Association between 25-Hydroxyvitamin D Levels and Glycemic Status-Juniper Publishers
Abstract
Aim: A significant body of literature supports that 25(OH) vitD deficiencies is associated with insulin resistance.
Methods: We studied the prevalence
of 25(OH) vit D deficiencies across the spectrum of glucose metabolism.
The study participants 441 total, 362 females (82.1%) had a mean age
(±SD) of 64.59 (±9.44) years. The study population was divided into 2
groups: Individuals with Diabetes (n=184), and controls with normal
glucose levels (n=257).
Results: Results: The mean 25(OH)
vitD (±SD) levels were significantly lower in subjects with diabetes
(18.6±10.6mg/ml) compared to normal subjects (24.2±12.2mg/ml), p=0.035.
25(OH) vitD deficiency was observed in 49.7% of the entire study
population and was significantly more frequent in patients with diabetes
compared to controls (60.9 vs 41.6% respectively).
Conclusion:This study illustrates the higher prevalence of 25(OH) vitD deficiencies among patients with diabetes.
Keywords: Diabetes; Vitamin D; HbA1cIntroduction
Diabetes is widely prevalent globally and around 285
million people have diabetes this number is expected to reach 438
million by the year 2030 [1]. Vitamin D deficiency is also an important
public health problem globally [2]. Exposure to ultraviolet light and
consumption of foods rich in fat-soluble vitamin D (egg, oily fish, meat
and eggs) are the main sources of vitamin D and its levels can be
measured by concentration of serum 25-hydroxyvitamin D (25(OH) vitD)
[3]. 25(OH) vitD levels are positively related to bone mineral density
[4], muscle mass and strength [5]. Moreover, there is a possible
association of 25(OH) vitD with certain types of cancer [6,7] infections
[8], autoimmune diseases [9] and cardiovascular disease [10]. 25(OH)
vitD levels vary with age [11], obesity [12], skin type [13] and
ethnicity [14], season [15], liver and kidney disease, medication,
nutritional habits and others [16]. Moreover, there is an association of
25(OH) vitD levels with type 2 diabetes mellitus [17,18]. The aim of
this study was to examine the association of vitamin D levels with
glycemic status in two groups of subjects: patients with diabetes and
normal subjects.
Methods
This study was conducted at the Outpatient and
Inpatient Departments of the Endocrinology Unit of a tertiary cancer
center (Metaxa Anticancer Hospital). The study was approved by the
Scientific Committee of the hospital. A total of 441 randomly selected
Greek Caucasian individuals, 79 males (17.9%) and 362 (82.1%) females
were recruited between August 2013 and October 2015 including all four
seasons. Their mean age was 64.59±9.44 (range=32-92 years).
A fasting venous blood sample after an overnight fast
of over 8 hours was collected to determine blood glucose, HbA1c and
serum 25(OH) vitD levels. Plasma glucose was estimated by the
Photometric method, Abbott’s ARCHITECT Abbott’s ARCHITECT c16000
Clinical Chemistry Analyzer, Abbott Diagnostics, North Chicago,
Illinois, USA. HbA1c was estimated by high pressure liquid
chromatography method Menarini’s ADAMS A1c HA-8160 Analyzer. The
prevalence of vitamin deficiency (<20mg/ml), insufficiency
(20–<30mg/ml) and sufficiency (≥30mg/ml) was estimated, as described
by the Endocrine Society Clinical Practice
guidelines [19]. The analytical assay for the determination
of total 25(OH)D was the Roche electrochemiluminescence
binding essay (ECL) on Elecsys immunoassay analyzers, Roche
Diagnostics GmbH, Mannheim, state D-68305, Germany.
Exclusion criteria were major illness (end stage kidney
disease, cirrhosis, pancreatitis, cancer and cardiovascular
disorders), recent surgery or diabetic keto acidosis in the last 6 months, use of glucocorticoids and secondary diabetes. The
control population was derived from patients of the obesity
and thyroid clinic with normal glucose and HbA1c levels
(Glu<100mg/dl and HbA1c<5.7%) and without any systemic
illness. Data were analyzed using the SPSS analytical software
22 (SPSS Inc-IBM Corporation, New York, United States). Data
are presented as mean, standard deviation (SD) and descriptive
statistics were used for the data analysis. Variables with p-values
of less than 0.05 were considered significant.
Results
The study population was divided into 2 groups
Patients with Diabetes Type 2 (n=184, 33 males) and subjects
with normal fasting blood glucose and HbA1c (n=257, 46 males).
The mean 25(OH) vitD values for males and females patients
was 22.9±11.6 and 21.6 ±11.9mg/ml respectively, p=0.815.
The mean 25(OH) vitD levels were higher in the control group
when compared with patients with diabetes (24.20±12.2, vs
18.6±10.6mg/ml, p=0.035, respectively). There was no difference
in the mean age of patients and sex distribution between the two
groups. Table 1 shows the mean values±SD for 25(OH) vitD, age,
plasma glucose levels and HbA1c for each group. 25(OH) vitD
deficiencies were seen in 49.7% of the entire study population.
The majority of diabetic patients studied had 25(OH) vitD serum
levels below the recommended threshold of 30mg/ml and only
26 of 184 (14.1%) of patients with diabetes had 25(OH) vitD
sufficiency, compared to 28.8% of subjects with normal glucose
(p<0.001). Table 2 shows the counts and percentages of subjects
with 25(OH) vitD deficiency, insufficiency and sufficiency, in each
group of subjects. There is statistically significant difference in
the prevalence of vitD deficiency and insufficiency between the
three groups (p-value is <0.001).
Discussion
There is a relationship between 25(OH) vitD deficiency and
risk of diabetes mellitus [20-23]. A high prevalence of 25(OH) vitD deficiencies has been reported in association with the
metabolic syndrome [24]. Type 1 and Type 2 Diabetes Mellitus
are multifactorial diseases and both genetic predisposition
and environmental factors contribute to their development.
25(OH) vitD deficiency is linked to type 1 and type 2 diabetes
development, and receptors for its activated form-1alpha,
25-dihydroxyvitamin D3-have been identified in beta cells and
immune cells. 25(OH) vitD deficiencies impair insulin synthesis
and secretion in humans and in animals, suggesting a role in
the development of type 2 diabetes. Besides, epidemiological
studies suggest a link between vitamin D deficiency in early life
and the later onset of type 1 diabetes [25].
There is also compelling evidence that 1, 25(OH)2D
regulates beta-cell function by different mechanisms, such as
influencing insulin secretion by regulating intracellular levels
of Ca2+, increasing beta-cell resistance to apoptosis, and possibly
also increasing beta-cell replication. The capacity of vitamin D,
more specifically 1, 25(OH)2D, to modulate immune responses
is of particular interest for the prevention and the therapy of
diabetes [26]. Diabetes itself can also result in lower circulating
25(OH) vitD concentrations [27]. Moreover, lower serum
25(OH) vitD levels are associated with prediabetes [28]. Vitamin
D supplementation in prediabetes subjects has been shown todecrease fasting plasma glucose, 2-h plasma glucose and HbA1c
levels [29].
Another important observation of our study is that the
majority of the study population has 25(OH) vitD deficiency in
general and respective of the underlying glycemic status. Greece
is considered a country of high sunlight levels. Based on the
important contribution of sunlight exposure to the production
and maintenance of serum 25(OH) vitD levels, one might
consider that 25(OH) vitD deficiency may be a problem limited
to countries located at higher latitudes and not Greece (Athens,
Greece: 37.9°C north of the equator). Nevertheless, we observed
a high prevalence of 25(OH) vitD deficiency and insufficiency,
especially among patients with diabetes.
The sample of our study represents Greek individuals and
there are some limitations. The data are aggregated and do not
permit analysis by body mass index, personal medical history,
complete medication of each patient or other covariates,
multivitamin use, skin pigmentation, clothing style, place,
duration of outdoor stay of each patient. Finally, we only had one
spot measurement for each participant.
However, our study has an important strength: We included
a large sample of individuals and divided them in two separate
groups, taking into account the underlying glycemic status.
Prospective studies with a large number of patients including
a representative Greek sample are required to study the link
between vitamin D deficiency and other factors related to the
diabetes mellitus. Since many individuals are vitamin D deficient
and at high risk of diabetes, vitamin D supplementation may
contribute to prevent diabetes and insulin resistance. Recent
observational data reports a positive effect of vitamin D on
preventing the onset of diabetes [18]. Nevertheless the possible
benefits of vitamin D supplementation on glycemic control are
still questioned. There is a need to conduct further studies to
evaluate the impact of vitamin D deficiency in relation to many
chronic diseases such as diabetes, and answer whether this link
is causative or not.
Conclusion
This study examined the relation between 25(OH) vitD
levels and glycemic status in Greek patients with diabetes and
normal subjects. We found that patients with diabetes had a
significantly higher prevalence of vitamin D deficiency compared
to normal subjects. From a clinical standpoint, specific advice
needs to be provided especially to people with diabetes. Vitamin
D supplements on a regular basis over the year and adequate
sun exposure could be also recommended in order to achieve
sufficient levels of 25(OH) vitD.
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