AimsRecent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.MethodsTo explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.ResultsThe difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (−3.9 for noDR and −4.9 for NPDR), without any relevant difference between them (−1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32–15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33–15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = −0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action −1, −2, −4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.ConclusionsEarly structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.

IntroductionThe oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy (AN) has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV.Patients and methodsTwenty type 1 diabetic patients were involved (age: 39.5 ± 3.4 years, duration of diabetes: 17.5 ± 2.5 years; HbA1c: 8.1 ± 0.2%, mean ± SE). AN was assessed by the cardiovascular reflex tests. The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on six consecutive days. GV was characterized by calculation of four parameters.ResultsSD of interstitial glucose values correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ = 0.47, p < 0.05; orthostasis-SD: ρ = 0.51, p < 0.05). Mean absolute glucose (MAG) correlated with three parameters of AN (AN-score-MAG: ρ = 0.62, p < 0.01; 30/15 ratio-MAG: ρ = −0.50, p < 0.05; orthostasis-MAG: ρ = 0.59, p < 0.01). The HbA1c also correlated with two parameters of GV (HbA1c-continuous overlapping net glycemic action: ρ = 0.56, p < 0.05; HbA1c-MAG: ρ = 0.45, p < 0.05). The frequency of hypoglycemia did not exhibit any correlation with measures of GV.ConclusionSeverity of glucose variability but not overall glucose load correlates with both parasympathetic and sympathetic dysfunctions in type 1 diabetes. Higher HbA1c is associated with more severe glucose variability. The observed correlation between increased glucose variability and the severity of AN necessitates the further exploration of this relationship.

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AimsThis study aims to evaluate the effectiveness and tolerability of once-weekly glucagon-like peptide receptor agonists (OW GLP-1RAs) and to assess the clinical benefits of switching from one GLP-1RA to another (switchers) in a routine clinical setting.Materials and MethodsThis is a retrospective, real-world cohort study, based on electronic medical records utilized in one Italian diabetes clinic. Estimated mean changes in HbA1c and body weight after 6 and 12 months from the first prescription of a long-acting GLP1-RA were evaluated using longitudinal linear mixed models for repeated measures. The effectiveness of the three long-acting GLP1-RAs was compared separately in the GLP1-RA naive and switchers cohorts, after propensity score adjustment.ResultsInitiating a long-acting GLP1-RA was associated with statistically significant improvements in HbA1c (−1%) and body weight (−2.6 kg) after 6 months, and benefits were maintained after 12 months. In GLP1-RA naive cohort, semaglutide showed the largest effect on HbA1c (−1.55%; 95%CI, −1.77;−1.34) and body weight (−3.76 kg; 95%CI, −5.05;−2.47) at 6 months, maintained at 12 months (−1.55%; 95%CI, −1.82;−1.28 and −6.29 kg; 95%CI, −7.94;−4.63). In the switchers’ cohort, statistically significant reductions at 6 months in HbA1c and body weight were documented with semaglutide and dulaglutide only, with semaglutide associated with the most marked reduction (−0.84%; 95%CI, −1.03;−0.65 and −3.43 kg; 95%, −4.67;−2.19). Dropout rates were 9.2%, 28.5%, and 41.7% in semaglutide, dulaglutide, and exenatide groups, respectively.ConclusionsThe effectiveness and tolerability of the OW GLP-1RAs in the real world were documented. Semaglutide was associated with the highest response without impact on safety. Clinical improvements were obtained even in switchers, especially in those switching to semaglutide.