Additional Impact of Glucose Tolerance on Telomere Length in Persons With and Without Metabolic Syndrome in the Elderly Ukraine Population

Abstract

Rationale: Association between different components of metabolic syndrome and the rate of age-related telomere shortening was reported repeatedly, although some findings are inconsistent across studies, suggesting the need for further research on the topic. In the present study, we examined relationships between different components of metabolic syndrome (MetS); glucose tolerance reflected in 2-h post-load plasma glucose (2hPG) levels and age on the leukocyte telomere length (LTL) in Ukraine population. Methods: The study was conducted on the 115 adult individuals residing in the Kyiv region (Ukraine). Among them, 79 were diagnosed with MetS according to the International Diabetes Federation definition. LTL were determined by a qPCR-based method. Multivariate logistic regression (MLR) and artificial neural networks (ANN) modeling were used for the analysis of the results. ROC-analysis was also performed to compare the predictively values of this models. Results: MetS was associated with a high (OR = 3.0 CI 1.3–6.7; p = 0.01) risk of having shorter telomeres that remained significant after adjusting for age, gender and 2hPG levels. Fasting plasma glucose (FPG) levels and other MetS components did not affect the magnitude of the relationship and did not reveal the independent influence of these factors. The level of 2hPG in turn, demonstrated a significant relationship (OR = 1.3 CI 1.0–1.6 per 1 mmol/l; p = 0.04) with LTL regardless of the presence of MetS. The non-linearity of the interactions between age, gender and 2hPG level was revealed by neural network modeling (AUC = 0.76 CI 0.68–0.84). Conclusion: Our study found that impaired glucose tolerance, but not FPG levels, affected the association between LTL and MetS, which may be also indicative for pathophysiological differences in these hyperglycemia categories. 2hPG levels can provide an opportunity for a more accurate diagnostics of MetS and for evaluating the rate of aging in patients with MetS. Further research, however, is needed to verify this assumption.

Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

“…An association of short LTL with higher risk for developing type 2 diabetes has been also demonstrated; this association, however, was significantly influenced by body mass index (BMI), diabetes type, age, region, and sex (Zhao et al, 2013 ; Willeit et al, 2014 ; Wang et al, 2016 ; Krasnienkov et al, 2018 ). Short LTL was also shown to be associated with different aspects of metabolic syndrome (Khalangot et al, 2017 , 2019 , 2020 ). Accelerated telomere shortening and low telomerase activity were shown to be associated with skeletal pathologies mediated by the age-related abnormal reconstruction of the subchondral bone, such as osteoporosis and osteoarthritis (Fragkiadaki et al, 2020 ).…”

Telomere length in different metabolic categories: Clinical associations and modification potential

“…The interactions between age, gender, and 2hPG levels were mostly non-linear, as shown by neural network modeling. 37 To our knowledge, such non-linearity of associations of LTL with age, glucose tolerance, and MetS has never been reported previously. Perhaps an increase in telomerase activity in individuals with the MetS subtype, which is characterized by a strong dyslipidemic profile along with the lack of hyperglycemia 40 could be the possible explanation for this phenomenon.…”

“…To address the question whether LTL is similarly associated with glucose levels in different hyperglycemic categories, we examined the correlations between LTLs and fasting and post-load glucose levels, and also several other metabolic characteristics in persons who did not receive glucose-lowering treatment in Ukraine. 35–37 In our research conducted in randomly selected rural residents of Kyiv region, an increase in telomere length (according to LTL quartiles) was found to be associated with better glucose tolerance according to OGTT 2hPG data ( P = 0.03) and only with a tendency to decrease fasting plasma glucose (FPG) levels. 35 In different glycemic categories (normal, prediabetes, and T2D), LTL was inversely associated with glucose tolerance (according to 2hPG) in all categories, but with FPG in the T2D category only.…”

“…38 This condition has been also shown to be associated with accelerated telomere attrition with age. 39 In our research, 37 we studied LTLs in the sample from adult population of Kyiv region, Ukraine depending on presence or absence of MetS and examined the impact of age and glucose tolerance on this association. MetS was identified in majority (69%) of study participants according to the IDF criteria.…”

Which diagnostic criteria of metabolic syndrome are predictors of cardiovascular diseases in elderly populations?

“…Elderly MetS patients may increase risk of CVD from shorten telomere. A previous study found that MetS had a high risk of shorter telomere by three times (p 0.01) [18] which leads to atherosclerosis and CVD [19] . However, only three of the five diagnostic criteria for MetS were independent predictors for CVD in the elderly including SBP, FPG, and HDL-c ( Table 4 ).…”