Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. Conclusions: The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications.

Background/Aims: Homocysteine is an important and independent risk factor for atherosclerotic diseases. The aim of this study was to evaluate serum levels of homocysteine in children with congenital adrenal hyperplasia (CAH) and their relation to carotid artery intima-media thickness (CA-IMT) and left ventricular (LV) function. Methods: This study included 36 children with classic CAH and 36 healthy children. All underwent anthropometric evaluation. Measurement of serum levels of total homocysteine was carried out. The LV mass (LVM) and function were assessed using conventional echocardiography. Duplex ultrasonography was used to measure CA-IMT. Results: Compared to the controls, the patients had higher homocysteine levels (p = 0.001), a thicker CA-IMT (p = 0.01), a higher LVM index (LVMI) (p = 0.001), and a prolonged mitral deceleration time (DcT) (p = 0.01). Abnormalities were marked in children who were uncontrolled on medical treatment. In multivariate analysis, homocysteine levels were significantly correlated with systolic (OR = 2.2; 95% CI: 1.10–1.18; p = 0.01) and diastolic blood pressures (OR = 2.9; 95% CI: 1.45–2.4; p = 0.01), atherogenic index (OR = 2.6; 95% CI: 1.33–2.89; p = 0.01), HOMA-IR (OR = 1.3; 95% CI: 1.04–1.34; p = 0.001), LVMI (OR = 2.6; 95% CI: 1.1– 1.13; p = 0.001), mitral DcT (OR = 2.4; 95% CI: 1.15–2.05; p = 0.01), and CA-IMT (OR = 1.6; 95% CI: 1.16–1.57; p = 0.01). Conclusions: Serum total homocysteine was elevated in children with classic CAH, particularly in those with poor control on medical treatment, and it was correlated with CA-IMT, LVMI, and mitral DcT. Measurement of homocysteine in children with CAH may help to identify those at high risk of developing LV dysfunction and subclinical atherosclerosis.

Background/Aims: Homocysteine is an important and independent risk factor for atherosclerotic diseases. The aim of this study was to evaluate serum levels of homocysteine in children with congenital adrenal hyperplasia (CAH) and their relation to carotid artery intima-media thickness (CA-IMT) and left ventricular (LV) function. Methods: This study included 36 children with classic CAH and 36 healthy children. All underwent anthropometric evaluation. Measurement of serum levels of total homocysteine was carried out. The LV mass (LVM) and function were assessed using conventional echocardiography. Duplex ultrasonography was used to measure CA-IMT. Results: Compared to the controls, the patients had higher homocysteine levels (p = 0.001), a thicker CA-IMT (p = 0.01), a higher LVM index (LVMI) (p = 0.001), and a prolonged mitral deceleration time (DcT) (p = 0.01). Abnormalities were marked in children who were uncontrolled on medical treatment. In multivariate analysis, homocysteine levels were significantly correlated with systolic (OR = 2.2; 95% CI: 1.10–1.18; p = 0.01) and diastolic blood pressures (OR = 2.9; 95% CI: 1.45–2.4; p = 0.01), atherogenic index (OR = 2.6; 95% CI: 1.33–2.89; p = 0.01), HOMA-IR (OR = 1.3; 95% CI: 1.04–1.34; p = 0.001), LVMI (OR = 2.6; 95% CI: 1.1– 1.13; p = 0.001), mitral DcT (OR = 2.4; 95% CI: 1.15–2.05; p = 0.01), and CA-IMT (OR = 1.6; 95% CI: 1.16–1.57; p = 0.01). Conclusions: Serum total homocysteine was elevated in children with classic CAH, particularly in those with poor control on medical treatment, and it was correlated with CA-IMT, LVMI, and mitral DcT. Measurement of homocysteine in children with CAH may help to identify those at high risk of developing LV dysfunction and subclinical atherosclerosis.

Background: Increasing body weight is a risk factor for development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Aim: We aimed to determine the relationship between insulin, C-peptide, leptin, cortisol, growth hormone (GH) and adiposity in obese and subjects with T2DM as data regarding this issue are still controversial. Study Design: Cross sectional study. Methodology: this study included 60 patients with T2DM, 60 obese non-diabetics and 30 healthy controls. Anthropometric parameters, glycemic and lipid profiles, insulin, C-peptide, leptin, cortisol and GH were measured. Results: Serum C-peptide (P=0.025, P=0.030, P=0.021), insulin (P=0.0001 for all) and leptin Original Research Article Hamed et al.; BJMMR, 12(2): 1-12, 2016; Article no.BJMMR.21457 2 (P=0.001, P=0.02, P=0.0001) were higher in obese (n=22) and non-obese diabetics (n=38) and obese non-diabetics versus controls. Cortisol was higher in obese non-diabetics versus obese (P=0.017) and non-obese (P=0.007) diabetics and controls (P=0.0001). GH was higher in obese non-diabetics versus obese diabetics (P=0.031). IR was reported in obese (72.70%) and nonobese (71.00%) diabetics and obese non-diabetics (38.30%). Central obesity was reported in obese (59.10%) and non-obese (34.20%) diabetics and obese non-diabetics (45.00%). In obese diabetics, a positive correlation was reported between leptin with C-peptide (P=0.001). In nonobese diabetics, positive correlations were reported between IR and cortisol (P=0.025) and waist/hip ratio (WHR) with insulin (P=0.029) but a negative correlation was reported between glycosylated hemoglobin (HBAIc) and leptin (P=0.047). In obese non-diabetics, positive correlations were reported between leptin with HbA1c (P=0.01) and cortisol (P=0.003), WHR with insulin (P=0.0001) and cortisol with leptin (P=0.003). Conclusion: The association of insulin and leptin resistances and hypercortisolemia with obesity supports the notion that the regulatory defects of blood glucose and obesity are associated with long-term metabolic complications.

Central nervous system (CNS) abnormalities are known in patients with type 2 diabetes mellitus (T2DM) and attributed mostly to diabetic vasculopathy. We aimed to determine the direct effect of chronic hyperglycemia on the brain in absence of numerous potential vascular confounders. we systematically investigated markers of brain compromise in 57 patients with T2DM. Cognition was tested using a sensitive battery of psychometric testing [Mini-mental State Examination or MMSE, Stanford Binet Intelligence Scales 4th edition (SBIS) and Wechsler Memory Scale-Revised or WMS-R] and by recording P300 component of event related potential [ERPs], a neurophysiological analogue for cognitive function. We also measured the serum levels of neuron specific enolase (NSE), a sensitive marker of neuronal cell damage. Compared to healthy subjects (n=40), patients had lower total scores of cognitive testing (MMSE, SBIS and WMS-R) (P=0.004), higher Beck Depression Inventory 2nd edition (BDI-II) scores (P=0.001), prolonged latencies and reduced amplitudes of P300 component of ERPs (P=0.0001 for both) and higher NSE concentrations (P=0.001). No differences in clinical, lab and ERPs variables, scores of cognition testing and depression and NSE concentrations were identified regardless the degree of control on anti-diabetic treatments. Significant correlations had been identified between total score of cognitive testing and age (r=-0.370, p=0.050), duration of illness (r=-0.658, p=0.001), blood glucose level (r=-0.543, p=0.010), ERPs latency (r=-0.560, p=0.004) and amplitude (r=0.340, p=0.053) and NSE concentrations (r=-0.698, p=0.001). After adjustment of confounders, the total scores of cognitive testing was significantly correlated with NSE concentrations regardless the level of glycemic control. This study indicates that direct brain damage may result from poor glycemic control and chronic hyperglycemia and this contributes to progressive cognitive deficits with

Abstract Type 2 diabetes mellitus (T2DM) is largely defined by hyperglycemia that promotes vascular complications. Abnormal angiogenesis has been claimed to have a role in this disease. This study aimed to investigate serum levels of both conventional and other markers of angiogenesis not well studied before in diabetes, and to correlate findings with age of the patients, glycemic control, presence of microvascular complications, and oxidative stress. Thirty-eight patients with T2DM and 13 age- and sex-matched healthy persons representing controls were recruited. Serum levels of basic fibroblast growth factor (b-FGF) was measured by immunosorbent assay kit; advanced glycosylation end products, platelet-derived endothelial cell growth factor (PD-ECGF), cathepsin-D (CD), gangliosides, hyaluronic acid (HA), nitric oxide (NO), lipid peroxides (LPER), superoxide dismutase, and total thiols by chemical methods; and copper (Cu) by atomic absorption flame photometry. Advanced glycosylation end products and angiogenic factors (b-FGF, PD-ECGF, CD, gangliosides, HA, and Cu) were significantly higher in patients than controls. Oxidative stress markers, NO, and LPER were significantly higher while total thiols were significantly lower in patients than controls. These changes were more pronounced with age, poor glycemic control, and presence of microvascular complications. Angiogenesis dysfunction coinciding with elevated levels of many angiogenic growth factors may point to their malfunctioning due to oxidative stress and/or protein glycation at the factor and the receptor levels. This necessitates further investigations.

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The adverse outcome after cerebrovascular stroke (CVS) is determined not only by the neurological deficits but also by medical comorbidities including kidney dysfunction. We studied the frequency of acute kidney injury (AKI) with CVS and its relationship to short-term mortality. This study included 80 patients with stroke (mean age: 62.5 ± 6.2 years). Stroke severity was determined using Scandinavian Stroke Scale (SSS). Serum creatinine (SCr), creatinine clearance (CrCl) and kidney injury molecule-1 (KIM-1) concentrations were the measured markers of AKI. Follow-up was done for 3-months or till death. Cox proportional hazards model was used to evaluate contributors to mortality. Compared to reference group, patients had higher SCr (p 0.05) and KIM-1 (p 0.001) and lower CrCl (p 0.01). The majority of patients (86.25%) had normal SCr, while 57.5% had lower CrCl (70 ml/min) and 92.5% had higher KIM-1 (>0.75 ng/ml). Mortality rate was 35%. Compared to survivors, patients who died had lower SSS, higher SCr and KIM-1 and lower CrCl (all p 0.001). Higher SCr [Hazard ratio (HR), 1.65; 95% CI, 1.41 to 1.93], KIM-1 [HR, 1.63; 95%CI, 1.21 to 2.19] and lower CrCl [HR, 1.34; 95% CI, 1.09 to 1.65] significantly predicted worse short-term survival. We conclude that AKI is a common complication of CVS. Increase in SCr, KIM-1 and decrease in CrCl concentrations are associated with worse short-term outcome with stroke.

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