scholarly journals First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy

Obesity Facts ◽  
2020 ◽  
Vol 13 (6) ◽  
pp. 584-595
Author(s):  
Rahel Nussbaumer ◽  
Anne Christin Meyer-Gerspach ◽  
Ralph Peterli ◽  
Thomas Peters ◽  
Christoph Beglinger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Sleeve Gastrectomy ◽  
Glycemic Control ◽  
Insulin Release ◽  
Severe Obesity ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Postoperative Change

<b><i>Background:</i></b> Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. <b><i>Objective:</i></b> To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. <b><i>Setting:</i></b> University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. <b><i>Methods:</i></b> Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. <b><i>Results:</i></b> Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0–60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0–10 min), second-phase insulin secretion (AUC 10–60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. <b><i>Conclusion:</i></b> Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.

Development of hyperinsulinemia and insulin resistance during the early stage of weight gain

2008 ◽  
Vol 294 (3) ◽  
pp. E568-E575 ◽  
Author(s):  
Johannes Erdmann ◽  
Bianca Kallabis ◽  
Ulrich Oppel ◽  
Oleg Sypchenko ◽  
Stefan Wagenpfeil ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Early Stage ◽  
Normal Range ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
First Time

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m2 BMI within 41/2 mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.

scholarly journals Influence of Tacrolimus on Glucose Metabolism before and after Renal Transplantation: A Prospective Study

2001 ◽  
Vol 12 (3) ◽  
pp. 583-588 ◽  
Author(s):  
ELLY M. VAN DUIJNHOVEN ◽  
JOHANNES M. M. BOOTS ◽  
MAARTEN H. L. CHRISTIAANS ◽  
BRUCE H. R. WOLFFENBUTTEL ◽  
JOHANNES P. VAN HOOFF
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Prospective Longitudinal Study ◽  
C Peptide ◽  
Before And After ◽  
Prospective Longitudinal

Abstract. Most studies concerning the influence of tacrolimus on glucose metabolism have been performed either in animals or after organ transplantation. These clinical studies have largely been transversal with patients who were using steroids. Therefore, this prospective, longitudinal study investigated the influence of tacrolimus on glucose metabolism before and after transplantation. Eighteen Caucasian dialysis patients underwent an intravenous glucose tolerance test before and 5 d after the start of tacrolimus. Insulin sensitivity index (kG), insulin resistance (insulin/glucose ratio and homeostasis model assessment), and C-peptide and insulin secretion were calculated. Trough levels of tacrolimus were measured. After transplantation, the occurrence of posttransplantation diabetes mellitus (PTDM) was prospectively monitored. Statistical analysis was performed using the Wilcoxon signed ranks test and Spearman's rho for correlation. Before tacrolimus, kG was indeterminate in three patients. During tacrolimus, kG decreased in 16 of 18 patients, from a median of 1.74 mmol/L per min to 1.08 mmol/L per min (P < 0.0001). The correlation between C-peptide and insulin data was excellent. Insulin secretion decreased from 851.0 mU × min/L to 558.0 mU × min/L (P = 0.014), whereas insulin resistance did not change. Insulin sensitivity correlated negatively with tacrolimus trough level. After transplantation, three patients developed PTDM; before tacrolimus, two had an indeterminate and one a low normal kG. During tacrolimus administration, kG decreased in almost all patients as a result of a diminished insulin secretion response to a glucose load, whereas insulin resistance did not change. Patients with an abnormal or indeterminate kG seem to be at risk of developing PTDM while on tacrolimus.

Ethanol inhibits insulin action on lipolysis and on insulin release in elderly men

1993 ◽  
Vol 265 (2) ◽  
pp. E197-E202 ◽  
Author(s):  
G. Boden ◽  
X. Chen ◽  
R. A. DeSantis ◽  
Z. Kendrick
Keyword(s):  
Insulin Resistance ◽  
Stable Isotopes ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Release ◽  
Insulin Action ◽  
Glucose Disposal ◽  
Elderly Men ◽  
C Peptide ◽  
Healthy Elderly

We have studied effects of ethanol on insulin's ability to suppress its own release and on its antilipolytic action in 12 healthy elderly men during euglycemic hyperinsulinemia. Insulin secretion was estimated from plasma C-peptide concentrations. Lipolysis was determined with the two stable isotopes [2H5]glycerol and [1-13C]palmitate. Hyperinsulinemia (approximately 350 pM) decreased plasma C-peptide by approximately 60% (from 325 to 122 pM, P < 0.05). Ethanol (approximately 10 mM) completely prevented the fall in C-peptide concentration. Ethanol decreased the antilipolytic action of insulin by approximately 40% [with insulin alone, glycerol rate of appearance (Ra) decreased from 1.8 to 0.6 mumol.kg-1 x min-1; with insulin + ethanol, it only decreased from 1.8 to 1.1 mumol.kg-1 x min-1]. Ethanol did not affect palmitate Ra, which fell from 1.4 to 0.6 mumol.kg-1 x min-1 with insulin and from 1.4 to 0.3 mumol.kg-1 x min-1 with insulin plus ethanol. Fatty acid reesterification was not affected by insulin but tripled (from 0.6 to 1.9 mumol.kg-1 x min-1) in response to insulin plus ethanol. Our data showed that modest concentrations of ethanol suppressed the inhibitory actions of insulin on its own release and on lipolysis. The inhibition by ethanol of various insulin actions, including glucose disposal, lipolysis, and insulin release, in diverse tissues such as muscle, adipose tissue, and pancreas raises the possibility that ethanol may produce a state of generalized insulin resistance.

scholarly journals Variability in Estimated Modelled Insulin Secretion

2021 ◽  
pp. 193229682199112
Author(s):  
Jennifer J. Ormsbee ◽  
Hannah J. Burden ◽  
Jennifer L. Knopp ◽  
J. Geoffrey Chase ◽  
Rinki Murphy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Parameters ◽  
Pancreatic Beta Cells ◽  
Compartment Model ◽  
Interquartile Range ◽  
Cumulative Distribution ◽  
Model Framework ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Model Based

Background: The ability to measure insulin secretion from pancreatic beta cells and monitor glucose-insulin physiology is vital to current health needs. C-peptide has been used successfully as a surrogate for plasma insulin concentration. Quantifying the expected variability of modelled insulin secretion will improve confidence in model estimates. Methods: Forty-three healthy adult males of Māori or Pacific peoples ancestry living in New Zealand participated in an frequently sampled, intravenous glucose tolerance test (FS-IVGTT) with an average age of 29 years and a BMI of 33 kg/m2. A 2-compartment model framework and standardized kinetic parameters were used to estimate endogenous pancreatic insulin secretion from plasma C-peptide measurements. Monte Carlo analysis (N = 10 000) was then used to independently vary parameters within ±2 standard deviations of the mean of each variable and the 5th and 95th percentiles determined the bounds of the expected range of insulin secretion. Cumulative distribution functions (CDFs) were calculated for each subject for area under the curve (AUC) total, AUC Phase 1, and AUC Phase 2. Normalizing each AUC by the participant’s median value over all N = 10 000 iterations quantifies the expected model-based variability in AUC. Results: Larger variation is found in subjects with a BMI > 30 kg/m2, where the interquartile range is 34.3% compared to subjects with a BMI ≤ 30 kg/m2 where the interquartile range is 24.7%. Conclusions: Use of C-peptide measurements using a 2-compartment model and standardized kinetic parameters, one can expect ~±15% variation in modelled insulin secretion estimates. The variation should be considered when applying this insulin secretion estimation method to clinical diagnostic thresholds and interpretation of model-based analyses such as insulin sensitivity.

scholarly journals Early Enhancements of Hepatic and Later of Peripheral Insulin Sensitivity Combined With Increased Postprandial Insulin Secretion Contribute to Improved Glycemic Control After Roux-en-Y Gastric Bypass

Diabetes ◽  
2013 ◽  
Vol 63 (5) ◽  
pp. 1725-1737 ◽  
Author(s):  
Kirstine N. Bojsen-Møller ◽  
Carsten Dirksen ◽  
Nils B. Jørgensen ◽  
Siv H. Jacobsen ◽  
Annette K. Serup ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Peripheral Insulin Sensitivity ◽  
Postprandial Insulin

scholarly journals Dual Mechanism for Type-2 Diabetes Resolution after Roux-en-Y Gastric Bypass

2009 ◽  
Vol 75 (6) ◽  
pp. 498-503 ◽  
Author(s):  
Edward Lin ◽  
S. Scott Davis ◽  
Jahnavi Srinivasan ◽  
John F. Sweeney ◽  
Thomas R. Ziegler ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose-insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.

scholarly journals Insulin-related dietary indices predict 24-h urinary C-peptide in adult men

2020 ◽  
pp. 1-8
Author(s):  
Dong Hoon Lee ◽  
Edward L. Giovannucci ◽  
Fred K. Tabung
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Positive Association ◽  
Significant Positive Association ◽  
Cross Sectional ◽  
C Peptide ◽  
Adult Men ◽  
Dietary Index ◽  
Sectional Analysis ◽  
Dietary Indices

Abstract The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men’s Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were calculated using validated FFQ. We conducted multivariable-adjusted linear regression to estimate relative and absolute concentrations of 24-h urinary C-peptide. In multivariable-adjusted models, we found a significant positive association between all three insulin-related dietary indices and 24-h urinary C-peptide (P < 0·05). Relative concentrations of 24-h urinary C-peptide per 1-sd increase in insulin-related dietary indices were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the association was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unchanged for dietary insulin index and dietary insulin load. In conclusion, EDIH, dietary insulin index and dietary insulin load were predictive of integrated insulin secretion assessed by 24-h urinary C-peptide. Findings after adjustment for BMI appear to confirm the relation of EDIH to insulin resistance and dietary insulin index/load to insulin secretion; the respective constructs of the two dietary indices.

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