Circulating hepcidin in type 2 diabetes: A multivariate analysis and double blind evaluation of metformin effects

Suárez-Ortegón, Milton Fabian; Moreno, María; Arbeláez, Alejandra; Xifra, Gemma; Mosquera, Mildrey; Moreno-Navarrete, José María; Plata, Cecilia Aguilar-de; Esteve, Eduardo; Ricart, Wifredo; Fernández-Real, José Manuel

doi:10.1002/mnfr.201500310

Cited by 21 publications

(23 citation statements)

References 40 publications

(54 reference statements)

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“…Previous studies have demonstrated a significant reduction of serum hepcidin in patients with T2D, in agreement with current findings . In rats, the administration of streptozotocin led to increased body iron stores (hepatic and serum iron content), increased intestinal ferroportin levels, and iron absorption in parallel to decreased serum hepcidin levels …”

Section: Discussionsupporting

confidence: 92%

“…In addition, the positive associations of both SLC40A1 and SLC11A2 mRNA levels with the ferritin‐to‐hepcidin ratio suggest insufficient hepcidin levels in relation to body iron stores. This ratio usually indicates inadequate production of hepcidin to decrease intestinal iron absorption . In fact, we here found a negative association between SLC40A1 mRNA levels and circulating hepcidin concentrations.…”

Section: Discussionmentioning

confidence: 42%

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Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

Moreno-Navarrete

Rodrı́guez

Becerril

et al. 2017

Molecular Nutrition Food Res

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 42%

Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

Moreno-Navarrete

Rodrı́guez

Becerril

et al. 2017

Molecular Nutrition Food Res

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“…The role of hepcidin in non-HH cases of T2D has been scantly investigated, with conflicting results. A cross-sectional analysis of 239 non-diabetic and 65 diabetic individuals revealed that diabetics had significantly lower circulating hepcidin levels, independent of inflammation status [ 48 ]. This study complements the observed high rate of diabetes in HH patients, who have reduced hepcidin expression.…”

Section: Hepcidin: a Potential Link Between Dietary Iron Adipose mentioning

confidence: 99%

Ironing out the Details: Untangling Dietary Iron and Genetic Background in Diabetes

Miranda

Lawson

2018

Nutrients

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The search for genetic risk factors in type-II diabetes has been hindered by a failure to consider dietary variables. Dietary nutrients impact metabolic disease risk and severity and are essential to maintaining metabolic health. Genetic variation between individuals confers differences in metabolism, which directly impacts response to diet. Most studies attempting to identify genetic risk factors in disease fail to incorporate dietary components, and thus are ill-equipped to capture the breadth of the genome’s impact on metabolism. Understanding how genetic background interacts with nutrients holds the key to predicting and preventing metabolic diseases through the implementation of personalized nutrition. Dysregulation of iron homeostasis is associated with type-II diabetes, but the link between dietary iron and metabolic dysfunction is poorly defined. High iron burden in adipose tissue induces insulin resistance, but the mechanisms underlying adipose iron accumulation remain unknown. Hepcidin controls dietary iron absorption and distribution in metabolic tissues, but it is unknown whether genetic variation influencing hepcidin expression modifies susceptibility to dietary iron-induced insulin resistance. This review highlights discoveries concerning the axis of iron homeostasis and adipose function and suggests that genetic variation underlying dietary iron metabolism is an understudied component of metabolic disease.

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“…In addition, the present study, for the first time to our knowledge, shows that persons with diabetes on insulin therapy have higher values of hepcidin, confirming similar results obtained from studies on rats [ 11 ]. Different studies have shown that hepcidin levels in DM type 2 are low [ 10 , 33 ]. Since insulin therapy in models of rats does recuperate hepcidin expression we believe that this is the case with our patients as well.…”

Section: Discussionmentioning

confidence: 99%

Insulin treatment corrects hepcidin but not YKL-40 levels in persons with type 2 diabetes mellitus matched by body mass index, waist-to-height ratio, C-reactive protein and Creatinine

et al. 2017

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BackgroundIt has been shown that hepcidin and YKL-40 levels change in persons with insulin resistance in different circumstances. However, variations of the levels of these parameters through the stages of prediabetes and type 2 diabetes mellitus are unclear. We hypothesized that hepcidin levels will decrease in persons with prediabetes, while these levels will tend to correct when persons with diabetes are treated with insulin. Finally we sought to determine the levels of YKL-40 in all groups of participants included in the study.MethodsSerum hepcidin levels and YKL-40 levels were measured in control group (n = 20), persons with prediabetes (n = 30) and persons with diabetes on insulin therapy (n = 30) using ELISA method. Patients in all three groups were matched by Body Mass Index, Waist-to-Height Ratio, C-Reactive Protein and creatinine levels.ResultsHepcidin levels were lower in persons with prediabetes compared to control, while persons with diabetes on insulin therapy had higher values than those with prediabetes (p = 0,00001). YKL-40 levels showed no significant changes.ConclusionsSerum hepcidin levels in matched persons with prediabetes are a stronger marker of early changes in glucose metabolism compared to YKL-40 levels. Also, treatment with insulin corrects hepcidin levels, but not YKL-40 levels. Correcting levels of hepcidin is important for reducing iron-overload, which is a risk factor for diabetes.

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Circulating hepcidin in type 2 diabetes: A multivariate analysis and double blind evaluation of metformin effects

Abstract: Circulating hepcidin was significantly and independently lower in type 2 diabetes. Metformin treatment is not associated with reductions in hepcidin but hypocaloric diet could be involved.

Cited by 21 publications

References 40 publications

Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

Increased Small Intestine Expression of Non‐Heme Iron Transporters in Morbidly Obese Patients With Newly Diagnosed Type 2 Diabetes

Ironing out the Details: Untangling Dietary Iron and Genetic Background in Diabetes

Insulin treatment corrects hepcidin but not YKL-40 levels in persons with type 2 diabetes mellitus matched by body mass index, waist-to-height ratio, C-reactive protein and Creatinine

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