Low vitamin D status is common in type 2 diabetes and associated with atherosclerosis

[Matti Nark]

The Italian study

Targher G, Bertolini L, Padovani R, Zenari L, Scala L,
Cigolini M, Arcaro G. Serum 25-hydroxyvitamin D3
concentrations and carotid artery intima-media thickness among
type 2 diabetic patients. Clin Endocrinol (Oxf). 2006
Nov;65(5):593-7. PMID: 17054459 [PubMed - in process]
doi:10.1111/j.1365-2265.2006.02633.x <http://www.blackwell-sy-
nergy.com/doi/abs/10.1111/j.1365-2265.2006.02633.x>

published in last November found that low vitamin D status is
more common in type 2 diabetic patients than in non-diabetic
people and that it is strongly and independently associated
with increased carotid intimal medial thickening (IMT), a
marker of preclinical atherosclerosis. Below the abstract of
the study:

"OBJECTIVE: To estimate the prevalence of hypovitaminosis
D among type 2 diabetic adults and to assess the
relationship between hypovitaminosis D and intimal medial
thickening (IMT) of the common carotid artery, a marker of
preclinical atherosclerosis. DESIGN, PATIENTS AND
MEASUREMENTS: We compared winter serum 25-hydroxyvitamin
D3 [25(OH)D] concentrations in 390 consecutive type 2
diabetic patients and 390 nondiabetic controls who were
comparable for age and sex. Common carotid IMT was
measured with ultrasonography only in diabetic patients by
a single trained operator blinded to subjects' details.
RESULTS: The prevalence of hypovitaminosis D (i.e. 25(OH)D
<or= 37.5 nmol/l) was higher in diabetic patients (34.0 vs
16.4%, P < 0.001) than in controls. Among diabetic
patients, those with hypovitaminosis
D (n= 130) had a marked increase in common carotid IMT
(1.10 +/- 0.15 vs 0.87 +/- 0.14 mm, P < 0.001) when
compared with their vitamin d-sufficient counterparts
(n = 260). These patients also had significantly
higher haemoglobin A1c, fibrinogen and C-reactive
protein (hs-CRP) concentrations. In multivariate
regression analysis, low 25(OH)D concentrations
independently predicted carotid IMT (P < 0.001) in
people with type 2 diabetes after adjustment for
classical risk factors, diabetes duration, HbA1c,
calcium, renal function tests, inflammatory markers,
use of medications, and presence of the metabolic
syndrome (as defined by the Adult Treatment Panel III
criteria). CONCLUSIONS: Hypovitaminosis D is highly
prevalent in type 2 diabetic adults and is strongly
and independently associated with increased carotid
IMT. Further investigation into whether vitamin D may
play a role in the prevention of atherosclerosis
appears to be warranted."

--
Matti Narkia

[Ironjustic]

Since they have found free floating iron in those with
diabetes .. then the finding of low vitamin D really comes as
no surprise .. because .. iron destroys vitamin D ..

**Specifically** ..

What significance is the fact iron destroys vitamin D or more
precisely in those with iron overload .. vitamin D is
decreased .. in those with supplemental iron induced iron
overload .. vitamin D is decreased.

Bleeding / venesection / bloodletting / phlebotomy .. RESTORES
.. vitamin D . <<snip>> The results reveal that the low serum
25-OHD concentration in patients with hemochromatosis is
directly related to the extent of iron loading and it is
improved by venesection therapy. <<snip>>

Iron induced decreased vitamin D.

<<snip>> when transferrin is saturated with iron, may impair
bone formation and aggravate osteomalacia. <<snip>>

Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro
inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin
D production in renal tubules. Sato K, Nohtomi K, Demura H,
Takeuchi A, Kobayashi T, Kazama J, Ozawa H Bone. 1997 Jul ;
21(1): 57-64

A 60-year-old man with portal hypertensive gastropathy due to
type C liver cirrhosis developed severe bone pains, marked
hypophosphatemia with inappropriately increased urinary
excretion of phosphate (%TRP; 9=2E6%), and hyperalkaline
phosphatasia, after intravenous administration of saccharated
ferric oxide (SFO) at a dose of 80-240 mg/week over a period
of more than 5 years. The total iron infused was estimated to
be more than 25 g. On a diagnosis of SFO-induced osteomalacia,
the infusion of iron was immediately discontinued, and
phosphate and vitamin D2 (1000 IU/day) were administered.
Serum levels of 25-OHD2 increased after 1 week, whereas levels
of 1,25-(OH)2D2 did not increase until 3 months later,
accompanied by improvement of renal tubular reabsorption of
phosphate and gradual improvement of the bone pains. The
patient has been doing well for the last 2 years, with normal
serum levels of phosphate, calcium, and alkaline phosphatase,
without any supplementation of phosphate, vitamin D, or
iron-containing agents. In primary culture of neonatal mouse
renal tubules, in which 1,25- (OH)2D3 was produced from
25-OHD3 in response to PTH, SFO significantly inhibited
PTH-induced production of 1,25-(OH)2D3 at 30 mumol/L, which is
attainable in the urine of patients receiving a therapeutic
intravenous dose of SFO. Furthermore, SFO decreased the
calcium content and inhibited 45Ca incorporation in cultured
fetal mouse parietal bones at 3 mumol/L. Such SFO
concentration may be transiently observed in the plasma of
patients receiving excessive intravenous doses of SFO for a
prolonged period. These in vitro findings together with the
clinical observations suggest that SFO, after filtration
through the glomerulus and reabsorption in the proximal renal
tubules, impaired proximal renal tubular function, such as
tubular reabsorption of phosphate and 1 alpha-hydroxylase
activity, leading to hypophosphatemic osteomalacia.
Furthermore, it is highly likely that SFO in the peripheral
blood, when transferrin is saturated with iron, may impair
bone formation and aggravate osteomalacia. Although
SFO-induced osteomalacia is reversible simply by
discontinuation of the agent, excessive and prolonged
administration of SFO should be avoided.

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1: Gastroenterology. 1985 Apr;88(4):865-9. Related
Articles, Links

Low serum 25-hydroxyvitamin D in hereditary hemochromatosis:
relation to iron status.

Chow LH, Frei JV, Hodsman AB, Valberg LS.

Under normal conditions, vitamin D absorbed from the diet or
synthesized in the skin is transported to the liver where it
undergoes hydroxylation. The purpose of this study was to
determine whether excess hepatic iron affects this process and
the subsequent production of 1,25-dihydroxyvitamin D
(1,25-[OH]2D) in the kidney. Mean serum 25-hydroxyvitamin D
(25-OHD) concentrations in untreated hereditary
hemochromatosis were 13 +/- 6 (SD) in 9 patients with
cirrhosis, 13 +/- 6 in 5 patients with hepatic fibrosis, and
22 +/- 6 in 10 patients with normal hepatic architecture aside
from siderosis and were significantly lower than the levels
found in 24 controls matched for age, sex, and season, p less
than 0.05. The mean serum 25-OHD levels in the two groups with
hemochromatosis and hepatic damage were significantly lower
than the value in the group with normal hepatic architecture,
p less than 0.05. Serum 25-OHD levels in individual patients
were inversely related to the size of body iron stores as
measured by exchangeable body iron, r =3D -0.64, or serum
ferritin, r =3D -0.47, p less than 0.05. In 15 patients
removal of excess body iron by venesection therapy produced a
significant increase in the mean serum 25-OHD from 20 ng/ ml
to 30 ng/ml, p less than 0.05. In contrast, mean serum
1,25-[OH]2D levels were similar in iron-loaded and control
subjects, indicating that the regulation of this metabolite
was intact in patients with hemochromatosis. The results
reveal that the low serum 25-OHD concentration in patients
with hemochromatosis is directly related to the extent of iron
loading and it is improved by venesection therapy.

PMID: 3838288 [PubMed - indexed for MEDLINE]

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http://health.enotes.com/genetic-disorders-encyclopedia/major-
-histoco...

Major histocompatibility complex

HLA disease associations Disease MHC allele Approximate
relative risk

Ankylosing spondylitis B27 77?90 Patients with ankylosing
spondylitis may have extremely low levels of 25(OH)D.
http://tinyurl.com/8tonv Celiac disease DR3 + DR7 5?10 A low
25-(OH)D vitamin concentration was a typical biochemical
abnormality in our patients (64% of men and 71% of women).
http://tinyurl.com/b7b9d Diabetes, Type 1 DR3 5 decreased zinc
and 25OHD serum levels in poorly controlled insulin-dependent
(Type I) diabetic patients http://tinyurl.com/73fsu Diabetes,
Type 1 DR4 5?7 Diabetes, Type 1 DR3 + DR4 20?40 Graves disease
DR3 5 [High prevalence of secondary hyperparathyroidism due to
vitamin D insufficiency in Graves' disease] http://www.hubmed-
.org/search.cgi?q=3D25-hydroxyvitamin+D+and+graves
Hemochromatosis A3 6?20 Lupus DR3 1?3 There was a high
prevalence of hypovitaminosis D (65.2%),
http://tinyurl.com/8wfws Multiple sclerosis DR2 2?4 Vitamin D
Defends Against MS http://www.hon.ch/News/HSN/516850.html
Myasthenia gravis B8 2.5?4
Psoriasis vulgaris Cw6 8 These data suggest that exogenous
active forms of vitamin D3 are effective for treatment of
psoriasis and that the endogenous 1,25-dihydroxyvitamin D
level also may be involved in the development of this skin
disease. http://tinyurl.com/9c88e Rheumatoid arthritis DR4
3?6 We suggest that there is a disturbance in vitamin D
metabolism in RA. http://tinyurl.com/df6zv -----------------
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Prabhala, A., R. Garg, and P. Dandona, Severe myopathy
associated with vitamin D deficiency in western New York. Arch
Intern Med, 2000. 160(8): p. 1199-203. Five cases of severe
myopathy associated with vitamin D deficiency are described.
Each patient was confined to a wheelchair because of weakness
and immobility. Two were elderly, 1 was a 37-year-old African
American with type 1 diabetes mellitus, 1 was being treated
for carcinoid syndrome, and 1 was severely malnourished due to
poor oral intake. In each, weakness had previously been
attributed to other causes, including old age, concomitant
diabetic neuropathy, or general debility. Correct diagnosis
was made initially by a high index of suspicion, following the
demonstration of clinical proximal myopathy; confirmation was
made by the demonstration of low 25-hydroxyvitamin D and
elevated parathyroid hormone concentrations. Treatment with
vitamin D caused a resolution of body aches and pains and a
restoration of normal muscle strength in 4 to 6 weeks. Four
patients became fully mobile and had normal 25-hydroxyvitamin
D concentrations, and the fifth also became mobile. In the 4
fully recovered cases, parathyroid hormone levels on follow-up
were lower but still elevated. This finding suggests a degree
of autonomy of parathyroid secretion known to occur in cases
of long-standing vitamin D deficiency. Myopathy, due to
chronic vitamin D deficiency, probably contributes to
immobility and ill health in a significant number of patients
in the northern United States. An awareness of this condition
may significantly improve mobility and quality of life in
patient populations vulnerable to vitamin D deficiency.

Who loves ya. Tom

Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com

Man Is A Herbivore! http://tinyurl.com/a3cc3

DEAD PEOPLE WALKING http://tinyurl.com/zk9fk

[Matti Nark]

On Mon, 12 Mar 2007 18:29:29 +0200, Matti Narkia
<mna@mbnet.fi> wrote:

>The Italian study
>
>Targher G, Bertolini L, Padovani R, Zenari L, Scala L,
>Cigolini M, Arcaro G. Serum 25-hydroxyvitamin D3
>concentrations and carotid artery intima-media thickness
>among type 2 diabetic patients. Clin Endocrinol (Oxf). 2006
>Nov;65(5):593-7. PMID: 17054459 [PubMed - in process]
>doi:10.1111/j.1365-2265.2006.02633.x <http://www.blackwell-s-
>ynergy.com/doi/abs/10.1111/j.1365-2265.2006.02633.x>
>
>published in last November found that low vitamin D status is
>more common in type 2 diabetic patients than in non-diabetic
>people and that it is strongly and independently associated
>with increased carotid intimal medial thickening (IMT), a
>marker of preclinical atherosclerosis. Below the abstract of
>the study:
>
> "OBJECTIVE: To estimate the prevalence of hypovitaminosis
> D among type 2 diabetic adults and to assess the
> relationship between hypovitaminosis D and intimal medial
> thickening (IMT) of the common carotid artery, a marker
> of preclinical atherosclerosis. DESIGN, PATIENTS AND
> MEASUREMENTS: We compared winter serum 25-hydroxyvitamin
> D3 [25(OH)D] concentrations in 390 consecutive type 2
> diabetic patients and 390 nondiabetic controls who were
> comparable for age and sex. Common carotid IMT was
> measured with ultrasonography only in diabetic patients
> by a single trained operator blinded to subjects'
> details. RESULTS: The prevalence of hypovitaminosis D
> (i.e. 25(OH)D <or= 37.5 nmol/l) was higher in diabetic
> patients (34.0 vs 16.4%, P < 0.001) than in controls.
> Among diabetic patients, those with hypovitaminosis
> D (n= 130) had a marked increase in common carotid IMT
> (1.10 +/- 0.15 vs 0.87 +/- 0.14 mm, P < 0.001) when
> compared with their vitamin d-sufficient
> counterparts (n = 260). These patients also had
> significantly higher haemoglobin A1c, fibrinogen and
> C-reactive protein (hs-CRP) concentrations. In
> multivariate regression analysis, low 25(OH)D
> concentrations independently predicted carotid IMT
> (P < 0.001) in people with type 2 diabetes after
> adjustment for classical risk factors, diabetes
> duration, HbA1c, calcium, renal function tests,
> inflammatory markers, use of medications, and
> presence of the metabolic syndrome (as defined by
> the Adult Treatment Panel III criteria).
> CONCLUSIONS: Hypovitaminosis D is highly prevalent
> in type 2 diabetic adults and is strongly and
> independently associated with increased carotid IMT.
> Further investigation into whether vitamin D may
> play a role in the prevention of atherosclerosis
> appears to be warranted."

Here some additional interesting references about vitamin D
and type diabetes:

Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R.
The effect of vitamin D3 on insulin secretion and peripheral
insulin sensitivity in type 2 diabetic patients. Int J Clin
Pract. 2003;57(4):258-261. (PubMed) <http://www.ncbi.nlm.nih.-
gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=128004-
53&dopt=Abstract>

"Our results suggest that vitamin D3 supplementation could
be an element in the complex treatment of type 2 diabetes
mellitus during the winter.

Inomata S, Kadowaki S, Yamatani T, Fukase M, Fujita T. Effect
of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes
mellitus. Bone Miner. 1986;1(3):187-192 <http://www.ncbi.nlm.-
nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=33-
34207&dopt=Abstract>

"The findings that 1 alpha (OH)D3 enhances insulin
secretion and reduces the levels of serum free fatty acid
in non- insulin-dependent diabetics provide us with the
possibility that vitamin D may play some role in the
regulation of insulin secretion."

--
Matti Narkia