Association of Single Nucleotide Polymorphism in OCT1 and OCT3 Genes with the Efficacy of Metformin Response in North Indian Type 2 Diabetes Mellitus Patients

In type 2 diabetes mellitus (T2DM) patients, metformin, the drug of choice, exhibits variable therapeutic response attributed to gene polymorphism. The current study aimed to investigate the association of MATE2 rs12943590, OCT2 rs7757336, and ATM rs11212617, which are hotspot single-nucleotide polymorphisms (SNPs), with metformin efficacy and glycemic control in T2DM patients. A total of 417 study subjects were enrolled, consisting of 217 newly diagnosed and drug-naive T2DM patients, while 200 individuals were healthy controls. Patients were further divided into two subgroups: metformin responsive and metformin-non-responsive individuals. Study patients were kept on exclusive metformin monotherapy for three successive months. Patients' basic parameters like age, fasting glucose, HbA1c, LDL, HDL, Cholesterol, and BMI were recorded. Real-time PCR involving melt curve analysis and subsequent agarose gel electrophoresis with Sanger sequencing was employed for genotype analysis. MATE2 (SLC47A2) rs12943590 GA genotype (OR 0.44, CI 95% 0.23-0.86, p = 0.01), OCT2 (SLC22A2) rs7757336 GG genotype (OR 5.82, 95% CI 1.40-24.24, p = 0.01), and G allele (OR 2.21, CI 95% 1.18-4.14, p = 0.01) were significantly associated with metformin response and glucose-lowering effect. No significant association (p > 0.05) was observed for ATM rs11212617.

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with and without nephropathy

High sensitivity C-reactive protein (Hs-CRP) is a sensitive marker of subclinical inflammation associated with atherosclerosis. Uncontrolled diabetes mellitus (DM) is one of the important risk factors of coronary heart disease (CHD). The aim of this study was to evaluate the association between Hs-CRP levels and both glycaemic control and CHD in Syrian type 2 diabetes mellitus (T2DM) patients. A random sample of 108 subjects was selected from T2DM and/or CHD patients seen in the National Centre for Diabetes, and the outpatient clinic of cardiology department at Tishreen University Hospital in Latakia. Four groups were formed: Group 1 [T2DM (+) CHD (-), N=29], Group 2 [T2DM (-) CHD (+), N=25], Group 3 [T2DM (+) CHD (+), N=29], and Group 4 (T2DM (-) CHD (-), N=25). Serum Hs-CRP and glycated haemoglobin (HBA1C) were determined. The SPSS 25.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Mean Hs-CRP level was higher in T2DM subjects with (5.23±1.56mg/l) or without (2.29±0.78mg/l) CHD compared to T2DM (-) CHD (-) patients (0.16±0.04mg/l), (p&lt;0.0001 for both). Mean Hs-CRP level in T2DM with CHD was not only higher than T2DM patients without CHD (p&lt;0.0001), but also than non-diabetic subjects with CHD (2.56±0.45mg/l) (p&lt;0.0001). There was a positive correlation between serum Hs-CRP and HBA1C in T2DM patients with CHD (r=0.781, P&lt;0.0001), Similarly, Hs-CRP levels were positively and significantly correlated with HBA1C in T2DM patients without CHD (r=0.800, p&lt;0.0001). We also noticed that for every 1.0% increase in HbA1c there was an 77% increase in the likelihood of having an elevated Hs-CRP. We concluded that Hs-CRP was strongly correlated with glycaemic control in T2DM patients. The highest Hs-CRP level was observed in T2DM with CHD patients. Hs-CRP could predict the incidence of coronary heart disease in T2DM patients.

Background:Metformin is one of the most commonly used drugs for the treatment of type 2 diabetes mellitus (T2DM). Despite its widespread use, there are considerable interindividual variations in metformin response, with about 35% of patients failing to achieve initial glycemic control. These variabilities that reflect phenotypic differences in drug disposition and action may indeed be due to polymorphisms in genes that regulate pharmacokinetics and pharmacodynamics of metformin. Moreover, interethnic differences in drug responses in some cases correspond to substantial differences in the frequencies of the associated pharmacogenomics risk allele.Aim:This study aims to highlight and summarize the overall effects of organic cation transporter 1(OCT1) polymorphisms on therapeutic responses to metformin and to evaluate the potential role of such polymorphisms in interethnic differences in metformin therapy.Methods:We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched for PubMed/MEDLINE, Embase, and CINAHL, relevant studies reporting the effects of OCT1 polymorphisms on metformin therapy in T2DM individuals. Data were extracted on study design, population characteristics, relevant polymorphisms, measure of genetic association, and outcomes. The presence of gastrointestinal side effects, glycated hemoglobin A1 (HbA1c) levels, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) concentrations after treatment with metformin were chosen as measures of the metformin responses. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO).Results:According to the data extracted, a total of 34 OCT1 polymorphisms were identified in 10 ethnic groups. Significant differences in the frequencies of common alleles were observed among these groups. Met408Val (rs628031) variant was the most extensively explored with metformin responses. Although some genotypes and alleles have been associated with deleterious effects on metformin response, others indeed, exhibited positive effects.Conclusion:Genetic effects of OCT1 polymorphisms on metformin responses were population specific. Further investigations in other populations are required to set ethnicity-specific reference for metformin responses and to obtain a solid basis to design personalized therapeutic approaches for T2DM treatment.

BackgroundCoronary artery disease (CAD) confers considerable morbidity and mortality in diabetes. However, the role of CAD in additive effect of left ventricular (LV) function has rarely been explored in type 2 diabetes mellitus (T2DM) patients. This study aimed to investigate how CAD affect LV systolic and diastolic function in T2DM patients.Materials and methodsA total of 282 T2DM patients {104 patients with CAD [T2DM (CAD +)] and 178 without [T2DM (CAD −)]} and 83 sex- and age- matched healthy controls underwent cardiac magnetic resonance scanning. LV structure, function, global strains [including systolic peak strain (PS), peak systolic (PSSR) and diastolic strain rate (PDSR) in radial, circumferential and longitudinal directions] and late gadolinium enhancement (LGE) parameters were measured. T2DM (CAD +) patients were divided into two subgroups based on the median of Gensini score (60) which was calculated to assess the severity of CAD. Multivariable linear regression analyses were constructed to investigate the determinants of reduced LV function.ResultsCompared with normal controls, T2DM (CAD −) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV global strains, while T2DM(CAD +) patients showed more marked increase and decrease than T2DM(CAD-) and healthy controls, except for longitudinal PDSR (PDSR-L) (all P < 0.017). All of LV global strains demonstrated a progressive decrease from normal controls, through Gensini score ≤ 60, to Gensini score > 60 group, except for PDSR-L (all P < 0.017). CAD was an independent predictor of reduced LV global circumferential PS (GCPS, β = 0.22, p < 0.001), PSSR (PSSR-C, β = 0.17, p = 0.005), PDSR (PDSR-C, β = 0.22, p < 0.001), global radial PS (GRPS, β = 0.19, p = 0.001), and global longitudinal PS (GLPS, β = 0.18, p = 0.003) in T2DM. The Gensini score was associated with decreased GCPS, PSSR-C, PDSR-C, GRPS, and GLPS in T2DM (CAD +) (all p < 0.05).ConclusionCAD has an additive deleterious effect on LV systolic and diastolic function in T2DM patients. Among T2DM (CAD +) patients, the Gensini score is associated with reduced LV contractile and diastolic function.Trial registration Retrospectively registered

Type 2 diabetes mellitus (T2DM) is a chronic disease that affects millions of people worldwide. Metformin is the optimal initial therapy for patients with T2DM. Genetic factors play a vital role in metformin response, including variations in drug efficacy and potential side effects. To determine the effects of genetic variants of multidrug and toxin extrusion protein 2 (MATE2), ataxia telangiectasia mutated (ATM), and serine/threonine kinase 11 (STK11) genes on metformin response in a cohort of Saudi patients. This prospective observational study included 76 T2DM newly diagnosed Saudi patients treated with metformin monotherapy and 80 control individuals. Demographic data, lipid profiles, creatinine levels, and hemoglobin A1c (HbA1c) levels were collected before and after treatment. All participants were genotyped for 5 single-nucleotide polymorphisms (SNPs), including rs4621031, rs34399035, rs2301759, rs1800058, and rs11212617, using TaqMan R genotyping assays. This study included 156 subjects. The subjects’ mean ± SD age was 50.4 ± 10.14 years. The difference in HbA1c levels in T2DM after treatment ranged from −1.20% to 8.8%, with a mean value of 0.927 ± 1.73%. In general, 73.7% of the patients with T2DM showed an adequate response to metformin (HbA1c < 7%). STK11 (rs2301759) significantly affects the response to metformin in T2DM patients. In the rs2301759 single-nucleotide polymorphisms, the prevalence of an adequate response to metformin was significantly higher among patients with C/C and T/C genotypes than among non-responders (P = .021). However, no statistically significant associations were observed for the other tested SNPs. Our study provides evidence of an association between STK11 (rs2301759) and response to metformin in Saudi patients with T2DM. The need for targeted studies on specific gene-drug associations is emphasized, and further studies with a larger population should be conducted.

AimsInsulin resistance (IR) is a pivotal factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Nevertheless, the impact of IR on cognitive dysfunction in T2DM patients with NAFLD remains inadequately understood. We aim to investigate the effect of IR on mild cognitive impairment (MCI) in T2DM individuals with NAFLD.Materials and methods143 T2DM individuals were categorized into Non-MCI and MCI groups, as well as Non-NAFLD and NAFLD groups. Clinical parameters and cognitive preference test outcomes were compared. Correlation and regression analyses were executed to explore the interconnections between IR and cognitive details across all T2DM patients, as well as within the subgroup of individuals with NAFLD.ResultsIn comparison to the Non-MCI group, the MCI group displayed elevated HOMA-IR levels. Similarly, the NAFLD group exhibited higher HOMA-IR levels compared to the Non-NAFLD group. Additionally, a higher prevalence of MCI was observed in the NAFLD group as opposed to the Non-NAFLD group. Notably, HOMA-IR levels were correlated with Verbal Fluency Test (VFT) and Trail Making Test-B (TMTB) scores, both related to executive functions. Elevated HOMA-IR emerged as a risk factor for MCI in the all patients. Intriguingly, increased HOMA-IR not only correlated with TMTB scores but also demonstrated an influence on TMTA scores, reflecting information processing speed function in patients with NAFLD.ConclusionIR emerges as a contributory factor to cognitive dysfunction in T2DM patients. Furthermore, it appears to underlie impaired executive function and information processing speed function in T2DM individuals with NAFLD.

Response to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic cation transporter 1 (OCT1) (SLC22A1 rs628031), OCT2 (SLC22A2 rs316019), multidrug and toxin extrusion protein 1 (MATE1) (SLC47A1 rs2289669), and MATE2 (SLC47A2 rs12943590) on the variation in metformin response. The glucose-lowering effects and improvement of insulin resistance of metformin were assessed in newly diagnosed, treatment-naive type 2 diabetic patients of Han nationality in Chaoshan China (n = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1C), homeostasis model assessment-insulin sensitivity (HOMA-IS), and homeostasis model assessment-insulin resistance (HOMA-IR) were the main metformin efficacy measurements. There were significant correlations between both SLC47A1 rs2289669 and SLC47A2 rs12943590 and the efficacy of metformin in individuals with T2DM. In normal weight T2DM patients, significant associations between the AA and GG genotypes of the rs2289669 variant of SLC47A1 and a greater reduction in FINS and HOMA-IR were detected. A significant correlation was observed between the AG genotype of the rs12943590 polymorphism of SLC47A2 and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-SLC47A2 rs12943590 was statistically significant. The variants of SLC47A1 rs2289669 and SLC47A2 rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-SLC47A2 rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of SLC47A1 and SLC47A2 are important determinants of metformin transport and response in type 2 diabetes mellitus.

Many studies have explored the risk factors associated with cognitive impairment in patients with Type 2 diabetes mellitus (T2DM). However, research on determining the optimal threshold for these risk factors and comparative studies on the therapeutic effects of insulin and metformin is limited. This study aims to establish the optimal threshold for cognitive impairment risk factors in T2DM patients and compare the efficacy of insulin and metformin in treating mild cognitive impairment (MCI). A total of 308 patients with T2DM were included. The optimal threshold for cognitive impairment risk factors was determined using receiver operating characteristic curve and binary logistic regression models. MCI patients were divided into three groups: insulin, metformin, and insulin with metformin. The treatment effect was evaluated after a 6-month follow-up. The study identified several factors that influenced cognitive function in T2DM patients, including female gender, duration of diabetes >13.50 years, years of education >7.50 years, and serum sodium level > 141.90 mmol/L. Metformin and insulin with metformin showed superior therapeutic effects compared to insulin alone, but no difference was observed between metformin and combination therapy. Special attention should be given to female and those with diabetes duration >13.50 years, as well as to individuals with educational level ≤ 7.50 years and serum sodium concentration ≤ 141.90 mmol/L. Metformin and insulin with metformin effectively improve MCI in patients with T2DM and outperform insulin monotherapy. The efficacy of metformin and combination therapy was found to be comparable.

Emerging evidence suggested widespread decreased gray matter volume (GMV) and tau hyperphosphorylation were associated with type 2 diabetes mellitus (T2DM). Insulin resistance is one of the mechanisms of neuron degeneration in T2DM; it can decrease the activity of protein kinase B and increase the activity of glycogen synthesis kinase-3β, thus promoting the hyperphosphorylation of tau protein and finally leading to neuronal degeneration. However, the association between GMV and serum tau protein phosphorylated at threonine 181 (P-tau-181) in T2DM patients lacks neuroimaging evidence. We aimed to investigate the difference in brain GMV between T2DM patients with different glycated hemoglobin A1c (HbA1c) levels and healthy control (HC) subjects and the correlation between serum P-tau-181 and GMV in T2DM patients. Clinical parameters, biochemical indicators, and MRI data were collected for 41 T2DM patients with high glycosylated hemoglobin level (HGL), 17 T2DM patients with normal glycosylated hemoglobin level (NGL), and 42 HC subjects. Voxel-based morphometry (VBM) method was applied to investigate GMV differences among groups, and multiple regression analysis was used to examine the correlation between serum P-tau-181 and GMV. Compared with HC subjects, the T2DM patients with HGL or NGL all showed significantly decreased GMV. Briefly, the GMV decreased in T2DM patients with HGL was mainly in the bilateral parahippocampal gyrus (PHG), right middle temporal gyrus (MTG), temporal pole (TPOmid), hippocampus (HIP), and left lingual gyrus. The GMV reduction in T2DM patients with NGL was in the right superior temporal gyrus (STG), and there was no significant difference in GMV between the two diabetic groups. The GMV values of bilateral PHG, right MTG, TPOmid, HIP, and STG can significantly (p < 0.0001) distinguish T2DM patients from HC subjects in ROC curve analysis. In addition, we found that serum P-tau-181 levels were positively correlated with GMV in the right superior and middle occipital gyrus and cuneus, and negatively correlated with GMV in the right inferior temporal gyrus in T2DM patients. Our study shows that GMV atrophy can be used as a potential biological indicator of T2DM and also emphasizes the important role of P-tau-181 in diabetic brain injury, providing new insights into the neuropathological mechanism of diabetic encephalopathy.

Significant links between low serum levels of vitamin D3 and insufficient glycemic control in patients with type 2 diabetes mellitus (T2DM) have been reported previously in the literature. However, there is no exciting evidence on the association between glycated hemoglobin (HbA1c) and vitamin D levels in T2DM individuals in our nation (Yemen). This study aimed to investigate the relationship between HbA1c and vitamin D levels in T2DM patients in a resource-limited setting. A retrospective cross-sectional study was conducted at the Al-Raffa Center, Ibb, Yemen between June 2018 and September 2023 including 396 patients diagnosed with T2DM. The patient characteristics, comorbidities, HbA1c, and vitamin D levels were gathered from patients' medical profiles. Linear regression analysis was used to find the factors associated with vitamin D deficiency (serum 25(OH)D levels < 20 ng/mL) among T2DM patients. Subsequently, the correlation between HbA1c and vitamin D levels was examined using receiver operating characteristic (ROC) curve analysis. The mean age was 44.6 ±14.6 years and most of them (n= 227, 57.3%) were female and from a rural area (n= 229, 57.8%). Comorbidities were hypertension, dyslipidemia disease, and cardiovascular disease in 176 (44.4%), 63 (15.9%), and 88 (22.2%) cases, respectively. The mean HbA1c was 8.1 ±2.5%. The mean vitamin D level was 26.9 ±16.5 ng/mL and low vitamin D was present in 260 (65.7%) (vitamin D deficiency in 160 (40.4%) and vitamin D insufficiency in 100 (25.3%) cases). In regression analysis, obesity (>30 kg/m2) (odds ratio (OR): 299.49; 95% confidence interval (CI):72.66 - 1234.42, p <0.0001), higher HbA1c levels (OR: 1.61; 95% CI:1.26 - 2.05, p =0.0001), and urban residence (OR: 23.98; 95% CI:5.62 - 102.42, p <0.0001) were associated with vitamin D deficiency. There was a negative correlation between the vitamin D level and HbA1c which was statistically significant (correlation coefficient r: -0.5452; 95% CI: -0.6109 to -0.4720, p <0.0001). Using the ROC analysis, the serum vitamin D value of ≤18.42 ng/ml was the best cut-off point to predict hyperglycemia (area under the curve: 0.633, 95% CI: 0.672 to 0.770, sensitivity: 52%, specificity: 84.71 %, Yoden's index: 0.3671, p <0.001). Based on this cut-off, 39.4% of individuals (37.5% in the normoglycemic group and 90.9% in the hyperglycemic group) were vitamin D deficient. In this study, low vitamin D was common among T2DM patients, especially those with poor glycemic control. We observed a link between HbA1c levels, urban residency, and BMI with vitamin D deficiency in T2DM patients. The association was distinguished by low vitamin D levels and elevated HbA1c. Additionally, we found that the serum vitamin D value of ≤18.42 ng/ml was the best cut-off point to predict hyperglycemia in T2DM patients with moderate agreement. To manage their disease, patients with T2DM should take their medications as prescribed and live a healthy lifestyle. This will increase their overall health, especially their vitamin D levels.

Introduction Uncontrolled blood pressure and poor glycaemic control may lead to increased morbidity and mortality (1). A systematic review of 40 studies reported beneficial effects of interventions conducted in community pharmacies in the management of diabetes and cardiovascular diseases (2). Aim To evaluate the impact of a tailored intervention on clinical outcomes in the management of hypertensive and/or type 2 diabetes mellitus (T2DM) patients in community pharmacies in a pilot implementation study. Methods The study (April to July 2019) utilized a mixed-method design. This included a cross-sectional survey among 133 consented community pharmacists and 390 T2DM and/or hypertensive patients at the pharmacies. Thirty-one item (pharmacists) and 29-item (patients) semi-structured questionnaires were used to gather information on their perception of pharmacists’ roles in the management of T2DM and/or hypertension. Barriers to implement identified roles by the pharmacists were documented. Thereafter, a prospective before- and after-intervention study was conducted in four consented pharmacies to address the barriers. Two pharmacists per pharmacy and 34 consented T2DM and/or hypertensive adult patients who had been on medications for ≥3 months participated. Pharmacists were provided with 2-hr one-on-one training on the management of T2DM and hypertension based on standard guidelines pre-intervention and at 4 weeks. Components of the pharmacist’s intervention included patient’s education, medication counselling , lifestyle modifications and self-care use of point of care devices. Systolic and diastolic blood pressure (SBP and DBP), fasting blood glucose (FBG) and body mass index (BMI) of all patients were measured at baseline, 4- and 8-week post-intervention. Weekly patient follow-up visits to the pharmacies were mandatory. Telephone calls and referral were incorporated, when necessary. Failure to show up for two consecutive visits disqualified patients from completing the study. Descriptive statistics (to summarise data), and paired t-test to compare mean differences in the measured parameters at α=0.05. Results Hypertensive and/or T2DM patients (374) and 71 pharmacists participated in the survey. The patients expected pharmacists to provide medication counselling (81;27.1%), education (47;12.6%), follow-up (18;4.8%), health outcomes monitoring (17;4.5%), and collaboration with physicians (12;3.2%). Sixty-nine (97.2%) pharmacists agreed that patients’ follow-up, patient counselling (71;100.0%), therapeutic plan design to achieve goals (67;94.4%) and collaboration with physicians (61;85.9%) were important. Barriers to providing adequate counsel to these patients were time constraints (23;32.4%), unconducive environment (7;9.9%) and patient’s impatience (33;46.5%). For the intervention component, 16 of the 34 patients enrolled were lost to follow-up (one hospitalized, seven failed two consecutive visits, and eight lost to referral). Effects of the tailored intervention on the parameters are in Table 1. Conclusion The patients’ and pharmacists’ perceived roles of the pharmacist in the management of hypertension and T2DM were in tandem. The 8-week tailored pharmacists’ intervention resulted in better control of blood pressure but increased FBG. This pilot study is limited by the small sample size of patients and pharmacists, as well as the lack of appropriate comparator. Future large-scale multi-site study with relevant comparator is required for a far-reaching conclusion on the impact of the tailored pharmacist intervention in the management of diabetes and hypertension.

Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM). A systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis. A total of 30 related eligible studies about OCT genes (SLC22A1, SLC22A2, and SLC22A3) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in SLC22A1, SLC22A2, and SLC22A3, respectively, were investigated. Meta-analysis showed that the SLC22A1 rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = -0.45 [-0.73--0.18]; p = 0.001). The GG genotype of the SLC22A1 rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = -0.60 [-1.04-0.16], p = 0.007; GG vs. AG: -0.45 [-0.67-0.20], p < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance. SLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.