High ferritin and low transferrin saturation are associated with pre-diabetes among a national representative sample of U.S. adults

Abstract

Background & aims: Iron overload is known to cause diabetes. However, the underlying mechanism is poorly understood. We therefore studied the association of different markers of iron metabolism, namely ferritin, erythrocyte protoporphyrin and transferrin saturation (TSAT, as defined by a percentage of transferrin that is saturated with iron) with pre-diabetes (preDM) in US adults without chronic kidney disease, anemia, and iron deficiency.

Methods: Data on 2575 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 who were free of diabetes, chronic kidney disease, iron deficiency, and anemia were analyzed. Data on 3876 participants of the NHANES III (1988-1994) were used as replication. Homeostasis model assessment of insulin resistance (HOMA-IR), blood glycosylated hemoglobin level (HbA1C), fasting glucose, insulin, and preDM (defined as a fasting plasma glucose 100-125 mg/dl or an HBA1C value 5.7-6.4%) were measured as the outcomes.

Results: Logistic regression analyses indicated independent associations of high ferritin (Ptrend = 0.028) and low TSAT (P(trend) = 0.029) with preDM after adjusting for sociodemographics, physical activity (active/sedementary), metabolic and inflammatory markers (triglycerides, total cholesterol, HDL cholesterol, mean arterial pressure, CRP, white cell count, and albumin), and liver enzymes (GGT, Alk phos, AST, and ALT). The NHANES III data showed similar associations. Combining the results showed a more significant association for high ferritin (P(meta) = 0.016) and low TSAT (P(meta) = 0.002). Moreover, TSAT was associated with HbA1C, fasting glucose, insulin, and HOMA-IR (P(meta) ≤ 0.001).

Conclusions: Higher ferritin and lower TSAT are associated with higher risk of preDM in a general population without confounding diseases. Further research is needed to examine the underlying mechanism of these two indices, especially TSAT, in the pathophysiology of preDM.

Keywords: ALT; AST; Alk phos; C-reactive protein; CRP; Ferritin; GFR; GGT; HOMA-IR; HbA1C; IFG; Inflammation; Iron; MAP; NHANES; National Health and Nutrition Examination Survey; Pre-diabetes; TSAT; Transferrin saturation; alanine transaminase; alkaline phosphatase; aspartate aminotransferase; gamma-glutamyl transpeptidase; glomerular filtration rate; glycosylated hemoglobin; homeostasis model assessment of insulin resistance; impaired fasting glucose; mean arterial pressure; transferrin saturation.