Relationship between glucose tolerance,insulin secretion,and insulin action in non-obese individuals with varying degrees of glucose tolerance

Summary Plasma glucose and insulin concentration following a 75 g oral glucose challenge and glucose uptake during a hyperinsulinaemic glucose clamp study were determined in 50 non-obese individuals. The study population was divided into five groups on the basis of their glucose tolerance: normal, impaired glucose tolerance, Type 2 (non-insulin-dependent) diabetes mellitus with fasting plasma glucose of less than 8 mmol/l, between 8–15 mmol/l, and more than 15 mmol/l. The plasma insulin response was significantly greater (p<0.001) than normal in those with either impaired glucose tolerance or Type 2 diabetes and a fasting plasma glucose concentration less than 8 mmol/l. In contrast, the plasma insulin response was similar to normal in the other two groups of patients with Type 2 diabetes, i.e. fasting plasma glucose concentration 8–15 mmol/l or greater than 15 mmol/l. Glucose uptake rates were significantly lower (p<0.001) than normal in subjects with impaired glucose tolerance and all three groups of patients with Type 2 diabetes. Although glucose uptake rates during the glucose clamp studies were relatively similar in all four groups of glucose intolerant subjects, the values were significantly lower in those patients with Type 2 diabetes who had a fasting plasma glucose concentration greater than 8 mmol/l (p<0.01), These data indicate that a significant degree of insulin resistance exists in patients with impaired glucose tolerance or Type 2 diabetes, relatively independent of fasting plasma glucose concentration. Indeed, glucose uptake during glucose clamp studies fell 8-fold over a range in fasting plasma glucose concentration of from 4.5 to 6.5 mmol/l. In contrast, the plasma insulin response increased over the same range of fasting plasma glucose concentrations. The fact that this defect in insulin action can be seen in patients who are hyperinsulinaemic, not hypoinsulinaemic, and only modestly hyperglycaemic, is consistent with the hypothesis that resistance to insulin-stimulate glucose uptake is a basic characteristic of patients with impaired glucose tolerance or Type 2 diabetes.     

Relationship between carbohydrate tolerance,insulin secretion,and insulin sensitivity of isolated fat cells from obese protodiabetics

Summary Six normal weight subjects without any heredity of diabetes (group 1), 3 obese subjects with normal (group 2) and 9 with pathological carbohydrate tolerance (group 3) were characterized by a 2-h glucose infusion test. Adipose tissue fragments were obtained from the abdominal wall by surgical biopsy under intracutaneous anesthesia. Adipocytes were isolated by collagenase digestion and incubated in buffer containing [1-¹⁴C] glucose and different concentrations of insulin. The metabolic effect of insulin was expressed as percent increase above control¹⁴CO₂ production. Maximal CO₂ raised to 207±25% and 154±9% in groups 1 and 2, respectively. These values were significantly higher than in obese subjects displaying a pathological carbohydrate tolerance (group 3; 119±6%). A negative correlation was found between blood glucose levels and biological activity of insulin on adipocytes. The results suggest that insulin sensitivity of target tissue seems to play an important role in the development of carbohydrate intolerance. These investigations have been carried out within the medical research project ‘Diabetes mellitus and disturbances of lipid metabolism’, Ministry of Health, GDR.     

Glucose tolerance, insulin secretion, insulin sensitivity and glucose effectiveness in normal and overweight hyperthyroid women

OBJECTIVE Inter-relationships between insulin sensi-tivity and body weight in patients with hyperthyroidism remain incompletely understood. We have examined whether a mild excess of body weight exacerbates the metabolic abnormalities of spontaneous hyperthyroidism. DESIGN AND PATIENTS Insulin-modified intravenous glucose tolerance tests were performed on 14 hyperthy-roid women with body mass indices (BMI) ranging from 21 to 31 kg/m². A control group of 19 healthy women matched for age and BMI was also studied. MEASUREMENTS Intravenous glucose tolerance (KG), first and second-phase integrated insulin responses to glucose, the integrated glucose area under the curve (AUC), and minimal model parameters of insulin sensitivity (SI) and glucose effectiveness (SG) were determined. RESULTS Hyperthyroid women had mean KG, glucose-induced insulin secretion and SG values similar to those in control women. The mean glucose AUC was higher in hyperthyroid patients (P<0.05). Lower insulin sensitivity was observed in hyperthyroid patients than in control women (SI=0.38±0.07 vs 0.59±0.07 l/min pmol 10⁴ (mean±SEM), P<0.05). A steeper decline in insulin sensitivity with increase in body mass index was found in hyperthyroid women when compared with the control group, after adjusting for age. When groups were compared according to their BMI, hyperthyroid women with normal weight (BMI≤25 kg/m², n=8) had mean KG, insulin response to glucose, glucose AUC, SG and SI values similar to those in normal weight control women (n=11). Overweight hyperthyroid patients (BMI>25 kg/m², n=6) had a higher (P<0.05) second-phase insulin response to glucose than normal weight patients, a higher glucose AUC (P<0.05) than normal weight patients and overweight controls (n=8), and a lower SI (P<0.05) than normal weight patients and overweight controls. SG was not influenced by BMI in hyperthyroid patients. CONCLUSIONS These results suggest that overall glucose tolerance was not significantly affected in normal weight hyperthyroid women. However, when a moderate excess of weight is also present, a state of clear insulin resistance occurs.     

Minimal model-derived insulin sensitivity, insulin secretion and glucose tolerance: relationships with blood rheology

Insulin resistance is associated with a mild hyperviscosity syndrome, which is more closely related to insulin resistance than to the clinical scoring of the metabolic syndrome. In studies using the intravenous glucose tolerance test with minimal model analysis we reported that low insulin sensitivity (SI) is associated with increased erythrocyte aggregability (EA). Actually, this issue is confusing because insulin resistance is often associated with compensatory hyperinsulinemia (insulin being a hormone with reported hemorheologic effects) and that a decline in insulin secretion has marked metabolic effects that modify blood rheology. From the intravenous glucose tolerance test (IVGTT) the minimal model allows the calculation of SI, insulin response, and an overall glucose tolerance parameter termed "disposition index" (DI) that measures whether insulin response is adequate or not for the level of insulin sensitivity. In this study we assessed SI, insulin response, and DI during an IVGTT in 335 subjects of both genders (age 8-77 yr; BMI 14-67 kg/m2). SI was only correlated (negatively) with EA (Myrenne M r = -0.285; p = 0.0001; M1 r = -0.240 p = 0.003). Fasting insulin was also correlated (positively) with EA (Myrenne M r = 0.233, 0.00880; M1 r = 0.320 p = 0.0003; SEFAM TA r = -0.342 p = 0.04; SEFAM S60 r = 0.419 p = 0.01) and SEFAM RBC disaggregation thresholds (γS = r = 0.372 p = 0.025; γD = r = 0.504 p = 0.002). Fasting DI (SI × fasting insulin) is negatively correlated to M (r = -0.274; p = 0.002) and M1 (r = -0.225; p = 0.01) but also positively to whole blood viscosity (r = 0.168; p = 0.01) and hematocrit (r = 0.142; p = 0.05). Stimulatory DI (SI × insulin peak) fails to be correlated with any parameter of EA but is negatively correlated to whole blood viscosity (r = -0.150; p = 0.02) and plasma viscosity (r = -0.163; p = 0.01). This study confirms that red cell aggregability is associated with insulin resistance and hyperinsulinemia, but plasma viscosity seems to be more related to overall glucose tolerance than to either SI or insulinemia.     

Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women.

OBJECTIVE: The major aim was to study the relation between habitual dietary intake and glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women. Dietary intake was also compared between women with normal (NGT) or impaired glucose tolerance (IGT). DESIGN: Habitual dietary intake was studied using a modified diet history method, from which the energy, carbohydrate, fat and protein intake was calculated. Glucose tolerance was determined as the 2 h glucose value after a 75 g oral glucose tolerance test. Insulin sensitivity was studied with a euglycemic, hyperinsulinaemic clamp, whilst insulin secretion was measured as the acute (2-5 min) response to iv arginine (5 g) at fasting, 14 and >25 mmol L(-1) glucose. SETTING: Clinical research unit at the University Hospital in Malmo, Sweden. Subjects. A total of 74 women (mean+/-SD age 58.7+/-0.4 years). RESULTS: In the entire group, the 2 h glucose level correlated with polyunsaturated fat intake (PUFA, r = 0.41, P < 0.001), and negatively with carbohydrate intake (r = -0.23, P = 0.05). The relation between 2 h glucose and PUFA was independent of body fat content and insulin sensitivity in a multivariate model. Insulin sensitivity correlated with energy intake (r = 0.31, P = 0.007) and PUFA (r = -0.27. P = 0.022). However, these correlations were not significant after adjustment for body fat content in a multivariate model. There were no correlations between insulin secretory variables and habitual dietary intake. Of the 74 women, 60 had NGT and 14 had IGT. The NGT and IGT groups did not differ in intakes of total energy, carbohydrate or protein. The IGT women had higher intake of PUFA (P = 0.003), whilst the total, saturated and monounsaturated fat intake did not differ between the groups. CONCLUSION: Dietary parameters are not independently associated with insulin sensitivity or insulin secretion in postmenopausal women. Furthermore, dietary habits are largely similar in women with NGT and IGT, although subtle differences cannot be excluded due to the small study size. Therefore, habitual intake of total carbohydrate or total fat seems not to be the major determinant of glucose tolerance in nondiabetic Caucasian postmenopausal women.     

Insulin sensitivity, insulin secretion, and glucose tolerance versus intima-media thickness in nondiabetic postmenopausal women

To study the association between insulin sensitivity and secretion vs. early manifestations of atherosclerosis, we performed a 5-yr prospective study in 84 nondiabetic, postmenopausal women, aged 58.7 +/- 0.4 yr (mean +/- SD). Insulin sensitivity was measured with the euglycemic, hyperinsulinemic clamp, and insulin secretion was measured as the acute response to iv arginine (5 g). Early atherosclerosis was studied by ultrasonography of the right carotid artery. Mean intima-media thickness (IMT), determined 1 cm proximal to the bifurcation, was 0.81 +/- 0.14 mm at baseline and increased by 0.012 +/- 0.014 mm/yr over the 5 yr (P < 0.001). The maximal IMT, determined in the carotid bifurcation, was 1.42 +/- 0.42 mm at baseline and increased by 0.035 +/- 0.049 mm/yr (P < 0.001). Neither basal IMT nor the increase in mean or maximal IMT correlated to insulin sensitivity or secretion. In contrast, both baseline IMT and the progression in IMT over the 5-yr follow-up (both mean common carotid artery IMT and maximal bifurcation IMT) correlated with systolic blood pressure and low-density lipoprotein cholesterol. We conclude that carotid intima-media thickness is not related to insulin sensitivity or secretion in nondiabetic, postmenopausal women. Instead, the strongest association is seen with systolic blood pressure and low-density lipoprotein cholesterol levels.     

Relationship between oral glucose tolerance and insulin sensitivity in healthy man and type 1 diabetic patients

The relationship between insulin sensitivity and oral glucose tolerance was studied in 8 conventionally treated type 1 diabetic patients (age 34 +/- 4 years, relative body weight (RBW) 113 +/- 5%) and in 11 healthy subjects (age 35 +/- 3 years, RBW 114 +/- 2%). In each subject and patient, oral glucose tolerance (75 g glucose) and in vivo sensitivity to insulin (euglycaemic clamp technique, 1 mU/kg/min insulin) were measured. The response to oral glucose in the diabetic patients was measured during maintenance of similar peripheral plasma free insulin levels as in the normal subjects during the oral glucose tolerance test (OGTT). During the OGTT, the post-glucose plasma glucose values in the diabetic patients were markedly higher (P less than 0.001) than in the normal subjects. During the clamp study, the rate of glucose metabolism in the diabetic patients (4.53 +/- 0.58 mg/kg/min) was 37% lower than in the normal subjects (7.19 +/- 0.67 mg/kg/min, P less than 0.02). The area under the glucose curve was inversely related to the rate of glucose metabolism in both the diabetic (r = -0.72, P less than 0.02) and the normal (r = -0.69, P less than 0.02) subjects. The slope of the curve was substantially steeper in the diabetic than the control subjects. Thus, peripheral insulin sensitivity contributes to oral glucose tolerance both in healthy man, and even to a greater extent, in type 1 diabetic patients.     

Pathogenetic relationship between insulin resistance, insulin secretion and impaired glucose tolerance in patients with obesity

The distribution of obese patients without diabetes based on the results of the oral glucose tolerance test (OGTT) made it possible to define 2 groups of patients: with normal (the 1st group) and disturbed (the 2nd group) OGTT. A moderate increase in the levels of insulin and C-peptide after GTT and almost unchanged sensitivity to insulin were observed in the 1st group. A considerable increase in the levels of insulin and C-peptide after glucose intake and a considerable decrease in the sensitivity to insulin were observed in the 2nd group. In obese patients with diabetes mellitus the levels of insulin and C-peptide after the GTT were significantly lower than those in the 1st and 2nd groups. A conclusion has been made that whereas certain stages of pathogenesis of diabetes mellitus in obesity are associated with hyperinsulinemia and GTT disorder, obvious diabetes mellitus is characterized by a decrease in secretory potentialities of the insular apparatus in parallel with glucose intolerance.     

Associations between glucose tolerance,insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study

Aims Studies suggest that adiponectin (APM1) and its receptors 1 and 2 (AdipoR1 and AdipoR2) play an important role in the development of insulin resistance (IR). Our objective was to examine associations between APM1 (+45T>G, +276G>T and –3971A>G), AdipoR1 (−100G>T and −3882T>C) and AdipoR2 (−35361A>G and –1352G>A) genes single-nucleotide polymorphisms (SNPs) and adiponectin plasma levels, indicators of glucose tolerance, insulin sensitivity (IS) and insulin secretion. Methods Six hundred and twenty-two non-diabetic subjects from the Quebec Family Study (QFS) underwent a 75-g oral glucose tolerance test (OGTT), with measurement of fasting adiponectin, glucose, insulin and C-peptide levels. Indices of glucose tolerance, IS and insulin secretion were derived from fasting and OGTT measurements. Results Significant evidence of association was found between indices of IS and APM1 and AdipoR1 SNPs. The APM1 –3971G/G homozygotes exhibited a reduced area under the curve of insulin during the OGTT (P = 0.007) and higher Cederholm index (P = 0.01) compared to the A/A homozygotes. The APM1+45T>G variant was also associated with fasting (P = 0.002) and 2-h (P = 0.007) glucose values as well as with higher Cederholm index (P = 0.04) and disposition index (P = 0.02). Finally, the AdipoR1−3882T>C SNP was associated with fasting glucose (P = 0.03), the homeostasis model assessment for insulin resistance (P = 0.04) and an index of insulin secretion (P30/G30, P = 0.02). No evidence of association was found with plasma adiponectin levels. Conclusions These results provide evidence for an influence of common SNPs in the APM1 and AdipoR1 genes on different phenotypes of glucose and insulin metabolism associated with increased risk of type 2 diabetes.     

肥胖和非肥胖糖耐量受损患者胰岛素敏感性和1相胰岛素分泌研究

目的研究肥胖和非肥胖糖耐量受损(IGT)患者的胰岛素敏感性和β细胞1相胰岛素分泌功能,以探讨在IGT患者中肥胖对胰岛素抵抗和1相胰岛素分泌的影响。方法共有99位受试者(包括正常对照者32名,肥胖IGT44例,非肥胖IGT23例)接受了口服75 g葡萄糖耐量试验(OGTT)和胰岛素改良的减少样本数(采血样12次)的Bergman微小模型技术结合静脉葡萄糖耐量试验(FSIGTT)。胰岛素抵抗由FSIGTT中胰岛素敏感性指数(SI)加以评估,而OGTT中糖负荷后30 min胰岛素增值与血糖增值之比值[ΔI30/ΔG30=(I30 min-I0 min) /(G30 min-G0 min)]和FSIGTT中急性胰岛素分泌反应(AIRg)则用以评价胰岛β细胞分泌功能。处理指数(DI =AIRg×SI)用于评价AIRg是否代偿机体的胰岛素抵抗。结果与正常对照组[(7.52±10.89)×10-4]相比,二组IGT患者之SI明显降低,而肥胖IGT组的SI[(1.72±1.11)×10-4]较非肥胖组[(3.15±1.49)×10-4]更低(均P<0.01); AIRg和ΔI30/ΔG30在正常组(412±191,14.45±8.47)和肥胖IGT组(378±235,17.02±11.30)之间差异无统计学意义,但均大于非肥胖组(196±160,8.93±6.69,均P<0.01);与正常组(2 851±1 180)相比,DI指数在二组IGT显著降低(595±485,584±517),但后二组间此值差异无统计学意义。SI与2 h胰岛素、体重指数、尿酸和胆固醇呈显著的负相关性(校正r2=0.603,P<0.01);而AIRg与ΔI30/ΔG30显著正相关,与空腹血糖负相关(校正r2=0.479,P<0.01)。结论IGT患者存在胰岛素抵抗和β细胞功能异常。与非肥胖IGT患者相比,肥胖IGT患者胰岛素抵抗程度更为严重,但胰岛β细胞胰岛素1相分泌相对充分。     

On the interplay beween insulin secretion and sensitivity as determinants of glucose tolerance

Both insulin secretion and sensitivity have been claimed to be the main characteristics in the determination of future detoriation in glucose tolerance. In this cross-sectional study insulin secretion and insulin sensiturity were determined in 228 subjects with varying degrees of glucose tolerance. Insulin secretion was measured in an intravenous glucose tolerance test (IVGTT) and insulin sensitivity by the hyperinsulinaemic euglycaemic clamp test. Both the early insulin response in the IVGTT (increment) and the glucose disposal rate in the clamp test (M-value) were found to be related hyperbolically to fasting glucose (r=–0.63 and –0.66, respectively; bothP<0.0001) and in a second-order polynomial manner to the glucose disappearence rate (k-value) in the IVGTT (r=0.53 and 0.48, respectively; bothP<0.0001). Multiple regression analysis showed the insulin increment in the IVGTT and theM-value in the clamp test to be equally important determinants of glucose tolerance, together explaining about 50% of the variation in fasting glucose and thek-value in the IVGTT. In conclusion, in this cross-sectional study insulin secretion and sensitivity studied over a broad range of glucose tolerance were found to be of amost equal importance in the determination of glucose tolerance. However, low levels of insulin increment in the IVGTT were more often associated with glucose intolerance than was a low insulin sensitivity.     

Reduced insulin secretion by subtotal pancreatectomy: preservation of insulin sensitivity and glucose tolerance in postoperative patients

This study investigated insulin sensitivity and glucose tolerance after subtotal pancreatectomy for carcinoma of the head of the pancreas. Twelve consecutive, non-diabetic patients were studied after potentially curative surgery at which the distal pancreas was stapled off, leaving approximately 15% of the pancreas in situ. Brief infusions of insulin (10 mU kg-1) and glucose (25 g) were given before and 4 days after operation. Postoperatively, blood glucose levels remained unchanged, whereas fasting levels of insulin. C-peptide, and pancreatic glucagon were decreased, although significantly (p less than 0.01) only for glucagon. The early and late phases of the insulin and C-peptide responses to glucose were severely reduced. Notably, the hypoglycemic action of insulin and the glucose tolerance were similar to those observed before operation. It is concluded that an acute reduction in pancreatic mass does not impair insulin action or glucose tolerance shortly after surgery. This contrasts with the insulin resistance and glucose intolerance seen shortly after pancreas-preserving intra-abdominal procedures of similar size. It is suggested that the decrease in glucagon levels is at least partly responsible for the preservation of insulin action after subtotal pancreatectomy.     

Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance

OBJECTIVE: This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT). METHODS: Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment. RESULTS: After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05). CONCLUSION: Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.     

Oral glucose tolerance test and insulin sensitivity in low insulin responders

Oral and iv glucose tolerance, insulin response to iv and oral glucose load as well as insulin sensitivity were evaluated in 58 'low insulin responders'. They were selected from a group of 226 healthy subjects with normal fasting blood glucose and normal iv glucose tolerance test on the basis of a low insulin response during a standardized glucose infusion test (GIT). The insulin response to GIT was analysed by parameter identification in a mathematical model (parameter KI). Insulin sensitivity was also measured by computer analysis of GIT (parameter KG) and, in a limited group of subjects, by a somatostatin infusion test. Thirty-three low insulin responders had normal OGTT, whereas 5 demonstrated borderline-1, 16 borderline-2, and 4 decreased OGTT. The first group of subjects demonstrated normal or enhanced insulin sensitivity. Borderline and decreased OGTT, in most instances, was accompanied by decreased insulin sensitivity, implying that a subgroup of low insulin responders exhibited signs of both impaired insulin response to glucose and insulin resistance. Since these defects characterize manifest type-2 diabetes, these subjects possibly may run a high risk to develop this type of diabetes. On the other hand, low insulin response in combination with increased insulin sensitivity may reflect adaptation of the secretory capacity of B-cells to the need of insulin.     

Failure to adequately adapt reduced insulin sensitivity with increased insulin secretion in women with impaired glucose tolerance

Summary To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined with arginine stimulation at three glucose levels (fasting, 14 and >25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g i. v. arginine at all three glucose levels and the slope_AIR, i. e. the glucose potentiation of insulin secretion, were markedly increased in the women with the lowest insulin sensitivity and NGT compared to those with medium or high insulin sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower in IGT than in NGT (at glucose 14 mmol/l p=0.015, and at >25 mmol/l p=0.048). The potentiation of AIR induced by low insulin sensitivity in women with NGT was reduced by 74% (AIR at 14 mmol/l glucose) and 57% (AIR at >25 mmol/l glucose), respectively, in women with IGT. Also the slope_AIR was lower in IGT than in NGT (p=0.025); the increase in slope_AIR due to low insulin sensitivity was abolished in IGT. In contrast, glucagon secretion was not different between women with IGT as opposed to NGT. We conclude that as long as there is an adequate beta-cell adaptation to low insulin sensitivity with increased insulin secretory capacity and glucose potentiation of insulin secretion, NGT persists.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - AIR acute insulin response - AGR acute glucagon response     

Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests.

Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to the relative acute insulin response in subjects with fasting glucose below 115 mg/dl and to total insulin response when fasting glucose levels were above 115 mg/dl. A calculated glucose disappearance rate of 1.06 per cent per minute was found when the acute isulin response was zero. All subjects with fasting glucose levels greater than 115 mg/dl had glucose disappearance rates greater than 1.06. These studies support 1) epidemiological data indicating 115 mg/dl as an upper limit of normal for fasting plasma glucose levels and 1.0 per cent per minute as a lower limit of normal for the glucose disappearance rate, and 2) evidence for an important role for the acute insulin response in the determination of glucose disappearance rates during intravenous glucose tolerance tests.