Glucose variability and inner retinal sensory neuropathy in persons with type 1 diabetes mellitus

Abstract

Purpose To quantify early neuroretinal alterations in patients with type 1 diabetes mellitus (T1DM) and to assess whether glycemic variability contributes to alterations in neuroretinal structure or function. Methods Thirty patients with T1DM and 51 controls underwent comprehensive ophthalmic examination and assessment of retinal function or structure with frequency doubling perimetry (FDP), contrast sensitivity, dark adaptation, fundus photography, and optical coherence tomography (OCT). Diabetic participants wore a subcutaneous continuous glucose monitor for 5 days, from which makers of glycemic variability including the low blood glucose index (LGBI) and area under the curve (AUC) for hypoglycemia were derived. Results Sixteen patients had no diabetic retinopathy (DR), and 14 had mild or moderate DR. Log contrast sensitivity for the DM group was significantly reduced (mean ± SD = 1.63 ± 0.06) compared with controls (1.77 ± 0.13, Po0.001). OCT analysis revealed that the inner temporal inner nuclear layer (INL) was thinner in patients with T1DM (34.9 ± 2.8 μm) compared with controls (36.5 ± 2.9 μm) (P = 0.023), although this effect lost statistical significance after application of the Bonferroni correction for multiple comparisons. Both markers of glycemic variability, the AUC for hypoglycemia (R = − 0.458, P = 0.006) and LGBI (R = − 0.473, P = 0.004), were negatively correlated with inner temporal INL thickness. Conclusions Patients with T1DM and no to moderate DR exhibit alterations in inner retinal structure and function. Increased glycemic variability correlates with retinal thinning on OCT imaging, suggesting that fluctuations in blood glucose may contribute to neurodegeneration.

Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability

“…These findings indicate that glucose is a fundamental energy substrate in conditions of ischemia and that the ability of the retina to metabolically compensate during periods of low oxygen availability is impaired by low levels of blood glucose, although this is advantageous in terms of delaying the progression of diabetic retinopathy [37]. Therefore, our results confirm the hypothesis that the hypoglycemic excursions may be associated with retinal neurodegeneration [13]. Moreover, we also demonstrate that GV evaluated as CONGA, but not HbA1c, was positively associated with INL thickness, suggesting that an increase in intraday glycaemic variation seems to be involved in the development of an early activation of Müller cells.…”

“…Moreover, Bandello F et al [21] reported that the increase in retinal thickness occurring in macular edema was predominantly located in the INL and extended to neighboring retinal layers in Type 2 DM patients. On the other hand, it has been recently showed a modest and selective reduction in the inner region of the INL in the temporal quadrant in Type 1 DM persons with no or mild RD [13], as well as in the pericentral area of macula in patients with minimal DR [22]. The subtle differences in the macular thickness described in these studies may be explained by the fact that the progressive phenomenon of retinal neurodegeneration was “photographed” in slightly different time phases, but with significantly different findings.…”

“…However, the association between GV and diabetes microvascular complications has yielded inconsistent findings. Recent evidence has emphasized the role of neuroretina in the interactions between neural alterations and microvascular abnormalities [12], and the relationship between GV and retinal neurodegeneration, in the early stages of RD, has been only very recently investigated [13]. …”

Future opportunities in diabetic retinopathy research

“…Moreover, glycemic control estimates are steady state measures whereas blood glucose concentrations often fluctuate widely in patients. Emerging evidence suggests that excess glycemic variability influences the risk of cardiac autonomic neuropathy and mild retinopathy 13, 14 .…”

No effect of yeast-like fungi on lipid metabolism and vascular endothelial growth factor level in children and adolescents with type 1 diabetes mellitus

“…First of all new insulin therapy technologies have been developed and implemented, such as personal insulin pumps integrated with continuous glucose monitoring systems (CGM) [14, 15]. Data from clinical trials and immunological studies point at the very important role of even minor blood glucose fluctuations in the development of both micro- and macrovascular complications [15–17]. …”