scholarly journals Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies?

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Carla Pollastro ◽  
Carmela Ziviello ◽  
Valerio Costa ◽  
Alfredo Ciccodicola

Type 2 diabetes is one of the major causes of mortality with rapidly increasing prevalence. Pharmacological treatment is the first recommended approach after failure in lifestyle changes. However, a significant number of patients shows—or develops along time and disease progression—drug resistance. In addition, not all type 2 diabetic patients have the same responsiveness to drug treatment. Despite the presence of nongenetic factors (hepatic, renal, and intestinal), most of such variability is due to genetic causes. Pharmacogenomics studies have described association between single nucleotide variations and drug resistance, even though there are still conflicting results. To date, the most reliable approach to investigate allelic variants is Next-Generation Sequencing that allows the simultaneous analysis, on a genome-wide scale, of nucleotide variants and gene expression. Here, we review the relationship between drug responsiveness and polymorphisms in genes involved in drug metabolism (CYP2C9) and insulin signaling (ABCC8,KCNJ11, andPPARG). We also highlight the advancements in sequencing technologies that to date enable researchers to perform comprehensive pharmacogenomics studies. The identification of allelic variants associated with drug resistance will constitute a solid basis to establish tailored therapeutic approaches in the treatment of type 2 diabetes.

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
M. Nishigaki ◽  
Y. Tokunaga-Nakawatase ◽  
J. Nishida ◽  
C. Taru ◽  
I. Miyawaki ◽  
...  

Relatives of type 2 diabetic patients are at a high risk of developing type 2 diabetes and should be regarded as target of intervention for diabetes prevention. However, it is usually hard to motivate them to implement preventive lifestyle changes, because of lack of opportunity to take advises from medical professionals, inadequate risk perception, and low priority for preventive behavior. Prevention strategy for them therefore should be highly acceptable and suited for them. The parallel, three-group trial is now being conducted to investigate the effects of genetic counseling and/or a computerized behavioral program on the prevention of type 2 diabetes in that population. The preventive strategies used in this study could provide a novel solution to the numbers of genetically high-risk individuals, if found to be effective. The objective of this paper is to describe the background, protocol, and baseline patient characteristics of the trial.


2020 ◽  
Vol 16 ◽  
Author(s):  
Shivashankara Bhat ◽  
Mukta Chowta ◽  
Nithyananda Chowta ◽  
Rajeshwari Shastry ◽  
Priyanka Kamath

Background: Type 2 diabetic patients often require insulin therapy for better glycaemic control. However, many of these patients do not receive insulin or do not receive it in a timely manner. Objective: The study was planned to assess the proportion of type 2 diabetic patients attaining treatment goals as per the ADA 2018 guidelines. In addition, patient’s perception on insulin therapy assessed and compared between insulin naïve and insulin initiated type 2 diabetic patients. Methods: The study was conducted in type 2 diabetic patients. Data on their demographics, medical history, duration of diabetes, history of diabetes related complications, the current antidiabetic medication received, most recent glycaemic parameters were noted. Patient’s perception on insulin initiation was recorded through structured interview. Results: A total of 129 patients were included in the study. Around 76.7% patients achieved HbA1c target (<7%). Duration of the disease is much higher in patients who did not meet the HBA1c target. A good number of patients felt that insulin injection would be physically painful (56.5%). Majority of the patients also felt that insulin will make their life less flexible (64.8%). Many patients are having the opinion that insulin is required for life long (73.2%). More number of patients on insulin agreed with the statement ‘Leads to good short-term outcomes as well as long-term benefits’ compared to insulin naïve patients. Conclusion: The results highlight that the proportion of patients achieving recommended glycaemic target is not satisfactory. Many patients who are inadequately controlled with oral antidiabetic drugs were reluctant to initiate insulin.


2006 ◽  
Vol 290 (1) ◽  
pp. E54-E59 ◽  
Author(s):  
Lucilla D. Monti ◽  
Emanuela Setola ◽  
Gabriele Fragasso ◽  
Riccardo P. Camisasca ◽  
Pietro Lucotti ◽  
...  

The aim of the present study was to evaluate the effect of prolonged inhibition of β-oxidation on glucose and lipid muscle forearm metabolism and cGMP and endothelin-1 forearm release in patients with type 2 diabetes mellitus and ischemic cardiomyopathy. Fifteen patients were randomly allocated in a double-blind cross-over parallel study with trimetazidine (20 mg tid) or placebo lasting 15 days. At the end of each period, all patients underwent euglycemic hyperinsulinemic clamps with forearm indirect calorimetry and endothelial balance of vasodilator and vasoconstricor factors. Compared with placebo, trimetazidine induced 1) an increase in insulin-induced forearm glucose uptake and glucose oxidation accompained by a reduction in forearm lipid oxidation and citrate release and 2) a decrease of endothelin-1 release paralleled by a significant increase in forearm cGMP release. Forearm glucose oxidation significantly correlated with cGMP release ( r = 0.37, P < 0.04), whereas forearm lipid oxidation positively correlated with endothelin-1 release ( r = 0.40, P < 0.03). In conclusion, for the first time, we demonstrated that insulin-induced forearm glucose oxidation and forearm cGMP release were increased whereas forearm endothelin-1 release was decreased during trimetazidine treatment. Muscle's metabolic and vascular effects of trimetazidine add new interest in the use of trimetazidine in type 2 diabetic patients with cardiovascular disease.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ping Song ◽  
Jin Xu ◽  
Yongfeng Song ◽  
Shiliang Jiang ◽  
Haitao Yuan ◽  
...  

Aims. This study aimed to investigate whether the change of plasma myeloperoxidase (MPO) level would be associated with the incidence of coronary artery disease (CAD) among diabetic patients.Methods. 339 patients with type 2 diabetes mellitus (DM) underwent coronary angiography. Of them, 204 cases had CAD and were assigned to CAD group and 135 cases without CAD were assigned to non-CAD group.Results. Compared to non-CAD group, CAD group had higher level of plasma MPO (p<0.01). Multiple linear regression analysis showed that plasma MPO level was correlated with Gensini score. Multiple logistic analysis showed that the odds ratios for CAD across increasing tertiles of MPO level were 1.191 (0.971–1.547) and 1.488 (1.115–2.228) (p=0.048,p=0.009versus 1st tertile of MPO level, resp.) by adjusting for age, sex, and other conventional risk factors for CAD. The subjects were stratified into nine groups according to tertiles of MPO and HbA1c. The odds ratio for CAD was significantly higher in group with highest levels of MPO and HbA1c (OR = 4.08,p<0.01).Conclusion. Plasma MPO level was positively correlated with the degree of coronary artery stenosis in type 2 diabetic patients, and increasing blood glucose might amplify the association between MPO and CAD.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Masakazu Nishigaki ◽  
Eiko Sato ◽  
Ryota Ochiai ◽  
Taiga Shibayama ◽  
Keiko Kazuma

Background. Offspring of type 2 diabetic patients are at a high risk of type 2 diabetes. Information on diabetes genetic susceptibility and prevention should be supplied to the offspring.Methods. A six-page booklet on diabetes genetic susceptibility and prevention was distributed to 173 patients who ere ordered to hand it to their offspring. The patients answered a self-administered questionnaire on booklet delivery and attitudinal and behavioral changes toward diabetes and its prevention in themselves and their offspring.Results. Valid responses were obtained from 130 patients. Forty-nine patients had actually handed the booklet. Booklet induces more relief than anxiety. From the patient's view, favorable attitudinal and/or behavioral changes occurred in more than half of the offspring who were delivered the booklet.Conclusion. The booklet worked effectively on attitudes and behaviors toward diabetes and its prevention both in patients and their offspring. However, the effectiveness of patients as information deliverers was limited.


2021 ◽  
Vol 8 (37) ◽  
pp. 3334-3338
Author(s):  
Satish Kumar

BACKGROUND Type 2 diabetes mellitus is common in the Indian population and awareness regarding the disease and its complications is low among the patients with diabetes. There is lack of studies regarding awareness of complications of diabetes among type 2 diabetic patients. The purpose of this study was to assess the awareness of diabetic complications among type 2 diabetic patients. METHODS This is an institutional based observational study. The sample comprised of 150 adult patients with type 2 diabetes mellitus who underwent treatment in the Department of Medicine, Medical College Kottayam and the patient’s age ranged from 18 - 77 years. RESULTS Majority of patients were in the age group 38 to 57 and the sample comprised of 56 % males and 44 % female patients. Out of 150 patients involved in the study, 120 patients (80 %) were aware of the complications of diabetes mellitus. Among the male patients, 70 (83.33 %) and among females, 50 (75.75 %) were aware of the complications in diabetes. In the study sample, 92 (61.33 %) were aware of the foot problems, 120 patients (80 %) were aware of renal complications, 91 patients were aware regarding eye problems of diabetes, 38 (25.33 %) regarding development of hypertension, 62 (41.33 %) regarding heart attack, 42 (28 %) patients were aware regarding development of stroke and 78 patients (52 %) had awareness regarding occurrence of recurrent infections. CONCLUSIONS Awareness regarding diabetes and its complications is fairly good among the diabetic patients in Kerala. Awareness regarding all complications of diabetes was higher among males than females. Providing awareness to type 2 diabetic patients by various educational programs may be of further help to prevent complications and to decrease the mortality and morbidity in type 2 diabetes patients. KEYWORDS Awareness, Diabetes


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ole Torffvit ◽  
Majid Kalani ◽  
Jan Apelqvist ◽  
Björn Eliasson ◽  
Jan W. Eriksson ◽  
...  

Fifty-four type 2 diabetic patients with neuroischemic foot ulcers were randomised to treatment with 5000 IU of dalteparin, (n=28), or physiological saline, (n=26), once daily until ulcer healing or for a maximum of 6 months. Thirty-three patients had normo-, 15 micro-, and 6 macroalbuminuria. The urinary levels of IgM and IgG2were elevated in 47 and 50 patients, respectively. Elevated urinary levels of IgM and IgG2indicate decreased glomerular size selectivity. Urine IgM levels were associated with IGF-1/IGFBP-1 and IGFBP-1 levels. Dalteparin treatment increased urinary levels of glycosaminoglycans (P<0.001) and serum IGFBP-1 (P<0.05) while no significant effects were seen in any of the other studied parameters. In conclusion, dalteparin therapy in patients with type 2 diabetes had no effects on urinary levels of albumin, IgM, or IgG2despite significantly increased glycosaminoglycans in urine. Elevated urinary levels of IgM and IgG2might be more sensitive markers of renal disease than albuminuria in patients with type 2 diabetes and antihypertensive therapy.


2016 ◽  
Vol 9 (5) ◽  
pp. 234
Author(s):  
Zahra Heidari ◽  
Zahra Sepehri ◽  
Aleme Doostdar

<p>In addition to known risk factors, the role of different micronutrients such as selenium in diabetes incidence has been proposed. Some previous studies have shown an association of selenium deficiency and type 2 diabetes mellitus, while other studies have not confirmed such a relationship. The aim of this study was to evaluate serum level of selenium in patients with Type 2 diabetes compared with the control group. This cross-sectional study was carried out on patients with type 2 diabetes in Zahedan, southeastern Iran. One hundred newly diagnosed type 2 diabetic patients were evaluated for serum selenium level. One hundred subjects from the general population who had normal fasting blood sugar levels were selected as the control group. The control group subjects were matched in pairs with each of patients on the basis of sex, age (± one year), and body mass index (±1). Serum level of selenium was determined by spectrometry method. Results were compared using t-test. The mean serum level of selenium in patients was 94.47±18.07 µg/L whereas in control group was 142.79±23.67 µg/L. The mean serum level of selenium was significantly different between the two groups (P&lt;0.001). Serum levels of selenium in diabetic patients with significant difference statistically were lower than the control group. In order to evaluate serum level of selenium in patients with diabetes, studies with larger sample size are required. Likewise, prospective studies along with selenium supplementation and investigating its effect on incidence of diabetes are accordingly needed.</p>


2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Lingfen Zeng ◽  
Jieming Sun ◽  
Ming Cui

Objective — To investigate whether serum lipoprotein(a) [Lp(a)] is an independent risk factor for abnormal blood pressure in patients with type 2 diabetes mellitus. Method — Analyzed data collected from diabetes patients and epidemiological survey from January 1,2020 to May 01,2021, with hypertension as a dependent variable, metabolic index such as glycosylated hemoglobin, serum total cholesterol, serum triglyceride and Lp(a) were independent variables, established logistic regression equation, analyze the influence of their variables on dependent variables. Results — The OR value of Lp(a) is 1.020, 95% confidence intervals (1.006, 1.035), p 0.006; The OR value of age is 1.073, 95% confidence interval (1.028, 1.119); and OR of the remaining parameters were tested no statistically different, p>0.05. Conclusions — The abnormal elevated Lp(a) level in the serum of type 2 diabetic patients may be related to the occurrence of hypertension. For patients with high Lp(a), Monitoring blood pressure may help to better detect and diagnose hypertension. At the same time, it is suggested that reducing serum Lp(a) level may reduce the risk of hypertension.


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