2023-06-20 21:21:30
Why is this important?
The natural history of type 1 diabetes gradually leads to a complete inability to secrete insulin. It is described that age or HLA genotype influences this kinetics from the onset of the disease. However, various studies have been able to show that the deficit was not always total, as reflected by the dosage of the C-peptide which, in certain studies, confirms the maintenance of residual endogenous secretion in certain patients, even in the long term. However, the clinical importance of this residual production is not clearly established. Among the available data, the DCCT study showed that secretion greater than 0.2 nmol/L was associated with better control of glycated hemoglobin (HbA1c) for lower doses of insulin administered, and less complications (episodes of hypoglycaemia, retinopathy) compared to subjects whose secretion was lower. Resulting from a follow-up over 5 years, this study had neither the duration nor the power necessary to refine the prognostic value of this secretion. The follow-up of three Finnish cohorts, in a country where the prevalence of the disease is among the highest, gives this new study unprecedented power, thanks to the number of patients and its long follow-up period.
Methodology
This analysis was carried out from the follow-up of subjects who had recently been diagnosed with type 1 diabetes, and cross-sectional data from patients followed over a long period. The first had benefited from regular blood glucose and C-peptide assays every 3 months during their follow-up. The second came from a cohort of people of European origin (FinnDiane) diagnosed following the age of 5, and from a registry (DIREVA) which had included participants from 2009. The study sought the association between C-peptide value, polygenic risk scores and clinical outcome.
Principle results
In total, the cross-sectional study involved 110 people positive for autoantibodies (anti-GAD, anti-IA2 or ICA) and diagnosed following the age of 16 years (median age at diagnosis 30.0 years, median follow-up post -diagnosis 3.3 years), as well as in 847 children diagnosed before the age of 16 (median age at diagnosis 8.0 years, median post-diagnosis follow-up 36 months).
Among the latter, once distributed according to age at diagnosis (<5 years, 5-9 years, 10-15 years), the median C-peptide level increased during an initial period of a few months, then gradually decreased. Age at diagnosis was correlated with decline in C-peptide secretion: following 3 years, more of them maintained a residual level (≥0.02 nmol/L) among those diagnosed the latest (31.4 %) compared to those diagnosed younger (18.8% and 6.8% respectively for 5-9 year olds and <5 year olds).
Multiple autoantibody positivity increased the risk by 3.12 ([1,35-7,21], p=0.0083) to have low residual insulin secretion. Having an HLA genotype at risk for type 1 diabetes was associated with a C-peptide level <0.2 mol/L (adjusted HR 2.15 [1,18-3,90]p=0.012 and 1.36 [1,05-1,75]p=0.022 for high-risk or medium-risk genotypes).
The cross-sectional analysis was conducted using 3,984 participants recruited in FinnDiane and 645 in DIREVA. After a median of 21.6 years, 19.4% of patients had residual C-peptide secretion. This secretion was associated with a lower polygenic risk of type 1 diabetes compared to participants without C-peptide (p<0 .0001).
Furthermore, having a trough level of serum C-peptide was inversely associated with having high blood pressure, a high HbA1c level or a high total cholesterol level. It was also independently associated with the risk of developing microvascular complications (adjusted OR 0.61 [0,38-0,96] et 0,55 [0,34-0,89] for nephropathy and retinopathy respectively, p significant).
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