A mathematical model for pattern of change in beta-cell reserve and factors affecting residual reserve within the first 2 years of type 1 diabetes

Abstract

The aim of this study was to investigate the effects of age, duration of diabetes, sex and ICA (Islet cell cytoplasmic antibody) on beta-cell reserves and to develop a model within the first 2 years of Type 1 diabetes. Beta-cell reserve is evaluated as fasting (FCp) and 1 mg i.v. glucagon stimulated C-peptide (SCp) levels in 58 Type 1 diabetics and in 12 normoglycemic subjects. Patients were divided into 3 groups according to duration of diabetes: Group I (2.5+/-0.3 weeks), Group II (13.4+/-1.2 months) and Group III (24.2+/-1.8 months). FCp/SCp level in nmol/l (mean+/-SE) were as follows. Group I: 0.21+/-0.02/0.38+/-0.04, Group II: 0.15+/-0.01/0.27+/-0.02, Group III: 0.07+/-0.01/0.11+/-0.02, CONTROL GROUP: 0.42+/-0.09/1.29+/-0.13. The scatter plots of C-peptide levels vs time in all the diabetic patients fitted in to a 4th-order polynomial regression (R: 0.96-0.98). Age was strongly correlated with FCp (rs: 0.46, p<0.05) and ICA positivity affected Cp-levels negatively (p>0.05). In conclusion, as the duration of diabetes increases, response time to glucagon prolongs and amplitude of it shortens. Duration of diabetes of less than 2 weeks, feminity, puberty and ICA positivity affect beta-cell reserve negatively, conversely, masculinity, post-puberty, older age and ICA negativity affect the reserve positively. The dynamics of C-peptide response to glucagon follow a mathematical model and Type 1 diabetes causes a decrease not only in the amplitude of the response but also in the duration of the response.