Type 2 Diabetes Mellitus Outcomes Research Articles

Association of Longitudinal Activity Measures and Diabetes Risk: An Analysis From the National Institutes of Health All of Us Research Program.

Prior studies of the relationship between physical activity and incident type 2 diabetes mellitus (T2DM) relied primarily on questionnaires at a single time point. We sought to investigate the relationship between physical activity and incident T2DM with an innovative approach using data from commercial wearable devices linked to electronic health records in a real-world population. Using All of Us participants' accelerometer data from their personal Fitbit devices, we used a time-varying Cox proportional hazards models with repeated measures of physical activity for the outcome of incident T2DM. We evaluated for effect modification with age, sex, body mass index (BMI), and sedentary time using multiplicative interaction terms. From 5677 participants in the All of Us Research Program (median age 51 years; 74% female; 89% White), there were 97 (2%) cases of incident T2DM over a median follow-up period of 3.8 years between 2010 to 2021. In models adjusted for age, sex, and race, the hazard of incident diabetes was reduced by 44% (95% CI, 15%-63%; P = 0.01) when comparing those with an average daily step count of 10 700 to those with 6000. Similar benefits were seen comparing groups based on average duration of various intensities of activity (eg, lightly active, fairly active, very active). There was no evidence for effect modification by age, sex, BMI, or sedentary time. Greater time in any type of physical activity intensity was associated with lower risk of T2DM irrespective of age, sex, BMI, or sedentary time.

Role of Ertugliflozin in the Management of Diabetes Mellitus.

The novel oral sodium-glucose cotransporter-2 (SGLT2) inhibitor Ertugliflozin (SteglatroTM) is introduced as a monotherapy or in conjunction with another antidiabetic drug regimen for the treatment of type 2 diabetes mellitus (T2DM).Additional safe and efficient treatment options for patients and physicians are of utmost importance as the incidence of T2DM rises. As a standalone therapy or an adjunctive treatment, ertugliflozin seems to be a reliable and safe option.This narrative review seeks to report and analyze ertugliflozin's effectiveness, safety, cardiovascular (CV), and renal outcomes in T2DM. Various combinations of drugs and drug classes have been tried to reduce mortality and comorbidities associated with the use of antidiabetic agents, especially cardiogenic events and renal diseases. With the administration of hypoglycemic drugs like ertugliflozin and the regulation of blood sugar levels, the incidence of therapy-induced hypertension, obesity, and dose-related hypoglycemia has been reduced to a significant extent. Additionally, ertugliflozin prevents hypertension caused by prolonged antidiabetic drug intake, which is advantageous for lowering the chances of end-stage cardiac events in type 2 diabetic patients. As far as the renal safety profile of ertugliflozin is concerned, it has been associated with the maintenance of eGFR (estimated glomerular filtration rate) and a decreased UACR (urine albumin-to-creatinine ratio) in patients with T2DM and coronary artery disease, which reduces the incidence of renal adverse effects due to long-term medication. As a result of common pathophysiological mechanisms, SGLT2 inhibitors represent a feasible therapeutic option and are advantageous for patients with type 1 and type 2 DM in terms of cardiovascular and renal outcomes.

Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease

Chronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately-one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparative effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with diagnosed incident CKD, CKD hospitalization, and eGFR < 45 mL/min in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors was significantly associated with lower risk of diagnosed CKD incidence in both primary analysis (hazard ratio, 0.43; 95 % CI, [0.22;0.87]; p-value,0.02) and secondary analysis (hazard ratio, 0.42; 95 % CI, [0.19;0.92]; p-value, 0.03) compared to use of Sulfonylureas (SU) as a second-line ADM. However, significant associations were not observed when using eGFR < 45 mL/min as the endpoint. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower risk of diagnosed incident CKD (hazard ratio, 0.7; 95 % CI, [0.53;0.96]; p-value, 0.03) and lower risk of CKD hospitalization (hazard ratio, 0.6; 95 % CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of glucagon-like peptide 1 receptor agonists (GLP-1RA), Thiazolidinediones (TZD), insulin and diagnosed CKD incidence, hospitalization or eGFR < 45 mL/min compared to use of SU as a second-line ADM.

The gender gap in prescription pattern of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes

Abstract Background The major benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) on cardiovascular outcome has been undoubtably proven in several landmark trials and different populations. In consideration of emerging evidence that there are clinically relevant gender-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is gender independent utilized in clinical practice. In this regard, real-world data are needed to determine whether there is a gender gap in SGLT2i prescription and if this influences long-term outcome. Methods Patients with T2DM admitted to a tertiary academic center between 01/2014 and 04/2020 were identified through a search of electronic health records. Data on antidiabetic therapy was acquired at discharge, and were screened for SGLT2i prescription. Subsequently, the entire cohort was prospectively followed. Results In total, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In direct comparison between sexes, females show lower rates of SGLT2i prescription (11,2% vs. 19,8%, p=0.003), despite comparable patient characteristics. Furthermore, males show a significantly higher probability of SGLT2i prescription, illustrated as an adjusted odds ratio of 2.59 (CI 95% 1.29–5.19; p=0.008). During a median follow-up time of 2.3 years, a total of 142 patients died due to cardiovascular causes – corresponding to 103 (18.0%) male and 39 (16.2%) female participants. Females who did not receive a SGLT2i showed higher rates of chronic kidney disease (CKD, 25.2% vs. 7.4%, p=0.039) and greater levels of proBNP (2092 pg/ml (IQR: 738–5279) vs. 825 pg/ml (IQR: 298–2479), p=0.011) as compared to non-SGLT2i females. Conclusion Despite clear evidence on the beneficial effect of SGLT2i, the present data suggest a gender-gap in SGLT2i prescription and thus missed potential in female patients. The most common reason for not prescribing a SGLT2i in females was the presence of CKD. However, SGLT2i (i.e. Empagliflozin) are approved to use in individuals with a glomerular filtration rate (GFR) as low as ≥20ml/min, and therefore more awareness has to be raised, that SGLT2i are feasible to prescribe in such vulnerable patients with present cardiovascular comorbidities, to achieve a benefit as shown in several landmark trials. Additionally, more attention is needed to address this gender-gap and ensure that both sexes receive equal attention, in terms of state of the art T2DM therapy to reduce mortality and morbidity. Funding Acknowledgement Type of funding sources: None.

Illness perceptions and diabetes self-care behaviours in Māori and New Zealand Europeans with type 2 diabetes mellitus: a cross-sectional study.

This study investigated differences in illness perceptions and self-care behaviours between Māori and New Zealand (NZ) Europeans with type 2 diabetes mellitus (T2DM), and how these perceptions were related to clinical outcomes. Participants were 85 Māori and 85 NZ European adults, recruited from outpatient clinics, who completed a cross-sectional questionnaire on illness perceptions and self-care behaviours. Clinical data, including HbA1c, retinopathy, neuropathy and nephropathy, were collected from medical records. Compared to NZ Europeans, Māori had higher HbA1c, lower adherence to medication and a healthy diet, and were more likely to smoke. Māori reported greater perceived consequences of diabetes on their lives, and more severe symptoms than NZ Europeans did. Māori were more likely to attribute T2DM to food and drink, whereas NZ Europeans were more likely to attribute T2DM to weight. Perceiving that treatment could help control diabetes was associated with lower HbA1c and higher medication adherence in Māori and NZ Europeans independently. Māori experienced and perceived worse T2DM outcomes than NZ Europeans did. Research is needed to develop and test clinical interventions to address these inequities and improve outcomes, possibly by asking patients about their perceptions, providing tailored and culturally appropriate education, and discussing patients' concerns.

Cytokines, Chemokines, Insulin and Haematological Indices in Type 2 Diabetic Male Sprague Dawley Rats Infected with Trichinella zimbabwensis

Diabetes mellitus is a chronic metabolic disease induced by the inability to control high blood glucose level. Helminth-induced immunomodulation has been reported to prevent or delay the onset of type 2 diabetes mellitus (T2DM), which, in turn, ameliorates insulin sensitivity. Therefore, there is a need to understand the underlying mechanisms utilized by helminths in metabolism and the induction of immuno-inflammatory responses during helminthic infection and T2DM comorbidity. This study aimed at using a laboratory animal model to determine the cytokines, chemokines and haematological indices in diabetic (T2DM) male Sprague Dawley (SD) rats infected with Trichinella zimbabwensis. One hundred and two male SD rats (160–180 g) were randomly selected into three experimental groups (i. T2DM-induced group (D) ii. T. zimbabwensis infected + T2DM group (TzD) and iii. T. zimbabwensis-infected group (Tz)). Rats selected for the D group and TzD group were injected with 40 mg/kg live weight of streptozotocin (STZ) intraperitoneally to induce T2DM, while animals in the Tz and TzD group were infected with T. zimbabwensis. Results showed that adult T. zimbabwensis worm loads and mean T. zimbabwensis larvae per gram (lpg) of rat muscle were significantly higher (p &lt; 0.001) in the Tz group when compared to the TzD group. Blood glucose levels in the D group were significantly higher (p &lt; 0.001) compared to the TzD group. An increase in insulin concentration was observed among the TzD group when compared to the D group. Liver and muscle glycogen decreased in the D when compared to the TzD group. A significant increase (p &lt; 0.05) in red blood cells (RBCs) was observed in the D group when compared to the TzD and Tz groups. An increase in haematocrit, haemoglobin, white blood cells (WBCs), platelet, neutrophils and monocyte were observed in the D group when compared to the TzD group. TNF-α, IFN-γ, IL-4, IL-10 and IL-13 concentrations were elevated in the TzD group when compared to the D and Tz groups, while IL-6 concentration showed a significant reduction in the Tz when compared to the D and the TzD groups. A significant increase in CCL5 in the D and TzD groups was observed in comparison to the Tz group. CXCL10 and CCL11 concentration also showed an increase in the TzD group in comparison to the Tz and the D groups. Overall, our results confirm that T. zimbabwensis, a parasite which produces tissue-dwelling larvae in the host, regulates T2DM driven inflammation to mediate a positive protective effect against T2DM outcomes.

Features of the course of type 2 diabetes mellitus in young people

The increase in the prevalence of type 2 diabetes mellitus (T2DM) worldwide in young people determines the high relevance in studying the course of this disease. There are difficulties in awareness of this pathology in young people, both in specialists and in patients due to the fact that the long-term outcomes of T2DM in young people are poorly understood. This leads to late diagnosis of diabetes and longer exposure to hyperglycemia leads to high risks of microand macrovascular complications. Clinical symptoms of T2DM with a debut at a young age are different in patients, so this disease is not always diagnosed on time. T2DM in young people (18–45 years) has a more aggressive course, the decrease in the level of β-cells occurs faster than in patients with late-onset T2DM. The risk of developing complications in T2DM with onset at a young age is higher than in late-onset diabetes, mainly due to the longer duration of the disease. With a duration of T2DM in young people of 13.3 ± 1.8 years it was shown that the incidence of nephropathy, neuropathy and retinopathy was 54.8%, 32.4% and 13.7%, respectively. According to the literature, in patients with T2DM at a young age, life expectancy is reduced by 14 and 16 years in males and females, respectively. The course of T2DM is more aggressive in relation to young patients than to middle-aged and elderly patients. T2DM with a debut at a young age is a socially significant disease, due to a decrease in the quality of life, the development of diabetic complications and early disability of the working population.

91-OR: Association between Complexity of Glucose Time Series and All-Cause Mortality in Patients with Type 2 Diabetes Mellitus: A Prospective Cohort study

Background: Continuous glucose monitoring (CGM) can comprehensively reflect the dynamic changes of blood glucose varying with time. CGM data with more patterns of change represents glucose time series with higher complexity. However, the relationship between complexity of glucose dynamics and clinical outcomes of diabetes remains unknown. Objective: To investigate the association between complexity of glucose time series, quantified by multiscale entropy (MSE) analysis, and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) in a prospective cohort study. Methods: Data of 6,001 adult inpatients with T2DM included from January 2005 to December 2015 in a single center was analyzed. Complexity of glucose index (CGI) of glucose time series from CGM was measured by MSE analysis at baseline. Participants were stratified by the tertiles of CGI: &amp;lt; 2.15,2.15∼2.99, and ≥ 3.00. Cox proportional hazards regression models were used to estimate the association between different levels of CGI and the risks of all-cause mortality. Results: During a median follow-up of 6.8 years, 799 deaths were identified. Multivariate Cox regression analysis revealed that the increase of CGI was associated with a lower risk of all-cause mortality (P for trend = 0.021) . The multivariable-adjusted HRs for all-cause mortality at different CGI levels [&amp;lt; 2.15 (reference group) , 2.15∼2.99, and ≥ 3.00] were 1.00, 0.49 (95%CI 0.30-0.79) , and 0.56 (95%CI 0.36-0.87) in patients with HbA1c &amp;lt; 7.0% (P for trend = 0.015) , while the association was nonsignificant in those with HbA1c ≥ 7.0%. And a significant interaction between HbA1c and CGI (P for interaction = 0.032) was noted in the study. Conclusion: Lower CGI is associated with an increased risk of all-cause mortality in T2DM achieving HbA1c target, which suggests that the improvement of CGI may further reduce the risk of long-term adverse outcomes in T2DM at an early stage or with good glycemic control. Disclosure J.Cai: None. J.Lu: None. Y.Shen: None. W.Lu: None. W.Zhu: None. J.Zhou: None. Funding The Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20161430)

The Effect of Bread Consumption on Glycemic Control – A Systematic Review and Meta-Analysis of Intervention Studies

ObjectivesBread is a main carbohydrate sources in most diets and may hence be relevant for several health outcomes. This systematic review evaluated the effect of bread consumption on glycemic control in adults with and without type 2 diabetes mellitus (T2DM). MethodsA systematic literature search was performed in September 2020 using Medline, Embase, Web of Science and the Cochrane Library. Eligible studies had to employ different types of bread in adults with or without T2DM and report glycemic outcomes (primary outcome: mean difference (MD) in fasting blood glucose between intervention and control groups; secondary outcomes: MD in fasting insulin, HOMA-IR, and glycated hemoglobin (HbA1c)). Data were pooled using generic inverse-variance with random effects model and presented as mean MD between treatments with 95% confidence intervals (95% CIs). ResultsTwenty-one studies met the inclusion criteria, providing data on 966 participants. Compared to control breads, the consumption of the intervention breads resulted in lower values of fasting blood glucose (MD –0.21 mmol/L, 95% CI –0.39 to –0.03, I2 = 89%), yet no differences in fasting insulin (MD –1.60 pmol/L, 95% CI –6.10 to 2.91, I2 = 42%), HOMA-IR (MD –0.08, 95% CI –0.39 to 0.23, I2 = 63%) or HbA1c (MD –0.12%, 95% CI –0.40 to 0.17, I2 = 60%). The included studies showed a great degree of heterogeneity. ConclusionsThe type of bread influences fasting blood glucose in adults with and without T2DM. This argues for a mechanistic role of bread quality in metabolic health and calls for its consideration in future health policies. Funding SourcesThe project has received funding from the German and Norwegian Research Council under the umbrella of European Joint programming Initiative “A healthy diet for a health life” (JPI-HDHL) and of the ERA-NET Cofund HDHL INTIMIC (GA N 727,565 of the EU Horizon 2020 Research and Innovation Programme).

Cross-Sectional Associations: Social Risks and Diabetes Care Quality, Outcomes

Social risks (e.g., food/transportation insecurity) can hamper type 2 diabetes mellitus (T2DM) self-management, leading to poor outcomes. To determine the extent to which high-quality care can overcome social risks' health impacts, this study assessed the associations between reported social risks, receipt of guideline-based T2DM care, and T2DM outcomes when care is up to date among community health center patients. A cross-sectional study of adults aged ≥18 years (N=73,484) seen at 186 community health centers, with T2DM and ≥1 year of observation between July 2016 and February 2020. Measures of T2DM care included up-to-date HbA1c, microalbuminuria, low-density lipoprotein screening, and foot examination, and active statin prescription when indicated. Measures of T2DM outcomes among patients with up-to-date care included blood pressure, HbA1c, and low-density lipoprotein control on or within 6‒12 months of an index encounter. Analyses were conducted in 2021. Individuals reporting transportation or housing insecurity were less likely to have up-to-date low-density lipoprotein screening; no other associations were seen between social risks and clinical care quality. Among individuals with up-to-date care, food insecurity was associated with lower adjusted rates of controlled HbA1c (79% vs 75%, p<0.001), and transportation insecurity was associated with lower rates of controlled HbA1c (79% vs 74%, p=0.005), blood pressure (74% vs 72%, p=0.025), and low-density lipoprotein (61% vs 57%, p=0.009) than among those with no reported need. Community health center patients received similar care regardless of the presence of social risks. However, even among those up to date on care, social risks were associated with worse T2DM control. Future research should identify strategies for improving HbA1c control for individuals with social risks. This study is registered at www. gov NCT03607617.

Fibroblast Growth Factor 21 Levels Exhibit the Association With Renal Outcomes in Subjects With Type 2 Diabetes Mellitus.

BackgroundWhether microalbuminuria predicts renal outcomes in patients with type 2 diabetes mellitus (T2DM) is argued. Fibroblast growth factor 21 (FGF-21) levels were elevated by the pathogenic process of diabetic kidney disease. The purpose of the study was to evaluate the associations of FGF-21 and renal outcomes in subjects with T2DM.MethodsChinese patients with T2DM were enrolled and then observed prospectively, and FGF-21 levels at baseline were measured. The associations of FGF-21 levels and renal composite events, defined by a drop > 30% of eGFR or worsening category of albuminuria, were evaluated using Cox analysis. The appropriate cut-off value of FGF-21 was mapped by the receiver operating characteristic (ROC) curve.ResultsAmong 312 subjects, higher FGF-21 levels were associated with higher risks of renal events in Cox analysis. The area under the curve of FGF-21 levels in the ROC curve was optimal (0.67, p < 0.001), and the cut-off value of 1.40 pg/dl exhibited the best sensitivity (76.2%) and specificity (53.5%). The frequency of renal composite events was higher in subjects with FGF-21 ≥ 1.40 pg/dl than in others (30% vs. 10%, p<0.001 by the log-rank test). The worse renal outcomes predicted by FGF-21 ≥ 1.40 pg/dl were confirmed using the adjustments of Cox sequential models (hazard ratio 2.28, 95% confidence interval 1.23–4.24, p=0.009) and consistent across subjects with different status of baseline characteristics and renal risks.ConclusionFGF-21 levels were proportional to the risks of renal events in broad- spectrum Chinese T2DM subjects, making it a potential biomarker to predict the renal outcomes of T2DM.

UNDERSTANDING PERCEIVED BARRIERS AND FACILITATORS TO ENGAGING IN CARE FOR KNEE OSTEOARTHRITIS IN PERSONS WITH TYPE 2 DIABETES MELLITUS: A QUALITATIVE STUDY USING THE THEORETICAL DOMAINS FRAMEWORK

Purpose: Symptomatic knee osteoarthritis (OA) frequently co-occurs in individuals with type 2 diabetes mellitus (T2DM) and may lead to worse T2DM outcomes, yet it remains undertreated. Studies suggest health care providers often assign OA a lower priority relative to other chronic conditions like T2DM, but there is no published literature on barriers and facilitators to OA care from the perspectives of persons living with T2DM. With view to developing an intervention to improve both diagnosis and treatment of knee OA in persons with T2DM, we sought to understand the perceived barriers and enablers to the behaviour of seeking and engaging in knee OA care in persons with T2DM.

Equity impact of participatory learning and action community mobilisation and mHealth interventions to prevent and control type 2 diabetes and intermediate hyperglycaemia in rural Bangladesh: analysis of a cluster randomised controlled trial

BackgroundA cluster randomised trial of mHealth and participatory learning and action (PLA) community mobilisation interventions showed that PLA significantly reduced the prevalence of intermediate hyperglycaemia and type 2 diabetes mellitus...

Social networks, perceived social support, and HbA1c in individuals with type 2 diabetes mellitus in urban Ghana

ABSTRACT Objectives: Although links between social relationships and health are well established, few studies have concurrently examined the effects of compositional, structural, and functional dimensions of social networks on glycemic (HbA1c) control in low- and middle-income countries such as Ghana. In these settings where informal social relationships are critical for access to resources, evaluating the links between social network characteristics, social support, and glycemic control may provide clarity about important relationships that facilitate the well-being of individuals with type 2 diabetes mellitus (T2DM). Design: In 2018, we conducted a hospital-based, cross-sectional survey of noninstitutionalized adults with T2DM in Ghana. Using data from 247 study participants, multivariable linear regression models were used to estimate associations between: 1) HbA1c and three social network characteristics (kin composition, household composition, and network density); 2) social support and the three social network characteristics; and 3) HbA1c and social support. We also examined gender differences in these associations and applied mediation techniques to determine if network characteristics operated through social support to affect HbA1c. Results: Findings indicated that higher kin composition and higher household composition were each significantly associated with increased social support. Neither social support nor social network characteristics were significantly related to HbA1c, and there were no gender differences in any of these associations. Conclusion: Although family and household members were identified as important sources of social support for diabetes management, the ways in which they influence HbA1c control among Ghanaians require further investigation. Future studies can examine whether changes in social support over time, social support satisfaction, or other dimensions of social relationships improve T2DM outcomes in countries like Ghana.

Kidney function assessment and endpoint ascertainment in clinical trials

Heterogeneity in the reporting of kidney function, kidney outcomes, and definitions for kidney endpoints in clinical trials makes it challenging to compare results and gauge incremental benefit of interventions across trials. We conducted a systematic review of the ascertainment of baseline kidney variables, reporting of kidney endpoints, and definitions used to characterize these endpoints in type 2 diabetes mellitus (T2DM), kidney, and heart failure (HF) trials. Medline, Scopus, and ClinicalTrials.gov were searched from January 2014 through January 2021 for large (>1000 participants) T2DM, HF, and kidney disease trials and their secondary analyses. Trial publication and supplementary appendices were searched to abstract relevant data. Thirty-three trials (16 T2DM; 10 HF; 7 kidney diseases) were included. Thirteen trials did not include patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and for trials that did, representation of this cohort ranged from 0.1% to 15%. Reporting of baseline kidney function and albuminuria remained low, especially in HF trials. Variability was observed in the definition of chronic kidney disease, sustained decline in eGFR, end-stage kidney disease, kidney death, and kidney composite endpoint across trials. eGFR slope was reported in less than half trials, with differences observed in statistical models, definition of acute or chronic slope, and follow-up duration across trials. Significant heterogeneity in reporting of kidney function and kidney outcomes in large T2DM, kidney, and HF trials underscores the need for future stakeholders to draft a consensus solution. Detailed profiling of patients at baseline, accrual of more patients with advanced kidney disease, and standardization of definitions in trials may improve the ability to compare the results across trials.

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence.

Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved.

Comparison of effects of SGLT-2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus patients with/without albuminuria: A systematic review and network meta-analysis

AimsIt remains unclear which sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are most effective for preventing cardiovascular and renal events in type 2 diabetes mellitus (T2DM) patients, depending on the presence of albuminuria. We conducted a network meta-analysis to compare the efficacy of these two drug classes in T2DM patients with/without albuminuria. MethodsWe searched the Medline, EMBASE, Cochrane Library databases, and gray literature up to April 20, 2021. We included randomized controlled trials that reported the risk of major adverse cardiovascular events (MACE) and composite of renal outcomes in T2DM. ResultsA total of nine studies (81,206 patients) were included. In patients with/without albuminuria, SGLT-2 inhibitors did not significantly reduce the risk of MACE compared with GLP-1 RAs (risk ratio [RR] [95% confidence interval]; 0.96 [0.82–1.12] and 0.94 [0.81–1.10], respectively). In contrast, compared with GLP-1 RAs, SGLT-2 inhibitors were associated with significantly lower renal risk in both patients with/without albuminuria (RR [95% CI]; 0.75 [0.63–0.89] and 0.59 [0.44–0.79], respectively). ConclusionsSGLT-2 inhibitors may be superior to GLP-1 RAs for renal outcomes in T2DM patients with/without albuminuria, although there was no difference in the risk of MACE.

Analysis of Use and Outcomes of the Balance Digital Disease Management Tool for Patients with Type 2 Diabetes.

Management of type 2 diabetes mellitus (T2DM) is a serious medical need for millions of patients and clinicians worldwide. Numerous smartphone apps for T2DM management are available. Due to their global accessibility, computing power and cellular connectivity, the pervasiveness of mobile phones now provide an opportunity for non-invasive Digital Therapeutics that have the potential to manage disease by modifying patient behavior as new modality for disease management and intervention. However, this novel approach has yet to be tested in large clinical studies. The BALANCE clinical study was designed to evaluate mobile phone App usage in a large multi-center clinical trial and its impact on T2DM outcomes. It included a digital aid for the management of, blood glucose, diet, physical activity, and medication adherence. Overall, patient use of the BALANCE-App was low (21% of significant patients users), and it diminished over time. BALANCE showed no effect on HbA1c or weight, what is consistent with other smartphone apps for T2DM which were tested on large clinical trials. Nevertheless, post-hoc subgroup analysis showed women using the App significantly achieved a significant reduction in HbA1c and weight.Clinical relevance Suitability of Digital Therapeutics, at least in the form of smartphone apps, for T2DM is under question. The low use indicates need for a strong focus in patient acceptability and patient engagement in the design process.

Cardiovascular Benefit of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors in Type 2 Diabetes: A Systematic Review.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide yet, despite advances in treatment, CVD remains an underestimated and undermanaged condition, with an even greater risk in Type 2 Diabetes Mellitus (T2DM). Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are a promising novel drug class reported to improve Cardiovascular (CV) and renal outcomes in T2DM. Recent large-scale trials have assessed their CV safety with unexpected findings of multiple systemic benefits that could potentially reverse CVD. In this systematic review, we examined ten Randomized Controlled Trials (RCTs) that looked at cardiovascular outcomes in Type 2 diabetics and SGLT-2i. The RCTs were appropriately screened, looking for clear primary or secondary outcomes on CV events, and compared with placebo or other antidiabetic drugs. The RCTs had an average sample population studied of 5,549 participants with a mean follow-up time of 2.66 years. Three of the studies focused on CV parameters and risk factors. The remaining had defined CV composite events, and all consistently observed at least one CV benefit when using SGLT-2i. Our review of SGLT-2i in Type 2 diabetics showed the greatest benefit in reducing Heart Failure (HF) exacerbation and modest lowering of CV complications in high CV risk participants. Overall, there is still uncertainty about the exact mechanisms of SGLT-2i in their CV benefit, and whether they would favor pre-diabetic populations and those at earlier stages of CVD.

O-5 PROGNOSTIC IMPORTANCE OF TRANSIENT ELASTOGRAPHY (FIBROSCAN®) FOR MORTALITY AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES

It remains unknown whether advanced liver fibrosis is associated with a higher risk of cardiovascular complications in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).The aim was to evaluate the prognostic value of transient elastography (TE) by Fibroscan® as a predictor of mortality and cardiovascular outcomes in T2DM. On a prospective study, T2DM patients with no other cause of liver disease except NAFLD underwent TE at baseline and were followed-up for the evaluation of outcomes, including all-cause mortality and occurrence of any cardiovascular event. The associations between TE scores and outcomes were evaluated by Cox regressions adjusted for other potential confounders. Liver stiffness measurement (LSM) and Controlled attenuation parameter (CAP) were evaluated as continuous variables and categorized as advanced fibrosis if LSM >7.9 or 7.2 kPa (M-XL probe) and severe steatosis if CAP>296 dB/m. 403 T2DM patients were included (64% female, mean age of 64±10 yrs) and followed for 94 months until March 2020. 395(98%) of the TE examinations were successful. At baseline, 104(26%) individuals had advanced fibrosis and 150(38%) had severe steatosis. During follow-up, 55(14%) patients died, 55(14%) had cardiovascular events, including 35 with coronary artery disease (CAD). As continuous variables, LSM (↑1 kPa) predicted all-cause mortality (HR 1.05, 95%CI 1.01-1.08,p=0.020) and CAP (↑20 dB/m) was associated with a significant reduced risk of cardiovascular mortality (HR 0.80,95%CI 0.66-0.96,p=0.014) and CAD (HR 0.81,95%CI 0.70-0.95,p=0.007). Increased LSM was associated with a significant 98% excess mortality risk (p=0.025), whereas a higher CAP was associated with a borderline 49% reduced risk (p=0.08). Advanced fibrosis is associated with all-cause mortality, independent of other potential risk factors. Severe steatosis could have some effect in the reduction of cardiovascular mortality and CAD events. Transient elastography may be useful to improve stratification risk of T2DM patients.