Modify Cardiovascular Risk Factors to Decrease Incidence of Neuropathy

Trigylceride levels, BMI, smoking patterns and hypertension appeared to affect the progression of diabetic neuropathy in this population.

The only current treatment for diabetic neuropathy is tight glycemic control. Investigators from the European Diabetes (EURODIAB) Prospective Complications Study, however, have suggested that modifying cardiovascular risk factors in type 1 diabetic patients may lower the incidence of diabetic neuropathy.¹ 

Reporting in The New England Journal of Medicine, Solomon Tesfaye, MD, and colleagues examined the risk factors of distal symmetric neuropathy in 1,172 patients who were non-neuropathic at baseline, mean age 32.7 ±10.2 years and diabetes duration 14.7 ±9.3 years. Investigators hoped to signal potential modifiable risk factors for neuropathy, as morbidity and mortality rates are high among diabetic patients with neuropathy, they noted.  

STRONG CONTRIBUTOR

Between 1989 and 1991, patients were randomly selected from 31 EURODIAB participating centers and assessed for total and LDL cholesterol, fasting triglycerides, body mass index, HbA1c and urinary albumin excretion rate during baseline clinical evaluations and quantitative sensory and autonomic-function testing. At mean follow-up (7.3 years), the cumulative instance of neuropathy was 23.5%, which, investigators wrote, “confirm[ed] the previously reported strong contributions of glycemic control and duration of diabetes to the risk of neuropathy.”

Neuropathy developed in patients who were older (average 3.8 years older) and had a longer duration of diabetes (average 3.3 years longer), investigators noted. Patients with hypertension, cardiovascular disease (CVD) or who smoked at baseline also developed neuropathy more frequently. Furthermore, patients with micro- or macroalbuminuria or retinopathy were at an increased risk for neuropathy.

After adjusting for diabetes duration and HbA1c, investigators concluded that an association existed between cardiovascular risk factors and incidence of neuropathy. When patients were hypertensive, had elevated triglyceride levels, smoked or were obese, neuropathy developed. If patients had CVD at baseline, their risk of neuropathy was doubled (Table 1).

Hypertension had the strongest relation to the incidence of neuropathy in type 1 diabetic patients (odds ratio 1.57), as determined with a multivariative logistic-regression model that adjusted for neuropathy risk factors. The relationship, however, lost statistical significance when the definition for neuropathy excluded autonomic symptoms and autonomic-function test results. “This is consistent with our previous report that systolic blood pressure was a risk factor for the development of cardiac autonomic neuropathy,” Dr. Tesfaye and colleagues wrote.

FURTHER STUDIES

There is a need for clinical trials to confirm that modifying cardiovascular risk factors is an effective treatment for diabetic neuropathy. Such a trial should assess the use of antihypertensive agents in reducing cardiovascular, and in return, neuropathy risk, they suggested.

PROPER DIAGNOSIS, TREATMENT

In a related editorial, Bruce A. Perkins, MD, MPH, and Vera Bril, MD,² proposed that a clinical trial of neuropathy for type 1 diabetic patients incorporate modification of cardiovascular risks. “The focus on glycemic control should not obscure the attention owned to modifications of vascular risk factors in clinical trials in patients with type 1 diabetes,” they wrote. Glycemic control, smoking cessation, blood-pressure control and dyslipidemia may be possible interventions against progression to diabetic neuropathy. Drs. Perkins and Bril are from the University of Toronto.

Of the three aspects of diabetic microvascular complications – diabetic neuropathy, diabetic retinopathy and diabetic nephropathy – neuropathy lacks proper diagnosis, prevention and treatment. “We need an indicator of early nerve damage before the development of diabetic neuropathy, akin to early retinal changes as an indicator of risk for retinopathy or microalbuminuria as an indicator of risk for nephropathy,” they wrote.

Solomon Tesfaye, MD, is from the diabetes research unit, Royal Hallamshire Hospital, Sheffield, UK. He has a financial interest in the form of consulting and/or lecture fees with the following companies: Eli Lilly and Company, AstraZeneca, Pfizer Inc, Takeda and GlaxoSmithKline. He can be reached at solomon.tesfaye@sth.nhs.uk. Vera Bril, MD, is from the division of neurology, department of medicine at the University of Toronto. She can be reached at vera.bril@utoronto.ca. Bruce A. Perkins, MD, PhD, also at the University of Toronto, is from the division of endocrinology and metabolism.

1. Tesfaye S, Chaturvedi N, Eaton SEM, et al. Vascular Risk Factors and Diabetic Neuropathy. N Eng J Med. 2005;352:341-350.
2. Perkins BA, Bril V. Early Vascular Risk Factor Modification in Type 1 Diabetes. N Eng J Med. 2005;352:408-409.