75-g Glucose Tolerance Test Research Articles

Insulin gene in familial NIDDM. Lack of linkage in Utah Mormon pedigrees.

Although non-insulin-dependent diabetes mellitus (NIDDM) is well recognized to be an inherited disease, the genetic lesion responsible remains to be determined. Several pedigrees have been reported in which defects of the insulin gene result in glucose intolerance or diabetes in affected members, but the role of insulin gene mutations in NIDDM is unknown. To evaluate this role, we ascertained 23 Caucasian pedigrees for a diabetic individual with at least one diabetic family member, sampled the unaffected individuals by a 75-g glucose tolerance test, and prepared leukocyte DNA on all family members. Included in the pedigrees ascertained were those with both predominantly lean and predominantly obese diabetic members and four pedigrees included as insulin-dependent diabetic individual. Insulin gene involvement was evaluated via previously described restriction-fragment-length polymorphisms (RFLPs) for the insulin gene and the nearby c-Ha-Ras oncogene (HRAS). Combination of these RFLPs resulted in the ability to trace the insulin alleles in all pedigrees studied. Analysis of individual pedigrees for sharing of insulin alleles was possible in 12 pedigrees, and lack of linkage was demonstrated in 6 of them. Neither linkage nor lack of linkage could be proved in the remaining pedigrees. Analysis of the pooled pedigree data failed to demonstrate linkage under several models, including autosomal-dominant and -recessive inheritance with different sporadic frequencies of diabetes and different prevalence figures. These results show that mutations of the insulin gene and the immediately surrounding area, including regulatory regions of the insulin gene, are unlikely to account for a significant subset of NIDDM in Caucasian individuals.

Clinical investigation on the mechanism of glucose intolerance in Cushing's syndrome

We investigated the mechanism of glucose intolerance in 51 patients with Cushing's syndrome. In an oral 100g glucose tolerance test, although prevalence of decreased glucose tolerance was very high as revealed in 36 of 47 patients (77%) studied, impairment was rather mild in the majority of patients and only 10 patients (21%) were judged as diabetic. Plasma insulin was measured in 12 patients and the mean values of these patients reached above normal levels after oral glucose load. When insulin secreting capacity was assessed by measuring the ratio of the incremental area of insulin above fasting level to the corresponding area of glucose during the test, Cushing's syndrome as a whole exhibited a normal ratio compared to 9 control subjects (113 +/- 115 vs. 144 +/- 78 microU/mg, M +/- SD, ns), but in 3 patients with severe impairment of glucose tolerance reaching the diabetic range, the ratio was lower than normal (27 +/- 20 vs. 144 +/- 78 microU/mg, M +/- SD, p less than 0.05). The hypoglycemic effect of iv insulin was studied in 23 patients and was demonstrated to have decreased. Thus, we confirmed the presence of decreased insulin sensitivity, i.e. insulin resistance in Cushing's syndrome. The age of patients showed positive correlation with the degree of impairment in glucose tolerance and insulin secreting capacity, but not with that of insulin sensitivity, that is, in patients with advanced age, glucose intolerance appeared to be severe with decreased insulin secreting capacity. 125I-insulin binding to red blood cells in 8 patients was examined to elucidate the mechanism of insulin resistance in Cushing's syndrome. Percent specific binding at tracer concentration of insulin in Cushing's syndrome was not different from the value obtained in 19 normal subjects (8.2 +/- 3.0 vs. 7.7 +/- 1.0%, M +/- SD, ns). Receptor concentration and affinity were also normal. From these observations, it is likely that glucose intolerance in Cushing's syndrome is primarily due to the effects of chronic glucocorticoid excess on tissue metabolism of glucose as characterized by the presence of insulin resistance, which is not due to a defect in insulin-receptor binding but rather caused by the alteration in post-receptor mechanism, and increased secretion of insulin can be considered as a compensatory mechanism. In some patients, however, a decrease in insulin secreting capacity, the cause of which is not clear but at least related to the patient's age, is found and seems to lead to severe glucose intolerance.

Plasma glucose and plasma insulin values during the 75 g glucose tolerance test (75 g GTT) in pregnancy.

The 75g GTT was performed on 722 pregnant women to clarify the glucose tolerance during pregnancy. The results were as follows : (1) Plasma glucose values after 75g GTT were the same in category A (with potential diabetes or glycosuria) before and after 28 weeks of pregnancy, but for women in categories B (without potential diabetes and glycosuria) and C (excluding the neonatal complications in category B), the plasma glucose values were higher during or after 28 weeks of pregnancy than before the 28th week. (2) The plasma glucose after glucose loading was higher in category A than in category B or C, but there was no difference between category B and C. (3) The plasma insulin values in category B were the same before and after 28 weeks of pregnancy; but for women in categories A and C, the values were significantly higher after 28 weeks of pregnancy. (4) The incidence of a low insulinogenic index was 12.1% in category A, which was significantly higher than the indexes for categories B and C. These results may be useful to establish the normal limit of glucose values after 75g glucose loading during pregnancy.

Glucose tolerance in young and older athletes and sedentary men.

Groups of endurance-trained masters athletes (60 +/- 2 yr), older untrained men (62 +/- 1 yr), lean older untrained men (61 +/- 2 yr), endurance-trained young athletes (26 +/- 1 yr), and young untrained men (28 +/- 1 yr) were studied to obtain information on the separate effects of age, physical activity, and body fatness on glucose tolerance and insulin sensitivity. Each subject underwent an oral 100-g glucose tolerance test. Skinfold thickness was determined at six sites. The trained groups had a higher maximum O2 uptake capacity and lower sum of skinfolds than their sedentary peers. The lean older untrained group had a sum of skinfolds similar to that of the young untrained group. The masters athletes, young athletes, and young untrained men exhibited similar glucose tolerance whereas the two older untrained groups had an almost twofold greater total area under the glucose curve (P less than 0.05). The masters and young athletes had significantly blunted plasma insulin responses compared with the other three groups (P less than 0.05). The young and the lean older untrained groups had similar plasma insulin responses with significantly lower insulin levels than the older untrained group (P less than 0.05). These results provide evidence that regularly performed vigorous exercise can, in some individuals, prevent the deterioration of glucose tolerance and insulin sensitivity with age.

動脈硬化における体液糖蛋白質の代謝・分泌・排泄に関する研究

Hourly changes of salivary total binding hexose (STBH) during 100g glucose tolerance test (GTT) were investigated in 129 cases with mild hypertension, diabetics and gastritis.And also as control, hourly changes of STBH by water administration of 500ml were observed in 5 cases of the young and 13 cases of the aged.Sephadex G-100 column chromatography of STBH was performed in 3 cases of the healthy young and 3 cases of the healthy aged.1) Though the amounts of STBH were not changed hourly by oral water administration, the amounts of STBH were obviously increased 30 minutes and 6 minutes after 100g GTT.2) The increased amounts of STBH by 100g GTT were in such relationships as “the young>the aged”, considering types of GTT.3) The STBH was separated at least into two fractions (FrI, FrII) by sephadex G-100 column chromatography. The molecular weight is in such relationships as “FrI>FrII”.The increased amounts of FrI and FrII by 100g GTT were in such relationships as “the healthy young>the healthy aged”. Therefore, there are close relationships between the both fractions and aging.4) It was speculated that the dry feeling of oral cavity in the aged related to the decreased secretion of STBH.