The use of electrophysiological (EP) tests as the primary basis for determining outcome in clinical trials of therapy for symptomatic diabetic polyneuropathy, and the frequently short duration of such trials, is based on assumptions at variance with the pathology and natural history of this disorder and with the evidence that the commonly employed EP tests predominantly reflect the status of the large myelinated nerve fibers. The course of painful, distal symmetrical, primarily sensory polyneuropathy was studied in nine chronic diabetics, aged 21--59 yr, selected for the absence of other forms of diabetic neuropathy, other causes of neuropathy, and other significant illness. All were treated with modifications of diet, insulin, and a daily multivitamin tablet, and, on a randomized basis, also received either placebo or myo-inositol tablets. Initially, and after 2, 4, and 6 mo, a standardized questionnaire was used to assess symptoms, and a standardized neurological examination and battery of EP tests were performed. A minimum of 6 mo was found necessary to assess the clinical course of this syndrome. Clinical improvement occurred in both legs and arms in four patients, as judged by improvement both in symptoms and in the extent of deficits in pinprick and temperature perception; abnormalities in sensory modalities mediated by large myelinated fibers, however, were generally unaltered after 6 mo. A nonuniform distribution of abnormal EP tests of sensory components of the commonly studied nerves of the leg and arm was demonstrated in the study group at the outset, and clinical improvement was not accompanied by evidence of any consistent pattern of improvement in the initially abnormal EP tests. A significant fraction of chronic diabetics with painful, distal symmetrical, primarily sensory polyneuropathy selected by standard criteria appear to have potential for clinical improvement over 6 mo, but primarily in sensory modalities that make it inappropriate to use the common EP tests as the primary basis of judging outcome.

Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.

Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple- than in the single-injection groups: 1.8 +/- 0.7 versus 7.2 +/- 1.9 (p less than 0.01; nonparametric test: p less than 0.02). Final values were, respectively, MAs: 15.2 +/- 4.9; 33.0 +/- 7.9; glycosuria (gm./24 hrs): 20.6 +/- 2.5; 27.5 +/- 4.3; FBS (mg./100 ml.): 154 +/- 15; 195 +/- 11. P values comparing the two groups were less than 0.02, less than 0.02, and less than 0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes.