Metabolic syndrome factors and modifiable lifestyle habits are associated with prevalence of diabetic polyneuropathy and neuropathic pain in patients with early type 2 diabetes, according to study results published in Diabetes Care.
Little is known about the risk factors associated with polyneuropathy and neuropathic pain in patients with type 2 diabetes. Coordinating data from the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort with other national health registries, investigators aimed to characterize the association between metabolic and lifestyle factors and the risk for diabetic polyneuropathy and neuropathic pain in early type 2 diabetes.
Questionnaires assessing neuropathy and pain were sent to patients at a median of 2.8 years (interquartile range, 1.8-3.7 years) after enrollment in the DD2 cohort. Questionnaires included the 15-item Michigan Neuropathy Screening Instrument Questionnaire, the 7-item Douleur Neuropathique en 4 Questions questionnaire, and general questions about pain localization, anthropometric data, and lifestyle factors. Obesity measures and metabolic data were obtained from the DD2 database and health registers.
Of the 5249 patients (42% women) who responded to the questionnaires, 938 (17.9%) had diabetic polyneuropathy, of which 386 cases (7.4%) were painful.
Higher measures of central obesity at baseline and follow-up were associated with a higher prevalence of diabetic polyneuropathy, including body mass index (BMI), waist circumference, waist to hip ratio, and waist to height ratio. When measures of central obesity were adjusted for BMI, all remained positively associated with diabetic polyneuropathy.
Several metabolic factors were associated with diabetic polyneuropathy as well. Low levels of high-density lipoprotein cholesterol (<1.0 mmol/L in men, <1.2 mmol/L in women) were associated with increased prevalence of diabetic polyneuropathy (adjusted prevalence ratio [aPR], 1.35; 95% CI, 1.12-1.62). High triglycerides (≥1.7 mmol/L; aPR, 1.36; 95% CI, 1.17-1.59), low-grade inflammation (high-sensitivity C-reactive protein level ≥3.0 mg/L; aPR, 1.66; 95% CI, 1.42-1.94), and antihypertensive drug treatment (aPR, 1.34; 95% CI, 1.16-1.55) were also associated with diabetic polyneuropathy. Increasing levels of C-peptide (≥850 pmol/L) and hemoglobin A1c (≥58 mmol/mol) were associated with increasing aPR for diabetic polyneuropathy as well.
Lower physical activity levels and a current or former smoker status at baseline were also associated with diabetic polyneuropathy. The prevalence of diabetic polyneuropathy was low in patients with increased physical activity levels over the course of follow-up (aPR, 0.67; 95% CI, 0.52-0.85) and high in patients whose activity level decreased over the same time period (aPR, 1.20; 95% CI, 1.00-1.46).
Among patients with diabetic polyneuropathy, alcohol consumption and current smoking status at baseline as well as current smoking status at follow-up were all associated with increased neuropathic pain prevalence. Increased physical activity levels from baseline to follow-up were associated with lower neuropathic pain prevalence (aPR, 0.82; 95% CI, 0.67-0.99).
The researchers noted that the use of questionnaires to assess the prevalence of diabetic polyneuropathy and neuropathic pain represented a limitation of the study, as diagnosis was not validated using neurologic examination.
“[T]hese data provide evidence that [diabetic polyneuropathy] in early type 2 diabetes is closely associated with specific risk factors in addition to hyperglycemia, including metabolic syndrome factors, insulin resistance, and low-grade inflammation. Moreover, unhealthy lifestyle habits, including smoking and physical inactivity, are modifiable factors strongly associated with [diabetic polyneuropathy],” the study authors concluded. “Pain occurrence in [diabetic polyneuropathy] may share some, but not all, of these modifiable risk factors.”
Disclosure: Funding for this study was provided by Novo Nordisk.
Christensen DH, Knudsen ST, Gylfadottir SS, et al. Metabolic factors, lifestyle habits, and possible polyneuropathy in early type 2 diabetes: a nationwide study of 5,249 patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort [published online April 15, 2020]. Diabetes Care. doi:10.2337/dc19-2277