Association between systemic iron status and β-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes

Abstract

Objective: Abnormal iron metabolism is related to the risk of diabetes, but the underlying mechanism of this association remains uncertain. This study was conducted to evaluate the contributions of systemic iron status to β-cell function and insulin sensitivity of patients with newly diagnosed T2DM.

Methods: A total of 162 patients with newly diagnosed T2DM and 162 healthy controls were enrolled in the study. Basic characteristics, biochemical indicators, and iron metabolism biomarkers, including serum iron (SI), ferritin (SF), transferrin (Trf), and transferrin saturation (TS), were collected. All patients underwent a 75 g oral glucose tolerance test. A series of parameters for assessing β-cell function and insulin sensitivity were calculated. The multivariate stepwise linear regression model was used to investigate the contributions of iron metabolism to β-cell function and insulin sensitivity.

Results: Compared with healthy controls, patients with newly diagnosed T2DM had significantly higher levels of SF. Among the diabetic patients, the SI and TS levels were higher, and the percentage of Trf levels below normal values was lower in men than in women. In all diabetic patients, SF was the independent risk factor associated with impaired β-cell function. Further stratification analysis showed that Trf was an independent protective factor for β-cell function in male patients, while SF was an independent risk factor for impaired β-cell function in female patients. However, systemic iron status did not affect insulin sensitivity.

Conclusion: Elevated SF levels and decreased Trf levels had a profound effect on impaired β-cell function in Chinese patients with newly diagnosed T2DM.

Keywords: iron; serum ferritin; transferrin; type 2 diabetes; β-cell function.

Figure 1

Heatmap showing Spearman correlation between β-cell function or insulin sensitivity and systemic iron status and the associated factors in all (A), male (B) and female (C) patients with newly diagnosed T2DM. Red indicates positive correlations and blue negative. *P<0.05; **P<0.01. SI, serum iron; SF, serum ferritin; Trf, transferrin; TS, transferrin saturation; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycosylated hemoglobin A1c; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; UA, uric acid; 25(OH)D, 25-hydroxyvitamin D; HOMA-β, homeostasis model assessment of β-cell function; CIR, corrected insulin response; IGI, insulinogenic index; AUC_Ins/AUC_Glu, the ratio of the area under the insulin curve to the area under the glucose curve; HOMA-IR, homeostasis model assessment of insulin resistant; ISI_Matsuda, the Matsuda index of insulin sensitivity.