Triglyceride Screening May Improve Cardiometabolic Disease Risk Assessment in Latinos with Poorly Controlled Type 2 Diabetes

2013 ◽  
Vol 24 (4) ◽  
pp. 1739-1755 ◽  
Author(s):  
Sonia Vega-López ◽  
Mariana C. Calle ◽  
Maria Luz Fernandez ◽  
Grace Kollannoor-Samuel ◽  
Jyoti Chhabra ◽  
...  
Author(s):  
Pyry Helkkula ◽  
Tuomo Kiiskinen ◽  
Aki S. Havulinna ◽  
Juha Karjalainen ◽  
Seppo Koskinen ◽  
...  

AbstractProtein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that associated with both lipid levels and cardiometabolic disease risk and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs also associated with risks of cardiometabolic diseases or 2,264 disease endpoints curated in the FinnGen Study (n = 176,899). Three PTVs were associated with both lipid levels and the risk of cardiometabolic disease: triglyceride-lowering variants in ANGPTL8 (−24.0[-30.4 to −16.9] mg/dL per rs760351239-T allele, P = 3.4× 10−9) and ANGPTL4 (−14.4[-18.6 to −9.8] mg/dL per rs746226153-G allele, P = 4.3 × 10−9) and the HDL cholesterol-elevating variant in LIPG (10.2[7.5 to 13.0] mg/dL per rs200435657-A allele, P = 5.0 × 10−13). The risk of type 2 diabetes was lower in carriers of ANGPTL8 (odds ratio [OR] = 0.67[0.47-0.92], P = 0.01), ANGPTL4 (OR = 0.70[0.60-0.82], P = 1.4× 10−5) and LIPG (OR = 0.67[0.48-0.91], P = 0.01) PTVs than in noncarriers. Moreover, the odds of coronary artery disease were 44% lower in carriers of a PTV in ANGPTL8 (OR = 0.56[0.38-0.83], P = 0.004). Finally, the phenome-wide scan of the ANGPTL8 PTV showed a markedly higher associated risk of esophagitis (585 cases, OR = 174.3[17.7-1715.1], P = 9.7 × 10−6) and sensorineural hearing loss (12,250 cases, OR = 2.45[1.63-3.68], P = 1.8 × 10−5). The ANGPTL8 PTV carriers were less likely to use statin therapy (53,518 cases, OR = 0.53[0.41-0.71], P = 1.2 × 10−5). Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 757-P
Author(s):  
ADRIAN ELZARKI ◽  
SESHAGIRI RAO NANDULA ◽  
HASSAN AWAL ◽  
SABYASACHI SEN

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuan Wang ◽  
M. Wade Calcutt ◽  
Jane F. Ferguson

Cardiometabolic disease affects the majority of individuals worldwide. The metabolite α-aminoadipic acid (2-AAA) was identified as a biomarker of Type 2 Diabetes (T2D). However, the mechanisms underlying this association remain unknown. DHTKD1, a central gene in the 2-AAA pathway, has been linked to 2-AAA levels and metabolic phenotypes. However, relatively little is known about its function. Here we report that DHTKD1 knock-out (KO) in HAP-1 cells leads to impaired mitochondrial structure and function. Despite impaired mitochondrial respiration and less ATP production, normal cell proliferation rate is maintained, potentially through a series of compensatory mechanisms, including increased mitochondrial content and Akt activation, p38, and ERK signaling. Common variants in DHTKD1 associate with Type 2 Diabetes and cardiometabolic traits in large genome-wide associations studies. These findings highlight the vital role of DHTKD1 in cellular metabolism and establish DHTKD1-mediated mitochondrial dysfunction as a potential novel pathway in cardiometabolic disease.


2013 ◽  
pp. 1-1
Author(s):  
Gbadebo Ajani ◽  
Rosemary Ikem ◽  
Adenike Enikuomehin ◽  
David Soyoye ◽  
Babatope Kolawole

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Salasyuk ◽  
S Nedogoda ◽  
I Barykina ◽  
V Lutova ◽  
E Popova

Abstract Background Metabolic syndrome (MetS) and abdominal obesity are one of the most common CVD risk factors among young and mature patients. However, the currently used CVD risk assessment scales may underestimate the CV risk in people with obesity and MS. Early vascular aging rather than chronological aging can conceptually offer better risk prediction. MetS, as accumulation of classical risk factors, leads to acceleration of early vascular aging. Since an important feature of MetS is its reversibility, an adequate risk assessment and early start of therapy is important in relation to the possibilities of preventing related complications. Purpose To derive a new score for calculation vascular age and predicting EVA in patients with MetS. Methods Prospective open cohort study using routinely collected data from general practice. The derivation cohort consisted of 1000 patients, aged 35–80 years with MetS (IDF,2005 criteria). The validation cohort consisted of 484 patients with MetS and carotid-femoral pulse wave velocity (cfPWV) values exceeding expected for average age values by 2 or more SD (EVA syndrome). Results In univariate analysis, EVA was significantly correlated with the presence of type 2 diabetes and clinical markers of insulin resistance (IR), body mass index (BMI), metabolic syndrome severity score (MetS z-score), uric acid (UA) level, hsCRP, HOMA-IR, total cholesterol (TC), triglycerides (TG), heart rate (HR), central aortic blood pressure (CBP), diastolic blood pressure (DBP). Multiple logistic regression shown, that presence of type 2 diabetes and IR were associated with greater risk of EVA; the odds ratios were 2.75 (95% CI: 2.34, 3.35) and 1.57 (95% CI: 1.16, 2.00), respectively. In addition, the risk of having EVA increased by 76% with an increase in HOMA-IR by 1 unit, by 17% with an increase in hsCRP by 1 mg/l, by 4% with an increase in DBP by 1 mm Hg, and by 1% with each 1 μmol / L increase in the level of UA. The area under the curve for predicting EVA in patients with MetS was 0,949 (95% CI 0,936 to 0,963), 0,630 (95% CI 0,589 to 0,671), 0,697 (95% CI 0,659 to 0,736) and 0,686 (95% CI 0,647 to 0,726), for vascular age, calculated from cfPWV, SCORE scale, QRISK-3 scale and Framingham scale, respectively. Diabetes mellitus and clinical markers of IR (yes/no), HOMA-IR and UA level were used to develop a new VAmets score for EVA prediction providing a total accuracy of 0.830 (95% CI 0,799 to 0,860). Conclusion cfPWV at present the most widely studied index of arterial stiffness, fulfills most of the stringent criteria for a clinically useful biomarker of EVA in patients with MetS. Although, parallel efforts for effective integration simple clinical score into clinical practice have been offered. Our score (VAmets) may accurately identify patients with MetS and EVA on the basis of widely available clinical variables and classic cardiovascular risk factors can prioritize using of vascular age in routine care. ROC-curves for predicting EVA in MetS Funding Acknowledgement Type of funding source: None


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