The KIND cohort profile: longitudinal assessment of glycaemic management and neurophysiological outcomes in paediatric type 1 diabetes in Switzerland

1 ABSTRACT Purpose The KIND (KINder mit Diabetes) cohort investigates diabetic peripheral neuropathy (DPN) in paediatric type 1 diabetes (T1D). Current guidelines recommend DPN screening at puberty or from 11 years and 2-5 years after T1D diagnosis, yet subclinical neurophysiological changes occur within the first 2 years. The cohort examines: (1) longitudinal associations between glycaemic metrics (HbA1c and continuous glucose monitoring-derived variability metrics) and peripheral nerve function and structure; (2) comparative predictive value of different variability metrics; (3) developmental trajectories of nerve maturation in T1D versus controls; (4) effects of residual beta-cell function on neuropathy progression; and (5) how early signs of DPN differ between patients with multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) therapy. Participants This prospective cohort, initiated in June 2019, continuously enrols children and young adults with T1D (≤21 years) at two Swiss centres. The care-embedded design integrates research into quarterly diabetes care and annual comprehensive assessments. So far, 141 T1D cohort participants (median age: 12.2; IQR: [8.4; 14.3] years; 47.5 % female) and 103 healthy controls (10.9 [7.5; 14.2] years; 53.4 % female) were recruited. Controls for neurophysiological examinations comprise measurements from the healthy, contralateral side of children with limb injuries in the surgical outpatient clinic of the Children’s hospital of Eastern Switzerland (OKS). Multimodal assessments comprise nerve conduction studies (peroneal, tibial, median motor and sensory) and high-resolution ultrasound, with development-adjusted analyses distinguishing diabetes effects from normal growth. Findings to date Cross-sectional analysis showed reduced nerve conduction velocities across all nerves, particularly peroneal in T1D patients (n=53) compared to healthy controls (n=50). Height-adjusted peroneal velocity (dNCV) correlated negatively with glucose variability (SD: r=-0.45, p=0.009), HbA1c (r=-0.27, p=0.049). During the first five years, dNCV correlated negatively with diabetes duration (r=-0.41, p=0.004), independent of glycaemic control. The cross-sectional area of the median nerve increased on average by 0.217 mm² per 1% HbA1c (p=0.004) and was already detectable with diabetes duration