VOLUME 10 NUMBER 2 • JUNE 2013
65
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Correspondence to: Dr Marli Conradie
MBChB MMed (Int Med) FCP (SA) Cert Endo &
Metab (Phys)
Consultant Physician and Endocrinologist
University of Stellenbosch Dept of Medicine
Tygerberg Academic Hospital
E-mail:
S Afr J Diabetes Vasc Dis
2013;
10
: 65–66
Vitamin D and diabetes – a D-lemna
MARLI CONRADIE
Introduction
The worldwide prevalence of diabetes, most notably Type 2 diabetes
(T2DM), is increasing rapidly. Estimated projections for Sub-Saharan
Africa are a prevalence of 18.6 million by 2030.
1
Most strategies
to halt this increase have been aimed at preventing or treating
obesity as a major risk factor for the development of diabetes.
Unfortunately, most efforts have failed and the prevalence of
obesity remains alarmingly high.
1
Novel risk factors for the development of diabetes have been
described.
2
Included are adipose-derived factors (e.g. adiponectin
and leptin), liver-derived factors (e.g. CRP and ALT/GGT ratio),
endothelial-derived factors, inflammatory markers and nutritional
factors. To be considered amongst the nutritional factors is the link
between hypovitaminosis D and diabetes.
What we do know about vitamin D?
Vitamin D exists in two forms (D2 or ergocalciferol and D3 or
cholecalciferol) and also as numerous circulating metabolites
thereof. Vitamin D3 is produced in the skin under the influence of
ultraviolet light (80%) or can be obtained from the diet (fatty fish,
egg yolks etc.). Vitamin D2 is found in plant sources or produced
commercially by the fortification of yeast.
3
Supplementation can
either be with vitamin D2 or D3. Both forms can be stored in adipose
tissue or alternatively undergo hydroxylation in the liver, producing
25-OH vitamin D (calcidiol). This form is converted mostly in the
kidney via 1– hydroxylase to 1,25-(OH)
2
vitamin D (calcitriol). This is
the biologically active form of vitamin D.
The vitamin D receptor (VDR) is a nuclear receptor of the thyroid
hormone receptor superfamily which is expressed by all tissues.
4
Many tissues including colon, pancreas, breast, prostate, immune
system, macrophages, vascular endothelium, epidermis, placenta
and others also possess the enzymes to produce calcitriol locally.
This may explain why vitamin D appears to play an essential role in
overall health.
4,5
Different polymorphisms of VDR have been associated with
diabetes (type 1 and type 2), metabolic syndrome, impaired fasting
glucose and impaired glucose tolerance. Furthermore, 1,25-(OH)
2
vitamin D regulates the expression of over 200 genes, including
those related to apoptosis and immune modulation.
6
Potential
mechanisms for the role of vitamin D in diabetes include its action
on insulin secretion (both directly, as well as through its role in
calcium homeostasis), insulin action (both directly and indirectly)
and a beneficial effect on systemic inflammation.
7
Measurement of vitamin D status
The 25-OH vitamin D level reflects the body’s overall vitamin D
status. It is more stable than 1,25-(OH)
2
vitamin D, with a much
longer half-life.
8
Assays in South Africa are not standardized at the
present time and a variety of methods (RIAs, enzyme linked assays
such as ELISA and liquid chromatography with mass spectrometry)
are used, with different reference ranges and units.
Normal vitamin D status is currently defined as a serum level
between 30-76 ng/ml (65-190 nmol/l).
8
The lower limit of normal
still remains a topic of much debate. The term vitamin D insufficiency
has more recently been introduced to describe suboptimal levels of
25-OH vitamin D, typically between 10-30 ng/ml (25-65 nmol/l),
associated with adverse outcomes.
3
The vitamin D status of the
South African population is not known at the present time.
A role in Type 1 diabetes?
It has been shown that there is an immunomodulatory effect of
1,25-(OH)
2
vitamin D, inhibiting upregulation of Th cells that are
crucial in the pathogenesis of type 1 diabetes mellitus (T1DM).
9
An
inverse relationship between vitamin D intake in infants and the
subsequent prevalence of T1DM was found in large population
based studies in Finland.
10
Interestingly, the incidence of T1DM also
increases as one moves further away from the equator, typically
reflecting the amount of sunlight received.
11
However, no cause
and effect have been demonstrated.
Type 2 diabetes
The epidemiology of T2DM corresponds with that of vitamin D
deficiency, being more prevalent in the older population as well as
in subjects with darker skins. Also, a seasonal variation in diabetes
control has been demonstrated, with control being worse in
winter.
12
Whether this is due to the general lack of sunlight, or
the fact that patients are more inclined to consume carbohydrate
loaded diets in winter, is of course not clear.
There is an overwhelming amount of research, mostly
observational, trying to link vitamin D deficiency with diabetes. A
systematic review and meta-analysis evaluating 19 cross-sectional
studies concluded that there were inverse associations between levels
of 25-OH vitamin D and measurements of glycaemia or prevalence
of T2DM; however, this was not consistent and not present in all
populations.
13
By combining data reporting on level of 25-OH vitamin
D and diabetes prevalence, a non-significant inverse association was
found (OR 0.54, 95% CI: 0.23-1.27 for highest vs. lowest 25-OH
vitamin D concentration). Similarly, in the Nurses’ Health Study, it
was found that those with the highest intake of both vitamin D and
calcium had the lowest incident relative risk for diabetes.
14
Other population based research also showed associations
between low vitamin D levels and markers of cardiometabolic risk
(blood pressure, lipids and hyperglycaemia) when adjusted for
obesity.
15,16
In addition, low vitamin D levels were associated with
markers of insulin resistance
17
as well as showing a non-linear
inverse association with HbA
1c
.
18
The problemwith these observational studies is the huge variability
in study cohorts as well as the presence of important confounders
Submitted 7/5/2013, accepted 27/5/2013
