The variability in beta-cell function in placebo-treated subjects with type 2 diabetes: application of the weight-HbA1c-insulin-glucose (WHIG) model.
Br J Clin Pharmacol
; 83(3): 487-497, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-27679422
ABSTRACT
AIM:
The weight-glycosylated haemoglobin (HbA1C)-insulin-glucose (WHIG) model describes the effects of changes in weight on insulin sensitivity (IS) in newly diagnosed, obese subjects receiving placebo treatment. This model was applied to a wider population of placebo-treated subjects, to investigate factors influencing the variability in IS and ß-cell function.METHODS:
The WHIG model was applied to the WHIG dataset (Study 1) and two other placebo datasets (Studies 2 and 3). Studies 2 and 3 consisted of nonobese subjects and subjects with advanced type 2 diabetes mellitus (T2DM). Body weight, fasting serum insulin (FSI), fasting plasma glucose (FPG) and HbA1c were used for nonlinear mixed-effects modelling (using NONMEM v7.2 software). Sources of interstudy variability (ISV) and potential covariates (age, gender, diabetes duration, ethnicity, compliance) were investigated.RESULTS:
An ISV for baseline parameters (body weight and ß-cell function) was required. The baseline ß-cell function was significantly lower in subjects with advanced T2DM (median difference Study 2 15.6%, P < 0.001; Study 3 22.7%, P < 0.001) than in subjects with newly diagnosed T2DM (Study 1). A reduction in the estimated insulin secretory response in subjects with advanced T2DM was observed but diabetes duration was not a significant covariate.CONCLUSION:
The WHIG model can be used to describe the changes in weight, IS and ß-cell function in the diabetic population. IS remained relatively stable between subjects but a large ISV in ß-cell function was observed. There was a trend towards decreasing ß-cell responsiveness with diabetes duration, and further studies, incorporating subjects with a longer history of diabetes, are required.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Peso Corporal
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Hemoglobinas Glicadas
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Resistência à Insulina
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
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Insulina
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article