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Glycemic Variability and Development of Retinopathy

Jan 26, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy

Study assesses glycemic variability via continuous glucose monitoring and compares it against incidence of diabetic retinopathy to determine if correlation exists.

Recently, variability in glycemic levels has garnered much interest in the research community. The evidence produced by this research suggests that glycemic variability causes increased oxidative stress on the vasculature, which ultimately results in an increased risk of a variety of micro- and macrovascular complications in those with diabetes. However, the currently available research has not yet determined if glycemic variability is correlated with increased risk of developing diabetic retinopathy. Likewise, recent studies have neglected to evaluate the effects of glycemic variability in latent autoimmune diabetes in adults (LADA). LADA refers to patients with diabetes who are positive for antibodies typically associated with type 1 diabetes, however they initially do not require insulin and the onset of symptoms is in adulthood. Patients with LADA typically exhibit a variety of metabolic and clinical signs and symptoms that place it somewhere between type 1 and type 2 diabetes. Consequently, the aim of this study is to evaluate if glycemic variability in patients with LADA and type 2 diabetes is associated with increased risk of developing retinopathy.

An observational study was selected as the trial design as the researchers only wished to determine if an association exists. Participants were recruited from a list of those admitted in the Department of Endocrinology and Metabolism of Shanghai Jiao Tong University Sixth People’s Hospital, in China, between the dates of July 2005 and December 2015.

The candidates were considered for inclusion if they were greater than or equal to 18 years of age, on a stable diabetes regimen for at least 3 months prior to inclusion, and had a diagnosis of type 2 diabetes or LADA. For the purposes of this study, LADA was defined as onset of diabetes at an age greater than or equal to 18 years of age, confirmed presence of autoantibodies (islet antigen 2 or glutamic acid decarboxylase), and insulin independence for at least 6 months post diagnosis. Patients were excluded if they had a history of recurrent hypoglycemia, diabetic ketoacidosis, or hyperglycemic hyperosmolar state. Those deemed eligible were given a continuous glucose monitor (produced by Medtronic Inc.), which then recorded their glycemic levels over the next 72 hours. The presence or absence of diabetic retinopathy was assessed via fundus photography with subsequent analysis by a study-blinded ophthalmologist. The glycemic variability was then compared against the presence or absence of diabetic retinopathy and deemed significant via logistic regression analysis.

Of the prospective participants, 3,119 (2,927 with type 2 diabetes and 192 with LADA) were deemed eligible and included in the study. When the study data was analyzed, it was found that for patients with type 2 diabetes, for each increase in standard deviation away from the mean, the incidence of diabetic retinopathy also increased (P = 0.017). However, for the patients with LADA, there was no statistically significant correlation observed between glycemic variation and incidence of diabetic retinopathy. It was also noted that the patients with LADA had fewer cardiometabolic risk factors yet exhibited significantly more glycemic variability than their counterparts with type 2 diabetes.

As with other diabetes complications that have been studied previously, incidence of diabetic retinopathy appears to be correlated with glycemic variability in patients with type 2 diabetes. However, the evidence suggests that this association does not extend to all forms of diabetes. Specifically, no significant association was observed between glycemic variability and incidence of diabetic retinopathy in patients with LADA. While further study is required to elucidate the full clinical significance of these findings, a reasonable conclusion would be that patients with LADA and patients with type 2 diabetes may require different treatment strategies. While people with type 2 require management of glycemic level as well as variability, those with LADA may respond well to merely achieving A1C target.

Practice Pearls:

  • Glycemic variability is significantly associated with risk of developing diabetic retinopathy in patients with type 2 diabetes.
  • No association exists between glycemic variability and risk of diabetic retinopathy in patients with LADA.
  • Different treatment goals and strategies may need to be implemented for the treatment of patients with LADA compared to those with type 2 diabetes.


Lu, Jingyi, et al. “Glycemic Variability Assessed by Continuous Glucose Monitoring and the Risk of Diabetic Retinopathy in Latent Autoimmune Diabetes of the Adult and Type 2 Diabetes.” Journal of Diabetes Investigation, July 2018, doi:10.1111/jdi.12957.

Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy