scholarly journals New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

2010 ◽  
Vol 42 (2) ◽  
pp. 105-116 ◽  
Author(s):  
Josée Dupuis ◽  
◽  
Claudia Langenberg ◽  
Inga Prokopenko ◽  
Richa Saxena ◽  
...  
2010 ◽  
Vol 42 (5) ◽  
pp. 464-464 ◽  
Author(s):  
Josée Dupuis ◽  
Claudia Langenberg ◽  
Inga Prokopenko ◽  
Richa Saxena ◽  
Nicole Soranzo ◽  
...  

Diabetologia ◽  
2019 ◽  
Vol 62 (12) ◽  
pp. 2298-2309 ◽  
Author(s):  
Ari V. Ahola-Olli ◽  
Linda Mustelin ◽  
Maria Kalimeri ◽  
Johannes Kettunen ◽  
Jari Jokelainen ◽  
...  

Abstract Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.


2013 ◽  
Vol 7 (3) ◽  
pp. 640-645 ◽  
Author(s):  
Nathan R. Hill ◽  
Apostolos Tsapas ◽  
Peter Hindmarsh ◽  
David R. Matthews

Diabetes ◽  
2008 ◽  
Vol 57 (8) ◽  
pp. 2253-2257 ◽  
Author(s):  
M. Vaxillaire ◽  
C. Cavalcanti-Proenca ◽  
A. Dechaume ◽  
J. Tichet ◽  
M. Marre ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3323
Author(s):  
Jose V. Sorlí ◽  
Rocío Barragán ◽  
Oscar Coltell ◽  
Olga Portolés ◽  
Eva C. Pascual ◽  
...  

Gene-age interactions have not been systematically investigated on metabolic phenotypes and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics. Taking into account that aging is typically associated with both impairment of the circadian system and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963 C>G variant that has been associated with fasting glucose concentrations, gestational diabetes, and type-2 diabetes. Therefore, our main aim was to investigate whether the association between the MTNR1B-rs10830963 polymorphism and fasting glucose is age dependent. Our secondary aims were to analyze the polymorphism association with type-2 diabetes and explore the gene-pregnancies interactions on the later type-2 diabetes risk. Three Mediterranean cohorts (n = 2823) were analyzed. First, a cross-sectional study in the discovery cohort consisting of 1378 participants (aged 18 to 80 years; mean age 41 years) from the general population was carried out. To validate and extend the results, two replication cohorts consisting of elderly individuals were studied. In the discovery cohort, we observed a strong gene-age interaction (p = 0.001), determining fasting glucose in such a way that the increasing effect of the risk G-allele was much greater in young (p = 5.9 × 10−10) than in elderly participants (p = 0.805). Consistently, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose concentrations in the two replication cohorts (mean age over 65 years) did not reach statistical significance (p > 0.05 for both). However, in the elderly cohorts, significant associations between the polymorphism and type-2 diabetes at baseline were found. Moreover, in one of the cohorts, we obtained a statistically significant interaction between the MTNR1B polymorphism and the number of pregnancies, retrospectively assessed, on the type-2 diabetes risk. In conclusion, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose is age-dependent, having a greater effect in younger people. However, in elderly subjects, associations of the polymorphism with type-2 diabetes were observed and our exploratory analysis suggested a modulatory effect of the number of past pregnancies on the future type-2 diabetes genetic risk.


PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0230815 ◽  
Author(s):  
Peitao Wu ◽  
Denis Rybin ◽  
Lawrence F. Bielak ◽  
Mary F. Feitosa ◽  
Nora Franceschini ◽  
...  

2021 ◽  
pp. 1-37
Author(s):  
Allison L. Unger ◽  
Thomas L. Jetton ◽  
Jana Kraft

Abstract Metabolic impairments associated with type 2 diabetes, including insulin resistance and loss of glycemic control, disproportionately impact the elderly. Lifestyle interventions, such as manipulation of dietary fat quality (i.e., fatty acid (FA) composition), have been shown to favorably modulate metabolic health. Yet, whether or not chronic consumption of beneficial FAs can protect against metabolic derangements and disease risk during aging is not well-defined. We sought to evaluate whether long-term dietary supplementation of fish-, dairy-, or echium-derived FAs to the average FA profile in a U.S. American diet may offset metabolic impairments in males and females during aging. One-month-old CD-1® mice were fed isoenergetic, high-fat (40%) diets with the fat content comprised of either 100% control fat blend (CO) or 70% CO with 30% fish oil, dairy fat, or echium oil for 13 months. Every three months, parameters of glucose homeostasis were evaluated via glucose and insulin tolerance tests. Glucose tolerance improved in males consuming a diet supplemented with fish oil or echium oil as aging progressed, but not in females. Yet, females were more metabolically protected than males regardless of age. Additionally, Spearman correlations were performed between indices of glucose homeostasis and previously reported measurements of diet-derived FA content in tissues and colonic bacterial composition, which also revealed sex-specific associations. This study provides evidence that long-term dietary fat quality influences risk factors of metabolic diseases during aging in a sex-dependent manner, thus, sex is a critical factor to be considered in future dietary strategies to mitigate type 2 diabetes risk.


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