scholarly journals 1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessandra Ghio ◽  
Giuseppe Seghieri ◽  
Cristina Lencioni ◽  
Roberto Anichini ◽  
Alessandra Bertolotto ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Insulin Action ◽  
Progressive Increase ◽  
Plasma Glucose Concentration ◽  
Linear Manner

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL,n=661; 120–139 mg/dL,n=710; 140–159 mg/dL,n=912; 160–179 mg/dL,n=885; and ≥180 mg/dL,n=996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCglucand AUCinsprogressively increased according to 1-hour plasma glucose concentrations (bothP<0.0001for trend). HOMA-B progressively declined (P<0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCglucdecreased in a linear manner across the 5 groups (P<0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (allP<0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes

2000 ◽  
Vol 279 (3) ◽  
pp. E520-E528 ◽  
Author(s):  
Thomas Laedtke ◽  
Lise Kjems ◽  
Niels Pørksen ◽  
Ole Schmitz ◽  
Johannes Veldhuis ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Plasma Glucose Concentration ◽  
Molar Ratio ◽  
Β Cell ◽  
First Phase Insulin Secretion ◽  
Clinical Experiments

Impaired insulin secretion in type 2 diabetes is characterized by decreased first-phase insulin secretion, an increased proinsulin-to-insulin molar ratio in plasma, abnormal pulsatile insulin release, and heightened disorderliness of insulin concentration profiles. In the present study, we tested the hypothesis that these abnormalities are at least partly reversed by a period of overnight suspension of β-cell secretory activity achieved by somatostatin infusion. Eleven patients with type 2 diabetes were studied twice after a randomly ordered overnight infusion of either somatostatin or saline with the plasma glucose concentration clamped at ∼8 mmol/l. Controls were studied twice after overnight saline infusions and then at a plasma glucose concentration of either 4 or 8 mmol/l. We report that in patients with type 2 diabetes, 1) as in nondiabetic humans, insulin is secreted in discrete insulin secretory bursts; 2) the frequency of pulsatile insulin secretion is normal; 3) the insulin pulse mass is diminished, leading to decreased insulin secretion, but this defect can be overcome acutely by β-cell rest with somatostatin; 4) the reported loss of orderliness of insulin secretion, attenuated first-phase insulin secretion, and elevated proinsulin-to-insulin molar ratio also respond favorably to overnight inhibition by somatostatin. The results of these clinical experiments suggest the conclusion that multiple parameters of abnormal insulin secretion in patients with type 2 diabetes mechanistically reflect cellular depletion of immediately secretable insulin that can be overcome by β-cell rest.

Maintenance of the postabsorptive plasma glucose concentration: insulin or insulin plus glucagon?

2005 ◽  
Vol 289 (2) ◽  
pp. E181-E186 ◽  
Author(s):  
Bharathi Raju ◽  
Philip E. Cryer
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Endogenous Glucose Production ◽  
Plasma Glucose Concentration ◽  
Alternative View ◽  
Physiological Range ◽  
Healthy Humans

The prevalent view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by the interplay of the glucose-lowering action of insulin and the glucose-raising action of glucagon. It is supported by a body of evidence derived from studies of suppression of glucagon (and insulin, among other effects) with somatostatin in animals and humans, immunoneutralization of glucagon, defective glucagon synthesis, diverse mutations, and absent or reduced glucagon receptors in animals and glucagon antagonists in cells, animals, and humans. Many of these studies are open to alternative interpretations, and some lead to seemingly contradictory conclusions. For example, immunoneutralization of glucagon lowered plasma glucose concentrations in rabbits, but administration of a glucagon antagonist did not lower plasma glucose concentrations in healthy humans. Evidence that the glycemic threshold for glucagon secretion, unlike that for insulin secretion, lies below the physiological range, and the finding that selective suppression of insulin secretion without stimulation of glucagon secretion raises fasting plasma glucose concentrations in humans underscore the primacy of insulin in the regulation of the postabsorptive plasma glucose concentration and challenge the prevalent view. The alternative view is that the postabsorptive plasma glucose concentration is maintained within the physiological range by insulin alone, specifically regulated increments and decrements in insulin, and the resulting decrements and increments in endogenous glucose production, respectively, and glucagon becomes relevant only when glucose levels drift below the physiological range. Although the balance of evidence suggests that glucagon is involved in the maintenance of euglycemia, more definitive evidence is needed, particularly in humans.

scholarly journals Salicylates Increase Insulin Secretion in Healthy Obese Subjects

2008 ◽  
Vol 93 (7) ◽  
pp. 2523-2530 ◽  
Author(s):  
José-Manuel Fernández-Real ◽  
Abel López-Bermejo ◽  
Ana-Belén Ropero ◽  
Sandra Piquer ◽  
Angel Nadal ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Treatment Period ◽  
Islets Of Langerhans ◽  
Glucose Concentration ◽  
Human Islets ◽  
Serum Glucose ◽  
Obese Subjects ◽  
Healthy Obese

Abstract Context: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. Objective: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. Design, Setting, and Participants: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. Main Outcome Measures: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. Results: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 μm of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 μm of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. Conclusions: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the β-cell.

scholarly journals Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

2009 ◽  
Vol 296 (6) ◽  
pp. R1695-R1701 ◽  
Author(s):  
Krishna M. Boini ◽  
Dirk Graf ◽  
Anita M. Hennige ◽  
Saisudha Koka ◽  
Daniela S. Kempe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Peak Plasma ◽  
Plasma Glucose Concentration ◽  
Α Subunit ◽  
Glucose Injection ◽  
Regulation Of Metabolism

The pore-forming K+-channel α-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K+ uptake and glucose metabolism. Insulin (100 nM)-induced K+ uptake was determined in isolated perfused livers from KCNQ1-deficient mice ( kcnq1−/−) and their wild-type littermates ( kcnq1+/+). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled 3H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K+ uptake was significantly more sustained in isolated perfused livers from kcnq1−/− mice than from kcnq1+/+mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1−/− than in kcnq1+/+ mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1−/− than in kcnq1+/+mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1−/− than in kcnq1+/+mice. Uptake of 3H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1−/− than in kcnq1+/+mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K+ uptake by insulin and thereby influences K+-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance

2001 ◽  
Vol 101 (3) ◽  
pp. 227-233 ◽  
Author(s):  
Toshikazu YAMANOUCHI ◽  
Tae INOUE ◽  
Eri OGATA ◽  
Akiko KASHIWABARA ◽  
Nobuyuki OGATA ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Inverse Correlation ◽  
Glycated Haemoglobin ◽  
Plasma Glucose Concentration ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Cross Sectional

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r = 0.281, P < 0.001), a significant inverse correlation (r =-0.824, P < 0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r =-0.539, P < 0.0001) and 2 h plasma glucose (r =-0.621, P < 0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

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