European Journal of Cardiovascular Medicine

Diabetes mellitus is a major global public health problem, with type 2 diabetes mellitus accounting for more than 90% of all cases worldwide.[¹,²] India bears a disproportionate share of this burden, and earlier age of onset combined with increased life expectancy substantially increases the lifetime risk of chronic microvascular complications.[^2,3]

Among these complications, diabetic neuropathy is one of the most common, heterogeneous, and disabling conditions, involving both peripheral and autonomic nervous systems. Peripheral neuropathy most frequently manifests as distal symmetrical sensorimotor polyneuropathy and is associated with neuropathic pain, sensory loss, foot ulceration, and risk of amputation.[^4,5] In contrast, cardiac autonomic neuropathy often remains clinically silent but is strongly linked to arrhythmias, orthostatic hypotension, silent myocardial ischemia, sudden cardiac death, and increased overall mortality.[^6,7]

The pathogenesis of diabetic neuropathy is multifactorial, involving chronic hyperglycaemia, oxidative stress, advanced glycation end-product accumulation, microvascular ischaemia, and impaired nerve repair mechanisms.[⁸] Although poor glycaemic control and longer duration of diabetes are recognised risk factors, cross-sectional studies have reported inconsistent correlations between HbA1c and neuropathy severity, suggesting the role of cumulative metabolic exposure or “metabolic memory.”[^9,10]

Indian studies simultaneously evaluating peripheral neuropathy and objectively assessed cardiac autonomic neuropathy within the same cohort remain limited. The present study was therefore undertaken to assess the burden and spectrum of peripheral and cardiac autonomic neuropathy and their relationship with duration of diabetes and glycaemic control in a tertiary care hospital setting.

Study Design and Setting This hospital-based cross-sectional observational study was conducted from June 2020 to November 2021 in the Departments of General Medicine and Neurology at R. G. Kar Medical College & Hospital, Kolkata. Ethical Approval Ethical clearance was obtained from the Institutional Ethics Committee (Approval No. RKC/136 dated 12.02.2020). Written informed consent was obtained from all participants prior to enrolment. Study Population Adults aged 20 years or above with a diagnosis of type 2 diabetes mellitus attending outpatient services or admitted to medical wards were consecutively enrolled. Exclusion Criteria Patients with type 1 diabetes mellitus, secondary causes of neuropathy, nutritional deficiencies, chronic infections, malignancy, stroke, autoimmune neurological disorders, hypertension, or a history of smoking were excluded. Assessment of Neuropathy Peripheral neuropathy was assessed by detailed neurological examination and confirmed using nerve conduction studies. Autonomic dysfunction was evaluated using autonomic symptom assessment, galvanic skin response testing, and standardised cardiac autonomic reflex tests assessing both parasympathetic and sympathetic function. Glycaemic Assessment Fasting blood glucose, post-prandial blood glucose, and HbA1c levels were recorded for all participants. Statistical Analysis Data were analysed using SPSS version 20.0. Continuous variables were expressed as mean ± standard deviation. Appropriate parametric or non-parametric tests were applied for group comparisons. A p-value <0.05 was considered statistically significant.

Peripheral neuropathy was detected in 39.8% of the study population, with distal symmetrical sensorimotor polyneuropathy being the most common subtype. Cardiac autonomic neuropathy was identified in 98.98% of patients, of whom 80.6% had severe or advanced involvement. Parasympathetic dysfunction was the predominant abnormality.

Neuropathy was more frequently observed among patients with longer duration of diabetes and poorer glycaemic indices; however, these associations did not reach statistical significance. A strong association was observed between the presence of autonomic neuropathy and diabetic retinopathy.

Table 1. Demographic Profile of Study Participants (N = 98)

Table 2. Clinical and Glycaemic Characteristics of Study Participants (N = 98)

Table 3. Spectrum of Diabetic Neuropathy in the Study Population (N = 98)

Table 4. Comparison of Glycaemic Control and Duration with Neuropathy Status

1. Peripheral Neuropathy (DPN+ vs DPN−)

1. Cardiac Autonomic Neuropathy (CAN+ vsCAN−)

* Statistically significant (p < 0.05)

Continuous variables were compared using independent t-test or Mann–Whitney U test as appropriate. Categorical variables were compared using Chi-square or Fisher’s exact test. A p-value <0.05 was considered statistically significant.

Figure 1: Key Outcome Parameters

Figure 2: Peripheral Neuropathy Subtype Distribution

This study demonstrates a high burden of both peripheral and cardiac autonomic neuropathy among patients with long-standing T2DM. The prevalence of peripheral neuropathy observed in the present study is comparable with earlier Indian and international reports.[¹³,¹4]

A notable finding was the near-universal presence of cardiac autonomic neuropathy, with a majority of patients showing severe or advanced involvement. Similar observations have been reported in hospital-based studies employing comprehensive autonomic testing protocols.[11,15] Parasympathetic dysfunction predominated, consistent with evidence suggesting earlier involvement of parasympathetic fibres in diabetes.[6,12]

Although neuropathy was more frequent among patients with longer disease duration and poorer glycaemic indices, the lack of statistical significance supports the concept of metabolic memory, whereby prior glycaemic exposure influences long-term complications independent of current HbA1c levels.[16,17] The strong association between autonomic neuropathy and diabetic retinopathy further reflects widespread microvascular involvement.[15,18]

Peripheral and cardiac autonomic neuropathy are highly prevalent among patients with long-standing T2DM. Cardiac autonomic neuropathy may develop early and independently of HbA1c levels. Routine autonomic assessment should be incorporated into standard diabetes care to enable early identification of high-risk patients and reduce cardiovascular morbidity and mortality.

Limitations

The cross-sectional design limits causal inference. As a single-centre hospital-based study, the findings may not be fully generalisable to the wider community.

Funding

Nil.

Conflict of Interest

The authors declare no conflict of interest.

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