Glycemic Variability and Diabetic Neuropathy in Young Adults With Type 1 Diabetes

Abstract

Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes. Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE). Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models. Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.

Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes

“…As described previously, the continuous glucose monitoring (CGM) sensor Enlite™ (Medtronic, Northridge, CA, USA) was inserted into the subcutaneous tissue of the abdomen or the upper arm and was worn for 5 days ( 24 ). The capillary finger blood glucose was monitored four times daily for calibration.…”

Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications

“…Recent studies revealed that HbA1c variability calculated by SD was independently associated with the severity of peripheral neuropathy and cardiovascular autonomic neuropathy in patients with T2DM [ 75 , 76 ]. Conversely, a cross-sectional study including 133 young adults with type 1 diabetes mellitus (T1DM) suggested that GV might not be a risk factor for diabetic neuropathy [ 77 ]. Longitudinal studies are required to confirm the elaborated role of GV in the progression of DPN.…”

Perspectives of glycemic variability in diabetic neuropathy: a comprehensive review

“…Similarly, Nyiraty et al revealed that GV marker calculated by SD and mean absolute glucose were associated with the severity of CAN in patients with T1DM 50 . Nevertheless, in a cross-sectional observational study including 133 young adults with T1DM from 18 to 24 years, Christensen et al reported that after adjusting for risk factors and multiple tests, only higher MAGE was associated with slightly increasing measures of heart rate variability, indicating that GV might not be a risk factor for CAN in young adults with T1DM 51 .…”