Assessing 1-h plasma glucose and shape of the glucose curve during oral glucose tolerance test

OBJECTIVE: To assess the cutoff values at different time points for impaired glucose regulation (IGR) and diabetes, the glucose curve and isolated 1-h hyperglycemia were monitored during an oral glucose tolerance test (OGTT). METHODS: Two thousand eight hundred and eighty-six subjects (1300 men and 1586 women) were recruited to have an OGTT. Plasma was collected at 0, 30, 60, 120, and 180 min to analyze glucose and insulin. The diagnosis of impaired fasting glucose, impaired glucose tolerance, and diabetes was based on World Health Organization and American Diabetes Association's criteria. Those with fasting plasma glucose (FPG) < 5.6 and 2-h plasma glucose (PG) < 7.8, but 1-h PG > or = 7.8 and < 11.1 mmol/l were defined as 1h-High7.8, and those with FPG < 7.0 and 2-h PG < 11.1, but 1-h PG > or =11.1 mmol/l as 1h-High11.1. The cutoff values were calculated by receiver operating characteristic (ROC) curve. The correlation between beta-cell function and the area under the curve of glucose (AUCg) and the shape index was analyzed with linear regression. RESULTS: The cutoff values for IGR were 5.6, 9.7, 10.1, 7.8 and 6.1 mmol/l for blood glucose at 0, 30, 60, 120 and 180 min, 24 for AUCg and 1.3 mmol/l for the shape index. The cutoff values for diabetes were 6.8, 11.2, 13, 11.1 and 7 mmol/l for 0, 30, 60, 120 and 180 min, 30.9 for AUCg and 2 mmol/l for the shape index. Both AUCg and the shape index were inversely related to beta-cell function. The profiles of glucose and insulin in the subgroup with isolated 1-h hyperglycemia were very different from those seen in subjects with normal glucose tolerance or IGR. CONCLUSIONS: The present study provides new information on measures other than the fasting and 2-h PG to evaluate glucose metabolism in vivo and stimulates further research aimed at assessing the value of the OGTT 1-h PG concentration prospectively.     

Interstitial glucose in skeletal muscle of diabetic patients during an oral glucose tolerance test.

AIM: The presence of a transcapillary arterial-interstitial gradient for glucose (AIG(glu)) in skeletal muscle may be interpreted as a consequence of intact cellular glucose uptake. We hypothesized that the AIG(glu) decreases in Type 2 diabetes mellitus as a consequence of insulin resistance, whereas it remains intact in Type 1 diabetes. METHODS: Glucose concentrations were measured in serum and interstitial space fluid of skeletal muscle during an oral glucose tolerance test (OGTT) in patients with Type 1 and Type 2 diabetes and in young and middle-aged healthy volunteers, using microdialysis. RESULTS: The area under the curve for glucose in serum (AUC(SE)) was higher than in interstitial space fluid of skeletal muscle (AUC(MU)) in healthy young (AUC(SE) = 1147 +/- 332 vs. AUC(MU) = 633 +/- 257 mM/min/ml; P = 0.006), healthy middle-aged volunteers (AUC(SE) = 1406 +/- 186 vs. AUC(MU) = 1048 +/- 229 mM/min/ml; P = 0.001) and in Type 1 diabetic patients (AUC(SE) = 2273 +/- 486 vs. AUC(MU) = 1655 +/- 178 mM/min/ml; P = 0.003). In contrast, in Type 2 diabetic patients AUC(SE) (2908 +/- 1023 mM/min/ml) was not significantly different from AUC(MU) (2610 +/- 722 mM/min/ml; P = NS). CONCLUSION: The present data indicate that AIG(glu) is compromised in Type 2 diabetes in contrast to Type 1 diabetes where it appears to be normal. Because no changes in muscle blood flow were detected, insulin resistance appears to be the main cause for the observed decreased AIG(glu) in skeletal muscle in Type 2 diabetic patients.     

Paradoxical release of growth hormone during oral glucose tolerance test in patients with abnormal glucose tolerance

Oral glucose tolerance tests were performed on 24 patients characterized as having abnormal glucose tolerance (AGT) and on 27 control subjects. Serums for glucose, growth hormone and insulin determinations were serially obtained for 4 hr after glucose administration. As serum glucose declined 2 hr or more after glucose ingestion a rise in growth hormone, as has been previously described, was observed in 40% of control subjects and 12% of AGT patients. However, of interest was a paradoxical early increase in growth hormone levels noted in 44% of lean AGT subjects occurring during the first 2 hr of the test with glucose levels rising. This response was seen in only one of 8 obese patients with AGT and in none of the control subjects. An abnormality in the hypothalamic glucose receptors in the ventromedial nucleus is a possible explanation for the changes observed. It is possible that this early inappropriate increase in growth hormone release may in some nonobese subjects with AGT contribute to the abnormal oral glucose tolerance tests observed.     

The ROC analysis for different time points during oral glucose tolerance test

This purpose was to discuss optimal reference value for normal glucose tolerance (NGT) at different time points during an oral glucose tolerance test (OGTT) by receiver operating characteristic (ROC) analysis. One thousand seven hundred and forty-six subjects from March 2004 to March 2005 were given 75 g OGTT and the blood samples were collected at 0, 30, 60, 120 and 180 min for glucose measurement. Other demographic data (e.g. age, sex, body mass index, BMI) were also recorded. The status of NGT, impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and DM was determined according to American Diabetes Association (ADA) criteria. IGT and IFG were merged as impaired glucose regulation (IGR). Using IGR as the assumed test, the cutoff values at 0, 30, 60, 120 and 180 min during OGTT for normal reference range were calculated by ROC analysis. The cutoff values were 5.6, 9.5, 10.1, 7.8 and 6.1 mmol/l at 0, 30, 60, 120 and 180 min, respectively, in whole subjects. In addition, we provided the ROC information in age-stratified groups since there are differences among different age groups. When the results of OGTT were considered, the present study provided a reference range value to evaluate the status of glucose tolerance. Because of the heterogeneity of diabetes, further studies are necessity. And the sample collection is continuing.     

The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes

Aims/hypothesis

We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion.

Methods

Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627). A monophasic curve was defined as an increase in OGTT glucose between 30 and 90 min followed by a decline of ≥ 0.25 mmol/l between 90 and 120 min. A biphasic response curve was defined as a decrease in glucose after an initial increase, followed by a second increase of ≥ 0.25 mmol/l. Associations of type 1 diabetes risk with glucose curve shapes were examined using cumulative incidence curve comparisons and proportional hazards regression. C-peptide responses were compared with and without adjustments for potential confounders.

Results

The majority of participants had a monophasic curve at baseline (n = 1732 [66%] vs n = 895 [34%]). The biphasic group had a lower cumulative incidence of type 1 diabetes (p < 0.001), which persisted after adjustments for age, sex, BMI z score and number of autoantibodies (p < 0.001). Among the monophasic group, the risk of type 1 diabetes was greater for those with a glucose peak at 90 min than for those with a peak at 30 min; the difference persisted after adjustments (p < 0.001). Compared with the biphasic group, the monophasic group had a lower early C-peptide (30–0 min) response, a lower C-peptide index (30–0 min C-peptide/30–0 min glucose), as well as a greater 2 h C-peptide level (p < 0.001 for all).

Conclusions/interpretation

Those with biphasic glucose curves have a lower risk of progression to type 1 diabetes than those with monophasic curves, and the risk among the monophasic group is increased when the glucose peak occurs at 90 min than at 30 min. Differences in glucose curve shapes between the monophasic and biphasic groups appear to be related to C-peptide responses.

     

Correlation between fasting plasma glucose and two-hour plasma glucose during oral glucose tolerance test in South Indians

The diagnostic criteria for diabetes have been recently revised and the fasting plasma glucose (FPG) level reduced to 126 mg/dL, since the earlier cutoff of 140 mg/dL was considered to correspond to a much higher level than the 2-hour postglucose (2 h PG) value of 200 mg/dL. However, there are few data directly correlating FPG and 2 h PG during an oral glucose tolerance test (OGTT). This study reports on a retrospective analysis of 5,936 OGTTs performed at a diabetes center in South India and attempts to correlate the FPG and 2 h PG values. Using a 2 h PG of 200 mg/dL or higher as the diagnostic criterion, 46.7% of the cohort had diabetes. The corresponding values using the old FPG of 140 mg/dL or higher and the new FPG of 126 mg/dL or higher were 31.7% and 39.8%, respectively. If the FPG was further reduced to 118 mg/dL, the "diabetic yield" increased to 45.8%, ie, it approached the figures based on a 2 h PG of > or =200 mg/dL. Various regression equations were used to correlate FPG and 2 h PG values. When FPG was used as the dependent variable, the semilogarithmic regression equation provided the best fit, and using this model, the 2 h PG of 200 mg/dL corresponds to a FPG of 118 mg/dL. When the 2 h PG was used as the dependent variable, the log-log model provided the best fit, and using this model, a 2 h PG of 200 mg/dL corresponds to a FPG of 118 mg/dL. Thus, a FPG of 118 mg/dL seems to correlate with a 2 h PG of 200 mg/dL in South Indians.     

The oral glucose tolerance test (OGTT) revisited

The oral glucose tolerance test (OGTT) has been the mainstay for diagnosing diabetes for decades. Recently, the American Diabetes Association (ADA) suggested abandoning the OGTT, while resorting to a simpler screening test, exclusively based on baseline fasting blood glucose concentration.This review article rewinds the history of OGTT and its recent advancements, and compares its power in detecting early diabetes with that of fasting blood glucose alone.The key point is that there are more diabetics originating from a population with normal fasting blood glucose than from subjects with impaired fasting glucose, those who can be detected by the new ADA recommendations. Conversely, the OGTT detects more efficiently early diabetes as well as subjects with IGT, as the glycemia at the second hour seems crucial as a diagnostic tool. We discuss the different significance of fasting versus second hour glycemia during OGTT, according to different mechanisms of glucose homeostasis.Finally, we provide recent evidence on very simple additional information that can be obtained from the OGTT, which renders this test even more useful, discussing pathophysiologic significance.     

Cortisol levels during an oral glucose tolerance test in lean and obese women

Because of the similarities between Cushing's syndrome and insulin resistance syndrome,cortisol metabolism in obesity has been investigated in numerous studies. Our study investigates serum glucose, insulin, and cortisol response to oral glucose stimulation in a group of obese and lean normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese [body mass index (BMI) 37Z +/- 6.3 kg/m2) and 14 lean (BMI: 21.5 +/- 1.0 kg/m2) age-matched healthy premenopausal women were included in the study. Serum glucose, insulin, and cortisol levels were measured at 30-minute intervals during 120 minutes of oral glucose tolerance testing (OGTT). Mean serum glucose and insulin levels were significantly higher in the obese group compared with lean subjects, and cortisol levels were similar during OGTT. There was not a significant difference for cortisol area under the curve (AUC) during OGTT between the two groups. No correlation between cortisol AUC, insulin AUC, and glucose AUC was noted for both groups. During OGTT, a decrease in cortisol levels was observed in both groups. The decrement occurred at 30 minutes of the OGTT in the obese group and at 60 minutes of the OGTT in the lean group. At 90 and 120 minutes of the OGTT, serum cortisol levels were similar to basal levels in both the obese group and the lean group. Previous studies reported altered hypotalamic-pituitary-adrenal axis activity, altered levels of urinary cortisol excretion, and increased metabolic clearance of cortisol in obesity. In our study in obese women, the only detected difference from lean subjects was a quicker suppression and recovery in serum cortisol levels after glucose administration.     

Thyrotropin secretion during oral glucose tolerance test in acromegalic patients and control subjects

It has been suggested that acute hyperglycemia stimulates somatostatin release from the hypothalamus, thus causing inhibition of growth hormone and thyrotropin secretion. Abnormal growth hormone secretory pattern to glucose load is characteristic of acromegaly, and it might reflect alterations in somatostatin release. We evaluated the sensitivity of serum thyrotropin response to presumed somatostatin inhibition during oral glucose tolerance test in 29 patients with active acromegaly, in 13 patients with inactive disease, and in 19 control persons suspected of impaired glucose tolerance. Both the acromegalic patients and the control subjects were euthyroid. Serum insulin, growth hormone, thyrotropin, free triiodthyronine, free thyroxine, and glucose were collected before and 30, 60, 90, and 120 min after the ingestion of 75 g glucose. While the free triiodthyronine and free thyroxine values did not change during the glucose test, the thyrotropin levels progressively and significantly declined in all groups. The basal to nadir thyrotropin ratio was higher in active acromegaly than in inactive disease and in control subjects (p<0.01), suggesting that the glucose load inhibited thyrotropin stronger in active acromegalic patients. These data suggest that there is a possible strong somatostatin response to glucose load in acromegalic patients, which inhibits thyrotropin secretion. These data do not support the concept of decreased somatostatin drive in acromegaly.     

Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test

Aims/hypothesis. We aimed to find if the relation between insulin sensitivity and beta-cell function assessed from fasting and OGTT measurements has a physiological shape (hyperbolic with the reference methods). Methods. Healthy women without diabetic first-degree relatives underwent a 75 g OGTT with plasma glucose and insulin (n = 35) concentrations being measured at 0, 30, 60 and 120 min. Beta-cell function and insulin sensitivity were estimated using previously described indices from fasting (1 for beta-cell function, 6 for insulin sensitivity) and OGTT measurements (3 for beta-cell function and 5 for insulin sensitivity). A hyperbolic relation was tested for the 21 beta-cell function-insulin sensitivity pairs using a non-lineal regression method. Results. The assessment of beta-cell function from OGTT was impossible in seven women and one had outlier indices. For the remaining 27 women, only 8 combinations adjusted to a hyperbolic relation. The best adjustment was achieved using the fasting glucose to insulin ratio as the estimation of insulin sensitivity and the homeostasis model assessment (HOMA) index (single fasting sample) as the estimation of beta-cell function (r ² 0.802, k 869.71, p < 0.001). Conclusion/interpretation. In this group of healthy women, the estimation of insulin sensitivity and beta-cell function by most methods using OGTT-derived glucose and insulin measurements did not adjust to a hyperbolic relation but all fasting indices combinations did. Beta-cell function estimated with the HOMA index and insulin sensitivity with fasting glucose to insulin ratio had the best adjustment. [Diabetologia (2000) 43: 1507–1511] Received: 29 June 2000 and in revised form: 16 August 2000     

Impaired glucose tolerance with late hypersecretion of insulin during oral glucose tolerance test in patients with vasospastic angina

Objectives.This study tested whether patients with vasospastic angina have impaired glucose tolerance or impaired insulin response.Background.Hyperinsulinemia has been demonstrated in patients with coronary artery disease and syndrome X.Methods.We performed an oral glucose tolerance test (75 g) in 30 patients with vasospastic angina in whom severe coronary vasospasm was induced by acetylcholine and in a matched group of 30 patients with atypical chest pain in whom no significant vasospasm was induced. The responses of insulin and glucose were compared between the two groups. No subjects had overt diabetes mellitus, hypertension, dyslipidemia, obesity or angiographically detected significant baseline coronary stenosis. Venous blood samples were taken during fasting and at 30, 60, 120 and 180 min after glucose load to obtain plasma glucose and immunoreactive insulin levels.Results.Impaired glucose tolerance was detected in the 19 (63%) of 30 patients with vasospastic angina and in none of 30 patients with atypical chest pain (p < 0.001). The immunoreactive insulin levels at 60 and 120 mins as well as the interval to peak insulin level were significantly greater in patients with vasospastic angina (p < 0.001). Among patients with vasospastic angina, those with acetylcholine-induced multivessel coronary vasospasm showed a significantly higher sum of insulin concentrations than those with single-vessel spasm (p < 0.01). During induction of coronary spasm, 10 patients with vasospastic angina presented ventricular arrhythmias. The sum of insulin concentrations was significantly greater in patients with than in those without ventricular arrhythmias.Conclusions.Patients with vasospastic angina exhibited a high incidence of impaired glucose tolerance and delayed and significantly higher insulin responses. These findings suggest that impaired glucose tolerance with late hypersecretion of insulin may contribute to the pathogenesis of severe coronary vasospasm.