scholarly journals Middle-Aged Indians with Type 2 Diabetes Are at Higher Risk of Biological Ageing with Special Reference to Serum CDKN2A

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Joyita Banerjee ◽  
Yogita Dhas ◽  
Neetu Mishra

Sedentary lifestyle and high visceral adiposity have elevated the risk of type 2 diabetes (T2DM) among Indians at younger age. In this study, we aimed to investigate the association of oxidative stress and chronic inflammatory mediators with ageing with special reference to the biological ageing marker cyclin-dependent kinase inhibitor 2A (CDKN2A) among middle-aged (31-50 years) Indian healthy and T2DM subjects. Malondialdehyde (MDA), oxidized LDL (oxLDL), interleukin-6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and CDKN2A were measured in T2DM patients (n=80) and controls (n=80) aged 31-50 years, further grouped into G1: 31-40 years and G2: 41-50 years. IL-6, TNF-α, MCP-1, and CDKN2A showed a significant association with ageing among both T2DM patients and controls. But the strength of the association of MCP-1 and CKDN2A with ageing was significantly stronger in T2DM patients than the controls. All the oxidative stress and proinflammatory mediators showed nonsignificant associations with CDKN2A in the controls. However, IL-6, TNF-α, and MCP-1 showed a strong association with CDKN2A in T2DM patients. An increased risk of high levels of CDKN2A was found in G1 T2DM patients (OR: 3.484 (95% CI: 1.246-9.747) p=0.017) and G2 T2DM patients (OR: 5.000 (95% CI: 1.914-13.061), p=0.001) with reference to the respective control groups. Our study reveals that the middle-aged Indians with T2DM are at higher risk of biological ageing. The development of T2DM is more common among middle-aged Indians. T2DM may exacerbate the ageing process and may subsequently predispose Indians to various age-related complications at a much early age.

2019 ◽  
Vol 9 (10) ◽  
pp. 262 ◽  
Author(s):  
Hayden

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.


2005 ◽  
Vol 62 (7-8) ◽  
pp. 529-536 ◽  
Author(s):  
Miroslava Zamaklar ◽  
Katarina Lalic ◽  
Natasa Rajkovic ◽  
Danijela Trifunovic ◽  
Mirjana Dragasevic ◽  
...  

Background. Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). Factors that contribute to endothelial cell dysfunction associated with the initiation of atherosclerosis include oxidative stress. The aim of this study was to investigate the relationship between lipid profile and oxidative stress in type 2 diabetics with and without ischemic heart disease (IHD). Methods. We studied 80 patients with T2D, 40 with IHD (group A1) and 40 without IHD (group A2). We also studied 51 non-diabetics, 31 with IHD (group B1), and 20 without IHD (group B2 - control group). Lipid profile was estimated by the total cholesterol, HDL cholesterol, LDL cholesterol, the level of triglyceride (Tg), lipoproteina a (Lp a), Apo A I, A II, B 100 and E. To evaluate the oxidative status we measured circulating oxidized LDL (ox LDL), erythrocyte antioxidative enzyme activity: superoxide dismutase (E-SOD), glutathione peroxidase (E-GPX), as well as the total antioxidative serum activity (TAS). Inflammatory reaction was estimated by C-reactive protein (CRP) and fibrinogen. Results. No significant difference was found in the lipid profile in groups A1, A2 and B1, but the group B2 had the lowest one. Lp a level was significantly higher in group B1 comparing to other groups (p < 0.05). There was no significant difference in the level of ox LDL between the groups. In diabetics, ox LDL positively correlated with the total cholesterol, LDL cholesterol, non HDL cholesterol, Apo B 100 and the relations between LDL/HDL and Tg/HDL (p < 0.001), as well as with Tg and fibrinogen (p < 0.05). In group B1, ox LDL positively correlated with total cholesterol, Tg (p < 0.01), LDL, and non HDL cholesterol (p < 0.05) and significantly with Apo B 100 (p < 0.001). There was no significant difference in the antioxidant enzyme activities between the groups of diabetics (A1 and A2), but fibrinogen was higher in the group with IHD (group A1, p < 0.05). Group B1 had lower ESOD activity than the groups A1 and A2 (p < 0.05), but CRP was higher (p < 0.05). There were no significant correlations between oxLDL and CRP in groups A1 and A2, but it was statistically significant in the group B1 (p < 0.05). Conclusion. In this study we demonstrated the increased oxidative stress in diabetics compared to non-diabetics regardless of the presence of IHD. Fibrinogen, but not CRP, was higher in diabetics with IHD, compared to diabetics without IHD. The increased oxidative stress, the reduced antioxidative activity E-SOD, and the higher level of CRP were found in non-diabetics with IHD compared to non-diabetics without IHD.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Denisha Spires ◽  
Oleg Palygin ◽  
Vladislav Levchenko ◽  
Sherif Khedr ◽  
Oksana Nikolaienko ◽  
...  

Diabetic kidney disease (DKD) is a severe complication of diabetes, which causes an increased risk of cardiovascular diseases and end-stage renal failure. Recent clinical data have demonstrated distinct sexual dimorphisms in the pathogenesis of DKD in humans, which impacts both severity- and age-related risk factors. A type 2 diabetic nephropathy (T2DN) rat model characterized by spontaneous development of an advanced form of diabetic nephropathy (DN) was used here to study sexual dimorphisms in the development of type 2 diabetes with DN. Male and female T2DN rats at late stages of the disease were used to evaluate hyperglycemia, renal injury, and kidney function. During late stage DKD (>46 weeks), glucose tolerance tests (GTT) revealed higher glucose levels in males (378 ± 19 vs. 183 ± 48 mg/dL) compared to females. This was accompanied by pathological changes in kidney function including urinary nephrin shedding, albuminuria (11.8 ± 5.7 vs. 0.98 ± 0.64 Alb/Cre ratio), and glomerular damage. To test the role of the endocrine environment in the pathophysiology of type 2 diabetes with DKD, we performed gonadectomies on male and female T2DN rats at 9 to 10 weeks of age, and animals were monitored until the full development of DKD (>46 weeks). All T2DN rats (intact and gonadectomized) maintained their diabetic phenotype, which was verified by higher end point blood glucose levels following a GTT (intact vs gonadectomized, male and female, respectively; 404 ± 21 vs 466 ± 32 and 264 ± 20 vs 291 ± 25 mg/dL). Based on kidneys to body weight ratios, gonadectomized male T2DN rats had a significant reduction in kidney hypertrophy (intact vs gonadectomized; males and females, respectively: 9.9 ± 0.2 vs 7.4 ± 0.2 and 7.7 ± 0.2 vs 7.0 ± 0.2 ratio). Moreover, FITC-inulin based GFR measurements revealed gonadectomized males had improved GFRs, whereas the GFRs of gonadectomized females rats were worsened (7.5 ± 1.5 vs. 4.1 ± 0.7 for male and 4.1 ± 0.2 vs. 7.3 ± 1.3 for female μg/mL/min; gonadectomy vs intact, correspondingly). In conclusion, male T2DN rats develop more severe DKD compared to age-matched females, and this phenotype is partially attenuated by the absence of sex hormones in males and exacerbated by the absence of hormones in females.


2008 ◽  
Vol 9 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Henri Tuomilehto ◽  
Markku Peltonen ◽  
Markku Partinen ◽  
Juha Seppä ◽  
Timo Saaristo ◽  
...  

2018 ◽  
Vol 15 (4) ◽  
pp. 336-339 ◽  
Author(s):  
Ding Liu ◽  
Lei Liu ◽  
Zhongyang Hu ◽  
Zhi Song ◽  
Yaqin Wang ◽  
...  

Aim: Type 2 diabetes mellitus is a polygenic metabolic disorder resulting from oxidative stress, the root cause of insulin resistance, β-cell dysfunction and impaired glucose tolerance. The aim of this study was to investigate the role of oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO in type 2 diabetes mellitus susceptibility in the Chinese Han population. Methods: A total of 396 type 2 diabetes mellitus patients and 678 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222, GPX1 rs1050450, GPX3 rs3828599 and MPO rs2107545 gene polymorphisms were genotyped. Results: We found one single-nucleotide polymorphism in the MPO gene was associated with type 2 diabetes mellitus susceptibility [rs2107545: odds ratio = 1.563 (1.166–2.096); p = 0.003], after adjusting for covariates. Furthermore, we also considered the likely complexity of effects of genetic and conventional risk factors in type 2 diabetes mellitus–related vascular complications, such as carotid plaques. Our analysis revealed that the GPX1 rs1050450 and MPO rs2107545 were significantly associated with increased risk of carotid plaques in type 2 diabetes mellitus patients. Conclusion: Our study presents novel evidence for main effects of MPO gene on type 2 diabetes mellitus susceptibility. Furthermore, our study supported the association between variants of oxidative stress–related genes ( GPX1 and MPO) and carotid plaques in type 2 diabetes mellitus patients, which indicated a modulation of type 2 diabetes mellitus–related vascular complication susceptibility by genetic predisposition.


2015 ◽  
Vol 116 (3) ◽  
pp. 573-582 ◽  
Author(s):  
Jonida Haxhi ◽  
Gaetano Leto ◽  
Alessandro Scotto di Palumbo ◽  
Paola Sbriccoli ◽  
Laura Guidetti ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document