Plasma Insulin and Glucose Responses of Healthy Subjects to Varying Glucose Loads During Three-hour Oral Glucose Tolerance Tests
TL;DR: The fact that incremental changes in glucose load particularly influenced plasma glucose and insulin concentrations relatively late in the glucose tolerance tests, and that mean insulin peakconcentrations did not differ, indicates that increasing glucose load results in a more prolonged insulinogenic stimulus rather than the acute release of greater quantities of insulin relatively abruptly.
Abstract: The plasma glucose and plasma immunoreactive insulin concentrations of twelve healthy, nonobese, adult subjects were compared following administration of oral glucose loads of 50, 75 and 100 gm., and 1.75 gm./kg. body weight. The time of occurrence and the magnitude of maximal plasma glucose and insulin concentrations were unaffected by the 25 gm. increases in glucose load. The 50 gm. glucose load gave the smallest plasma glucose response during the three-hour tests and this response was statistically distinguishable from the plasma glucose responses due to the 100 gm. and 1.75 gm./kg. loads (p < 0.05). The plasma glucose responses due to the other loads did not differ from each other. Insulin responses, estimated by either summing allthe plasma insulin values or by measuring the areas under the curves, increased approximately 35 per cent with the first 25 gm. glucose load increment (50 to 75 gm.) and 27 per cent with the second 25 gm. load increment (75 to 100 gm.) during the three-hour study. The differences in insulinresponses between the 50 gm. load and the 100 gm. or 1.75 gm./kg. loads were highly significant (p < 0.01) while the difference between the insulin responses following the 75 gm. and 1.75 gm./kg. loads had lower significance (p < 0.05). Differences in insulin responses of the other loads were not significant. Increases in glucose loads above 120 gm. did not further increase the insulin response. This provides evidence that maximal insulin responses provoked by an oral glycemic stimulus alone in subjects are achieved with 100 gm. A wide range was observed in the plasma insulin concentrations among these healthy individuals for any given load, at any one time, and was probably due to biological variation.
The fact that incremental changes in glucose load particularly influenced plasma glucose and insulin concentrations relatively late in the glucose tolerance tests, and that mean insulin peakconcentrations did not differ, indicates that increasing glucose load results in a more prolongedinsulinogenic stimulus rather than the acute release of greater quantities of insulin relatively abruptly. These studies provide evidence that the response associated with increasing glucose load is to some extent a function of the quantity of glucose ingested, and that the significant increases in insulin response commonly occur in association with concurrent alterations in plasma glucose concentrations. The results also indicate that the 50 gm. glucose load results in a different plasma glucose response than does the 100 gm. and 1.75 gm./kg. loads and consequently requires different criteria for interpretation of glucose tolerance testing.
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TL;DR: A discrepancy between the estimates of the incretin effect derived from peripheral venous insulin responses, and C-peptide responses or calculated insulin secretion rates, exists, which suggests that elimination kinetics of insulin differ between oral and iv glucose administration.
Abstract: Integrated insulin secretion rates calculated from peripheral venous C-peptide measurements by two-compartment kinetic analysis were measured in six young normal subjects after increasing oral glucose loads of 25, 50, and 100 g and respective isoglycemic glucose infusions. The differences in B-cell secretory responses between oral and iv glucose challenges were attributed to factors other than glycemia itself (incretin effect). Both insulin and C-peptide concentrations as well as calculated integrated insulin secretion rates increased with increasing oral glucose loads. Due to the similarity in the glucose profiles after all oral loads, almost identical amounts of iv glucose (approximately 20 g) were infused in all "isoglycemic" infusion experiments, with resulting similar hormone profiles and insulin secretion rates. The percent contribution of incretin factors to total immunoreactive insulin responses after 25, 50, and 100 g glucose (85.6%, 74.9%, and 93.0%; response to oral load, 100%) was significantly higher than their contribution to integrated C-peptide responses (27.6-62.9%) or calculated integrated insulin secretion rates (19.2-61.0%). These findings indicate that the degree of incretin stimulation of insulin secretion depends on the amount of glucose ingested. A discrepancy between the estimates of the incretin effect derived from peripheral venous insulin responses, on the one hand, and C-peptide responses or calculated insulin secretion rates, on the other hand, exists. Inasmuch as peripheral insulin values reflect both insulin secretion and hepatic insulin removal, this discrepancy suggests that elimination kinetics of insulin differ between oral and iv glucose administration. This difference can be related to a significantly reduced fractional hepatic insulin extraction after oral (46.9-54.6%) compared to iv (63.4-76.5%) glucose administration when calculated by a three-compartment kinetic model. This reduction in fractional hepatic insulin extraction could be caused by gastrointestinal factors (hormones or nerves) stimulated in the course of glucose ingestion.
804 citations
TL;DR: Although the OGTT is the "gold standard" for diagnosing diabetes, it is known to be poorly reproducible and is often not performed, so measurement of HbA 1c levels may represent a reasonable approach to identifying treatment-requiring diabetes.
Abstract: Objective. —To determine whether a glycosylated hemoglobin level can be used in place of an oral glucose tolerance test (OGTT) to diagnose diabetes. Data Sources/Study Selection. —An augmented MEDLINE search was performed to identify all reports from 1966 through June 1994 in which glycosylated hemoglobin levels were measured concurrently with performance of OGTTs in the same study. The corresponding authors were contacted and asked to provide individual data for all subjects tested. A total of 31 investigators representing 34 possible studies responded, and 18 were able to provide us with the data requested. Overall fasting plasma glucose concentrations, 2-hour postdextrose glucose concentrations, and glycosylated hemoglobin levels were available from 11 276 individuals. Data Extraction —To define normal glucose tolerance, impaired glucose tolerance (IGT), and diabetes, modified World Health Organization criteria were used. Data Synthesis. —An analysis of the methods used for measurement of glycosylated hemoglobin levels revealed that the HbA 1c assay showed the least variance in normal subjects. Therefore, only data from the 8984 subjects who had HbA 1c levels measured were used. When we used the mean HbA 1c level plus 4 SDs as a cutpoint, the sensitivity was 36% and specificity was 100% compared with the results of the OGTT. Because of the lack of agreement between OGTT results and HbA 1c levels, models were created to analyze the distribution of HbA 1c levels in each study. Using these models, we identified 3 subpopulations. The third subpopulation was likely to represent subjects with diabetes. When we applied an HbA 1c level of 7.0% as a cutpoint, the sensitivity was 99.6% for the third subpopulation. When this cutpoint was reapplied to the OGTT results, of those subjects with an HbA 1c level of at least 7.0%, 89% had diabetes, 7% had IGT, and 4% were normal. Conclusions. —Although the OGTT is the "gold standard" for diagnosing diabetes, it is known to be poorly reproducible and is often not performed. Not only is use of an HbA 1c level to diagnose diabetes more convenient, but therapeutic decisions are based on this value, regardless of the findings on the OGTT. An HbA 1c level of 7.0% or higher often requires pharmacological intervention and is most often associated with the diagnosis of diabetes by World Health Organization standards. An HbA 1c level below 7.0% would generally be treated with diet and exercise, regardless of the diagnosis of IGT or diabetes by OGTT. Thus, measurement of HbA 1c levels may represent a reasonable approach to identifying treatment-requiring diabetes.
321 citations
TL;DR: Impaired β-cell function and obesity at diagnosis of GDM were associated with the development of diabetes during a 5-yr, follow-up period and studies designed to prevent diabetes in this high-risk group should examine strategies to maintain both optimal β- cell function and maximum insulin sensitivity.
Abstract: OBJECTIVE To identify phenotypic, genotypic, and metabolic parameters measured at the time of antepartum diagnosis of gestational diabetes mellitus that can indicate the risk of diabetes mellitus at early postpartum (≤6 mo after delivery) and at a 5-yr follow-up. RESEARCH DESIGN AND METHODS The recommendations from the National Diabetes Data Group and International Workshop Conferences on Gestational Diabetes Mellitus were used for screening, diagnosing, and subclassifying gestational diabetes mellitus. National Diabetes Data Group criteria were also used for classification of glucose tolerance postpartum. Plasma glucose, insulin, and free fatty acids were measured after an overnight fast. Plasma glucose and insulin were measured 15, 30, 60, 120, and 180 min after the 100-g oral glucose load. Postpartum glucose tolerance was evaluated at 3–6 mo (early), 1 yr, and annually thereafter. RESULTS The 5-yr cumulative incidence of diabetes during follow-up after gestational diabetes mellitus was nearly 50%. Among those who had diabetes within 5 yr, a history of diabetes in only the mother was nearly threefold more common than a history of diabetes in only the father (30 vs. 11%, P CONCLUSIONS Impaired β-cell function and obesity at diagnosis of GDM were associated with the development of diabetes during a 5-yr, follow-up period. Studies designed to prevent diabetes in this high-risk group should examine strategies to maintain both optimal β-cell function and maximum insulin sensitivity.
276 citations
Cites background from "Plasma Insulin and Glucose Response..."
...In normal subjects, peak plasma glucose concentrations and their return toward baseline over 2 h are very similar with 75- and 100-g oral glucose loads (30); whereas, postchallenge insulin secretion increases substantially in proportion to the glucose load....
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TL;DR: Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people.
Abstract: Information on the metabolic response in people with non-insulin-dependent diabetes mellitus (NIDDM) to ingested individual macronutrients is limited. Available information is reviewed herein. The major absorbed products of carbohydrate-containing foods are glucose, fructose, and galactose. The quantitative effect of these on the plasma glucose and insulin response is different for each. In addition, available data indicate that the glucose and particularly the insulin response is different from that in nondiabetic people. The quantitative effect of dietary proteins and fats on the circulating glucose and insulin concentrations in nondiabetic and NIDDM subjects also has been reviewed. Neither has a significant effect on the glucose concentration. Protein stimulates insulin secretion, and this is relatively more prominent in people with NIDDM. A strong synergistic interaction with glucose on insulin secretion is present, but this is absent in nondiabetic people. Ingested fat does not independently stimulate insulin secretion. However, when ingested with carbohydrate, it may have a considerable effect on the plasma glucose and/or insulin response to that carbohydrate, and the responses are different in nondiabetic and NIDDM subjects. This is probably not due to altered carbohydrate absorption. Intestinal hormones undoubtedly are playing a large role in the insulin secretory response in all of these studies, but this remains to be completely elucidated. Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people. In our opinion, much more information is required before dietary recommendations for NIDDM subjects can be made based on solid scientific data.
162 citations
TL;DR: It was confirmed that serum glucose levels are unaffected by the amount of glucose given, and little fructose seems to be converted to glucose judging by the serum fructose levels following sucrose and fructose, and by the small insulin response to oral fructose.
146 citations
References
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TL;DR: A two antibody system of insulin assay for immunoassay of insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.
Abstract: It has been demonstrated that insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.\" Lysis of sensitized red blood cells, paper electrophoresis,\" and salt precipitation have been used in methods of immunoassay of insulin. In a preliminary report the authors described a two antibody system of insulin assay. The present paper describes the method in greater detail and presents results of assays of rat plasma.
2,590 citations
1,295 citations
TL;DR: A new method for evaluating glucose metabolism in man using an oral glucose load and the calculation of a blood glucose disappearance rate constant is described, which makes it possible to compare quantitatively the response to oral and intravenous glucose administration in a given individual.
Abstract: This paper describes a new method for evaluating glucose metabolism in man using an oral glucose load. The procedure permits the calculation of a blood glucose disappearance rate constant (K) and thereby makes it possible to compare quantitatively the response to oral and intravenous glucose administration in a given individual. Ten metabolically normal adult humans were studied under carefully controlled conditions. Each received similar amounts (20 g) of glucose both orally and intravenously (2–7 days apart) by constant infusion for 1 hr. The effects on blood glucose disappearance rate constants (K) and plasma insulin concentrations (immunoassay) during and for 1 hr following the infusion were compared. Blood glucose concentrations and K values with the 2 routes of glucose administration were similar. In contrast, plasma insulin responses showed a significant difference: oral glucose resulted in a significant and sustained rise, whereas intravenous glucose was associated with a smaller and transient inc...
848 citations
659 citations
TL;DR: The dynamics of insulin release in response to relatively long infusions of glucose were studied in the isolated perfused rat pancreas and Histological examination of the perfused pancreases and measurement of oxygen consumption by these tissues indicated that optimal physiological conditions were used.
Abstract: The dynamics of insulin release in response to relatively long infusions of glucose were studied in the isolated perfused rat pancreas. Insulin secretion was determined by immunochemical assay of the total portal vein effluent. Histological examination of the perfused pancreases and measurement of oxygen consumption by these tissues indicated that optimal physiological conditions were used. It was observed that, when glucose was infused for a period of approximately 1 hr into a perfused pancreas, there appeared 2 distinctly different phases of insulin release. There was an early, or rapid, release of insulin which subsided within approximately 2 min, followed by a late, or slow release phase which continually increased in rate until termination of the glucose infusion. The contribution of newly synthesized insulin to either phase was determined by comparing the insulin release by normal control preparations to that by preparations which were treated with puromycin. Incorporation of L-valine-14C was used a...
613 citations