Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.

Block, Christophe EM De; Campenhout, C M Van; Leeuw, Ivo H. De; Keenoy, Begoña Manuel y; Martin, M. De; Hoof, Viviane Van; Gaal, Luc F. Van

doi:10.2337/diacare.23.9.1384

Cited by 51 publications

(37 citation statements)

References 33 publications

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“…Transferrinuria, particularly in patients with impaired renal function and proteinuria, may also contribute to iron deficiency. Autoimmune gastritis in type 1 diabetes has been associated with iron deficiency (23), although in our survey there was no appreciable difference in Hb between type 1 and type 2 diabetes. Infection with Helicobacter pylori, the major risk factor for atrophic gastritis, may be more common in patients with diabetes and more often associated with the presence of endoscopic lesions and chronic gastritis (24).…”

Section: ϫ2contrasting

confidence: 46%

Unrecognized Anemia in Patients With Diabetes

et al. 2003

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OBJECTIVE -Anemia is common in diabetes, potentially contributing to the pathogenesis of diabetes complications. This study aims to establish the prevalence and independent predictors of anemia in a cross-sectional survey of 820 patients with diabetes in long-term follow-up in a single clinic. RESEARCH DESIGN AND METHODS-A full blood count was obtained in addition to routine blood and urine test results for all patients over a 2-year period to encompass all patterns of review. Predictors of the most recent Hb concentration and anemia were identified using multiple and logistic regression analysis.RESULTS -A total of 190 patients (23%) had unrecognized anemia (Hb Ͻ12 g/dl for women and Ͻ13 g/dl for men). This prevalence is two to three times higher than for patients with comparable renal impairment and iron stores in the general population. Independent predictors for Hb were transferrin saturation, glomerular filtration rate (GFR), sex, albumin excretion rate, and HbA 1c level (all P Ͻ 0.0001). Microalbuminuric patients were Ͼ2 times (odds ratio [OR] 2.3) and macroalbuminuric patients Ͼ10 times (OR 10.1) as likely to have anemia than normoalbuminuric patients with preserved renal function (GFR Ͼ80 ml/min).CONCLUSIONS -Anemia is a common accompaniment to diabetes, particularly in those with albuminuria or reduced renal function. Additional factors present in diabetes may contribute to the development of increased risk for anemia in patients with diabetes. Diabetes Care 26:1164 -1169, 2003D iabetes is the single most common cause of end-stage renal disease (1) and therefore the most common cause of renal anemia. In addition, anemia may be more common in diabetes (2) and develop earlier than in patients with renal impairment from other causes (3). The predominance of damage to renal interstitium, systemic inflammation, and autonomic neuropathy have all been suggested as contributors to anemia in diabetic nephropathy (DN) (3). Like many pathophysiological changes of DN, dysfunction may be apparent before demonstrable changes in the glomerular filtration rate (GFR).It is unproven whether anemia directly contributes to the acceleration of complications in DN or to the progression of diabetic renal disease. However, patients with diabetes may be more vulnerable to the effects of anemia because many also have significant cardiovascular disease and hypoxia-induced organ damage. In addition, a number of studies (4 -6) have suggested that Hb levels may be linked to the risk of cardiovascular events, hospitalization, and mortality. Against this, there is no conclusive evidence that correcting anemia significantly improves outcomes in patients with failing renal function, apart from quality of life (7).Because most patients with DN have little overt renal impairment, the majority are supervised by their primary care physician or endocrinologist. However, significant pathology may be present in patients with DN before meeting criteria for referral to a nephrologist (GFR ϳ30 ml/min) (8). In this population, renal anemia may g...

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Section: ϫ2contrasting

confidence: 46%

Unrecognized Anemia in Patients With Diabetes

et al. 2003

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“…Deficiency of insulin signaling could lead to HIO, probably through loss of restricted control of serum iron level, and an HFD seemed to have no impact on iron metabolism if it did not cause insulin decompensation, as reflected by increased fasting blood glucose. Different from DM2, in patients with type 1 diabetes mellitus, body iron store was not changed (34) or even deficient (35) as opposed to overload, and hepcidin was also reported not changed (34). Autoimmune gastritis in type 1 diabetes mellitus, caused by its specific autoimmune disorder (36), takes the most responsibility for the iron deficiency (37), and the inflammation may contribute to maintain hepcidin synthesis (24).…”

Section: Discussionmentioning

confidence: 99%

Hepcidin Is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Streptozotocin-Induced Diabetic Rats

et al. 2014

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Iron overload is frequently observed in type 2 diabetes mellitus (DM2), but the underlying mechanisms remain unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2. We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption, and liver hepcidin expression in rats treated with streptozotocin (STZ), which was given alone or after insulin resistance induced by a high-fat diet. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells. STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption and serum and hepatic iron content. Insulin obviously upregulated hepcidin expression in HepG2 cells and enhanced signal transducer and activator of transcription 3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when the signal transducer and activator of transcription 3 pathway was blocked and could be partially inhibited by U0126. In conclusion, the current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hepcidin synthesis may be an important reason for the iron overload in DM2.

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“…13 C Urea breath tests were performed as previously described (34). Antrum, corpus, and fundus biopsies were examined for HP colonization using modified Giemsa and/or immunostaining (35).…”

Section: Methodsmentioning

confidence: 99%

“…PCAs target gastric H ϩ / K ϩ ATPase (6,7) and denote autoimmune gastritis (8 -10). Chronic autoaggression to the proton pump may result in hypo/ achlorhydria, hypergastrinemia, and iron deficiency anemia (11)(12)(13)(14). PCAs may also inhibit intrinsic factor secretion, leading to pernicious anemia, which is 10 times more common in type 1 diabetic than in nondiabetic subjects (15,16).…”

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confidence: 99%

Autoimmune Gastropathy in Type 1 Diabetic Patients With Parietal Cell Antibodies

et al. 2003

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OBJECTIVE -Approximately 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H ϩ /K ϩ ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA ϩ than in PCA -patients. RESULTS -Autoimmune gastritis (AG) was present in 57% of PCA ϩ and 10% of PCA -cases (OR 12.5, P Ͻ 0.0001). PCA positivity (␤ ϭ 1.44; P ϭ 0.04) and hypergastrinemia (␤ ϭ 0.01; P ϭ 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P ϭ 0.015), pernicious anemia (OR ϭ 4.6, P ϭ 0.022), and hypochlorhydria (OR ϭ 20.0, P ϭ 0.0002) were more frequent in AG ϩ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA ϩ subjects: ECL cell hyperplasia in 7 AG ϩ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG ϩ patients, including 1 with linitis plastica. RESEARCH DESIGN AND METHODS CONCLUSIONS -PCAϩ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA ϩ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.

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Soluble transferrin receptor level: a new marker of iron deficiency anemia, a common manifestation of gastric autoimmunity in type 1 diabetes.

Cited by 51 publications

References 33 publications

Unrecognized Anemia in Patients With Diabetes

Unrecognized Anemia in Patients With Diabetes

Hepcidin Is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Streptozotocin-Induced Diabetic Rats

Autoimmune Gastropathy in Type 1 Diabetic Patients With Parietal Cell Antibodies

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