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Published in: Diabetologia 7/2006

01-07-2006 | Article

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

Authors: D. A. McClain, D. Abraham, J. Rogers, R. Brady, P. Gault, R. Ajioka, J. P. Kushner

Published in: Diabetologia | Issue 7/2006

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Abstract

Aims/hypothesis

The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.

Subjects and methods

Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed.

Results

The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40–79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.

Conclusions/interpretation

Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.
Literature
1.
go back to reference Edwards C (1999) Hemochromatosis. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM (eds) Wintrobe’s Clinical Hematology. Williams & Wilkins, Baltimore, Massachusetts, pp 1056–1070 Edwards C (1999) Hemochromatosis. In: Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM (eds) Wintrobe’s Clinical Hematology. Williams & Wilkins, Baltimore, Massachusetts, pp 1056–1070
2.
go back to reference Bothwell THCR, Motulsky AG (1995) Hemochromatosis. In: Scriver CR, Beaudet A, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 2237–2269 Bothwell THCR, Motulsky AG (1995) Hemochromatosis. In: Scriver CR, Beaudet A, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 2237–2269
3.
go back to reference Feder JN, Gnirke A, Thomas W et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408PubMedCrossRef Feder JN, Gnirke A, Thomas W et al (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408PubMedCrossRef
4.
go back to reference Feder JN, Tsuchihashi Z, Irrinki A et al (1997) The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem 272:14025–14028PubMedCrossRef Feder JN, Tsuchihashi Z, Irrinki A et al (1997) The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression. J Biol Chem 272:14025–14028PubMedCrossRef
5.
go back to reference Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C (2005) Hepcidin is decreased in TFR2 hemochromatosis. Blood 105(4):1803–1806PubMedCrossRef Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C (2005) Hepcidin is decreased in TFR2 hemochromatosis. Blood 105(4):1803–1806PubMedCrossRef
6.
go back to reference Nemeth E, Tuttle MS, Powelson J et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093PubMedCrossRef Nemeth E, Tuttle MS, Powelson J et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093PubMedCrossRef
7.
go back to reference Edwards CQ, Dadone MM, Skolnick MH, Kushner JP (1982) Hereditary haemochromatosis. Clin Haematol 11:411–435PubMed Edwards CQ, Dadone MM, Skolnick MH, Kushner JP (1982) Hereditary haemochromatosis. Clin Haematol 11:411–435PubMed
8.
go back to reference Buysschaert M, Paris I, Selvais P, Hermans MP (1997) Clinical aspects of diabetes secondary to idiopathic haemochromatosis in French-speaking Belgium. Diabetes Metab 23:308–313PubMed Buysschaert M, Paris I, Selvais P, Hermans MP (1997) Clinical aspects of diabetes secondary to idiopathic haemochromatosis in French-speaking Belgium. Diabetes Metab 23:308–313PubMed
9.
go back to reference Moirand R, Adams PC, Bicheler V, Brissot P, Deugnier Y (1997) Clinical features of genetic hemochromatosis in women compared with men. Ann Intern Med 127:105–110PubMed Moirand R, Adams PC, Bicheler V, Brissot P, Deugnier Y (1997) Clinical features of genetic hemochromatosis in women compared with men. Ann Intern Med 127:105–110PubMed
10.
go back to reference Hramiak IM, Finegood DT, Adams PC (1997) Factors affecting glucose tolerance in hereditary hemochromatosis. Clin Invest Med 20:110–118PubMed Hramiak IM, Finegood DT, Adams PC (1997) Factors affecting glucose tolerance in hereditary hemochromatosis. Clin Invest Med 20:110–118PubMed
11.
go back to reference Merkel PA, Simonson DC, Amiel SA et al (1988) Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N Engl J Med 318:809–814PubMedCrossRef Merkel PA, Simonson DC, Amiel SA et al (1988) Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N Engl J Med 318:809–814PubMedCrossRef
12.
go back to reference Mendler MH, Turlin B, Moirand R et al (1999) Insulin resistance-associated hepatic iron overload. Gastroenterology 117:1155–1163PubMedCrossRef Mendler MH, Turlin B, Moirand R et al (1999) Insulin resistance-associated hepatic iron overload. Gastroenterology 117:1155–1163PubMedCrossRef
13.
14.
go back to reference Bugianesi E, Manzini P, D’Antico S et al (2004) Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 39:179–187PubMedCrossRef Bugianesi E, Manzini P, D’Antico S et al (2004) Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 39:179–187PubMedCrossRef
15.
go back to reference Cooksey RC, Jouihan HA, Ajioka RS et al (2004) Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology 145:5305–5312PubMedCrossRef Cooksey RC, Jouihan HA, Ajioka RS et al (2004) Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology 145:5305–5312PubMedCrossRef
16.
go back to reference Adams PC, Reboussin DM, Barton JC et al (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778PubMedCrossRef Adams PC, Reboussin DM, Barton JC et al (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778PubMedCrossRef
17.
go back to reference Guttridge MG, Thompson J, Worwood M, Darke C (1998) Rapid detection of genetic mutations associated with haemochromatosis. Vox Sang 75:253–256PubMedCrossRef Guttridge MG, Thompson J, Worwood M, Darke C (1998) Rapid detection of genetic mutations associated with haemochromatosis. Vox Sang 75:253–256PubMedCrossRef
18.
go back to reference Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef
19.
go back to reference Saad MF, Steil GM, Riad-Gabriel M et al 1997 Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol. Diabetes 46:2044–2048PubMedCrossRef Saad MF, Steil GM, Riad-Gabriel M et al 1997 Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol. Diabetes 46:2044–2048PubMedCrossRef
20.
go back to reference Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN (2003) MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 5:1003–1015PubMedCrossRef Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN (2003) MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 5:1003–1015PubMedCrossRef
21.
go back to reference Kenny S, Aubert RE, Geiss LS (1995) Prevalence and incidence of non-insulin-dependent diabetes. In: Health NIo, Diseases NIoDaDaK (eds) National Diabetes Data Group. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, pp 47–68 Kenny S, Aubert RE, Geiss LS (1995) Prevalence and incidence of non-insulin-dependent diabetes. In: Health NIo, Diseases NIoDaDaK (eds) National Diabetes Data Group. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, pp 47–68
22.
go back to reference Bulaj ZJ, Ajioka RS, Phillips JD et al (2000) Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 343:1529–1535PubMedCrossRef Bulaj ZJ, Ajioka RS, Phillips JD et al (2000) Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 343:1529–1535PubMedCrossRef
23.
go back to reference Kahn SE, Prigeon RL, McCulloch DK et al (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42:1663–1672PubMedCrossRef Kahn SE, Prigeon RL, McCulloch DK et al (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42:1663–1672PubMedCrossRef
24.
go back to reference Chen H, Sullivan G, Quon MJ (2005) Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes 54:1914–1925PubMedCrossRef Chen H, Sullivan G, Quon MJ (2005) Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes 54:1914–1925PubMedCrossRef
26.
go back to reference Kwan T, Leber B, Ahuja S, Carter R, Gerstein HC (1998) Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene. Clin Invest Med 21:251–257PubMed Kwan T, Leber B, Ahuja S, Carter R, Gerstein HC (1998) Patients with type 2 diabetes have a high frequency of the C282Y mutation of the hemochromatosis gene. Clin Invest Med 21:251–257PubMed
27.
go back to reference Moczulski DK, Grzeszczak W, Gawlik B (2001) Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy. Diabetes Care 24:1187–1191PubMedCrossRef Moczulski DK, Grzeszczak W, Gawlik B (2001) Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathy. Diabetes Care 24:1187–1191PubMedCrossRef
28.
go back to reference Braun J, Donner H, Plock K, Rau H, Usadel KH, Badenhoop K (1998) Hereditary haemochromatosis mutations (HFE) in patients with type II diabetes mellitus. Diabetologia 41:983–984PubMedCrossRef Braun J, Donner H, Plock K, Rau H, Usadel KH, Badenhoop K (1998) Hereditary haemochromatosis mutations (HFE) in patients with type II diabetes mellitus. Diabetologia 41:983–984PubMedCrossRef
29.
go back to reference Dubois-Laforgue D, Caillat-Zucman S, Djilali-Saiah I et al (1998) Mutations in HFE, the hemochromatosis candidate gene, in patients with NIDDM. Diabetes Care 21:1371–1372PubMedCrossRef Dubois-Laforgue D, Caillat-Zucman S, Djilali-Saiah I et al (1998) Mutations in HFE, the hemochromatosis candidate gene, in patients with NIDDM. Diabetes Care 21:1371–1372PubMedCrossRef
30.
go back to reference Frayling T, Ellard S, Grove J, Walker M, Hattersley AT (1998) C282Y mutation in HFE (haemochromatosis) gene and type 2 diabetes. Lancet 351:1933–1934PubMedCrossRef Frayling T, Ellard S, Grove J, Walker M, Hattersley AT (1998) C282Y mutation in HFE (haemochromatosis) gene and type 2 diabetes. Lancet 351:1933–1934PubMedCrossRef
31.
go back to reference Halsall DJ, McFarlane I, Luan J, Cox TM, Wareham NJ (2003) Typical type 2 diabetes mellitus and HFE gene mutations: a population-based case–control study. Hum Mol Genet 12:1361–1365PubMedCrossRef Halsall DJ, McFarlane I, Luan J, Cox TM, Wareham NJ (2003) Typical type 2 diabetes mellitus and HFE gene mutations: a population-based case–control study. Hum Mol Genet 12:1361–1365PubMedCrossRef
32.
go back to reference Sampson MJ, Williams T, Heyburn PJ et al (2000) Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes. J Lab Clin Med 135:170–173PubMedCrossRef Sampson MJ, Williams T, Heyburn PJ et al (2000) Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes. J Lab Clin Med 135:170–173PubMedCrossRef
33.
go back to reference Conte D, Manachino D, Colli A et al (1998) Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus. Ann Intern Med 128:370–373PubMed Conte D, Manachino D, Colli A et al (1998) Prevalence of genetic hemochromatosis in a cohort of Italian patients with diabetes mellitus. Ann Intern Med 128:370–373PubMed
34.
go back to reference Ellervik C, Mandrup-Poulsen T, Nordestgaard BG et al (2001) Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study. Lancet 358:1405–1409PubMedCrossRef Ellervik C, Mandrup-Poulsen T, Nordestgaard BG et al (2001) Prevalence of hereditary haemochromatosis in late-onset type 1 diabetes mellitus: a retrospective study. Lancet 358:1405–1409PubMedCrossRef
35.
go back to reference Valenti L, Conte D, Piperno A et al (2004) The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. J Med Genet 41:946–950PubMedCrossRef Valenti L, Conte D, Piperno A et al (2004) The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis. J Med Genet 41:946–950PubMedCrossRef
36.
go back to reference Bulaj ZJ, Griffen LM, Jorde LB, Edwards CQ, Kushner JP (1996) Clinical and biochemical abnormalities in people heterozygous for hemochromatosis. N Engl J Med 335:1799–1805PubMedCrossRef Bulaj ZJ, Griffen LM, Jorde LB, Edwards CQ, Kushner JP (1996) Clinical and biochemical abnormalities in people heterozygous for hemochromatosis. N Engl J Med 335:1799–1805PubMedCrossRef
37.
go back to reference Van Lerberghe S, Hermans MP, Dahan K, Buysschaert M (2002) Clinical expression and insulin sensitivity in type 2 diabetic patients with heterozygous mutations for haemochromatosis. Diabetes Metab 28:33–38PubMed Van Lerberghe S, Hermans MP, Dahan K, Buysschaert M (2002) Clinical expression and insulin sensitivity in type 2 diabetic patients with heterozygous mutations for haemochromatosis. Diabetes Metab 28:33–38PubMed
38.
go back to reference Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291:711–717PubMedCrossRef Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291:711–717PubMedCrossRef
39.
go back to reference Wilson JG, Lindquist JH, Grambow SC, Crook ED, Maher JF (2003) Potential role of increased iron stores in diabetes. Am J Med Sci 325:332–339PubMedCrossRef Wilson JG, Lindquist JH, Grambow SC, Crook ED, Maher JF (2003) Potential role of increased iron stores in diabetes. Am J Med Sci 325:332–339PubMedCrossRef
40.
go back to reference Tuomainen TP, Nyyssonen K, Salonen R et al (1997) Body iron stores are associated with serum insulin and blood glucose concentrations. Population study in 1,013 eastern Finnish men. Diabetes Care 20:426–428PubMedCrossRef Tuomainen TP, Nyyssonen K, Salonen R et al (1997) Body iron stores are associated with serum insulin and blood glucose concentrations. Population study in 1,013 eastern Finnish men. Diabetes Care 20:426–428PubMedCrossRef
41.
go back to reference Mangiagli A, Italia S, Campisi S (1998) Glucose tolerance and beta-cell secretion in patients with thalassemia major. J Pediatr Endocrinol Metab 11:985–986PubMed Mangiagli A, Italia S, Campisi S (1998) Glucose tolerance and beta-cell secretion in patients with thalassemia major. J Pediatr Endocrinol Metab 11:985–986PubMed
42.
go back to reference Pelot D, Zhou XJ, Carpenter P, Vaziri ND (1998) Effects of experimental hemosiderosis on pancreatic tissue iron content and structure. Dig Dis Sci 43:2411–2414PubMedCrossRef Pelot D, Zhou XJ, Carpenter P, Vaziri ND (1998) Effects of experimental hemosiderosis on pancreatic tissue iron content and structure. Dig Dis Sci 43:2411–2414PubMedCrossRef
44.
go back to reference MacDonald MJ, Cook JD, Epstein ML, Flowers CH (1994) Large amount of (apo)ferritin in the pancreatic insulin cell and its stimulation by glucose. FASEB J 8:777–781PubMed MacDonald MJ, Cook JD, Epstein ML, Flowers CH (1994) Large amount of (apo)ferritin in the pancreatic insulin cell and its stimulation by glucose. FASEB J 8:777–781PubMed
45.
go back to reference Cario H, Holl RW, Debatin KM, Kohne E (2003) Insulin sensitivity and beta-cell secretion in thalassemia major with secondary haemochromatosis: assessment by oral glucose tolerance test. Eur J Pediatr 162:139–146PubMed Cario H, Holl RW, Debatin KM, Kohne E (2003) Insulin sensitivity and beta-cell secretion in thalassemia major with secondary haemochromatosis: assessment by oral glucose tolerance test. Eur J Pediatr 162:139–146PubMed
46.
go back to reference Fernandez-Real JM, Lopez-Bermejo A, Ricart W (2002) Cross-talk between iron metabolism and diabetes. Diabetes 51:2348–2354PubMedCrossRef Fernandez-Real JM, Lopez-Bermejo A, Ricart W (2002) Cross-talk between iron metabolism and diabetes. Diabetes 51:2348–2354PubMedCrossRef
47.
go back to reference Turlin B, Mendler MH, Moirand R, Guyader D, Guillygomarc’h A, Deugnier Y (2001) Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients. Am J Clin Pathol 116:263–270PubMedCrossRef Turlin B, Mendler MH, Moirand R, Guyader D, Guillygomarc’h A, Deugnier Y (2001) Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients. Am J Clin Pathol 116:263–270PubMedCrossRef
48.
go back to reference Dubois-Laforgue D, Caillat-Zucman S, Boitard C, Timsit J (2000) Clinical characteristics of type 2 diabetes in patients with mutations of HFE. Diabetes Metab 26:65–68PubMed Dubois-Laforgue D, Caillat-Zucman S, Boitard C, Timsit J (2000) Clinical characteristics of type 2 diabetes in patients with mutations of HFE. Diabetes Metab 26:65–68PubMed
49.
go back to reference Caronia S, Taylor K, Pagliaro L et al (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063PubMedCrossRef Caronia S, Taylor K, Pagliaro L et al (1999) Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology 30:1059–1063PubMedCrossRef
Metadata
Title
High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis
Authors
D. A. McClain
D. Abraham
J. Rogers
R. Brady
P. Gault
R. Ajioka
J. P. Kushner
Publication date
01-07-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0200-0

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