Association of interferon-γ and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

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Serum levels of sCD23, interleukin-10 and interferon-γ in patients with coeliac disease

Journal of Gastroenterology and Hepatology ◽

10.1111/j.1440-1746.1997.tb00535.x ◽

1997 ◽

Vol 12 (9-10) ◽

pp. 685-689 ◽

Cited By ~ 2

Author(s):

AS BANSAL ◽

J BRUCE ◽

A THOMSON ◽

P KERLIN

Keyword(s):

Coeliac Disease ◽

Serum Levels ◽

Interleukin 10 ◽

Interferon Γ

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Interleukin-10 Gene Promoter Region Polymorphisms in Patients with Type 1 Diabetes and Autoimmune Thyroid Disease

Annals of the New York Academy of Sciences ◽

10.1196/annals.1288.055 ◽

2003 ◽

Vol 1005 (1) ◽

pp. 344-347 ◽

Cited By ~ 6

Author(s):

AKANE IDE ◽

EIJI KAWASAKI ◽

NORIO ABIRU ◽

FUYAN SUN ◽

TETSUYA FUKUSHIMA ◽

...

Keyword(s):

Type 1 Diabetes ◽

Thyroid Disease ◽

Promoter Region ◽

Autoimmune Thyroid Disease ◽

Gene Promoter ◽

Interleukin 10 ◽

Autoimmune Thyroid ◽

Gene Promoter Region

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Interferon-γ Limits Diabetogenic CD8 + T-Cell Effector Responses in Type 1 Diabetes

Diabetes ◽

10.2337/db16-0846 ◽

2016 ◽

Vol 66 (3) ◽

pp. 710-721 ◽

Cited By ~ 12

Author(s):

John P. Driver ◽

Jeremy J. Racine ◽

Cheng Ye ◽

Deanna J. Lamont ◽

Brittney N. Newby ◽

...

Keyword(s):

Type 1 Diabetes ◽

T Cell ◽

Cd8 T Cell ◽

Interferon Γ ◽

Cell Effector

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Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-16-0099 ◽

2016 ◽

Vol 2016 ◽

Cited By ~ 2

Author(s):

Marcelo Maia Pinheiro ◽

Felipe Moura Maia Pinheiro ◽

Margareth Afonso Torres

Keyword(s):

Diabetes Mellitus ◽

Immune Response ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Vitamin D3 ◽

Clinical Remission ◽

Insulin Production ◽

C Peptide ◽

New Onset

Summary Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission. Learning points: The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production. The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells. Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission. The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.

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Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes

BioMed Research International ◽

10.1155/2019/6128410 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Agnieszka Polkowska ◽

Izabela Elżbieta Pasierowska ◽

Marta Pasławska ◽

Elżbieta Pawluczuk ◽

Artur Bossowski

Keyword(s):

Type 1 Diabetes ◽

Glucose Metabolism ◽

Statistical Significance ◽

Serum Levels ◽

Control Group ◽

Diabetic Patients ◽

Serum Concentrations ◽

Novel Biomarkers ◽

Varied Duration

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.

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Moderate intensity exercise in hypoxia increases IGF-1 bioavailability and serum irisin in individuals with type 1 diabetes

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820925326 ◽

2020 ◽

Vol 11 ◽

pp. 204201882092532 ◽

Cited By ~ 1

Author(s):

Aleksandra Żebrowska ◽

Marcin Sikora ◽

Anna Konarska ◽

Anna Zwierzchowska ◽

Tomasz Kamiński ◽

...

Keyword(s):

Type 1 Diabetes ◽

Serum Levels ◽

Cycle Ergometer ◽

Moderate Intensity ◽

Moderate Intensity Exercise ◽

Physiological Variables ◽

Hypoxic Conditions ◽

Study Results ◽

Glycaemia Control

Aim: This study aimed to determine the effect of moderate intensity continuous exercise (Ex) and hypoxia (Hyp) on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and its binding protein-3 (IGFBP-3), irisin and cytokines levels in patients with type 1 diabetes (T1D). Methods: A total of 14 individuals with T1D (age: 28.7 ± 7.3 years) and 14 healthy adults (age: 27.1 ± 3.9 years) performed 40-min continuous Ex at moderate intensity (50% lactate threshold) on a cycle ergometer in normoxia (Nor) and Hyp (FiO2 = 15.1%) Biochemical factors, glucose concentrations and physiological variables were measured at rest, immediately and up to 24 h after both Ex protocols. Results: Patients with T1D had significantly lower pre-Ex serum concentrations of BDNF ( p < 0.05, p < 0.01), and total IGF-1 ( p < 0.001, p < 0.05) and significantly higher irisin levels ( p < 0.05, p < 0.01) in Nor and Hyp, compared with healthy subjects. Ex significantly increased in T1D group serum BDNF (in Nor only p < 0.05) and total IGF-1 levels in Nor and Hyp ( p < 0.001 and p < 0.01, respectively). Immediately after Ex in Hyp, freeIGF-1 ( p < 0.05) and irisin levels ( p < 0.001) were significantly higher compared with the levels induced by Ex alone. Free IGF-1 and irisin serum levels remained elevated in 24 h post-Ex in Hyp. In T1D, significant blood glucose (BG) decrease was observed immediately after Ex in Hyp ( p < 0.001) and in 24 h recovery ( p < 0.001) compared with pre-Ex level. Conclusion: The study results suggest that moderate intensity continuous Ex has beneficial effect on BDNF and IGF-1 levels. Ex in hypoxic conditions may be more effective in increasing availability of IGF-1. The alterations in the post-Ex irisin levels and IGF-1 system may be contributing to more effective glycaemia control in patients with T1D.

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