Browsing by Subject "Glucose intolerance"

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  • Helminen, Olli; Pokka, Tytti; Tossavainen, Paivi; Ilonen, Jorma; Knip, Mikael; Veijola, Riitta (2016)
    Aims: Continuous glucose monitoring (CGM) parameters, self-monitored blood glucose (SMBG), HbA1c and oral glucose tolerance test (OGTT) were studied during preclinical type 1 diabetes mellitus. Methods: Ten asymptomatic children with multiple (>= 2) islet autoantibodies (cases) and 10 age and sex-matched autoantibody-negative controls from the Type 1 Diabetes Prediction and Prevention (DIPP) Study were invited to 7-day CGM with Dexcom G4 Platinum Sensor. HbA1c and two daily SMBG values (morning and evening) were analyzed. Five-point OGTTs were performed and carbohydrate intake was assessed by food records. The matched pairs were compared with the paired sample t-test. Results: The cases showed higher mean values and higher variation in glucose levels during CGM compared to the controls. The time spent >= 7.8 mmol/l was 5.8% in the cases compared to 0.4% in the controls (p = 0.040). Postprandial CGM values were similar except after the dinner (6.6 mmol/l in cases vs. 6.1 mmol/l in controls; p = 0.023). When analyzing the SMBG values higher mean level, higher evening levels, as well as higher variation were observed in the cases when compared to the controls. HbA1c was significantly higher in the cases [5.7% (39 mmol/mol) vs. 5.3% (34 mmol/mol); p = 0.045]. No differences were observed in glucose or C-peptide levels during OGTT. Daily carbohydrate intake was slightly higher in the cases (254.2 g vs. 217.7 g; p = 0.034). Conclusions: Glucose levels measured by CGM and SMBG are useful indicators of dysglycemia during preclinical type 1 diabetes mellitus. Increased evening glucose values seem to be common in children with preclinical type 1 diabetes mellitus. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Deshmukh, Harshal A.; Madsen, Anne Lundager; Vinuela, Ana; Have, Christian Theil; Grarup, Niels; Tura, Andrea; Mahajan, Anubha; Heggie, Alison J.; Koivula, Robert W.; De Masi, Federico; Tsirigos, Konstantinos K.; Linneberg, Allan; Drivsholm, Thomas; Pedersen, Oluf; Sorensen, Thorkild I. A.; Astrup, Arne; Gjesing, Anette A. P.; Pavo, Imre; Wood, Andrew R.; Ruetten, Hartmut; Jones, Angus G.; Koopman, Anitra D. M.; Cederberg, Henna; Rutters, Femke; Ridderstrale, Martin; Laakso, Markku; McCarthy, Mark; Frayling, Tim M.; Ferrannini, Ele; Franks, Paul W.; Pearson, Ewan R.; Mari, Andrea; Hansen, Torben; Walker, Mark (2021)
    Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 x 10(-9)) and rs9368219 in the CDKAL1 (P value = 3.15 x 10(-9)) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
  • Åström, Max J.; von Bonsdorff, Mikaela B.; Perälä, Mia M.; Salonen, Minna K.; Rantanen, Taina; Kajantie, Eero; Simonen, Mika; Pohjolainen, Pertti; Osmond, Clive; Eriksson, Johan G. (2018)
    Aims To assess whether disturbances in glucose regulation are associated with impairment in physical performance during a 10-year follow-up. Methods 475 Men and 603 women from the Helsinki Birth Cohort Study were studied. Glucose regulation was evaluated with a 2-h 75-g oral glucose tolerance test (OGTT) in 2001-2004. Subjects were categorised as having either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), newly diagnosed diabetes or previously known diabetes. Physical performance was assessed approximately 10 years later using the validated senior fitness test (SFT). The relationship between glucose regulation and the overall SFT score was estimated using multiple linear regression models. Results The mean age was 70.8 years for men and 71.0 years for women when physical performance was assessed. The mean SFT score for the whole population was 45.0 (SD 17.5) points. The SFT score decreased gradually with increased impairment in glucose regulation. Individuals with previously known diabetes had the lowest overall SFT score in the fully adjusted model (mean difference compared to normoglycaemic individuals -11.56 points, 95% CI - 16.15 to - 6.98, p <0.001). Both individuals with newly diagnosed diabetes and individuals with IGT had significantly poorer physical performance compared to those with normoglycaemia. No significant difference in physical performance was found between those with IFG and those with normoglycaemia. Conclusions Among older people, impaired glucose regulation is strongly related with poor physical performance. More severe disturbances in glucose regulation are associated with a greater decrease in physical function, indicating the importance of diagnosing these disturbances at an early stage.