Combined peripheral and autonomic neuropathy was associated with a more than threefold increased risk of major adverse liver outcomes (HR 3.21) compared to type 2 diabetes without neuropathy.
Cohort (n=5,274,866)
Yes
Does diabetic neuropathy increase the risk of major adverse liver outcomes in adults with Type 2 diabetes?
Diabetic neuropathy, particularly autonomic and combined forms, is strongly associated with an increased risk of major adverse liver outcomes in patients with Type 2 diabetes, serving as a potential marker of advanced systemic metabolic injury.
Effect estimate: HR 3.21 (95% CI 3.03, 3.41)
p-value: p=< 0.01
INTRODUCTION: Type 2 diabetes (T2D) is a risk factor for the progression of liver disease, particularly relating to metabolic dysfunction-associated steatotic liver disease (MASLD), and consequent major adverse liver outcomes (MALO). Given that diabetic neuropathy reflects advanced metabolic and microvascular injury, we investigated whether somatic and autonomic neuropathy in T2D is associated with MALO. METHODS: In this retrospective cohort study using a large, federated health research network (TriNetX), adults with T2D were stratified into (i) diabetes alone, without coding of neuropathy, (ii) diabetes with peripheral neuropathy coding, (iii) diabetes with autonomic neuropathy coding, and (iv) diabetes with combined peripheral and autonomic neuropathy coding. Propensity score matching was performed to balance demographic, metabolic, and comorbidity profiles. The primary outcome was incident MALO, defined as hepatic decompensation, portal hypertension/stable varices, hepatocellular carcinoma, liver failure, or liver transplantation. Secondary outcomes included individual MALO endpoints, major adverse cardiovascular events (MACE) and all-cause mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: After matching, a clear gradient was evident between the increased risk of MALO and the presence of neuropathy: peripheral neuropathy and risk of MALO (HR 1.95 95% CI 1.85, 2.05), autonomic neuropathy (HR 2.62 2.52, 2.72) and combined neuropathy (HR 3.21 3.03, 3.41). Associations were consistent across individual MALO endpoints, irrespective of obesity status, and remained significant following temporal washout analyses. Neuropathy also conferred greater risk for MALO compared to other microvascular complications (vs. retinopathy; 2.21 2.05, 2.39). CONCLUSION: Diabetic neuropathy is associated with an elevated risk of MALO in T2D. Autonomic, and to a lesser extent peripheral, neuropathy identifies a particularly high-risk phenotype, supporting neuropathic burden as a surrogate marker, and potential driver, of advanced systemic metabolic injury and progressive liver risk.
Henney et al. (Tue,) conducted a cohort in Type 2 diabetes (n=5,274,866). Combined peripheral and autonomic neuropathy vs. Type 2 diabetes without neuropathy was evaluated on Incident major adverse liver outcomes (MALO) (HR 3.21, 95% CI 3.03, 3.41, p=< 0.01). Combined peripheral and autonomic neuropathy was associated with a more than threefold increased risk of major adverse liver outcomes (HR 3.21) compared to type 2 diabetes without neuropathy.