scholarly journals Circulating Ribonucleic Acids and Metabolic Stress Parameters May Reflect Progression of Autoimmune or Inflammatory Conditions in Juvenile Type 1 Diabetes

2011 ◽  
Vol 11 ◽  
pp. 1496-1508 ◽  
Author(s):  
Gordana Kocic ◽  
Radmila Pavlovic ◽  
Stevo Najman ◽  
Goran Nikolic ◽  
Dusan Sokolovic ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Metabolic Stress ◽  
Antiviral Response ◽  
Diabetic Patients ◽  
Ribonucleic Acids ◽  
Inflammatory Conditions ◽  
Juvenile Type ◽  
And Control ◽  
Stress Parameters

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.

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
Keyword(s):  
Type 1 Diabetes ◽  
Statistical Significance ◽  
Group Versus ◽  
Diabetic Patients ◽  
Nucleotide Polymorphisms ◽  
Ptpn22 Gene ◽  
Egyptian Children ◽  
Significant Difference ◽  
And Control

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.

scholarly journals Lower Frequency of CD62Lhighand Higher Frequency of TNFR2+Tregs Are Associated with Inflammatory Conditions in Type 1 Diabetic Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Monika Ryba ◽  
Karolina Rybarczyk-Kapturska ◽  
Katarzyna Zorena ◽  
Małgorzata Myśliwiec ◽  
Jolanta Myśliwska
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Lower Percentage ◽  
Diabetic Patients ◽  
Autoreactive T Cells ◽  
Inflammatory Conditions ◽  
Type 1 Diabetic Patients ◽  
Chronic Autoimmune Disease

Diabetes type 1 is a chronic autoimmune disease in which insulin-producing cells are gradually destroyed by autoreactive T cells. Human regulatory cells play important role in controlling autoimmunity, and their qualitative or quantitative dysfunctions may result in ineffective suppression of autoreactive T cells. CD62L is a surface molecule that plays role in homing capabilities of Tregs, and only cells with high expression of CD62L have high suppressive potential. Tregs are also characterized by the constant expression of TNFR2. The frequency of Tregs carrying TNFR2 is higher in inflammatory conditions. We investigated blood regulatory T cells with CD62L expression and regulatory T cells expressing TNFR2 in type 1 diabetic patients. We found differences in these populations when comparing to healthy individuals. We propose that these may be associated with inflammatory conditions that are present in patients with type 1 diabetes. The lower percentage of Tregs and Treg CD62Lhighmay contribute to ineffective suppression of proinflammatory cytokines production during type 1 diabetes.

Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients

2001 ◽  
Vol 281 (5) ◽  
pp. E1029-E1036 ◽  
Author(s):  
Raymond R. Russell ◽  
Deborah Chyun ◽  
Steven Song ◽  
Robert S. Sherwin ◽  
William V. Tamborlane ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Radionuclide Angiography ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
Plasma Catecholamine ◽  
Ventricular Ejection Fraction ◽  
Type 1 Diabetic Patients

Insulin-induced hypoglycemia occurs commonly in intensively treated patients with type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these patients are not known. We studied left ventricular systolic [left ventricular ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by equilibrium radionuclide angiography during insulin infusion (12 pmol · kg−1 · min−1) under either hypoglycemic (∼2.8 mmol/l) or euglycemic (∼5 mmol/l) conditions in intensively treated patients with type 1 diabetes and healthy nondiabetic subjects ( n = 9 for each). During hypoglycemic hyperinsulinemia, there were significant increases in LVEF (ΔLVEF = 11 ± 2%) and PFR [ΔPFR = 0.88 ± 0.18 end diastolic volume (EDV)/s] in diabetic subjects as well as in the nondiabetic group (ΔLVEF = 13 ± 2%; ΔPFR = 0.79 ± 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but occurred earlier in the nondiabetic group. A blunted increase in plasma catecholamine, cortisol, and glucagon concentrations occurred in response to hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF also increased in both the diabetic (ΔLVEF = 7 ± 1%) and nondiabetic (ΔLVEF = 4 ± 2%) groups, but PFR increased only in the diabetic group. In the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia, only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac output in the hypoglycemic study ( P < 0.05 for each). Thus intensively treated type 1 diabetic patients demonstrate delayed augmentation of ventricular function during moderate insulin-induced hypoglycemia. Although diabetic subjects have a more pronounced cardiac response to hyperinsulinemia per se than nondiabetic subjects, their response to hypoglycemia is blunted.

scholarly journals Prevalence of dental caries in children and adolescents with type 1 diabetes: a systematic review and meta-analysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Wang ◽  
Lin Xing ◽  
Hui Yu ◽  
LiJuan Zhao
Keyword(s):  
Type 1 Diabetes ◽  
Dental Caries ◽  
Children And Adolescents ◽  
Metabolic Control ◽  
Meta Analysis ◽  
Preventive Treatment ◽  
Diabetic Patients ◽  
China National Knowledge Infrastructure ◽  
Pooled Prevalence

Abstract Background Dental caries and type 1 diabetes are responsible for a large burden of global disease; however, the exact prevalence of dental caries among children and adolescents with type 1 diabetes remains controversial, and no quantitative meta-analysis exists. Thus, we performed a meta-analysis to evaluate the prevalence of dental caries among children and adolescents with type 1 diabetes. Methods We performed a systematic search strategy using PubMed, EMBASE and China National Knowledge Infrastructure for relevant studies investigating the prevalence of dental caries in children and adolescents with type 1 diabetes from July 1971 until December 2018. The pooled prevalence with 95% confidence intervals (95%CIs) and subgroup analyses were calculated using a random effects model. Results After screening 358 non-duplicated articles, a total of 10 articles involving 538 individuals were included. The overall prevalence of dental caries among children and adolescents with type 1 diabetes was 67% (95% CI: 0.56–0.77%; I2 = 83%). The prevalence was highest in South America (84%) and lowest in diabetic patients with good metabolic control (47%). Conclusions The prevalence of dental caries was high among children and adolescents with type 1 diabetes. Screening and preventive treatment should be included in dental clinical routines for diabetic children and adolescents, especially in those with poor metabolic control.

scholarly journals Prevalence and risk of appearence of skin lesions considered to be cutaneous markers of diabetes in a population group in bihor county

2012 ◽  
Vol 19 (3) ◽  
pp. 285-290
Author(s):  
Denisa Kovacs ◽  
Luiza Demian ◽  
Aurel Babeş
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Skin Lesion ◽  
Skin Diseases ◽  
Population Group ◽  
Skin Lesions ◽  
Diabetic Patients ◽  
Cutaneous Lesions

Abstract Objectives: The aim of the study was to calculate the prevalence rates and risk ofappearance of cutaneous lesions in diabetic patients with both type-1 and type-2diabetes. Material and Method: 384 patients were analysed, of which 47 had type-1diabetes (T1DM), 140 had type-2 diabetes (T2DM) and 197 were non-diabeticcontrols. Results: The prevalence of the skin lesions considered markers of diabeteswas 57.75% in diabetics, in comparison to 8.12% in non-diabetics (p<0.01). The riskof skin lesion appearance is over 7 times higher in diabetic patients than in nondiabetics.In type-1 diabetes the prevalence of skin lesions was significantly higherthan in type-2 diabetes, and the risk of skin lesion appearance is almost 1.5 timeshigher in type-1 diabetes than type-2 diabetes compared to non-diabetic controls.Conclusions: The diabetic patients are more susceptible than non-diabetics todevelop specific skin diseases. Patients with type-1 diabetes are more affected.

scholarly journals T-cell mediated autoimmunity to the insulinoma-associated protein 2 islet tyrosine phosphatase in type 1 diabetes mellitus

1999 ◽  
pp. 272-278 ◽  
Author(s):  
F Dotta ◽  
S Dionisi ◽  
V Viglietta ◽  
C Tiberti ◽  
MC Matteoli ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Type 1 Diabetes ◽  
T Cell ◽  
T Lymphocyte ◽  
Tyrosine Phosphatase ◽  
T Cell Response ◽  
T Cell Proliferation ◽  
Diabetic Patients ◽  
Hla Dr

The target molecules of the T-cell response in type 1 diabetes, despite their pathogenic importance, remain largely uncharacterized, especially in humans. Interestingly, molecules such as insulin and glutamic acid decarboxylase (GAD) have been shown to be a target not only of autoantibodies, but also of autoreactive T-lymphocytes both in man and in the non-obese diabetic (NOD) mouse. In the present study we aimed to determine the existence of a specific T-cell response towards the insulinoma-associated protein 2 (IA-2) islet tyrosine phosphatase, a recently identified autoantigen which is the target of autoantibodies strongly associated with diabetes development. Human recombinant IA-2 produced in Escherichia coli, was tested for its reactivity with peripheral blood lymphocytes obtained from 16 newly diagnosed type 1 diabetic patients and from 25 normal controls, 15 of whom were HLA-DR-matched. A T-cell proliferation assay was performed in triplicate employing freshly isolated cells in the absence or in the presence of the antigen to be tested (at two different concentrations: 2 microg/ml and 10 microg/ml). A specific T-cell proliferation (defined as a stimulation index (S.I.) >/=3) was observed against IA-2 used at a concentration of 10 microg/ml (but not of 2 microg/ml) in 8/16 diabetic patients, in 1/15 HLA-DR-matched control subjects (P<0.01 by Fisher exact test) and in 0/10 of the remaining normal individuals. A statistically significant difference (P<0.003 by Mann-Whitney U test) was also observed in S.I. values between patients (3.1+/-1.4) and HLA-DR-matched controls (1.7+/-0.54) employing IA-2 at a concentration of 10 microg/ml. However, when IA-2 was used at a concentration of 2 microg/ml, the difference in S. I. between patients (1.65+/-0.8) and controls (1.0+/-0.3) did not reach statistical significance. In conclusion, these data show the presence of a specific, dose-dependent T-lymphocyte response against the IA-2 islet tyrosine phosphatase at the onset of type 1 diabetes. Consequently, this molecule appears to be a target not only at the B-lymphocyte but also at the T-lymphocyte level, reinforcing the potential pathogenic role of this autoantigen in the islet destructive process.

scholarly journals Molecular-genetic, immunological bases and prophylaxis of diabetes mellitus in children

2011 ◽  
Vol 57 (1) ◽  
pp. 9-18
Author(s):  
E V Titovich
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Russian Population ◽  
Research Centre ◽  
Diabetic Patients ◽  
Genetic Studies

Since the autoimmune nature of type 1 diabetes mellitus came to become known some 40 years ago, continuous investigations have been carried out in an attempt to improve approaches to prognostication of this disease and develop new safe and efficacious methods for its prevention. For all that, many aspects of diabetes pathogenesis still remain far from clear. In most cases (roughly 85%), type 1 diabetes mellitus (DM1) develops sporadically in the absence of a relevant familial or hereditary history of this condition. Accordingly, the first-degree relatives account for only 15% of all DM1 patients. The risk of development of DM1 in the Russian population estimated by the researchers of the Children' Department, Endocrinological Research Centre, is relatively low (0.2%). It depends on many factors, such as the number of ill and healthy relatives, the chronological age of a given patient and the age of onset of clinical manifestations in his (her) relatives. Type 1 diabetes-predisposing and protective haplotypes were identified in the Russian population based on the results of molecular-genetic studies involving 599 children and adolescents with DM1. These and immunological data were used to distinguish between risk groups in the families of diabetic patients and the rationale was proposed for the dynamic follow-up of these subjects. It is concluded that estimation of the risk of type 1 diabetes mellitus based on the results of molecular-genetic studies and monitoring immunological markers constitutes the first step in the elaboration of preventive measures designed to prevent or delay the development of the disease.

scholarly journals Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes

2020 ◽  
Author(s):  
Lea Aigner ◽  
Björn Becker ◽  
Sonja Gerken ◽  
Daniel R. Quast ◽  
Juris J. Meier ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Cross Sectional ◽  
Chronic Hyperglycemia ◽  
Fasting Plasma

<b>Objective:</b> Acute experimental variations in glycemia decelerate (hyperglycemia) or accelerate (hypoglycemia) gastric emptying. Whether spontaneous variations in fasting plasma glucose (FPG) have a similar influence on gastric emptying is yet unclear. <p><b>Research design and methods:</b> Gastric emptying of a mixed meal was prospectively studied three times in 20 patients with type 1 diabetes and 10 healthy subjects with normal glucose tolerance using a <sup>13</sup>C-CO<sub>2</sub> octanoate breath test with Wagner-Nelson analysis. The velocity of gastric emptying was related to fasting plasma glucose (FPG) measured before the test (grouped as low, intermediate, or high). In addition, gastric emptying data from 255 patients with type 1 diabetes studied for clinical indications were compared by tertiles of baseline FPG. </p> <p><b>Results:</b> Despite marked variations in FPG (by 4.8 (3.4; 6.2) mmol/l), gastric emptying did not differ between the three prospective examinations in patients with type 1 diabetes (D T<sub>1/2</sub> between highest and lowest FPG: 1 [95 % CI: -35; 37] min; p = 0.90). The coefficient of variation for T<sub>1/2 </sub>determined three times was 21.0 %. Similar results at much lower variations in FPG were found in healthy subjects. In the cross-sectional analysis, gastric emptying did not differ between the tertiles of FPG (D T<sub>1/2</sub> between highest and lowest FPG: 7 [95 % CI: - 10; 23] min; p = 0.66), when FPG varied by 7.2 (6.7; 7.8) mmol/l. However, higher HbA<sub>1c</sub> was significantly related to slower gastric emptying.</p> <p><b>Conclusions:</b> Day-to-day variations in FPG not induced by therapeutic measures do not influence gastric emptying significantly. These findings are in contrast with those obtained after rapidly clamping plasma glucose in the hyper- or hypoglycemic concentrations range and challenge the clinical importance of short-term glucose fluctuations for gastric emptying in type 1-diabetic patients. Rather, chronic hyperglycemia is associated with slowed gastric emptying.</p>

scholarly journals Volume rendered 3D OCTA assessment of macular ischemia in patients with type 1 diabetes and without diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Enrico Borrelli ◽  
Domenico Grosso ◽  
Mariacristina Parravano ◽  
Eliana Costanzo ◽  
Maria Brambati ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Healthy Subjects ◽  
Diabetic Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Vascular Volume ◽  
Patients With Diabetes ◽  
Perfusion Density

AbstractThe aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

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