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Shehata M.M.,Ain Shams University | Kamal M.M.,Ain Shams University | El-Hefnawy M.H.,National institute of Diabetes and Endocrinology NIDE | EL-Mesallamy H.O.,Ain Shams University
Journal of Diabetes and its Complications | Year: 2017

Aim: Beta-cell dysfunction is the critical determinant for type 2 diabetes. The novel PANcreatic DERived factor (PANDER) has been identified as interesting islet-secreted cytokine that might be involved in beta-cell dysfunction, a role that has n"ot been clinically elucidated yet. Therefore, this study was designed to study the potential clinical association of this cytokine with beta-cell dysfunction in type 2 diabetes. Methods: Anthropometric parameters, routine biochemical markers and serum levels of PANDER were measured in 63 diabetic subjects including; recently diagnosed type 2 diabetic patients with duration of diabetes ≤. 6. months and long-standing type 2 diabetic patients with duration of diabetes ≥. 5. years then compared to 16 healthy control volunteers. Proinsulin, C-peptide, insulin and PANDER were measured by ELISA. Beta-cell dysfunction was assessed by HOMA2-%β, proinsulin, proinsulin-to-insulin (PI/I) ratio and proinsulin-to-C-peptide (PI/C-pep) ratio. Relations among various parameters were studied using simple and multiple linear regressions. Results: Serum PANDER levels were found to be significantly elevated in long-standing diabetics as compared to recently diagnosed diabetics and controls. In addition, PANDER was found to be significantly correlated negatively to HOMA2-%β, as well as positively to proinsulin, PI/I and PI/C-pep ratios. Conclusion: PANDER is associated with beta-cell dysfunction in diabetic patients. © 2017 Elsevier Inc.


El Mesallamy H.O.,Ain Shams University | Hamdy N.M.,Ain Shams University | Mostafa D.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE
Journal of Interferon and Cytokine Research | Year: 2014

Chronic inflammation and insulin resistance form hallmarks of type 2 diabetes mellitus (T2DM). An increased circulating level of the serine protease granzyme B (GzmB) is observed during prolonged inflammation and is implicated in the pathogenesis of several chronic inflammatory diseases. Moreover, insulin receptor cleavage by unknown proteases, yielding elevated levels of insulin receptor α-subunit (IRα), was observed in T2DM and was proposed as a new mechanism of insulin resistance. Therefore, a possible association between GzmB and IRα is suggested. Accordingly, this study was set to explore whether GzmB and IRα levels are altered in T2DM patients with the impact of obesity. Furthermore, we aimed to identify if GzmB contributes towards inflammation and insulin resistance through its suggested extracellular activities. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition, fasting plasma insulin, GzmB, interleukin-1β (IL-1β), and IRα levels were estimated by enzyme linked immunosorbent assay. Levels of GzmB and IRα were found to be significantly elevated in T2DM patients compared to nondiabetic subjects. In addition, GzmB levels were positively correlated with measures of obesity and insulin resistance, IL-1β, IRα, and other metabolic parameters. While multiple linear regression analysis revealed that both T2DM and central obesity were predicting factors for GzmB, our findings reveal a possible role of GzmB in T2DM. © Mary Ann Liebert, Inc.


Noureldein M.H.,Ain Shams University | Abd El-Razek R.S.,Ain Shams University | El-Hefnawy M.H.,National Institute of Diabetes and Endocrinology NIDE | El-Mesallamy H.O.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2015

Aims: The aim of the current study is to investigate the effect of fenofibrate alone and in combination with pioglitazone on serum sirtuin 1 and fetuin A of obese patients with Type 2 Diabetes Mellitus (T2DM). MethodsIntervention effect on inflammatory parameters was assessed before and after treatment. The study was conducted on 60 postmenopausal females of whom, only 44 patients completed the study. They were distributed as follows; obese patients without T2DM (n= 15) who administered fenofibrate (160. mg/day) once for 8 weeks, obese patients with T2DM (n= 15) who administered fenofibrate (160. mg/day) once for 8 weeks, obese patients with T2DM (n= 14) who administered fenofibrate (160. mg/day) and pioglitazone (15. mg/day) combination once for 8 weeks.We measured fasting plasma glucose, glycated hemoglobin (HbA1c), serum lipids. Inflammatory markers (high sensitivity C-reactive protein "hs-CRP", interleukin-6 "IL-6", fetuin A, and sirtuin 1) of patients were measured in serum using enzyme-linked immunoassay (ELISA) kits. ResultsSirtuin 1 levels in obese patients with T2DM were significantly lower than its levels in obese patients while fetuin A levels were significantly higher (P<. 0.001). Fenofibrate, alone and in combination with pioglitazone, significantly decreased triacylglycerol, hs-CRP, IL-6, fetuin A and increased sirtuin 1 levels (P<. 0.001) which suggests that it can be used to delay the complications of obesity and T2DM. There is a strong correlation between fetuin A, sirtuin 1, IL-6 and hs-CRP levels suggesting a shared common pathway. ConclusionsFenofibrate was shown to increase serum sirtuin 1 and decrease serum fetuin A levels in obese patients. Trial numberPACTR201407000856135. © 2015 Elsevier Ireland Ltd.


El-Mesallamy H.O.,Ain Shams University | Kassem D.H.,Ain Shams University | El-Demerdash E.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE
Metabolism: Clinical and Experimental | Year: 2011

Recently, vaspin and visfatin/Nampt have been identified as interesting novel adipokines having insulin-sensitizing and insulin-mimetic effects, respectively. However, the relationship between them has not been elucidated; and their circulating levels in type 2 diabetes mellitus (T2DM) have not been adequately studied. Therefore, this study was designed to investigate whether their levels are altered in Egyptian T2DM patients and to study the correlation of these novel adipokines with each other and with insulin resistance, interleukin-6 (IL-6), and other biochemical parameters. The levels of vaspin, visfatin/Nampt, IL-6, insulin, and other parameters were measured in nonobese and obese T2DM patients together with matched healthy nondiabetic control subjects. Vaspin, visfatin/Nampt, and IL-6 levels were measured by enzyme-linked immunosorbent assay, whereas insulin levels were measured by chemiluminescence technique. Vaspin and visfatin/Nampt levels were found to be significantly elevated in nonobese (1.62 ± 0.22 and 25.9 ± 3.44 ng/mL, respectively) and obese T2DM patients (2.76 ± 0.38 and 45.4 ± 4.60 ng/mL, respectively) compared with control subjects (0.42 ± 0.05 and 9.37 ± 1.98 ng/mL, respectively) at P < .01. In addition, vaspin and visfatin/Nampt levels were found to be significantly positively correlated with each other and with other biochemical parameters. In conclusion, both vaspin and visfatin/Nampt might play an important role in the pathogenesis of T2DM. In addition, the 3 adipokines-vaspin, visfatin/Nampt, and IL-6-are significantly interrelated with each other. Other possible mechanisms of action for vaspin should be considered besides the inhibition of unknown substrate proteases. © 2011 Elsevier Inc. All rights reserved.


El-Mesallamy H.O.,Ain Shams University | Mostafa A.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE | El Demerdash E.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2011

Recently, YKL-40 has been identified as a new inflammatory marker of type 2 diabetes mellitus (T2DM), while leptin is one of the most important adipose derived hormones. However, the relationship between them has not been elucidated. Therefore this study aimed to study their correlation in obese T2DM patients. © 2011 Elsevier Ireland Ltd.


Aboouf M.A.,Ain Shams University | Hamdy N.M.,Ain Shams University | Amin A.I.,National Institute of Diabetes and Endocrinology NIDE | El-Mesallamy H.O.,Ain Shams University
Diabetes Research and Clinical Practice | Year: 2015

Highlights: Aims: Apelin is one of adipokines that plays a pivotal role in energy metabolism, insulin sensitivity and vascular integrity. A definite genetic variant of apelin gene (APLN), rs3115757, was recently introduced to potentially influence apelin expression in adipocytes. The aim of our study was to explore the sights of a potential association of this functional variant with obesity traits, insulin resistance indices as well as type 2 diabetes mellitus (T2DM) prevalence. Methods: Genotype screening for rs3115757 variant in 151 Egyptian female samples was conducted. Fasting levels of serum insulin and lipid profile, in addition to plasma glucose were measured. Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and obesity using a case-control design. Results: The homozygous G risk allele carriers showed higher values of body mass index (BMI) and waist circumference (P=0.001,0.02, respectively) as compared to CC or CG genotypes. As for GG genotype carriers, the risk of developing morbid obesity in lean subjects, (BMI. <. 25), is twelve times the risk in subjects carrying other genotypes (OR. =12.09, 95% CI: 1.4, 104.8, P=0.024). On the other hand, GG carriers are shown to be more resistant to insulin. Significantly after correction for BMI and age effects, GG genotype carriers showed 14% and 41% increment in insulin level and resistance (OR. =1.14, 95% CI: 1.06, 1.23, P=0.001), (OR. =1.42, 95% CI: 1.19, 1.70, P<. 0.001), respectively. Conclusion: These results suggest a prospective role mediated by this variant in mounting obesity disorders and as significant as insulin resistance complications. © 2015 Elsevier Ireland Ltd.


PubMed | Ain Shams University and National Institute of Diabetes and Endocrinology NIDE
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2015

Apelin is one of adipokines that plays a pivotal role in energy metabolism, insulin sensitivity and vascular integrity. A definite genetic variant of apelin gene (APLN), rs3115757, was recently introduced to potentially influence apelin expression in adipocytes. The aim of our study was to explore the sights of a potential association of this functional variant with obesity traits, insulin resistance indices as well as type 2 diabetes mellitus (T2DM) prevalence.Genotype screening for rs3115757 variant in 151 Egyptian female samples was conducted. Fasting levels of serum insulin and lipid profile, in addition to plasma glucose were measured. Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and obesity using a case-control design.The homozygous G risk allele carriers showed higher values of body mass index (BMI) and waist circumference (P=0.001,0.02, respectively) as compared to CC or CG genotypes. As for GG genotype carriers, the risk of developing morbid obesity in lean subjects, (BMI<25), is twelve times the risk in subjects carrying other genotypes (OR=12.09, 95% CI: 1.4, 104.8, P=0.024). On the other hand, GG carriers are shown to be more resistant to insulin. Significantly after correction for BMI and age effects, GG genotype carriers showed 14% and 41% increment in insulin level and resistance (OR=1.14, 95% CI: 1.06, 1.23, P=0.001), (OR=1.42, 95% CI: 1.19, 1.70, P<0.001), respectively.These results suggest a prospective role mediated by this variant in mounting obesity disorders and as significant as insulin resistance complications.


Sayed A.,Cairo University | Taha A.,Cairo University | Taha A.,National Institute of Diabetes and Endocrinology NIDE | Elkholy M.,National Institute of Diabetes and Endocrinology NIDE | And 2 more authors.
International Angiology | Year: 2012

Aim. Patients with severe critical limb ischemia (CLI) due to tibial disease are commonly treated nowadays with tibial angioplasty. However, the benefits and complications of treating "more than one tibial vessel" have not yet been determined. This study compares the outcome of angioplasty of one vessel versus that of more than one vessel in patients with CLI due to tibial disease. Methods. We retrospectively reviewed all consecutive diabetic patients with tibial disease with no concomitant proximal lesions who were treated by angioplasty. Among 82 patients with isolated tibial disease 48 patients were selected. All patients had to have more than one diseased tibial vessel that can be treated by angioplasty. Group A patients (N.=25) had only one tibial vessel treated while group B patients (N.=23) had more than one tibial vessel treated. We compared both groups with respect to patients' characteristics, lesion morphology, and limb salvage rate. Results. Lesion morphology was worse in group A than B: anterior tibial artery showed more long lesions (17 vs. 8), more multiple lesions (22 vs. 11), and peroneal artery showed more long lesions (23 vs. 10), more multiple lesions (24 vs. 12), and more occlusions (18 vs. 10). Limb salvage rate at 12 months was similar (91%) in both groups. There were 5 complications in each group. Conclusion. The lesion morphology was worse in group A. Simpler lesions in group B motivated performing more than one vessel angioplasty. There was no difference in the limb salvage rate in the medium term among both groups. Additional vessels angioplasty in less diseased arteries was not associated with substantial additional morbidity.


Hashim A.A.,Helwan University | Ali S.A.,Helwan University | Emara I.A.,National Institute of Diabetes and Endocrinology NIDE | El-Hefnawy M.H.,National Institute of Diabetes and Endocrinology NIDE
Journal of Medical Biochemistry | Year: 2016

Background:In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. Methods: Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l "CTX") were measured and compared to the results of 20 age-matched healthy controls. Results: After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. Conclusions: Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sexrelated reference. © by Sahar A. Ali 2016.

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