Plasma adrenomedullin as a marker of vascular complications in type-2 diabetes : relationship with c-reactive protein, adiponectin and other metabolic factors

الملخص EN

Background: Patients with type-2 diabetes are at risk for vascular complications.

Dyslipidemia, insulin resistance and endothelial dysfunction are thought to contribute to these complications.

Several vasoactive factors have been implicated.

Among these factors, adrenomedullin -a novel 52 amino acid peptide- has drawn great attention in type-2 diabetes. Objective: To determine plasma adrenomedullin levels in type-2 diabetic patients with and without nephropathy in a trial to elucidate the potential involvement in the pathogenesis of diabetic vascular complications.

Moreover, we investigated the relationships between adrenomedullin, vascular function and the major metabolic and inflammatory factors traditionally associated with endothelial injury and diabetic vasculopathy including insulin resistance, dyslipidemia, adiponectin and highly sensitive C-reactive protein (hs-CRP). Study design: Seventy subjects were enrolled in our study.

Fifteen healthy with normal glucose tolerance (control group), fifteen with impaired fasting glucose (IFG group), twenty diabetic patients with no evidence of nephropathy (DM group) and twenty diabetic patients with established nephropathy (DN group).

All patients and controls were subjected to the following: anthropometric and blood pressure measurements.

Serum glucose, creatinine, lipid profile (total cholesterol, HDL-C, triglycerides), urinary albumin and creatinine were assayed on Synchron CX-9 autoanalyzer.

Serum insulin, hs-CRP, adiponectin and plasma adrenomedullin were assayed using enzyme immunoassay technique.

Homeostasis model assessment for insulin resistance (HOMA-IR) and albumin-creatinine ratio (ACR) were calculated, lastly, endothelial function was assessed in all subjects using high-resolution ultrasound to measure flow-mediated dilatation (FMD) of the brachial artery. Results: Plasma adrenomedullin was significantly elevated in diabetic patients with and without nephropathy as compared to the control group and IFG group (p<0.001, respectively).

It was significantly elevated in diabetic nephropathy group (DN group) when compared to the uncomplicated diabetic group (DM group) (p<0.001).

It has been found that the most sensitive discriminating marker between IFG, DM and DN groups was adrenomedullin followed by triglycerides, urinary ACR, hs-CRP and finally HOMA-IR.

Moreover, adrenomedullin was the only parameter that shows high significant difference between each two groups.

Stepwise logistic multiregression analysis which was performed using diabetic vascular complications as the dependent variable revealed that both urinary ACR (>235 mg/g, p=0.0371) with adrenomedullin (>25 ng/mL, p=0.0805) were significant predictors for these complications (F-ratio=25.3, p<0.001).

The correlation study revealed a significant negative correlation between adrenomedullin concentrations and each of FMD of the brachial artery and adiponectin in our diabetic subjects, in addition to significant positive correlations with fasting insulin, HOMA-IR, hs-CRP, urinary ACR, triglycerides and LDL-C.

On the other hand, non-significant correlations were recorded between adrenomedullin and each of total cholesterol and HDL-C. Conclusion: Plasma adrenomedullin concentration was elevated in type-2 diabetes which was further accentuated in the presence of diabetic nephropathy.

Several metabolic and inflammatory factors were associated with plasma adrenomedullin.

Our study suggested that both urinary ACR and plasma adrenomedullin were significant predictors of vascular complications in diabetic subjects.

Moreover, our study demonstrated a significant negative correlation between endothelial vascular function assessed as FMD and adrenomedullin suggesting that the increased adrenomedullin concentrations in diabetic subjects could probably be a physiological response to endothelial dysfunction and consequently it can be used as a marker for endothelial dysfunction.

Therefore, modulating adrenomedulli