scholarly journals ANGPTL8 protein-truncating variant and the risk of coronary disease, type 2 diabetes and adverse effects

2020 ◽  
Author(s):  
Pyry Helkkula ◽  
Tuomo Kiiskinen ◽  
Aki S. Havulinna ◽  
Juha Karjalainen ◽  
Seppo Koskinen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Disease Risk ◽  
Low Frequency ◽  
Hdl Cholesterol ◽  
Cardiometabolic Disease ◽  
Lipid Levels ◽  
Finnish Population ◽  
Artery Disease

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.

scholarly journals ANGPTL8 protein-truncating variant associated with lower serum triglycerides and risk of coronary disease

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009501
Author(s):  
Pyry Helkkula ◽  
Tuomo Kiiskinen ◽  
Aki S. Havulinna ◽  
Juha Karjalainen ◽  
Seppo Koskinen ◽  
...  
Keyword(s):  
Low Frequency ◽  
Cardiometabolic Disease ◽  
Efficacy And Safety ◽  
Lipid Levels ◽  
Finnish Population ◽  
Lower Serum ◽  
Serum Triglycerides ◽  
Artery Disease

Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that were associated with both lipid levels and the risk of coronary artery disease (CAD) or type 2 diabetes (T2D) 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 were also associated with the risks of T2D or CAD, as well as 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). Two PTVs were associated with both lipid levels and the risk of CAD or T2D: 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). The risk of T2D was lower in carriers of the ANGPTL4 PTV (OR = 0.70[0.60–0.81], P = 2.2 × 10−6) than noncarriers. The odds of CAD were 47% lower in carriers of a PTV in ANGPTL8 (OR = 0.53[0.37–0.76], P = 4.5 × 10−4) than noncarriers. Finally, the phenome-wide scan of the ANGPTL8 PTV showed that the ANGPTL8 PTV carriers were less likely to use statin therapy (68,782 cases, OR = 0.52[0.40–0.68], P = 1.7 × 10−6) compared to noncarriers. Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.

scholarly journals The long-term coronary heart disease risk of previously obese patients with type 2 diabetes mellitus

2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Ritsuko Yamamoto-Honda ◽  
Hideki Ehara ◽  
Hiroji Kitazato ◽  
Yoshihiko Takahashi ◽  
Shoji Kawazu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Disease Risk ◽  
Obese Patients ◽  
Heart Disease Risk

scholarly journals Genetic basis underlying connection between hyperglycemia and dyslipidemia in Apoe-deficient mice

2015 ◽  
Author(s):  
Qian Wang ◽  
Andrew Grainger ◽  
Ani Manichaikul ◽  
Emily Farber ◽  
Suna Onengut-Gumuscu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Fasting Glucose ◽  
Hdl Cholesterol ◽  
Western Diet ◽  
Chromosome 9 ◽  
Lipid Levels ◽  
Glucose Levels ◽  
Cholesterol Levels

Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe−/−) strains, was fed a Western diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after Western diet feeding. 144 genetic markers across the entire genome were used for analysis. One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was detected when mice were fed chow or Western diet and named Bglu16. Bglu17 coincided with a significant QTL for HDL and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice fed either diet. A significant correlation between fasting glucose and triglyceride levels was observed on the Western but not chow diet. Haplotype analysis revealed that ???lipid genes??? Sik3 and Apoc3 were probable candidates for Bglu17. We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential causal genes suggest that dyslipidemia and type 2 diabetes are genetically connected.

scholarly journals Curcumin in Autoimmune and Rheumatic Diseases

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1004 ◽  
Author(s):  
Melissa Yang ◽  
Umair Akbar ◽  
Chandra Mohan
Keyword(s):  
Type 2 Diabetes ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Therapeutic Agent ◽  
Standard Of Care ◽  
Cohort Size ◽  
Lipid Levels ◽  
Current Standard

Over recent decades, many clinical trials on curcumin supplementation have been conducted on various autoimmune diseases including osteoarthritis, type 2 diabetes, and ulcerative colitis patients. This review attempts to summarize the highlights from these clinical trials. The efficacy of curcumin either alone or in conjunction with existing treatment was evaluated. Sixteen clinical trials have been conducted in osteoarthritis, 14 of which yielded significant improvements in multiple disease parameters. Eight trials have been conducted in type 2 diabetes, all yielding significant improvement in clinical or laboratory outcomes. Three trials were in ulcerative colitis, two of which yielded significant improvement in at least one clinical outcome. Additionally, two clinical trials on rheumatoid arthritis, one clinical trial on lupus nephritis, and two clinical trials on multiple sclerosis resulted in inconclusive results. Longer duration, larger cohort size, and multiple dosage arm trials are warranted to establish the long term benefits of curcumin supplementation. Multiple mechanisms of action of curcumin on these diseases have been researched, including the modulation of the eicosanoid pathway towards a more anti-inflammatory pathway, and the modulation of serum lipid levels towards a favorable profile. Overall, curcumin supplementation emerges as an effective therapeutic agent with minimal-to-no side effects, which can be added in conjunction to current standard of care.

Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective

2004 ◽  
Vol 286 (3) ◽  
pp. F442-F450 ◽  
Author(s):  
James T. Lane
Keyword(s):  
Type 2 Diabetes ◽  
Native Americans ◽  
Disease Risk ◽  
Insulin Resistance Syndrome ◽  
Temporal Perspective ◽  
Relative Contribution ◽  
Markers Of Inflammation ◽  
Diabetes In Youth

Microalbuminuria is a marker for diabetic nephropathy. It also signifies cardiovascular disease, as well as nephropathy, in type 2 diabetes (DM2). Microalbuminuria may precede DM2, occurring with the insulin resistance syndrome and its components, including obesity and hypertension. Other indicators of cardiovascular risk, such as markers of inflammation, are associated with microalbuminuria in populations of patients with and without diabetes. With the rising prevalence of DM2 in minority youth, especially in Native Americans, a marker for future disease risk would allow earlier prevention strategies to be tested. Before microalbuminuria can be used in a prevention strategy, more needs to be known about the mechanism(s) of the association between elevated excretion, its relationship to glucose intolerance, and its relative contribution to cardiovascular and renal disease. These questions are especially applicable as we begin to observe the long-term complications of diabetes in youth.

GlutathioneS-transferase T1- and M1-null genotypes and coronary artery disease risk in patients with Type 2 diabetes mellitus Cardiovasc

2009 ◽  
Vol 10 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Samantha Manfredi ◽  
Debora Calvi ◽  
Martina del Fiandra ◽  
Nicoletta Botto ◽  
Andrea Biagini ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Coronary Artery ◽  
Disease Risk ◽  
Coronary Artery Disease Risk ◽  
Artery Disease

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 ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Assessment ◽  
Disease Risk ◽  
Cardiometabolic Disease ◽  
Cardiometabolic Disease Risk

scholarly journals Comparison of the long-term effects of high-fat v. low-fat diet consumption on cardiometabolic risk factors in subjects with abnormal glucose metabolism: a systematic review and meta-analysis

2014 ◽  
Vol 111 (12) ◽  
pp. 2047-2058 ◽  
Author(s):  
Lukas Schwingshackl ◽  
Georg Hoffmann
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Hdl Cholesterol ◽  
Long Term Effects ◽  
High Fat ◽  
Low Fat

The aim of the present systematic review and meta-analysis was to examine the long-term effects ( ≥ 12 months) of high-fat (HF) v. low-fat (LF) diet consumption on the indicators of glycaemic control as well as cardiovascular risk factors in pre-diabetic and diabetic individuals. Literature search was carried out using the electronic databases MEDLINE, Embase and the Cochrane Trial Register until November 2013. Study-specific weighted mean differences (MD) were pooled using a random-effects model of the Cochrane software package Review Manager 5.1 and Stata 12.0 was used for meta-regressions. A total of fourteen trials met the inclusion criteria and a maximum of 1753 subjects were included in the meta-analysis. HF regimens were found to result in a significant decrease in TAG levels (MD − 0·19 mmol/l, 95 % CI − 0·23, − 0·14, P< 0·001; I2= 0 %, P= 0·58) and diastolic blood pressure (MD − 1·30 mmHg, 95 % CI − 1·73, − 0·87, P< 0·001; I2= 0 %, P= 0·60) and a significant increase in HDL-cholesterol levels (MD 0·05 mmol/l, 95 % CI 0·01, 0·08, P= 0·01; I2= 57 %, P= 0·01). In addition, MD in the reductions of fasting glucose levels ( − 0·41 mmol/l, 95 % CI − 0·74, − 0·08, P= 0·01; I2= 56 %, P= 0·02) were significantly high in patients with type 2 diabetes adhering to a HF diet. HF and LF diets might not be of equal value in the management of either pre-diabetes or type 2 diabetes, leading to emphasis being placed on the recommendations of HF diets.

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