Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development

Dimitrios Tsilingiris; Lukas Schimpfle; Ekaterina von Rauchhaupt; Alba Sulaj; Lukas Seebauer; Hannelore Bartl; Stephan Herzig; Julia Szendroedi; Stefan Kopf; Zoltan Kender

doi:10.1210/clinem/dgad248

Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development

J Clin Endocrinol Metab. 2023 Sep 18;108(10):e979-e988. doi: 10.1210/clinem/dgad248.

Authors

Dimitrios Tsilingiris^{1

2}, Lukas Schimpfle¹, Ekaterina von Rauchhaupt^{1

2}, Alba Sulaj^{1

2}, Lukas Seebauer¹, Hannelore Bartl³, Stephan Herzig^{2

4

5}, Julia Szendroedi^{1

2

4}, Stefan Kopf^{1

2}, Zoltan Kender^{1

2}

Affiliations

¹ Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany.
² German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany.
³ Department of General, Visceral and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
⁴ Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany.
⁵ Helmholtz Center Munich, Institute for Diabetes and Cancer, 85764 Munich-Neuherberg, Germany.

Abstract

Aim: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.

Methods: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence.

Results: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011).

Conclusion: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.

Trial registration: ClinicalTrials.gov NCT03022721.

Keywords: advanced glycation end products; diabetic polyneuropathy; early neuropathy; insulin resistance; metabolic syndrome; quantitative sensory testing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Glycation End Products, Advanced
Humans
Insulin Resistance*
Male
Metabolic Syndrome* / complications
Metabolic Syndrome* / epidemiology
Peripheral Nervous System Diseases* / epidemiology
Peripheral Nervous System Diseases* / etiology

Substances

Glycation End Products, Advanced

Associated data

ClinicalTrials.gov/NCT03022721