Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure: A meta-analysis of randomized placebo-controlled outcome trials.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D. METHODS: Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death. RESULTS: In total, 54 092 patients with T2D from seven randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared with placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history: HR 0.96, 95% CI: 0.84-1.08, but reduced this outcome in patients without HF history: HR 0.84, 95% CI: 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history: HR 0.98, 95% CI: 0.86-1.11, but reduced mortality in patients without HF history: HR 0.85, 95% CI: 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history: HR 0.85, 95% CI: 0.75-0.97 with HF, and HR 0.88, 95% CI: 0.83-0.93 without HF. CONCLUSIONS: Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status.

Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.

AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta-analysis of placebo-controlled randomized trials.

Our aim was to study the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random-effects meta-analysis of placebo-controlled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP-1 RA. During follow-up, 673 participants receiving GLP-1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP-1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70-0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP-1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP-1 RA for reducing the cardiovascular risk of these patients.

Influence of diabetes on response to ultrasound guided hydrodistension treatment of adhesive capsulitis: a retrospective study.

BACKGROUND: Diabetes is associated with microvascular and macrovascular complications. Although it is less recognized, diabetes also has an important role in the development of musculoskeletal disorders. Our objective was to evaluate the effect of type 2 diabetes (T2D) on the severity of adhesive capsulitis of the shoulder (AC) and on the efficacy of ultrasound guided hydrodistension treatment. METHODS: We conducted a retrospective longitudinal observational study, of patients with AC who underwent ultrasound guided hydrodistension at our Centre. Severity was measured with DASH (Disabilities of Arm, Shoulder and Hand) score and pain was evaluated with a score between 0 and 10. The association of T2D with baseline characteristics of AC, and with outcomes at 6-12 months was analyzed using linear and logistic regression models. RESULTS: We evaluated 120 ultrasound guided hydrodistension treatments of AC, 85 in patients without diabetes and 35 in patients with T2D. Patients with diabetes had a higher prevalence of dyslipidemia, hypertension and higher HbA1c values. The average duration of diabetes was 4.8 years (2.0, 7.9). The baseline characteristics of AC were not significantly different between patients with and without diabetes. Patients with T2D relapsed more frequently and required more reinterventions than patients without diabetes (20.0% vs 4.7%, p = 0.008), had higher post-intervention pain scale values [4.0 (0.0-5.0) vs 0.0 (0.0-5.0), p = 0.022] and higher post-intervention DASH score [0.8 (0.0-1.8) vs 0.0 (0.0-0.8), p = 0.038]. CONCLUSION: Although baseline characteristics of AC in patients with diabetes were similar to those without diabetes, patients with diabetes had a worse response to treatment, more frequent relapses and a greater need for new interventions.

Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: A meta-analysis of randomized clinical trials.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function. MATERIALS AND METHODS: Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p < 0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p < 0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p < 0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p < 0.0.1). CONCLUSIONS: Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.

Breastfeeding Associated with Lower Prevalence of Metabolic Syndrome in Women with Gestational Diabetes in the Very Early Postpartum Period.

OBJECTIVE: The aim of this study is to examine the association of breastfeeding with metabolic syndrome (MetS) in women with recent gestational diabetes mellitus (GDM) in the very early postpartum (PP) period. STUDY DESIGN: We performed a secondary analysis of the Balance After Baby Intervention (BABI) study which enrolled women with recent GDM. Data collected during an early (∼8 weeks) PP visit were used in this analysis. At this visit, weight, height, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), and lipids were obtained. MetS was classified per National Cholesterol Education Program Adult Treatment Program III (NCEP-ATP III) criteria. We defined breastfeeding as currently breastfeeding or not currently breastfeeding for the main analysis. RESULTS: Of 181 women enrolled in BABI, 178 were included in this analysis (3 excluded for missing lipids). Thirty-four percent were Hispanic. Of non-Hispanics, 31.5% were White, 18.5% Asian, and 12.9% Black/African American. The prevalence of MetS was 42.9% in women not breastfeeding versus 17.1% in women breastfeeding (p < 0.001; adjusted odds ratio [aOR] = 0.16 [95% confidence interval (CI): 0.06-0.41]). Breastfeeding women had significantly lower odds of FPG ≥100 mg/dL (aOR = 0.36 [95% CI: 0.14-0.95], p = 0.039), HDL < 50 mg/dL (aOR = 0.19 [95% CI: 0.08-0.46], p < 0.001), and triglycerides (TG) ≥ 150 mg/dL (aOR = 0.26 [95% CI: 0.10-0.66], p = 0.005). When evaluated as continuous variables, WC, FPG, and TG were significantly lower and HDL significantly higher in women breastfeeding in the very early PP period (vs. not breastfeeding). CONCLUSION: In a diverse population of women with recent GDM, there was lower prevalence of MetS in women breastfeeding compared with those not breastfeeding in the very early PP period. This study extends the findings of an association of breastfeeding with MetS previously reported at time points more remote from pregnancy to the very early PP period and to an ethnically and racially diverse population. KEY POINTS: · MetS prevalence in women with recent GDM was lower in breastfeeding than not breastfeeding women.. · FPG, HDL, WC, and TG were improved in the breastfeeding group.. · This study extends prior findings to the very early PP period and to a diverse population..

Intensive Blood Pressure Treatment Reduced Stroke Risk in Patients With Albuminuria in the SPRINT Trial.

Background and Purpose- Albuminuria is associated with stroke risk among individuals with diabetes. However, the association of albuminuria with incident stroke among nondiabetic patients is less clear. Methods- We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial), which examined the effect of higher versus lower intensity blood pressure management on mortality in 8913 participants without diabetes. We fit unadjusted and adjusted Cox proportional hazards models to estimate the association of baseline albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g versus<30 mg/g) with stroke risk. We also assessed effect modification according to treatment arms. Results- Mean age was 68±9 years, 35% were female, and 30% were black. Median follow-up was 3.2 years, and 19% patients had baseline albuminuria. Incident stroke occurred in 129 individuals during follow-up. Albuminuria was associated with increased stroke risk (unadjusted hazard ratio, 2.24; 95% CI, 1.55-3.23; adjusted hazard ratio 1.73; 95% CI, 1.17-2.56). The association of albuminuria with incident stroke differed according to the randomized treatment arm (P interaction=0.03). In the intensive treatment arm, the association of albuminuria and stroke was nonsignificant (unadjusted hazard ratio, 1.25; 95% CI, 0.69-2.28), whereas, in the standard treatment arm, it was significant (unadjusted hazard ratio, 3.44; 95% CI, 2.11-5.61). Conclusions- In a post hoc analysis of SPRINT, baseline albuminuria (versus not) was associated with a higher risk of incident stroke, but this relationship appeared to be restricted to those in the standard treatment arm. Further studies are required to conclusively determine if reduction of albuminuria in itself is beneficial in reducing stroke risk. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Long-term diabetes outcomes after bariatric surgery-managing medication withdrawl.

BACKGROUND/OBJECTIVES: Bariatric surgery leads to type 2 diabetes mellitus (T2DM) remission, but recurrence can ensue afterwards. However, literature provides heterogenous remission/recurrence criteria and there is no consensus on long-term T2DM management after surgery. We aim to assess T2DM remission/recurrence rates using standardized criteria and to identify relapse predictors. We also intend to analyze the management of residual T2DM and the impact of maintaining/withdrawing metformin in avoiding future relapse. SUBJECTS/METHODS: We investigated a cohort of 110 obese patients with T2DM who underwent bariatric surgery and were followed for 5 years (Y0-Y5). Patients who ever attained remission were accounted for cumulate remission, while prevalent remission was considered for individuals who were on remission in a specific visit. RESULTS: A complete prevalent remission of 47.3% was reached at Y1 and it remained stable till Y5 (46.4-48.2%). Complete cumulative rate was of 57.3% at Y5. Five-year T2DM recurrence rate was 15.9% and it was associated with higher pre-operative HbA1c levels (ß = 1.06; p < 0.05) and a milder excess body weight loss (EBWL) (ß = 0.49; p < 0.05). Glucose-lowering agents were fully stopped in 51.4% of the patients till Y1 and in 16.2% of them afterwards. Medication withdrawal was mainly attempted in patients with a lower baseline HbA1c (ß = 0.54; p < 0.01) and higher first-year EBWL (ß = 1.04; p < 0.01). Patients that kept metformin after reaching a HbA1c in the complete remission range (<6.0%) did not have greater odds of avoiding relapse in the next visit (OR = 0.33; p = 0.08). CONCLUSIONS: Baseline HbA1c and EBWL were the main variables driving both T2DM relapse after bariatric surgery and the attempt to withdrawal anti-diabetic medication. In our population keeping metformin once an HbA1c < 6.0% is achieved did not seem to diminish relapse but further studies on this matter are needed.

Preoperative thyroid function and weight loss after bariatric surgery.

Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded. The preoperative levels of TSH and FT4 were not associated with weight loss after bariatric surgery. The variation of FT3 within the reference range was also not associated with weight loss. In contrast, the subgroup with FT3 above the reference range (12.3% of patients) had a significantly higher excess weight loss than patients with normal FT3. This difference remained significant after adjustment for age, sex, BMI, type of surgery, TSH and FT4. In conclusion, we observed an association between high FT3 and a greater weight loss after bariatric surgery, highlighting a group of patients with an increased benefit from this intervention. Our results also suggest a novel hypothesis: the pharmacological modulation of thyroid function may be a potential therapeutic target in patients undergoing bariatric surgery.

Caffeine consumption and mortality in chronic kidney disease: a nationally representative analysis.

BACKGROUND: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains uncertain. METHODS: We analysed 4863 non-institutionalized USA adults with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a nationwide study using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was evaluated by 24-h dietary recalls at baseline and all-cause, cardiovascular and cancer mortality were evaluated until 31 December 2011. We also performed an analysis of caffeine consumption according to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption were <28.2 mg/day (Q1), 28.2-103.0 (Q2), 103.01-213.5 (Q3) and >213.5 (Q4). RESULTS: During a median follow-up of 60 months, 1283 participants died. Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all-cause mortality was 0.74 [95% confidence interval (CI) 0.60-0.91] for Q2, 0.74 (95% CI 0.62-0.89) for Q3 and 0.78 (95% CI 0.62-0.98) for Q4 (P = 0.02 for trend across quartiles). There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. CONCLUSIONS: We detected an inverse association between caffeine consumption and all-cause mortality among participants with CKD.

The Role of Thyroid Hormones in Heart Failure.

Cardiovascular diseases are the leading cause of death worldwide. Heart failure is the terminal manifestation of cardiovascular diseases, and its morbidity and mortality remain high. The prevalence of heart failure with preserved ejection fraction (HFpEF) among heart failure patients remains uncertain. However, recent studies have found that it ranged from 40 to 71%. There is still no effective treatment for HFpEF. Thyroid hormones (TH) have central regulatory actions in the cardiovascular system, particularly in the heart. Changes in plasmatic or tissue thyroid hormone levels are associated with significant alterations in cardiovascular function. A significant proportion of patients with heart failure presents some form of thyroid dysfunction including hypothyroidism, hyperthyroidism, and low T3 syndrome. Furthermore, thyroid hormones can vary at a local level independently of the serum TH levels. This may lead to local cardiac hypothyroidism in heart failure. Based on these findings and the role that TH play in cardiovascular regulation, they were proposed as a potential target for heart failure therapy. Several clinical and experimental studies have shown beneficial effects of TH supplementation. Data from epidemiological studies supports a higher risk of heart failure and a worse prognosis in heart failure patients with low levels of TH. In addition, animal studies and small clinical studies suggest that TH supplementation may improve cardiac function in heart failure. Although further studies are needed to evaluate the safety and efficacy of TH in this context, the available evidence suggests that TH modulation is a promising therapeutic approach to heart failure.

Can Adiponectin Help us to Target Diastolic Dysfunction?

Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates with body weight and obesity-linked cardiovascular complications. Diastolic dysfunction is the main mechanism responsible for approximately half of all heart failure cases, the so-called heart failure with preserved ejection fraction (HFpEF), but therapeutic strategies specifically directed towards these patients are still lacking. In the last years, a link between adiponectin and diastolic dysfunction has been suggested. There are several mechanisms through which adiponectin may prevent most of the pathophysiologic mechanisms underlying diastolic dysfunction and HFpEF, including the prevention of myocardial hypertrophy, cardiac fibrosis, nitrative and oxidative stress, atherosclerosis and inflammation, while promoting angiogenesis. Thus, understanding the mechanisms underlying adiponectin-mediated improvement of diastolic function has become an exciting field of research, making adiponectin a promising therapeutic target. In this review, we explore the relevance of adiponectin signaling for the prevention of diastolic dysfunction and identify prospective therapeutic targets aiming at the treatment of this clinical condition.