Cardiac autonomic neuropathy associated with global metabolic risk status in individuals at risk of type 2 diabetes

Introduction: In prediabetes and in individuals at increased risk of diabetes, data on the relationship between continuous glucose monitoring (CGM)-derived glycaemic burden and autonomic neural dysfunction remain limited. Therefore, the objective of the present study was to investigate whether early neuropathic changes in these populations are related to short-term glycaemic variability or broader metabolic risk. Materials and methods: Increased risk of prediabetes was defined by the Finnish Diabetes Risk Score (HbA1c<5.7% and FINDRISC ≥12 points: n=14; controls <12 points, n=12; and prediabetes by HbA1c 5.70-6.49% (n=15); total number of participants n=41). Associations between metabolic status, CGM-derived metrics and autonomic function (RMSSD, pNN50, E/I ratio) were assessed using univariable and multivariable models. Cardiac autonomic neuropathy (CAN) was analysed by logistic regression, metabolic status by multinomial regression. Results: CAN was present in 16 participants (39%). Age showed a borderline association with autonomic neuropathy (OR = 1.06 per year; p=0.059), which was attenuated after adjustment for metabolic status. Both increased risk of prediabetes and prediabetes groups were significantly associated with older age (RRR = 1.11 and 1.43 per year; p=0.03 and p=0.002, respectively). In regression models, increased prediabetes risk (OR ~8.4) and prediabetes (OR ~7.0) status emerged as potential determinants of CAN independent of age, although confidence intervals were wide. Among CGM-derived metrics, only mean interstitial glucose differed across metabolic groups, while no glycaemic marker was associated with CAN. Conclusion: In this exploratory pilot cohort, CAN appeared to be more closely associated with metabolic risk status than with short-term glycaemic variability. CGM-derived metrics did not predict autonomic or sensory neuropathy, suggesting that early neural impairment in prediabetes and increased diabetes risk may be more closely linked to broader metabolic risk factors beyond short-term glycaemic variability. Larger longitudinal studies are warranted.