Ten-year Follow-up of Subjects with Impaired Glucose Tolerance: Prevention of Diabetes by Tolbutamide and Diet Regulation

Abstract

In a diabetes detection survey carried out between 1962 and 1965, 2477 (1.1%) of 228,883 subjects had Clinistix-positive glucosuria after a carbohydrate-rich luncheon meal. Of these 2477, 578 displayed impaired tolerance to oral glucose without having manifest diabetes. From this group, 267 men were divided into five groups and subjected to the following treatments and controls: (a) diet regulation and 0.5 g tolbutamide t.i.d. (N = 49), annual oral glucose tolerance test (OGTT); (b) diet regulation and one placebo tablet t.i.d. (N = 48), annual OGTT; (c) diet regulation only (N = 50), annual OGTT; (d) no treatment (N = 61), annual OGTT; and (e) no treatment, OGTT at follow-up (N = 59 at follow-up). In addition, a control group was included comprised of men with normal OGTT (N = 52). At follow-up, 29% of those without diet regulation and medication (group e: N = 59) had developed diabetes. Of those on diet regulation, but without active medication (group b plus group c, N = 98), 13% had diabetes. No individual maintaining tolbutamide and diet regulation (N = 23) had progressed to diabetes. In this group, 80% of those later examined (N = 11) had serum tolbutamide concentrations in the therapeutic range. No individual with initially normal OGTT developed diabetes or impaired OGTT. The findings suggest that normal oral glucose tolerance signifies little risk of progress to impaired glucose tolerance and manifest diabetes, whereas impaired glucose tolerance is associated with a high risk of progression to diabetes. In addition, it seems possible that treatment with diet regulation, in combination with tolbutamide, may prevent or postpone progression from impaired glucose tolerance to manifest diabetes.

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland

“…Despite these considerations and positive findings, neither the Bedford (sulphonylurea) nor Whitehall (biguanides) studies in England established that either diet or oral antidiabetic agents have a discernible effect on the subsequent incidence of diabetes [24,26]. On the other hand, both the Malmöhus study and the Malmö feasibility study in Sweden suggest the possibility of a reduction in diabetes incidence by at least 30 % through intervention [23,27,44]. In the Malmöhus study in Sweden, persons with IGT were randomly assigned to one of three groups, all of which received diet treatment.…”

“…We needed 3252 person years, which means that the study centres had to recruit 650 subjects to be followed for 5 years, or 542 subjects to be followed for 6 years. The possibility of a reduction in diabetes incidence by at least 35 % is suggested by the results of the Malmöhus study, the Malmö feasibility study and the Da Qing study in which the effects of intervention were at least 40 % [23,27,28]. Furthermore, we are assuming that non-compliance in the DPS will not be worse than in these previous studies, making further adjustment for non-compliance unnecessary.…”

“…In the tolbutamide group, however, the diabetes incidence was 10 %, and among those who did not receive any medication it was 13 %. The data were also analysed according to estimates of compliance and none of those who continued to take tolbutamide developed diabetes [23].…”

A study of the effects of acarbose on glucose metabolism in patients predisposed to developing diabetes: the Dutch acarbose intervention study in persons with impaired glucose tolerance (DAISI)

“…The World Health Organization distinguishes this glucose intolerance category for its two-fold risk of cardiovascular disease [4][5][6][7][8][9]. Moreover, approximately a third of persons with IGT develop type 2 diabetes within 5-10 years [10][11][12][13][14].…”

Prediabetes: the cat is out!

“…The successful interventions tested were diet and exercise [7], metformin [8], tolbutamide [9], orlistat [10], and acarbose [11].…”