Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients.

BACKGROUND AND AIMS: Neuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). METHODS: The study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. RESULTS: T2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. CONCLUSIONS: A robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

Inactive Matrix Gla Protein in Relation to Renal and Cardiac Functions and Cardiac Valvular Calcification Among Type 2 Diabetes Patients.

Background: Matrix Gla protein (MGP) is a robust innate suppressor of the detrimental process of vascular calcification in the human body. Objectives: The interrelationship between circulating MGP levels and renal and cardiac dysfunction, besides echocardiographic calcification score (ECS) was investigated in a sample of type 2 diabetes (T2D) patients. Methods: The study included 130 subjects. They were 95 patients with T2D and 35 age- and sex-matched healthy controls. Patients were further subdivided into 52 T2D patients without DKD (eGFR ⩾ 60 ml/minute/1.73 m²) and 43 T2D persons with DKD (eGFR > 60 ml/minute/1.73 m²). Serum MGP levels, determined by ELISA, renal function tests, lipid profile, and echocardiography were studied in all participants. Results: Significantly elevated circulating inactive MGP level was noted in individuals having T2D compared to controls. It correlated negatively with eGFR and left ventricular (LV) diastolic and systolic functions and positively with indices of LV hypertrophy. ECS was significantly increased in both T2D groups compared to controls and in DKD group compared to the diabetic group without DKD. A significant positive correlation was observed between inactive MGP and ECS. Conclusion: Serum inactive MGP may contribute to the development of DKD and to the associated process of cardiac valvular calcification. It may be a beneficial diagnostic marker for early prediction of cardiac calcification and preclinical LV systolic and diastolic dysfunction in T2D patients, especially in those complicated with DKD.

Inactive matrix Gla protein in relation to diabetic retinopathy in type 2 diabetes.

Background and Aims: The contribution of inactive Matrix Gla protein (MGP) to ectopic vascular calcification associated with type 2 diabetes mellitus (T2DM) is well recognized. However, its role in diabetic microvascular complications remains unknown. The study aim was to identify any association between inactive MGP and diabetic retinopathy (DR). Its relation to insulin resistance was also explored. Methods: The study included 90 participants, 65 Type 2 diabetic patients (25 without DR and 40 with DR) and 25 healthy controls. Serum inactive MGP was measured using ELISA. HOMA-IR was also assessed. Results: Inactive MGP was significantly higher in both diabetic groups compared to controls (P < 0.001), as well as in Type 2 diabetic patients with retinopathy compared to Type 2 diabetes without retinopathy (P = 0.002). Inactive MGP was positively correlated with HbA1c, HOMA-IR, LDL-C and triglycerides (P < 0.001), and negatively correlated with HDL-C (P = 0.008) and eGFR (P < 0.001). Logistic Regression Analysis showed that inactive MGP was one of the most associated factors with DR. Conclusions: Inactive MGP was found to be related to DR, insulin resistance and other dysmetabolic risk factors. These findings highlight that inactive MGP may be a significant contributor to the pathogenesis, evolution, and progression of DR.

Serum salusin-ß in relation to atherosclerosis and ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Salusin-ß is a newly defined biomarker that plays a role in atherogenesis and in homeostasis. The study aimed to assess serum salusin-ß level in relation to atherosclerosis and ventricular dysfunction in type 2 diabetes mellitus (T2DM) patients. METHODS: Sixty T2DM patients and twenty-five age-matched healthy controls were included. Serum salusin-ß was determined by ELISA. Echocardiography and carotid ultrasonography were carried out for all individuals. RESULTS: Serum salusin-ß level was significantly elevated in patients with T2DM than in controls (P < 0.001). It was positively correlated with obesity parameters, insulin resistance index (r = 0.280,P < 0.001), atherogenic dyslipidemia and with carotid intima media thickness (CIMT) (r = 0.411, P < 0.001). Echocardiographic findings showed a positive correlation between salusin-ß and left ventricular hypertrophy (LVH) parameters and a negative correlation with left ventricular (LV) diastolic and systolic functions. Regression analysis showed that serum salusin-ß level was a significant predictor of diastolic dysfunction. CONCLUSION: Serum salusin-ß may be associated with atherosclerosis and LV dysfunction in T2DM.

Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study.

Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. IN CONCLUSION: T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels.

Androgen Deficiency and Erectile Dysfunction in Patients with Type 2 Diabetes.

BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and low total serum testosterone (LST) has been identified in several cross-sectional studies. OBJECTIVES: To assess the prevalence of androgen deficiency and erectile dysfunction (ED) and their relation to glycemic control within a sample of Egyptian men with T2DM. RESEARCH DESIGN AND METHODS: A cross-sectional study including 70 men having T2DM. Their ages ranged from 30 to 50 years. They were evaluated for symptoms of androgen deficiency and ED, using a validated Arabic-translated Androgen Deficiency in Aging Males questionnaire and five-items version of the International Index of Erectile Function-5, respectively. Total testosterone (TT), glycated hemoglobin (HbA1c), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were measured for all study subjects. Penile hemodynamics was assessed using penile duplex study for subjects who gave history of ED. RESULTS: LST was found in 40% of studied men, and 92.9% of them reported overt symptoms of androgen deficiency. ED was detected in 85.7% of those with LST, as opposed to 31.0% of those with normal TT (P < 0.000). TT was lower in diabetic men with ED compared to those without ED (12.04 ± 5.36 vs 17.11 ± 7.11 nmol/L, P < 0.001). Significant negative correlation was found between TT and age, body mass index, waist circumference, systolic and diastolic blood pressures, and HBA1c (P < 0.00). FSH, LH, and prolactin levels were within the normal reference range in all subjects. HbA1c was higher in patients who had LST with ED, compared to those with normal TT and without ED. However, multivariate logistic regression analysis did not reveal a significant association between HBA1c and LST levels. CONCLUSION: LST, symptoms of androgen deficiency, and ED are common in the studied sample of Egyptian men with T2DM. Inappropriately normal FSH and LH in face of LST may denote a state of hypogonadotropic hypogonadism. HBA1c was found to be more significantly associated with ED than with LST.

Plantar pressure as a risk assessment tool for diabetic foot ulceration in egyptian patients with diabetes.

BACKGROUND: Diabetic foot ulceration is a preventable long-term complication of diabetes. In the present study, peak plantar pressures (PPP) and other characteristics were assessed in a group of 100 Egyptian patients with diabetes with or without neuropathy and foot ulcers. The aim was to study the relationship between plantar pressure (PP) and neuropathy with or without ulceration and trying to clarify the utility of pedobarography as an ulceration risk assessment tool in patients with diabetes. SUBJECTS AND METHODS: A total of 100 patients having diabetes were selected. All patients had a comprehensive foot evaluation, including assessment for neuropathy using modified neuropathy disability score (MNDS), for peripheral vascular disease using ankle brachial index, and for dynamic foot pressures using the MAT system (Tekscan). The studied patients were grouped into: (1) diabetic control group (DC), which included 37 patients who had diabetes without neuropathy or ulceration and MNDS ≤2; (2) diabetic neuropathy group (DN), which included 33 patients who had diabetes with neuropathy and MNDS >2, without current or a history of ulceration; and (3) diabetic ulcer group (DU), which included 30 patients who had diabetes and current ulceration, seven of those patients also gave a history of ulceration. RESULTS: PP parameters were significantly different between the studied groups, namely, forefoot peak plantar pressure (FFPPP), rearfoot peak plantar pressure (RFPPP), forefoot/rearfoot ratio (F/R), forefoot peak pressure gradient (FFPPG) rearfoot peak pressure gradient (RFPPG), and forefoot peak pressure gradient/rearfoot peak pressure gradient (FFPPG/RFPPG) (P < 0.05). FFPPP and F/R were significantly higher in the DU group compared to the DN and DC groups (P < 0.05), with no significant difference between DN and DC. FFPPG was significantly higher in the DU and DN groups compared to the DC group (P < 0.05). RFPPP and FFPPG/RFPPG were significantly higher in the DU and DN groups compared to the DC group (P < 0.05) with no significant difference between the DN and DU groups (P > 0.05). FFPPP, F/R ratio, FFPPG, and FFPPG/RFPPG correlated significantly with the severity of neuropathy according to MNDS (P < 0.05). These same variables as well as MNDS were also significantly higher in patients with foot deformity compared to those without deformity (P < 0.05). Using the receiver operating characteristic analysis, the optimal cut-point of PPP for ulceration risk, as determined by a balance of sensitivity, specificity, and accuracy was 335 kPa and was found at the forefoot. Multivariate logistical regression analysis for ulceration risk was statistically significant for duration of diabetes (odds ratio [OR] = 0.8), smoking (OR = 9.7), foot deformity (OR = 8.7), MNDS (OR = 1.5), 2-h postprandial plasma glucose (2 h-PPG) (OR = 0.9), glycated hemoglobin (HbA1c) (OR = 2.1), FFPPP (OR = 1.0), and FFPPG (OR = 1.0). CONCLUSION: In conclusion, persons with diabetes having neuropathy and/or ulcers have elevated PPP. Risk of ulceration was highly associated with duration of diabetes, smoking, severity of neuropathy, glycemic control, and high PP variables especially the FFPPP, F/R, and FFPPG. We suggest a cut-point of 355 kPa for FFPPP to denote high risk for ulceration that would be more valid when used in conjunction with other contributory risk factors, namely, duration of diabetes, smoking, glycemic load, foot deformity, and severity of neuropathy.