Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: the Shanghai Changfeng study

Abstract

Associations between ferritin and insulin sensitivity have been described in recent studies. The possible association showed conflicting results by sex and menopausal status. We aimed to investigate the cross-sectional association of ferritin levels with insulin resistance and β-cell function. A total of 2518 participants (1033 men, 235 pre-menopausal women and 1250 post-menopausal women) were enrolled from the Changfeng Study. A standard interview was conducted, as well as anthropometric measurements and laboratory analyses, for each participant. The serum ferritin level was measured using electrochemiluminescence immunoassay. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. The results showed that the serum ferritin levels were 250·4 (sd 165·2), 94·6 (sd 82·0) and 179·8 (sd 126·6) ng/ml in the men, pre-menopausal and post-menopausal women, respectively. In fully adjusted models (adjusting for age, current smoking, BMI, waist:hip ratio, systolic blood pressure, diastolic blood pressure, TAG, HDL-cholesterol, LDL-cholesterol, log urine albumin:creatinine ratio, leucocytes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transpeptidase), serum ferritin concentrations are significantly associated with insulin resistance in men and post-menopausal females, and the null association was observed in pre-menopausal females. Interestingly, an increased β-cell function associated with higher ferritin was observed in post-menopausal participants, but not in male participants. In conclusion, these results suggested that elevated serum ferritin levels were associated with surrogate measures of insulin resistance among the middle-aged and elderly male and post-menopausal women, but not in pre-menopausal women.

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“…Consequently, COVID-19-induced morbidity and mortality risk are directly proportional to age ( Grasselli et al, 2020 ; Team, 2020 ; Zheng et al, 2020 ), and male sex is also a significant risk factor for COVID-19-induced morbidity and mortality ( Grasselli et al, 2020 ). Individuals with metabolic syndrome (obesity ( Kim et al, 2015 ; Lecube et al, 2008 ; Moreno-Navarrete et al, 2017 ), diabetes ( Batchuluun et al, 2014 ; Simcox and McClain, 2013 ; Ma et al, 2018 ), and cardiovascular disease ( Milman and Kirchhoff, 1999 ; Cheng et al, 1999 ; Lee et al, 2018 )) have higher COVID-19-induced morbidity and mortality due to abnormally high iron stores compared to matched-healthy individuals. Several studies have demonstrated that COVID-19 patients exhibit abnormally high iron stores (using serum ferritin levels ( Gordeuk et al, 2008 ; Camaschella and Poggiali, 2009 ) as a surrogate marker) ( Chen et al, 2020 ; Gomez-Pastora et al, 2020 ), and a retrospective, multicenter cohort study of hospitalized COVID-19 patients confirmed that abnormally high iron stores constitute a significant determinant of COVID-19-induced mortality ( Gomez-Pastora et al, 2020 ; Zhou et al, 2020 ; Ruscitti et al, 2020 ; Edeas et al, 2020 ).…”

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study

“…Indeed, recent data suggest that iron-induced reactive oxygen species (ROS) initiate an oxidative stress cascade causing lipid peroxidation and disturbances in insulin signaling. Increased free radicals might contribute to insulin resistance via increased free fatty acids oxidation, reduction of glucose uptake by the muscle, and impaired insulin release [40,41]. At the same time, the damage produced to hepatic cells might induce an increase in circulating ferritin concentration [16].…”

Is Serum Ferritin Level Different Between Healthy Individuals and Newly Diagnosed Patients With Type 2 Diabetes Mellitus?: A Case-Control Study

“…In a recent study investigating the association of ferritin levels with insulin resistance according to gender and menopausal state, reported that increased serum ferritin levels had significant relationship with insulin resistance in men and post-menopausal women, but not in pre-menopausal women (34). Similarly, in a nationwide population-based study from Korea, serum ferritin levels were found to be positively associated with insülin resistance in postmenopausal women (35).…”