Near-normoglycaemia and development of neuropathy: a 24-year prospective study from diagnosis of type 1 diabetes

OBJECTIVE Complete prevention of diabetic neuropathies has not been previously demonstrated. We sought to determine whether long-term near-normoglycaemia maintained from the diagnosis of type 1 diabetes is associated with polyneuropathy and cardiac autonomic dysfunction. DESIGN Prospective observational study over 24 years. SETTING Ambulatory care. PARTICIPANTS 32 newly diagnosed patients with type 1 diabetes aged 20.3 ± 1.0 years, duration of diabetes 2.7 ± 0.3 weeks. INTERVENTION Insulin therapy according to standards of care. PRIMARY AND SECONDARY OUTCOME MEASURES Motor and sensory nerve conduction velocity (MNCV and SNCV), heart rate variability (HRV), and confirmed clinical polyneuropathy measured at 15 time points over 24 years and quantitative sensory testing (QST) determined over 20-22 years. RESULTS 11 patients were well controlled over 24 years with mean glycated haemoglobin (HbA1c) <7.0% (6.5 ± 0.1%; group 1), whereas 21 patients were poorly controlled (mean HbA1c ≥ 7.0%: 8.3 ± 0.2%; group 2). After 24 years, MNCV was faster in group 1 versus group 2 in the median (55.5 ± 1.6 vs 48.9 ± 1.6 m/s), ulnar (56.5 ± 1.5 vs 49.3 ± 1.7 m/s) and peroneal nerve (44.7 ± 1.6 vs 36.8 ± 2.5 m/s), while SNCV was faster in the median (53.6 ± 1.6 vs 45.5 ± 2.8 m/s), ulnar (54.7 ± 1.8 vs 43.0 ± 3.9 m/s), and sural nerve (44.5 ± 1.8 vs 35.5 ± 2.6 m/s; all p<0.05). The annual decline in peroneal MNCV and sural SNCV in group 1 was sixfold and threefold faster in group 2 than in group 1, respectively. Likewise, impairment in QST and HRV developed at faster rates in group 2. After 24 years, 64% of patients in group 2, but none in group 1, developed confirmed clinical polyneuropathy. CONCLUSIONS Near-normoglycaemia maintained from the diagnosis of type 1 diabetes over 24 years was associated with a complete prevention of the decline in hyperglycaemia-related peripheral and autonomic nerve function, and development of confirmed clinical polyneuropathy.