Newly Diagnosed T2D Subtypes Show No Difference in Retinal Microvascular Structure


A multivariate linear mixed model regression analysis of eyes without DR indicates no statistically significant differences in retinal venular or arteriolar width between subtypes and patients with classical T2D.

Frederik N. Pedersen

Frederik N. Pedersen

A new cross-sectional study investigating retinal microvascular markers in type 2 diabetes (T2D) subphenotypes reported no significant difference between patients with newly diagnosed type 2 diabetes subphenotypes compared to classical T2D.1

The data suggest, however, that diabetic retinopathy (DR) was twice as likely to be prevalent in patients with hyperinsulinaemic T2D compared to those with classical T2D, after excluding patients with known cardiovascular disease (CVD)

“In a clinical setting, it is important to differentiate in risk of diabetic complications across different subphenotypes in order to provide optimal individual treatment and management including a differentiated DR screening interval between subphenotypes.,” investigators wrote.1

To better define risk differentiation, Frederik N. Pedersen, Department of Ophthalmology, Odense University, and colleagues, examined if early retinal microvascular damage was detectable in different subphenotypes of patients with newly diagnosed T2D or latent autoimmune diabetes of adults (LADA) before the onset of DR. In addition, they examined if the presence of DR varied between the T2D subphenotypes or LADA.

This population-based, cross-sectional study was embedded in a larger cohort study in Denmark and included adult patients with newly, clinically diagnosed T2D. In total, 341 patients with newly diagnosed T2D were screened with fundus images. A clinical examination obtained a history of CVD and T2D phenotype evaluation was performed by investigators.

T2D was categorized according to the estimated beta-cell function and insulin sensitivity into three subphenotypes. The subphenotypes were classical T2D (low insulin sensitivity and low beta-cell function), hyperinsulinemic T2D (low insulin sensitivity and high beta-cell function), and insulinopenic T2D (high insulin sensitivity and low beta-cell function), or LADA. In analysis, retina, 6-field images were graded according to the International Clinical DR Severity Scale by a retinal expert, and retinal microvascular structures were analyzed in eyes by semi-automatic software.

Overall, a total of 340 patients were included in the analysis, of which 218, 86, 20, and 16 individuals were categorized into classical T2D, hyperinsulinemic T2DM, insulinopenic T2DM, and LADA, respectively. The median age and duration of diabetes were 58.1 and 0.9 years, respectively, and 56.8% of the included study population was male.

A linear mixed regression model adjusted for age and sex of eyes without DR (n = 570) indicated patients with hyperinsulinemic T2D and LADA had a tendency toward wide retinal venular caliber compared to patients with classical T2D (276 μm vs. 270 μm p = 0.075 and 279 μm vs. 270μm p = 0.087, respectively), although the association was not statistically significant.

Meanwhile, eyes across the subphenotypes did not differ according to retinal vessel density, tortuosity, or fractal dimension compared to patients with classical T2D, based on the findings.

In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure, and history of CVD, the results suggest people with hyperinsulinemic T2D were more likely to have DR (odds ratio [OR], 1.97; 95% confidence interval [CI], 0.95 - 4.09) compared to classical T2D.

A further sensitivity analysis excluded patients with known prior CVD and observed patients with hyperinsulinemic T2DM were more likely to have DR compared to classical T2DM (OR, 2.31; 95% CI, 1.04 - 5.10). The results additionally indicate an increased presence of DR in patients with LADA, compared to patients with classical T2D.

Investigators plan to continue follow-up with the cohort to examine changes in retinal microvascular markers in patients with newly diagnosed T2D subphenotypes.

“This cohort will be followed with annual retinal photos, which enable us to examine retinal microvascular markers over time in T2D subphenotypes and LADA along incidence and progression of DR,” they wrote.1


  1. Pedersen, F.N., Stidsen, J.V., Rasmussen, M.N., Nielsen, H.-B., Henriksen, J.E., Olesen, T.B. et al. (2023) Retinal microvascular markers in type 2 diabetes subphenotypes and latent autoimmune diabetes of adults. Acta Ophthalmologica, 00, 1–8. Available from:

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