Relative Iron "Overload" in Offspring of Patients with Type 2 Diabetes Mellitus: A New Component in the Conundrum of Insulin Resistance Syndrome?

Abstract

There are a few reports suggesting that subtle disturbances of iron metabolism are frequently found in patients with type 2 diabetes (DM2), but it is not known if these disturbances precede or accompany the diabetic state. We investigated the serum iron indices in 41 offspring of DM2 parents (group I) with normal glucose tolerance, and in 49 offspring whose parents had no history of DM2 and were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and blood pressure (group II). Serum iron, ferritin, total iron binding capacity (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high density lipoprotein (HDL) and glucose and insulin values during an oral glucose tolerance test were measured. Insulin resistance was assessed using the homeostasis model assessment (HOMA - Insuline resistence index-IRI). In comparison to controls (group II), the offspring of DM2 subjects (group I) had higher fasting serum triglycerides (mean +/- SD 2.25+/-2.08 vs. 1.6+/-0.8 mmol/L, p<0,05), lower HDL cholesterol (0.96 +/- 0.2 vs. 1.1 +/- 0.2 mmol/L, p<0.001), higher total cholesterol (5.5 +/- 1.1 vs. 5.1 +/- 0.8 mmol/L, p < 0.05), higher apo-B-lipoprotein (133.2+/-34.3 vs. 125.5+/-30.5 mg/dl, p<0.05), higher LDL-C (3.7 +/- 0.8 vs. 3.2 +/- 0.6 mmol/L), higher gamma-GT (28+/-10 vs. 17+/-5.6 iu/L, p<0.01) higher insulin in the Area Under the Curve (204.7+/-140.8 v. 153.1 +/- 63.0 microU/ml, p<0.05) and higher HOMA-IRI (2.84+/-1.39 vs. 1.67+/-0.77, p<0.001), higher serum ferritin concentrations (98.3+/-57.7 vs. 62.0+/-41.1 ng/ml, p<0.01), higher serum iron concentration (20.2+/-6.0 micromol/L vs. 14.5+/-4.3, p<0.001) and higher transferrin saturation index (31.3+/-8.4 vs. 22.6+/-7.3, p<0.0001). By single linear analysis in the offspring of DM2 parents, there was a positive correlation of IRI with transferrin saturation (r=0.400, p<0.01), fibrinogen (r=0.377, p=0.025) and ferritin concentration (r=0.344, p=0.041), and a negative correlation with TIBC (r=-0.477, p < 0.0001), while stepwise multiple regression analysis, IRI showed a positive correlation with fibrinogen (b=0.64, t=3.746, p<0.001), triglycerides (b=0.37, t=2.619, p<0.01) and ferritin (b=0.20, t=1.827, p=0.05). No correlation of IRI, with any of the above parameters was seen in the offspring of normal parents. By logistic regression analysis the parameters characterizing the offspring of parents with DM2 were IRI (OR 14.9 CI 2.4-91.0) serum iron (OR 44.2 CI 6.9-281), TIBC (OR 6.1 CI 1.01-37.0 and gamma-GT (OR 29.6 CI 5.0-174). In conclusion, the data indicate that the iron load, is significantly increased in offspring of DM2 subjects with unaffected glucose tolerance. Furthermore, ferritin concentration is related to insulin resistance. Hence, the relative iron "overload" in offspring of type 2 diabetics is present along with insulin resistance and might worsen the hepatic insulin insensitivity already present in these patients.