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Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.

ABSTRACT: AIMS/HYPOTHESIS:Beta cell function in type 1 diabetes is commonly assessed as the average plasma C-peptide concentration over 2 h following a mixed-meal test (CPAVE). Monitoring of disease progression and response to disease-modifying therapy would benefit from a simpler, more convenient and less costly measure. Therefore, we determined whether CPAVE could be reliably estimated from routine clinical variables. METHODS:Clinical and fasting biochemical data from eight randomised therapy trials involving participants with recently diagnosed type 1 diabetes were used to develop and validate linear models to estimate CPAVE and to test their accuracy in estimating loss of beta cell function and response to immune therapy. RESULTS:A model based on disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose most accurately estimated loss of beta cell function (area under the receiver operating characteristic curve [AUROC] 0.89 [95% CI 0.87, 0.92]) and was superior to the commonly used insulin-dose-adjusted HbA1c (IDAA1c) measure (AUROC 0.72 [95% CI 0.68, 0.76]). Model-estimated CPAVE (CPEST) reliably identified treatment effects in randomised trials. CPEST, compared with CPAVE, required only a modest (up to 17%) increase in sample size for equivalent statistical power. CONCLUSIONS/INTERPRETATION:CPEST, approximated from six variables at a single time point, accurately identifies loss of beta cell function in type 1 diabetes and is comparable to CPAVE for identifying treatment effects. CPEST could serve as a convenient and economical measure of beta cell function in the clinic and as a primary outcome measure in trials of disease-modifying therapy in type 1 diabetes.

SUBMITTER: Wentworth JM

PROVIDER: S-EPMC6518395 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.

Wentworth John M JM Bediaga Naiara G NG Giles Lynne C LC Ehlers Mario M Gitelman Stephen E SE Geyer Susan S Evans-Molina Carmella C Harrison Leonard C LC

Diabetologia 20180830 1

<h4>Aims/hypothesis</h4>Beta cell function in type 1 diabetes is commonly assessed as the average plasma C-peptide concentration over 2 h following a mixed-meal test (CP<sub>AVE</sub>). Monitoring of disease progression and response to disease-modifying therapy would benefit from a simpler, more convenient and less costly measure. Therefore, we determined whether CP<sub>AVE</sub> could be reliably estimated from routine clinical variables.<h4>Methods</h4>Clinical and fasting biochemical data fro ...[more]

PMID: 30167735

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Project description:Aims/hypothesisSouth Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored.MethodsTwo cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan's Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank.ResultsThe prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24-39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353-616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively.Conclusions/interpretationThe prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function.

Dataset Information

Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.

Publications

Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.

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