Prediabetes influences the structure of the macula: thinning of the macula in the Northern Finland Birth Cohort

Abstract

Background/AimThe aim of this study was to evaluate the effect of prediabetes and diabetes on macular thickness and retinal vascular calibres in our population-based cohort (Northern Finland Birth Cohort).MethodsThe population of 2005 individuals was divided into diabetes (n=57), prediabetes (n=1638) and normal glucose metabolism (NGM) groups (n=310). Total thickness of the macula was measured using Cirrus HD-OCT 4000. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) calibres were measured from the fundus images. The diagnosis of diabetes and prediabetes was made according to WHO 2006 diagnostic standards.ResultsSignificant macular thinning was observed in subjects with prediabetes (−2.69 μm (95% CI −4.29 to −1.09), p<0.05 and −0.10 mm3 (95% CI −0.16 to −0.04), p<0.05 for macular cube average thickness and cube volume, respectively) and it was greatest in the pericentral area. Macular cube average thickness and macular cube volume decreased significantly by worsening glucose metabolism. Furthermore, CRAE was decreased by increases in 2-hour post-load glucose, glucose area under the curve and increase in Matsuda index (p<0.001, 0.019 and <0.001, respectively). In mediation analysis, macular thickness had significant average causal mediation effect (ACME) on CRVE and CRAE in subjects with prediabetes.ConclusionWe detected significant thinning of the macula in subjects with prediabetes. The diameters of retinal arteries were decreased by impaired glucose metabolism. This study provides a new perspective since it revealed that the early and subtle changes caused by prediabetes as macular thinning had significant ACME on retinal vessels, therefore supporting the neurodegenerative theory of diabetes-induced changes in the retina.

The measurement and consequences of daily glucose variability

“…The findings on GMS, hyperglycemia and RNFL thickness (Chapter 7) are in line with current literature [119][120][121][122][123][124][125] and extend previous work of The Maastricht Study on the microvascular and neuronal branch of the "ticking clock hypothesis" [126][127][128][129][130][131] , which postulates that hyperglycemia-induced damage is a continuous, gradual process that starts in prediabetes, progresses with the onset of type 2 diabetes, and continues during type 2 diabetes 13,132 . At present, no other studies have investigated the associations of daily GV with RNFL thickness or measures of microvascular function.…”

(Pre)Diabetes, Greater Glycemia, and Greater Daily Glucose Variability are Associated with Lower Retinal Nerve Fiber Layer Thickness, an Index of Neurodegeneration and Precursor of Diabetic Retinopathy– The Maastricht Study

“…Our ndings are in line with and extend observations from most previous studies. 13,[19][20][21][22][23][24] The present study is the rst large population-based study to comprehensively report associations of GMS, measures of glycemia, and indices of daily glucose variability with RNFL thickness, and also adjust for an extensive set of potential confounders. Additionally, the present study is the rst to present associations of SAF, duration of diabetes, and indices of daily glucose variability with RNFL thickness.…”

“…The current literature on the associations of hyperglycemia with RNFL thickness has some important limitations. First, in previous population-based studies, several important confounders were not included, such as age, [13][14][15] sex, 14,15 socioeconomic status, [13][14][15][16][17][18][19][20][21][22][23] cardiovascular risk factors, 13-15, 19, 21-24 and lifestyle factors (e.g., alcohol use, 13,[16][17][18][19]21 diet, [13][14][15][16][17][18][19][20][21][22][23][24] and physical activity). [13][14][15][16][17][18][19][21][22][23][24] Second, no population-based studies have yet investigated whether advanced glycation endproducts (AGEs) or daily glucose variability are associated with RNFL thickness.…”

“…First, in previous population-based studies, several important confounders were not included, such as age, [13][14][15] sex, 14,15 socioeconomic status, [13][14][15][16][17][18][19][20][21][22][23] cardiovascular risk factors, 13-15, 19, 21-24 and lifestyle factors (e.g., alcohol use, 13,[16][17][18][19]21 diet, [13][14][15][16][17][18][19][20][21][22][23][24] and physical activity). [13][14][15][16][17][18][19][21][22][23][24] Second, no population-based studies have yet investigated whether advanced glycation endproducts (AGEs) or daily glucose variability are associated with RNFL thickness. It is important to establish to what extent hyperglycemia (including AGEs) and daily glucose variability contribute to RNFL thinning over the entire range of glucose tolerance because early diagnosis and treatment of hyperglycemia as well as novel strategies to monitor glycemic exposure may contrib...…”

Diabetes Mellitus Associated Progressive Neurovascular Retinal Injury: Recommendations for Imaging and Functional Testing and Potential Role for Early Intervention with Modern Retinal Laser Therapy

“…This is expected to double in the next 25 years [1], with approximately 37% of US adults older than 20 years and 51% older than 65 having prediabetes with predicted high rates of conversion to type 2DM with aging [2]. Because of this, prediabetes, along with diabetes, are now recognized as a major risk factor for the development and progression of retinal, optic nerve, and brain neurovascular dysfunction [3][4][5][6][7][8], resulting in severe vision loss [9,10]. The focus of the medical industry predominantly has been to examine the effect of hyperglycemia control along with other aggravating comorbid factors (hypertension, hyperlipidemia, smoking, obesity, and sleep apnea) on the progression of large vessel occlusive disease, because of the rising incidence of stroke and myocardial infarction [11,12,13].…”