Prediabetes, Obesity May Impact Risk of Polyneuropathy

Diabetic Nerve Pain
Diabetic Nerve Pain
Diabetes, waist circumference, and prediabetes were the main metabolic factors associated with neuropathy.

In a study conducted by researchers from the University of Michigan, polyneuropathy was common in obese patients, even if they had normal blood sugar levels, when compared with lean control participants. Rates of polyneuropathy were also increased in diabetic and prediabetic participants, leading the researchers to conclude that diabetes, prediabetes, and obesity are likely metabolic drivers of polyneuropathy. The findings were published in JAMA Neurology.1

The researchers noted that while diabetes is well-established as a risk factor for neuropathy,2 previous studies have shown mixed results on whether prediabetes is or is not a risk factor for neuropathy.3,4,5

However, only one of these population-based studies used a rigorous definition of polyneuropathy that included neurologic examination, and this study also required that nerve conduction studies show abnormalities to meet the definition of polyneuropathy.5 This may have improperly categorized those who had early polyneuropathy. In addition, not all of the studies required an oral glucose tolerance test to classify glycemic status.

In this study, led by Brian C. Callahan, MD, MS, from the Department of Neurology at the University of Michigan in Ann Arbor, researchers recruited participants from the University of Michigan Weight Management Program between November 1, 2010 through December 31, 2014 before they started a diet and exercise regimen. They enrolled 102 obese participants (mean [SD] age, 52.9 [10.2] years; 48 men, 54 women). Of the 102 participants, 45 had normoglycemia (44.1%), 31 had prediabetes (30.4%), and 26 had type 2 diabetes (25.5%). They also enrolled 53 lean controls (mean [SD] age, 48.5 [9.9] years; 16 men, 37 women).

The researchers found the following rates of polyneuropathy in the different groups:

  • 11.1% in obese participants with normoglycemia (n= 5)
  • 3.8% in lean controls (n= 2)
  • 29% in obese participants with prediabetes (n= 9)
  • 34% in obese participants with diabetes (n= 9) (P< .01 for trend)

Factors that were significantly associated with polyneuropathy included age (odds ratio [OR] 1.09; 95% CI, 1.02-1.16), diabetes (odds ratio, 4.90; 95% CI, 1.06-22.63), and waist circumference (OR 1.24; 95% CI, 1.00-1.55). Notably, prediabetes was not significantly associated with neuropathy (OR 3.82; 95% CI, 0.95-15.41).

“Our study, which used a definition of neuropathy based on a neurologic examination and history, lends further support to prediabetes as a cause of polyneuropathy. The neuropathy prevalence of 29% among the obese participants with prediabetes approached that seen in the obese participants with diabetes,” the authors wrote.

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The researchers also noted that their study did not show a significant association between polyneuropathy and hypertension, HDL cholesterol, or triglycerides.

“Our data support obesity, more than other metabolic factors, as one of the main metabolic drivers of polyneuropathy in addition to hyperglycemia, and provide support for targeting this component in intervention trials designed to prevent or improve polyneuropathy,” they wrote. “Specifically, weight loss interventions may be more likely to be successful at preventing or improving polyneuropathy than efforts to improve hyperlipidemia and hypertension.”

Future studies are needed to confirm whether these metabolic factors may cause neuropathy, as well as what the best interventions are to prevent and improve neuropathy in those who are obese.

Summary & Clinical Applicability

Researchers found that polyneuropathy was common in obese patients, even when they had normal blood sugar levels. They also found increased rates of polyneuropathy in diabetic and prediabetic participants. This led the researchers to conclude that diabetes, prediabetes, and obesity are likely metabolic drivers of polyneuropathy.

“Current clinical practice concentrates on the management of diabetes in those with neuropathy. However, our data also support management of obesity and prediabetes more than other metabolic factors, such as hyperlipidemia and hypertension,” the authors concluded.


  • The study had a small sample size
  • The population was primarily non-Hispanic whites, which may limit generalizability
  • The control group was recruited through a university research website, which may have created selection bias
  • The difference in age between the obese and lean control participants is a potential confounder


  1. Callaghan BC, Xia R, Reynolds E, et al. Association between metabolic syndrome components and polyneuropathy in an obese population. JAMA Neurol. 2016; doi:10.1001/jamaneurol.2016.3745[LS1] 
  2. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;6(6):CD007543
  3. Novella SP, Inzucchi SE, Goldstein JM. The frequency of undiagnosed diabetes and impaired glucose tolerance in patients with idiopathic sensory neuropathy. Muscle Nerve. 2001;24(9):1229-1231
  4. Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2001;24(8):1448-1453
  5. Dyck PJ, Clark VM, Overland CJ, et al. Impaired glycemia and diabetic polyneuropathy: the OC IG Survey. Diabetes Care. 2012;35(3):584-591