| Objective: To study the association of serum leptin, adiponectin, resistin, visfatin and retinol-binding protein-4(RBP-4) levels with insulin resistance as well as β-cell dysfunction in first-degree relatives(FDR) of type 2 diabetes mellitus (T2DM), and to investigate the role of those adipocytokins in pathogenesis of T2DM.Methods: Serum levels of adipocytokine profile including leptin, adiponectin, resistin, visfatin and RBP-4, as well as fasting true insulin (FTI), proinsulin (FPI) levels in 71 patients with newly diagnosed of T2DM, 55 subjects with IGT/IFG and 174 NGT from first-degree relatives of T2DM, and 114 subjects of NGT without T2DM family history as control group (NC) were measured. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR) and β-cell function was evaluated by HOMA-β and fasting PI-to-TI ratio (FPI/TI). Lipid profile, liver function and kidney function were also tested. Meanwhile the anthropometrical parameters such as body mass index (BMI), waist circumference and blood pressure were recorded. Furthermore, life style and food intake spectrum were also investigated.Results: (1) Insulin resistance status: HOMA-IR was increased progressively from NC group to NGT, IGT/IFG and T2DM group (F=22.6, p<0.001). (2) β cell function: if evaluated by FPI and FPI/TI, both lnFPI (1.4±0.6, 1.9± 0.6, 2.2±0.7 and 2.8±0.8, p<0.001) and FPI/TI (0.12±0.07, 0.18±0.12, 0.20±0.15 and 0.49±0.50, p<0.01) were increased progressively from NC group to NGT, IGT/IFG and T2DM group; but as for HOMA-β, a significant decrease could be shown only in diabetes group. (3) From NC group to NGT, IGT/IFG and T2DM group, the serum levels of leptin were increased gradually, which positively correlated with HOMA-IR and FPI. (4)The serum levels of adiponectin were significantly decreased from NC to NGT , IGT/IFG and T2DM groups and negatively correlated with HOMA-IR and FPI. The adiponectin /leptin ratio was reduced significantly in groups of diabetic pedigree from NGT to IFG/IGT and T2DM, and correlated with HOMA-IR,HOMA-β and FPI significantly. (5)Therewere no significant difference of serum resistin levels among the four groups. (6) Serum visfatin levels of four groups were 41.4±12.9 ng/ml, 35.9±11.1 ng/ml, 33.5±10.4 ng/ml and 32.5±10.6 ng/ml, respectively. The serum visfatin levels of DM group,IGT/IFG and NGT group were lower than NC group (p<0.05) ; There were no significant difference among DM group,IGT/IFG group and NGT .The serum visfatin level was not corelated with HOMA-IR and obesity markers, but negatively correlated with fasting blood glucose,2h postprandial blood glucose and blood pressure (p<0.05) . (7) Serum RBP-4 levels of four groups were 18.2±7.2 ug/ml,21.6±8.0 ug/ml,23.8±9.3 ug/ml and 25.6±8.7 ug/ml, respectively. It was increased progressively from NC to NGT and IGT/IFG (p<0.001), but there was no difference between IGT/IFG and DM group. Serum RBP-4 level was positively correlated with HOMA-IR, FPI and FPI/TI and negatively correlated with adiponectin and visfatin. Furthermore, it was also closely correlated with other parameters related to the metabolic syndrome.(8)Lifestyle investigation resluts showed that cigarette smoking in male as well as animal fat intake in all subjects were the independent risk factors for development of insulin resistance.Conclusion: (1) Insulin resistance and β-cell dysfunction (the serum levels of PI and TI increased disproportionately), which may be the representation of the genetic susceptibility to T2DM, were existed in the FDRs of T2DM when glucose tolerance was still in normal status. Furthermore,these changes were deteriorated from NGT to IGT, DM progressively. HOMA-IR calculated by true insulin could discrinminate different insulin resistance status, while, FPI/TI could differentiate β-cell dysfunction in different glucose tolerance status, but HOMA-β could not detect thoses difference sensitively.These results implayed that HOMA-IR and FPI/TI could detect insulin resistance and β-cell dysfunction respectively in early stage of glucose intolerance. (2) The adipokine profile in FDRs of T2DM had already altered distinctively before the development of impaired glucose tolerance. Serum levels of leptin and RBP-4, which were positively correlated with insulin resistance, were elevated significantly; while adiponectin and visfatin, which had beneficial effects on glucose metabolism, were decreased significantly in serum levels.These results showed that changes of the adipocytokine profile might play an important role in the pathogenesis of T2DM. Moreover, these adpokine genesmay also be the prone gene of T2DM. Comparatively, adiponectin, leptin and RBP-4 were more closely correlated with insulin resistance and therefore may be the better predictors of T2DM and the new targets of early prevention and treatment of T2DM.(3)Adiponectin and RBP-4 were closely related to metabolic syndrome. (4) Cigarette smoking in male as well as animal fat intake in all subjects were the independent risk factors for insulin resistance.
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