Enhanced Glucose Control for Preventing and Treating Diabetic Neuropathy in Type 1 Diabetes

Summary

A Cochrane review [Abstract] 1 included 17 studies to investigate the effects of enhanced glycaemic control on neuropathy in patients with DM after at least one year of intervention. Primary outcome was defined as development of clinical neuropathy. Secondary outcomes included motor nerve conduction velocity and quantitative vibration testing. Definition of enhanced glucose control varied across studies; included were all measures aimed to improve control (multiple injections, insulin pump, education etc.). Results of the The studies concerning patients with type 1 DM are summarized here.

Three studies measured clinical neuropathy, which was defined as the presence of 2 or more of the following: symptoms, sensory examination findings, and decreased or absent reflexes. The cohort was divided to primary prevention group (IDDM of 1 to 5 years' duration, no detectable retinopathy, and urinary albumin excretion less than 40 mg/24 hour) and secondary prevention group (IDDM of 1 to 15 years' duration, very mild to moderate non-proliferative retinopathy, and urinary albumin excretion less than 200 mg/24 hour).

At five years in the primary prevention cohort, there was a decrease in the incidence of clinical neuropathy in the participants randomized to intensive treatment (n=251) compared to standard treatment (n=292): annualized RD -1.53% (95% CI -2.54 to -0.51), RR 0.47 (95% CI 0.27 to 0.80).

In the secondary prevention cohort (n = 642, 327 intensive, 315 conventional), the annualized RD was -1.97% (95% CI -3.04 to -0.90) in favor of enhanced glucose control at five years (RR 0.48, 95% CI 0.32 to 0.73).

Another Cochrane review [Abstract] 2 included 12 studies with a total of 2 230 adults and children with type 1 diabetes. Under intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for retinopathy, nephropathy, and neuropathy (table T2). Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy) (table T2) . Major macrovascular outcomes (stroke and myocardial infarction) occurred very rarely. intensive glucose control increased the risk for severe hypoglycaemia, however the results were heterogeneous and only the 'Diabetes Complications Clinical Trial' (DCCT) showed a clear increase in severe hypoglycaemic episodes under intensive treatment. A subgroup analysis according to the baseline haemoglobin A1c (HbA1c) of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).

A study 3 assessed risk factors for diabetic peripheral neuropathy. The Michigan Neuropathy Screening Instrument (MNSI) was used to assess neuropathy in 1734 youth with T1D (mean ± SD age 18 ± 4 years, T1D duration 7.2 ± 1.2 years, and HbA1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA1c 9.4 ± 2.3%), and had ≥5 years of diabetes duration.Neuropathy was defined as an MNSI exam score of >2. Glycemic control over time was estimated as area under the curve for HbA1c. The prevalence of neuropathy was 7% in youth with T1D and 22% in youth with T2D. Risk factors for with T1D were older age, longer diabetes duration, smoking, increased diastolic blood pressure, obesity, increased LDL cholesterol and triglycerides, and lower HDL cholesterol (HDL-c). In youth with T2D, risk factors were older age, male sex, longer diabetes duration, smoking, and lower HDL-c. Glycemic control over time was worse among those with neuropathy compared with those without for T1D (odds ratio 1.53, 95% CI 1.24 to 1.88) but not for youth with T2D (1.05, [0.7 to 1.56).