Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers

Mechanick, Jeffrey I.; Farkouh, Michael E.; Newman, Jonathan; Garvey, W. Timothy

doi:10.1016/j.jacc.2019.11.044

Cited by 154 publications

(144 citation statements)

References 181 publications

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“…A novel model of cardiometabolic-based chronic disease (CMBCD) including adiposity-based chronic disease (ABCD, defined as abnormalities in the amount, distribution, and function of adipose tissue) and dysglycemia-based chronic disease (DBCD) is now proposed ‘to provide a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and mitigate the development and ravages of cardiovascular disease’. 48 CMBCD focuses on three primary drivers (genetics, environment, and behavior) and two metabolic drivers (adiposity and dysglycemia). Insulin resistance is at the intersection between ABCD and DBCD, and further weight gain can worsen insulin resistance and intensify inflammation, oxidative stress, and glucose intolerance.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and energetic benefits of microRNA-22 inhibition

Thibonnier¹,

Esau²,

Ghosh

et al. 2020

BMJ Open Diab Res Care

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IntroductionWe previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as KDM3A, KDM6B, PPARA, PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.Research design and methodsWe now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Body composition, various blood parameters and energy expenditure were measured at several timepoints between week 12 and week 27 of age.ResultsWeekly subcutaneous injections of APT-110 for 12 weeks produced a sustained increase of energy expenditure as early as day 11 of treatment, a significant fat mass reduction, but no change of appetite nor physical activity. Insulin sensitivity as well as circulating glucose, cholesterol and leptin were improved. There was a dramatic reduction of liver steatosis after 3 months of active treatment. RNA sequencing revealed an activation of lipid metabolism pathways in a tissue-specific manner.ConclusionsThese original findings suggest that microRNA-22-3p inhibition could lead to a potent treatment of fat accumulation, insulin resistance, and related complex metabolic disorders such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease.

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Section: Discussionmentioning

confidence: 99%

Metabolic and energetic benefits of microRNA-22 inhibition

Thibonnier¹,

Esau²,

Ghosh

et al. 2020

BMJ Open Diab Res Care

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“…For the first time, CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed that inhibition of the interleukin (IL)-1b pathway in patients with CAD could reduce the risk of cardiovascular events by approximately 17% [ 7 ]. Actually, insulin resistance (IR), which has a strong relationship with dyslipidemia and inflammation [ 8 ], has not received much attention. The residual risk after lipid-lowering agents could be attributed to IR to a large degree [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Discordance between the triglyceride glucose index and fasting plasma glucose or HbA1C in patients with acute coronary syndrome undergoing percutaneous coronary intervention predicts cardiovascular events: a cohort study from China

Zhang

Liu

et al. 2020

Cardiovasc Diabetol

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Background Previous studies have investigated the relationship of the triglyceride glucose (TyG) index with the incidence of cardiovascular events. However, to date, there have been no studies comparing the predictive values of fasting plasma glucose (FPG), glycosylated hemoglobin A (HbA1C) and the TyG index for the risk of cardiovascular events. This study aimed to use discordance analysis to evaluate and compare the effectiveness of FPG, HbA1C and the TyG index to predict the risk of cardiovascular events. Methods Patients diagnosed with acute coronary disease (ACS) undergoing percutaneous coronary intervention (PCI) were enrolled in this study. The TyG index was computed using the following formula: ln [fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. We categorized patients into 4 concordance/discordance groups. Discordance was defined as a TyG index equal to or greater than the median and an FPG or HbA1C less than the median, or vice versa. The primary outcome was the composite of death, nonfatal myocardial infarction, nonfatal stroke and unplanned repeat revascularization. A Cox proportional hazards regression model was performed to estimate the risk of cardiovascular events according to the concordance/discordance groups. Sensitivity analysis was performed on each patient group divided into high or low categories for HbA1C or FPG and were repeated according to diabetes status. Results In total, 9285 patients were included in the final statistical analysis (male: 75.3%, age: 59.9 ± 10.05 years, BMI: 26.2 ± 9.21 kg/m 2 , diabetes: 43.9% and dyslipidemia: 76.8%). The medians defining concordance/discordance were 6.19 mmol/L for FPG, 6.1% for HbA1C and 8.92 for the TyG index. The TyG index was strongly related to triglycerides and HDL-C (r = 0.881 and -0.323, respectively; both P < 0.001). During the 17.4 ± 2.69 months of follow-up, there were 480 (5.1%) incident cardiovascular events. Among patients with a lower HbA1C or FPG, 15.6% and 16.3%, respectively, had a discordantly high TyG index and a greater risk of cardiovascular events compared with patients with a concordantly low TyG index after full adjustment (HR: 1.92, 95% CI 1.33–2.77; HR: 1.89, 95% CI 1.38–2.59; for HbA1C and FPG, respectively). Repeat risk estimation using high or low categories for FPG or HbA1C and diabetes status confirmed the results. Conclusions Patients with a discordantly high TyG index had a significantly greater risk of cardiovascular events regardless of diabetes status. The TyG index might be a better predictor of cardiovascular risk than FPG or HbA1C for patients with ACS undergoing PCI. This discordance may support better cardiovascular risk management regardless of diabetes status.

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“…Due to the limitations of BMI, which cannot distinguish fat mass and lean mass [6,9], recent evidences support that considering the presence or absence of combined metabolic abnormality in addition to obesity defined on the basis of BMI can more effectively stratify the prognostic implication of obesity as a risk factor of cardiovascular diseases (CVDs) including HF [10][11][12][13]. As a result, concepts of unique obesity sub-phenotypes, including metabolically healthy obesity (MHO) and metabolically unhealthy non-obesity (MUNO) have emerged.…”

mentioning

confidence: 99%

Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study

Lee

Kim

et al. 2020

Cardiovasc Diabetol

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Background: We aimed to investigate the hazard of hospitalization for heart failure (hHF) according to the transitions in metabolic health and obesity status. Methods: The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this nationwide, longitudinal, population-based study. The hazard of hHF was analyzed according to the eight groups stratified by stability in metabolic health and transition in obesity status among initially metabolically healthy adults who underwent two cycles of health examinations in 2009-2010 and 2013-2014 (N = 7,148,763). Results: During two examinations, 48.43% of the initially metabolically healthy obese (MHO) individuals and 20.94% of the initially metabolically healthy non-obese (MHNO) individuals showed changes in their metabolic health and obesity status. During a mean follow-up of 3.70 years, 3151 individuals were hospitalized for HF. When stable MHNO individuals were set as the reference, transition to metabolically unhealthy phenotype was associated with an increased hazard of hHF; the hazard ratio (HR) and 95% confidence interval (CI) in the individuals who transformed from MHO to metabolically unhealthy non-obese was 2.033 (1.579-2.616). The constant MHO group had a 17.3% increased hazard of hHF compared with the stable MHNO group [HR (95% CI) 1.173 (1.039-1.325)]. Individuals who shifted from MHO to MHNO showed a 34.3% lower hazard of hHF compared with those who maintained the MHO category [HR (95% CI) 0.657 (0.508-0.849)]. Conclusion: Dynamic changes in metabolic health and obesity status were observed during a relatively short interval of 3-5 years. Loss of metabolic health was significantly associated with an increased hazard of hHF. Even if metabolic health was maintained, persistent obesity remained as a risk factor for hHF, and transition from MHO to MHNO had a protective effect against hHF. Therefore, the prevention and control of obesity while maintaining metabolic health would be crucial in preventing hHF.

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Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers

Cited by 154 publications

References 181 publications

Metabolic and energetic benefits of microRNA-22 inhibition

Metabolic and energetic benefits of microRNA-22 inhibition

Discordance between the triglyceride glucose index and fasting plasma glucose or HbA1C in patients with acute coronary syndrome undergoing percutaneous coronary intervention predicts cardiovascular events: a cohort study from China

Hospitalization for heart failure incidence according to the transition in metabolic health and obesity status: a nationwide population-based study

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