The role of adrenomedulin and leptin in type 2 diabetes mellitus: can be used as early predictors for its microvascular complications?

Background Microvascular vasodegeneration is the major factor in progression of diabetic complications. Adipocytokines secrete a variety of hormones and cytokines, which contribute to the development of vascular and renal diseases. Elevated levels of leptin are observed in chronic renal failure and hypertension. Adrenomedulin (AM), with its antiproliferative effects, is considered as an associated factor in the course of vascular and diabetic insults. However, there is lack of knowledge about the precise role, regulation, production and release at the systemic level of AM, and its correlation with the peripheral blood flow in diabetic vascular insult.Aim We aimed to assess the levels of AM and leptin in type 2 diabetes mellitus (T2DM) patients, to assess their correlations with glycemic control and microvascular complications, and to assess whether these levels vary with the stage of diabetic nephropathy (DN).Patients and methods This is a prospective study including 100 T2DM patients, aged 32–48 years old. Patients were classified into two groups according to albuminuria (group A) and according to estimated glomerular filtration rate (group B). Participants were subjected to history taking, and clinical and fundus examinations. Peripheral hemogram, liver and kidney function tests, lipogram, glycosylated hemoglobin, urine albumin/creatinine ratio, serum leptin and AM were performed. They also underwent ECG and transthoracic echocardiogram.Results The levels of leptin and AM were significantly higher in T2DM patients with microvascular complications than in those without (P<0.001 for each). Leptin and AM levels were progressively elevated in all stages of DN, and the increment was dependent on the severity of DN (P<0.001, for each). There was a significant correlation between AM levels and glycosylated hemoglobin among diabetic patients with microvascular complications. Multivariate logistic regression analysis showed that the odds ratio for the presence of DN in the highest leptin was 4.1 (95% confidence interval: 3.88–5.03, P=0.001); therefore, leptin was an independent risk factor for DN.Conclusion AM and leptin play a role in the pathogenesis of microvasculopathy in T2DM patients. An increased AM and leptin level correlates with poor metabolic control.