How DR progresses in type 1 diabetes

May 1, 2018

While the majority of publications on diabetic retinopathy (DR) and diabetic macular edema (DME) tend to concentrate on patients with type 2 diabetes, several recent publications on complications and associations for those with type 1 diabetes (T1D) may give better insight into how DR progresses in these (typically) younger patients.

While the majority of publications on diabetic retinopathy (DR) and diabetic macular edema (DME) tend to concentrate on patients with type 2 diabetes, several recent publications on complications and associations for those with type 1 diabetes (T1D) may give better insight into how DR progresses in these (typically) younger patients.

From 2001-2009, the prevalence of T1D in people under the age of 20 increased by more than 20%, and one in three people with T1D show early signs of complications or comorbidities after just 8 years of average diabetes duration.1

Quantifying additional risks

Early complications co-occur in adolescents and young adults with T1D more frequently than expected, according to one U.S.-based cohort study.1

In the first study to assess co-occurrences and related risk factors of multiple diabetes-related complications and co-morbidities among adolescents and young adults with T1D, Sauder et al. suggest the need for monitoring and early interventions to prevent lifelong debilitating morbidities is warranted. In their analysis of 1,327 participants with T1D, the mean age of participants was 10·1 (SD 3·9) years at the time of T1D diagnosis, 10.9 (3.9) years at the baseline visit (with 0.8 years [0.5] diabetes duration), and 18.0 (4.1) years at the follow-up visit.

Of the individually occurring complications, retinopathy had the lowest frequency (1.8%), but occurred with another complication more often than expected in kidney disease and arterial stiffness (p = 0.0007 and p = 0.0016, respectively) but not as often as expected with peripheral neuropathy (p = 0.087) or cardiovascular autonomic neuropathy (p = 0.15).

“The co-occurrence of two or more early diabetes-related complications at a relatively young age (mean 18 years) and short duration of diabetes (mean 7.8 years)” was unexpected, the authors wrote, but added their findings determined adolescents and young adults with T1D who develop any one complication are likely to develop comorbidities.

“Individuals with high-risk profiles at baseline and follow-up tend to develop multiple complications more frequently than individuals with less adverse profiles,” they wrote.

In the first cohort study to explore the risk factors for the development of DR in a Dutch population with T1D, study authors found a relatively low cumulative incidences of DR, vision-threatening DR and visual impairment. Higher mean A1c, A1c variability, age of onset of T1D, and total cholesterol were independently associated with the risk of DR development, and a protective association was found for HDL cholesterol in subjects with T1D. Mean A1c and presence of albuminuria were associated with progression of DR.2

“We hypothesize that subjects with a higher age of onset of T1DM develop DR faster, because the natural aging process contributes to retinal degeneration, independently of hyperglycemia,” they wrote, concluding that A1c variability must be taken into account when optimizing glycemic control.2

Evidence is now emerging that specific lipid components may have a protective effect against DR in patients with T1D.

In a two-center study on patients with T1D with DR (n = 103) and without DR (n = 144), 3 subjects with DR showed a lower intake of total fat (p = 0.036) than that of their non-DR counterparts. DR was associated with increasing age (p = 0.004), hypertension (p < 0.001), and diabetes duration (p < 0.001), however there was a negative association with high educational level (p = 0.018). The multivariate-adjusted analysis showed that the intake of complex carbohydrates was positively related to the presence of DR (p = 0.031).

In contrast, the intakes of total fat (p = 0.009), monounsaturated fatty acids (p = 0.012), oleic acid (p = 0.012), and vitamin E (p = 0.006) were associated with the absence of DR.

“The potential mechanism of action of the association between lipids and DR is also unclear,” the authors wrote.3

The cumulative incidence of various cardiovascular disease events, including coronary heart disease (CHD), peripheral artery disease (PAD), and stroke, retrieved from registries, was evaluated in 1,683 individuals with at least a 30-year duration of T1D drawn from the Finnish Diabetic Nephropathy Study (FinnDiane).4

During 12,872 person-years of follow-up, 416 incident cardiovascular disease events occurred. Even in the absence of diabetic kidney disease, severe DR increased the risk of any cardiovascular disease (hazard ratio 1.46 [95% CI 1.11-1.92]; P < 0.01), after adjustment for diabetes duration, age at diabetes onset, sex, smoking, blood pressure, waist-to-hip ratio, history of hypoglycemia, and serum lipids. In particular, severe DR alone was associated with the risk of PAD (1.90 [1.13-3.17]; P < 0.05) and CHD (1.50, [1.09-2.07; P < 0.05), but not with any stroke.

The authors noted this suggests that severe DR, independent of common cardiovascular risk factors in patients with T1D, increases the cardiovascular risk in these patients.

Better diagnostic capabilities

Two studies were recently published that may add to the diagnostic capabilities for treating clinicians.

In the first of these studies, Cennamo et al.5 measured macular pigment density and microvascular density on optical coherence tomography angiography (OCTA) in a cohort of T1D mellitus (T1DM) patients with retinopathy in the attempt to shed light on the pathophysiology of this condition.

They evaluated 82 consecutive eyes (59 patients) with DR at a single center in Italy and compared them to age-matched controls. There were no significant age differences between patients and controls. Both macular pigment measurements and vessel density measured by OCTA were significantly lower in patients than in controls. A moderate correlation was found between vessel density in all ETDRS sectors and macular pigment parameters.

Cennamo et al. said the reduction in OCTA vessel density and macular pigment “may have prognostic value in determining disease progression.”

In a second study, 6 adults with T1D (n = 69) underwent coronary artery calcification (CAC) volume scoring by wide-volume computerized tomography. CAC scores were much higher in people with T1D, and was associated with large-nerve fiber neuropathy and retinopathy, but not with renal hemodynamic function.

The authors suggested these findings means the major complications of diabetes-neuropathy, retinopathy, and macrovascular calcification-share common risk factors.

References:

1. Sauder KA, Stafford JM, Mayer-Davis EJ, et al. Co-occurrence of early diabetes-related complications in adolescents and young adults with T1D: an observational cohort study. The Lancet Child & Adolescent Health 2018 Nov 5.
2. Schreur V, van Asten F, Ng H, et al. Risk factors for development and progression of diabetic retinopathy in Dutch patients with T1D mellitus. Acta Ophthalmol 2018;96(5):459-64.
3. Granado-Casas M, Ramirez-Morros A, Martin M, et al. Type 1 Diabetic Subjects with Diabetic Retinopathy Show an Unfavorable Pattern of Fat Intake. Nutrients 2018;10(9).
4. Pongrac Barlovic D, Harjutsalo V, Gordin D, et al. The Association of Severe Diabetic Retinopathy With Cardiovascular Outcomes in Long-standing T1D: A Longitudinal Follow-up. Diabetes Care 2018.
5. Cennamo G, Lanni V, Abbate R, et al. The Relationship between Macular Pigment and Vessel Density in Patients with T1D Mellitus. Ophthalmic Res 2018:1-7.
6. Lovshin JA, Bjornstad P, Lovblom LE, et al. Atherosclerosis and Microvascular Complications: Results From the Canadian Study of Longevity in T1D. Diabetes Care 2018.