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Vitamin D deficiency and risk of diabetes I and II

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Title: Vitamin D deficiency and risk of diabetes I and II


1
Vitamin D deficiency and risk of diabetes I and II
  • MD, phd student Ulla Kampmann
  • Medical research laboratory, Medical Department M
    (Endocrinology and Diabetes), Aarhus University
    Hospital, NBG
  • Silkeborg Regional Hospital
  • Supervisors
  • Professor MD Niels Møller
  • Medical Department M (Endocrinology and
    Diabetes), Aarhus University Hospital, NBG
  • MD, med. sci. ,Lotte Ørskov
  • Silkeborg Regional Hospital.
  • Professor Bent Honoré
  • Institute of Medical Biochemistry, University of
    Aarhus.
  • Professor, MD Leif Mosekilde
  • Medical Department C, Aarhus University Hospital,
    THG

2
Causes and Consequences of Vitamin D deficiency
Holick, M. F., BMJ 2008 336 1318-1319
3
Vitamin D and Diabetes
  • Type 1 diabetes is more prevalent in higher
    latitudes (Keen H, Ekoe JM, Br Med Bull 1984)
  • There is a seasonal variation in the incidence of
    Type 1 diabetes (Diabetes Epidemiology Research
    Int Group, Diabetes 1988)
  • Glycemic control in type 2 diabetes depends on
    season with lowest HbA1c levels during summer
    (Ishii et al, Diabetes Care 2001)
  • Obesity is associated with the risk of having a
    lower plasma Vitamin D (Wortsman et al, Am J Clin
    Nutr., 2000)

4
Vitamin D deficiency and Type 1 DM
  • In animals the administration of vitamin D seems
    to prevent development of type 1 DM (Mathieu et
    al. Diabetologia 1994)
  • Vitamin D supplementation in infancy is
    associated with a decreased risk of Type 1
    diabetes (The EURODIAB substudy 2, Diabetologia
    1999)
  • Cod liver oil taken during pregnancy is
    associated with reduced risk of Type 1 diabetes
    in the offspring (Stene et al. , Diabetologia
    2000)

5
Vitamin D deficiency and Type 1 DM
  • Hypponen et al.
  • 12055 pregnant women from nothern Finland, due to
    give birth in 1966 were enrolled.
  • Data was collected about vitamin D
    supplementation in the first year of life
  • Primary outcome diagnosis of Type 1 DM by the
    end of 1997
  • Of 10366 children included in analyses, 81 were
    diagnosed with Type 1 DM

6
Vitamin D deficiency and Type 1 DiabetesIntake
of vitamin D and risk of type 1 diabetes a
birth-cohort study.Hyppönen et al, Lancet, 2001
7
Vitamin D deficiency and Type 1 Diabetes
Intake of vitamin D and risk of type 1 diabetes
a birth-cohort study. Hyppönen et al, Lancet, 2001
8
Vitamin D deficiency and Type 1 DM
  • Hypponen et al.
  • Conclusion
  • Dietary vitamin D supplementation is associated
    with reduced risk of type 1 diabetes.
  • Increasing the current allowance of vitamin D for
    infants and children might be indicated.

9
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • A large cross-sectional study shows that low
    serum 25(OH)D is inversely associated with
    insulinresistance (Scragg et al., Diabetes Care
    2004)
  • An inverse association between serum 25(OH)D
    concentration and incidence of type 2 diabetes
    has been found in large cohort studies (Mattila
    et al. Diabetes Care 2007, Pittas et al.
    Diabetes Care, 2006)

10
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • In the prospective Ely-study inverse associations
    between baseline serum 25(OH)D and future
    glycemia and insulin resistance are found
    (Forouhi et al. Diabetes 2008)
  • Vitamin D deficiency reduces pancreatic insulin
    secretion (Gedik et al. Diabetologia 1986)

11
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • Borrisova et al. IJCP, 2003.
  • Aim to evaluate the effect of vitamin D3
    supplementation on insulin secretion and insulin
    resistance.
  • 10 females with type 2 diabetes treated with oral
    hypoglycemic agents
  • 17 age- and BMI matched females with normal
    glucose tolerance served as controls

12
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • Borrisova et al. IJCP, 2003.
  • First and second phases of insulin secretion were
    studied during IVGTT before and after
    intervention
  • Peripheral insulin resistance was measured using
    the HOMA index
  • The diabetic patients were treated with
    cholecalciferol 1332 IU daily for 1 month

13
Insulinresponse during IVGTT
Borissova, IJCP, 2003
14
Borrisova et al. IJCP, 2003Mean serum 25(OH)D
level in diabetics
70 were vitamin D deficient at baseline (lt 50
nmol/l) 70 achieved normal vitamin D levels
after 1 month
15
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • Borrisova et al. IJCP, 2003
  • Conclusion
  • Vitamin D deficiency probably affects First Phase
    of Insulin Secretion (FPIS)
  • Vitamin D deficiency may contribute to the
    impairment of beta cell function and insulin
    action.
  • Vitamin D3 supplementation could be an element in
    the complex treatment of type 2 diabetes.

16
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • Pittas et al., Diabetes Care 2007
  • Determine the effects of combined calcium and
    vitamin D supplementation on glucose metabolism
  • A double blind, randomized, controlled clinical
    trial
  • 314 healthy adults gt 65 years
  • Recieved either 500 mg calcium citrat and 700 IU
    vitamin D3 or placebo daily for 3 years
  • Primary endpoint 3-year change from baseline in
    FPG
  • Secondary endpoint 3-year change from baseline
    in HOMA-IR

17
Effects of combined calcium and vitamin D
supplementation on FPG (A) and HOMA-IR (B)
Placebo
Calcium and vitamin D supplementation
Pittas et al. Diabetes Care, 2007
18
Vitamin D deficiency and Type 2 Diabetes Mellitus
  • Pittas et al., Diabetes Care 2007
  • Conclusion
  • The results provide support for an important
    role of calcium and vitamin D3 supplementation to
    lower risk of progression to clinical diabetes in
    individuals with IGT

19
Targets for the effects of vitamin D on diabetes
I and II
  • Presence of specific vitamin D receptors (VDR) in
    pancreatic beta cells and cells of the immune
    system (Johnson et al. Am J Physiology, 1994)
  • Expression of 1-alfa-hydroxylase enzyme in
    pancreatic beta cells and cells of the immune
    system (Bland et al. J Steroid biochem Mol Biol,
    2004)
  • Transcriptional activation of the promotor
    regions of target genes (Maestro et al. Cell
    Biochem Funct, 2002)
  • Presence of intracellular vitamin D receptors in
    skeletal muscle tissue (Bischoff et al. The
    Histochemical journal, 2001)

20
Major targets and actions of vitamin D3 on
peripheral tissues
Palomer et al. Diabetes, Obesity and Metabolism,
2007
21
Genomic actions of 1,25(OH)2D3
Mathieu et al. Diabetologia, 2005.
22
Potential mechanisms for the effects of vitamin D
on Type 1 diabetes
  • Direct beta cell damage by cytokines is important
    in the pathogenesis of type 1 diabetes
  • The beneficial effects of 1,25(OH)2D3 are mainly
    attributed to its immunomodulatory actions
  • (Mathieu et al. Diabetologia 2005)

23
Potential mechanisms for the effects of vitamin D
on Type 2 diabetes
  • 1,25(OH)2D3 exerts its insulinotropic effect by
    the VDR, causing an increased calcium influx
    through the beta cell membrane (Kajikawa et al.
    Endocrinology, 1999)
  • 1,25(OH)2D3 affects insulin secretion by
    stimulating insulin biosynthesis in the
    pancreatic beta cells (Bourlon et al. J
    Endocrinology, 1999)
  • Type 2 diabetes is associated with systemic
    inflammation (Duncan et al. Diabetes 2003)
  • 1,25(OH)2D3 may improve insulin sensitivity and
    promote beta cell survival by modulating the
    generation and effects of cytokines (Mathieu et
    al. Diabetologia 2005)

24
Possible links between vitamin D and Type 1 and
2 diabetes
  • A link between VDR gene polymorphisms and Type 1
    and 2 diabetes has been demonstrated (Ortlepp et
    al. Diabet. Med. 2003))
  • Genetic variants of DBP have been associated with
    diabetes (Speeckaert et al. Clin Chim Acta, 2006)
  • CYP1alfa polymorphisms may lead to
    susceptibility to Type 1 and 2 Diabetes (Palomer
    et al. Diabetes, Obesity and Metabolism 2007)

25
Conclusion
  • 1,25 OH2D3 reduces the risk of type 1 diabetes
    primarily through immunomodulatory effects
  • 1,25 OH2D3 may increase insulinsecretion and
    improve insulinresistance in type 2 diabetes
  • The possible role of vitamin D in the
    pathogenesis of type 2 diabetes is far from being
    understood.
  • Futher investigations are warranted

26
Metabolic effects of vitamin D in patients with
type 2 diabetes a controlled clinical trial
  • Phd-study
  • Insulin resistance and type 2 diabetes
    metabolic effects of vitamin D and mechanisms
    behind severe insulinresistance
  • A double blind randomized controlled trial
  • 24 patients with type 2 diabetes and vitamin
    D-insufficiency (50nmol/l)
  • Receive either cholecalciferol (11200 IE for 2
    weeks and 5600 IE for 10 weeks) or placebo for 12
    weeks

27
Metabolic effects of vitamin D in patients with
type 2 diabetes a controlled clinical trial
  • Primary endpoints
  • effect on in insulinsensitivity and
    insulinsecretion
  • Secondary endpoints
  • effect on glycemic control, lipidstatus, markers
    of inflammation (CRP, IL-6, IL-10. TNF-alfa) and
    BMD
  • Methods hyperinsulinemic euglycemic clamp,
    biopsies (muscle and adipose tissue), proteomics
  • Starts december 2008

28
  • Thank you ?
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