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- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010
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| 2. |
- Ising, Erik, et al.
(författare)
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Vibrotactile sense in children with type 1 diabetes
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 66:Suppl 1, s. 153-153
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Konferensbidrag (refereegranskat)abstract
- Introduction: Diabetic peripheral neuropathy (DPN) is a devastating complication to DM, potentially leading to diabetic foot ulcers. Studies using electrophysiology shows high occurrence of subclinical DPN among children, but it is unclear when and how to start screen children with T1D for DPN. Aim: To investigate whether evaluation of the vibrotactile sense, using a multi-frequency method, in the right hand and foot can detect underlying sensory neuropathy in children with T1D, and whether the DPN has any correlation to, for example, gender, age, duration of disease and metabolic control measured as HbA1c values. Methods: Vibration perception thresholds (VPTs), resulting in curves and numeric values, were evaluated using a VibroSense Meter. VPTs were related to normative data obtained from healthy children, and evaluated in relation to different characteristics. Subjects were 8-18 years old T1D patients. Subjects that failed to produce at least one visibly evaluable curve were excluded. Z-values of >2.0 were considered pathological. Subjects needed at least 3 pathological frequencies at the same site in order to claim the examined site as pathological. Results: 73 children (boys = 39) with mean age 13.2 [8.39-17.96] years and duration of T1D of 5.9 [0.54-14.58] years met the inclusion and exclusion criteria. On index and little fingers, 5/73 (6.8%) and 4/73 (5.5%) children respectively had pathological values. On metatarsal heads one and five, 9/73 (12.3%) children had pathological values on each site. In total 15/73 (21.0%) children had at least one pathological site and 3 (4.1%) had pathological values on all sites examined. Presence of pathological values on all sites correlated to the height of the subject (p = 0.011) but not to gender, duration of disease or HbA1c. Conclusion: Our findings suggests that DPN, reflected by impaired vibrotactile sense, is present among children with T1D. Since up to 21% of the children showed signs of impaired vibrotactile sense, it may be important to screen children with T1D for early detection of DPN.
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