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Invited Commentary
Ophthalmology
September 27, 2021

Insulin Pump Use and Diabetic Retinopathy—Is Technology the Key to Preventing Retinopathy in Young People With Type 1 Diabetes?

Author Affiliations
  • 1Department of Paediatrics, University of Otago, Christchurch, New Zealand
  • 2Department of Paediatrics, Canterbury District Health Board, Christchurch, New Zealand
  • 3Paediatric Endocrinology Service, Starship Children’s’ Hospital, Auckland District Health Board, Auckland, New Zealand
  • 4Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
JAMA Netw Open. 2021;4(9):e2127955. doi:10.1001/jamanetworkopen.2021.27955

Vascular complications such as diabetic retinopathy (DR) are the major causes of long-term disability and mortality in young people with diabetes. Although vascular disease is broadly associated with metabolic control, there are multiple potentially confounding factors, including socioeconomic status and race or ethnicity. Ferm and colleagues1 report that, among a large cohort of 1640 young patients aged 5 to 21 years with diabetes (25.4% of whom had type 2 diabetes), DR was associated with a longer duration of diabetes, higher mean hemoglobin A1c levels, and Black or African American race. Notably, race and ethnicity were not associated with DR in the multivariate analysis, suggesting that socioeconomic factors rather than race or ethnicity itself may be underlying this serious health disparity.

In a novel finding, the use of an insulin pump (ie, continuous subcutaneous insulin infusion [CSII]) was independently associated with lower rates of DR in the subset of 1217 participants with type 1 diabetes. This finding adds to the increasing data suggesting that insulin pump use among young patients with diabetes is associated with both better metabolic control and reduction in the risk of DR compared with other treatment approaches, such as multiple daily injections.2 This information is useful for young people with diabetes and their parents. Unfortunately, there was an insufficient number of patients with type 2 diabetes who were receiving CSII to evaluate whether this therapy was equally protective for type 2 diabetes; this issue will be important to examine in the future.

The authors reasonably hypothesize that the association between the use of an insulin pump and lower DR rates was mediated by reduced glycemic variability or reduced time in range but were unable to test this hypothesis because only a small number of patients were using continuous glucose monitors (CGMs). Two assumptions underpin this proposed protective mechanism: first, that insulin pump therapy reduces glycemic variability, and second, that glycemic variability accelerates the development of DR independent of the impact of mean glucose as measured by hemoglobin A1c levels. Thankfully, the converse, which is the possibility that long-acting insulins, such as glargine, might increase DR, has been previously ruled out.3 There are data suggesting that the addition of CGM to CSII further improves time in range and glucose variability.4 However, it is notable that Ferm and colleagues1 did not find that CGM use was associated with a reduced risk of DR. This lack of association may reflect CGM use in routine practice rather than its use in focused studies.

Thus, although it is highly plausible that CSII is associated with reductions in glycemic variability, we will need to wait for prospective registries that collect CGM data to mature before we can truly understand the association between glycemic variability and the development of long term diabetes complications, such as DR. The mechanisms by which glycemic variability might increase retinal damage are unclear. There are some indirect signs suggesting that glycemic variability can promote the development of diabetes complications. For example, rapid improvement in glycemic control with insulin or other therapies can accelerate DR,5 which is potentially associated with changes in transepithelial osmotic pressure or control of arterial blood pressure. This process supports the concept that reduced daily glycemic fluctuation could help dampen such physiological responses.

The Ferm et al1 study adds to the body of data supporting the use of technologies to improve glycemia, both in terms of the traditional hemoglobin A1c measure and its established association with DR6 and in terms of newer measures, such as glycemic variability and time in range. In this context, it is important to appreciate that automated insulin delivery may be even more beneficial in improving overall metabolic control than CSII or CGM.6,7 However, as Ferm and colleagues1 highlight, socioeconomically deprived young patients who have limited means to access diabetes technologies continue to have the worst glycemic indices and remain at the highest risk for developing complications. Improving technologies simply will not improve outcomes when those who need them most cannot access them. Thus, a focus on health equity to enable universal access to diabetes technologies is important if we are to make meaningful changes in the long-term prognosis of young patients with diabetes.

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Article Information

Published: September 27, 2021. doi:10.1001/jamanetworkopen.2021.27955

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 de Bock M et al. JAMA Network Open.

Corresponding Author: Alistair J. Gunn, MBChB, PhD, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand (aj.gunn@auckland.ac.nz).

Conflict of Interest Disclosures: Dr Gunn reported receiving grants from the Health Research Council of New Zealand outside the submitted work. No other disclosures were reported.

References
1.
Ferm  ML, DeSalvo  DJ, Prichett  LM, Sickler  JK, Wolf  RM, Channa  R. Clinical and demographic factors associated with diabetic retinopathy among young patients with diabetes. JAMA Netw Open. 2021;4(9):e2126126. doi:10.1001/jamanetworkopen.2021.26126
2.
Downie  E, Craig  ME, Hing  S, Cusumano  J, Chan  AKF, Donaghue  KC.  Continued reduction in the prevalence of retinopathy in adolescents with type 1 diabetes: role of insulin therapy and glycemic control.   Diabetes Care. 2011;34(11):2368-2373. doi:10.2337/dc11-0102PubMedGoogle ScholarCrossref
3.
Rosenstock  J, Fonseca  V, McGill  JB,  et al.  Similar progression of diabetic retinopathy with insulin glargine and neutral protamine hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study.   Diabetologia. 2009;52(9):1778-1788. doi:10.1007/s00125-009-1415-7PubMedGoogle ScholarCrossref
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Thomas  MG, Avari  P, Godsland  IF, Lett  AM, Reddy  M, Oliver  N.  Optimising type 1 diabetes after multiple daily injections and capillary blood monitoring: pump or sensor first? a meta-analysis using pooled differences in outcome measures.   Diabetes Obes Metab. Published online July 19, 2021. doi:10.1111/dom.14498PubMedGoogle Scholar
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Bain  SC, Klufas  MA, Ho  A, Matthews  DR.  Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: a review.   Diabetes Obes Metab. 2019;21(3):454-466. doi:10.1111/dom.13538PubMedGoogle ScholarCrossref
6.
DiMeglio  LA, Acerini  CL, Codner  E,  et al.  ISPAD Clinical Practice Consensus Guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes.   Pediatr Diabetes. 2018;19(suppl 27):105-114. doi:10.1111/pedi.12737PubMedGoogle ScholarCrossref
7.
Pease  A, Lo  C, Earnest  A, Kiriakova  V, Liew  D, Zoungas  S.  The efficacy of technology in type 1 diabetes: a systematic review, network meta-analysis, and narrative synthesis.   Diabetes Technol Ther. 2020;22(5):411-421. doi:10.1089/dia.2019.0417PubMedGoogle ScholarCrossref
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