Información del artículo
El metabolismo del hierro se halla últimamente ligado a la expresividad clínica de numerosas enfermedades sistémicas. La presencia de hierro tisular en exceso contribuye a producir y potenciar la lesión ocasionada por radicales libres y a modular la lesión inflamatoria, sobre todo a nivel hepático. La importancia que este hierro de depósito posee sobre la afección sistémica de la aterosclerosis y la diabetes mellitus se ha empezado a conocer en los últimos años. En esta revisión se intenta resumir el conocimiento acumulado en esta materia, haciendo especial hincapié en los aspectos terapéuticos. La flebotomía es sencilla y barata y con muy escasos efectos secundarios. A pesar de ello, todavía no se ha generalizado su uso ni en aquellos casos en los que la sobrecarga férrica es evidente.
Palabras clave:
Hierro
Ferritina, Hemocromatosis
DM tipo 2
Aterosclerosis
Iron metabolism is intimately linked to the clinical expression of several systemic diseases. Excess tissue iron plays a role in producing and potentiating injury caused by radicals and in modulating the inflammatory lesion, mainly in the liver. In the last few years, the importance of iron excess in the systemic modulatory effects of atherosclerosis and diabetes mellitus has begun to be described. This review describes knowledge of this field and places special emphasis on therapeutic aspects. Blood letting is simple, inexpensive and almost without side effects. However, the use of blood letting in the management of manifest iron overload is not widespread.
Key words:
Iron
Ferritin
Hemochromatosis
Type 2 diabetes mellitus
Atherosclerosis
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Bibliografía
[1.]
J.N. Feder, A. Gnirke, W. Thomas, Z. Tsuchihashi, D.A. Ruddy, A. Basava, et al.
A novel MHC class I-like gene is mutated in pacientes with hereditary haemochromatosis.
Nat Genet, 13 (1996), pp. 399-408
[2.]
B. Turlin, M.H. Mendler, R. Moirand, D. Guyader, A. Guillygo-march, Y. Deugnier.
Histologic features of the liver in insulin resistance-associated iron overload.
Am J Clin Pathol, 116 (2001), pp. 263-270
[3.]
C. Ellervik, T. Mandrup-Poulsen, B.G. Nordestgaard, L.E. Larsen, M. Appleyard, M. Frandsen, et al.
Prevalence of hereditary hemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study.
Lancet, 358 (2001), pp. 1405-1409
[4.]
E.C. Theil.
Regulation of ferritin and transferrin receptor mRNAs.
J Biol Chem, 265 (1990), pp. 4771-4774
[5.]
P. Aisen.
Iron transport and storage proteins.
Ann Rev Biochem, 49 (1980), pp. 357-393
[6.]
J. Balla, K.A. Nath, G. Balla, M.B. Juckett, H.S. Jacob, G.M. Vercellotti.
Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo.
Am J Physiol, 268 (1995), pp. L321-L327
[7.]
G. Cairo, L. Tacchini, G. Pogliaghi, E. Anzon, A. Tomasi, A. Bernelli-Zazzera.
Induction of ferritin synthesis by oxidative stress.
J Biol Chem, 270 (1995), pp. 700-703
[8.]
G. Balla, H.S. Jacob, J. Balla, M. Rosenberg, K. Nath, F. Apple, et al.
Ferritin: a cytoprotective antioxidant strategem of endothelim.
J Biol Chem, 267 (1992), pp. 18148-18153
[9.]
D.W. Reif.
Ferritin as a source of iron for oxidative damage.
Free Rad Biol Med, 12 (1992), pp. 417-427
[10.]
C.E. Thomas, L.A. Morehouse, S.D. Aust.
Ferritin and superoxidedependent lipid peroxidatio.
J Biol Chem, 260 (1985), pp. 3275-3280
[11.]
Y. Qi, T.M. Jamindanar, G. Dawson.
Hypoxia alters iron homeostasis and induces ferritin synthesis in oligodendrocytes.
J Neurochem, 64 (1995), pp. 2458-2464
[12.]
B.J. Van Lenten, J. Prieve, M. Navab, S. Hama, A.J. Lusis, A.M. Fogelman.
Lipid-induced changes in intracellular iron homeostasis in vitro and in vivo.
J Clin Invest, 95 (1995), pp. 2104-2110
[13.]
S.D. Aust.
Ferritin as a source of iron and protection from ironinduced toxicities.
Toxicol Lett, 82 (1995), pp. 941/4
[14.]
M.B. Juckett, J. Balla, G. Balla, J. Jessurun, H.S. Jacob, G.M. Vercellotti.
Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.
Am J Pathol, 147 (1995), pp. 782-789
[15.]
C.L. Smith, M.J. Mitchinson, O.I. Aruoma, B. Halliwell.
Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherostatic lesions.
Biochem J, 286 (1992), pp. 901-905
[16.]
G.C. Hunter, M.A. Dubick, C.L. Keen, C.D. Eskelson.
Effects of hypertension of aortic antioxidant status in human abdominal aneurysmal and occlusive disease.
Proc Soc Exp Biol Med, 196 (1991), pp. 273-279
[17.]
Baynes JW-Role of oxidative stress in development of complications in diabetes.
Diabetes, 40 (1991), pp. 405-412
[18.]
T. Sakurai, S. Kimura, M. Nakano, H. Kimura.
Oxidative modification of glycate low density lipoprotein in the presence of iron.
Biochem Biophys Res Comm, 177 (1991), pp. 433-439
[19.]
S. Fujimoto, N. Kawakami, A. Ohara.
Nonenzymatic glycation of transferrin: Decrease of Iron-binding capacity and increase of oxygen radical production.
Biol Pharm Bull, 18 (1995), pp. 396-400
[20.]
J.C. Sibille, H. Kondo, P. Aisen.
Uptake of ferritin and iron bound to ferritin by hepatocytes: modulation by apotransferrin, iron chelators and chloroquine.
Biochem Biophys Acta, 1010 (1989), pp. 204-209
[21.]
T.B. Kaye, A.T. Guay, D.C. Simonson.
Non-insulin dependent diabetes mellitus and elevated serum ferritin level.
J Diabetes Complications, 7 (1993), pp. 246-249
[22.]
J.B. Redmon, K.L. Pyzdrowski, R.P. Robertson.
No effect of deferoxamine therapy on glucose homeostasis and insulin secretion in individuals with NIDDM and elevated serum ferritin.
Diabetes, 42 (1993), pp. 544-549
[23.]
G. Gallou, I. Guilhem, J.Y. Poirier, A. Ruelland, B. Legras, L. Cloarec.
Increased serum ferritin in insulin-dependent diabetes mellitus: relation to glycemic control.
Clin Chem, 40 (1994), pp. 947-948
[24.]
S.F. Dinneen, M.S. O'Mahony, T. O'Brien, C.C. Cronin, D.M. Murray, D.J. O'Sullivan.
Serum ferritin in newly diagnosed and poorly controlled diabetes mellitus.
Ir J Med Sci, 161 (1992), pp. 636-638
[25.]
B.A. Van Oost, B. Van den Beld, LGLM Cloin, J.J.M. Marx.
Measurement of ferritin in serum: application in diagnostic use.
Clin Biochem, 17 (1984), pp. 263-269
[26.]
G. Phelps, I. Chapman, P. Hall, W. Braund, M. Mackinnon.
Prevalence of genetic haemochromatosis among diabetic patients.
Lancet, 2 (1989), pp. 223-224
[27.]
D. Conte, D. Manachino, A. Colli, A. Guala, G. Aimo, M. Andreoletti, et al.
Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus.
Ann Intern Med, 128 (1998), pp. 370-373
[28.]
T. Frayling, S. Ellard, J. Grove, M. Walker, A.T. Hattersley.
C282Y mutation in HFE (haemochromatosis) genet and type 2 diabetes.
Lancet, 351 (1998), pp. 1933-1934
[29.]
J. Braun, H. Donner, K. Plock, H. Rau, K.H. Usadel, K. Badenhoop.
Hereditary haemochromatosis mutations (HFE) in patients with type 2 diabetes mellitus.
Diabetologia, 41 (1998), pp. 983-984
[30.]
D. Dubois-Laforgue, S. Caillat-Zucman, I. Djilali-Saiah, E. Larger, A. Mercadier, C. Boitard, et al.
Mutations in HFE the hemochromatosis candidate gene, in patients with NIDDM.
Diabetes Care, 21 (1998), pp. 1371-1372
[31.]
J.M. Fernández-Real, J. Vendrell, M. Baiget, E. Gimferrer, W. Ricart.
C292Y and H63D mutations of the hemochromatosis candidate gene in type 2 diabetes.
Diabetes Care, 22 (1999), pp. 525-526
[32.]
J.N. Feder, D.M. Penny, A. Irrinki, V.K. Lee, J.A. Lebron, N. Watson, et al.
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding.
Proc Natl Acad Sci USA, 95 (1998), pp. 1472-1477
[33.]
G. Porto, H. Alves, P. Rodrigues, J.M. Cabeda, C. Portal, A. Ruivo, et al.
Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis.
Immunogenetics, 47 (1998), pp. 404-410
[34.]
M. Sampietro, A. Piperno, L. Lupica, C. Arosio, A. Vergani, N. Corbetta, et al.
High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda.
Hepatology, 27 (1998), pp. 181-184
[35.]
D.K. Moczulski, W. Greszczak, B. Gawlik.
Role for hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy.
Diabetes Care, 24 (2001), pp. 1187-1191
[36.]
R.F. Gillum.
Association of serum ferritin and indices of body fat distribution and obesity in Mexicam American men– the Third National Health and Nutrition Examination Survey.
Int J Obes Real Metab Dis, 25 (2001), pp. 639-645
[37.]
T-P Tuomainen, K. Nyysönen, R. Salonen, A. Tervahauta, H. Korpela, T. Lakka, et al.
Body iron stores are associated with serum insulin and blood glucose concentrations.
Diabetes Care, 20 (1997), pp. 426-428
[38.]
J.M. Fernández-Real, W. Ricart, E. Arroyo, R. Balança, R. Casamitjana, D. Cabrero, et al.
Serum ferritin as a component of the insulin resistance syndrome.
Diabetes Care, 21 (1998), pp. 62-68
[39.]
W. Zidek, W. Tenschert, C. Karoff, H. Vetter.
Treatment of resistant hypertension by phlebotomy.
Klin Wohenschr, 63 (1985), pp. 762-764
[40.]
M. Barenbrock, C. Spieker, K.H. Rahn, W. Zidek.
Therapeutic efficiency of phlebotomy in posttransplant hypertension associated with erythrocytosis.
Clin Nephrol, 40 (1993), pp. 241-243
[41.]
A. Dávalos, J.M. Fernández-Real, W. Ricart, S. Soler, A. Molins, E. Planas, et al.
Iron related damage in ischemic acute stroke.
Stroke, 25 (1994), pp. 1543-1546
[42.]
R. Moriand, A. Mortaji, O. Loréal, F. Paillard, P. Brissot, Y. Deugnier.
A new syndrome of liver iron overload with normal transferrin saturation.
Lancet, 349 (1997), pp. 95-97
[43.]
N. Milman.
Serum ferritin in Danes: studies of iron status from infancy to old.
Int J Hematol, 63 (1996), pp. 103-135
[44.]
Z.B. Bulaj, L.M. Griffen, L.B. Jorde, C.Q. Edwards, J.P. Kushner.
Clinical and biochemical abnormalities in people heterozygous for hemochromatosis.
N Engl J Med, 335 (1996), pp. 1799-1805
[45.]
P. Dandona, M.A.M. Hussain, Z. Varghese, D. Politis, D.M. Flynn, A.V. Hoffbrand.
Insulin resistance and iron overload.
Ann Clin Biochem, 20 (1983), pp. 77-79
[46.]
C. Niederau, M. Berger, W. Stremmel, A. Starke, G. Strohmeyer, R. Ebert, et al.
Hyperinsulinemia in non-cirrhotic haemochromatosis: Impaired hepatic insulin degradation?.
Diabetologia, 26 (1984), pp. 441-444
[47.]
A.I. Shafer, R.G. Cheron, R. Dluhy, B. Cooper, R.E. Gleason, J.S. Soeldner, et al.
Clinical consequences of acquired transfusional iron overload in adults.
N Engl J Med, 304 (1981), pp. 319-324
[48.]
L.D. Katz, M.G. Glickman, S. Rapoport, E. Ferannini, R.A. DeFronzo.
Splanchnic and peripheral glucose disposal of oral glucose in man.
Diabetes, 32 (1983), pp. 675-679
[49.]
M. Bertelsen, E.E. Anggard, M.J. Carrier.
Oxidative stress impairs insulin internalization in endothelial cells in vitro.
Diabetologia, 44 (2001), pp. 605-613
[50.]
D. Mauricio, A. Perez, A. Riera, J.A. Arroyo, A. de Leiva, E. Gimferrer.
Serum parameters of iron metabolism in type I (insulin dependent) diabetes mellitus.
Diab Nutr Metab, 8 (1993), pp. 315-316
[51.]
N. Yokomori, Y. Iwasa, K. Aida, M. Inoue, M. Tawata, T. Onaya.
Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells.
Endocrinology, 128 (1991), pp. 1474-1480
[52.]
P.A. Merkel, D.C. Simonson, S.A. Amiel, G. Plewe, R.S. Sherwin, H.A. Pearson, et al.
Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion.
N Engl J Med, 318 (1988), pp. 809-814
[53.]
K. Dmochowski, D.T. Finegood, W. Francombe, B. Tyler, B. Zinman.
Factors determining glucose tolerance in patients with thalassemia major.
J Clin Endocrinol Metab, 77 (1993), pp. 478-483
[54.]
P. Cavallo-Perin, G. Pacini, F. Cerutti, A. Bessone, C. Condo, L. Sacchetti, et al.
Insulin resistance and hyperinsulinemia in homozygous β-thalassemia.
Metabolism, 44 (1995), pp. 281-286
[55.]
T.T. Lao, P.L. Chan, K.F. Tam.
Gestational diabetes mellitus in the last trimester .a feature of maternal iron excess?.
Diabetic Med, 18 (2001), pp. 218-223
[56.]
T.T. Lao, K.F. Tam.
Maternal serum ferritin and gestational impaired glucose tolerance.
Diabetes Care, 20 (1997), pp. 1368-1369
[57.]
B. Bacon, M.J. Farahvash, C.G. Janney, B.A. Neuschwander-Tetri.
Nonalcoholic statohepatitis: an expanded clinical entity.
Gastroenterology, 107 (1994), pp. 1103-1109
[58.]
D. George, S. Goldwrum, G. MacDonald, L.L. Cowley, N.I. Walker, P.J. Ward, et al.
Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.
Gastroenterology, 114 (1998), pp. 311-318
[59.]
H. Bonkowsky, Q. Jawaid, K. Tortorelli, P. LeClair, J. Cobb, R.W. Lambrecht, et al.
Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis.
J Hepatol, 31 (1999), pp. 421-429
[60.]
G. Marchesini, M. Brizi, G. Bianchi, S. Tomassetti, E. Gubianesi, M. Lenzi, et al.
Nonalcoholic fatty liver disease. A feature of the metabolic syndrome.
Diabetes, 50 (2001), pp. 1844-1850
[61.]
B. Turlin, M.H. Mendler, R. Moirand, D. Guyader, A. Guillygomarch, Y. Deugnier.
Histologic features of the liver in insulin resistance-associated iron overload.
Am J Clin Pathol, 116 (2001), pp. 263-270
[62.]
M. Mendler, B. Turlin, R. Moirand, A.m. Juanolle, T. Sapey, D. Guyader, et al.
Insulin resistance-associated iron overload.
Gastroenterology, 117 (1999), pp. 1155-1163
[63.]
J.M. Petit, J.B. Bour, C. Galland-Jos, A. Minello, B. Vergese, M. Guiguet, et al.
Risk factors for diabetes mellitus and early insulin resistance in chronic hepatitis C.
J Hepatol, 35 (2001), pp. 279-283
[64.]
C. Hernandez, J. Genesca, J. Ignasi Esteban, L. Garcia, R. Simo.
Relacion entre los depositos de hierro y diabetes mellitus en pacientes infectados por el virus de la hepatitis C: estudio caso-control.
Med Clin (Barc), 115 (2000), pp. 21-22
[65.]
M.T. Johnstone, S.J. Creager, K.M. Scales, J.A. Cusco, B.K. Lee, M.A. Creager.
Impaired endothelium-dependent vasodilatation in patients with insulin-dependent diabetes.
Circulation, 88 (1993), pp. 2510-2516
[66.]
A. Nitenberg, P. Valensi, R. Sachs, M. Dali, E. Aptecar, J. Attali.
Impairment of coronary vascular reserve and Ach-induced vasodilatation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function.
Diabetes, 43 (1993), pp. 1017-1025
[67.]
G.E. McVeigh, G.M. Brennan, G.D. Johnston, B.J. McDermott, L.T. McGrath, W.R. Henry, et al.
Impaired endothelium-dependent and independent vasodilatation in patients with type 2 (non-insulin-dependent) diabetes mellitus.
Diabetologia, 35 (1992), pp. 771-776
[68.]
H.O. Steinberg, G. Brechtel, A. Johnson, N. Fineberg, A.D. Baron.
Insulin-medited skeletal muscle vasodilatation is nitric oxide dependent.
J Clin Invest, 1 (1994), pp. 172-179
[69.]
U. Schrrer, D. Randin, P. Vollenweider, L. Vollenweider, P. Nicod.
Nitric oxide release accounts for insulin's vascular effects in humans.
J Clin Invest, 94 (1994), pp. 2511-2515
[70.]
G. Bohlen, J.M. Lash.
Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilatation of normal rat arterioles.
Am J Physiol, 265 (1993), pp. H219-H225
[71.]
B. Tesfamariam, R.A. Cohen.
Free radicals mediate endothelial cell dysfunction caused by elevated glucose.
Am J Physiol, (1992), pp. H321-H326
[72.]
R. Bucala, D.J. Tracey, A. Cerami.
Advanced glycosylation products quench nitric oxide and mediate defective endotheliumdependent vasodilatation in experimental diabetes.
J Clin Invest, 87 (1991), pp. 432-438
[73.]
S. Makimattila, M. Mantysaari, P-H Groop, P. Summanen, A. Virkamaki, A. Schlenzka, et al.
Hyperreactivity to nitrovasodilators in forearm vasculature is related to autonomic dysfunction in insulin-dependent diabetes mellitus.
Circulation, 95 (1997), pp. 618-625
[74.]
S. Makimattila, A. Virkamaki, P-H Groop, J. Cockroft, T. Utriainen, J. Fagerudd, et al.
Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus.
Circulation, 94 (1996), pp. 1276-1282
[75.]
W.F. Graier, S. Simecek, W.R. Kukovetz, G.M. Kostner.
High Dglucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions.
Diabetes, 45 (1996), pp. 1386-1395
[76.]
J.V. Hunt, C.C.T. Smith, S.P. Wolff.
Autooxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose.
Diabets, 39 (1990), pp. 1420-1424
[77.]
S.K. Jain.
Hyperglycemia can cause membrane lipids peroxidation and osmotic fragility in human red blood cells.
J Biol Chem, 264 (1989), pp. 21340-21345
[78.]
S.P. Wolff, R.T. Dan.
Glucose autooxidation and protein modification. The potential role of oxidative glycosylation in diabetes.
Biochem J, (1987), pp. 245-250
[79.]
M.S.M. Chen, M.L. Hutchinson, R.E. Pecoraro, W.Y. Lee, R.F. Labbe.
Hyperglycemia-induced intracellular depletion of ascorbic acid in human mononuclear leukocytes.
Diabetes, 32 (1983), pp. 1078-1081
[80.]
J.J. Cunninham, S.L. Ellis, K.L. McVeigh, R.E. Levine, J. Calles-Escandon.
Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consumming adequate dietary vitamin C.
Metab Clin Exp, 40 (1991), pp. 146-149
[81.]
D.K.S. Yue, S. McLennon, E. Fisher, S. Hefferman, C. Capogreco, G.R. Ross, et al.
Ascorbic acid status and polyol pathway in diabetes.
Diabetes, 38 (1989), pp. 257-261
[82.]
D.J. Diederich, J. Skopec, A. Diederich, F. Dai.
Endothelial dysfunction in mesenteric resistance arteries of diabets rats: role of free radicals.
Am J Physiol, 266 (1994), pp. H1153-H1161
[83.]
H.H. Ting, F.K. Timini, K.S. Boles, S.J. Creager, P. Ganz, M.A. Creager.
Vitamin C improves endothelium-dependent vasodilatation in patients with non-insulin-dependent diabetes mellitus.
J Clin Invest, 97 (1996), pp. 22-28
[84.]
P. Langenstroer, G.M. Pieper.
Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals.
Am J Physiol, 263 (1992), pp. H257-H265
[85.]
Y.H. Hattori, H. Kawasaki, A. Kazuhiro, M. Kanno.
Superoxide dismutase revovers altered endothelium-dependent relaxation in diabetic rat aorta.
Am J Physiol, 261 (1991), pp. H1086-H1094
[86.]
G. Paolisso, A. Gambardella, M.R. Tagliamonte, F. Saccomanno, T. Salvatore, P. Gualdiero, et al.
Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?.
J Clin Endocrinol Metab, 81 (1996), pp. 4244-4248
[87.]
G.M. Pieper, W. Siebeneich.
Diabetes-induced endothelial dysfunction is prevented by long-term treatment with the modified iron chelator, hydroxyethyl starch conjugated-deferoxamine.
J Cardiovasc Pharmacol, 30 (1997), pp. 734-738
[88.]
A. Nitenberg, F. Paycha, S. Ledoux, R. Sachs, J-R Attali, P. Valensi.
Coronary artery responses to phsysiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors.
Circulation, 97 (1998), pp. 736-743
[89.]
S.J. Duffy, E.S. Biegelsen, M. Holbrook, J.D. Russell, N. Gokce, J.F. Keaney Jr., et al.
Iron chelation improves endothelial in patients with coronary artery disease.
Circulation, 103 (2001), pp. 2799-2804
[90.]
N.E. Cameron, M.A. Cotter.
Effects of an extracellular metal chelator on neurovascular function in diabetics rats.
Diabetologia, 44 (2001), pp. 621-628
[91.]
J.S. Beckman, T.W. Beckman, J. Chen, P.A. Marshall, B.A. Freeman.
Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.
Proc Natl Acad Sci USA, 87 (1990), pp. 1620-1624
[92.]
Fernández-Real JM, Peñarroja G, Castro A, Laínez B, García-Bragado F, Ricart W. Blood letting in high-ferritin type 2 diabetes mellitus. Improvement in vascular dysfunction after decreasing circulating iron [en prensa].
[93.]
J.J. Graham, R.G. Ryall, P.H. Wise.
Glycosylated haemoglobin and relative polycythaemia in diabetes mellitus.
Diabetologia, 18 (1980), pp. 205-207
[94.]
J. Angulo, C.F. Sanchez-Ferrer, C. Peiro, J. Marin, L. Rodriguez-Manas.
Impairment of endothelium-dependent relaxation by increasing percentages of glycosylated human hemoglobin: possible mechanisms involved.
Hypertension, 28 (1996), pp. 583-592
[95.]
B. Faivre-Fiorina, A. Caron, C. Fassot, I. Fries, P. Menu, P. Labrude, et al.
Presence of hemoglobin inside aortic cells afeter cell-free hemoglobin administration in guinea-pigs.
Am J Physiol, 276 (1999), pp. H766-H770
[96.]
M. Barbieri, E. Ragno, E. Benvenutti, G.A. Zito, A. Corsi, L. Ferruci, et al.
New aspects of the insulin resistance syndrome: impact on haematological parameters.
Diabetologia, 44 (2001), pp. 232-237
[97.]
C. Catalano, E. Muscelli, A. Quinones, S. Baldi, D. Ciociaro, G. Seghieri, et al.
Reciprocal association between insulin sensitivity and the hematocrit in man.
Diabetes, 45 (1996), pp. 323A
[98.]
S.G. Wannamethee, A.G. Perry.
Hematocrit and risk of NIDDM.
Diabetes, 45 (1996), pp. 576-579
[99.]
P.W. Wilson, D.L. McGee, W.B. Kannel.
Obesity, very low density lipoproteins and glucose intolerance over fourteen years: the Framingham Study.
Am J Epidemiol, 114 (1981), pp. 697-704
[100.]
J.H. Medaile, C.M. Perrier, U. Goldbourt, J.B. Herman.
Major factors in the development of diabetes mellitus in 10,000 men.
Arch Intern Med, 135 (1975), pp. 811-817
[101.]
J.T. Salonen, T-P Tuomainen, K. Nyyssonen, H-M Lakka, K. Punnonen.
Relation between iron stores and non-insulindependent diabetes in men: case-control study.
BMJ, 317 (1999), pp. 727-730
[102.]
I.S. Young, S. Tate, J.H. Lighbody, D. McMaster, E.R. Trimble.
The effects of desferrioxamine and ascorbate on oxidative stress in the streptozotin diabetic rat.
Free Radical Biol Med, 18 (1995), pp. 833-840
[103.]
J.F. Yale, M. Grose, T.A. Seemayer, E.B. Marliss.
Diabetes prevention in BB rats by frequent blood withdrawal started at a young age.
Diabetes, 37 (1988), pp. 327-333
[104.]
A. Ascherio, E.B. Rimm, E. Giovannucci, W.C. Willett, M.J. Stampfer.
Blood donations and risk of coronary heart disease in men.
Circulation, 103 (2001), pp. 52-57
[105.]
C. Bofill, J. Joven, J. Bages, E. Vilella, T. Sans, P. Cavalle, et al.
Response to repeated phlebotomies in patients with non-insulin-dependent diabetes mellitus.
Metabolism, 54 (1994), pp. 614-620
[106.]
W.D. Davis, W.R. Arrowsmith.
The treatment of haemochromatosis by massive-venesection.
Ann Intern Med, 39 (1953), pp. 723-734
[107.]
I.W. Dymock, J. Cassar, D.A. Pyke, W.G. Oakley, R. Williams.
Observations on the pathogenesis, complications and treatment of diabetes in 115 cases of hemochromatosis.
Am J Med, 52 (1972), pp. 203-210
[108.]
C.Q. Edwards, G.E. Cartwright, M.H. Skolnick, D.B. Amos.
Homozygosity for hemochromatosis: Clinical manifestations.
Ann Intern Med, 93 (1980), pp. 519-525
[109.]
E. Eschwege, R. Saddi, H. Wacjman, R. Levy, N. Thibult, A. Duchateau.
haemoglobin AIc in patients on venesection therapy for haemochromatosis.
Diabetes Metab, 8 (1982), pp. 137-140
[110.]
L.W. Powell, J.F.R. Kerr.
Reversal of “cirrhosis” in idiopatic haemochromatosis following long-term intensive venesection therapy.
Australas An Med, 1 (1970), pp. 54-57
[111.]
R. Williams, P.M. Smith, E.J.F. Spicer, M. Barry, S. Sherlock.
Venessection therapy in idiopatic haemochromatosis. An analysis of 40 treated and 18 untreated patients.
Q J Med, 149 (1969), pp. 1-16
[112.]
C. Niederau, R. Fischer, A. Sonnenberg, W. Stremmel, H.J. Trampisch, G. Strohmeyer.
Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis.
N Engl J Med, 313 (1985), pp. 1256-1262
[113.]
P. Cutler.
Deferoxamine therapy in high-ferritin diabetes.
Diabetes, 38 (1989), pp. 1207-1210
[114.]
F.S. Facchini.
Effect of phlebotomy on plasma glucose and insulin concentrations.
Diabetes Care, 21 (1998), pp. 2190
[115.]
J.T. Salonen, H. Korpela, K. Nyysonen, E. Porkkala, T-P Tuomainen, J.D. Belcher, et al.
Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins: a randomised cross-over trial in male smokers.
J Intern Med, 237 (1995), pp. 161-168
[116.]
J.M. Fernandez-Real, G. Penarroja, A. Castro, F. Garcia-Bragado, I. Hernandez, W. Ricart.
Blood letting in high-ferritin type 2 diabetes mellitus. Effects on insulin sensitivity and β-cell function.
Diabetes, 51 (2002), pp. 1000-1004
[117.]
N.W. Hua, R.A. Stoohs, F.S. Facchini.
Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.
Br J Nutr, 86 (2001), pp. 515-519
[118.]
C.A. Finch, H. Huebers.
Perspectives in iron metabolism.
N Engl J Med, 306 (1982), pp. 1520-1528
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