scholarly journals Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes

2020 ◽  
Vol 66 (4) ◽  
pp. 35-44
Author(s):  
Ekaterina N. Dudinskaya ◽  
Olga N. Tkacheva ◽  
Natalia V. Brailova ◽  
Irina D. Strazhesko ◽  
Marina V. Shestakova

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

2021 ◽  
Vol 53 (12) ◽  
pp. 825-825
Author(s):  
Tomoyuki Kawada

Dear Editor,I read the article by Wang et al., who conducted a meta-analysis to investigate the association between serum irisin levels and diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) 1. The mean serum irisin level in T2DM patients with microalbuminuria was significantly lower than that in T2DM patients with normoalbuminuria. In addition, the mean serum irisin level in T2DM patients with macroalbuminuria was significantly lower than that in T2DM patients with microalbuminuria. Furthermore, the mean serum irisin level in T2DM patients with estimated glomerular infiltration rate (eGFR)<60 ml/min 1.73 m2 was significantly lower than that in T2DM patients with eGFR≥60 ml/min 1.73 m2. The authors concluded that decreased serum irisin level was associated with albuminuria and reduced eGFR in T2DM patients. DN was significantly related to decreased serum irisin level in T2DM patients with dose-response manner. Progression of DN may be considered as advanced DM status, and serum irisin level would reflect glucose intolerance via insulin resistance. I have a comment about their study with special reference to the fundamental relationship between the types of DM and serum irisin levels.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Natalia Brailova ◽  
Ekaterina Dudinskaya ◽  
Valentina Pykhtina ◽  
Ekaterina Plochova ◽  
Irina Strazhesko ◽  
...  

Introduction: Type 2 diabetes mellitus (T2DM) contribute to vascular aging. The telomere length (TL) and telomerase activity (TA) are considered as biomarkers of cellular aging. TL and TA are insufficiently studied in diabetic patients. Hypothesis: Telomere biology is associated with vascular aging in diabetic patients. Methods: The study group included 50 patients with T2DM (mean age 58.4±7.83 years) and 139 healthy patients (mean age 57.45±8.14 years). All subjects were measured for TL and TA by quantitative polymerase chain reaction; oxidative stress marked by malondialdehyde (MDA); inflammation marked by C-reactive protein (CRP); arterial stiffness evaluated by pulse wave velocity (PWV); carotid intima-media thickness (IMT), plaque presence (PP) and endothelial dysfunction evaluated by flow-mediated endothelium-dependent vasodilation (FMV). Results: All patients were divided into 4 groups by the median of TL (9.75): «short» telomeres (T2DM+ (n=15) and T2DM- (n=63) and «long» telomeres (T2DM+ (n=35) and T2DM- (n=76)). Patients with T2DM and «long» TL had the state of vessels, oxidative stress, inflammation, TA as similar as in healthy people: PWV 11.54±3.57 (T2DM+) vs 10.98±1.83 m/s (T2DM-) ((=0.58), IMT 0.83±0.13 vs 0.76±0.16 mm (=0.13), PP 1.36±0.33 vs 1.23±0.20 (=0.79); MDA 2.81±0.78 vs 3.24±0.78 mkmol/l (=0.08); CRP 3.59±0.58 vs 3.66±0.50 mg/l (=0.93); TA 0.51±0.09 vs 0.60±0.05 (p=0.36). FMV was higher in diabetic patients: 11.87±3.36 vs 10.18±2.79 % (=0.049). In contrast patients with «short» TL and T2DM had more pronounced vascular aging, inflammation and lower TA than healthy people: PWV 13.48±3.24 vs 11.59±2.03 m/s (=0.003), IMT 0.95±0.17 vs 0.78±0.14 mm (<0.001), PP 2.23±0.27 vs 1.38±0.17 (=0.006), FMV 8.51±3.20 vs 11.04±3.01% (=0.0002; CRP 7.39±1.47 vs 4.03±0.62 mg/l (=0.046); TA 0.47±0.08 vs 0.62±0.07 (p=0.06). Conclusion: In patients with short telomeres and T2DM signs of vascular aging, chronic inflammation and cellular aging were more pronounced than in healthy people. In contrast, in patients with long telomeres and T2DM vascular changes, oxidative stress, chronic inflammation and TA were as similar as in healthy people. Perhaps long telomeres protect patients with T2DM from accelerated vascular aging.


2016 ◽  
Vol 62 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Natalia Vasil'evna Brailova ◽  
Ekaterina Nail'evna Dudinskaya ◽  
Olga Nikolaevna Tkacheva ◽  
Marina Vladimirovna Shestakova ◽  
Irina Dmitrievna Strazhesko ◽  
...  

Aim.To study the association of chronic inflammation, oxidative stress with telomere biology in people with type 2 diabetes mellitus (T2DM).Material and Methods.A total 50 patients with T2D and without cardiovascular disease (CVD) and 139 people from control group were included in the study. All subjects were measured for carbohydrate metabolism; oxidative stress (malondialdehyde (MDA)); inflammation (C-reactive protein — CRP, fibrinogen, interleukin-6); lymphocyte telomere length, telomerase activity.Results.In diabetic patients telomeres were shorter than in controls (9.59±0.54 and 9.76±0.47; p=0.031), telomerase activity was lower (0.47±0.40 and 0.62±0.36; p=0.039), inflammation (CRP, elevated fibrinogen) was higher. All patients were divided by telomere length. In T2DM group CRP was higher in patients with «short» telomeres (7.39±1.47 and 3.59±0.58 mg/L; p=0.02). There were no significant differences in the level of chronic inflammation and oxidative stress in ‘long’ telomeres group: CRP 3.59±0.58 and 3.66±0.50 mg/L (p=0.93), MDA 2.81±0.78 and 3.24±0.78 mmol/l (p=0.08). Diabetic patients in «short» telomeres group had greater chronic inflammation: CRP 7.39±1.47 and 4.03±0.62 mg/L (p=0.046), increased fibrinogen, 0.371 and 0.159 (p=0.022). All patients were divided by telomerase activity. Severity of chronic inflammation was greatest in T2DM and the «low» activity of telomerase. There were relationship between telomere length and CRP in T2DM patients (r=–0.40; p=0.004).Conclusions. Chronic inflammation and cell aging were more pronounced in patients with T2DM. However, despite diabetes, signs of chronic inflammation were minimal in patients with «long» telomeres compared to healthy people. Perhaps long telomeres protect diabetic patients from the damaging effect of chronic inflammation.


2015 ◽  
Vol 2 ◽  
pp. 2333794X1456845 ◽  
Author(s):  
Soulmaz Fazeli Farsani ◽  
Marloes P. van der Aa ◽  
Catherijne A. J. Knibbe ◽  
Anthonius de Boer ◽  
Marja M. J. van der Vorst

Objectives. To evaluate body mass index standard deviation score (BMI-SDS), insulin sensitivity, and progression to type 2 diabetes mellitus (T2DM) in children at risk for T2DM approximately 3 years after being diagnosed with overweight/obesity and insulin resistance (measured by Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]). Methods. Out of 86 invited children, 44 (mean age 15.4 ± 3.6 years) participated. Medical history, physical examination, and laboratory workup were performed. Results. While the mean BMI-SDS significantly increased from 2.9 to 3.4, the mean HOMA-IR significantly decreased from 5.5 to 4.6 (baseline vs follow-up visit). Change in HOMA-IR was only due to a decrease in mean fasting plasma insulin (24.1 vs 21.1, P = .073). Conclusions. Although increase in BMI-SDS in these children is worrisome, the American Diabetes Association recommended screening interval of 3 years for children at risk for T2DM is not too long based on the fact that none of our study participants developed T2DM.


2014 ◽  
Vol 17 (3) ◽  
pp. 31-38 ◽  
Author(s):  
Ekaterina Nailyevna Dudinskaya ◽  
Olga Nikolaevna Tkacheva ◽  
Marina Vladimirovna Shestakova ◽  
Natalya Vasilyevna Brailova ◽  
Irina Dmitrievna Strazhesko ◽  
...  

Aim. To study the relationship between changes in the artery structure and function and peripheral lymphocyte telomere length in patients with type 2 diabetes mellitus (DM2). Materials and methods. A total of 50 patients with T2DM and without clinical manifestations of cardiovascular disease (CVD) were included in the study; the control group consisted of 49 people. The following tests were conducted for all study participants: carbohydrate metabolism evaluation, carotid artery duplex scan to measure intima?media complex thickness (IMT) and to determine the presence of atherosclerotic plaques, carotid?femoral pulse wave velocity (PWV) measurement and lymphocyte telomere length measurement. Results. The vascular changes were more pronounced in patients with T2DM than in controls. The telomeres were shorter in patients with T2DM than in those without diabetes (9.53?0.1 vs 9.86?0.1, p=0.033). The participants were divided according to the telomere length. Among patients with T2DM, there were significant differences in the condition of the vascular wall [PWV: 10.58?0.1 m/s in patients with ?long? telomeres and 15.08?1.3 m/s in patients with ?short? telomeres; IMT: 0.80?0.09 mm in patients with ?long? telomeres and 0.87?0.05 mm in patients with ?short? telomeres (p=0.024)]. There were no significant differences in the arterial structure between the patient and control groups with ?long? telomeres [PWV: 10.58?0.1 m/s vs 10.5?0.5 m/s (p=0.913); IMT: 0.080?0.09 mm vs 0.73?0.03 mm (p=0.12). However, there were significant differences in the vascular wall condition between the patient and control groups with ?short? telomeres [PWV: 15.08?1.3 m/s vs, 10.7?0.5 m/s (p=0.015); IMT: 0.87?0.1 vs 0.78?0.1 (p=0.03)]. Conclusions. The signs of vascular ageing were more pronounced in patients with T2DM than in controls. However, despite diabetes, vascular changes were minimal in patients with ?long? lymphocyte telomeres, comparable with the state of the vascular walls in healthy individuals. Thus, enhanced lymphocyte telomere length may have a protective effect on the vascular wall and may prevent damage from carbohydrate metabolism disorders.


2019 ◽  
Vol 94 (5) ◽  
pp. 33-38 ◽  
Author(s):  
A. K. Alexandrova ◽  
V. A. Smolyannikova

Multiple seborrheic keratosis (SK), especially when there is overexpression of the epidermal growth factor receptor (EGFR), is considered paraneoplastic dermatosis, but it is almost always associated with multiple fibroepithelial polyps (PF) and pseudoacanthosis, skin diseases in which the leading role is played by insulin resistance and type 2 diabetes mellitus. The study examines the possibility of the effect of disorders of carbohydrate metabolism on the clinical picture of multiple SK and the expression of EGFR.Aims. To study the clinical features of multiple SC and the expression of EGFR in patients, depending on the presence of concomitant type 2 diabetes mellitus.Materials and methods. There were 65 patients with multiple SK at the age from 55 to 77 years, including women (44) and men (21). All the patients were examined skin, consultation of the endocrinologist. For a histological and immunohis-tochemical study (IHC), a single SK was surgically excised in each patient. IHC-reactions were carried out with monoclonal antibodies to EGFR. The result was assessed by the number of stained cytoplasmic membranes of tumor cells.Results. In 81.5 % of cases, multiple SK was associated in patients with type 2 diabetes mellitus. The location of the SK was also characteristic mainly in large folds of the skin, in contrast to patients without disorders of carbohydrate metabolism, in which the SK were located mainly on the lateral surfaces of the trunk and abdomen, without affecting the large folds of the skin. Multiple PF were also characteristic of individuals with type 2 diabetes mellitus. In IHC studies EGFR expression was detected in 100 % of cases in individuals with multiple SC and type 2 diabetes mellitus in over 30 % of tumor cells, and only in 16.7 % of cases in individuals with multiple SK without violations of carbohydrate metabolism.Conclusions. The presence of multiple SK in patients, in combination with multiple PFs with characteristic tumor localization in large folds of the skin, serves as a diagnostic marker of carbohydrate metabolism disorders or predispositions to the development of type 2 diabetes. Increased expression of EGFR plays a leading role in the pathogenesis of multiple SK, stimulating the proliferation and growth of SK, in turn, as a consequence of impairment of insulin signaling pathways and insulin resistance.


2021 ◽  
Vol 27 (1) ◽  
pp. 36-56
Author(s):  
Phillip S. Gordon ◽  
Gary J. Farkas ◽  
David R. Gater

The population with SCI is at a significant risk for both insulin resistance and type 2 diabetes mellitus (T2DM) secondary to neurogenic obesity. The prevalence of insulin resistance and T2DM in persons with SCI suggests that disorders of carbohydrate metabolism are at epidemic proportions within the population. However, the true frequency of such disorders may be underestimated because biomarkers of insulin resistance and T2DM used from the population without SCI remain nonspecific and may in fact fail to identify true cases that would benefit from intervention. Furthermore, diet and exercise have been used to help mitigate neurogenic obesity, but results on disorders of carbohydrate metabolism remain inconsistent, likely because of the various ways carbohydrate metabolism is assessed. The objective of this article is to review current literature on the prevalence and likely mechanisms driving insulin resistance and T2DM in persons with SCI. This article also explores the various assessments and diagnostic criteria used for insulin resistance and T2DM and briefly discusses the effects of exercise and/or diet to mitigate disorders of carbohydrate metabolism brought on by neurogenic obesity.


2021 ◽  
Vol 93 (10) ◽  
pp. 1203-1208
Author(s):  
Igor A. Sklyanik ◽  
Marina V. Shestakova

Background. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are innovative drugs that effectively reduce glycemic levels and overweight in patients with type 2 diabetes mellitus (T2DM). However, the criteria for predicting the hypoglycemic effect of this group of drugs have not been practically defined. Aim. To assess the factors contributing to the achievement the glycemia normalization in patients with diabetes mellitus and obesity by adding to antihyperglycemic therapy (AT) a drug from the GLP-1 RA group liraglutide 3.0 mg per day. Materials and methods. A single-center, prospective, non-randomized study was provided. The objects of the study were patients with T2DM and obesity (n=22). Liraglutide 3.0 mg per day was added to the current AT of patients. Initially, the parameters of carbohydrate metabolism, hormones of the incretin system on an empty stomach and during the mixed-meal test, insulin resistance using the euglycemic hyperinsulinemic clamp test, and body composition were studied. After 9 months of therapy, all studies were repeated and a search for possible predictors of the carbohydrate metabolism normalization was made. Results. The body mass index of patients decreased from 42.4 [37.7; 45.0] to 35.9 [33.0; 40.9] kg/m2. Fasting blood glucose and glycated hemoglobin levels decreased from 9.02 [7.40; 11.37] mmol/L and 7.85 [7.43; 8.65]% up to 5.90 [5.12; 6.18] mmol/L and 6.40 [5.90; 6.60]%, respectively. 14 (63.6%) patients reached normoglycemia. Insulin resistance according to the clamp test did not change over the study. Basal concentrations of oxyntomodulin, glycentin and the area under the GLP-1, oxyntomodulin, glycentin curve significantly decreased 9 months after liraglutide administration. The prognostic marker of the achievement of normoglycemia during therapy with liraglutide 3.0 mg/day is the level of endogenous GLP-15.5 pmol/L before the appointment of arGPP-1 therapy. Conclusion. The concentration of endogenous GLP-1 before the appointment of liraglutide therapy at a dose of 3.0 mg per day can be used for prediction the drug hypoglycemic effect and achieving normoglycemia possibility.


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