Signs of low-grade systemic inflammation in female offspring of women with type 1 diabetes: The EPICOM study

Objective: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. Design: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. Methods: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor α receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. Results: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (r=−0.244, P=0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; r=−0.231, P=0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. Conclusions: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.

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Persisting gender-related differences in low-grade inflammation and dyslipidemia in children, adolescents and young adults with type 1 diabetes

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.06.581 ◽

2021 ◽

Vol 331 ◽

pp. e191

Author(s):

D. Smigoc Schweiger ◽

E. Plesnik ◽

M. Macedoni ◽

E. Giani ◽

T. Hovnik ◽

...

Keyword(s):

Type 1 Diabetes ◽

Young Adults ◽

Adolescents And Young Adults ◽

Low Grade ◽

Low Grade Inflammation

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Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study

Diabetologia ◽

10.1007/s00125-009-1263-5 ◽

2009 ◽

Vol 52 (4) ◽

pp. 705-714 ◽

Cited By ~ 50

Author(s):

J. W. M. Nin ◽

I. Ferreira ◽

C. G. Schalkwijk ◽

M. H. Prins ◽

N. Chaturvedi ◽

...

Keyword(s):

Cardiovascular Disease ◽

Type 1 Diabetes ◽

Renal Dysfunction ◽

Low Grade ◽

Soluble Receptor ◽

Low Grade Inflammation

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Urine α-Glutathione S-Transferase, systemic inflammation and arterial function in juvenile type 1 diabetes

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2012.03.023 ◽

2012 ◽

Vol 26 (3) ◽

pp. 199-204 ◽

Cited By ~ 4

Author(s):

Peter Holmquist ◽

Petru Liuba

Keyword(s):

Type 1 Diabetes ◽

Systemic Inflammation ◽

Glutathione S Transferase ◽

Arterial Function ◽

Juvenile Type

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Leukotriene Involvement in the Insulin Receptor Pathway and Macrophage Profiles in Muscles from Type 1 Diabetic Mice

Mediators of Inflammation ◽

10.1155/2019/4596127 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

João Pedro Tôrres Guimarães ◽

Luciano Ribeiro Filgueiras ◽

Joilson Oliveira Martins ◽

Sonia Jancar

Keyword(s):

Type 1 Diabetes ◽

Insulin Receptor ◽

Signaling Pathway ◽

Receptor Gene ◽

Tolerance Test ◽

Low Grade ◽

Diabetic Mice ◽

Insulin Receptor Gene ◽

Akt Phosphorylation

Type 1 diabetes (T1D) is a metabolic disease associated with systemic low-grade inflammation and macrophage reprogramming. There is evidence that this inflammation depends on the increased systemic levels of leukotriene (LT) B4 found in T1D mice, which shifts macrophages towards the proinflammatory (M1) phenotype. Although T1D can be corrected by insulin administration, over time T1D patients can develop insulin resistance that hinders glycemic control. Here, we sought to investigate the role of leukotrienes (LTs) in a metabolically active tissue such as muscle, focusing on the insulin signaling pathway and muscle-associated macrophage profiles. Type 1 diabetes was induced in the 129/SvE mouse strain by streptozotocin (STZ) in mice deficient in the enzyme responsible for LT synthesis (5LO-/-) and the LT-sufficient wild type (WT). The response to insulin was evaluated by the insulin tolerance test (ITT), insulin concentration by ELISA, and Akt phosphorylation by western blotting. The gene expression levels of the insulin receptor and macrophage markers Stat1, MCP-1, Ym1, Arg1, and IL-6 were evaluated by qPCR, and that of IL-10 by ELISA. We observed that after administration of a single dose of insulin to diabetic mice, the reduction in glycemia was more pronounced in 5LO-/- than in WT mice. When muscle homogenates were analyzed, diabetic 5LO-/- mice showed a higher expression of the insulin receptor gene and higher Akt phosphorylation. Moreover, in muscle homogenates from diabetic 5LO-/- mice, the expression of anti-inflammatory macrophage markers Ym1, Arg1, and IL-10 was increased, and the relative expression of the proinflammatory cytokine IL-6 was reduced compared with WT diabetic mice. These results suggest that LTs have an impact on the insulin receptor signaling pathway and modulate the inflammatory profile of muscle-resident macrophages from T1D mice.

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Low Grade Inflammation in Juvenile Obesity and Type 1 Diabetes Associated with Early Signs of Atherosclerosis

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2004-821023 ◽

2004 ◽

Vol 112 (07) ◽

pp. 378-382 ◽

Cited By ~ 78

Author(s):

H. Mangge ◽

K. Schauenstein ◽

L. Stroedter ◽

A. Griesl ◽

W. Maerz ◽

...

Keyword(s):

Type 1 Diabetes ◽

Low Grade ◽

Early Signs ◽

Juvenile Obesity ◽

Low Grade Inflammation

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IVS1 −397T>C Estrogen ReceptorαPolymorphism Is Associated with Low-Grade Systemic Inflammatory Response in Type 1 Diabetic Girls

Mediators of Inflammation ◽

10.1155/2014/839585 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Monika Ryba-Stanisławowska ◽

Karolina Rybarczyk-Kapturska ◽

Agnieszka Brandt ◽

Małgorzata Myśliwiec ◽

Jolanta Myśliwska

Keyword(s):

Type 1 Diabetes ◽

Estrogen Receptor ◽

Inflammatory Response ◽

Th17 Cells ◽

Microvascular Complications ◽

Estradiol Level ◽

Low Grade ◽

Serum Estradiol ◽

Serum Estradiol Level

Purpose. The study aimed to investigate the influence of estrogen receptorα(ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes.Methods. 152 young regularly menstruating girls with diagnosed type 1 diabetes and 84 young, healthy menstruating girls were recruited. ER-αgenotyping was carried out by PCR. Serum concentrations of 17β-estradiol, as well as IL-6, TNF-α, VEGF, and IL-10, were measured. CD4+Foxp3+TH17 cells were isolated and analyzed by flow cytometry.Results. Type 1 diabetic girls carrying TT genotype were characterized by the lowest serum estradiol level and IL-10 and highest IL-6, TNF-α, and VEGF. The association between the level of certain cytokine and the genetic variant of estrogen receptorαpolymorphism was analyzed. Frequencies of CD4+Foxp3+TH17 cells were also enhanced in TT bearing girls with type 1 diabetes and correlated with the level of analyzed cytokines. In addition, the correlation between serum estradiol level and cytokine concentrations was observed.Conclusions. We propose that TT variant of estrogen receptorαpolymorphism may be associated with enhanced inflammatory response, which in turn may lead to acceleration of diabetic retino- and nephropathy in girls with type 1 diabetes. This finding may help the physicians to predict the onset and progression of diabetic microvascular complications.

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