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Inadequate vitamin D status: does it contribute to the disorders comprising syndrome ‘X’?

Published online by Cambridge University Press:  09 March 2007

B. J. Boucher
Academic Medical Unit and Cellular Mechanisms Research Group, St. Bartholomew's and the Royal London Hospital Medical & Dental School, Queen Mary Westfield, London El 1BB, UK
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Environmental factors are important in the aetiology of glucose intolerance, type II diabetes and IHD. The lack of vitamin D, which is necessary for adequate insulin secretion, relates demographically to increased risk of myocardial infarction. These disorders are connected, degenerative vascular disease increasing with glucose intolerance and diabetes and, with its risk factors, comprising syndrome ‘X’. Evidence is presented suggesting that vitamin D deficiency may be an avoidable risk factor for syndrome ‘X’, adding another preventative measure to current recommendations which are aimed at reducing the worldwide epidemic of these disorders. Experimentally, vitamin D deficiency progressively reduces insulin secretion; glucose intolerance follows and becomes irreversible. Relationships between vitamin D status, glucose tolerance and 30 min insulin secretion during oral glucose tolerance tests are reported in British Asians; insulin secretion, but not glycaemia, improving with short-term supplementation. Studies showing reduction in blood pressure and in risk of heart attack and diabetes with exercise (usually outdoor), rarely consider the role of vitamin D status. Glycaemia and insulin secretion in elderly European men, however, relate to vitamin D status, independent of season or physical activity. Prolonged supplementation can improve glycaemia. Hypertension improves with vitamin D treatment with or without initial deficiency. Vitamin D status and climate are reviewed as risk factors for myocardial infarction; the risk reducing with altitude despite increasing cold. Glycaemia and fibrinogenaemia improve and insulin secretion increases in summer. Variation in vitamin D requirements could arise from genetic differences in vitamin D processing since bone density can vary with vitamin D-receptor genotype. Vitamin D receptors are present in islet β cells and we report insulin secretion in healthy Asians differing profoundly with the Apa I genotype, being independent of vitamin D status. Those at risk of vitamin D deficiency include the elderly, those living indoors or having a covered-up style of dress, especially dark-skinned immigrants, and pregnant women, and these are groups recognized as being at increased risk of diabetes.

Review Article
Copyright © The Nutrition Society 1998


Auwerx, J, Bouillon, R & Kesteloot, H (1992) Relation between 25-hydroxyvitamin D3, apolipoprotein A-1, and high density lipoprotein cholesterol. Arteriosclerosis and Thrombosis 12, 671674.CrossRefGoogle ScholarPubMed
Balarajan, R (1996) Ethnicity and variations in mortality from coronary heart disease. Health Trends 28, 4551.Google Scholar
Balarajan, R, Yuen, P & Machin, D (1987) Inequalities in health: Changes in RHA's in the past decade. British Medical Journal 294, 15611564.CrossRefGoogle Scholar
Bansal, S, Rizui, SNA, Rao, MB & Vaishana, H (1975) Effect of hypocalcaemia on glucose tolerance, insulin release and free fatty acid levels in human subjects. Postgraduate Medical Journal 51, 471475.CrossRefGoogle ScholarPubMed
Barger-Lux, MJ & Heaney, RP (1994) The role of calcium intake in preventing bone fragility, hypertension, and certain cancers. Journal of Nutrition 124, 1406S1411S.CrossRefGoogle ScholarPubMed
Barker, DJP, Hales, CN, Fall, CHD, Osmond, C, Phipps, K & Clark, PMS (1993) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36, 6267.CrossRefGoogle ScholarPubMed
Barragry, JM, France, MW, Corless, D, Gupta, SP, Switala, S, Boucher, BJ & Cohen, RD (1978) Intestinal cholecalciferol absorption in the elderly and in younger subjects. Clinical Science and Molecular Medicine 55, 213220.Google Scholar
Baynes, K, Boucher, BJ, Feskens, EJM & Kromhout, D (1997) Vitamin D, glucose tolerance and insulinaemia in elderly men. Diabetologia 40, 344347.CrossRefGoogle ScholarPubMed
Beaulieu, C, Kestekian, R, Havrankova, J & Gascon-Barre, M (1993) Calcium is essential in normalizing intolerance to glucose that accompanies vitamin D depletion in vivo. Diabetes 42, 3543.CrossRefGoogle ScholarPubMed
Billaudel, B, Faure, A, Labriji-Mestaghanmi, H & Sutter, BCJ (1989) Direct in vitro effect of 1,25-dihydroxyvitamin D3 on islet insulin secretion in vitamin deficient rats: Influence of D3 pretreatment. Diabete et Metabolisme 15, 8587.Google ScholarPubMed
Boucher, BJ, Ewen, SW & Stowers, JM (1994) Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their Fl and F2 offspring. Diabetologia 37, 4955.CrossRefGoogle Scholar
Boucher, BJ (1995) Strategies for reduction in the prevalence of NIDDM; the case for a population-based approach to the development of policies to deal with environmental factors in its development. Diabetologia 38, 11251129.CrossRefGoogle ScholarPubMed
Boucher, BJ, Mannan, N, Noonan, K, Hales, CN & Evans, SJW (1995) Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in East London Asians. Diabetologia 38, 12391245.CrossRefGoogle ScholarPubMed
Braun, A, Bichmaier, R & Cleve, H (1992) Molecular analysis of the gene for the human vitamin-D-binding protein (group- specific component): allelic difference of the common genetic GC types. Human Genetics 89, 401406.CrossRefGoogle Scholar
Brommage, R & De Luca, HF (1984) A maternal defect is responsible for growth failure in vitamin D-deficient rat pups. American Journal of Physiology 246, E216E220.Google ScholarPubMed
Brown, AC & Brenton, B (1994) Dietary survey of Hopi native American elementary students. Journal of the American Dietetic Association 94, 517522.CrossRefGoogle ScholarPubMed
Byrne, PM, Freaney, R & McKenna, MJ (1995) Vitamin D supplementation in the elderly: review of safety and effectiveness of different regimes. Calcified Tissues International 56, 518520.CrossRefGoogle ScholarPubMed
Cade, C & Norman, AW (1986) Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-deficient rat in vivo. Endocrinology 119, 8490.CrossRefGoogle ScholarPubMed
Cantatore, FP, Loperfido, MC, Magli, DM, Mancini, L & Carrozzo, M (1991) The importance of vitamin C for hydroxylation of vitamin D3 to 1,25(OH)2D3 in man. Clinical Rheumatology 10, 162167.CrossRefGoogle ScholarPubMed
Chen, LZ, Easteal, S, Board, PG, Summers, KM, Bhatia, KK & Kirk, RL (1990) Albumin-vitamin-D-binding protein haplotypes in Asian-Pacific populations. Human Genetics 85, 8997.CrossRefGoogle ScholarPubMed
Chertow, BS & Baker, GR (1978) The effects of vitamin A on insulin release and glucose oxidation in isolated rat islets. Endocrinology 103, 15621572.CrossRefGoogle ScholarPubMed
Chertow, BS, Blaner, WS, Rajan, N, Primerano, DA, Meda, P, Cirulli, V, Krozowksi, Z, Smith, R & Cordle, MB (1993) Retinoic acid receptor, cytosolic retinol-binding and retinoic acid binding protein mRNA transcripts and proteins in rat insulin-secreting cells. Diabetes 42, 11091114.CrossRefGoogle ScholarPubMed
Chertow, BS, Driscoll, HK, Goking, NQ, Primerano, D, Cordle, MB & Mathews, KA (1997) Retinoid-X receptors and the effects of 9-cis-retinoic acid on insulin secretion from RINm5F cells. Metabolism 46, 656660.CrossRefGoogle ScholarPubMed
Chertow, BS, Sivitz, WI, Baranetsky, NG, Styer, TB, Sorensen, BJ, Schickman, CH, Norris, RM & Ozuk, BA (1982) Vitamin A palmitate decreases intravenous glucose tolerance in man. Acta Vitaminologica et Enzymologica 4, 291298.Google ScholarPubMed
Clark, SA, Stumpfe, WE & Sar, M (1981) Effect of 1,25 dihydroxyvitamin D3 on insulin secretion. Diabetes 30, 382386.CrossRefGoogle ScholarPubMed
Colston, KW (1996) New concepts in hormone receptor action. Lancet 342, 6768.CrossRefGoogle Scholar
Constans, J, Hazout, S, Garruto, RM, Gajdusek, DC & Spees, EK (1985) Population distribution of the human vitamin D binding protein: anthropological considerations. American Journal of Physical Anthropology 68, 107122.CrossRefGoogle ScholarPubMed
Corless, D, Boucher, BJ, Cohen, RD, Beer, M & Gupta, SP (1975) Vitamin-D status in long-stay geriatric patients. Lancet i, 14041406.CrossRefGoogle Scholar
Cruickshank, JK (1995) Challenging the orthodoxy of insulin resistance. Lancet 346, 772773.CrossRefGoogle ScholarPubMed
Dandona, P, Fonseca, V & Menon, RK (1986) Vitamin D deficiency and the endocrine pancreas. Diabetologia 29, 468469.CrossRefGoogle Scholar
Darwish, HM & DeLuca, HF (1996) Recent advances in the molecular biology of vitamin D action. Progress in Nucleic Acid Research and Molecular Biology 53, 321344.CrossRefGoogle ScholarPubMed
Davies, H (1989) Coronary heart disease: The significance of coronary pathology in infancy and the role of mitogens such as vitamin D. Medical Hypotheses 30, 179185.CrossRefGoogle ScholarPubMed
Department of Health (1979) Ultraviolet Light and Vitamin D Metabolism. Report on Health and Social Subjects no. 15. London: H.M. Stationery Office.Google Scholar
Desai, M, Bryne, J, Zhang, SJ, Petry, A, Lucas, A & Hales, CN (1997 a) Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed an isocaloric protein restricted diet. American Journal of Physiology 272, Suppl., G1083-G1090.Google ScholarPubMed
Desai, M, Petrie, CJ, Wang, CL, O'Connell, DA & Hales, CN (1997 b) Effects of maternal and early vitamin D deficiency on glucose and lipid metabolism in rat offspring. Diabetic Medicine 14, Suppl., S38 Abstr.Google Scholar
Dhawan, J, Bray, CL, Warburton, R, Ghambhir, DS & Morris, J (1994) Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant Asians. Genetic or environmental effect? British Heart Journal 72, 413421.CrossRefGoogle ScholarPubMed
Dowse, GK, Zimmet, PZ, Finch, CF & Collins, VR (1991) Decline in incidence of epidemic glucose intolerance in Nauruans: implications for the ‘thrifty genotype’ hypothesis. American Journal of Epidemiology 133, 10931104.CrossRefGoogle Scholar
Ebeling, PR, Sandgren, ME, DiMagno, EP, Lane, AW, DeLuca, HF & Riggs, BL (1992) Evidence of an age-related decrease in intestinal responsiveness to vitamin D: Relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptor concentrations in normal women. Journal of Clinical Endocrinology and Metabolism 75, 176182.Google ScholarPubMed
Fahlen, M, Oden, A, Bjorntorp, P & Tibblin, G (1971) Seasonal influence on insulin secretion in man. Clinical Science 41, 453458.CrossRefGoogle ScholarPubMed
Ferrannini, E, Buzzigoli, G, Bonadonna, R, Giorico, MA, Oleggini, M, Graziadei, L, Pedrinelli, R, Brandi, L & Bevilacqua, S (1987) Insulin resistance in essential hypertension. New England Journal of Medicine 317, 350357.CrossRefGoogle ScholarPubMed
Ferrari, S, Rizzoli, R, Chevally, T, Slosman, D, Eisman, JA & Bonjour, J (1995) Vitamin-D-receptor-gene polymorphisms and change in lumbar-spine bone mineral density. Lancet 345, 423424.CrossRefGoogle ScholarPubMed
Feskens, EJM, Bowles, CH & Kromhout, D (1991) Inverse association between fish intake and risk of glucose intolerance in normoglycaemic elderly men and women. Diabetes Care 14, 935942.CrossRefGoogle Scholar
Feskens, EJM, Bowles, CH & Kromhout, D (1993) Association between fish intake and coronary heart disease mortality. Diabetes Care 16, 10211034.CrossRefGoogle ScholarPubMed
Frankel, BJ, Heldt, AM & Grodsksy, GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209, 823825.Google Scholar
Fraser, DR (1995) Fat-soluble vitamins. Vitamin D. Lancet 345, 104107.CrossRefGoogle Scholar
Gedik, O & Akalin, S (1986) Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man. Diabetologia 29, 142145.CrossRefGoogle ScholarPubMed
Grimes, DS, Hindle, E & Dyer, T (1996) Sunlight, cholesterol and coronary heart disease. Quarterly Journal of Medicine 89, 579589.CrossRefGoogle ScholarPubMed
Groop, L, Miettenen, A, Groop, PH, Meri, S, Koskimies, S & Bottazzo, GF (1988) Organ-specific autoimmunity and HLA-DR antigens as markers for beta-cell destruction in patients with type II diabetes. Diabetes 37, 99103.CrossRefGoogle ScholarPubMed
Haddad, JG (1992) Vitamin D – solar rays, the milky way, or both?. New England Journal of Medicine 326, 12131215.CrossRefGoogle ScholarPubMed
Hales, CN & Barker, DJP (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35, 595601.CrossRefGoogle ScholarPubMed
Helgasen, T, Danielsen, R & Thorsson, AV (1992) Incidence and prevalence of Type 1 (insulin-dependent) diabetes mellitus in Icelandic children 1970–1989. Diabetologia 35, 880883.CrossRefGoogle Scholar
Henry, RR (1994) Prospects for primary prevention of type 2 diabetes mellitus. Diabetes Reviews International 3, 25.Google Scholar
Hewison, M (1992) Vitamin D and the immune system. Journal of Endocrinology 132, 173175.CrossRefGoogle ScholarPubMed
Hitman, GA, Mannan, N, McDermott, MF, Aganna, E, Hales, CN & Boucher, BJ (1998) Vitamin D polymorphisms influence insulin secretion in Bangladeshi Asians. Diabetes (In the Press).Google Scholar
Hjermann, I (1992) The metabolic cardiovascular syndrome, syndrome X, Reavens syndrome, insulin resistance syndrome, atherothrombogenic syndrome. Journal of Cardiovascular Pharmacology 55, S5S10.Google Scholar
Holick, MF (1995) Noncalcaemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 17, 107S111S.CrossRefGoogle Scholar
Hutchinson, HS & Shah, SJ (1921) The aetiology of rickets, early and late. Quarterly Journal of Medicine 15, 167194.Google Scholar
Ihde, AJ (1975) Studies on the history of rickets. Pharmacy in History 17, 1558.Google ScholarPubMed
Ikeda, K, Matsumoto, T, Morita, K, Kawanobe, Y, Ezawa, I & Ogata, E (1987) Role of insulin in the stimulation of renal 25-hydroxyvitamin D3−1 alpha-hydroxylase by phosphorous deprivation in rats. Metabolism: Clinical and Experimental 36, 555557.CrossRefGoogle ScholarPubMed
Ishida, H, Cunningham, NS, Henry, HL & Normal, AW (1988) The number of 1,25-dihydroxyvitamin D3 receptors is decreased in both intestine and kidney of genetically diabetic db/db mice. Endocrinology 122, 24362443.CrossRefGoogle ScholarPubMed
Iyengar, S, Hamman, RF, Marshall, JA, Majumder, PP & Ferrell, RE (1989) On the role of vitamin D binding globulin in glucose homeostasis: Results from the San Luis Valley Diabetes Study. Genetic Epidemiology 6, 691698.CrossRefGoogle ScholarPubMed
Iyer, P (1991) Rock and roll ghost town (Iceland). In Falling off the Map: Some Lonely Places in the World, pp. 7794. Reading: Black Swan.Google Scholar
Johnson, JA, Grande, JP, Roche, PC & Kumar, R (1994) Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. American Journal of Physiology 267, E356E360.Google ScholarPubMed
Kadowski, S & Norman, AW (1984) Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas. Journal of Clinical Investigation 73, 759766.CrossRefGoogle Scholar
Kamboh, MI & Ferrell, RE (1986) Ethnic variation in vitamin D-binding protein (Gc): a review of isoelectric focusing studies in human populations. Human Genetics 72, 281293.CrossRefGoogle ScholarPubMed
Kannel, WB, Wilson, PW & Zhang, TJ (1991) The epidemiology of impaired glucose intolerance and hypertension. American Heart Journal 121, 12681273.CrossRefGoogle ScholarPubMed
Kautsky-Willer, A, Pacini, G, Barnas, U, Ludvik, B, Streli, C, Graf, H & Prager, R (1995) Intravenous calcitriol normalizes insulin sensitivity in uremic patients. Kidney International 47, 200206.CrossRefGoogle Scholar
Khaw, KT (1994) Genetics and environment: Geoffrey Rose revisited. Lancet 343, 838839.CrossRefGoogle Scholar
Khaw, KT (1995) Temperature and cardiovascular mortality. Lancet 345, 353355.CrossRefGoogle ScholarPubMed
Kishimoto, H, Tsumura, K, Fujioka, S, Uchimoto, S & Morji, H (1993) Chronic parathyroid hormone administration reverses the antihypertensive effect of calcium loading in young spontaneously hypertensive rats. American Journal of Hypertension 6, 234240.Google ScholarPubMed
Knox, E (1973) Ischaemic-heart-disease mortality and dietary intake of calcium. Lancet i, 14651467.CrossRefGoogle Scholar
Kocian, J (1992) Diabetic osteopathy. Favourable effect of treatment of osteomalacia with vitamin D and calcium on high blood glucose levels (In Czech). Vnitrni Lekarstvi 38, 353356.Google Scholar
Kromhout, D, Bosschieter, EB & De Lezenne Coulander, C (1985) The inverse relationship between fish consumption and 20-year mortality from coronary heart disease. New England Journal of Medicine 312, 12051209.CrossRefGoogle Scholar
Kumar, S, Davies, M, Zakaria, Y, Mawer, EB, Gordon, C, Olukoga, AO & Boulton, AJ (1994) Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D. Postgraduate Medical Journal 70, 440443.CrossRefGoogle Scholar
Kuoppala, T (1988) Alterations in vitamin D metabolites and minerals in diabetic pregnancy. Gynaecology and Obstetric Investigation 25, 99105.CrossRefGoogle ScholarPubMed
Labriji-Mestaghanmi, H, Billaudel, B, Gamier, PE & Sutter, BCJ (1988) Vitamin D and pancreatic islet function. 1. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion. Journal of Endocrine Investigation 11, 577587.CrossRefGoogle ScholarPubMed
LaPorte, RE (1995) Patterns of disease: Diabetes mellitus and the rest. British Medical Journal 310, 545546.CrossRefGoogle Scholar
Levy, J, Gavin, JR & Sowers, JR (1994) Diabetes mellitus: a disease of abnormal cellular calcium metabolism?. American Journal of Medicine 96, 260263.CrossRefGoogle ScholarPubMed
Lind, L, Lithell, H, Skarfors, E, Wide, L & Ljunghall, S (1988) Reduction of blood pressure by treatment with alphacalcidol. A double-blind, placebo-controlled study in subjects with impaired glucose tolerance. Acta Medica Scandinavica 223, 211217.CrossRefGoogle ScholarPubMed
Lind, L, Pollare, T, Hvarfner, A, Lithell, H, Sorensen, OH & Ljunghall, S (1989 a) Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. Diabetes Research 11, 141147.Google ScholarPubMed
Lind, L, Wengle, B, Wide, L & Ljunghall, S (1989 b) Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study. American Journal of Hypertension 2, 2025.CrossRefGoogle ScholarPubMed
Ljunghall, S, Lind, L, Lithell, H, Skarfors, E, Selinus, I, Sorensen, OH & Wide, L (1987) Treatment with one-alpha-hydroxycholecal-ciferol in middle-aged men with impaired glucose tolerance – a prospective randomized double-blind study. Acta Medica Scandinavica 222, 361367.CrossRefGoogle ScholarPubMed
Lloyd, EL (1991) The role of cold in ischaemic heart disease: a review. Public Health 105, 205215.CrossRefGoogle ScholarPubMed
McCarron, DA & Morris, CD (1987) The calcium deficiency theory of hypertension. Annals of Internal Medicine 107, 9191022.CrossRefGoogle Scholar
McDermott, MF, Ramachandran, A, Aganna, E, Ogunkolade, W, Curtis, D, Boucher, BJ, Snehalatha, C & Hitman, GA (1997) Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians. Diabetologia 40, 971975.CrossRefGoogle ScholarPubMed
McGrath, N, Singh, V & Cundy, T (1993) Severe vitamin D deficiency in Auckland. New Zealand Medical Journal 106, 524526.Google ScholarPubMed
McKeigue, P (1994) Diets for secondary prevention of coronary heart disease: can linoleic acid substitute for fish oil? Lancet 343, 1445.CrossRefGoogle Scholar
McKeigue, PM, Pierpoint, T, Ferrie, JE & Marmot, MG (1992) Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in South Asians and Europeans. Diabetologia 35, 785791.Google ScholarPubMed
McLaughlin, M, Fairney, A, Lester, E, Raggatt, PR, Brown, DJ & Wills, MR (1974) Seasonal variation in serum 25-hydroxy cholecalciferol in healthy people. Lancet i, 536537.CrossRefGoogle Scholar
Mak, R (1994) Renal disease, insulin resistance, and glucose intolerance. Diabetes Reviews 2, 1928.Google Scholar
Mak, RH (1992 a) Intravenous 1,25 dehydroxycholecalciferol corrects glucose intolerance in haemodialysis patients. Kidney International 41, 10491054.CrossRefGoogle Scholar
Mak, RHK (1992 b) Amelioration of hypertension and insulin resistance by 1,25-dihydroxycholecalciferol in hemodialysis patients. Pediatric Nephrology 6, 345348.CrossRefGoogle ScholarPubMed
Marya, RK, Rathee, V, Lata, V & Mudgil, S (1987) Effects of vitamin D supplementation in pregnancy. Gynaecological and Obstetric Investigation 12, 155161.CrossRefGoogle Scholar
Mathieu, C, Waer, M, Casteels, K, Laureys, J & Bouillon, R (1995) Prevention of Type 1 diabetes in NOD mice by non hypercalcaemic doses of a new structural analogue of 1,25-dihydroxyvitamin D, KH1060. Endocrinology 136, 866872.CrossRefGoogle Scholar
Maxwell, JD (1994) Seasonal variation in vitamin D. Proceedings of the Nutrition Society 53, 533543.CrossRefGoogle ScholarPubMed
Maxwell, JD, Ang, L & Brooke, IR (1981) Vitamin D supplements enhance weight gain and nutritional status in pregnant Asians. British Journal of Obstetrics and Gynaecology 88, 987991.CrossRefGoogle ScholarPubMed
Metz, AL, Walser, MM & Olson, WG (1985) The interaction of dietary vitamin A and vitamin D related to skeletal development in the turkey poult. Journal of Nutrition 115, 929935.CrossRefGoogle ScholarPubMed
Milner, RDG & Hales, CN (1967) The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia 3, 4749.CrossRefGoogle ScholarPubMed
Ministry of Food (1945) Food Facts: Welfare Foods for Children. London: H.M. Stationery Office.Google Scholar
Misselwitz, J, Hesse, V & Markestad, T (1990) Nephrocalcinosis, hypercalcuria and elevated levels of 1,25-dihydroxyvitamin D in children. Possible link to vitamin D toxicity. Acta Paediatrica Scandinavica 79, 637643.CrossRefGoogle ScholarPubMed
Moon, J, Bandy, B & Davison, AJ (1992) Hypothesis; etiology of atherosclerosis and osteoporosis: are imbalances in the calciferol endocrine system implicated?. Journal of the American College of Nutrition 11, 567583.CrossRefGoogle ScholarPubMed
Morrison, NA, Qi, JC, Tokita, A, Kelly, PJ, Crofts, L, Nguyen, TV, Sambrook, PNS & Eisman, JAE (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367, 284287.CrossRefGoogle ScholarPubMed
Motahar, V & Boucher, BJ (1997) Induction of hyperglycaemia in CD1 mice by the betel-nut (Areca catechu) nitrosamine MNPN, inhibition by beta-carotene and enhancement by vitamins A and E. Clinical Science 99, 14p Abstr.Google Scholar
Nap, RC & Hazewinkel, HA (1994) Growth and skeletal development in the dog in relation to nutrition; a review. Veterinary Quarterly 16, 5059.CrossRefGoogle ScholarPubMed
Neel, JV (1962) Diabetes mellitus; a thrifty genotype rendered detrimental by ‘progress’?. American Journal of Human Genetics 14, 353362.Google Scholar
Nyomba, BL, Bouillon, R & De, Moor P (1984) Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit. Endocrinology 115, 191197.CrossRefGoogle ScholarPubMed
O'Hara-May, J & Widdowson, EM (1976) Diets and living conditions of Asian boys in Coventry with and without signs of rickets. British Journal of Nutrition 36, 2326.CrossRefGoogle Scholar
Orwoll, E, Riddle, M & Prince, M (1994) Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. American Journal of Clinical Nutrition 59, 10831087.CrossRefGoogle ScholarPubMed
Ozono, K, Seino, Y, Yano, H & Yamoaka, K (1990) 1,25-Dihydroxyvitamin D3 enhances the effect of refeeding on steady state preproinsulin messenger ribonucleic acid levels in rats. Endocrinology 126, 20412045.CrossRefGoogle ScholarPubMed
Park, EA (1923) The aetiology of rickets. Physiological Reviews 3, 106163.CrossRefGoogle Scholar
Parviainen, MT, Kumpusalo, E, Halonen, P, Neittaanmali, L & Pekkarinen, H (1992) Epidemiology of vitamins A, E, D and C in rural villages in Finland: biochemical, nutritional and socioeconomic aspects. International Journal for Vitamin and Nutrition Research 62, 238243.Google Scholar
Petri, CJ, Desai, M, Ozanne, SE & Hales, CN (1997) Early and late nutritional windows for diabetes susceptibility. Proceedings of the Nutrition Society 56, 233242.CrossRefGoogle Scholar
Phillips, DI, Barker, DJP, Hales, CN, Hirst, S & Osmond, C (1994) Thinness at birth and insulin resistance in adult life. Diabetologia 37, 150154.CrossRefGoogle ScholarPubMed
Phillips, DIW, Barker, DJP, Fall, CHD, Whorwood, CB, Walker, BR & Wood, PJ (1997) Low birthweight and raised plasma cortisol concentrations in adult life. Diabetic Medicine 14, S11 Abstr.Google Scholar
Pritchard, BNC, Smith, CCT, Ling, KL & Betteridge, DJ (1995) Fish oils and cardiovascular disease. British Medical Journal 310, 819820.CrossRefGoogle Scholar
Quin, ID & Gumpert, JRW (1997) Remission of non-insulin-dependent diabetes mellitus following resection of a parathyroid adenoma. Diabetic Medicine 14, 8081.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Reaven, GM (1995) The fourth Musketeer – from Alexandre Dumas to Claude Bernard. Diabetologia 38, 313.CrossRefGoogle Scholar
Rhodes, CJ & Alarcon, C (1994) What beta cell defect could lead to hyperproinsulinaemia in NIDDM?; some clues from recent advances made in understanding the proinsulin-processing mechanism. Diabetes 43, 511517.CrossRefGoogle Scholar
Roth, J, Bonner-Weir, S, Norman, AW & Orci, L (1982) Immunohistochemistry of vitamin D dependent calcium binding protein in chick pancreas; exclusive localization in beta cells. Endocrinology 116, 22162218.CrossRefGoogle Scholar
Riggs, BL, Hamstra, A & DeLuca, HF (1981) Assessment of 25-hydroxyvitamin D 1 alpha-hydroxylase reserve in postmeno-pausal osteoporosis by administration of parathyroid extract. Endocrinology and Metabolism 53, 833835.CrossRefGoogle Scholar
Rutter, GA, Pouli, AE & Hutton, JC (1997) A phogrin-aequorin chimera to measure free Ca2+ concentration in the vicinity of secretory granules. Diabetic Medicine 14, S34 Abstr.Google Scholar
Scarabin, PY, Bara, L, Nicaud, JP, Cambou, DA, Luc, G, Evans, AE & Cambien, F (1994) Seasonal variation of plasma fibrinogen in elderly people. Lancet 343, 975976.Google ScholarPubMed
Scragg, R (1996) Sunlight, vitamin D, and cardiovascular disease. In Calcium Regulating Hormones and Cardiovascular Function, pp. 213237 [Crass, MF and Aviol, LV, editors]. Boca Raton, FL: CRC Press.Google Scholar
Scragg, R, Holdaway, I, Jackson, R & Lim, T (1992) Plasma 25-hydroxyvitamin D3 and its relation to physical activity and other heart disease risk factors in the general population. Annals of Epidemiology 2, 697703.CrossRefGoogle ScholarPubMed
Scragg, R, Jackson, R, Holdaway, IM, Lim, T & Beaglehole, R (1995 a) Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. International Journal of Epidemiology 19, 559563.CrossRefGoogle Scholar
Scragg, R, Khaw, KT & Murphy, S (1995 b) Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults. European Journal of Clinical Nutrition 49, 640646.Google ScholarPubMed
Scragg, R, Khaw, KT & Murphy, S (1995 c) Life-style factors associated with winter serum 25-hydroxyvitamin D levels in elderly adults. Age and Ageing 24, 271275.CrossRefGoogle ScholarPubMed
Sedrani, SH (1984) Vitamin D status of Saudi men. Tropical and Geographical Medicine 36, 181187.Google ScholarPubMed
Serhan, E, Khokov, MA & Singh, BM (1997) Hypovitaminosis D in Indo-Asian patients with diabetes. Diabetic Medicine 14, S42 Abstr.Google Scholar
Specker, BL (1994) Do North American women need supplemental vitamin D during pregnancy or lactation? American Journal of Clinical Nutrition 59, 484S490S.CrossRefGoogle ScholarPubMed
Stanbury, SW & Mawer, EB (1990) Metabolic disturbances in acquired osteomalacia. In The Metabolic and Molecular Basis of Acquired Disease, pp. 17171739 [Cohen, RD, Lewis, B, Alberti, KGMM and Denman, AM, editors]. London: Balliere Tindall.Google Scholar
Strachan, DP, Powell, ICJ, Thaker, A, Millard, F & Maxwell, JD (1995) Vegetarian diet as a risk factor for tuberculosis in immigrant South London Asians. Thorax 50, 175180.CrossRefGoogle ScholarPubMed
Szathmary, EJ (1987) The effect of Gc genotype on fasting insulin level in Dogrib Indians. Human Genetics 75, 368372.CrossRefGoogle ScholarPubMed
The Eurowinter Group (1997) Cold exposure and winter mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes in warm and cold regions of Europe. Lancet 349, 13411346.CrossRefGoogle Scholar
The Nutrition Society (1997) Symposium on ‘Diabetes towards the year 2000’ (Nutrition Society Summer Meeting 24–26 June 1996). Proceedings of the Nutrition Society 56, 225290.Google Scholar
Tremoli, E, Petroni, A, Socini, A, Maderna, P, Colli, S, Paoletti, R, Galli, C, Ferro-Luzzi, A, Strazullo, P, Mancini, M, Puska, P, Iacono, J & Daugherty, R (1986) Dietary interventions in north Karelia, Finland and south Italy. Modification of thromboxane Br formation in platelets of male subjects only. Arteriosclerosis 59, 101111.CrossRefGoogle Scholar
Trowell, H (1974) Diabetes mellitus death-rates in England and Wales 1920–70 and food supplies. Lancet ii, 9981002.CrossRefGoogle Scholar
van der Wielen, RP, Lowik, MR, van den, Berg H, de Groot, LC, Haller, J, Moreiras, O & van Staveren, WA (1995) Serum vitamin D concentrations amongst elderly people in Europe. Lancet 346, 207210.CrossRefGoogle Scholar
WHO (1985) Diabetes Mellitus: report of a WHO study group on diabetes mellitus. World Health Organization Technical Report SeriesGeneva:WHO.Google Scholar
Widdowson, EM & McCance, RA (1975) A review: New thoughts on growth. Pediatric Research 9, 154156.CrossRefGoogle ScholarPubMed
Wilmshurst, P (1994) Temperature and cardiovascular mortality. British Medical Journal 309, 10291030.CrossRefGoogle ScholarPubMed
Woodhouse, PR, Khaw, KT & Plummer, M (1993) Seasonal variation of blood pressure and its relationship to ambient temperature in an elderly population. Journal of Hypertension 11, 12671274.CrossRefGoogle Scholar
Woodhouse, PR, Khaw, KT, Plummer, M, Foley, A & Meade, TW (1994) Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 343, 435439.CrossRefGoogle ScholarPubMed