scholarly journals Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Denis A. Lebedev ◽  
Elena A. Lyasnikova ◽  
Elena Yu. Vasilyeva ◽  
Nikolai P. Likhonosov ◽  
Maria Yu. Sitnikova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Type I ◽  
Procollagen Type ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

scholarly journals Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
D. A. Lebedev ◽  
E. A. Lyasnikova ◽  
E. Yu Vasilyeva ◽  
A. Yu Babenko ◽  
E. V. Shlyakhto
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Clinical Manifestations ◽  
Type I ◽  
Procollagen Type ◽  
Galectin 3

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05 ). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF ( p = 0.01 and p = 0.03 , respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF ( p = 0.043 and p = 0.033 , respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area ( r = − 0.58 , p = 0.001 ), PIIINP, TIMP-1, and LV end-diastolic volume ( r = − 0.68 and p = 0.042 and r = 0.38 and p = 0.02 , respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.

Abstract 15516: Predicting Heart Failure Hospitalization in Type 2 Diabetes Mellitus: Validation of the TRS-HFDM Score in the ACCORD Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Malik Elharram ◽  
Thao Huynh ◽  
Jiayi Ni ◽  
João P Ferreira ◽  
Abhinav Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Risk Score ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Event Rates

Background: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk for developing heart failure (HF), and clinical models are needed to identify patients with a greater risk for HF hospitalization (HHF). The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM) was recently developed and validated to predict HHF in patients with T2DM in two large clinical trials (SAVOR-TIMI 53 and DECLARE-TIMI 58). We aimed to validate the TRS-HFDM in another cohort of patients with T2DM. Methods: We validated the TRS-HFDM score in 5,123 patients with T2DM for fatal or non-fatal HHF in the placebo arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes Study Group). The TRS-HFDM included: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. We evaluated discrimination with the Harrell C index, and calibration by comparing observed event rates for HHF with predicted risk, and the Nam-D’Agostino statistic. Results: During a mean follow up of 4.8 years, 212 patients (4.14%) experienced at least one HHF. The mean age was 63 ±6.7 years, and 38% were female. The baseline hemoglobin A1C was 8.3%, and 36% were on insulin. The ACCORD patients had less comorbidities with a lower proportion of patients with renal dysfunction (8% vs. 16% vs. 17%), established cardiovascular disease (35% vs.79% vs. 41%) and pre-existing HF (5% vs. 13% vs. 10%) compared to patients enrolled in the SAVOR-TIMI 53 and DECLARE TIMI-58 trials respectively. In our cohort, the TRS-HFDM score predicted well HHF events with a Harrel C index of 0.78. The integer-based score was well calibrated, with the observed Kaplan-Meier HHF rates closely predicting the Kaplan-Meier event rates at the end follow up (Nam D`Agostino test: 65.39 (p<0.0001). Discussion: Our findings confirm the applicability of the TRS-HFDM in a large cohort of patients with T2DM with less high-risk features than the SAVOR-TIMI 53 and DECLARE-TIMI 58 populations. Future validation of this risk score in observational cohort studies is needed to evaluate its external validity in a general clinical setting.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 11 ◽  
pp. 204062232096159
Author(s):  
Yake Lou ◽  
Ying Yu ◽  
Junchao Duan ◽  
Sining Bi ◽  
Khaing Nyein Chan Swe ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Subgroup Analysis ◽  
Controlled Trials ◽  
Risk Of Fracture ◽  
Randomized Controlled ◽  
Increased Risk

Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fracture compared with those without T2DM. Some oral glucose-lowering agents may increase the incidence of fracture. Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) are associated with increased risk of fracture remains unclear. Methods: We retrieved articles from PubMed, Embase, Cochrane Library database, and other sources up to 24 October 2019. We included randomized controlled trials (RCTs) that reported fractures and analyzed the fracture incidence of SGLT2i, canagliflozin, dapagliflozin, and empagliflozin. Subgroup analysis was also performed based on baseline characteristics. Results: A total of 78 RCTs with 85,122 patients were included in our analysis. The overall SGLT2i fracture incidence was 2.56% versus 2.77% in the control group [odds ratio (OR), 1.03; 95% confidence interval (CI) (0.95, 1.12); p = 0.49]. Compared with the control treatment, treatment with canagliflozin led to a higher rate of fractures [OR, 1.17; 95% CI (1.00, 1.37); p = 0.05], but no significant difference was observed when compared with dapagliflozin [OR, 1.02; 95% CI (0.90, 1.15); p = 0.79] or empagliflozin [OR, 0.89; 95% CI (0.73, 1.10); p = 0.30]. Subgroup analysis showed that, in a follow-up of less than 52 weeks, SGLT2i decreased the incidence of fracture by 29% [OR, 0.71; 95% CI (0.55, 0.93); p = 0.01], but this benefit was lost when the follow-up extended to more than 52 weeks [OR, 1.08; 95% CI (0.98, 1.18); p = 0.12]. Conclusion: Canagliflozin seems to increase the risk of fracture, while other SGLT2is do not result in a higher incidence of fracture.

Euglycemic Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter Type 2 Inhibitors in Patients With Type 2 Diabetes Mellitus Receiving Oral Therapy

2017 ◽  
Vol 32 (2) ◽  
pp. 240-243 ◽  
Author(s):  
Ryan B. Dull ◽  
Mikayla L. Spangler ◽  
Emily L. Knezevich ◽  
Britney M. Lau
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Case Reports ◽  
Serious Adverse Events ◽  
Type 2 Dm ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Introduction and Objective: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. Case Reports: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. Discussion: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. Conclusion: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.

scholarly journals The Role of Combined SGLT1/SGLT2 Inhibition in Reducing the Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Bertram Pitt ◽  
Gabriel Steg ◽  
Lawrence A. Leiter ◽  
Deepak L. Bhatt
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Relative Increase ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Sglt2 Inhibition

Abstract Purpose In patients with type 2 diabetes mellitus (T2DM), both sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide receptor agonists (GLP-1 RAs) have demonstrated significant improvements in cardiovascular and kidney outcomes independent of their glycemic benefits. This paper will briefly compare the effect of SGLT2is and GLP-1 RAs to that of the SGLT1/2 inhibitor sotagliflozin on the incidence of myocardial infarction (MI) and stroke in patients with T2DM and further postulate mechanisms to account for these findings. Methods and Results Thus far, the results from SCORED and SOLOIST (trials studying the SGLT1/2 inhibitor sotagliflozin) suggest that an increase in SGLT1 inhibition when added to SGLT2 inhibition may contribute to reductions in MI and stroke in patients with T2DM. This benefit is beyond what SGLT2is alone can accomplish and at least similar to GLP-1 RAs but with the added benefit of a reduction in hospitalizations and urgent visits for HF. Larger and longer studies are required to confirm the effectiveness of SGLT1/SGLT2 inhibition in reducing MI and stroke in patients with T2DM and elucidate the mechanisms associated with this finding. Conclusions The role of SGLT1/2 inhibition as an addition to GLP-1 RAs in patients with and without T2DM at increased risk for MI and stroke requires further study. Regardless, the finding that a relative increase in SGLT1/2 inhibition reduces the risk of MI and stroke as well as hospitalizations and urgent visits for heart failure could improve quality of life and reduce the healthcare burden associated with T2DM.

scholarly journals Prognostic Value of Secreted Frizzled-Related Protein 5 in Heart Failure Patients With and Without Type 2 Diabetes Mellitus

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Jiandi Wu ◽  
Haoxiao Zheng ◽  
Xinyue Liu ◽  
Peisong Chen ◽  
Yunlong Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Prognostic Value ◽  
Primary Outcome ◽  
Related Protein

Background: Patients with heart failure (HF) with diabetes mellitus have distinct biomarker profiles compared with those without diabetes mellitus. SFRP5 (secreted frizzled-related protein 5) is an anti-inflammatory adipokine with an important suppressing role on the development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the prognostic value of SFRP5 in patients with HF with and without T2DM. Methods: The study included 833 consecutive patients with HF, 312 (37.5%) of whom had T2DM. Blood samples were collected at presentation, and SFRP5 levels were measured. The primary outcome was the composite end points of first occurrence of HF rehospitalization or all-cause mortality during follow-up. Results: During median follow-up of 2.1 years, 335 (40.2%) patients in the cohort experienced the composite primary outcome. After adjustment for multiple risk factors, each doubling of SFRP5 level was associated with a 21% decreased risk of primary outcomes in the overall study population ( P <0.001). Subgroup analyses showed that the association between level of SFPR5 and primary outcomes may be stronger in patients with T2DM (hazard ratio, 0.69 [95% CI, 0.61–0.79]) than in patients without T2DM (hazard ratio, 0.89 [95% CI, 0.79–1.01]; interaction P =0.006). Similar associations were observed when taking SFRP5 as a categorical variable. Addition of SFRP5 significantly improved discrimination and reclassification of the incident primary outcomes beyond clinical risk factors and N-terminal pro-B-type natriuretic peptide in all patients with HF and those with T2DM (all P <0.01). Conclusions: SFRP5 is an independent novel biomarker for risk stratification in HF, especially in HF with T2DM.

scholarly journals Serum creatinine levels and risk of incident type 2 diabetes mellitus or dysglycemia in middle-aged Japanese men: a retrospective cohort study

2018 ◽  
Vol 6 (1) ◽  
pp. e000492 ◽  
Author(s):  
Mamoru Takeuchi ◽  
Hironori Imano ◽  
Isao Muraki ◽  
Yuji Shimizu ◽  
Mina Hayama-Terada ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Creatinine ◽  
Incident Type ◽  
Increased Risk ◽  
Incident Type 2 Diabetes ◽  
Fasting Plasma Glucose Concentration

ObjectiveTo assess the association between low serum creatinine levels and an increased risk of type 2 diabetes mellitus and dysglycemia.Research design and methodsWe conducted a retrospective cohort study of 3313 Japanese male workers aged 30–55 years, who underwent annual health check-ups during 2001–2008 and showed no type 2 diabetes mellitus, and underwent follow-up examinations until March 2013. Dysglycemia was defined as a fasting plasma glucose concentration of ≥110 mg/dL (6.1 mmol/L), or a non-fasting plasma glucose concentration of ≥140 mg/dL (7.8 mmol/L). A Cox proportional model was used to calculate HRs and 95% CIs for developing type 2 diabetes mellitus or dysglycemia.ResultsDuring the median 6.7-year follow-up, there were 207 cases of incident type 2 diabetes mellitus and 596 cases of incident dysglycemia, including 115 cases of type 2 diabetes mellitus among the subjects with normal glucose concentrations at baseline. After adjustment for age, body mass index and known diabetes risk factors, the multivariable HR of type 2 diabetes mellitus for the lowest category of serum creatinine (<0.7 mg/dL) vs the highest category (0.9–1.1 mg/dL) was 1.9 (95% CI 1.2 to 2.9; P for trend 0.03). The multivariable HRs of dysglycemia for the lowest category of serum creatinine versus the highest category was 1.5 (95% CI 1.1 to 1.9; P for trend 0.01).ConclusionsLow serum creatinine levels were associated with an increased risk of type 2 diabetes mellitus and dysglycemia.

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