The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM)

To determine whether a difference in HbA(1c) could be safely sustained betw een a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in commun ity practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy. A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/-. 4 yea rs. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to att ain near-normal glycemia and a clinically significant separation of glycohe moglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening i nsulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR varia tion (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c ) at or below 7.3% (p = 0.001 versus STD). Baseline prevalence of periphera l neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence i ncreased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0.008 versus baseline, but no different than STD). Though INT did not rever se all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT, By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline an d no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 7 3% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating sym ptoms. Our conclusion was that 2 years of meticulous glycemic control did not decr ease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. The re was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT. (C) 2000 Elsevier Scienc e Inc.