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- Ortqvist, E., et al.
(författare)
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Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 27:9, s. 2191-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
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- Zachrisson, I, et al.
(författare)
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Determinants of growth in diabetic pubertal subjects
- 1997
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 20:8, s. 1261-1265
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects.RESEARCH DESIGN AND METHODS: In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS).RESULTS: The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3-5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = -0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth.CONCLUSIONS: In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.
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- Zachrisson, I, et al.
(författare)
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Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.
- 2000
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 10:6, s. 324-31
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Tidskriftsartikel (refereegranskat)abstract
- Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.
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- Zachrisson, I, et al.
(författare)
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Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.
- 2000
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 89:9, s. 1044-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. CONCLUSION: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.
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