Association between cardiac autonomic neuropathy and fat distribution in autoimmune vs type 2 diabetes

Aims: To investigate whether the association between cardiac autonomic neuropathy (CAN) and body fat distribution differs between individuals with autoimmune diabetes (AD) and those with type 2 diabetes (T2D).

Methods: CAN was screened using CARTs tests (deep breathing test, lying-to standing test, orthostatic hypotension test) to assess early CAN in presence of 1 abnormal test. Body fat distribution was evaluated using Dual X-ray absorptiometry (DXA) to assess total fat mass, Visceral Adipose Tissue (VAT) Mass, Trunk Fat Mass, and Trunk to Legs Fat Mass Ratio (TLR). Serum adiponectin and leptin concentrations were assessed using BioVendor ELISA kits to calculate the adiponectin/leptin ratio (ALR). 143 individuals with diabetes (44 with AD and 99 with T2), mean age was 67 (61-70) years and mean BMI was 27.3 (24.3-30.7) kg/m2. 50 patients had ≥1/3 abnormal CARTs (15 with AD and 35 with T2D) and only 11 of them had ≥2/3 abnormal CARTs (2 with AD and 9 with T2D).

Results: In participants with AD, those with CAN exhibited significantly greater VAT mass (530 [376-665] g vs. 251 [189-360] g, p = 0.001), total fat mass (22708 [20200–27845] g vs. 15434 [12981–21879] g, p = 0.016), and TLR (0.88 [0.75-1.04] vs. 0.70 [0.56-0.78], p = 0.023) compared to those without CAN, independent of BMI, age, sex, HbA1c, and diabetes duration. These associations were not observed in individuals with type 2 diabetes.

Conclusions: This study demonstrated that ectopic fat distribution is associated with the presence of CAN in individuals with AD, but not in those with T2D. Specifically, among participants with AD, those with CAN exhibited a visceral adiposity phenotype, characterized by higher total fat mass, trunk fat mass, VAT mass, and TLR compared to those without CAN.

Comments: Given the increasing prevalence of overweight and obesity among individuals with AD, these findings highlight the clinical importance of assessing and managing body fat distribution, rather than focusing only on overall body weight. The observed association between visceral adiposity and the presence of CAN underscores the need for early, targeted interventions. Comprehensive strategies - including lifestyle modifications and integrated, multidisciplinary care - are essential to reduce cardiometabolic risk and to prevent or slow the progression of CAN in this population.

While causality between CAN and ectopic fat accumulation cannot be determined yet, these results underscore the potential role of dysfunctional adipose tissue expansion in the autonomic profile of individuals with AD. Further investigation is needed to evaluate the impact of adiposity on autonomic dysfunction in AD.

Ilenia D’Ippolito

Reference: Risi R, Amendolara R, Pantano AL, Fassino V, D'Onofrio L, Coraggio L, Luverà D, Masi D, Watanabe M, Gnessi L, Buzzetti R, Maddaloni E. Cardiac autonomic neuropathy is associated with ectopic fat distribution in autoimmune but not in type 2 diabetes. Cardiovasc Diabetol. 2025 Feb 14;24(1):74. doi: 10.1186/s12933-025-02635-6. PMID: 39953513; PMCID: PMC11829334.

🔗 https://cardiab.biomedcentral.com/articles/10.1186/s12933-025-02635-6