Dataset Information

Finnish Diabetes Risk Score Is Associated with Impaired Insulin Secretion and Insulin Sensitivity, Drug-Treated Hypertension and Cardiovascular Disease: A Follow-Up Study of the METSIM Cohort.

ABSTRACT: We investigated the association of the Finnish Diabetes Risk Score (FINDRISC) with insulin secretion, insulin sensitivity, and risk of type 2 diabetes, drug-treated hypertension, cardiovascular (CVD) events and total mortality in a follow-up study of the Metabolic Syndrome in Men (METSIM) cohort. The METSIM study includes 10,197 Finnish men, aged 45-73 years, and examined in 2005-2010. Of 8,749 non-diabetic participants of the METSIM study 693 developed incident type 2 diabetes, 225 started antihypertensive medication, 351 had a CVD event, and 392 died during a 8.2-year follow-up. The FINDRISC was significantly associated with decreases in insulin secretion and insulin sensitivity (P<0.0001), and with a 4.14-fold increased risk of incident type 2 diabetes, 2.43-fold increased risk of drug-treated hypertension, 1.61-fold increased risk of CVD, and 1.55-increased risk of total mortality (the FINDRISC ?12 vs. < 12 points). In conclusion, the FINDRISC predicts impairment in insulin secretion and insulin sensitivity, the conversion to type 2 diabetes, drug-treated hypertension, CVD events and total mortality.

SUBMITTER: Fizelova M

PROVIDER: S-EPMC5112858 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Finnish Diabetes Risk Score Is Associated with Impaired Insulin Secretion and Insulin Sensitivity, Drug-Treated Hypertension and Cardiovascular Disease: A Follow-Up Study of the METSIM Cohort.

Fizelova Maria M Jauhiainen Raimo R Stančáková Alena A Kuusisto Johanna J Laakso Markku M

PloS one 20161116 11

We investigated the association of the Finnish Diabetes Risk Score (FINDRISC) with insulin secretion, insulin sensitivity, and risk of type 2 diabetes, drug-treated hypertension, cardiovascular (CVD) events and total mortality in a follow-up study of the Metabolic Syndrome in Men (METSIM) cohort. The METSIM study includes 10,197 Finnish men, aged 45-73 years, and examined in 2005-2010. Of 8,749 non-diabetic participants of the METSIM study 693 developed incident type 2 diabetes, 225 started anti ...[more]

PMID: 27851812

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Project description:Finnish-specific gene variant p.P50T/AKT2 (minor allele frequency (MAF) = 1.1%) is associated with insulin resistance and increased predisposition to type 2 diabetes. Here, we have investigated in vitro the impact of the gene variant on glucose metabolism and intracellular signalling in human primary skeletal muscle cells, which were established from 14 male p.P50T/AKT2 variant carriers and 14 controls. Insulin-stimulated glucose uptake and glucose incorporation into glycogen were detected with 2-[1,2-3H]-deoxy-D-glucose and D-[14C]-glucose, respectively, and the rate of glycolysis was measured with a Seahorse XFe96 analyzer. Insulin signalling was investigated with Western blotting. The binding of variant and control AKT2-PH domains to phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) was assayed using PIP StripsTM Membranes. Protein tyrosine kinase and serine-threonine kinase assays were performed using the PamGene® kinome profiling system. Insulin-stimulated glucose uptake and glycogen synthesis in myotubes in vitro were not significantly affected by the genotype. However, the insulin-stimulated glycolytic rate was impaired in variant myotubes. Western blot analysis showed that insulin-stimulated phosphorylation of AKT-Thr308, AS160-Thr642 and GSK3β-Ser9 was reduced in variant myotubes compared to controls. The binding of variant AKT2-PH domain to PI(3,4,5)P3 was reduced as compared to the control protein. PamGene® kinome profiling revealed multiple differentially phosphorylated kinase substrates, e.g. calmodulin, between the genotypes. Further in silico upstream kinase analysis predicted a large-scale impairment in activities of kinases participating, for example, in intracellular signal transduction, protein translation and cell cycle events. In conclusion, myotubes from p.P50T/AKT2 variant carriers show multiple signalling alterations which may contribute to predisposition to insulin resistance and T2D in the carriers of this signalling variant.

Dataset Information

Finnish Diabetes Risk Score Is Associated with Impaired Insulin Secretion and Insulin Sensitivity, Drug-Treated Hypertension and Cardiovascular Disease: A Follow-Up Study of the METSIM Cohort.

Publications

Finnish Diabetes Risk Score Is Associated with Impaired Insulin Secretion and Insulin Sensitivity, Drug-Treated Hypertension and Cardiovascular Disease: A Follow-Up Study of the METSIM Cohort.

Similar Datasets

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