Diabetic tubulopathy: effect of toll-like receptor 2, toll-like receptor 4, and nuclear factor κb in elderly type 2 diabetes mellitus patients Suzan N Abou-Raya, Montasser M Zeid, Mona W Ayad, Maher K Abdnaby, Mohamed H Arafa Egyptian Journal of Obesity, Diabetes and Endocrinology 2018 4(2):31-37 Objective The aims of the current study were to investigate the role of toll-like receptor (TLR)2, TLR4, and nuclear factor κB (NF-κB) expression in the pathogenesis of diabetic nephropathy (DN) in elderly type 2 diabetics, and also to determine the functional role of TLR2, TLR4, and NF-κB in tubular inflammation. Background Chronic kidney disease is one of the major complications of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. There is growing evidence indicating that chronic low-grade inflammatory response is a recognized factor in the pathogenesis and progression of diabetic renal injury. Patients and methods Our study included a human part and an animal part, in the human part, participants were divided into four groups; old patients: 30 T2DM patients aged 65 years and above with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy, old control: 20 age- matched and sex-matched healthy persons aged 65 years and above serving as a control group, young patients: 30 T2DM patients aged less than 65 years with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy and young control: 20 age-matched and sex-matched healthy persons aged less than 65 years serving as a control group. We took a full history of all patients and concluded complete physical examination. Mean arterial pressure, BMI and fundus examination were done. We measured fasting plasma glucose, 2 h postprandial plasma glucose, glycated haemoglobin, complete urine analysis, serum creatinine, blood urea nitrogen, C-reactive protein, urinary albumin/creatinine ratio, estimated glomerular filtration rate using Modification of Diet in Renal Disease Abbreviated Equation, level of TLR2, TLR4, and nuclear NF-κB. In the animal part, the study was conducted on 20 aged (1.5-year old) male wistar rats, the rats were divided into two main groups; group I (control): 10 normal healthy male rats, group II (diabetic): 10 rats with high-fat diet)/streptozotocin-induced diabetes. Blood samples were collected for the determination of fasting plasma glucose, fasting serum insulin, insulin resistance was assessed by calculating the homeostatic model assessment of insulin resistance, blood urea nitrogen, serum creatinine and C-reactive protein and analysis of TLR2, TLR4, and NF-κB in renal tissue was done. Results In the human part of our study: the level of TLRs2, TLR4, and NF-κB was significantly higher in old diabetic patients group than young diabetic patients group and control group. In the animal part of our study: the level of TLRs2 and 4 and NF-κB was significantly higher in diabetic rat group than healthy rat control group. Conclusion TLRs2, TLR4, and NF-κB were higher in old diabetic patients compared with young diabetic patients and normal individuals. These observations significantly added to the emerging role of TLRs in T2DM development and its possible role in the pathogenesis and progression of DN. Also, the present study showed that the TLR system was closely related to the ageing of the kidneys.

Insulin resistance and Alzheimer’s disease: the role of defective insulin signaling and inflammation Suzan N Abou-Raya, Ashraf M Abdou, Maher Abdel-Nabi Kamel, Ali M.A. Ramadan Egyptian Journal of Obesity, Diabetes and Endocrinology 2018 4(2):38-57 Introduction Alzheimer’s disease (AD) is the most common form of dementia in the elderly, accounting for 60–80% of cases. The present study was to explore the role of insulin resistance and inflammatory processes in AD patients and to assess the effect of an insulin sensitizer (pioglitazone) on cognition and plasma levels of the amyloid beta derivative. Also, the study aimed to verify experimentally the effect of pioglitazone on the components of brain insulin signaling pathway and inflammatory pathway. Materials and methods We studied the impact of pioglitazone treatment on diabetic AD patients for 6 months with concomitant study of pioglitazone effect on insulin signaling pathway on diabetic AD rats. Results We report that pioglitazone 6 months treated patients has a positive effect on cognitive deficit, improve neurometabolic and decreasing neuroinflammation in diabetic AD patients, and it also was associated with a positive effect on insulin-signaling pathway plus its antioxidant effect on the brain of rats. Conclusion There is a strong association between AD and type 2 diabetes mellitus indicating that they share similar underlying pathophysiological mechanisms. Pioglitazone-treated diabetic AD patients were associated with improvement in cognition.

Does subclinical hypothyroidism confer an increased risk of coronary heart disease in the elderly? Sekina I Ahmed, Noha M ElSabbagh, Maha E Bondok, Amr K Mohamed, Mohammed H Eldin, Mohamed S Gongo Egyptian Journal of Obesity, Diabetes and Endocrinology 2018 4(2):58-71 Background Subclinical hypothyroidism (SCH) is defined as an isolated elevation of thyroid stimulating hormone (TSH) levels in conjugation with normal circulating levels of free triiodothyronine and free thyroxine. It is a highly prevalent disease especially in the elderly population. Thyroid hormones affect the heart and vasculature by both genomic and nongenomic pathways. However, the impact of SCH on the cardiovascular system is a matter of debate. Researches have been conducted to study the effect of SCH on cardiovascular system, yielding conflicting results. Although some studies support increased risk of cardiovascular events in patients with SCH, others show no significant increased risk. Aim This study was conducted to evaluate if SCH is associated with higher risk of coronary heart diseases in the elderly and if dyslipidemia, endothelial dysfunction as measured by flow-mediated dilatation (FMD) and carotid artery intima-media thickness were associated with SCH. Patients and methods Fifty elderly individuals aged 65 years and older were enrolled in this study and were divided into two groups, group I: 30 patients with SCH and group II comprised 20 age-matched and sex-matched euthyroid elderly serving as a control group. In all participants we performed serum TSH, free thyroxine, and antithyroperoxidase antibodies. SCH was defined as an elevated thyrotropin (TSH) (>4.5 mU/l) and normal free thyroxine level. Complete lipid profile, thyroid ultrasound, echocardiography to assess cardiac function and markers of endothelial dysfunction namely carotid artery intima-media thickness and FMD of the brachial artery (BA) after occlusion were done to all cases. Results The mean age of group I was 69.2±3.1 years and the mean age of group II was 68.6±3.2 years. Overall, 50% of the elderly patients with SCH (group I) were suffering from hypertension, whereas 35% in the elderly euthyroid group (group II) were hypertensive. The systolic and diastolic blood pressures are higher in group I as compared with group II (140±20 and 86±12, respectively vs. group II were 131±19 and 82±12, respectively), but the differences were statistically insignificant (P=0.12 and 0.21, respectively). No significant statistical difference was observed when the elderly SCH patients were compared with a euthyroid control group as regards the mean cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein levels (P=0.69, 0.79, 0.77, 0.42, respectively). For the elderly SCH group I the mean BA diameter before dilation was 3.12±0.44 versus 3.44±0.68 mm for euthyroid group II. However, the mean BA diameter after dilation was 3.64±0.60 mm compared with 4.05±0.73 mm for the euthyroid group. The mean percentage of FMD% of BA after occlusion was 16.2±5.7 in group I versus 17.9±5.5 in group II. There was no statistically significant difference between the two groups as regards flow-mediated vasodilatation% of the BA after occlusion (P=0.29). Conclusion This study did not find a significant association between thyroid function, lipid profile, and vascular parameters in patients who were similar with respect to age, BMI, smoking and menopausal status, and endothelial function modifiers.