scholarly journals TNFα Mediates the Interaction of Telomeres and Mitochondria Induced by Hyperglycemia: A Rural Community-Based Cross-Sectional Study

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Lu Lyu ◽  
Shuli He ◽  
Huabing Zhang ◽  
Wei Li ◽  
Jingbo Zeng ◽  
...  

This study is aimed at evaluating the relationship between leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in a noninterventional rural community of China with different glucose tolerance statuses. In addition, we investigate whether the indicators of oxidative stress and inflammation were involved and identify mediators among them. A total of 450 subjects in rural China were included and divided into two groups according to a 75 g oral glucose tolerance test (OGTT): the abnormal glucose metabolism (AGM, n=257, 57.1%) group and the normal glucose tolerance (NGT, n=193, 42.9%) group. Indicators of oxidative stress (superoxide dismutase (SOD) and glutathione reductase (GR)) and inflammatory indices (tumor necrosis factor α (TNFα) and interleukin-6 (IL-6)) were all determined by ELISA. LTL and mtDNAcn were measured using a real-time PCR assay. Linear regressions were used to adjust for covariates that might affect the relationship between LTL and mtDNAcn. Mediation analyses were utilized to evaluate the mediators. In the AGM, LTL was correlated with mtDNAcn (r=0.214, p=0.001), but no correlation was found in the NGT. The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM (p=0.087). LTL and mtDNAcn were both inversely related to HbA1c, IL-6, TNFα, and SOD activity. Mediation analysis demonstrated that TNFα was a significant mediator in the telomere-mitochondrial interactome in the AGM. This result suggests that inflammation and oxidative stress may play a vital role in telomere shortening as well as mitochondrial dysfunction. In the subjects with hyperglycemia, a significant positive correlation is observed between LTL and mtDNAcn, which is probably mediated by TNFα. TNFα may be considered a potential therapeutic target against aging-related disease in hyperglycemia.

2018 ◽  
Vol 7 ◽  
Author(s):  
Taylor A. Breuninger ◽  
Anna Riedl ◽  
Nina Wawro ◽  
Wolfgang Rathmann ◽  
Konstantin Strauch ◽  
...  

AbstractType 2 diabetes mellitus (T2DM) is a global public health epidemic. Diet and lifestyle changes have been demonstrated as effective measures in managing T2DM and preventing or delaying the progression from prediabetes to diabetes, yet the relationship between diet, prediabetes and diabetes is still not entirely clear. The present study aimed to further elucidate the relationship between diet, diabetes and especially prediabetes. A total of 1542 participants of the cross-sectional, population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) were included in this analysis. Dietary intake was derived using a method combining information from a FFQ and repeated 24-h food lists. Glucose tolerance status was assessed via oral glucose tolerance tests in all participants without a previous physician-confirmed diagnosis of T2DM, and was classified according to the 2003 American Diabetes Association criteria. Crude and fully adjusted multinomial logistic regression models were fitted to examine associations between diet and prediabetes, undetected diabetes mellitus (UDM) and prevalent T2DM. After adjusting for major covariates, fruit was significantly inversely and total meat, processed meat, sugar-sweetened beverages and moderate alcohol significantly associated with UDM and/or prevalent diabetes. Sex-specific analyses showed that in men, coffee was significantly inversely (OR 0·80; 95 % CI 0·67, 0·96) and heavy alcohol significantly (OR 1·84; 95 % CI 1·14, 2·95) associated with prediabetes. Our findings on diet and T2DM are consistent with current literature, while our results regarding coffee, heavy alcohol consumption and prediabetes highlight new possible targets for primary prevention of the derangement of glucose homeostasis.


Author(s):  
Lu Lyu ◽  
Jie Yu ◽  
Yiwen Liu ◽  
Shuli He ◽  
Yuan Zhao ◽  
...  

Abstract Context The hemoglobin glycation index(HGI) is correlated with metabolic diseases and inflammations. Whether the HGI is associated with the ageing process and how inflammation and oxidative stress affect the relationship remain unclear. Objective We aim to analyze links between HGI and ageing biomarkers, and to explore a potential role of inflammation and oxidative stress in the correlations. Methods A cross-sectional study of 434 subjects with different glucose intolerances in a rural community was enrolled. The HGI was calculated as the difference between the measured and predicted hemoglobin A1c(HbA1c). The population was categorized into tertiles of HGI. Telomere length(LTL) and mitochondrial DNA copy number(mtDNAcn) determined by PCR assay. Tumor necrosis factor α(TNFα) and interleukin 6(IL-6), 8-oxo-2′-deoxyguanosine(8-oxo-dG), superoxide dismutase(SOD) activities and glutathione reductase(GR) were measured. Result Participants in the high HGI group were older and reported a shorter LTL, higher levels of TNFα, SOD activities and HbA1c. Correlation analyses demonstrated that HGI was correlated with LTL(r=-0.25,p<0.001) and TNFα(r=0.19,p<0.001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI(β=-0.238,95%CI(-0.430,-0.046),p=0.015) and TNFα(β=-0.02,95%CI(-0.030,-0.014),p<0.001) were proved to be correlated with LTL independently using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects in High-HGI, the possibilities of a higher-level LTL was 5.29-fold in Low-HGI(OR5.29,95%CI(2.45,11.41),p<0.001), 2.41-fold in Moderate-HGI (OR2.41,95%CI(1.35,4.30),p=0.003) after controlling for confounding variables. Mediation analyses indicated that TNFα accounted for 30.39% effects of HGI on LTL. Conclusion HGI was negatively related to telomere attrition, independent of HbA1c. TNFα acted as a mediator of the relationship between HGI and LTL.


2020 ◽  
Vol 07 (03) ◽  
pp. 16-19
Author(s):  
Kuldeep Kumar ◽  

Aim:The aim of this study was to establish the relationship between the glycemic variation in patients of Acute Coronary Syndrome (ACS) with hyperglycemia, oxidative stress and pre-discharge assessment of glycemic status by Oral Glucose Tolerance Test (OGTT). Materials and Method: Nineteen non-diabetic patients who presented with acute coronary syndrome with random blood sugar ≥200 mg/dl were recruited and glycemic variation was measured using CGMS followed by measurement of 8-isoprostanes PG-2alpha as a marker of oxidative stress, and pre-discharge OGTT was done to know the glycemic status at the time of discharge. Result: Mean MAGE (A parameter of glycemic variation) was 106.92±22.66 and mean 8-isoprostanes level was 206.05±179.57. There was no relationship between these two values. On doing OGTT, out of 19 non diabetic patients 11 turned out to be frank diabetic and 8 were having impaired glucose tolerance after OGTT, none were euglycemic. Conclusion:The study highlighted the issue of hyperglycaemia in ACS patients and their abnormal glucose tolerance in the short term, most of them turning to be frankly diabetic and being totally asymptomatic till the time of index event, although no correlation was found between glycemic variability and oxidative stress.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tara Ahanian ◽  
Philip Curman ◽  
Ivone U. S. Leong ◽  
Kerstin Brismar ◽  
Etty Bachar-Wikstrom ◽  
...  

Abstract Background Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes. Methods Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function). Results DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher. Conclusion Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mluleki Luvuno ◽  
Andile Khathi ◽  
Musa V. Mabandla

Abstract Changes associated with cognitive function in the high-fat high-carbohydrate diet-induced prediabetes animal model and effect of exercise remain unclear. Rats were randomly assigned to the following groups (n = 6): non-diabetic (ND), prediabetic (PD), intermittent exercising PD (PD + IE) and regular exercising PD (PD + RE). After exercise cessation, oral glucose tolerance (OGT), Novel Object Recognition Test (NORT) and Morris-Water Maze (MWM) tests were performed to assess cognitive function. After sacrifice, malonaldehyde, glutathione peroxidase, interleukin-1β and dopamine concentration in the prefrontal cortex (PFC) and hippocampus were measured. Impaired OGT response in PD animals was accompanied by poor performance on behavioural tasks. This was associated with increased oxidative stress markers and impaired dopamine neurotransmission as evidence by elevated dopamine concentration in the PFC and hippocampal tissue. Improved OGT response by exercise was coupled with improved performance on behavioural tasks, oxidative stress markers and increased interleukin-1β concentration. In regular exercise, this was further coupled with improved dopamine neurotransmission. Cognitive function was affected during prediabetes in animals. This was partly due to oxidative stress and impaired dopamine neurotransmission. Both intermittent and regular exercise improved cognitive function. This was partly mediated by improved glucose tolerance and oxidative stress as well as a subclinical increase in interleukin-1β concentration. In regular exercise, this was further mediated by improved dopamine neurotransmission.


2013 ◽  
Vol 38 (12) ◽  
pp. 1254-1259 ◽  
Author(s):  
Adèle Coriati ◽  
Belinda Elisha ◽  
Sandrine Virassamynaik ◽  
Maude Phaneuf ◽  
Sophie Ziai ◽  
...  

Adult patients with cystic fibrosis (APCF) are at high risk of developing impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) and thus an annual screening with a 2-h oral glucose tolerance test (OGTT) is recommended. This population would greatly benefit from a simplified and harmless alternative to the standard OGTT. Thus, we aimed to compare the diagnostic values of HbA1c and glycemias at interval time points during the 2-h OGTT for IGT and CFRD detection in APCF. To do so, we conducted a cross-sectional analysis of 194 APCF with normal fasting plasma glucose values (≤7.0 mmol·L−1) who underwent a 2-h OGTT. Receivers operating characteristic area under the curves (ROC-AUC) were analyzed to assess the diagnostic value of HbA1c and intermediate OGTT glycemias using 2-h OGTT glycemia as reference. For both IGT and CFRD diagnoses, ROC-AUC values obtained from glycemia at 90 min were significantly higher than HbA1c and remaining intermediate glycemias (p < 0.001). The best 90-min OGTT cut-off values for these diagnoses were >9.3 mmol·L−1 (IGT) and ≥11.5 mmol·L−1 (CFRD). A 90-min OGTT glycemia might be a simplified alternative to 2-h OGTT glycemia for earlier glucose tolerance abnormalities diagnosis in APCF. This finding should be confirmed in other APCF cohorts and its predictive value should be established prospectively.


2008 ◽  
Vol 295 (2) ◽  
pp. E401-E406 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Masafumi Matsuda ◽  
Rucha Jani ◽  
Christopher P. Jenkinson ◽  
Dawn K. Coletta ◽  
...  

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT ( n = 293) and IGT ( n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations. The insulin secretion/insulin resistance (IS/IR) or disposition index was calculated as ΔISR/ΔG ÷ IR. As FPG increased in NGT subjects, the IS/IR index declined exponentially over the range of FPG from 70 to 125 mg/dl. The relationship between the IS/IR index and FPG was best fit with the equation: 28.8 exp(−0.036 FPG). For every 28 mg/dl increase in FPG, the IS/IR index declined by 63%. A similar relationship between IS/IR index and FPG was observed in IGT. However, the decay constant was lower than in NGT. The IS/IR index for early-phase insulin secretion (0–30 min) was correlated with the increase in FPG in both NGT and IGT ( r = −0.43, P < 0.0001 and r = −0.20, P = 0.001, respectively). However, the correlation between late-phase insulin secretion (60–120 min) and FPG was not significant. In conclusion, small increments in FPG, within the “normal” range, are associated with a marked decline in glucose-stimulated insulin secretion and the decrease in insulin secretion with increasing FPG is greater in subjects with NGT than IGT and primarily is due to a decline in early-phase insulin secretion.


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