B: subgroup
of patients with baseline serum 25(OH)D <50 nmol/L, and C: subgroup of patients with serum 25(OH)D <30 nmol/L
Vitamin D group (n = 129)
Placebo group (n = 132)
0 months
6 months
0 months
6 months
P value
P value
,0.01
0.95
0.97
0.85
0.74
0.84
P value
,0.01
0.02
29.8 (26.031.1)
29.6 (26.531.0)
29.8 (27.630.5)
29.1 (28.030.8)
0.62
8.0 (7.08.3)
14.7 6 6.8
4.27 (3.336.75)
7.9 (6.910.2)
15.1 6 8.0
5.38 (3.057.17)
7.2 (6.38.2)
22.0 6 13.6
5.10 (3.919.47)
8.1 (6.68.3)
24.9 6 14.8
7.94 (3.7111.66)
0.40
0.58
0.87
0 months
6 months
0 months
6 months
6 months
6 months
Data are expressed as mean 6 SD, unless otherwise stated. Signicance between groups was tested with linear regression analysis. *Analyses based
on natural logarithms. Analyses adjusted for baseline value, age, BMI, ethnicity, sex, and season of measurement. Analyses adjusted for baseline
value, age, and season of measurement.
of oral vitamin D3 supplementation on glycemic control was investigated in patients with well-controlled type 2
diabetes. We did not nd a signicant
effect of vitamin D supplementation on
glycemic control and metabolic prole in
the entire study population, despite a
signicant increase in serum 25(OH)D
in patients who received vitamin D. A signicant effect of vitamin D supplementation on HbA1c was seen after 6 months in
severe vitamin Ddecient patients.
However, despite adjusting for the baseline HbA1c value, this signicant result
may be explained by the imbalance in
the baseline HbA1c value between the
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