UNASSIGNED: Autonomic neuropathy (AN) in cirrhotic patients has been linked to a higher risk of cirrhosis-related complications and worse outcomes before, during or after liver transplantation (LT). However, only a few studies exist with inconsistent results.
UNASSIGNED: We searched for all articles published until September 2023 that described a diagnosis of AN based on cardiovascular autonomic reflex tests (CARTs), assessment of the rate-corrected QT interval (QTc), heart rate variability (HRV), and baroreflex sensitivity (BRS) tests, in order to evaluate the predictive role of AN in cirrhosis and/or peri-/post-LT prognosis.
UNASSIGNED: Twenty-five studies were included: 5, 12, 9, and 1 study, respectively, assessed the predictive role of CARTs, prolonged QTc, HRV indices, and BRS in cirrhosis or peri-/post-LT prognosis. In CARTs-based analysis, the pre-LT pooled mortality rate was significantly higher in cirrhotics with AN compared to those without AN (20% vs. 6%; P=0.01). However, no difference was found between patients with and without pre-LT prolonged QTc in the pre-LT pooled mortality rates (41% vs. 18%; P=0.08), pooled peri-transplant risk of major complications (29% vs. 17%; P=0.08) or post-LT pooled mortality rates (15% vs. 12%; P=0.36). In HRV-based analysis, the standard deviation of normal-to-normal intervals was significantly lower in non-survivors, compared to survivors with cirrhosis: standardized mean difference -2.59, 95% confidence interval -4.75 to -0.43; P=0.04.
UNASSIGNED: The presence of CARTs- and HRV-based AN was a good predictor of mortality in the pre-LT setting. Preoperative prolonged QTc did not seem to be associated with the outcome before or after LT.

UNASSIGNED: Cardiovascular autonomic neuropathy (CAN) is a debilitating complication of diabetes mellitus. To date, there is no systematic review on all the available drug treatments for CAN in diabetic patients, except for one review focusing on aldose reductase inhibitors.
UNASSIGNED: To evaluate available drug treatment options for CAN in diabetic patients.
UNASSIGNED: A systematic review was conducted with a search of CENTRAL, Embase, PubMed and Scopus from database inception till 14th May 2022. Randomised controlled trials (RCTs) of diabetic patients with CAN that investigated the effect of treatment on blood pressure, heart rate variability, heart rate or QT interval were included.
UNASSIGNED: Thirteen RCTs with a total of 724 diabetic patients with CAN were selected. There was a significant improvement in the autonomic indices of diabetic patients with CAN given angiotensin-converting enzyme inhibitor (ACEI) for 24 weeks (p<0.05) to two years (p<0.001), angiotensin-receptor blocker (ARB) for one year (p<0.05), single dose of beta blocker (BB) (p<0.05), omega-3 polyunsaturated fatty acids (PUFAs) for three months (p<0.05), alpha-lipoic acid (ALA) for four months (p < 0.05) to six months (p=0.048), vitamin B12 in combination with ALA, acetyl L‑carnitine (ALC), superoxide dismutase (SOD) for one year (p=0.001)  and near significant improvement in the autonomic indices of diabetic patients with CAN given vitamin E for four months (p = 0.05) compared to the control group. However, there was no significant improvement in the autonomic indices of patients given vitamin B12 monotherapy (p ≥ 0.05).
UNASSIGNED: ACEI, ARB, BB, ALA, omega-3 PUFAs, vitamin E, vitamin B12 in combination with ALA, ALC and SOD could be effective treatment options for CAN, while vitamin B12 monotherapy might be unlikely to be recommended for the treatment of CAN due to its lack of efficacy.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13340-023-00629-x.

Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.

Rigorous glycaemic control-reflected by low HbA1c goals-is of the 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 also important to consider as excessive glucose fluctuations may have an additional impact on the development of diabetic complications. The potential relationship between GV and the risk of 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. An 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 using 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 the methodological approach made it difficult to compare different studies. Future studies should therefore use uniformly evaluated continuous glucose monitoring-derived parameters of GV, while standardized assessment of HRV, CARTs and other potential cardiac autonomic function parameters is needed for an unambiguous definition of CAN.