Complications of hemochromatosis and iron overload

Clin Med�Insights�Arthritis�Musculoskelet Disord

2012

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BackgroundDupuytren’s contracture (DC) and HFE hemochromatosis occur in some of the same at-risk populations and present with similar comorbid conditions.MethodsWe estimated DC prevalence in two cohorts of white Alabama hemochromatosis probands (294 C282Y homozygotes, 67 C282Y/H63D compound heterozygotes) in a retrospective study. We performed logistic regressions on DC using the following independent variables: age, body mass index, heavy ethanol consumption, serum ferritin, elevated serum AST/ALT, non-alcoholic fatty liver disease, viral hepatitis, cirrhosis, and diabetes.ResultsOne man and two women with C282Y homozygosity had DC (prevalence 1.02%; 95% CI 0.35%–2.96%). A man with C282Y/H63D had DC (prevalence 1.49%; 95% CI 0.26%–7.98%). DC occurred as an autosomal dominant trait in his kinship. In regression analyses, no single variable predicted DC. We observed no new DC cases after the diagnosis of hemochromatosis (mean follow-up 12.9 ± 7.5 years (1 SD), and 9.0 ± 5.1 years, respectively).ConclusionsOur prevalence estimates of DC in white Alabama hemochromatosis probands are similar to those found in the white US population cohorts. DC risk was unrelated to the variables we studied.

Section: Discussionsupporting

confidence: 90%

Dupuytren's Contracture in AlabamaHFEHemochromatosis Probands

Clin Med�Insights�Arthritis�Musculoskelet Disord

2012

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“…p.C282Y homozygosity accounts for ~90% of whites of European descent with “classical” hemochromatosis iron phenotypes [ 13 – 15 ]. Severe iron overload in p.C282Y homozygotes may cause cirrhosis, primary liver cancer, diabetes, other endocrinopathies, and cardiomyopathy [ 15 , 16 ].…”

Section: Hfe Hemochromatosismentioning

confidence: 99%

Diabetes inHFEHemochromatosis

Journal of Diabetes Research

Acton

2017

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Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis.

“…Probands who had symptoms or physical examination findings in hand joints suggestive or typical of hemochromatosis arthropathy at diagnosis were evaluated with hand radiographs and other studies, as appropriate. The objective criteria we used to classify probands as having hemochromatosis hand arthropathy included 1) symmetrical polyarthropathy, typically with hypertrophy and related abnormalities of metacarpophalangeal and proximal interphalangeal joints; 2) subchondral cysts with sclerotic margins at the metacarpal heads, especially of the second and third metacarpophalangeal joints; and 3) joint space narrowing, usually with asymmetric cartilage loss (4,23). Other abnormalities were detected in some probands, especially those with severe arthropathy (4,23).…”

Section: Definition Of Hemochromatosis Hand Arthropathymentioning

confidence: 99%

“…Iron overload, especially if severe, may cause cirrhosis, primary liver cancer, diabetes, other endocrinopathy, and cardiomyopathy (3,4). A diagnostic triad for hemochromatosis of hyperpigmentation, diabetes, and cirrhosis was proposed in the 19th century (5).…”

mentioning

confidence: 99%

“…Thus, a critical multivariable assessment of the relationships of the type(s) of diabetes, severity of iron overload, occurrence of liver disease, family history of diabetes, and other variables in people with hemochromatosis and HFE C282Y homozygosity has not been reported (4). We sought to identify factors associated with increased risk of diabetes at diagnosis in 159 nonscreening hemochromatosis probands, each of whom also had HFE C282Y homozygosity.…”

mentioning

confidence: 99%

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Diabetes in First-Degree Family Members: A Predictor of Type 2 Diabetes in 159 Nonscreening Alabama Hemochromatosis Probands With HFE C282Y Homozygosity

Acton

2013

Diabetes Care

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OBJECTIVEWe sought to identify predictors of diabetes diagnosed before hemochromatosis. RESEARCH DESIGN AND METHODSWe studied these 16 variables in 159 nonscreening hemochromatosis probands with HFE C282Y homozygosity: age; sex; BMI; diabetes reports in first-degree family members (dichotomous); heavy ethanol consumption; cigarette smoking; elevated serum alanine aminotransferase/aspartate aminotransferase levels; nonalcoholic fatty liver; chronic viral hepatitis; cirrhosis; hand arthropathy; iron removed by phlebotomy; and positivity for HLA-A*01, B*08; A*03, B*07; and A*03, B*14 haplotypes. We performed univariable and multivariable analyses. RESULTSTwenty-three probands (14.5%) had diabetes; 19 were men. Each of the 23 probands had type 2 diabetes. Mean BMI was greater in probands with diabetes (31.7 6 8.5 [SD] kg/m 2 vs. 27.6 6 5.1 kg/m 2 ; P = 0.032). Reports of any first-degree family member with diabetes were more prevalent in probands with than in probands without diabetes (69.6 vs. 17.6%; P < 0.0001). In probands with diabetes, the odds ratio (OR) of maternal diabetes was 6.7 (95% CI 2.3-19.7; P = 0.0005) and of sibling diabetes was 11.7 (3.0-45.5; P = 0.0004). In a logistic regression model, predictors of diabetes at hemochromatosis diagnosis in 159 probands were diabetes reports in family members .8]; P < 0.0001) and BMI (1.1 [1.0-1.2]; P = 0.049). This model explained 26.0% of total deviance contributing to diabetes. CONCLUSIONSIn nonscreening hemochromatosis probands with HFE C282Y homozygosity, a heritable factor(s) increases the risk of diabetes diagnosed before hemochromatosis.