Impact of tofogliflozin on hepatic outcomes: a systematic review.

PURPOSE: Studies have demonstrated a high prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM) patients. The aim was to review the effect of tofogliflozin on hepatic outcomes in T2DM patients. METHODS: A literature search in PubMed, Science Direct and Cochrane Central Register of Controlled Trials was conducted for randomised clinical trials of tofogliflozin by applying predetermined inclusion and exclusion criteria. RESULTS: A total number of four randomised clinical trials, including 226 subjects, were included in the review. There was a significant decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in the tofogliflozin group as compared to the control or active comparator groups. Additionally, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and magnetic resonance imaging proton density fat fraction (MRI-PDFF) levels were also significantly decreased in the tofogliflozin group. However, no significant difference was observed in levels of adiponectin. CONCLUSION: Overall, an improvement in levels of hepatic parameters was observed in T2DM patients with concurrent liver disorders. However, a large number of clinical trials are needed to prove the efficacy of tofogliflozin on hepatic outcomes in patients with T2DM.

Metformin alone and in combination with sitagliptin induces depression and impairs quality of life in type 2 diabetes mellitus patients: An observational study.

BACKGROUND: Various studies have reported the association of cognition and depression with diabetes. Literature suggests that metformin and sitagliptin used to control hyperglycemia in type 2 diabetes mellitus (T2DM) possess a beneficial effect on neurological symptoms associated with diabetes. However, there are scarce data in the clinical setting. Thus, this study aims to compare depression, cognitive impairment, and quality of life (QoL) of newly diagnosed T2DM patients with those of healthy individuals. Further, the impact of metformin alone or in combination with dipeptidyl peptidase-4 inhibitors on cognition, depression, and QoL of T2DM patients was also compared with newly diagnosed T2DM patients. MATERIALS AND METHODS: This was a prospective observational study in 120 subjects. The subjects were equally divided into four groups: healthy controls, newly diagnosed T2DM patients, and T2DM patients taking either metformin alone or in combination with sitagliptin. We assessed cognition using Mini-Mental State Examinations (MMSE), depression using Hamilton Depression Rating Scale (HAM-D), and health status using Short-Form Health Survey-36 (SF-36). RESULTS: No significant change in MMSE score was observed among the groups. However, a significant increase in the HAM-D score of newly diagnosed patients (p < 0.001), T2DM patients receiving metformin alone (p < 0.05), and in combination with sitagliptin (p < 0.001) was observed as compared to healthy controls (p < 0.001). Also, a statistically significant increase in HAM-D score was observed in patients receiving sitagliptin in combination with metformin as compared to metformin alone (p < 0.01). A decrease in SF-36 scores was observed in all groups as compared to healthy controls. CONCLUSION: To conclude, this preliminary study indicates that T2DM patients are most likely to suffer from depression and impaired QoL. Moreover, both the conventional and recent antidiabetic agents might lead to neurobehavioral complications and adverse impact on the QoL of these patients. Thus, we warrant the assessment of cognitive functions, depression, and QoL in patients receiving metformin and sitagliptin.

Venous thromboembolism is linked to severity of disease in COVID-19 patients: A systematic literature review and exploratory meta-analysis.

PURPOSE: Coronavirus disease-2019 (COVID-19) may predispose to venous thromboembolism (VTE) and arterial thromboembolism because of excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. Thus, in this meta-analysis, we aim to assess the association of VTE with the severity of COVID-19 disease. METHODS: A literature search was conducted on PubMed and Cochrane Central Register of Controlled Trials using the keywords "COVID-19 and thromboembolism" and "COVID-19 and embolism," till 20 February 2021. Thirteen studies including 6648 COVID-19 patients were incorporated in this systematic review and exploratory meta-analysis. RESULTS: The analysis revealed nearly three times more risk than intensive care unit (ICU) care in patients with VTE compared to non-VTE patients (RR: 2.78; 95% CI: 1.75-4.39; P < .001; I2 : 65.1%). Patients with pulmonary embolism and deep vein thrombosis are at increased risk of being admitted to ICU (RR: 2.21; 95% CI: 1.86-2.61; P < .001; I2 : 41.2%) and (RR: 2.69; 95% CI: 2.37-3.06; P < .001; I2 : 0.0%), respectively. The quality assessment indicated that the included studies were of fair quality. CONCLUSIONS: Our findings suggest that VTE either deep vein thrombosis or pulmonary embolism may have a negative effect on the health status of COVID-19 patients. This study highlights the need to consider measures for reducing thromboembolism risk amongst COVID-19 patients.

Prevention of diabetes from prediabetes in real world setting in South India.

AIM: The aim was to explore the effect of lifestyle modification in a real world situation to prevent the progression to diabetes in India. METHODS: Participants who underwent OGTT from August 2017-2022 and were diagnosed as having Prediabetes (n = 200) were assigned into control (group1, n = 100) received standard care and intervention (group2, n = 100) received intensive counseling on physical activity (PA) and diet. PA included walking for 150 min/week and personalized advice based on the profession. OGTTs were repeated once every 6 months for 5 years and primary outcome was development of DM. RESULTS: The conversion rate was significantly higher in the control group than the intervention group (44.6 vs.7.9 %, p < 0.0001). Individuals who reverted back to normal was significantly higher in Group2 compared to Group1 (34.9 vs.6.2 %; p < 0.001). A significant increase in weight, BMI and waist circumference in group1 and significant reduction in glucose and HbA1c was noted in group2. Mean (95%CI) survival time for Group1 was 25.4 (20.8-29.9) and Group2 was 36.4months (32.6-40.1; p < 0.001). The factors which influenced the conversion of prediabetes to DM were averaged BMI, fasting and 2hr glucose levels of all follow up visit measurements. CONCLUSION: We can prevent diabetes in individuals with prediabetes using real world strategies in India.

Effect of ipragliflozin on liver enzymes in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

INTRODUCTION: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is estimated to affect upto 70-80% of people with type 2 diabetes mellitus (T2DM). Although several anti-hyperglycemic drugs have been shown to be effective in such patients, there remains an unmet need for newer drugs. The objective of this meta-analysis was to analyze the effect of ipragliflozin on aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) levels in patients with T2DM. METHODS: A literature search on electronic databases was conducted to identify potential randomized clinical trials (RCT) as per predetermined study selection criteria. Mean difference (MD) was calculated using Cochrane review manager. RESULTS: Twelve studies were included in the meta-analysis, including 1349 subjects. Compared to the control group, ipragliflozin as a monotherapy showed a significant reduction in levels of ALT at week 12 (p = 0.02) and at week 24 (p = 0.007), GGT at week 12 (p < 0.00001). Ipragliflozin as an add-on therapy showed significant reduction in levels of AST at week 24 (p < 0.00001), ALT at week 12 (p = 0.002), ALT at week 24 (p < 0.00001), and GGT at week 24 (p < 0.00001). CONCLUSION: Findings suggest the beneficial effects of ipragliflozin on liver enzymes. Further large-scale RCTs are required to confirm ipragliflozin's role for liver-related conditions in T2DM.

A systematic review on effect of sodium-glucose cotransporter-2 inhibitors on the metabolic and endocrinological profile of patients with polycystic ovarian syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) has been a common metabolic and endocrinal disorder, prevalent amongst women belonging to the reproductive age group. The aim of this systematic review was to assess the safety and efficacy profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors (Canagliflozin, Dapagliflozin, Empagliflozin, and Licogliflozin) for the treatment of women suffering from PCOS. METHODS: A literature search in PubMed, Science Direct, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov was conducted for randomized clinical trials of SGLT-2 inhibitors in PCOS patients by applying predetermined inclusion and exclusion criteria. The articles in English language were included. RESULTS: Four randomized controlled trials including 146 subjects were included in the review. The clinical studies indicated a significant decrease in the levels of total testosterone, free androgen index, total body fat, homeostasis model assessment-estimated insulin resistance (HOMA-IR), body mass index (BMI), dehydroepiandrosterone sulfate (DHEAS) and fasting plasma glucose (FPG). However, no significant difference was reported in levels of sex hormone-binding globulin (SHBG). Overall, there was improvement in metabolic and endocrine profiles, suggesting a potentially beneficial impact of SGLT2 inhibitors in the management of PCOS. CONCLUSION: There is a requirement for large extensive clinical trials to demonstrate the efficacy of SGLT-2 inhibitors in PCOS patients.

Longitudinal efficacy of Ertugliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

INTRODUCTION: Ertugliflozin, a sodium-glucose cotransporter-2 inhibitor, seems to improve glycemic control in type 2 diabetes mellitus (T2DM). We aim to evaluate the efficacy of Ertugliflozin across multiple time intervals (18, 26, and 52 weeks) in T2DM patients. METHODS: A literature search was conducted on electronic databases. Data was extracted from eligible studies at both 5 mg and 15 mg doses in monotherapy and as add-on therapy. Cochrane RevMan was used to perform the meta-analysis. RESULTS: Ertugliflozin, at both 5 mg and 15 mg doses, demonstrated a significant improvement in HbA1c levels at 18 weeks 5 mg [P = 0.00001], 15 mg [P = 0.05], and at 26 weeks in monotherapy 5 mg [P = 0.006], monotherapy 15 mg [P = 0.006], 5 mg as add-on therapy [P = 0.00001], 15 mg add-on therapy [P = 0.00001] respectively. At 52 weeks, the reduction in HbA1c was significant in 15 mg add-on therapy [P = 0.0001]. Additionally, ertugliflozin as an add-on therapy also led to a significant reduction in FPG, body weight, and systolic blood pressure. CONCLUSION: Ertugliflozin showed clinical efficacy in improving glycemic control, fasting plasma glucose, body weight, and systolic blood pressure in T2DM patients over the studied time intervals compared to placebo.

Vitamin D Deficiency and Comorbidities as Risk Factors of COVID-19 Infection: A Systematic Review and Meta-analysis.

OBJECTIVES: Extensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection. METHODS: We searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Significantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; p=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; p<0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; p=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally non-significant, associations with COVID-19 infection. CONCLUSIONS: Low serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.

Impact of cardiovascular diseases on severity of COVID-19 patients: A systematic review.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) cases are increasing rapidly worldwide. Similar to Middle East respiratory syndrome where cardiovascular diseases were present in nearly 30% of cases, the increased presence of cardiovascular comorbidities remains true for COVID-19 as well. The mechanism of this association remains unclear at this time. Therefore, we reviewed the available literature and tried to find the probable association between cardiovascular disease with disease severity and mortality in COVID-19 patients. METHODS: We searched Medline (via PubMed) and Cochrane Central Register of Controlled Trials for articles published until Sept 5, 2020. Nineteen articles were included involving 6,872 COVID-19 patients. RESULTS: The random-effect meta-analysis showed that cardiovascular disease was significantly associated with severity and mortality for COVID-19: odds ratio (OR) 2.89, 95% confidence interval (CI) 1.98-4.21 for severity and OR 3.00, 95% CI 1.67-5.39 for mortality, respectively. Risk of COVID-19 severity was higher in patients having diabetes, hypertension, chronic obstructive pulmonary disease, malignancy, cerebrovascular disease and chronic kidney disease. Similarly, patients with diabetes, hypertension, chronic liver disease, cerebrovascular disease and chronic kidney disease were at higher risk of mortality. CONCLUSION: Our findings showed that cardiovascular disease has a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid cardiovascular disease are urgently needed to understand the extent of these concerning comorbidities.

Hyperglucagonemia and impaired insulin sensitivity are associated with development of prediabetes and type 2 diabetes - A study from South India.

BACKGROUND AND AIMS: Glucagon levels and glucagon suppression in response to oral glucose load has not been elucidated at different stages of glucose intolerance in India. METHODS: A total of 81 subjects underwent OGTT and were classified into three groups as having normal glucose tolerance (NGT) (n = 23), prediabetes (PreDM) (n = 33), newly diagnosed diabetes (NDM) (n = 25). Insulin and glucagon at fasting, 30 and 120 min was measured by ELISA. HOMA-IR, measures of insulin sensitivity, early, late and overall glucagon suppression during OGTT was calculated. RESULTS: Plasma glucagon levels were higher at all-time points in the PreDM and NDM groups. Fasting glucagon levels were higher than post glucose load glucagon in all groups. There was a significant difference in the fasting(p = 0.001), 30 min(p = 0.004) and 120 min(p = 0.032) glucagon between the groups. HOMA-IR increased and insulin sensitivity decreased with worsening of glucose intolerance(p < 0.0001). The groups did not differ in terms of early glucagon suppression(p = 0.094). NDM group suppressed glucagon more than NGT from 30 to 120 min after glucose intake. CONCLUSION: This study demonstrated higher fasting glucagon levels. Prediabetes and newly diagnosed diabetes individuals had higher glucagon levels, high insulin resistance and lower insulin sensitivity. Hyperglucagonemia may contribute to type 2 diabetes.

Elevated urinary IL-36α and IL-18 levels are associated with diabetic nephropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Inflammatory cytokines have been reported to be pathogenic factors for the development and progression of diabetic nephropathy (DN). Interleukin (IL)-36α is a newly discovered member of the IL-1 cytokine family that has been implicated in animal models of renal impairment. However, little is known about the role of IL-36α in DN in humans. The purpose of the present study was to assess the levels of IL-36α and IL-18 in type 2 diabetic patients (T2DM) patients with and without DN. METHODS: Subjects were divided into 3 groups: Control (N.=20), T2DM without DN (N.=30), and T2DM with DN (N.=30). Urinary IL-36α and IL-18 levels were assessed using ELISA. Correlation analysis was performed to determine the association of the IL levels with clinical markers of T2DM and DN. RESULTS: IL-36α and IL-18 levels were significantly elevated in T2DM patients with DN, when compared to T2DM patients without DN (P<0.0001, P=0.0025, respectively) and controls (P<0.0001, for both). IL-36α levels showed a positive correlation with urinary albumin excretion (r=0.754, P<0.0001), HbA1c (r=0.433, P=0.0168), fasting plasma glucose (r=0.433, P=0.0168) and negative correlation with glomerular filtration rate (r=-0.852 P<0.0001). CONCLUSIONS: The results highlighted the association of IL-36α with DN. However, further extensive studies are suggested for evaluating the association.

TCF7L2 polymorphism a prominent marker among subjects with Type-2-Diabetes with a positive family history of diabetes.

The greatest risk of developing type2 diabetes (T2DM) was conferred by rs7903146 SNP of Transcription factor7-like2 (TCF7L2) gene in many ethnic populations. The aim was to investigate the association of TCF7L2 (rs7903146) gene polymorphism among newly diagnosed diabetes subjects with different parental diabetes registry. A total of 171 subjects were categorized into 3 groups based on parental diabetes registry i.e. Conjugal Diabetes Registry (CDR) (n = 50), One Parental Diabetes Registry (OPDR) (n = 56) and Non Parental Diabetes Registry (NPDR) (n = 62) (control group). Kompetitive allele specific PCR (KASP) genotyping assay was used in real time PCR for identifying the genotypes. None of the biochemical parameters showed any significant difference between groups except age at onset of diabetes (p = 0.001). The T allele of TCF7L2 (rs7903146) was associated with significant risk of diabetes. TT genotype which doubles the diabetes risk showed significant association among OPDR whereas in CDR both CT and TT genotypes showed significant association than CC wild type. The 'T' allele of TCF7L2 SNP was associated with significant risk when compared between OPDRvsNPDR (OR 2.45, p = 0.003) and CDRvsNPDR (OR 2.82, p = 0.0007). In conclusion, TCF7L2 gene polymorphism and positive family history of diabetes are strongly associated irrespective of the presence of other risk factors among diabetes subjects.

Association of diabetes and hypertension with disease severity in covid-19 patients: A systematic literature review and exploratory meta-analysis.

AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 COVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p = 0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p = 0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p<0.001; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p = 0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p = 0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.

Increased serum interleukin-9 and interleukin-1ß are associated with depression in type 2 diabetes patients.

BACKGROUND: Co-morbid diabetes and depression are prevalent chronic conditions negatively affecting quality of life (QoL). Inflammation has been considered as an integral mechanism in patients with both diabetes and depression. OBJECTIVE: The aim of the present study was to investigate depression and its association with interleukins (IL)-1ß and IL-9 in type 2 diabetic patients (T2DM) and controls. The QoL in diabetic patient was also assessed. METHODS: Eighty subjects were included, distributed among three groups: Group 1 - Healthy controls; Group 2 - T2DM patients without depression; Group 3 - T2DM patients with depression. Depression and QoL were assessed using Patient Health Questionnaire (PHQ-9) and The Audit of Diabetes-Dependent QoL (ADDQoL), respectively. IL-1ß and IL-9 were measured in serum samples of all the patients using ELISA kit. RESULTS: The PHQ score in the Group 3 was significantly higher as compared to Group 1. The ADDQoL scores in the Group 3 were significantly higher as compared to Group 2. Levels of IL-9 and IL-1ß were elevated in Group 3, as compared to the other groups. CONCLUSION: This study showed positive association between depression and IL-1ß, IL-9 in T2DM patients. Additionally, the diabetic patients have poorer quality of life, which is further worsened by the presence of depression. Thus, routine assessment for the presence of depression is suggested in T2DM patients.

Detection and Management of Pregnancy in Rudimentary Horn of Uterus.

Pregnancy in rudimentary horn is extremely rare and usually terminates in rupture during first and second trimester of pregnancy. Diagnosis of rudimentary horn pregnancy and its rupture is difficult and can be missed in routine ultrasound scan; and in majority of cases, it is detected after rupture. It requires high index of suspicion. We present a case report of a woman who was misdiagnosed as having missed miscarriage; and termination was attempted, which ended up in failure and rupture of rudimentary horn was the consequence followed by laparotomy. With advances in prenatal ultrasound in recent decades, it is prudent to detect such a life-threatening condition earlier resulting in a lower incidence of maternal morbidity and mortality.

Elevated one hour with normal fasting and 2 h plasma glucose helps to identify those at risk for development of Type2 Diabetes-11 years observational study from south India.

AIMS: To compare conversion rates of diabetes in subjects with elevated 1 h plasma glucose (1hrPG) during an OGTT with normal glucose tolerance(NGT) subjects over a period of 11 years. METHODS: 4023 subjects were selected from electronic data base of medical records.233 subjects who were followed up for a period of 11 years were included.160 with isolated prediabetes and their combinations were excluded.The remaining 73 were categorized into group1 NGT (n = 37) and group-2 (n = 36) with elevated 1hrPG.Kaplan Meier curves for incident diabetes and Cox proportional hazard model were compared between groups. RESULTS: During follow up, 10.8% and 44.4% converted to DM in group1 and group2 (p = 0.003). Elevated 1hrPG was associated with incident diabetes(HR 7.9[95%CI 2.2-28.1](p = 0.001)provided better risk assessment.The adjusted risk of event in subjects with elevated 1hrPG is likely to be 7 times more when compared to NGT.Subjects with elevated1hrPG remained free of diabetes for a median period of 7.6 years (95% CI 5.8-7.8) whereas NGT subjects remained free for 10 years (95% CI 8.5-10.0) (p < 0.001). CONCLUSION: In conclusion, conversion to DM was higher and risk was 7 times more in subjects with elevated 1hrPG. Elevated 1hrPG during OGTT has to be considered as a distinct entity.

Attenuated serum 25-hydroxyvitamin D and vitamin D binding protein associated with cognitive impairment in patients with type 2 diabetes.

PURPOSE: Clinical studies suggest that 25-hydroxyvitamin D (25[OH]D) deficiency plays a pivotal role in both type 2 diabetes mellitus (T2DM) and cognitive impairment. However, it is unclear if 25(OH)D deficiency could be a possible cause of cognitive impairment in T2DM. Vitamin-D binding protein (VDBP) acts as a major 25(OH)D transporter. Preclinical study has demonstrated improvement in cognitive function by VDBP via inhibiting synaptic degeneration. The aim of the study was to assess the association between serum 25(OH)D, VDBP and cognitive impairment in T2DM patients. PATIENTS AND METHODS: In this case-control study, cognitive function was assessed using the Mini-Mental State Examination (MMSE) and serum 25(OH)D and VDBP levels were estimated using ELISA kits. RESULTS: A total of 88 subjects were included in the study. T2DM patients had lower serum 25(OH)D (p=0.02), VDBP levels (p=0.04) and MMSE scores (p<0.0001) than controls. T2DM patients had higher prevalence of 25(OH)D deficiency and insufficiency, aOR 0.322 (0.128-0.809), p=0.016 and cognitive impairment, aOR 4.405 (1.617-12.002); p=0.004. Cognitive impairment was associated with serum 25(OH)D, aOR 0.131 (0.027-0.638); p=0.014 and VDBP, aOR 1.008 (1.001-1.015), p=0.029. A general linear model showed a significant association of MMSE with serum 25(OH)D (p=0.022). CONCLUSION: Serum 25(OH)D deficiency and cognitive impairment was higher in T2DM patients. Routine assessment of cognitive function is suggested to prevent further behavioral complications. The association of VDBP and cognitive impairment in T2DM needs further exploration.

Factors Influencing Participation Of Healthy Volunteers In Clinical Trials: Findings From A Cross-Sectional Study In Delhi, North India.

PURPOSE: To identify the specific motivations that drive healthy volunteers to consent for their participation in clinical studies. Additionally, the study aimed to document the socio-demographic determinants of participation in the trial related solely to the intention of securing financial gains. PATIENTS AND METHODS: This cross-sectional study was conducted among subjects who participated as healthy volunteers in clinical trials conducted by Contract Research Organizations (CROs) of Delhi. Pre-tested, validated semi-structured questionnaires were used to collect baseline socio-demographic data, information about factors motivating participation in clinical trials, and pattern of utilisation of money received against participation in the trial. Logistic regression analysis was done to determine the factors that influenced participation in the trial related purely to the motive of securing financial gains. RESULTS: A total of 400 participants were selected. The majority of the volunteers (77.5%) reported that their sole reason for participating in clinical trials was for monetary gain. Around a tenth of the volunteers participated with the intent to advance scientific knowledge and another 4.5% participated due to benefits of free medical check-ups. Participants in the age group of 29-38 years, those that were married, those residing in an urban slum, male participants, those with a high number of dependent family members (ie, 5 to 8), and those earning less than 5000 INR (71 USD) a month had higher odds of participating in a clinical trial purely for the financial benefits. Those educated till intermediate and above had lower odds of participation in the trial due to monetary benefits. CONCLUSION: Our study shows that healthy volunteers in Delhi consider participation in clinical trials mainly because of the prospect of financial reward. More research is needed to inform judgments around the ethics of providing financial rewards and enrollment of healthy research volunteers.

Study of Awareness and Practice of Informed Consent Process Among Clinical Trial Participants and Their Motives Behind Participation.

Process to obtain informed consent is an essential component in research involving human subjects. However, much is not known about the level of awareness participants have about optimal consenting process and the motives that drive their participation in the trials. A cross-sectional study was conducted among volunteers who had been participating in clinical trials in contract research organizations of Delhi. Validated questionnaires were used to assess their knowledge, attitude, and practice of informed consent process. Most of the volunteers, 226 (56.5%), had participated in 1 to 3 clinical trials. Majority (54%) were unaware about any informed consent document. None of them were aware of their right of profession competence, privacy and integrity, transparency, nonexploitation, and nonusage of their biological samples. Effective implementation of principles of informed consenting is largely lacking among contract research organizations in Delhi, India. This could potentially cause risk to the participants.

Efficacy and safety of canagliflozin in type 2 diabetes mellitus: systematic review of randomized controlled trials.

BACKGROUND: Currently available antihyperglycemic agents (AHAs), despite being effective, do not provide adequate glycemic control in some cases and are associated with side effects. A sodium glucose co-transporter 2 inhibitor, canagliflozin, is a newer AHA, which acts by decreasing the reabsorption of filtered glucose thereby elevating the urinary glucose excretion in diabetics. AREAS COVERED: This systematic review was completed to assess the clinical effectiveness and safety of canagliflozin in T2DM. A literature search in PubMed, MEDLINE, Cochrane and ClinicalTrials.gov was conducted for randomized clinical trials of canagliflozin as an AHA by applying predetermined inclusion and exclusion criteria. Total 13 studies were included in the systematic review. The main outcomes assessed were change in HbA1c and fasting plasma glucose. EXPERT OPINION: Canagliflozin monotherapy or combination therapy has the potential to decrease inadequately controlled hyperglycemia in T2DM. It acts by a novel insulin independent mechanism which complements the action of the existing AHA and improves glycemic control and decreases the body weight. Safety profile of canagliflozin indicates lower number of hypoglycemic episodes. Some manageable adverse events include genital mycotic infections, urinary tract infections, osmotic diuresis-related events etc. These findings affirm the utility of canagliflozin in T2DM; however, data on long-term safety and efficacy are needed.