OGTT and random plasma glucose in the prediction of type 1 diabetes and time to diagnosis

Abstract

Aims/hypothesis We assessed the utility of the OGTT and random plasma glucose concentrations in predicting the time to diagnosis of type 1 diabetes. Methods A population-derived cohort of 14,876 newborns with HLA-conferred risk of type 1 diabetes were invited to regular follow-up for islet autoantibodies. When two or more autoantibodies were detected, an OGTT was performed once a year and random plasma glucose analysed twice a year. During follow-up, 567 children developed multiple autoantibodies, 255 (45%) of whom were diagnosed with type 1 diabetes, while 312 remained non-diabetic by December 2011.Results Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were risk factors for type 1 diabetes (HR 3.2 [95% CI 1.5, 7.0] and 8.3 [95% CI 6.0, 11.5], respectively). When a random plasma glucose value ≥7.8 mmol/l was observed, the HR for diabetes was 6.0 (95% CI 4.3, 8.6). The median time to diagnosis after the detection of IFG was 5.2 years (interquartile range [IQR] 3.4, 6.3); after IGT, 0.7 years (IQR 0.3, 1.9); and, after a random plasma glucose ≥7.8 mmol/l, 1.0 years (IQR 0.3, 1.5). In a retrospective analysis, both OGTT-derived 2 h plasma glucose and random plasma glucose started to increase 1.5 years before diagnosis (p<0.001 and p=0.004, respectively). Conclusions/interpretation Dysglycaemia detected in an OGTT or based on random plasma glucose is a useful marker in the prediction of time to onset of type 1 diabetes in high-risk children. Random plasma glucose is a simple and low-cost measurement with comparable predictive characteristics to that of OGTT-derived 2 h glucose.

Characteristics of the pre‐diabetic period in children with high risk of type 1 diabetes recruited from the general Swedish population—The ABIS study

“…Study inclusion was solely based on positivity to multiple autoantibodies, without considering genetic risk. HLA‐genotype was however determined after inclusion, and the distribution of genotypes associated to low, medium, or high risk of T1D showed that few individuals were classified as having high risk ( n = 4), while the vast majority had moderate ( n = 8) or low ( n = 9) risk (Table ). To increase the number of individuals in each subgroup and enable comparison between progressors and non‐progressors, we also grouped the children into those with increased risk (HLA‐genotypes conferring moderate or high risk) or without increased risk (low HLA‐risk genotypes).…”

“…Although dysglycemia was seen in many of the progressors long before disease onset, disturbed glycemic control was in fact observed in the majority of participants (14/21) without any significant difference between progressors and non‐progressors. The possibilities to predict diabetes and estimate time of disease onset based on measures of dysglycemia in high‐risk individuals have been addressed by previous studies . In the DIPP study, dysglycemia detected by random plasma glucose or during OGTT was a useful marker of progression to diabetes .…”

“…Sequence specific primers were used to identify polymorphic regions of DQB1, DQA1, and DRB1, more specifically the alleles DQA1: *01, *02, *03, *04, *05, *06, DQB1: *02, *03 (subtypes *0301/*0302/*0303/*0304), *04, *05, *06 (subtypes *0601/*0602/*0603), and DRB1: *03, *04 (subtypes *0403/*0407), *07, *09. Genotypes were classified into the risk categories low, moderate, and high, based on previous studies , . Briefly, high risk was defined as heterozygosity for DRB1*04:01/2/4/5/8‐DQA1*03‐DQB1*03:02/4 and DRB1*03‐DQA1*05‐DQB1*02, while moderate risk was defined as homozygosity for any of those risk haplotypes or DRB1*04:01/2/4/5/8‐DQA1*03‐DQB1*03:02/4 with a neutral haplotype, or the genotype DRB1*03‐DQA1*05‐DQB1*02/DRB1*09‐DQA1*03‐DQB1*03.…”

Dysregulation of glucose metabolism in preclinical type 1 diabetes

“…FPIR is constantly higher in non‐progressors than in progressors. Adapted from the original data from refs Koskinen et al , Helminen et al , Sosenko et al .…”

“…In a series of 403 DIPP children with multiple islet autoantibodies impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in an OGTT as defined by WHO were predictive for T1D with a HR of 3.2 and 8.3, respectively. The median time to diagnosis after IGT was 0.7 years showing that the simple 2‐point OGTT may also provide important information when estimating the time to clinical diagnosis of T1D .…”