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- Delgado-Lista, J., et al.
(författare)
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Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome : From the LIPGENE study
- 2011
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 214:1, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.
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| 3. |
- Tierney, A C, et al.
(författare)
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Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome-LIPGENE : a European randomized dietary intervention study
- 2011
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 35:6, s. 800-809
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Tidskriftsartikel (refereegranskat)abstract
- Background:Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS.Objective:This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS.Design:A free-living, single-blinded dietary intervention study.Subjects and Methods:MetS subjects (n=417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined.Results:In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P<0.01), particularly in men.Conclusion:There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.
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| 5. |
- Cesta, CE, et al.
(författare)
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Antidiabetic medication use during pregnancy: an international utilization study
- 2019
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 7:1, s. e000759-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed.Research design and methodsData sources included individually linked data from the nationwide health registers in Denmark (2006–2016), Finland (2006–2016), Iceland (2006–2012), Norway (2006–2015), Sweden (2006–2015), state-wide administrative and claims data for New South Wales, Australia (2006–2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006–2012, public) and IBM MarketScan (2012–2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy.ResultsPrevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%–62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used.ConclusionsPrevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period.
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| 6. |
- Gjelstad, I. M. F., et al.
(författare)
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Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance
- 2012
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Ingår i: Archives of Physiology and Biochemistry. - : Informa UK Limited. - 1381-3455 .- 1744-4160. ; 118:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.
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| 10. |
- Perez-Martinez, Pablo, et al.
(författare)
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Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:5, s. 1136-1141
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Tidskriftsartikel (refereegranskat)abstract
- Background: Calpain-10 protein (intracellular Ca2+-dependent cysteine protease) may play a role in glucose metabolism, pancreatic beta cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism. Objective: The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS. Design: The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of beta cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort. Results: The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele. Conclusion: The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at clinicaltrials. gov as NCT00429195.
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