scholarly journals Associations of Glucose Control with Insulin Sensitivity and Pancreatic β-Cell Responsiveness in Newly Presenting Type 2 Diabetes

2002 ◽  
Vol 87 (1) ◽  
pp. 198-203 ◽  
Author(s):  
Ahmed I. Albarrak ◽  
Stephen D. Luzio ◽  
Ludovic J. Chassin ◽  
Rebecca A. Playle ◽  
David R. Owens ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Glucose Control ◽  
Interindividual Variability ◽  
Postprandial Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Fasting Plasma

We examined the ability of indices of insulin sensitivity and pancreatic β-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 ± 1 yr; body mass index, 30.5 ± 0.7 kg/m2; mean ± se) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (SI), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M0) and postprandial (MI) pancreatic β-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA1C). All measures of pancreatic β-cell responsiveness (M0, MI, and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P < 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P < 0.05). SI demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. MI followed by disposition index (composite index of insulin sensitivity and pancreatic β-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70–80% interindividual variability of fasting plasma glucose, FPI, HbA1C, and insulin responses to MTT, and only 25–40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic β-cell responsiveness explain fasting glucose and HbA1C well but fail to explain postprandial glucose.

The Glucagon Receptor Antagonist LY2409021 has No Effect on Postprandial Glucose in Type 2 Diabetes

2021 ◽  
Author(s):  
Sofie Hædersdal ◽  
Asger Lund ◽  
Henrik Maagensen ◽  
Elisabeth Nielsen-Hannerup ◽  
Lærke S Gasbjerg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Postprandial Glucose ◽  
Glucagon Receptor ◽  
Fasting Plasma ◽  
Glucagon Receptor Antagonist

Objective: Type 2 diabetes (T2D) pathophysiology includes fasting and postprandial hyperglucagonemia, which has been linked to hyperglycemia via increased endogenous glucose production (EGP). We used a glucagon receptor antagonist (LY2409021) and stable isotope tracer infusions to investigate consequences of hyperglucagonemia in type 2 diabetes. Design: A double-blinded, randomized, placebo-controlled crossover study was conducted. Methods: Ten patients with T2D and ten matched non-diabetic controls underwent two liquid mixed meal tests preceded by single-dose administration of LY2409021 (100 mg) or placebo. Double-tracer technique was used to quantify EGP. Antagonist selectivity towards related incretin receptors was determined in vitro. Results: Compared to placebo, LY2409021 lowered fasting plasma glucose from 9.1 to 7.1 mmol/L in patients and from 5.6 to 5.0 mmol/L in controls (both P<0.001) by mechanisms involving reduction of EGP. Postprandial plasma glucose excursions (baseline-subtracted area under the curve) were unaffected by LY2409021 in patients and increased in controls compared to placebo. Glucagon concentrations more than doubled during glucagon receptor antagonism. The antagonist interfered with both glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptors, complicating the interpretation of the postprandial data. Conclusions: LY2409021 lowered fasting plasma glucose concentrations but did not improve postprandial glucose tolerance after a meal in patients with T2D and controls. The metabolic consequences of postprandial hyperglucagonemia are difficult to evaluate using LY2409021 because of its antagonizing effects on the incretin receptors.

scholarly journals Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

2014 ◽  
Vol 307 (9) ◽  
pp. E822-E829 ◽  
Author(s):  
Thomas P. J. Solomon ◽  
Steven K. Malin ◽  
Kristian Karstoft ◽  
Sine H. Knudsen ◽  
Jacob M. Haus ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Normal Glucose

Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.

Relationship between β-cell responsiveness and fasting plasma glucose in Caucasian subjects with newly presenting Type 2 diabetes

2001 ◽  
Vol 18 (10) ◽  
pp. 797-802 ◽  
Author(s):  
R. Hovorka ◽  
A. Albarrak ◽  
L. Chassin ◽  
S. D. Luzio ◽  
R. Playle ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Β Cell ◽  
Fasting Plasma

scholarly journals Efficacy of Glyburide/Metformin Tablets Compared with Initial Monotherapy in Type 2 Diabetes

2003 ◽  
Vol 88 (8) ◽  
pp. 3598-3604 ◽  
Author(s):  
Alan J. Garber ◽  
Daniel S. Donovan ◽  
Paresh Dandona ◽  
Simon Bruce ◽  
Jong-Soon Park
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Glycosylated Hemoglobin ◽  
Postprandial Glucose ◽  
Initial Therapy ◽  
Double Blind ◽  
Fasting Plasma

Many patients with type 2 diabetes fail to achieve or maintain the American Diabetes Association’s recommended treatment goal of glycosylated hemoglobin levels. This multicenter, double-blind trial enrolled patients with type 2 diabetes who had inadequate glycemic control [glycosylated hemoglobin A1C (A1C), &gt;7% and &lt;12%) with diet and exercise alone to compare the benefits of initial therapy with glyburide/metformin tablets vs. metformin or glyburide monotherapy. Patients (n = 486) were randomized to receive glyburide/metformin tablets (1.25/250 mg), metformin (500 mg), or glyburide (2.5 mg). Changes in A1C, fasting plasma glucose, fructosamine, serum lipids, body weight, and 2-h postprandial glucose after a standardized meal were assessed after 16 wk of treatment. Glyburide/metformin tablets caused a superior mean reduction in A1C from baseline (−2.27%) vs. metformin (−1.53%) and glyburide (−1.90%) monotherapy (P = 0.0003). Glyburide/metformin also significantly reduced fasting plasma glucose and 2-h postprandial glucose values compared with either monotherapy. The final mean doses of glyburide/metformin (3.7/735 mg) were lower than those of metformin (1796 mg) and glyburide (7.6 mg). First-line treatment with glyburide/metformin tablets provided superior glycemic control over component monotherapy, allowing more patients to achieve American Diabetes Association treatment goals with lower component doses in drug-naive patients with type 2 diabetes.

scholarly journals Impact of a mild decrease in fasting plasma glucose on β-cell function in healthy subjects and patients with type 2 diabetes

2016 ◽  
Vol 310 (11) ◽  
pp. E919-E924 ◽  
Author(s):  
Marta Seghieri ◽  
Eleni Rebelos ◽  
Brenno D. Astiarraga ◽  
Simona Baldi ◽  
Andrea Mari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Time Course ◽  
Cell Function ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Β Cell ◽  
Β Cell Function

Restoring euglycaemia for weeks or months improves insulin secretion in patients with type 2 diabetes (T2D). We tested whether mild decrements in fasting glucose (FPG) acutely affect β-cell function and insulin sensitivity. Thirteen normotolerant (NGT) and 10 T2D patients volunteered in pairs. In an isoglycemic test (Iso), after 100 min of stabilization, an incremental glucose infusion over 3 h was applied to raise plasma glucose to >22 mmol/l, followed by an arginine challenge; in a subisoglycemic test (Sub), a glucose infusion matching the plasma glucose time course of Iso was preceded by an insulin infusion period (100 min) aimed at maintaining a mild FPG reduction while avoiding hypoglycaemia. β-Cell function was assessed by mathematical modeling, whereas the acute insulin response (AIR) to arginine was determined from C-peptide levels. In the Sub, FPG was lowered by 17% in NGT and 31% in T2D patients. On the glucose ramp, total insulin release was lower in Sub than in Iso in both groups [from 106 (43) to 75 (39) nmol/m−2 in NGT and from 71 (63) to 64 (41) nmol/m−2 in T2D, P = 0.001]. In the Sub, β-cell glucose sensitivity was significantly ( P = 0.008) reduced in NGT [from 50 (31) to 43 (21) pmol·min−1·m−2·mM−1] but not in T2D [19 (20) to 20 (20) pmol·min−1·m−2·mM−1]. Likewise, AIR was lowered in NGT [8.9 (4.6) to 7.1 (4.4) nmol/l, P = 0.048] but not in T2D [4.7 (3.3) to 5.3 (3.2) nmol/l]. Insulin sensitivity improved in NGT but only marginally in T2D. Prestimulatory glucose levels acutely influence both β-cell function and insulin sensitivity differentially in nondiabetic and type 2 diabetic individuals.

scholarly journals Synthetic Exendin-4 (Exenatide) Significantly Reduces Postprandial and Fasting Plasma Glucose in Subjects with Type 2 Diabetes

2003 ◽  
Vol 88 (7) ◽  
pp. 3082-3089 ◽  
Author(s):  
Orville G. Kolterman ◽  
John B. Buse ◽  
Mark S. Fineman ◽  
Eling Gaines ◽  
Sonja Heintz ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Fasting Glucose ◽  
Glucagon Secretion ◽  
Postprandial Glucose ◽  
Study Medication ◽  
Fasting Plasma ◽  
New Treatments

Despite the advent of new treatments, glucose control in the type 2 diabetes population is unsatisfactory. AC2993 (synthetic exendin-4; exenatide), a novel glucose-dependent insulinotropic agent, exhibited notable antidiabetic potential in two clinical studies in patients with type 2 diabetes. In study A, 24 subjects received sc injections of study medication (0.1 μg/kg AC2993 or placebo) twice daily with meals for 5 d. Statistically significant reductions in mean postprandial circulating concentrations of glucose, insulin, and glucagon occurred following treatment with AC2993. In study B, 13 subjects receiving a single dose of study medication (0.05, 0.1, or 0.2 μg/kg AC2993 or placebo) following an overnight fast had reduced fasting plasma glucose concentrations during the subsequent 8-h period. The relative glucose and insulin concentration profiles were consistent with glucose-dependent insulinotropism. AC2993 was well tolerated. Mild transient headache, nausea, and vomiting were the main adverse events. In conclusion, AC2993 acutely and markedly reduces fasting and postprandial glucose concentrations in patients with type 2 diabetes. During fasting, glucose-dependent enhancement of insulin secretion and suppression of glucagon secretion are the predominant mechanisms, and postprandially, slowing of gastric emptying is additionally operative. This robust antidiabetic effect warrants further evaluation of AC2993.

Sign in / Sign up

Export Citation Format

Share Document