| 81. |
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| 82. |
- Weng, Jianping, et al.
(författare)
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An automated fluorescent single strand conformation polymorphism technique for high throughput mutation screening
- 2001
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 114:11, s. 1147-1150
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a high throughput mutational detection method by multiple fluorescence-labeled polymerase chain reaction (PCR) products. METHODS: A total of 27 known mutations including 22 substitutions, 3 insertions (1, 2 and 7 bp) and 2 deletions (1 and 2 bp) in the hepatocyte nuclear factor (HNF)-4 alpha, glucokinase and HNF-1 alpha genes were tested. During nested PCR, amplified fragments were labeled with three fluorescent dyes. PCR products were visualized with an ABI-377 fluorescence sequencer using 5% glycerol or 10% sucrose in non-denaturing gel conditions. RESULTS: Twenty-five of 27 variants (93%) could be detected by combining 5% glycerol and 10% sucrose gel matrix conditions. Twenty-two of 27 (82%) and 18 of 27 (67%) variants were identified using 5% glycerol and 10% sucrose conditions, respectively. CONCLUSION: This fluorescence-based PCR single strand conformation polymorphism technique represents a simple, non-hazardous, time-saving and sensitive method for high throughput mutation detection.
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| 83. |
- Weng, J., et al.
(författare)
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Functional consequences of mutations in the MODY4 gene (IPF1) and coexistence with MODY3 mutations
- 2001
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 44:2, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. The aim of this study was to examine the putative role of mutations in the insulin promoter 1 (IPF1) gene in early-onset diabetes. Methods. We carried out mutation screening of the IPF1 gene in 115 Scandinavian families with at least two members with onset of diabetes younger than 40 years. The allele frequencies were also tested in 183 unrelated patients with late-onset Type II (noninsulin-dependent) diabetes mellitus and in 92 nondiabetic control subjects. Results. Two novel IPF1 variants (G212R and P239Q) and one previously reported (D76N) IPF1 variant were identified in the 115 families (3.5%). The D76N variant was found in one MODY3 family (S315fsinsA of HNF1 alpha) and also in two families with late-onset Type II diabetes. The P239Q variant was identified in two families with early-onset diabetes including one with MODY3 (R272C of HNF1 alpha) and in three families with late-onset Type II diabetes. Despite the fact that the variants did not segregate completely with diabetes, the non-diabetic carriers of the IPF1 variants had increased blood glucose concentrations (p < 0.05) and reduced insulin:glucose ratios (p < 0.05) during an oral glucose tolerance test compared with non-diabetic family members without these variants. In addition, when the G212R and P239Q variants were expressed in cells without IPF1 i.e.. Nes2y cells, both variants showed about a 50% reduction in their ability to activate insulin gene transcription compared to wild-type IPF1, as measured by reporter gene assay. Conclusion/interpretation. Although mutations in the IPF-1 gene are rare in early- (3.5%) and late-onset (2.7%) Type II diabetes, they are functionally important and occur also in families with other MODY mutations.
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| 84. |
- Weng, Jianping, et al.
(författare)
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Screening for MODY mutations, GAD antibodies, and type 1 diabetes--associated HLA genotypes in women with gestational diabetes mellitus.
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 25:1, s. 68-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS: There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1alpha gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS: MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.
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| 85. |
- Ylonen, K, et al.
(författare)
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Associations of dietary fiber with glucose metabolism in nondiabetic relatives of subjects with type 2 diabetes - The Botnia Dietary Study
- 2003
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Ingår i: Diabetes Care. - 1935-5548. ; 26:7, s. 1979-1985
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To study cross-sectional associations of dietary fiber intake with insulin resistance, insulin secretion, and glucose tolerance in a population at high risk for type 2 diabetes. RESEARCH DESIGN AND METHODS - The subjects consisted of 248 male and 304 female adult nondiabetic relatives of patients with type 2 diabetes. Dietary intake was measured by means of two 3-day food records. Associations of total, water-insoluble, and water-soluble fiber with measures of glucose metabolism based on an oral glucose tolerance test, were analyzed by multiple linear regression analysis adjusting for sex, age, length of education, physical activity, BMI, waist-to-hip ratio, systolic blood pressure, and serum triglyceride and HDL cholesterol concentrations. The homeostasis model assessment insulin resistance index, the incremental 30-min serum insulin concentration divided by the incremental 30-min glucose concentration, and fasting and 2-h glucose concentrations were the outcome variables. RESULTS - The dietary intake of total as well as water-insoluble and water-soluble fiber was inversely associated with insulin resistance: -0.17 (0.07), P = 0.012; -0.15 (0.07), P = 0.024; and -0.14 (0.07), P = 0.049 [regression coefficients (SE)]. Fiber variables were unrelated to insulin secretion and plasma glucose concentrations. CONCLUSIONS - The results support evidence that a high intake of dietary fiber is associated with enhanced insulin sensitivity and therefore may have a role in the prevention of type 2 diabetes.
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| 86. |
- Ylonen, K, et al.
(författare)
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Dietary intakes and plasma concentrations of carotenoid's and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study
- 2003
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 77:6, s. 1434-1441
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of antioxidants in the pathogenesis of type 2 diabetes is uncertain. Objective: We evaluated cross-sectional relations of dietary intakes and plasma concentrations of antioxidants with glucose metabolism in a high-risk population. Design: The subjects, were 81 male and 101 female first- and second-degree, nondiabetic relatives of patients with type 2 diabetes. Antioxidant intake data were based on 3-d food records. Subjects taking supplements containing beta-carotene or alpha-tocopherol were excluded. Plasma antioxidant concentrations were measured by HPLC. By using multiple linear regression analysis and adjusting for demographic, anthropometric, and lifestyle covariates, we studied whether dietary and plasma alpha- and beta-carotene, lycopene, and alpha- and gamma-tocopherol were related to fasting and 2-h concentrations of glucose and nonesterified fatty acids during an oral-glucose-tolerance test, to the homeostasis model assessment index of insulin resistance, and to measures of beta cell function (incremental 30-min serum insulin concentration during an oral-glucose-tolerance test and first-phase insulin secretion during an intravenous-glucose-tolerance test). Results: In men, dietary carotenoids were inversely associated with fasting plasma glucose concentrations (P < 0.05), plasma beta-carotene concentrations were inversely associated with insulin resistance (P = 0.003), and dietary lycopene was directly related to baseline serum concentrations of nonesterified fatty acids (P = 0.034). In women, dietary alpha-tocopherol and plasma beta-carotene concentrations were inversely and directly associated, respectively, with fasting plasma glucose concentrations (P < 0.05). In both sexes, cholesterol-adjusted alpha-tocopherol concentrations were directly associated with 2-h plasma glucose concentrations (P < 0.05). Conclusion: The data suggest an advantageous association of carotenoids, which are markers of fruit and vegetable intake, with glucose metabolism in men at high risk of type 2 diabetes.
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| 87. |
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