Insulin resistance–associated hepatic iron overload

Mendler, Michel; Turlin, Bruno; Moirand, Romain; Jouanolle, Anne–Marie; Sapey, Thierry; Guyader, Dominique; Gall, Jean‐Yves Le; Brissot, Pierre; David, Véronique; Deugnier, Yves

doi:10.1016/s0016-5085(99)70401-4

Cited by 452 publications

(314 citation statements)

References 45 publications

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“…The association of insulin resistance with iron overload is largely based on studies of subjects with beta thalassaemia, transfusion iron overload, coexistent liver disease or idiopathic hyperferritinaemia [11,12,40,45,46]. The different distributions of iron in these conditions compared with haemochromatosis (reticuloendothelial vs hepatocellular) [1,47] may explain the differing phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…This may be a simple association based on the fact that exposure to high levels of iron for long periods may damage the liver and beta cell in parallel. Cirrhosis, hepatitis and hepatic iron overload are themselves, however, associated with insulin resistance [12,49]. Hramiak et al reported that in the absence of cirrhosis and diabetes, Si was normal in subjects with haemochromatosis [10].…”

Section: Discussionmentioning

confidence: 99%

“…The overall prevalence of abnormal fasting glucose values in this group were: IFG 13% (95% CI [8][9][10][11][12][13][14][15][16][17][18][19][20]; diabetes 26% (95% CI 20-34). Thirty-two of the males (31%) and four of the females (12%) had diabetes.…”

Section: Historical Review Of Diabetes Prevalence Data In Haemochromamentioning

confidence: 99%

“…Many of these studies are affected by selection bias, with diabetes being assessed in subjects who have sought medical help because of associated morbidity. The pathophysiology of the diabetes associated with haemochromatosis and iron overload is poorly understood, with evidence suggesting that both insulin deficiency and insulin resistance are contributing factors [10][11][12]. Some of these studies are difficult to interpret, because subjects with established diabetes were studied, in which case the attendant hyperglycaemia may itself have resulted in insulin resistance and insulin secretory abnormalities [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Historical Review Of Diabetes Prevalence Data In Haemochromamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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“…However, most studies do not [134][135][136][137][138]. On the contrary, 30% of the patients with NAFLD have elevated ferritin levels [139][140][141], and there is an association between insulin resistance and liver iron [142,143]. Therefore, it sounds rationale that iron causes oxidative stress because it is a well-known prooxidant and possesses negative effects upon the mitochondria [144,145].…”

Section: Ironmentioning

confidence: 99%

Role of free radicals in liver diseases

2009

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Reactive oxygen and nitrogen species (ROS and RNS) are produced by metabolism of normal cells. However, in liver diseases, redox is increased thereby damaging the hepatic tissue; the capability of ethanol to increase both ROS/RNS and peroxidation of lipids, DNA, and proteins was demonstrated in a variety of systems, cells, and species, including humans. ROS/RNS can activate hepatic stellate cells, which are characterized by the enhanced production of extracellular matrix and accelerated proliferation. Cross-talk between parenchymal and nonparenchymal cells is one of the most important events in liver injury and fibrogenesis; ROS play an important role in fibrogenesis throughout increasing platelet-derived growth factor. Most hepatocellular carcinomas occur in cirrhotic livers, and the common mechanism for hepatocarcinogenesis is chronic inflammation associated with severe oxidative stress; other risk factors are dietary aflatoxin B 1 consumption, cigarette smoking, and heavy drinking. Ischemia-reperfusion injury affects directly on hepatocyte viability, particularly during transplantation and hepatic surgery; ischemia activates Kupffer cells which are the main source of ROS during the reperfusion period. The toxic action mechanism of paracetamol is focused on metabolic activation of the drug, depletion of glutathione, and covalent binding of the reactive metabolite N-acetyl-pbenzoquinone imine to cellular proteins as the main cause of hepatic cell death; intracellular steps critical for cell death include mitochondrial dysfunction and, importantly, the formation of ROS and peroxynitrite. Infection with hepatitis C is associated with increased levels of ROS/RNS and decreased antioxidant levels. As a consequence, antioxidants have been proposed as an adjunct therapy for various liver diseases.

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Diabetes Secondary to Acquired Disease to the Pancreas

Prato¹,

Coppelli²,

Tiengo³

2004

International Textbook of Diabetes Mellitus

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Secondary diabetes is a condition of hyperglycemia which develops after the destruction of the pancreatic tissue by an acquired disease with subsequent impairment of exocrine and endocrine pancreatic functions. In general, any pathologic process of the pancreatic acinar tissue may results in an insult to its endocrine component, leading to some degree of hormone insufficiency. This condition was first described in 1788 by Sir Thomas Cawley, but it was soon appreciated that hyperglycemia can ensues acute and chronic pancreatitis, partial and total pancreatectomy, neoplasia as well as systemic processes involving the pancreas, such as hemochromatosis and cystic fibrosis. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association has identified these forms of diabetes as “diabetes secondary to diseases of the exocrine pancreas.” The new diagnostic criteria for diabetes introduced by the ADA and WHO Expert Committees are likely to influence the prevalence of diabetes in patients with diseases of the exocrine pancreas, but direct assessment using the new criteria is still too scanty. When the 1979 NDDG and 1985 WHO criteria are used, it can be calculated that diabetes secondary to disease of the exocrine pancreas represents, approximately, 0.5% of all cases of diabetes mellitus. Its frequency is likely to be twice as high in populations with heavy alcohol consumption. In the tropics, the prevalence of diabetes secondary to fibrocalculous pancreatitis can be as high as 10–20%. At variance with the selective B‐cell destruction occurring in type 1 diabetes, pancreatic diabetes is characterized by concomitant destruction of all endocrine cells of the islet of Langherans. The dual insulin–glucagon deficit is responsible for many of the metabolic and clinical manifestation of this form of diabetes, including lower risk for ketoacidosis and more frequent and severe hypoglycemic episodes. Since the late 1950s, the general idea has been that secondary diabetes was not associated with vascular complications. However, with the improved life expectancy of these patients during the past few years, a similar prevalence of retinopathy and microalbuminuria has been described in pancreatic and type 1 diabetes mellitus. The knowledge of the hormonal, metabolic, and clinical features of these forms of diabetes is essential in defining the most appropriate therapeutic strategies.

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Insulin resistance–associated hepatic iron overload

Cited by 452 publications

References 45 publications

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

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

Role of free radicals in liver diseases

Diabetes Secondary to Acquired Disease to the Pancreas

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