scholarly journals Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

2016 ◽  
Vol 101 (5) ◽  
pp. 1954-1962 ◽  
Author(s):  
Ling Hinshaw ◽  
Michele Schiavon ◽  
Vikash Dadlani ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Insulin Sensitivity ◽  
Area Under The Curve ◽  
Postprandial Glucose ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Glucose Turnover ◽  
Plasma Glucagon

Abstract Context: Early postprandial hyperglycemia and delayed hypoglycemia remain major problems in current management of type 1 diabetes (T1D). Objective: Our objective was to investigate the effects of pramlintide, known to suppress glucagon and delay gastric emptying, on postprandial glucose fluxes in T1D. Design: This was a single-center, inpatient, randomized, crossover study. Patients: Twelve patients with T1D who completed the study were analyzed. Interventions: Subjects were studied on two occasions with or without pramlintide. Triple tracer mixed-meal method and oral minimal model were used to estimate postprandial glucose turnover and insulin sensitivity (SI). Integrated liver insulin sensitivity was calculated based on glucose turnover. Plasma glucagon and insulin were measured. Main Outcome Measure: Glucose turnover and SI were the main outcome measures. Results: With pramlintide, 2-hour postprandial glucose, insulin, glucagon, glucose turnover, and SI indices showed: plasma glucose excursions were reduced (difference in incremental area under the curve [iAUC], 444.0 mMmin, P = .0003); plasma insulin concentrations were lower (difference in iAUC, 7642.0 pMmin; P = .0099); plasma glucagon excursions were lower (difference in iAUC, 1730.6 pg/mlmin; P = .0147); meal rate of glucose appearance was lower (difference in iAUC: 1196.2 μM/kg fat free mass [FFM]; P = .0316), endogenous glucose production was not different (difference in iAUC: −105.5 μM/kg FFM; P = .5842), rate of glucose disappearance was lower (difference in iAUC: 1494.2 μM/kg FFM; P = .0083). SI and liver insulin sensitivity were not different between study visits (P > .05). Conclusions: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

scholarly journals Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function

2014 ◽  
Vol 307 (6) ◽  
pp. E494-E502 ◽  
Author(s):  
Ling Hinshaw ◽  
Michele Schiavon ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
Rita Basu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Insulin Sensitivity ◽  
Delayed Gastric Emptying ◽  
Cell Function ◽  
Postprandial Glucose ◽  
Β Cell ◽  
C Peptide ◽  
Β Cell Function

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

scholarly journals Postprandial glucose fluxes and insulin sensitivity during exercise: A study in healthy individuals

2013 ◽  
Vol 305 (4) ◽  
pp. E557-E566 ◽  
Author(s):  
Michele Schiavon ◽  
Ling Hinshaw ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
Giovanni Sparacino ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Acute Exercise ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Fat Free Mass ◽  
Glucose Turnover ◽  
Sensitivity Index ◽  
Moderate Exercise ◽  
Insulin Sensitivity Index

Quantifying the effect size of acute exercise on insulin sensitivity (SIexercise) and simultaneous measurement of glucose disappearance (Rd), endogenous glucose production (EGP), and meal glucose appearance in the postprandial state has not been developed in humans. To do so, we studied 12 healthy subjects [5 men, age 37.1 ± 3.1 yr, body mass index 24.1 ± 1.1 kg/m2, fat-free mass (FFM) 50.9 ± 3.9 kg] during moderate exercise at 50% V̇o2max for 75 min, 120–195 min after a triple-tracer mixed meal consumed at time 0. Tracer infusion rates were adjusted to achieve constant tracer-to-tracee ratio and minimize non-steady-state errors. Glucose turnover was estimated by accounting for the nonstationary kinetics introduced by exercise. Insulin sensitivity index was calculated in each subject both in the absence [time ( t) = 0–120 min, SIrest] and presence ( t = 0–360 min, SIexercise) of physical activity. EGP at t = 0 min (13.4 ± 1.1 μM·kg FFM−1·min−1) fell at t = 120 min (2.4 ± 0.4 μM·kg FFM−1·min−1) and then rapidly rose almost eightfold at t = 180 min (18.2 ± 2.6 μM·kg FFM−1·min−1) before gradually falling at t = 360 min (10.6 ± 0.9 μM·kg FFM−1·min−1). Rd rapidly peaked at t = 120 min at the start of exercise (89.5 ± 11.6 μM·kg FFM−1·min−1) and then gradually declined at t = 195 min (26.4 ± 3.3 μM·kg FFM−1·min−1) before returning to baseline at t = 360 min. SIexercise was significantly higher than SIrest (21.6 ± 3.7 vs. 12.5 ± 2.0 10−4 dl·kg−1·min−1 per μU/ml, P < 0.0005). Glucose turnover was estimated for the first time during exercise with the triple-tracer technique. Our results, applying state-of-the-art techniques, show that moderate exercise almost doubles postprandial insulin sensitivity index in healthy subjects.

scholarly journals Postprandial Glucose Control in Type 1 Diabetes: Importance of the Gastric Emptying Rate

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1559 ◽  
Author(s):  
Roberta Lupoli ◽  
Federica Pisano ◽  
Brunella Capaldo
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Glucose Control ◽  
Postprandial Glucose ◽  
Key Factors ◽  
Glucose Response ◽  
Gastric Emptying Rate ◽  
Factors Affecting ◽  
Infusion Systems

The achievement of optimal post-prandial (PP) glucose control in patients with type 1 diabetes (T1DM) remains a great challenge. This review summarizes the main factors contributing to PP glucose response and discusses the likely reasons why PP glucose control is rarely achieved in T1DM patients. The macronutrient composition of the meal, the rate of gastric emptying and premeal insulin administration are key factors affecting the PP glucose response in T1DM. Although the use of continuous insulin infusion systems has improved PP glucose control compared to conventional insulin therapy, there is still need for further ameliorations. T1DM patients frequently present a delayed gastric emptying (GE) that produces a lower but more prolonged PP hyperglycemia. In addition, delayed GE is associated with a longer time to reach the glycemic peak, with a consequent mismatch between PP glucose elevation and the timing of premeal insulin action. On this basis, including GE time and meal composition in the algorithms for insulin bolus calculation of the insulin delivery systems could be an important step forward for optimization of PP glucose control in T1DM.

scholarly journals Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes

2009 ◽  
Vol 94 (9) ◽  
pp. 3297-3305 ◽  
Author(s):  
Burak Salgin ◽  
Maria L. Marcovecchio ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Leslie J. Bluck ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Growth Hormone ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Context: Because GH stimulates lipolysis, an increase in circulating free fatty acid levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and free fatty acids to the development of insulin resistance in patients with T1D. Patients: Seven (four females, three males) nonobese patients with T1D aged 21–30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia overnight (P = 0.008), elevated basal endogenous glucose production (P = 0.007), decreased basal peripheral glucose uptake (P = 0.03), and reduced glucose uptake during step 1 of the clamp (P &lt; 0.0001). Coadministration of rhGH and acipimox reversed these effects and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity. Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis. Growth hormone decreases insulin sensitivity through increases in free fatty acid levels.

scholarly journals Exercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach

2015 ◽  
Vol 308 (12) ◽  
pp. E1106-E1115 ◽  
Author(s):  
Ashwini Mallad ◽  
Ling Hinshaw ◽  
Michele Schiavon ◽  
Chiara Dalla Man ◽  
Vikash Dadlani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Metabolism ◽  
Insulin Pump ◽  
Postprandial Glucose ◽  
Insulin Pump Therapy ◽  
Moderate Intensity ◽  
Glucose Turnover ◽  
Moderate Intensity Exercise ◽  
Pump Therapy

To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V̇o2max) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia.

scholarly journals Separating Insulin-Mediated and Non-Insulin-Mediated Glucose Uptake during Aerobic Exercise in People with Type 1 Diabetes

2020 ◽  
Author(s):  
Thanh-Tin P. Nguyen ◽  
Peter G. Jacobs ◽  
Jessica Castle ◽  
Leah M. Wilson ◽  
Kerry Kuehl ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Aerobic Exercise ◽  
Glucose Uptake ◽  
Area Under The Curve ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Intense Exercise ◽  
Muscle Work ◽  
Exercise Period

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin resistance after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three studies at three insulin rates (100%, 150%, 300% of basal). After 3-hours run-in, participants performed 45 minutes aerobic exercise (moderate or intense). We determined area-under-the-curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 minutes from exercise start. A novel application of linear regression of Rd across the three insulin studies allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during and after exercise. ­AUCRd increased 12.45 mmol/L (CI=10.33-14.58, p<0.001) and 13.13 mmol/L (CI=11.01-15.26, p<0.001) while AUCEGP increased 1.66(CI=1.01-2.31, p<0.001) and 3.46 mmol/L (CI=2.81-4.11, p<0.001) above baseline during moderate and intense exercise respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI=0.91-3.37, p<0.001) compared to moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI=0.05-0.07, p<0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, while non-insulin mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin and non-insulin mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov (ID: NCT03090451).

A Human Randomized Controlled Trial Comparing Metabolic Responses to Single and Repeated Hypoglycemia in Type 1 Diabetes

2020 ◽  
Vol 105 (12) ◽  
pp. e4699-e4711
Author(s):  
Mads Bisgaard Bengtsen ◽  
Julie Støy ◽  
Nikolaj Fibiger Rittig ◽  
Thomas Schmidt Voss ◽  
Nils Erik Magnusson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Intracellular Signaling ◽  
Glucose Transporter ◽  
Controlled Trial ◽  
Hormone Sensitive Lipase ◽  
Metabolic Responses ◽  
Glucose Turnover

Abstract Aims Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counter-regulatory responses to hypoglycemia. Our study was designed to test whether (1) the metabolic responses and insulin sensitivity are impaired, and (2) whether they are affected by short-lived antecedent hypoglycemia in participants with T1D. Materials and Methods In a randomized, crossover, 2x2 factorial design, 9 male participants with T1D and 9 comparable control participants underwent 30 minutes of hypoglycemia (p-glucose &lt; 2.9 mmol/L) followed by a euglycemic clamp on 2 separate interventions: with and without 30 minutes of hypoglycemia the day before the study day. Results During both interventions insulin sensitivity was consistently lower, while counter-regulatory hormones were reduced, with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5- to 10-fold increased ketone body concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake, and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue phosphatase and tensin homolog (PTEN) content, hormone-sensitive lipase (HSL) phosphorylation, and muscle glucose transporter type 4 (GLUT4) content were decreased compared with controls. And antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity. Conclusions Participants with T1D displayed insulin resistance and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact and ketogenic responses were amplified. We observed subtle alterations of intracellular signaling and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.

Gastric emptying and postprandial glucose excursions in adolescents with type 1 diabetes

2008 ◽  
Vol 9 (6) ◽  
pp. 561-566 ◽  
Author(s):  
Rubina A Heptulla ◽  
Luisa M Rodriguez ◽  
Kimberly J Mason ◽  
Morey W Haymond
Keyword(s):  
Type 1 Diabetes ◽  
Gastric Emptying ◽  
Postprandial Glucose

scholarly journals An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes

2016 ◽  
Vol 11 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Dimitri Boiroux ◽  
Tinna Björk Aradóttir ◽  
Kirsten Nørgaard ◽  
Niels Kjølstad Poulsen ◽  
Henrik Madsen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Unscented Kalman Filter ◽  
Postprandial Glucose ◽  
Continuous Glucose Monitor ◽  
Bolus Size ◽  
Meal Time ◽  
Glucose Dynamics ◽  
Basal Bolus

Background: Bolus calculators help patients with type 1 diabetes to mitigate the effect of meals on their blood glucose by administering a large amount of insulin at mealtime. Intraindividual changes in patients physiology and nonlinearity in insulin-glucose dynamics pose a challenge to the accuracy of such calculators. Method: We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal size. Following meal announcements, the meal compartment and the meal time constant are estimated, otherwise insulin sensitivity is estimated. Results: We compare the performance of a conventional linear bolus calculator with the proposed bolus calculator. The proposed basal-bolus calculator significantly improves the time spent in glucose target ( P < .01) compared to the conventional bolus calculator. Conclusion: An adaptive nonlinear basal-bolus calculator can efficiently compensate for physiological changes. Further clinical studies will be needed to validate the results.

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