scholarly journals Cardiovascular safety of oral antidiabetic therapy in type 2 diabetes mellitus- review article

Author(s):  
P. S. Singh ◽  
Sudhir K. Yadav ◽  
Himanshu Sharma ◽  
Manoj Kumar

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (DM). There is twofold increased risk of cardiovascular (CV) mortality among diabetic patients as compared with nondiabetic patients. The glycemic efficacy of anti-diabetic drugs does not necessarily provide cardiovascular safety. Since 2008, US Food and Drug Administration has recommended that new drugs for type 2 DM should undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, European medicine agencies issued a similar recommendation. In this review, we have tried to examine the cardiovascular safety of oral antidiabetic agents in major published trials. Metformin remains the initial drug of choice in type2 DM till date. The sulfonylureas, one of oldest oral anti-diabetic drugs, have adverse cardiovascular events and are gradually being out classed by other second line drugs. The glitazones have been found to have adverse outcome in heart failure. The incretin based drugs have been found to have cardiovascular safety in various trials in recent past and their performances have been reassuring. There is lack of enough cardiovascular outcome data for meglitinides and glucosidase inhibitors. Various current trials have found sodium glucose cotransporter-2 inhibitors to have a potential for cardiovascular benefit. Careful selection of drug therapy with special attention for cardiovascular risk is important in selection and optimization of diabetic therapy.

Author(s):  
NITHYA K ◽  
ANGELINE T ◽  
PRISCILLA AS ◽  
ASIRVATHAM AJ

Objective: Glutamate carboxypeptidase II (GCPII), reduced folate carrier 1 (RFC1), and methionine synthase (MTR) genes involved in the folate metabolic pathway may play a key role in the pathogenesis of diabetes and its complications. The present study aimed to investigate the prevalence of genetic polymorphisms of GCPII C1561T, RFC1 A80G, and MTR A2756G in individuals with type 2 diabetes mellitus (T2DM) among South Indians. Methods: The study subjects consisted of 100 healthy individuals and 200 patients with T2DM. Genetic polymorphisms (GCPII C1561T, RFCI A80G, and MTR A2756G) in the folate metabolic pathway were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis was performed to test the level of significance. Results: With regard to GCPII C1561T and MTR A2756G gene polymorphisms, significant differences were not found when diabetic patients (with and without complications) and controls were compared according to different statistical models (dominant, recessive, and overdominant) p>0.05. A case–control genetic association analysis of RFC1 A80G gene polymorphism has shown that there was 3.7-fold increased risk for patients without complications and 4.9-fold increased risk for diabetic patients with complications. Conclusions: Our findings suggest that the GCPII C1561T and MTR A2756G gene polymorphisms were not significantly associated with diabetes and its complications. Whereas, the RFCI A80G gene polymorphism involved in folate metabolism confers increased risk for diabetes and its complications in South Indian population.


2021 ◽  
Vol 8 ◽  
Author(s):  
Liang Ma ◽  
Shaoting Wang ◽  
Hailing Zhao ◽  
Meijie Yu ◽  
Xiangling Deng ◽  
...  

This study aimed to investigate the susceptibility of 8 polymorphisms in ApoB and PCSK9 genes to diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus. This is a case-control association study, including 575 DKD cases and 653 controls. Genotypes were determined using ligase detection reaction method, and data are analyzed using STATA software. The genotype distributions of rs1042034 and rs12720838 differed significantly between the two groups (P < 0.001 and P = 0.008, respectively). After adjusting for confounding factors, the mutations of rs1042034 and rs12720838 were associated with the significantly increased risk of DKD. For instance, carriers of rs1042034 T allele (CT and TT genotypes) were 1.07 times more likely to have DKD than carriers of rs1042034 CC genotype [odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.03–1.10, P < 0.001]. Further, haplotype T-A-G-T in ApoB gene was overrepresented in cases (18.10%) compared with controls (12.76%) (PSimulated = 0.045), and haplotype T-A-G-T was associated with a 33% increased risk of DKD (OR = 1.33, 95% CI: 1.04, 1.70). In further haplotype-phenotype analysis, significant association was only noted for hypertension and omnibus haplotypes in ApoB gene (PSimulated = 0.001). Our findings indicate that ApoB gene is a candidate gene for DKD in Chinese patients with type 2 diabetes mellitus.


Author(s):  
Askandar Tjokroprawiro ◽  
Sri Murtiwi ◽  
Raymond R. Tjandrawinata

AbstractBackgroundDLBS3233, a combined bioactive fraction ofMethodsThis was an open and prospective clinical study for 12 weeks of therapy, involving type-2 diabetes mellitus patients who had been treated with two oral antidiabetic agents for at least 3 months prior to screening, yet, with HbAResultsAfter 12 weeks of treatment, the HbAConclusionsThe add-on oral antidiabetes therapy with DLBS3233 at the dose of 100 mg once daily helped type-2 diabetes mellitus patients to improve their glycemic control, enhance insulin sensitivity, lipid profile, and adiponectin level. In addition, DLBS3233 treatment concomitantly with other oral antidiabetic agents was proven safe and tolerable in type-2 diabetes subjects.


2018 ◽  
Vol 73 (4) ◽  
pp. 271-281 ◽  
Author(s):  
Zhi-chun Sun ◽  
Jing Yu ◽  
Yi-Lan Liu ◽  
Zhen-zhen Hong ◽  
Lin Ling ◽  
...  

Background: Brain-derived neurotrophic factor (BDNF) is involved in obesity, type 2 diabetes mellitus (T2DM), and cognitive dysfunction. The present study sought to assess the role of serum levels of BDNF in the pathophysiological process of mild cognitive impairment (MCI), a preclinical phase of dementia in 715 Chinese patients with T2DM. Methods: Cross-sectional data were obtained from 715 patients with T2DM recruited from a Chinese diabetes center. Serum levels of BDNF were measured with sandwich enzyme-linked immunosorbent assay. The influence of BDNF on MCI was examined using univariate and multivariate binary logistic regression analyses. Results: In univariate and multivariate logistic regression analyses, for each one-unit increase of BDNF, the unadjusted and adjusted risk of MCI decreased by 9% (OR 0.91; 95% CI 0.88–0.93, p < 0.001) and 6% (0.94; 0.87–0.98, p < 0.001) respectively. In multivariate models comparing the first (Q1), second and third quartiles against the fourth quartile of BDNF, BDNF in Q1 and Q2 were associated with MCI, and increased risk of MCI by 275% (OR 3.75; 95% CI 2.38–6.03) and 155% (2.55; 1.32–4.02). These results suggested that for each 1 ng/mL increase of serum level of BDNF, the association became stronger among obese diabetic patients (OR 0.91, 95% CI 0.85–0.96; p < 0.001) versus nonobese diabetic patients (OR 0.95, 95% CI 0.86–0.98; p = 0.001). Conclusion: The present data demonstrated that reduced serum levels of BDNF were associated with increased risk of MCI and might be useful for identifying diabetic patients at risk of dementia for early prevention strategies.


Author(s):  
A. Popruha

Type 2 diabetes and obesity are among the most common diseases worldwide. Due to the extremely high prevalence of these diseases that has been reached in recent years, at present they are recognized as non-infectious epidemics. Obesity is the leading modifying pathogenetic factor of type 2 diabetes. Almost 90% of diabetic patients are overweight or obese. Today, adipose tissue is positioned as an endocrine organ that produces numerous proteins with autocrine, paracrine, and endocrine functions. As a result, chronic activation of the body's immune system occurs with overproduction of a wide range of pro-inflammatory cytokines with subsequent development and progression of chronic non-specific systemic inflammation and oxidative stress, which make a significant contribution to the development of many chronic diseases. Based on the relationship of the pathogenetic moments between type 2 diabetes and obesity, attention should be paid to study the role of genetic factors of the antioxidant defence system, and, in particular, the glutathione peroxidase-1 (GPx1) gene polymorphism, on the development and course of these pathologies. Therefore, we investigated the specific effects of the Pro197Leu polymorphism of the GPx1 gene on the development of diabetic and cardiovascular complications in patients with type 2 diabetes and patients with type 2 diabetes and comorbid obesity in the Poltava region. Significant relationship was found out between the presence of the Leu allele and the increased risk of both type 2 diabetes and type 2 diabetes in combination with obesity. It has been established that in the patients with type 2 diabetes and patients with type 2 diabetes and comorbid obesity, the carriage of the Pro allele can be a protective factor with a protective effect towards preventing the development of complications in the clinical and pathogenetic course of both diseases, while the presence of the mutant Leu allele in the homo- and heterozygous state of the GPx1 gene is associated with an increased risk of the development of the diseases studied as well as concomitant diabetic and cardiovascular complications with more adverse clinical course of both diseases.


Author(s):  
Manoj Kumar Mali

Background: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Diabetic patients with hypothyroidism also are at an increased risk of cardiovascular disease. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. Methods: All patients were evaluated for thyroid status; assessment of T3, T4 and TSH levels and Blood glucose levels and HbA1c. Results: 22.00% patients were present with subclinical hypothyroidism, 18.00% patients were present with hypothyroidism and 4.00% patients present with hyperthyroidism Conclusion: Screening for thyroid disease disease among patients with diabetes mellitus should be routinely performed for early detection and treatment of thyroid dysfunction to delay the complications of diabetes Keywords: Thyroid, Type-2DM, Complication


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