Is Prevention Possible?
Medscape: According to the statement, enhanced glucose control is very effective in preventing diabetic peripheral neuropathy in patients with type 1 diabetes, but is less successful in those with type 2. Why is that?
Dr Busui: Patients with type 2 diabetes are typically very different from patients with type 1 diabetes. They also have other risk factors. Most are overweight or obese. Many have hypertension, metabolic syndrome, and the dyslipidemia associated with metabolic syndrome. All of these factors have been shown to be important in inducing nerve fiber damage, and may explain in part why glucose control alone has not been as effective in preventing diabetic neuropathy in patients with type 2 diabetes.
Patients with type 2 diabetes may also live with the disease for years without it being clearly diagnosed. It is thus likely that most of the patients included in interventional studies that looked specifically at glucose control, and captured some measures of neuropathy, may have been already in a more advanced stage of the disease.
In contrast, the Diabetes Control and Complications Trial (DCCT) included patients with type 1 diabetes early in their course of disease, with no neuropathy at baseline, hypertension, or other complications, except very minimal retinopathy in a subgroup by study design. In addition, a most comprehensive assessment of neuropathy was conducted in the DCCT cohort at baseline and over time in a standardized fashion. Other trials that included patients with type 2 diabetes, such as ACCORD, UK Prospective Diabetes Study (UKPDS), the Veterans Affairs Diabetes Trial (VADT), or BARI 2D, involved patients with more advanced disease.
Another possibility is that neuropathy has been defined differently in many of these trials, or some very insensitive measures were used. For instance, in the VADT, neuropathy was defined only on the basis of patient-reported symptoms, which have a high degree of subjectivity.
DSPN in patients with type 2 diabetes typically presents at a more advanced stage because these patients have a constellation of risk factors that can induce nerve damage.
DSPN in patients with type 2 diabetes typically presents at a more advanced stage because these patients have a constellation of risk factors that can induce nerve damage. That is probably the main reason that we see less protective benefit from enhanced glucose control in these patients.