Thirty years of adolescent type 1 diabetes: progress that stopped

Design

longitudinal clinic cohort analysed by decade using generalised estimating equations, 1990-2019

Population

2,761 adolescents aged 12-20 with type 1 diabetes of at least five years' duration, 5,487 visits

Primary outcome

retinopathy, albuminuria, peripheral nerve and autonomic function by decade

Effect

retinopathy 40% to 21% to 20% (p<0.001); twice-daily insulin versus MDI/pump OR 1.59 (1.23-2.06) for retinopathy; higher HbA1c coefficient of variation associated with albuminuria 1.26 (1.04-1.52) and autonomic abnormality 1.49 (1.08-2.05)

Complication rates in young people with type 1 diabetes fell steeply in the 1990s, and the assumption has been that they kept falling. This analysis of 2,761 adolescents aged 12 to 20 with at least five years of diabetes, seen over 5,487 visits between 1990 and 2019, tested that by decade.

Retinopathy fell from 40% in the 1990s to 21% in the 2000s and then stopped, at 20% in the 2010s. Early rises in albumin-to-creatinine ratio followed the same shape (35%, 29%, 28%). Peripheral nerve abnormality fell between the last two decades (35% to 28%), while heart rate variability abnormality (37% to 38%) and frank albuminuria (6%, 4%, 4%) did not move at all. Over the same period the proportion reaching an HbA1c under 7.0% rose only from 7.4% to 14.1%, despite multiple daily injections and pumps largely replacing twice-daily insulin.

Two associations in the multivariable model are worth carrying into clinic. Twice-daily insulin was associated with more retinopathy and more early albumin elevation than multiple daily injections or pump therapy. And after adjusting for mean HbA1c, greater HbA1c variability — the coefficient of variation between visits — was independently associated with early albumin elevation, albuminuria and autonomic abnormality. Consistency, not just the average, appears to matter, which is an argument for the technology that smooths glucose rather than only lowering it.

• Look at HbA1c variability across visits, not only the latest value
• Twice-daily insulin regimens were associated with more retinopathy and early albumin elevation
• Continue annual retinal and urine albumin screening from five years of diagnosis
• Autonomic dysfunction did not improve across three decades — it is not being addressed
• Fewer than one in seven adolescents reached HbA1c under 7% even in the most recent decade

The statistics, in plain English

These are repeated measures on the same adolescents, handled with generalised estimating equations so that multiple visits per person do not count as independent observations. An odds ratio of 1.59 (95% CI 1.23-2.06) for retinopathy with twice-daily insulin is an association in an era when regimen and everything else about care changed together, so it cannot be read as the regimen causing the retinopathy. The HbA1c variability associations (1.27, 1.26, 1.49) are modest, adjusted for mean HbA1c, and consistent across three different outcomes, which is what makes them worth noting rather than any single value.

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