Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes

Abstract

Objective: Subclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes. Design and methods: Motor and sensory NCV was assessed in individuals with recently diagnosed type 2 (nZ352) or type 1 diabetes (nZ161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammationrelated biomarkers, DSPN and NCV sum scores were estimated using multiple regression models. Results: In type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV. Conclusions: Our results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

“…The second main finding of this study is the identification of higher serum levels of the proinflammatory cytokines IL-6 and TNF-a in individuals with incident DSPN compared with those without incident DSPN after adjustment for anthropometric or metabolic risk factors for DSPN. The finding for IL-6 not only corroborates the report from the KORA F4 study (8) but also is in line with other cross-sectional studies investigating DSPN or impaired nerve conduction (5,17). By contrast, associations between higher TNF-a and DSPN or its components have so far been limited to small studies that did not adjust for confounding factors (6,7,9,15,31), whereas no associations were found in studies that considered confounders (5,8).…”

“…The inverse association between adiponectin and DSPN in the age-and sex-adjusted model in our study is also interesting because cross-sectional studies reported associations between higher adiponectin and DSPN and/or impaired nerve conduction (10,11,17). This discrepancy suggests some degree of residual confounding or reverse causality in the latter analyses, which seems to be no longer relevant in studies using a prospective design.…”

“…These biomarkers were selected for this study based on previous reports describing their associations with DSPN in cross-sectional analyses (5)(6)(7)(8)(9)(10)(11)(12)(13)(16)(17)(18).…”

“…However, the crosssectional design of almost all clinical and epidemiological studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) so far precludes inferences regarding the temporal relationship between inflammation and DSPN, which are essential for any conclusions about causality. One small prospective study assessed plasma levels of soluble adhesion molecules in 28 individuals with diabetes during a 5-year study period and suggested that endothelial activation is associated with nerve conduction slowing (18).…”

Inflammatory markers are associated with cardiac autonomic dysfunction in recent-onset type 2 diabetes

“…Serum concentrations of high-sensitivity C-reactive protein (hsCRP), IL-6, IL-18, total and high-molecular-weight (HMW) adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were measured as described 9 10…”