Obesity and hyperlipidemia are risk factors for early diabetic neuropathy

Abstract

The Utah Diabetic Neuropathy Study (UDNS) examined 218 type 2 diabetic subjects without neuropathy symptoms, or with symptoms of<5 years, in order to evaluate risk factors for neuropathy development. Each subject completed symptom questionnaires, the Utah Early Neuropathy Scale (UENS), nerve conduction studies (NCS), quantitative sensory testing (QST) for vibration and cold detection, quantitative sudomotor axon reflex testing (QSART), and skin biopsy with measurement of intraepidermal nerve fiber density (IENFD). Those with abnormalities of≥3 were classified as having probable, and those with 1-2 as possible neuropathy. The relationship between glycemic control, lipid parameters (high density lipoprotein and triglyceride levels), blood pressure, and obesity, and neuropathy risk was examined. There was a significant relationship between the number of abnormalities among these features and neuropathy status (p<0.01). Hypertriglyceridemia, obesity and 3 or more abnormalities increased neuropathy risk (risk ratios 2.1 p<0.03, 2.9 p>0.02 and 3.0 p<0.004 respectively). Multivariate analysis found obesity and triglycerides were related to loss of small unmyelinated axons based on IENFD whereas elevated hemoglobin A1c was related to large myelinated fiber loss (motor conduction velocity). These findings indicate obesity and hypertriglyceridemia significantly increase risk for peripheral neuropathy, independent of glucose control. Obesity/hypertriglyceridemia and hyperglycemia may have differential effects on small versus large fibers.

Keywords: Diabetes; Hyperlipidemia; Obesity; Peripheral neuropathy.

Figure 1

(A) Chi squared analysis revealed a significant relationship between the number of risk factors present and peripheral neuropathy criteria fulfilled (p<0.009). (B) Subjects with probable or possible neuropathy had abnormalities of more risk factors than those without neuropathy (p<0.07).

Figure 2

Obesity, hypertriglyceridemia and abnormalities of ≥ 3 risk factors each significantly increased the risk for peripheral neuropathy, while there was a trend for reduced HDL cholesterol doing so (A). These relationships were more robust when only subjects with well controlled diabetes (HbA1c 6–8%) were considered (B).

Figure 3

IENFD at each biopsy site was significantly correlated to BMI (proximal thigh cc −0.23, p<0.001), but not HbA1c. Sural sensory amplitude correlated with both BMI (cc −0.23, p<0.001) and HbA1c (cc −0.24, p<0.001), whereas Peroneal motor conduction velocity (a relatively pure large fiber metric) only correlated with HbA1c (cc −0.35, p<0.001).