The relationship between glycaemic variability and cardiovascular autonomic dysfunction in patients with type 1 diabetes: A systematic review

Abstract

Rigorous glycaemic control -reflected by low HbA1c goals -is of utmost importance in the prevention and management of complications in patients with type 1 diabetes mellitus (T1DM). However, previous studies suggested that short-term glycaemic variability (GV) is important to consider as well, as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk for cardiovascular autonomic neuropathy (CAN), a clinical expression of cardiovascular autonomic dysfunction, is of increasing interest. This systematic review aimed to summarize existing evidence concerning the relationship between GV and cardiovascular autonomic dysfunction in T1DM.Electronic database search of Medline (Pubmed), Web of Science and Embase was performed, up to October 2019. There were no limits concerning year of publication. Methodological quality was evaluated with the Newcastle Ottawa Scale for observational studies. Six studies (four cross-sectional and two prospective cohorts) were included. Methodological quality of the studies varied from level C to A2. Two studies examined the association between GV and heart rate variability (HRV) and both found significant negative correlations.Regarding cardiovascular autonomic reflex tests (CARTs), two studies did not while two other studies did find significant associations between GV parameters and CART-scores. However, associations were attenuated after adjusting for covariates such as HbA1c, age and disease duration. In conclusion, this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM. Hence, uncertainty remains whether high GV can independently contribute to the onset or progression of CAN. The heterogeneity in methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated CGM-derived parameters of GV, while standardised assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN. KEYWORDSType 1 diabetes • Complications • Glycaemic variability • Cardiovascular autonomic dysfunction • Cardiovascular autonomic neuropathy • Cardiovascular reflex tests • Heart rate variability ABBREVIATIONS This article is protected by copyright. All rights reserved. BRS Baroreflex sensitivity CAN Cardiovascular autonomic neuropathy CART Cardiovascular autonomic reflex test CGM Continuous glucose monitoring CONGA Continuous overlap net glycaemic action COV Coefficient of variation DAN Diabetic autonomic neuropathy DCCT Diabetes Control and Complications Trial GV Glycaemic variability HBGI High blood glucose index HRV Heart rate variability LBGI Low blood glucose index MBG Mean blood glucose MAG Mean absolute glucose difference MAGE Mean amplitude of glycaemic excursions MODD Mean of daily differences SDT Total standard deviation of glucose values T1DM Type 1 diabetes mellitus RESEARCH IN CONTEXT BOXWha...

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“…Another phenomenon that could hypothetically alter the relationship between GV and mood is impaired cardiovascular autonomic modulation, 39,40 as is the case in cardiovascular autonomic neuropathy, one of the complications of diabetes. 41 Understanding interindividual differences in emotional reactivity to GV could help predict which persons with diabetes could profit most from more stable blood glucose levels in terms of their emotional health.…”

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“…Furthermore, physical exercise has been proved to improve HRV in patients with diabetes [21]. Although HRV is not an obligatory measurement in the management of diabetes, it has a predictive and prognostic value owing to its association with diabetic complications and mortality [22]. Inappropriate management of diabetes results both in increased HbA1c levels and hypoglycemic attacks, which is linked to reduced HRV levels [23].…”

The Role of Glycemic Variability in Cardiovascular Disorders

“…Recently, it has been recognized that an essential parameter to consider when evaluating GV, which would facilitate safe and effective therapeutic decision making, is also the time spent in the various glycemic ranges (i.e., time per day within target glucose range (TIR), time below target glucose range (TBR), and time above target glucose range (TAR) [23]. Since each index has its limitations, to better compare data across different studies, the clinical community should design standardized guidelines to precisely measure GV [24]. Achieving this goal will be a key point to identify the biological mechanisms underlying GV.…”

“…The association between GV and increased risk of cardiovascular complications, such as cardiovascular autonomic neuropathy (CAN) in T1DM, was exanimated in a recently published systematic review [24]. This review showed high heterogeneity in the methodological approaches of different studies, and thus, it is difficult to compare them and come to an unambiguous conclusion regarding GV implication.…”