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61.
  • Prokopenko, Inga, et al. (författare)
  • Variants in MTNR1B influence fasting glucose levels
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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62.
  • Boström, Kristina Bengtsson, et al. (författare)
  • Polymorphisms in alpha - and betaadrenergic receptor genes, hypertension and obstructive sleep apnea. The Skaraborg Sleep Study. J Hypertension
  • 2010
  • Ingår i: International Journal of Hypertension. - 2090-0392. ; 2010:Art ID 458410
  • Tidskriftsartikel (refereegranskat)abstract
    • The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α(2B)-, β(1)-, and β(2)-adrenergic receptor genes and obstructive sleep apnea (OSA) in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β(1)-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02-4.7). Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4-21.2).
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63.
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64.
  • Ahlqvist, Emma, et al. (författare)
  • Genetics of type 2 diabetes
  • 2011
  • Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 57:2, s. 241-254
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Type 2 diabetes (T2D) is a complex disorder that is affected by multiple genetic and environmental factors. Extensive efforts have been made to identify the disease-affecting genes to better understand the disease pathogenesis, find new targets for clinical therapy, and allow prediction of disease.Content: Our knowledge about the genes involved in disease pathogenesis has increased substantially in recent years, thanks to genomewide association studies and international collaborations joining efforts to collect the huge numbers of individuals needed to study complex diseases on a population level. We have summarized what we have learned so far about the genes that affect T2D risk and their functions. Although more than 40 loci associated with T2D or glycemic traits have been reported and reproduced, only a minor part of the genetic component of the disease has been explained, and the causative variants and affected genes are unknown for many of the loci.Summary: Great advances have recently occurred in our understanding of the genetics of T2D, but much remains to be learned about the disease etiology. The genetics of T2D has so far been driven by technology, and we now hope that next-generation sequencing will provide important information on rare variants with stronger effects. Even when variants are known, however, great effort will be required to discover how they affect disease risk.
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65.
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66.
  • Abdul-Ghani, Muhammad A., et al. (författare)
  • Fasting Versus Postload Plasma Glucose Concentration and the Risk for Future Type 2 Diabetes Results from the Botnia Study
  • 2009
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 32:2, s. 281-286
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE - The purpose of this study was to assess the efficacy of the postload plasma glucose concentration in predicting future risk of type 2 diabetes, compared with prediction models based oil measurement. of the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS - A total of 2,442 subjects from the Botnia Study, who were free Of type 2 diabetes at baseline, received an oral glucose tolerance test (OGTT) at baseline and after 7-8 years of follow-up. Future risk for type 2 diabetes was assessed with area under the receiver-operating characteristic curve for prediction models based up measurement of the FPG concentration 1) with or without a 1-h plasma glucose concentration during the OGTT and 2) with or without the metabolic syndrome. RESULTS - Prediction models based on measurement of the FPG concentration were weak predictors for the risk of Future type 2 diabetes. Addition of a 1-h plasma glucose Concentration markedly enhanced prediction Of the risk of future type 2 diabetes. A cut point of 155 mg/dl for the 1-h plasma glucose concentration during the OGTT and presence Of the metabolic syndrome were used to Stratify subjects in each glucose tolerance group into low, intermediate, and high risk for future type 2 diabetes. CONCLUSIONS - The plasma glucose concentration at 1 h during the OGTT is a Strong predictor of future risk for type 2 diabetes and adds to the prediction power of models based on measurements made during the fasting state. A plasma glucose cut point of 155 mg/dl Plus the Adult Treatment Panel III criteria for the metabolic syndrome can be used to stratify nondiabetic subjects into low-, intermediate-, and high-risk groups.
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67.
  • Abdul-Ghani, Muhammad A., et al. (författare)
  • Minimal Contribution of Fasting Hyperglycemia to the Incidence of Type 2 Diabetes in Subjects With Normal 2-h Plasma Glucose
  • 2010
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:3, s. 557-561
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE - To assess the relative contribution of increased fasting and postload plasma glucose concentrations to the incidence of type 2 diabetes in subjects with a normal 2-h plasma glucose concentration. RESEARCH DESIGN AND METHODS - A total of 3,450 subjects with 2-h plasma glucose concentration < 140 mg/dl at baseline were followed up in the San Antonio Heart Study (SAHS) and the Botnia Study for 7-8 years. The incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations. RESULTS - in subjects with 2-h plasma glucose < 140 mg/dl, the incidence of type 2 diabetes increased with increasing fasting plasma glucose (FPG) and 1-h and 2-h plasma glucose concentrations. In a multivariate logistic analysis, after adjustment for all diabetes risk factors, the FPG concentration was a Strong predictor Of type 2 diabetes in both the SAHS and the Botnia Study (P < 0.0001). However, when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG concentration was no longer a significant predictor of type 2 diabetes in both Studies (NS). When subjects were matched for the level of 1-h plasma glucose concentration, the incidence Of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes. CONCLUSIONS - An increase in postload glycemia in the normal range is associated with an increase in the incidence of type 2 diabetes. After controlling for 1-h plasma glucose concentration, the increase in FPG concentration is not associated with an increase in the incidence of type 2 diabetes.
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68.
  • Abdul-Ghani, Muhammad A., et al. (författare)
  • The shape of plasma glucose concentration curve during OGTT predicts future risk of type 2 diabetes
  • 2010
  • Ingår i: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 26:4, s. 280-286
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The aim of the study is to assess the relationship between the shape of plasma glucose concentration during the OGTT and future risk for T2DM. Methods 2445 non-diabetic subjects from the Botnia study received an OGTT at baseline and after 7-8 years of follow-up. Results NGT and IFG subjects who returned their plasma glucose concentration following an ingested glucose load below FPG within 60 min had increased insulin sensitivity, greater insulin secretion and lower risk for future T2DM compared to NGT and IFG subjects whose post-load plasma glucose concentration required 120 min or longer to return their plasma glucose level to FPG level. IGT subjects who had a lower plasma glucose concentration at 1-h compared to 2-h during oGrr had greater insulin sensitivity, better beta cell function and lower risk for future T2DM. Conclusions These data suggest that the shape of glucose curve can be utilized to assess future risk for T2DM. Copyright (C) 2010 John Wiley & Sons, Ltd.
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69.
  • Abdul-Ghani, Muhammad A., et al. (författare)
  • Two-Step Approach for the Prediction of Future Type 2 Diabetes Risk
  • 2011
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 34:9, s. 2108-2112
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-To develop a model for the prediction of type 2 diabetes mellitus (T2DM) risk on the basis of a multivariate logistic model and 1-h plasma glucose concentration (1-h PG). RESEARCH DESIGN AND METHODS-The model was developed in a cohort of 1,562 non-diabetic subjects from the San Antonio Heart Study (SAHS) and validated in 2,395 nondiabetic subjects in the Botnia Study. A risk score on the basis of anthropometric parameters, plasma glucose and lipid profile, and blood pressure was computed for each subject. Subjects with a risk score above a certain cut point were considered to represent high-risk individuals, and their 1-h PG concentration during the oral glucose tolerance test was used to further refine their future T2DM risk. RESULTS-We used the San Antonio Diabetes Prediction Model (SADPM) to generate the initial risk score. A risk-score value of 0.065 was found to be an optimal cut point for initial screening and selection of high-risk individuals. A 1-h PG concentration >140 mg/dL in high-risk individuals (whose risk score was >0.065) was the optimal cut point for identification of subjects at increased risk. The two cut points had 77.8, 77.4, and 44.8% (for the SAHS) and 75.8, 71.6, and 11.9% (for the Botnia Study) sensitivity, specificity, and positive predictive value, respectively, in the SAHS and Botnia Study. CONCLUSIONS-A two-step model, based on the combination of the SADPM and 1-h PG, is a useful tool for the identification of high-risk Mexican-American and Caucasian individuals. Diabetes Care 34:2108-2112, 2011
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70.
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