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A systematic review of the prevalence, risk factors and screening tools for autonomic and diabetic peripheral neuropathy in children, adolescents and young adults with type 1 diabetes

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Abstract

Aims

We aimed to estimate the prevalence of Diabetic peripheral neuropathy (DPN) and Cardiac autonomic neuropathy (CAN) in youth with type 1 diabetes; identify key risk factors; identify the most useful tests for the diagnostic evaluation of DPN and CAN; identify key treatment options for DPN and CAN.

Methods

A systematic search was performed including studies published in the last 15 years. PICO framework was used in the selection process and evidence was assessed using the GRADE system.

Results

A total of 758 studies were identified and a final number of 49 studies were included in this systematic review. According to moderate-high level quality studies, the prevalence of probable DPN, ranged between 13.5 and 62%; subclinical DPN between 22 and 88%; confirmed DPN between 2.6 and 11%. The Michigan Neuropathy Screening Instrument was the tool with higher sensitivity and specificity for detecting DPN, which needs to be confirmed by nerve conduction velocity. The prevalence of CAN was 4–39%. Specific treatment options for DPN or CAN in patients younger than 25 years are not available. Key risk factors for DPN and CAN are hyperglycemia/HbA1c, age, diabetes duration, the presence of other microvascular complications, waist/height ratio, lipid profile and blood pressure. For CAN, additional risk factors were cigarette smoking, BMI and total daily insulin.

Conclusions

Prevalence of neuropathy in youth with type 1 diabetes varies depending on different screening methods and characteristics of the study populations. However, the assessed studies confirmed a relatively high prevalence of subclinical neuropathy, reiterating the importance of early identification of risk factors to prevent this complication.

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Data availability

All databases generated for this study are included in the article.

Abbreviations

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

DKA:

Diabetic ketoacidosis

DN:

Diabetic neuropathy

DPN:

Diabetic peripheral neuropathy

NDS:

Neuropathy disability score

NSS:

Neuropathy symptom score

QST:

Quantitative sensory testing

VPT:

Vibration perception threshold

TT:

Thermal threshold

VT:

Vibration threshold

MNSI:

Michigan neuropathy screening instrument examination

NCS:

Nerve conduction studies

NCV:

Nerve conduction velocity

EMG:

Electromyography

SD:

Standard deviation

US:

Ultrasound

HbA1c:

Hemoglobin A1c

BMI SDS:

Body mass index standard deviation score

CAN:

Cardiac autonomic neuropathy

PAN GI:

Gastrointestinal

GP:

Gastroparesis

CARTs:

Cardiovascular tests

BP:

Blood pressure

BRS:

Baroreflex sensitivity

HR:

Heart rate

HRV:

Heart rate variability

ECG:

Electrocardiography

EDC:

Pittsburgh epidemiology of diabetes complications

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  1. Roberto Franceschi and Enza Mozzillo equally contributed to this work.

Authors and Affiliations

  1. Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d’Oro, 9, 38122, Trento, Italy

    Roberto Franceschi, Letizia Leonardi, Alice Liguori, Francesca Micheli & Vittoria Cauvin

  2. Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy

    Enza Mozzillo, Francesca Di Candia, Francesco Maria Rosanio & Adriana Franzese

  3. Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Gynecology and Pediatrics, University and Azienda Ospedaliera, Universitaria Integrata of Verona, Verona, Italy

    Claudia Anita Piona

  4. Department of Paediatrics, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    M. Loredana Marcovecchio

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Contributions

RF, EM, MLM conceived the study. RF and EM made a substantial contribution to the design of this literature review and screened abstracts. FDC, FR, LL, AL, FM, CAP conducted the full paper analysis. EM and RF independently assessed the certainty of the evidence for each of the outcomes. MLM resolved discrepancies. VC, AF, MLM wrote the manuscript. All the authors approved the final version of the manuscript.

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Correspondence to Roberto Franceschi.

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Franceschi, R., Mozzillo, E., Di Candia, F. et al. A systematic review of the prevalence, risk factors and screening tools for autonomic and diabetic peripheral neuropathy in children, adolescents and young adults with type 1 diabetes. Acta Diabetol 59, 293–308 (2022). https://doi.org/10.1007/s00592-022-01850-x

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