Internal Medicine

Is neutrophil-lymphocyte ratio a novel biomarker for macrovascular and microvascular complications of type 2 diabetes? Walaa H Mohammad, Ahmad B Ahmad, Muhammad H Al-Maghraby, Mohamed Z Abdelrhman, Sanaa Ezzate The Egyptian Journal of Internal Medicine 2019 31(1):1-7 Background/aim The neutrophil-to-lymphocyte (N/L) ratio is a biomarker of inflammation. We aimed to test the hypothesis that macrovascular and microvascular complications of type 2 diabetes mellitus (DM) involve an inflammatory process. Patients and methods This is a cross-sectional study conducted on patients with type 2 DM. Demographic and clinical examination data of eligible patients were recorded. The blood samples for laboratory variables were collected and measured by the standard methods. A standard ultrasound examination was done to measure both carotid artery intima-media thickness (cIMT), and the averages of three results of each side were recorded. Results The current study showed that N/L ratio was an independent predictor of cIMT in patients with type 2 DM (B=0.003, t=8.325, P=0.000), in addition to other conventional cardiovascular risk factors including age, male sex, smoking index, duration of diabetes, estimated glomerular filtration rate, low-density lipoprotein-cholesterol, urinary albumin creatinine ratio, and HBA1c. Moreover, N/L ratio was an independent predictor of albuminuria in patients with type 2 DM (B=0.110, t=3.638, P=0.006), in addition to duration of diabetes, HBA1c, SBP, BMI, and estimated glomerular filtration rate. Conclusion N/L ratio was an independent predictor of cIMT and albuminuria. This supports the hypothesis that diabetic macrovascular and microvascular complications involve an inflammatory process. Therefore, NLR may serve as a cost-effective and readily accessible marker of diabetic vascular complications.

Genetic variants of two-pore calcium channel 2 rs1551305 and its association with type 2 diabetes risk Kareem Essam The Egyptian Journal of Internal Medicine 2019 31(1):8-13 Context The prevalence of diabetes is highest in the Eastern Mediterranean Region, with Egypt leading the region (11% for both sexes) and lowest in the European Region (7% for both sexes). Genome-wide association studies of single-nucleotide polymorphisms (SNPs) have identified a number of variants that are associated with β-cell function and insulin resistance. Two-pore calcium channel 2 (TPCN2) localizes to the lysosome and is a likely receptor for the calcium-mobilizing agent nicotinic acid adenine dinucleotide phosphate. Several studies have indicated that nicotinic acid adenine dinucleotide phosphate may play a role in the insulin signaling of β-cells. Aim of the study The aim of this study was to investigate the association between TPCN2 rs1551305 SNPs and the development of type 2 diabetes. Patients and methods A sample of 158 Egyptian participants was divided into two groups. Group one included 79 type 2 diabetic patients and group two included 79 healthy controls. TPCN2 rs1551305 SNPs were determined by the real-time PCR technique. Results A significant increase in the frequency of G/G genotype in diabetic patients was found. A/A genotype was significantly more frequent in the control group (P=0.001). G allele was also significantly higher in diabetic patients (P=0.008). The G/G genotype showed a 21.37-fold increase in the risk of developing diabetes mellitus. Conclusion The previous findings suggest that TPCN2 rs1551305 SNP is associated with the risk of type 2 diabetes development.

The influence of single-nucleotide polymorphisms of interleukin-1β −511 and +3954 on the susceptibility to Hashimoto's thyroiditis in Egyptian women: immune-endocrine interactions Nearmeen M Rashad, Manar H Soliman, Mayada M Mousa, Azza H Abd El-Fatah The Egyptian Journal of Internal Medicine 2019 31(1):14-21 Background Hashimoto’s thyroiditis (HT) is a T-cell-mediated autoimmune disease. Cytokines play a crucial role in modulating immune responses that affect the balance between maintenance of self-tolerance and initiation of autoimmunity. Thus, we aimed to explore the possible associations of interleukin (IL-1β) −511C/T (rs16944) and IL-1β +3954C/T (rs1143634) gene polymorphisms with susceptibility of HT, and to clarify the impact of these polymorphisms on thyroid function of Egyptian women. Patients and methods Polymorphisms of the IL-1β −511 and IL-1β +3954 genes were assessed in a case–control study comprising 110 HT patients and 90 controls. Genetic variants were genotyped by multiplex PCR. Polymorphisms of the IL-1β were studied by PCR-restriction fragment length polymorphism analysis. Results Our results revealed that the IL-1β −511 CT genotype distribution was significantly higher in HT patients than in controls. With regard to IL-1β +3954 gene polymorphisms, our results showed that there was a nonsignificant difference between the control and HT groups. Women carrying TT and CT genotype of IL-1β −511 had significantly higher values of C-reactive protein, thyroid-stimulating hormone, anti-thyroid peroxidase, and anti-thyroglobulin. As regards the IL-1β serum level, women carrying TT and TC genotype of IL-1β −511 had significantly higher values compared with patients carrying the CC genotype. Moreover, anti-thyroglobulin and free thyroxine were the only independently correlated factors with IL-1β serum level by linear regression analysis. Conclusion CT genotype distribution was significantly higher in patients with HT than in controls with regard to IL-1β −511 (C>T) gene polymorphisms.

The impact of stevioside supplementation on glycemic control and lipid profile in patients with type 2 diabetes: a controlled clinical trial Nearmeen M Rashad, Mona A.E Abdelsamad, Atef M Amer, Mahmoud Z Sitohy, Mayada M Mousa The Egyptian Journal of Internal Medicine 2019 31(1):22-30 Background Stevia is a naturally occurring non-nutritive sweetener that has been reported as sugar substitutes for diabetic patients. We aimed to assess the impact of stevia supplementation on glycemic control in patients with type 2 diabetes mellitus (T2DM). Also, we aimed to examine the association between stevia supplementation and anthropometric measures as well as lipid profile in both obese and diabetic patients. Patients and methods The controlled clinical trial included unrelated 150 participants; 40 patients with T2DM and 60 obese patients and 50 healthy controls. Obese patients were then subdivided into two subgroups according to their fasting blood sugar: nondiabetic (n=30) and 30 patients with T2DM. The participants received stevia (4 mg/kg/body weight) as an alternative to artificial sweetener for 24 weeks. Results Our results found that stevioside supplementation for diabetic patients’ increased the total caloric intake and decreased BMI, waist circumference, waist–hip ratio, and fat mass index, in the obese group. Our results have shown a significant increase of BMI, waist circumference, waist–hip ratio, and fat mass index after 24 weeks of stevia supplementation. In the diabetic group, stevioside for 24 weeks improved the lipid profile and glycemic control, fasting plasma glucose, 2-h plasma glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and hemoglobin A1c (HbA1c), as well as total cholesterol, triglycerides, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol in all studied intervention groups. Logistic regression test revealed that among clinical and laboratory waist circumference, fasting plasma glucose and HbA1c were independent predictors of response to stevioside. Conclusion Stevioside supplementations for 24 weeks improved cardiometabolic risk in diabetic patients. However, in the obese group, stevioside supplementations increased body weight.

Serum macrophage migration inhibitory factor levels in Hashimoto's thyroiditis MN Ayman Abd Elrahman, Nagwa S Said, Azza Moustafa The Egyptian Journal of Internal Medicine 2019 31(1):31-37 Background Hashimoto’s thyroiditis (HT) is the most common autoimmune thyroid disease. The actual mechanism by which the immunological factors lead to HT has remained obscure. Macrophage migration inhibitory factor (MIF) is recently recognized as a cytokine that has a broad range of inflammatory and immune effects. The aim of this study is to assess the role of MIF in the pathogenesis of HT. Patients and methods One hundred and twenty-nine patients were classified into three groups: (a) overt hypothyroidism, (b) subclinical hypothyroidism, and (c) the control group. A complete history taking, clinical examination, and laboratory investigations were done. Laboratory investigations included thyroid function tests [thyroid-stimulating hormone (TSH), triiodothyronine, and thyroxine], antithyroid antibodies (antithyroid peroxidase antibodies and thyroglobulin antibodies), and MIF level. Results There is highly statistically significant difference between the three groups regarding MIF, the highest level being in group 1>group 2>group 3. In both hypothyroid groups (1 and 2), there are statistically significant positive correlations between MIF with TSH, thyroid peroxidase antibodies, and thyroglobulin antibodies, but there is no statistically significant correlation between MIF with thyroid functions tests and antithyroid antibodies in the control group. Conclusion Serum MIF levels increased in overt and subclinical hypothyroidism and its levels were positively correlated to TSH and thyroid-specific autoantibodies. Serum MIF levels play a role in the pathogenesis of thyroid autoimmune responses in patients with HT. We recommend further larger studies to assess the MIF role in the prognosis of the HT and its treatment by a new strategy.

Salivary versus serum testosterone levels in boys with constitutional delay of growth and puberty Eman H El-Adawy, Enas T El-Khamisy, Ghada El-Said, Amal Seleem The Egyptian Journal of Internal Medicine 2019 31(1):38-42 Background Salivary testosterone (Sal-T) has been established as a noninvasive biomarker in the diagnosis of androgen deficiency in men. However, available data on its utility in adolescent boys with constitutional delay of growth and puberty (CDGP) are not conclusive. Our study was designed to compare salivary versus serum measurements of free testosterone (FT) from the samples collected simultaneously and correlated them with the clinical parameters in boys with CDGP. Patients and methods The study enrolled 25 adolescent boys with CDGP and 20 healthy controls matched for age and sex. Weight, height, BMI, testicular volume, bone age, serum follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed. Simultaneous morning saliva and serum samples were obtained for FT measurements by radioimmunoassay and Sal-T by the enzyme-linked immunosorbent assay technique. Results Adolescent boys with CDGP had significantly lower Sal-T and serum free-T than normal controls (P<0.001). Sal-T positively correlated with BMI, bone age, testicular volume, serum FSH, LH, and FT. With multiple regression analysis BMI, FSH, LH, and serum FT remained independently correlated with Sal-T. Using the receiver operating characteristic curve, Sal-T was found to be more sensitive than serum FT (76 vs. 69%) in the clinical assessment of boys with CDGP. Conclusion Our data shows that Sal-T strongly correlates with FT and provides a sensitive, simple, noninvasive, and diagnostic approach for androgen status in adolescent boys with CDGP.

The relationship between the level of serum-free testosterone and depression in obese adolescent men in Sharkia Governorate MN Ayman Abd-Elrahman, Amira A Fouad, Hossam E Salah The Egyptian Journal of Internal Medicine 2019 31(1):43-51 Background Obesity among children and adolescents is considered as one of the most serious public health concerns; low levels of testosterone have been associated with higher levels of morbidity and may have been associated with depression. Objective To assess the relationship between the level of serum-free testosterone and depression in obese adolescent men in Sharkia Governorate. Patients and methods The present study was conducted on 240 age-matched healthy Egyptian adolescent men, collected from the obesity clinic, Internal Medicine Department, Zagazig University Hospital and five high schools in Sharkia Governorate; all the included participants were subjected to: (a) history taking; (b) physical examination (weight, height, BMI, waist circumference, waist to hip ratio, and Tanner stage using Prader orchidometer); (c) hormonal investigations (free testosterone, estradiol, follicular-stimulating hormone, and luteinizing hormone); (d) psychological assessment for depression using: Mini International Neuropsychiatric Interview for Children and Adolescents and children’s depression inventory. Results There was a significant inverse correlation between free testosterone levels and waist circumference among both control and obese cases (r=−0.31, P=0.031 and r=−0.30, P=0.01, respectively). The free testosterone level was significantly lower in obese cases with depression (2.81±2.32 pg/ml) in comparison with obese cases without depression (3.63±2.65 pg/ml) (P=0.04) and testosterone levels was significantly lower in obese cases having some depressive symptoms (feeling depressed, feeling restless, feeling guilty, eating disorders, sleeping disorders, feeling restless, and suicidality). There were significant inverse correlations (P<0.05) between mean free testosterone level and both mild and moderate depression (r=−0.45, P=0.02 and r=−0.58, P=0.012, respectively), and with the following depressive symptoms; feeling depressed, feeling restless, feeling guilty, eating disorder, sleeping disorders, poor concentration, and suicidality. Conclusion Obese adolescent men in Sharkia Governorate are significantly associated with lower free testosterone levels. Most of the depression symptoms and their degree are inversely correlated with the levels of free testosterone, otherwise the levels of luteinizing hormone, follicular-stimulating hormone, and estradiol showed no correlation with the depression symptoms or their degree. We recommend further larger studies to prove the relationship between the level of serum-free testosterone and depression in obese adolescent men and try to put a management protocol.

Serum β-CrossLaps as a predictor for osteoporosis in postmenopausal women with early diabetic nephropathy Ashraf Mohamed The Egyptian Journal of Internal Medicine 2019 31(1):52-56 Background Osteoporosis is a progressive bone disease with an increased risk of fracture. Objective To estimate bone turnover through an early marker, β-CrossLaps (β-CTx), in postmenopausal women with type 2 diabetes mellitus (DM) and early diabetic nephropathy (DN). Patients and methods A case–control study comprised 80 Egyptian postmenopausal nonsmoker women: 26 women without DM (group 1) as a control group, 28 women had type 2 DM without DN (group 2), and 26 woman were type 2 DM with early DN (group 3). All demographic and clinical data were collected. Laboratory tests including serum calcium, phosphorus, alkaline phosphatase (ALP), bone ALP, β-CTx, glycated hemoglobin, microalbuminuria, serum creatinine, and blood sugar levels were estimated. Results Regarding bone minerals, there was a significant lower serum level of calcium and phosphorus in group 3 compared with groups 1 and 2 (P=0.029 and <0.0001, respectively). Groups 2 and 3 had significantly lower serum levels of total ALP (P=0.011 and 0.006, respectively) and bone ALP (with lowest level in group 3) (P<0.0001) compared with group 1. Groups 2 and 3 had significantly higher serum levels of β-CTx (with highest level in group 3) compared with group 1 (P=0.016 and 0.003, respectively). Dual-energy X-ray absorptiometry scan revealed a significant elevation in osteoporosis percent in group 3 (63.4%) in comparison with group 1 (26.9%) (P=0.001), whereas osteopenia percent was significantly higher in group 2 (P=0.004) compared with group 3. Conclusion In diabetic postmenopausal women, serum β-CTx and microalbuminuria are potentially useful tools for assessing bone resorption state.

Association of serum growth differentiation factor 15 and hepatocellular carcinoma in Egyptian patients Mohamed-Naguib Wifi, Rania A Zayed, Nevine Fouad, Ahmed Y Hassan, Maha A Hussien, Mohamed G Sokar The Egyptian Journal of Internal Medicine 2019 31(1):57-63 Background Liver cirrhosis and hepatocellular carcinoma (HCC) are consequences of chronic hepatitis C virus (HCV) infection. HCC is one of the fastest rising causes of cancer-related mortality. This dismal prognosis is related to late diagnosis with currently available screening methods. The aim of our study was to evaluate the diagnostic power of serum growth differentiation factor (GDF) 15 in HCC detection and its ability to distinct HCC from cirrhosis in chronic hepatitis C Egyptian patients. Patients and methods Ninety participants were included in the study; 30 patients with HCV-cirrhosis, 30 patients with HCV-Cirrhosis and HCC, and 30 gender and age-matched healthy subjects as the control group. The patients were subjected to history taking, clinical examinations, routine laboratory analysis, and α-fetoprotein (AFP) determination. Serum GDF15 was measured using an enzyme-linked immunosorbent assay kit. Results The mean level of GDF15 in HCV-cirrhosis patients was 140.28±128.66 pg/ml, in HCV-HCC patients 154.45±123.74 pg/ml, and in the control group it was 81.19±42.53 pg/ml. Statistically significant difference in GDF15 level was found between HCV-HCC patients and controls, P=0.012, while no statistically significant difference was found on comparing HCV-cirrhosis patients to controls or to HCV-HCC patients, P=0.064 and 0.473, respectively. The cut-off value of GDF15 to discriminate HCV-HCC patients from controls was 122.3 pg/ml with 53.3% sensitivity and 86.7% specificity and an area under the receiver operating characteristic (AUROC) of 0.692. AFP at a cut-off value of 20.85 ng/l was able to discriminate HCV-HCC patients from HCV-cirrhosis patients with 73.3% sensitivity and 73.3% specificity and an AUROC of 0.744. AUROC for combined AFP and GDF15 showed lower performance than AFP alone in discrimination of HCV-HCC from HCV-cirrhosis patients (AUROC=0.642). Conclusion GDF15 is not a potential diagnostic marker for the distinction of HCC from cirrhosis in chronic hepatitis C Egyptian patients.

The role of hepatitis C virus and possible risk factors in development of hepatocellular carcinoma: 400 patients based study Fatema Abu-bakr Abdelmoez, Hala Mostafa Imam, Naglaa kamal Idriss, Lobna Abdel Wahid, Wael Ahmed Abbas, Mohamed Abozaid Ali Abozaid, Hossam Mahmoud Abdelwahab The Egyptian Journal of Internal Medicine 2019 31(1):64-72 Background and aims Hepatocellular carcinoma (HCC) is one of the commonest tumors and considered the fifth most common malignant neoplasm and a major cause of death. Egypt has increased incidence of HCC cases, as Egypt has the highest prevalence of hepatitis C virus (HCV) infection. The aim was to study the epidemiological characteristics of HCC in Assiut, Egypt. Patients and methods A descriptive observational study design was applied for the present study. The studied population was 400 patients with HCC (288 of them were male and 112 were female) who fulfilled the diagnostic criteria for HCC. Data were analyzed for exploring the clinical, etiological, radiological, and tumor characteristics of the studied patients. Results The mean age of the patients was 59.85±9.1 years. Most cases (68%) were from rural areas, 38% of the patients were in agricultural occupation, and 32% of the patients were accidentally discovered to have HCC .The most frequent symptom was abdominal pain (15%). HCV antibody was present in 63% of the patients, HBV infection was recorded in 28%, coinfection was seen in 3%, and no viral infection was present in 6%. Diabetes mellitus was present in 37% and obesity in 24% of the patients. Right lobe of the liver was the most frequent affected lobe (61%), and 69% of the cases had a single lesion. Conclusion HCC incidence had been increasing in the past years in Egypt. The high prevalence of HCV infection in Egypt makes the surveillance strategies important for early detection of HCC in these patients to provide better curative treatment modalities in the early stages.