Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep;8(5):646-655.
doi: 10.1111/jdi.12650. Epub 2017 May 3.

Peripheral neuropathy in prediabetes and the metabolic syndrome

Amro M Stino  1 , Albert G Smith  2
Affiliations
Review

Peripheral neuropathy in prediabetes and the metabolic syndrome

Amro M Stino et al. J Diabetes Investig. 2017 Sep.

Abstract

Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome.

Keywords: Metabolic syndrome; Peripheral neuropathy; Prediabetes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) Skin biopsy stained with PGP 9.5 shows normal intra‐epidermal nerve fiber density at the distal leg in a control participant. (b) Intra‐epidermal nerve fiber density is significantly reduced in a patient with distal symmetric polyneuropathy and type 2 diabetes mellitus. Images courtesy of the University of Utah Cutaneous Nerve Laboratory.
Figure 2
Figure 2
(a) Corneal confocal microscopy from a normal participant shows a normal nerve fiber density of 66.7 fibers/mm2 and nerve fiber length of 37.8 mm/mm2. (b) Images from a patient with distal symmetric polyneuropathy show reduced nerve fiber density (12.0 fibers/mm2) and nerve fiber length (12.0 mm/mm2). There is also proliferation of dendritic cells (Langerhans cells), similar to what is observed in skin biopsies of patients with diabetic neuropathy (arrowhead).
Figure 3
Figure 3
Diabetic neuropathy (DPN) and cryptogenic sensory peripheral neuropathy associated with metabolic syndrome likely share common disease mechanisms. Insulin resistance is a core metabolic feature of type 2 diabetes. Obesity and insulin resistance each lead to overlapping and self‐reinforcing mechanisms that converge on direct axonal injury, as well as endothelial injury and abnormal vascular reactivity, each of which in turn lead to axonal injury. AGEs, advanced glycosylation end‐products FA, fatty acid; FFA, free fatty acids; eNOS, endothelial nitric oxides synthase; NADPH, nicotinamide adenine dinucleotide phosphate hydrogen; NO, nitric oxide; ROS, reactive oxygen species; TNFα, tumor necrosis factor alpha.
Figure 4
Figure 4
The capsaicin axotomy technique can be used to assess peripheral nerve regenerative capacity in vivo. (a) At baseline, a 3‐mm punch biopsy is obtained from the distal lateral thigh. The baseline intra‐epidermal nerve fiber density is 21.1 fibers/mm (×40 magnification). (b) Topical capsaicin is placed for 48 h and a biopsy is repeated from the area treated. The post‐capsaicin intra‐epidermal nerve fiber density is markedly reduced (1.0 fibers/mm2). (c) One month after capsaicin application, a skin biopsy is repeated adjacent to the prior biopsies, showing significant nerve fiber regeneration (intra‐epidermal nerve fiber density 10.4 fibers/mm).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Global report on diabetes. World Health Organization, Geneva, 2016. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/ Accessed January 3, 2017.
    1. International Diabetes federation . IDF Diabetes Atlas, 5th edn Brussels: International Diabetes Federation, 2011.
    1. American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33: S62–S69. - PMC - PubMed
    1. Balion CM, Raina PS, Gerstein HC, et al Reproducibility of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) classification: a systematic review. Clin Chem Lab Med 2007; 45: 1180–1185. - PubMed
    1. Grundy SM, Cleeman JI, Daniels SR, et al Diagnosis and management of the metabolic syndrome an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation 2005; 112: 2735–2752. - PubMed

MeSH terms

LinkOut - more resources

  NODES
Association 5
INTERN 2
twitter 2