scholarly journals PTPN22 gene and IL2RA rs11594656, rs2104286 gene variants: additional insights of polygenic single-nucleotide polymorphisms’ pattern among Egyptian children with type 1 diabetes

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Soheir S. Abou El Ella ◽  
Maha A. Tawfik ◽  
Zeinab Sabri Mohammed ◽  
Naglaa Fathy Barseem

Abstract Background Type 1 diabetes mellitus (T1D) results from environmental and genetic factors. We aimed to investigate the distribution of PTPN22, IL2RA rs11594656, and rs2104286 variants and its association with T1D in children. A case-control study conducted on 100 diabetic patients and 100 control children. PTPN22 gene, IL2RA rs11594656, and rs2104286 polymorphisms study were done by PCR followed by restriction fragment length polymorphism (RFLP) assay. Results T allele of PTPN22 gene was presented more frequently 47% in patient group versus 30% in controls, while C allele was 53% in the diabetic group versus 70% in controls showing a statistically significant difference between patient and control groups. Similarly, TT 1858 genotype was found in higher frequency with a statistically significant difference in favor of T1D patients (p = 0.038), OR (CI 95% 3.16 (1.28–7.09). For IL2RA rs11594656 polymorphism, the frequency of TT, TA, and AA in patients at percentages of 20%, 60%, and 20% versus 4%, 60%, and 36% in controls respectively showed significant difference (p = 0.045). Also, T allele was detected more in patients group as evidenced by p = 0.059, OR (95% CI) of 2.38(1.49–6.12). Whereas, IL2RA rs2104286 polymorphism revealed a difference of otherwise non-statistical significance (p = 0.091). Those who harbored homozygous pattern of both IL2RA polymorphisms frequently had DKA and high mean HbA1C values. Conclusion PTPN22 (C1858T) and IL2RA rs11594656 polymorphisms increased the risk of T1DM development, while IL2RA rs2104286 polymorphism did not display any significant association among children with T1D. Having more than one risk allele could affect progression and control of T1D.

2003 ◽  
Vol 60 (5) ◽  
pp. 555-564 ◽  
Author(s):  
Tamara Dragovic ◽  
Rajko Hrvacevic ◽  
Boris Ajdinovic ◽  
Svetlana Vujanic

Aim. To determine the efficacy of AT1 receptor antagonist (valsartan) in decreasing of urinary excretion of albumin in normotensive patients with type 1 diabetes and incipient diabetic nephropathy (DN). Methods. This was a prospective, randomised, placebo-controlled study, which included 20 patients with insulin-dependent diabetes mellitus, mean age 25.15, and the duration of diabetes of 13.95 years. All the patients were normotensive, with persistent microalbuminuria (incipient phase of DN). Patients were randomly divided into two groups (10 patients each): valsartan group treated with 80 mg valsartan daily during 6 months, and the group treated with placebo during the same period. Both groups were similar and comparable concerning the observed parameters at the beginning of the study. Results. After 6 months therapy, valsartan caused significant decrease of urinary albumin excretion rate (UEAR) by 69.1% from 64.8 to 21.1 mg/24 h, while in placebo group there was an insignificant increase of UEAR by 29.8%. During the follow-up of UEA in the observed groups, at the beginning and the end of the mentioned period highly significant decrease of albumine secretion (p<0.001) was observed. Valsartan significantly lowered mean systolic blood pressure (from 122.0 ? 10.1 to 110.0 ? 11.8 mmHg). After 6 months therapy, the reduced values of total cholesterol and LDL-cholesterol fraction were registered in the valsartan group, while the difference in serum trigliceride values reached statistical significance (1.42 ? 0.79 vs. 1.21 ? 0.89 mmol/L; p<0.05). Neither significant difference in glycoregulation quality between the two groups, nor the occurence of hyperkalemia was detected throughout the study period. Conclusion. Valsartan's efficacy in the decrease of microalbuminuria after 6 months of therapy could justify the use of this group of renin/angiotensin blockers in delaying the clinically manifested DN. Valsartan was well tolerated and did not influence the quality of glycoregulation. It did not increase the level of serum lipids and could be recomended in the treatment of diabetic patients.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Polkowska ◽  
Izabela Elżbieta Pasierowska ◽  
Marta Pasławska ◽  
Elżbieta Pawluczuk ◽  
Artur Bossowski

Introduction. The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). Aim of the Study. Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. Materials and Methods. The study consisted of 138 patients aged 5–18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p<0.05. Results. The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. Conclusions. Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.


1998 ◽  
pp. 44-48 ◽  
Author(s):  
CC Chang ◽  
CN Huang ◽  
LM Chuang

OBJECTIVE: Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD). Genetic susceptibility to autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about the situation in the Chinese population. We have, therefore, investigated the prevalence of anti-thyroid peroxidase (anti-TPO) in type 1 diabetic patients, and compared the effect of anti-glutamate decarboxylase (anti-GAD) on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Taiwan. SUBJECTS AND METHODS: Two hundred and forty-three subjects with type 1 diabetes mellitus and seventy unrelated normal controls were recruited for the detection of anti-TPO. Two hundred and seventeen sera from two hundred and forty-three type 1 diabetic patients were tested for anti-GAD. RIA and immunoprecipitation were used for anti-TPO and anti-GAD detection respectively. RESULTS: The intra-assay and interassay coefficients of variation of anti-TPO detected by the RIA method ranged from 5.5% to 11.1%. Among 243 type 1 diabetic patients, 53 (21.8%) were positive for anti-TPO. Compared with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female:male, 99:91 vs 37:16 respectively). Among the type 1 diabetic patients with thyroid autoimmunity, anti-TPO tended to occur in those of older age or with long-standing disease. The frequency of anti-GAD was 45.6%, (99 of 217), without gender preponderance (males:females, 18.0% vs 27.61%). Compared with those with negative anti-GAD, no significant difference of anti-TPO positivity for the type 1 diabetic patients with positive anti-GAD was found. CONCLUSION: Our data indicated that the RIA method for anti-TPO detection is sensitive and precise for routine clinical use. The presence of anti-TPO in 21.8% of our type 1 diabetic patients confirmed the strong association of ATD and type 1 diabetes mellitus without ethnic differences. The absence of correlation between anti-TPO and anti-GAD in our type 1 diabetic patients suggested genetic heterogeneity in the role of autoimmunity of type 1 diabetes mellitus and ATD among races.


Author(s):  
Imen Boussaid ◽  
Asma Boumiza ◽  
Ramzi Zemni ◽  
Elyes Chabchoub ◽  
Latifa Gueddah ◽  
...  

AbstractBackground:Enteroviral infections have long been suspected in having a role in β cell destruction and therefore leading to the onset of clinical type 1 diabetes (T1D). The frequency of enterovirus (EV)-related T1D in North Africa is still unknown. The aim of the present study was to investigate the relationship between infection with EV and T1D in Tunisia.Methods:A total of 95 T1D patients (41 children and 54 adults) and 141 healthy control subjects (57 children and 84 adults) were tested for the presence of EV-RNA by a highly sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) method.Results:EV-RNA was detected more frequently in plasma from diabetic patients than in plasma of controls (31.6% vs. 7.8%, p<0.0001; OR=5.45; 95% CI 2.44–12.43). RT-PCR revealed positive in 53.7% of T1D children and 14.8% of T1D adults. There was a statistically significant difference between children and adults with T1D (p<0.0001). Positivity of EV-RNA according to the time after the occurrence of the disease did not show any significant difference (p=0.34). Anti-glutamic acid decarboxylase (GAD) antibodies were not associated with EV-RNA (p=0.65).Conclusions:EV-RNA is associated with T1D mellitus in the Tunisian population especially in children. These results support the hypothesis that EV act as environmental risk factors for T1D.


2019 ◽  
Vol 19 (8) ◽  
pp. 1172-1176 ◽  
Author(s):  
Esma Mihoubi ◽  
Rachida Raache ◽  
Habiba Amroun ◽  
Malha Azzouz ◽  
Assia Galleze ◽  
...  

Background: We aimed to assess Vitamin D levels in patients with Type 1 Diabetes (T1D) and to investigate the correlation between vitamin D and metabolic imbalance. Material and Methods: For our study, we selected thirty-one patients with T1D without complications and fifty-seven healthy controls. Diabetic patients were diagnosed using the criteria of the World Health Organization/American Diabetes Association. Vitamin D, Parathyroid Hormone (PTH), insulin and C peptide assay were performed using chimilunescence. Glucose level, lipid profile, glycated haemoglobin (HbA1c) and ionogram were also analysed. Results: Vitamin D, HbA1c and Gly levels were found to be significant in T1D patients than in controls (P<0.5). However, for PTH, no significant difference was observed (P > 0. 05) and the results show a non-significant difference of total cholesterol potassium, sodium, phosphor and calcium concentration averages. Conclusion: Our results indicate that the deficiency of VD is associated with an increased risk of T1DM in Algerian population.


2021 ◽  
Vol 37 (7) ◽  
Author(s):  
Imad Mohamed ◽  
Iman M. Talaat ◽  
Hamed A. Alghamdi ◽  
Gamal Allam

Background & Objective: Type-1 diabetics (T1D) usually do not meet guidelines for glycaemic control. This study aimed to determine the benefit of free style libre-flash glucose monitoring system (FSL-FGM) in lowering glycated hemoglobin (HbA1c) in poorly controlled T1D patients. Methods: This prospective two single arm clinical study included 273 T1D patients, and data collected at one, six and 18 months with concomitant extraction of samples for HbA1c basal and at six and 18 months. The study was conducted in Prince Mansour Military Hospital at Taif, Saudi Arabia from June 2017 to November 2018. Results: HbA1c % was significantly diminished in patients used FSL-FGM at 6 and 18 months. The median percentage difference in HbA1c at 6 and 18 months versus basal was significantly decreased in those using FSL-FGM. Within diabetics using FSL-FGM, the median difference in HbA1c after 18 months was significantly decreased in patients with HbA1c >10% compared to those with HbA1c <10%. Estimated HbA1c by FSL showed a significant correlation with HbA1C assayed in the blood. The snapshot information showed a highly significant difference in average glucose with low significant difference in hypoglycemia parameters. The FSL-FGM provides significant changes in HbA1c in diabetic patients without observed risk for hypoglycemia. Conclusions: The dynamic way of blood glucose monitoring using FSL-FGM provides improvement in HbA1c in diabetic patients without observed risk for hypoglycemia. doi: https://doi.org/10.12669/pjms.37.7.4114 How to cite this:Mohamed IAA, Talaat IM, Alghamdi HA, Allam G. Role of free style Libre–Flash Glucose Monitoring: Glycemic control of Type-1 Diabetes. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4114 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2018 ◽  
Vol 21 (4) ◽  
pp. 264-270
Author(s):  
Olga R. Grigoryan ◽  
Natalia S. Krasnovskaya ◽  
Robert K. Mikheev ◽  
Elena N. Andreeva ◽  
Ivan I. Dedov

Background: Premature aging are frequently observed among individuals with type 1 diabetes. Decrease of ovarian reserve may be one of the characteristics of such process. Aims: To evaluate the ovarian reserve function in female patients of reproductive age with type 1 diabetes in comparison with healthy women. Materials and methods: This study evaluated 224 Caucasian women, age 1837 years with type 1 diabetes and 230 healthy women of comparable age. Serum concentrations of anti-Mullerian hormone (AMH), inhibin B, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and testosterone were compared on the 23 day of menstrual cycle as ovarian volume and antral follicle count (AFC). In addition, glycated hemoglobin level (HbA1c%) was evaluated. Results: We reveal statistically significant difference in following parameters in diabetic women in comparison with healthy women: AMH, AFC. But even in diabetic patients parameters remained within reference ranges. There was a pronounced negative relationship between the levels of HbA1c% and AMG. Conclusions: Ovarian reserve function parameters decrease in young women with type 1 diabetes in comparison with healthy women, but ovarian reserve parameters are in normal reference range. These findings are important in pregnancy planning consulting by gynecologists and endocrinologists. We must recommend to women with type 1 diabetes more early planning of natural pregnancy for treatment with reproductive technology in cases of prolog absence of nature pregnancy.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fabio Scarinci ◽  
Fabiana Picconi ◽  
Gianni Virgili ◽  
Monica Varano ◽  
Paola Giorno ◽  
...  

Abstract This study aimed to explore differences in vascular and structural parameters using optical coherence tomography angiography in patients with type 1 diabetes (DM1) with mild signs of diabetic retinopathy (DR) over a two-year follow-up period. Parafoveal vessel density (PVD) and foveal avascular zone (FAZ) area were analyzed. The thickness of three predefined retinal slabs was measured, including the inner limiting membrane (ILM)–inner plexiform layer (IPL), IPL–inner nuclear layer (INL), and the IPL–outer nuclear layer (ONL). Twenty-two patients with DM1 and 21 controls were included. There was no significant difference in the FAZ area, perimeter and acircularity index between cohorts over time. Baseline superficial capillary plexus PVD was approximately 10% lower in patients with diabetes than in controls (p = 0.001), and was 12% lower at 2 years (p = 0.002). There was no difference in the annual linear trend between the groups (− 0.5% in diabetics vs. controls, p = 0.736). Baseline deep capillary plexus (DCP) PVD was slightly lower in diabetics than in controls (− 4.4%, p = 0.047) and the difference increased at 2 years (− 12.6%, p < 0.001). The annual linear trend was − 2.7% in diabetic patients compared to controls (p = 0.009). In addition, the PVD of the DCP and the intermediate capillary plexus (ICP) were evaluated separately. Regarding the DCP PVD, no statistically significant difference at any time points in diabetic patients compared to controls and no statistically significant difference in the linear trend was found (p > 0.1). Conversely, no difference was recorded for parafoveal ICP density at individual time points (p > 0.1), but a statistically significant difference in the linear trend over time in diabetic patients compared to controls was recoded (− 3.2% per year, p = 0.001). Despite the apparent intergroup differences at baseline in structural OCT parameters, the differences including ILM–IPL (p = 0.273), IPL–INL (p = 0.708), and IPL–ONL (p = 0.054) were modest and not statistically significant with time. Therefore, the microvascular change of the deeper vessels might be a robust biomarker to evaluate the clinical progression of DR in DM1.


2011 ◽  
Vol 11 ◽  
pp. 1496-1508 ◽  
Author(s):  
Gordana Kocic ◽  
Radmila Pavlovic ◽  
Stevo Najman ◽  
Goran Nikolic ◽  
Dusan Sokolovic ◽  
...  

The sensing of ribonucleic acids (RNAs) by the monocyte/macrophage system occurs through the TLR7/8 Toll-like receptor family, the retinoic acidi–nducible protein I (RIG-I), and the melanoma differentiation–associated protein-5 (MDA-5). The aim of the present study was to evaluate the effect of circulating RNAs, isolated from juvenile type 1 diabetic patients and healthy control children, on the inflammatory, apoptotic, and antiviral response in human peripheral blood mononuclear cells (PBMCs) isolated from a healthy donor. Obtained effects were compared to the effects of metabolic stress parameters (hyperglycemia, oxidative and nitrosative stress). Forty-eight patients with juvenile type 1 diabetes and control children were included in the study. By performing the chromatographic analysis of circulating RNAs, the peak at the retention time 0.645 min for diabetic and control RNA samples was identified. To determine whether circulating RNAs have an agonistic or antagonistic effect on the signaling pathways involved in inflammatory, apoptotic, and antiviral cascade, their effect on TLR8, RIG-I, MDA-5, MyD88, NF-κB, IRF-3, phosphoIRF-3, IRF-7, RIP, and p38 was evaluated. A significantly lower level was achieved by cultivating PBMCs with circulating RNAs isolated from type 1 diabetic children, compared to the intact PBMCs, in relation to TLR-8, MDA-5, NF-κB, phospho IRF-3, and RIP, while it was higher for Bax. All the metabolic stress conditions up-regulated NF-κB, Bcl-2, and Bax. The NF-κB, determination seems to be the most sensitive parameter that may reflect disease processes associated with the progression of autoimmune or inflammatory conditions, while the IRF3/phosphoIRF3 ratio may suggest an insufficient antiviral response.


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