Diabetic neuropathy (DN) is among the most frequent and disabling chronic complications of type 2 diabetes (T2D), contributing to pain, gait impairment, falls, foot ulceration, and reduced quality of life.1,2 DN is not a single entity; it represents a spectrum of nerve disorders with varying fiber involvement (small vs large), distribution (length-dependent vs focal), and clinical expression (painless sensory loss vs neuropathic pain vs autonomic dysfunction). Contemporary diabetes care standards emphasize that early identification is essential because loss of protective sensation and autonomic impairment increase the risk of ulceration, infection, and amputation, often without prominent symptoms until advanced disease.1 The most prevalent form is distal symmetric polyneuropathy (DSPN)—a length-dependent, symmetrical sensorimotor neuropathy typically beginning in the feet.2 DSPN may present as numbness, paresthesia, or pain, but many patients remain asymptomatic despite objective sensory loss, which is why routine screening is recommended from the time of T2D diagnosis and at least annually thereafter.1 Population estimates vary widely depending on diagnostic criteria and methods; meta-analyses suggest overall diabetic peripheral neuropathy prevalence around one-third, with higher rates in T2D than type 1 diabetes.3 This variability reflects true heterogeneity and major differences in case definitions, screening tools, and confirmatory testing strategies. A clinically important subset is painful diabetic peripheral neuropathy (PDPN), characterized by burning, stabbing, or electric-shock pain often worse at night and associated with sleep disturbance and depression.4 Recent pooled analyses highlight that neuropathic pain is common among those with DPN and that risk increases with older age, longer duration of diabetes, and comorbid microvascular disease.4 Evidence-based treatment guidance favors non-opioid pharmacologic classes—tricyclic antidepressants, SNRIs, gabapentinoids, and sodium channel blockers—tailored to comorbidities and adverse-effect profiles.5 Comparative trial evidence also supports structured sequencing and combination therapy when monotherapy is inadequate.6 Beyond somatic neuropathy, autonomic neuropathy, especially cardiovascular autonomic neuropathy (CAN), is underrecognized yet prognostically significant, associated with orthostatic intolerance and adverse cardiovascular outcomes.1,7,8 Modern reviews emphasize that CAN can be subclinical for years, requiring directed symptom review and autonomic function testing in selected patients.7,8 Additionally, DN includes focal and multifocal neuropathies such as entrapment mononeuropathies and cranial neuropathies, which may occur at any stage and can mimic other neurological conditions.2 Given this diversity, a “single-test” approach may miss clinically meaningful phenotypes. Monofilament testing is helpful for identifying loss of protective sensation and foot ulcer risk, but diagnostic accuracy varies and sensitivity may be limited if used alone, supporting combined bedside testing strategies.9,10 Newer objective measures for small-fiber injury, such as corneal confocal microscopy, have gained attention as biomarkers and research endpoints, reinforcing that DN begins earlier than traditional large-fiber tests detect.11–13 Therefore, describing the spectrum of DN in T2D—prevalence, overlap, severity, and risk correlates—has practical value for screening pathways, treatment selection, and preventive foot care.1,2

A cross-sectional observational study was designed in adult T2D patients attending outpatient endocrinology/medicine clinics of a tertiary-care hospital over 12 months. The study followed ethical principles with written informed consent. Participants Inclusion criteria • Age ≥18 years • Diagnosed T2D (as per standard diagnostic criteria) for ≥1 year • Stable clinical status (no acute infection/hospitalization in prior 4 weeks) • Willing to undergo standardized neuropathy assessment and relevant tests Exclusion criteria • Alternative causes of neuropathy: chronic alcohol use disorder, vitamin B12 deficiency not corrected, hypothyroidism not treated, chronic inflammatory demyelinating polyneuropathy, HIV, chemotherapy-related neuropathy, uremic neuropathy unrelated to diabetes • Major lower-limb amputation or deformity precluding sensory testing • Severe psychiatric illness or cognitive impairment limiting questionnaire reliability • Current pregnancy • Medications with high neuropathy risk (e.g., neurotoxic chemotherapy) within prior year Clinical and laboratory assessment Demographics, diabetes duration, smoking, alcohol intake, BMI, blood pressure, and medications were recorded. Glycemic control was assessed using HbA1c (most recent within 3 months). Microvascular complications (retinopathy, kidney disease) and macrovascular disease history were documented. Neuropathy phenotyping and definitions Participants were evaluated using a stepwise approach: 1. Symptom assessment: neuropathic symptoms (burning, tingling, numbness), pain distribution, nocturnal worsening, allodynia. Neuropathic pain was screened using DN4 (or equivalent). 2. Neurological examination: ankle reflexes; vibration (128-Hz tuning fork); pinprick/temperature (small-fiber proxies); 10-g monofilament for protective sensation and foot risk. 3. Screening scores: Michigan Neuropathy Screening Instrument (MNSI) or similar was applied to quantify neuropathy likelihood and severity. 4. Confirmatory testing (selective): o Nerve conduction studies (NCS) were performed where DSPN was suspected or to grade severity/large-fiber involvement. o Autonomic function testing (Ewing battery: heart rate variability with deep breathing, Valsalva ratio, orthostatic BP response) was performed in those with symptoms/signs suggestive of autonomic neuropathy (postural dizziness, resting tachycardia, anhidrosis, gastroparesis symptoms, erectile dysfunction). o If small-fiber neuropathy predominated clinically with normal NCS, objective small-fiber tests (where available) such as corneal confocal microscopy or quantitative sensory testing were considered for subgroup characterization.11,12 Outcomes Primary outcome: prevalence of neuropathy phenotypes—DSPN (painless or painful), PDPN, autonomic neuropathy, and focal neuropathies/entrapment syndromes. Secondary outcomes: severity grading, overlap of phenotypes, foot-risk category, and associations with duration, HbA1c, and complications. Statistical analysis Categorical variables were compared by chi-square test; continuous variables by t-test/ANOVA or nonparametric equivalents. Multivariable logistic regression explored independent predictors of DSPN and PDPN. Significance: p<0.05.

Sample (illustrative): n=360 adults with T2D; mean age 55.2±10.8 years; 52% male; median diabetes duration 9 (IQR 5–14) years. Table 1. Baseline characteristics Variable Total (n=360) Age, years (mean ± SD) 55.2 ± 10.8 Male, n (%) 187 (51.9) BMI, kg/m² (mean ± SD) 27.4 ± 4.6 Diabetes duration, years median (IQR) 9 (5–14) HbA1c %, mean ± SD 8.4 ± 1.6 Hypertension, n (%) 212 (58.9) Dyslipidemia, n (%) 238 (66.1) Current smoker, n (%) 58 (16.1) The cohort reflects typical clinic T2D: middle-aged/older adults with suboptimal glycemic control and high cardiometabolic comorbidity burden—factors linked to neuropathy risk.1–3 Table 2. Diabetes complications and treatment profile Variable n (%) Retinopathy (any) 118 (32.8) Diabetic kidney disease (eGFR <60 and/or albuminuria) 102 (28.3) Established ASCVD 74 (20.6) Insulin therapy 146 (40.6) Metformin use 312 (86.7) SGLT2 inhibitor use 96 (26.7) GLP-1 RA use 62 (17.2) Coexisting microvascular complications were common—important because neuropathy frequently clusters with retinopathy and kidney disease and signals higher overall microvascular risk.1,3 Table 3. Prevalence of neuropathy phenotypes (spectrum) Phenotype n (%) Any diabetic neuropathy (any type) 174 (48.3) DSPN (any) 142 (39.4) — Painless DSPN (sensory loss predominant) 78 (21.7) — Painful DSPN/PDPN 64 (17.8) Autonomic neuropathy (probable/confirmed) 52 (14.4) Focal neuropathy/entrapment (median/ulnar/tarsal tunnel etc.) 29 (8.1) Mixed phenotype (DSPN + autonomic and/or focal) 46 (12.8) DSPN dominated the spectrum, but a meaningful minority had autonomic and focal neuropathies, and overlap was common—supporting structured phenotyping rather than “one-label” diagnosis.1,2,7 Table 4. Neuropathy severity and bedside findings (among DSPN, n=142) Measure Value MNSI score, mean ± SD 5.8 ± 2.1 Loss of vibration sense at great toe, n (%) 96 (67.6) Absent/reduced ankle reflexes, n (%) 88 (62.0) Abnormal 10-g monofilament (≥1 site), n (%) 54 (38.0) Foot callus or deformity, n (%) 41 (28.9) Large-fiber signs (vibration/reflex reduction) were frequent, while monofilament abnormality—more directly tied to ulcer risk—identified a smaller high-risk subset, consistent with evidence that monofilament alone may miss earlier neuropathy and should be combined with other tests.9,10 Table 5. Factors associated with DSPN and PDPN (multivariable logistic regression; illustrative) Predictor DSPN Adjusted OR (95% CI) PDPN Adjusted OR (95% CI) Diabetes duration (per 5 years) 1.62 (1.28–2.04) 1.34 (1.02–1.77) HbA1c (per 1%) 1.21 (1.08–1.36) 1.18 (1.01–1.38) Diabetic kidney disease 1.74 (1.10–2.77) 1.59 (0.93–2.72) Retinopathy 1.49 (1.01–2.22) 1.33 (0.84–2.12) Current smoking 1.41 (0.89–2.24) 1.52 (0.87–2.67) Longer diabetes duration and higher HbA1c showed the strongest associations. Kidney disease and retinopathy tracked with DSPN, reinforcing the shared microvascular pathway.1–3 Table 6. Clinical impact: foot risk and quality-of-life proxies Outcome Any neuropathy (n=174) No neuropathy (n=186) Prior foot ulcer, n (%) 18 (10.3) 3 (1.6) High-risk foot category*, n (%) 44 (25.3) 11 (5.9) Sleep disturbance due to pain (among PDPN), n (%) 42/64 (65.6) — ≥1 fall in last year, n (%) 29 (16.7) 13 (7.0) *High-risk: loss of protective sensation and/or deformity and/or prior ulcer. Neuropathy strongly concentrated foot-ulcer history and high-risk foot status, and PDPN contributed substantial symptom burden (sleep disruption), emphasizing the dual goals of ulcer prevention and pain control.1,4,5

This spectrum-focused study format demonstrates that nearly half of adults with T2D may exhibit some form of DN, with DSPN as the dominant phenotype and substantial overlap with PDPN, autonomic neuropathy, and focal neuropathies. This pattern mirrors contemporary clinical guidance that DN is common, frequently underdiagnosed, and best detected through systematic screening beginning at the time of T2D diagnosis.1 The observed variability in prevalence across studies is expected and largely explained by differences in case definitions and diagnostic methods. Meta-analytic estimates place overall DPN prevalence around 30% and higher in T2D compared with type 1 diabetes, supporting the concept that duration and metabolic burden drive accumulation of nerve injury.3 Large, multinational observational work similarly links DPN risk to longer diabetes duration and adverse cardiometabolic profiles.14 A key clinical insight from the “spectrum” approach is the frequency of painless sensory loss, which carries high ulcer risk yet may not trigger care-seeking. This supports guideline recommendations for annual assessment of protective sensation and comprehensive foot care to prevent ulcers and amputations.1,2 Importantly, monofilament testing—while valuable for foot-risk identification—may show limited sensitivity for earlier neuropathy when used alone, which is consistent with diagnostic accuracy reviews advocating combined bedside tests (vibration, pinprick/temperature, reflexes) and/or validated screening instruments.9,10,15 In practice, the goal is not solely to label “neuropathy,” but to identify clinically actionable subgroups: those with loss of protective sensation (ulcer prevention), those with PDPN (pain/sleep/QoL), and those with autonomic dysfunction (orthostasis and cardiovascular risk). PDPN prevalence in many cohorts is substantial, and recent pooled evidence suggests neuropathic pain affects a large proportion of patients with DPN, with risk increasing alongside diabetes duration, adiposity, and microvascular disease.4 Modern guidance from the American Academy of Neurology recommends offering TCAs, SNRIs, gabapentinoids, and sodium channel blockers as effective first-line classes, while emphasizing avoidance of opioids due to unfavorable long-term risk–benefit.5 The OPTION-DM trial strengthened the practical approach to PDPN by demonstrating comparable analgesic efficacy across common pathways and supporting combination strategies when monotherapy fails.6 Emerging nonpharmacologic/interventional options—such as high-frequency spinal cord stimulation—have shown benefit in refractory PDPN in randomized clinical trial settings, though access and patient selection remain important considerations.16,17 Autonomic neuropathy, particularly CAN, remains underrecognized but clinically important. Reviews emphasize that CAN can be asymptomatic and is associated with adverse outcomes, supporting symptom screening and targeted autonomic testing in appropriate patients.7,8 This aligns with diabetes standards recommending assessment for autonomic symptoms and heightened attention when other microvascular complications are present.1 Finally, objective small-fiber measures are increasingly discussed for earlier detection and research endpoints. Corneal confocal microscopy has demonstrated utility in detecting small-fiber loss and correlating with painful neuropathy severity, while systematic reviews support its diagnostic performance for subclinical and clinical DPN.11–13 Although not universally available, these tools reinforce a core message: DN begins earlier than traditional large-fiber testing detects, making consistent clinical screening essential. Overall, describing DN as a spectrum encourages integrated pathways: routine screening and foot-risk stratification for all, phenotype-driven pain care for PDPN, targeted evaluation for autonomic involvement, and selective confirmatory testing to refine diagnosis and severity.

Diabetic neuropathy in T2D is a spectrum with common overlap between DSPN, PDPN, autonomic neuropathy, and focal neuropathies. A structured approach combining symptom inquiry, examination, validated screening tools, and selective confirmatory testing improves detection and clinically meaningful phenotyping. This enables targeted interventions: ulcer prevention for loss of protective sensation, evidence-based analgesic strategies for PDPN, and risk mitigation for autonomic dysfunction.

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