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Micaela Morettini,Carlo Castriota,Christian Göbl,Alexandra Kautzky-Willer,Giovanni Pacini,Laura Burattini,Andrea Tura 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.2
Background: This study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (SG), namely calculated SG (CSG), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM). Methods: CSG was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CSG was then tested on a population of women with pGDM (n=57). Each subject underwent a 3-hour IM-IVGTT; women with pGDM were observed early postpartum and after a follow-up period of up to 7 years and classified as progressors (PROG) or non-progressors (NONPROG) to T2DM. The minimal model analysis provided a reference SG. Results: CSG was described as CSG=1.06×10–2+5.71×10–2×KG/Gpeak, KG being the mean slope (absolute value) of loge glucose in 10–25- and 25–50-minute intervals, and Gpeak being the maximum of the glucose curve. Good agreement between CSG and SG in the general population and in the pGDM group, both at baseline and follow-up (even in PROG and NONPROG subgroups), was shown by the Bland-Altman plots (<5% observations outside limits of agreement), and by the test for equivalence (equivalence margin not higher than one standard deviation). At baseline, the PROG subgroup showed significantly lower SG and CSG values compared to the NONPROG subgroup (P<0.03). Conclusion: CSG is a valid SG predictor. In the pGDM group, glucose effectiveness appeared to be impaired in women progressing to T2DM.
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, Tanya M.,Musunuru, Kiran,Smith, Albert V.,Edmondson, Andrew C.,Stylianou, Ioannis M.,Koseki, Masahiro,Pirruccello, James P.,Ripatti, Samuli,Chasman, Daniel I.,Willer, Cristen J.,Johansen, C Nature Publishing Group, a division of Macmillan P 2010 Nature Vol.466 No.7307
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P??<??5?????10<SUP>??8</SUP>), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes??GALNT2, PPP1R3B and TTC39B??with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.