ESPEYB20 8. Type 1 Diabetes New Paradigms (3 abstracts)
8.9. Elevations in blood glucose before and after the appearance of islet autoantibodies in children
Warncke K , Weiss A , Achenbach P , von dem Berge T , Berner R , Casteels K , Groele L , Hatzikotoulas K , Hommel A , Kordonouri O , Elding Larsson H , Lundgren M , Marcus BA , Snape MD , Szypowska A , Todd JA , Bonifacio E , Ziegler AG & GPPAD POInT Study Groups
J Clin Invest 2022;132(20):e162123.PMID: 36250461
Brief summary: In this longitudinal study, blood glucose trajectories and their relationship with autoantibodies appearance were assessed in 1050 children with high genetic risk of type 1 diabetes (T1D) between 4 months and 3.6 years. Post-prandial blood glucose levels increased around 2 months prior to autoantibody seroconversion, with further increases thereafter, suggesting that islet autoimmunity co-occurs or follows insults on the β-cells.
This recent study proposes a re-assessment of the classical cascade of events in the natural history of T1D, which states that genetically susceptible individuals develop islet autoimmunity, followed after a variable time by the appearance of glucose abnormalities (1). The authors measured pre- and postprandial blood glucose concentrations in a large number of children at increased genetic risk of developing T1D, recruited in the Primary Oral Insulin Trial (POInT) (2). The findings reveal a dynamic process of glucose regulation during infancy and early childhood. Of interest, pre-prandial glucose levels showed a U-shaped curve, with the highest levels in infancy, a nadir at 12-18 months of age, and a subsequent increase up to 3.5 years. The finding of decreasing glucose levels was novel, and the reported patterns likely reflect changes in the pancreatic islet cells and suggest the need to study physiological maturation of glucose metabolism and β-cell function earlier in life. Glucose trajectories were influenced by sex, BMI, and genetic factors, including the T1D susceptibility genotype at the insulin gene, INS.
Increased blood glucose concentrations were observed in children who developed islet autoantibodies, with the 30-minute post-prandial blood glucose levels being 0.3 mmol/l (6 mg/dl) higher already 2 months before autoantibody seroconversion. After seroconversion there was a further increase in post-prandial and subsequent rises in pre-prandial values. These findings suggest that the onset of early islet autoimmunity is associated with or preceded by insults or changes to the pancreatic β-cells that deregulate glucose metabolism.
Overall, the study highlights that impaired glucose homeostasis is present earlier in the T1D disease process than previously thought. There is a need for further research to understand the molecular basis of the early deterioration of glucose homeostasis and β-cells. Future studies should assess fasting glucose and consider a better standardization for post-prandial glucose measurements, as well as included children seroconverting at a later age, to assess if glucose changes occur independently of age.
References: 1. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10): 1964–1974. 2. Ziegler AG, Achenbach P, Berner R, et al. Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol. BMJ Open. 2019;9(6): e028578.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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