Download - Diabetes and Vitamin D Stefania Maggi CNR Center on Aging Padua, Italy

Diabetes and Vitamin DDiabetes and Vitamin D

Stefania Maggi

CNR Center on Aging

Padua Italy

bull Vitamin D metabolism and actions

bull Epidemiology of hypovitaminosis D

bull Association of low Vitamin D status and chronic diseases

bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions


The primary function of calcitriol or 125 (OH)2D3 in the intestine is increased absorption of calcium and phosphorous Vitamin D is carried into the nucleus of the enterocyte where it binds to receptor proteins and acts as a steroid hormone resulting in the stimulation and synthesis of new messenger RNA moleculesThese messenger RNA molecules are then translated to produce a protein Calbindin a calcium binding protein in the intestinal mucosa that is synthesized in response to the action of calcitriol (active vit D) This calcium binding protein is needed for Ca transport across the cell membranes

Calcitriol and the BonePTH alone or with calcitriol directs the mobilization of Ca and P from the bones to help achieve a normal blood Ca concentration The bodyrsquos needs for calcium is regulated by the production of calcitriol by the kidneysldquoHypocalcemiardquo increases the secretion of parathyroid hormone which in turna) Stimulates the conversion of some of the circulating 25(OH)2D3 to 125(OH)2D3 (calcitriol) in the kidneysb) This active 125(OH)2D3 (calcitriol) then causeselevation of serum Ca and P by acting on kidney bone and GI Tract

Vitamin D metabolism and actions Vitamin D metabolism and actions

Maalouf NM Current opinion in Nephrology and hypertension 2008






Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status

according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations

Stages of vitamin D status

25(OH)D concentrations

(ngmL)

Deficiency 0ndash12

Insufficiency gt12ndash30

Adequacy gt30 to 100

Toxicity gt100

Souberbielle JC et al Autoimmune reviews 2010

Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis

ndash Sunscreen use skin pigment aging season latitude

bull Decreased bioavailabilityndash Malabsorption obesity

bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)

bull Breast feedingndash Poor vit D content in human milk

bull Decreased synthesis of 25(OH)Dndash Liver failure

bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome

bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure

50-97

35-73

80 in aged 42 in adolescents

30-80

Hypovitaminosis D a global perspective

Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009

Van der Meer M et al Ospeop Int 2011

Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations

89 in adolescents

Copyright copy2001 The Endocrine Society

Lips P Endocr Rev 200122477-501

Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study

The lowest values were found in Greece Spain and Italy






Vitamin D deficiencyVitamin D deficiency

1048707 Rickets--------------Children

1048707 Osteomalacia------ Adults

1048707 Osteoporosis-------Adults

helliphelliphellip And much more


Copyright restrictions may apply

Dobnig H et al Arch Intern Med 20081681340-1349

Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality

Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349

Prospective cohort study of 3258 patients undergoingcoronary angiography



Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)

Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality


Martins D et al Arch Intern Med 20071671159-1165

Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels

Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)

Vit D and Metabolic SyndromeVit D and Metabolic Syndrome

Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults

JP Reis D von Muhlen ER Miller

European Journal of Endocrinology 159 2008

We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function

The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)

Vit D increases insulin receptor capacity and responsiveness for glucose transport






Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies

Janghorbani M et al Am J Epidemiol 2007166495-505

American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg




Tuominen et al Diabetes Care 1999

0

01

02

03

04

05

06

07

08

09

1

Men Women

Type 1Type 2Controls

Plt005

Plt0005

Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes


Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD

Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture

Bone quality vs bone densityBone quality vs bone density

Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo


Rosen CJ et al Nature 2006

Decreased Vit D bioavailability

Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus

Palomer et al Diabetes Obesity and Metabolism 2008

Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes

Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk

Knekt Epidemiology Volume 19(5)September 2008666-671

Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching

Pittas AG et al Diabetes Care 33(9) 2010

Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis


Parker J et al Maturitas 2009

Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes

Penckofer et al 2008

Diabetes Care 33(10) 2010

Vitamin D and diabetesVitamin D and diabetes

The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects

Review

Vitamin D and diabetesC Mathieu et al Diabetologia 2005

Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation

Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low

vitamin D levelsJ A Sugden J I Davies M D Withamet al

DIABETIC Medicine 2007

Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2

diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al

AJCN 2011

Vitamin D as an analgesic for patients with T2Dand neuropathic pain

Lee P Chen R Arch Intern Med 2008

Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention

regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases

Holick Am J Clin Nutr 2004

November 2010

Major challengesMajor challenges

bull Measuring 25(OH)Dndash Techniques available

ndash Clinical reporting of circulating 25(OH)D concentrations

bull Defining doses of Vitamin D supplements

Recommendations for clinical practiceRecommendations for clinical practice

Souberbielle JC et al Autoimmunity reviews 2010


Heaney R P et al J Clin Endocrinol Metab 201196E447-E452

Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans

D2

D3

ConclusionsConclusions

bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes

bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated

bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective

Diabetes and Vitamin D

Slide 2

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Vitamin D metabolism and actions

Slide 7

Suggested terminology to describe vitamin D status according to circulating 25(OH)D concentrations

Causes of hypovitaminosis D

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Vitamin D deficiency

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Vit D and Metabolic Syndrome

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Bone quality vs bone density

Has Fat a Protective Role for the Skeleton ldquoPros amp Consrdquo

Slide 25

Serum Vitamin D and Subsequent Occurrence of Type 2 Diabetes

Slide 27

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Factors Contributing to Low Vitamin D Levels in Diabetes

Slide 30

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Vitamin D and diabetes

Slide 33

Evidence of the efficacy of Vit D supplementation

Schematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention regulation of immune function and decreased risk of autoimmune diseases

Slide 36

Slide 37

Major challenges

Recommendations for clinical practice

Slide 40

Conclusions



















(ngmL)

Deficiency 0ndash12



Toxicity gt100










50-97

35-73


30-80





89 in adolescents
















































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Major challenges


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Conclusions









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30-80





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Men Women


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Major challenges


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Conclusions
















































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Review








AJCN 2011






November 2010










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D3






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Major challenges


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Conclusions























Review








AJCN 2011






November 2010










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D3






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Major challenges


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Conclusions







AJCN 2011






November 2010










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D3






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Major challenges


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Conclusions




November 2010










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Major challenges


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Conclusions










D2

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Major challenges


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Conclusions






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Major challenges


Slide 40

Conclusions

Download - Diabetes and Vitamin D Stefania Maggi CNR Center on Aging Padua, Italy

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