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Carbohydrate metabolism and capillary basement-membrane thickness in children. II. Longitudinal studies
Insights
This study in children with diabetes found that adding tolazamide to phenformin improved glucose tolerance, but this effect wasn't sustained. Capillary basement membrane thickness and glucose tolerance showed a significant inverse relationship.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Vascular Biology
Background:
- Oral hypoglycemic agents are used in pediatric diabetes management.
- Understanding the long-term effects on glucose metabolism and vascular parameters is crucial.
Purpose of the Study:
- To investigate the longitudinal effects of oral hypoglycemic agents on glucose tolerance and capillary basement membrane thickness (BMT) in children.
- To explore the relationship between glucose disappearance rate (K) and BMT.
Main Methods:
- Longitudinal biochemical and histologic studies in 11 children (5 with suspected diabetes, 6 with diabetes).
- Treatment involved phenformin alone, followed by the addition of tolazamide.
- Measurements included fasting plasma glucose (FPG), glucose disappearance rate (K), fasting plasma insulin, peak insulin response, and capillary BMT.
Main Results:
- Phenformin alone did not significantly alter FPG.
- Addition of tolazamide significantly decreased FPG within 6-10 weeks, but this was not sustained.
- A significant inverse relationship was observed between glucose disappearance rate (K) and both average and minimum BMT (P < 0.001 and P < 0.05, respectively).
- Individual changes in K and BMT did not correlate well in magnitude.
Conclusions:
- Glucose tolerance and capillary basement membrane thickness exhibit a close interdependence in children with diabetes.
- The therapeutic effects of combined phenformin and tolazamide on glucose tolerance may not be sustained long-term.
- Further research is needed to elucidate the complex variables influencing BMT and K.
Abstract:
Longitudinal biochemical and histologic studies were carried out in 11 children receiving oral hypoglycemic agents. There were five "suspected" diabetics (with evidence of glucose intolerance but without repeated fasting hyperglycemia) and six diabetics. Mean fasting plasma glucose (FPG) values showed no significant change during treatment with phenformin alone. The mean FPG decreased significantly within six to 10 weeks after addition of tolazamide to the regimen, but the decrease was not sustained during long-term observation (seven months to four years). Glucose disappearance rate (K) generally increased as FPG decreased, but the number of observations was smaller, and mean values showed no significant change. Mean values for fasting plasma insulin and for peak insulin response to intravenously administered glucose did not change significantly. Changes in capillary basement membrane thickness (BMT) were found to be statistically significant in a number of individual instances. Decreasing BMTs were associated with increasing Ks and vice versa. A similar trend was apparent among other patients, in whom individual changes in BMT were not statistically significant. The pooled data were therefore subjected to chi-square analysis; K and average BMT were found to change in opposite directions (P less than 0.001); a similar relationship held for K and minimum BMT (P less than 0.05). But K and BMT did not correlate well as regards magnitude of change. Influences of phenformin and tolazamide on these changes could not be evaluated. Both BMT and K may be influenced by many complex variables, but the present findings indicate that glucose tolerance and BMT have a close interdependence.