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Impaired endothelial function in siblings of patients with diabetic mellitus type 2.

ABSTRACT: Endothelial dysfunction is considered as a risk factor for cardiovascular disease, which is a consistent finding in diabetic mellitus type 2 (DMT2). First-degree relatives of DMT2 patients have a higher risk of developing DMT2 later on the life. We aimed to investigate whether impaired endothelial function exists in siblings of DMT2 patients.As endothelial function markers, plasma E-selectin, soluble inter-cellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) were measured on 27 DMT2 patients (9 m/18f; mean age: 48.48 ± 6.75 years), 28 siblings of DMT2 patients (14 m/14f; mean age: 44.54 ± 7.10 years), and 30 control subjects (18 m/12f; mean age: 44.72± 7.56 years) without any family history of diabetes. All the groups were matched by gender, age, and body mass index (BMI).Plasma levels of ET-1, sICAM-1, and E-selectin were significantly higher in the DMT2 group compared to the control group (ET-1:0.79 ± 1.63 pg/ml vs. 0.33 ± 0.08 pg/ml; PCD = 0.049, sICAM-1: 71.15 ± 27.20 ng/ml vs. 34.57 ± 22.56 ng/ml; PCD = 0.001, E-selectin: 22.45 ± 11.57 ng/ml vs. 16.28 ± 7.50 ng/ml; PCD =0.026). There was a significant difference in sICAM-1 levels between siblings (62.08 ± 26.37 ng/ml) and controls (PCS = 0.002), but not between siblings and DMT2 patients (PSD = 0.411). Moreover, a significant difference was observed in ET-1 levels between siblings (0.75 ± 1.26 pg/ml) and controls (PCS = 0.031), but not between siblings and DMT2 patients (PSD = 0.751). There was also a significant difference in E-selectin levels between DMT2 patients and siblings (16.56 ± 8.71 ng/ml; PSD =0.028); however, the difference in E-selectin levels was not statistically significant between siblings and controls (PCS = 0.919).Endothelial function markers in the siblings of DMT2 patients are increased in comparision to the control group Therefore; family history in the DMT2 patients seems to be a risk factor for endothelial function. Furthermore, endothelial dysfunction is available very early in the DMT2 patients, even before overt hyperglycemia ensues (in siblings), and may play a key role in the etiopathology of the vasculopathy associated with DMT2.

SUBMITTER: Rasmi Y

PROVIDER: S-EPMC4929751 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Diabetic polyneuropathy (DPN) and endothelial dysfunction are prevalent complications of diabetes mellitus. Currently, there are two non-invasive markers for endothelial dysfunction: flow-mediated dilation and reactive hyperaemia peripheral arterial tonometry (RH-PAT). However, the relationship between diabetic small fibre neuropathy and macroangiopathy remains obscure thus far. Corneal confocal microscopy (CCM) has emerged as a new diagnostic modality to assess DPN, especially of small fibre. To clarify the relationship between diabetic small fibre neuropathy and vascular dysfunction, we aimed to determine the functions of peripheral nerves and blood vessels through clinical tests such as nerve conduction study, coefficient of variation in the R-R interval, CCM, and RH-PAT in 82 patients with type 2 diabetes. Forty healthy control subjects were also included to study corneal nerve parameters. Correlational and multiple linear regression analyses were performed to determine the associations between neuropathy indices and markers for vascular functions. The results revealed that patients with type 2 diabetes had significantly lower values for most variables of CCM than healthy control subjects. RH-PAT solely remained as an explanatory variable significant in multiple regression analysis for several CCM parameters and vice versa. Other vascular markers had no significant multiple regression with any CCM parameters. In conclusion, endothelial dysfunction as revealed by impaired RH-PAT was significantly associated with CCM parameters in patients with type 2 diabetes. This association may indicate that small fibre neuropathy results from impaired endothelial dysfunction in type 2 diabetes. CCM parameters may be considered surrogate markers of autonomic nerve damage, which is related to diabetic endothelial dysfunction. This study is the first to report the relationship between corneal nerve parameter as small fibre neuropathy in patients with type 2 diabetes and RH-PAT as a marker of endothelial dysfunction.

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Impaired endothelial function in siblings of patients with diabetic mellitus type 2.

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