Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin

Abstract

Aims/hypothesis: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI).

Methods: This is a retrospective cohort study using the Scottish Care Information - Diabetes database for retinal screening outcomes and HbA_1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan-Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA_1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA_1c and change in HbA_1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts.

Results: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA_1c and higher diastolic BP at baseline. There was a larger reduction in HbA_1c at 1 year in those on CSII vs MDI (-6 mmol/mol [-0.6%] vs -2 mmol/mol [-0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA_1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA_1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group.

Conclusions/interpretation: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA_1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA_1c.

Keywords: Clinical diabetes; Clinical science; Insulin therapy; Microvascular complications; Retinopathy.

Fig. 1

Flow chart showing number of people assessed and analysed for CSII and MDI groups and exclusions

Fig. 2

Retinopathy in comparator treatment groups (a) and HbA_1c subgroups (b–e). Kaplan–Meier survival plots compare event-free survival rates in CSII/MDI treatment groups (a) and HbA_1c subgroups (b–e). An event corresponds to diabetic retinopathy progression and was defined as a minimum one-grade worsening in either eye from the baseline grading. Vertical dashes indicate participants who were censored due to incomplete 3 year follow-up. (a) Comparison of CSII (blue) and MDI (red) participants for the entire cohort. CSII was associated with significantly reduced retinopathy progression over 3 years compared with MDI (p=0.0097). (b, c) Comparison of participants with baseline HbA_1c <58 mmol/mol (7.5%) (low: lilac), 58–75 mmol/mol (7.5–9%) (middle: blue) or >75 mmol/mol (9%) (high: red) in the CSII group (b) and the MDI group (c). High baseline HbA_1c (>75 mmol/mol [9%]) was associated with increased diabetic retinopathy progression in the MDI group (p=0.0049) but was not a determinant of diabetic retinopathy progression in the CSII group (p=0.93). (d, e) Comparison of unmatched participants with change in HbA_1c at 1 year of less than −5 mmol/mol (0.5%) (decrease: lilac), −5 to 5 mmol/mol (0.5 to 0.5%) (stable: blue) or more than 5 mmol/mol (0.5%) (increase: red) in the CSII group (d) and the MDI group (e). Change in HbA_1c at follow-up did not significantly impact diabetic retinopathy progression in either cohort