Lecce vitamina d 8.4.2014


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Ipovitaminosi D ed Obesità

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Lecce vitamina d 8.4.2014

  1. 1. VITAMINA D COME FATTORE DI RISCHIO POTENZIALE NELL’OBESITA’ Massimiliano Andrioli EndocrinologiaOggi, Roma, Lecce Endocrinologia, Istituto Auxologico Italiano, Milano
  2. 2. TIPI DI VITAMINA D • vitamina D3 o Colecalciferolo (animale) • vitamina D2 o Ergocalciferolo (vegetale) • 80-90% produzione endogena • 10-20% alimentare (animale/ vegetale)
  3. 3. 7-Dehydrocholesterol7-Dehydrocholesterol Pre-Vitamin DPre-Vitamin D33 Vitamin DVitamin D33 EpidermisEpidermis LatitudeLatitude PollutionPollution ClothingClothing Melanin pigmentationMelanin pigmentation Duration of exposureDuration of exposure FISIOLOGIA
  4. 4. FISIOLOGIA calcifediolo calcitriolo colecalciferolo
  5. 5. Colecalciferolo (vitamina D3) • Di-base gtt 10.000 UI/ml (1 gtt = 250 IU, 1 mcg = 40 UI) • Di-base flaconcino 25.000 IU • Di-base fl os/im 100.000-300.000 UI Calcifediolo (25-OH-colecalciferolo) • Didrogyl gtt (uso selettivo) NB 5 ug (200 IU) colecalciferolo = 1 ug (40 IU) calcifediolo Calcitriolo (1,25 OH vitamina D3) • Rocaltrol 0,25-0,50 ug cpr (uso selettivo) • 1-alfa-OH-colecalciferolo (alfa-calcidolo) • Dediol/Diserinal cpr 0,25-1 ug (uso selettivo) Ergocalciferolo (Vitamina D2 ) • Ostelin fl os/im 400.000 UI (meno efficace, poco utilizzata) FARMACI
  6. 6. FUNZIONE 1,25(OH)1,25(OH)22DD BoneBoneDietary calciumDietary calcium IntestinesIntestines
  7. 7. Bone Density and Fractures – Risk of osteoporosis may be reduced with adequate intake of vitamin D and calcium. – Studies support the concept that vitamin D at doses between 700 and 800 IU/d with calcium supplementation effectively increase hip bone density and reduced fracture risk, whereas lower vitamin D doses may have less effect. VITAMINA D - OSSO
  8. 8. Cells containing 25OH-VitD3-1-alpha-OHase Breast, prostate, lung, skin, lymph nodes, colon, pancreas, adrenal medulla, brain, placenta » Holllick MF. Am J Clin Nutr. 2004. 79(3):362. » Zehnder et al. J Clin Endocrin Metab. 2001;86(2) Cells containing Nuclear VDR Pancreatic islet cells, monocytes, transformed B cells, activated T cells, neurons, prostate, ovaries, pituitary, aortic endothelium, placenta, skeletal muscle cells. » Zittermann A. Br J Nutr. 2003;89(5):552. » Bischoff HA, et al. Histochem J 2001;33:19. EFFETTI EXTRASCHELETRICI
  9. 9. • Involved in cellular growth, differentiation and apoptosis • Simulates insulin secretion • Modulates the immune system. • Reduces inflammation • Muscle development EFFETTI EXTRASCHELETRICI
  10. 10. Role in Cancer Prevention – Low intake of vitamin D and calcium has been associated with an increased risk of non-Hodgkin lymphomas, colon, ovarian, breast, prostate, and other cancers. – The anti-cancer activity of vitamin D is thought to result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. These effects may be mediated through vitamin D receptors expressed in cancer cells. – Vitamin D is not currently recommended for reducing cancer risk VITAMINA D - TUMORI Role in All Cause Mortality –Researches concluded that having low levels of vitamin D (<17.8 ng/mL) was independently associated with an increase in all- cause mortality in the general population. VITAMINA D – MORTALITA’
  11. 11. Autoimmune Disease – Vitamin D supplementation is associated with a lower risk of autoimmune diseases. – In a Finnish birth cohort study of 10,821 children, supplementation with vitamin D at 2000 IU/d reduced the risk of type 1 diabetes by approximately 78%, whereas children who were at risk for rickets had a 3-fold higher risk for type 1 diabetes. – In a case-control study of 7 million US military personnel, high circulating levels of vitamin D were associated with a lower risk of multiple sclerosis. – Similar associations have also been described for vitamin D levels and rheumatoid arthritis. VITAMINA D – AUTOIMMUNITA’
  12. 12. Role in Cardiovascular Diseases – Vitamin D deficiency activates the renin-angiotensin-aldosterone system and predisposes to hypertension and left ventricular hypertrophy. – Vitamin D deficiency increases PTH, which increases insulin resistance secondary to down regulation of insulin receptors and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. VITAMINA D - CARDIOVASCOLARE Role in Reproductive Health – Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia. VITAMINA D - RIPRODUZIONE
  13. 13. Robert P. 2008. Vitamin D in Health and Disease. Clin J Am Soc Nephrol 3:1535-1541. Disorder Strength of Evidence Osteoporosis ++++ Falls ++++ Type 1 DM ++ Cancer ++++ Autoimmune diseases ++ Hypertension +++ Periodontal disease ++++ Multiple sclerosis ++ Susceptibility/poor response to infection ++++ Osteoarthritis ++ DISORDINI CAUSATI O AGGRAVATI DA IPOVITAMINOSI D
  17. 17. (Rizzoli R. Current Medical Research & Opinion 2013) DEFINIZIONE
  18. 18. - increased age - female sex - darker skin pigmentation - reduced sun exposure - seasonal variation - distance from the equator - inter-assay and inter-laboratory 25(OH)D variability 25OHD ASSESSMENT
  19. 19. • Poor dietary intake of vitamin D • Lower sun exposure • Sedentary lifestyle • Clothing practices • Decreased oral absorption • Decreased cutaneous synthesis • Increased clearance • Enhanced production of 1,25(OH) D. Negative feedback on 25(OH)D • 25(OH)D may increase glucocorticoid which regulates adipose tissue • Vitamin D decreases PPAR-gamma, leading to other metabolic processes in the preadipocyte. EZIOLOGIA
  20. 20. • Olson et al JCEM 2011 – 92% of obese subjects had a 25(OH)D level below 30 ng/ml vs 68% in non overweight children – 50% of obese subjects were below 20 ng/l vs 22% in non overweight children • Alemzedeh et al Metabolism 2008 – 74% had 25(OH)D levels less than 30 ng/ml and 32.3% had 25(OH)D < 20 ng/ml EPIDEMIOLOGIA
  21. 21. – selective deposition of vitamin D, a lipophilic molecule, in subcutaneous and visceral adipose tissue – BMI and body fat were inversely related to serum 25(OH) vitamin D – positive correlation between serum and fat tissue 25(OH) vitamin – visceral compartment volume more closely associated with vitamin D deficiency compared with subcutaneous fat – independent association between hypovitaminosis D and dysmetabolic conditions such as MS, T2D, hypertension and liver steatosis – hypovitaminosis D has been hypothesized as a primary cause of obesity VITAMINA D - OBESITA’ - obesity leads to lower vitamin D levels and not the other way around Vimaleswaran, PLoS Med. 2013
  22. 22. Proteins linking vitamin D to obesity: - vitamin D receptor - toll-like receptors - renin-angiotensin system - apolipoprotein E - vascular endothelial growth factor - poly (DP-ribose) polymerase-1 IPOVITAMINOSI D – GENETICA Vitamin D cell-signaling mechanisms: - matrix metalloproteinases - mitogen-activated protein kinase pathways - reduced form of nicotinamide
  23. 23. IPOVITAMINOSI D – SINDROME METABOLICA – Vitamin D insufficiency involves more than 75% of patients with metabolic syndrome (MS) – serum 25(OH) vitamin D3 levels are significantly lower in obese patients affected by MS than in obese subjects without MS – A powerful association between hypovitaminosis D and MS in obese patients independently from body fat mass and its clinical correlates. – The association between low 25(OH) D3 levels and MS is not merely induced by vitamin D deposition in fat tissue – active form of vitamin D3 exerts an insulinsensitizing action by increasing the expression of insulin receptors in peripheral tissues and facilitating insulin- mediated glucose transport. – In addition, vitamin D3 directly regulates the free fatty acids (FFA) metabolism acting on the PPAR and improves insulin resistance induced by FFA. – Hypovitaminosis D represent a crucial independent determinant of MS.
  24. 24. IPOVITAMINOSI D – ADIPONECTINA – Lower vitamin D and adiponectin levels were strongly associated with metabolic risk factors and obesity in Turkish children and adolescent
  25. 25. IPOVITAMINOSI D – IPERTENSIONE - inverse association of vitamin D levels with the renin-angiotensin- aldosterone system activity - endothelial function - secondary hyperparathyroidism
  26. 26. 60 70 80 90 100 110 120 0 10 20 30 40 50 60 70 80 25 OH(D) (ng/mL) FastingGlucose(mg/dL) Johnson et al, Journal of Pediatrics 2010 VITAMINA D - GLICEMIA
  27. 27. VITAMINA D - DIABETE – low vitamin D levels high risk of developing diabetes in the future – VDR, 1-α-hydroxylase expressed in pancreatic beta cells, potential role of vitamin D on beta cell function – calcium crucial for insulin synthesis and secretion – vitamin D-induced stimulation of osteocalcin, which may improve insulin sensitivity – the currently available literature on vitamin D does not support the notion that vitamin D supplementation is useful for the prevention and/or treatment of diabetes mellitus
  28. 28. – Vitamin D treatment of animals with diabetes mellitus type 1 slows the progression of diabetes – High doses of vitamin in high risk-group children reduces diabetes incidence VITAMINA D - DIABETE
  29. 29. 20 40 60 80 100 120 140 0 10 20 30 40 50 60 70 80 25 OH(D) (ng/mL) HDL(mg/dL) VITAMINA D – COLESTEROLO HDL – association of vitamin D deficiency with lower high density lipoprotein (HDL) – higher triglycerides – higher apolipoprotein E levels – no significant effect on blood lipids when vitamin D supplementation
  31. 31. In generale: forme inattive (non 1-alfa-idrossilate) •Colecalciferolo •Calcifediolo (25OHD3) Tre indicazioni alla terapia con forme attive (1-alfa-idrossilate) •Calcitriolo •1-alfa-calcidolo: - IRC in stadio avanzato - ipoparatiroidismo cronico - malassorbimento grave Adami S et al, Reumatismo 2011 IPOVITAMINOSI D – TRATTAMENTO
  32. 32. CONCLUSIONI - ipovitaminosi D è frequente in obesità - ipovitaminosi D è una conseguenza - ipovitaminosi D si associa a: MS, ipertensione, diabete, ipercolesterolemia, rischio CV - trattamento integrativo
  33. 33. GRAZIE PER L’ATTENZIONE….. www.endocrinologiaoggi.it