In a long-term comparative clinical trial, the efficacy of oral hypoglycemic agents and diet therapy in diabetic retinopathy was evaluated. A total of 286 patients participated in the trial, which extended over a two-year period. The trial involved some original innovations or new concepts both in its design and in the methodology of data assessment. This, together with a large amount of pertinent data collected, led us to present the report on the trial in four separate parts. In Part I, the newly designed protocol for the long-term trial is dealt with in detail. The evaluation of retinopathy as the main objective of the trial, in particular, was performed using three different methods by means of the blind technique in which the evaluating physicians were kept blind. Also introduced was the parameter of “degree of satisfaction with treatment of diabetes mellitus, ” which was assessed by medical specialists who were kept uninformed of the method of treatment undertaken as well as the names of the patients and the institutions. Many aspects of the present trial, such as the management and analysis of data and even randomization of the patients were extensively computerized. Only the objective of the trial and the methods employed are dealt with in this section; details on the results of the trial, discussion and conclusion will appear in the succeeding parts.

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A long-term comparative clinical trial was made with oral hypoglycemic agents to evaluate their efficacy in diabetic retinopathy. The protocol for the trial was fully described in the preceding paper. In this paper, the results obtained, particularly as regards the degree of satisfaction with the treatment of diabetes mellitus as well as the criteria for the acceptability of data collected, the analysis of background factors and the safety of oral hypoglycemic agents are dealt with. Of a total of 286 patients participating in the trial, 279 were finally included in the analysis of pertinent data [84 receiving Gliclazide (SE), 116 receiving other sulfonylureas (SU) and 79 on dietary treatment (Diet) alone]. Patients receiving SE and those receiving SU were found to be populations with nearly identical background factors; those on Diet alone were obviously somewhat dissimilar to these populations in this respect. Most patients in the SE group had previously received SU. The degree of satisfaction with the treatment of the disease was higher with the Diet group, with a score of 3.1±1.8 compared to 4.2±2.0 for the SE and 4.7±1.9 for the SU groups respectively. Rating the parameter on an ordinary scale consisting of the categories of “good”, “fair” and “poor”, it was also found that Diet was accepted significantly more satisfactorily, the response being good or better in 70.8 per cent and fair or better in 86.0 per cent of the patients treated as compared to 47.6 and 67.8 per cent with SE and 34.5 and 67.3 per cent with SU, respectively. These data were subjected to further analysis in different stratified subgroups of patients. Evaluation of safety was in terms of manifestations of hypoglycemia, ECG findings, adverse reactions and laboratory values. No remarkable side-effects were observed with SE with the exception of skin rash, which was somewhat more common with the agent.

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A long-term comparative clinical trial with oral hypoglycemic agents was performed to assess their efficacy in diabetic retinopathy. In the preceding papers, the objective of the trial and the methods used were discussed along with some background factors of the patients treated, the degree of satisfaction with the treatment of diabetes, and the relative safety of the drugs studied. This paper deals with the fasting blood glucose, serum lipids and patient's body weight as indices of control of diabetes together with the characteristic effects of Gliclazide (SE) on platelet adhesiveness and the equivalent doses of oral hypoglycemic agents as information that is useful in the clinical application of SE in actual practice. The degree of control of fasting blood glucose was essentially parallel with the degree of satisfaction with the treatment of diabetes: the fasting blood glucose was well controlled in 73.1 per cent of the patients on Diet alone as compared with 51.9 per cent with SE and 40.5 per cent with SU. As to the serum lipids, no marked difference was present among the three groups in total cholesterol or triglyceride, whereas HDL cholesterol was more satisfactorily controlled in patients receieving SU. The body weight of patients was somewhat increased with SE, tended to decrease with SU and remained almost unchanged with Diet. The actual dosage of SE ranged from 5-240 mg daily with a mean of 80 mg daily. Estimation of equivalent doses of the drugs studied and other oral hypoglycemic agents showed that one tablet (40 mg) of SE is as potent as 500 mg of tolbutamide, 250 mg of acetohexamide, 1.25 mg of glibenclamide or 125 mg of chlorpropamide.

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A long-term comparative clinical trial with oral hypoglycemic agents was performed to evaluate their efficacy in diabetic retinopathy. In the preceding papers, the objective of the trial, methods used, background factors of the patients and the results of analyses of medical data on the control of diabetes were discussed. This paper deals with the ophthalmologic evaluation of diabetic retinopathy as the main aspect of the trial. Ophthalmoscopy and photofluorography of the eye ground were performed in all cases to compare the results obtained before with those after treatment (at 18 to 24 months). Three new methods for evaluating the disease were introduced: classification according to the severity of the disease, evaluation by paired comparison and ranking of photofluorographic findings (by a panel of three ophthalmologists). All procedures of evaluation were performed by a blind technique. It was found that the results of evaluation varied with the method employed: the rate of aggravation was lower with Gliclazide (SE) when estimated according to the severity of the disease, whereas no difference existed among the groups when the parameter was evaluated by the paired comparison method. The rate of aggravation estimated by ranking of photofluorographic findings, in turn, was higher with SE than with other sulfonylureas (SU). Evaluation of individual parameters also yielded results that varied considerably from method to method, indicating the questionable validity of the combination of the methods of evaluation employed. Reasonably uniform results were obtained, however, with regard to the incidence of progression to proliferative retinopathy, which was higher with SU with a figure of 6.6 per cent compared to 1.8 per cent with SE and 0.8 per cent with Diet; such a tendency was confirmed by the funduscopic findings. It was thus concluded the SE is an oral hypoglycemic agent that is both effective and safe in the treatment of diabetes and worthwhile, particularly in case of diabetic retinopathy.

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The present report concerns two cases of foot gangrene caused by iliac artery occlusion in diabetic patients, who had been resistant to medication and amputation of the lower extremity, but were improved by vascular surgery.
The first case was a 58-year-old female. Although she had been diagnosed as diabetes mellitus 7 years previously, she had neglected treatment until one month earlier, when she was penetrated by a thorn, and her first and second digits developed gangrene. The clinical findings of the patient were as follows. Pulsation of the femoral artery was weak at the right and normal at the left. Dorsal artery of the foot was not palpable bilaterally. X-P revealed calcification along the femoral artery. An angiogram of the right lower extremity showed narrowing and occlusion of the artery. The gangrene was resistant to conservative medical treatment and amputation of the lower extremity. Translumbar aortography demonstrated occlusion of the right iliac artery and narrowing of the left iliac artery. Aorto-femoral bypass operation was very effective in this ease.
The second case was a 66-year-old male. His DM had been pointed out 20 years previously. Two months earlier, he complained of gangrene of the first digit. Translumbar aortography demonstrated occlusion of the bilateral iliac arteries. He was improved by left axillo-bilateral femoral bypass with a left femoro-popliteal bypass operation.
In order to diagnose diabetic gangrene and to determine the treatment plan, angiograms have often been used, generally below the femoral artery. These cases suggest that angiograms from a higher position, i. e., from the abdominal aorta, may be required. Vascular surgery is also necessary for the treatment of gangrene from the early stage of the disease.

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