Association between glucose variability as assessed by continuous glucose monitoring (CGM) and diabetic retinopathy in type 1 and type 2 diabetes

Abstract

There is a growing debate in the literature on whether glucose variability contributes, as well as high HbA1c levels and longstanding diabetes, to the onset and progression of diabetic retinopathy (DR) in patients with diabetes types 1 (DM1) and 2 (DM2). Few data, obtained only by self-monitoring of blood glucose, support this hypothesis. We used continuous glucose monitoring (CGM) to investigate the association between DR and glucose variability parameters (SD, CONGA 2, MAGE), acute hyperglycemia (HBGI) and chronic exposure to glucose (AG and AUC tot). We studied 68 patients from 19 to 69 years old, 35 with DM1 and 33 with DM2. The prevalence of retinopathy was 43 % in DM 1 patients and 39 % in DM 2 patients. The values of all indicators were obtained by CGM for 72 h. DR was diagnosed on direct or indirect ophthalmoscopic examination, after inducing mydriasis with tropicamide. HbA1c was measured at the baseline and 6 weeks after CGM to test the stability of the patients' glycemic control. Univariate analysis showed a close association between DR and duration of diabetes (OR 1.11; 1.04-1.19), intensive insulin therapy (OR 5.6, CI 1.14-27.30), SD (OR 1.03; CI 1.01-1.06) and CONGA 2 (OR 1.02; CI 1.00-1.04)-both indicators of variability and HBGI (OR 1.1, CI 1.01-1.18)-a parameter reflecting acute hyperglycemia. There was no significant correlation with HbA1c (p = 0.070). Multivariate regression analysis showed that disease duration is the parameter most significantly correlating with DR (OR 1.05; 1.01-1.15). These results reinforce the evidence that longstanding disease is the factor most closely associated with DR. Our data also suggest, however, that glucose variability-regardless of HbA1c-may also have a role as a risk factor for DR, particularly in the case of acute fluctuations (as represented by CONGA 2 and SD) and acute hyperglycemia (as represented by HBGI).

Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

“…Of note, previous reports suggested that acute oscillations of blood glucose have a more deleterious effect on endothelial function than constant hyperglycemia in patients with type 2 diabetes (T2DM) (3,4), which may support the concept that glycemic variability can induce oxidative stress and thereby affect the pathophysiologic pathways through which diabetes complications arise (5). However, although some studies have reported that increased glycemic variability may be associated with the incidence of diabetic retinopathy (6,7), diabetic neuropathy (8), and coronary artery calcification (9) in patients with T2DM and type 1 diabetes (T1DM), other studies have not supported this association (10)(11)(12). Nevertheless, although its relevance to vascular complications remains uncertain (13), at a given level of glycemia, increased glucose variability raises the risk of hypoglycemia (14)(15)(16) and, hence, is clinically important.…”

Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes

“…Indeed, other studies have correlated glycemic variability to risk of diabetes complications, notably neuropathy and retinopathy. [23][24][25] Bajaj et al demonstrated reduced glucose variability with basal insulin and GLP-1 RA therapy compared to other insulin-based regimens. 26 In 160 T2D patients with HbA1c £7.5%, using blinded CGM for 6 days, this study showed that basal insulin with GLP-1 RA therapy reduced the standard deviation of daily glucose compared to basal insulin with oral medications, basal/bolus regimen, and premixed insulin regimens (P = 0.03, P = <0.01, and P = 0.01, respectively).…”

Postprandial dysmetabolism: Too early or too late?

“…64 Data from another study of 68 patients with DM1 and DM2 suggest that glucose variability may constitute a risk factor for diabetic retinopathy, particularly in the context of acute fluctuations and acute hyperglycemia, regardless of HbA1c. 65 As far as nephropathy is concerned, a study of 12,833 individuals without a history of renal disease or diabetes indicated that impaired glucose tolerance, but not isolated impaired fasting glucose, is associated with increased GFR and a higher risk of glomerular hyperfiltration (estimated GFR above the age-and gender-specific 95th percentile for apparently healthy subjects) (OR 1.34, 95%CI: 1.107-1.66, p=0.009).…”