Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

Lb, Hinshaw; Schiavon, Michele; Dadlani, Vikash; Mallad, Ashwini; Man, Chiara Dalla; Bharucha, Adil E.; Basu, Rita; Geske, Jennifer R.; Carter, Rickey E.; Cobelli, Claudio; Basu, Ananda; Kudva, Yogish C.

doi:10.1210/jc.2015-3952

Cited by 25 publications

(30 citation statements)

References 39 publications

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“…The maximum postprandial EGP suppression of 68% is in line with previous findings . The regulation of postprandial EGP suppression is complex and depends mainly on circulating insulin, glucose and glucagon concentrations .…”

Section: Discussionsupporting

confidence: 91%

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Basu

Pieber

Hansen

et al. 2018

Diabetes Obesity Metabolism

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AimTo investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast‐acting insulin aspart (faster aspart) than with insulin aspart (IAsp).Materials and methodsIn a randomized, double‐blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1‐13C] glucose). PPG turnover was determined by the triple‐tracer meal method using continuous, variable [6‐3H] glucose and [6,6‐2H2] glucose infusion.ResultsInsulin exposure within the first hour was 32% greater with faster aspart than with IAsp (treatment ratio faster aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59‐mmol/L non‐significantly smaller PPG increment at 1 hour (ΔPG1h; treatment difference faster aspart–IAsp −0.59 mmol/L [95% CI –1.19; 0.01]; P = .055). The trend towards reduced ΔPG1h with faster aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042).ConclusionsThe trend towards improved PPG control with faster aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance.

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Section: Discussionsupporting

confidence: 91%

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Basu

Pieber

Hansen

et al. 2018

Diabetes Obesity Metabolism

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“…Amylin was later characterized as an amyloidogenic peptide, isolated from a beta cell tumour and called islet amyloid polypeptide (IAPP), and then, amylin (Westermark et al ., ). Physiologically, amylin functions as a glucoregulatory and satiety‐inducing hormone, which is protective against postprandial spikes in blood glucose and overeating (see Hay et al ., ; Hinshaw et al ., ). Under disease conditions, amylin becomes dysregulated, misfolds, self‐associates and forms amyloid deposits (see Akter et al ., ), but the role of amylin in disease pathogenesis remains unclear.…”

Section: Introduction To Amylin and The Calcitonin Family Of Peptidesmentioning

confidence: 97%

Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development

Bower

Hay

2016

British J Pharmacology

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Amylin is an important, but poorly understood, 37 amino acid glucoregulatory hormone with great potential to target metabolic diseases. A working example that the amylin system is one worth developing is the FDA-approved drug used in insulin-requiring diabetic patients, pramlintide. However, certain characteristics of pramlintide pharmacokinetics and formulation leave considerable room for further development of amylin-mimetic compounds. Given that amylin-mimetic drug design and development is an active area of research, surprisingly little is known about the structure/function relationships of amylin. This is largely due to the unfavourable aggregative and solubility properties of the native peptide sequence, which are further complicated by the composition of amylin receptors. These are complexes of the calcitonin receptor with receptor activity-modifying proteins. This review explores what is known of the structure-function relationships of amylin and provides insights that can be drawn from the closely related peptide, CGRP. We also describe how this information is aiding the development of more potent and stable amylin mimetics, including peptide hybrids.

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“…One study in 22 participants with Type 1 diabetes receiving synthetic amylin (pramlintide) demonstrated an improvement in postprandial blood glucose rate of change suggesting that the variability in response to meals is lower [26]. Pramlintide lowers postprandial glucose excursions by primarily delaying gastric emptying and inhibiting postprandial glucagon excursions [27]. Similarly, use of a GLP-1 receptor agonist (liraglutide) in 20 participants with Type 2 diabetes showed decreased in SD of blood glucose as well as area under the curve (AUC) and mean amplitude of glycaemic excursions (MAGE) [28].…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

Beyond HbA_1c: using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision‐making

2019

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Assessment of glycaemic outcomes in the management of Type 1 and Type 2 diabetes has been revolutionized in the past decade with the increasing availability of accurate, user-friendly continuous glucose monitoring (CGM). This advancement has brought a need for new techniques to appropriately analyse and understand the voluminous and complex CGM data for application in research-related goals and clinical guidance for individuals. Traditionally, HbA 1c was established using the Diabetes Control and Complications Trial (DCCT) and other trials as the ultimate measure of glycaemic control in terms of efficacy and, by default, risk of microvascular complications of diabetes. However, it is acknowledged that HbA 1c alone is inadequate at describing an individual's daily glycaemic variation and risks for hypoand hyperglycaemia, and it does not provide the guidance needed to decrease those risks. CGM data provide means by which to characterize an individual's daily glycaemic excursions on a different time scale measured in minutes rather than months. As a consequence, clinical reports, such as the ambulatory glucose profile, increasingly include summary statistics related to averages (mean glucose, time in range) as well as markers related to glycaemic variability (coefficient of variation, standard deviation). However, there is a need to translate those metrics into specific risks that can be addressed in an actionable plan by individuals with diabetes and providers. This review presents several clinical scenarios of glycaemic outcomes from CGM data that can be analysed to describe glycaemic variability and its attendant risks of hyperglycaemia and hypoglycaemia, moving towards relevant interpretation of the complex CGM data streams.

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Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

Abstract: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Cited by 25 publications

References 39 publications

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development

Beyond HbA_1c: using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision‐making

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Effect of Pramlintide on Postprandial Glucose Fluxes in Type 1 Diabetes

Abstract: Inhibition of glucagon and gastric emptying delaying reduced 2-hour prandial glucose excursions in T1D by delaying meal rate of glucose appearance.

Cited by 25 publications

References 39 publications

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart

Amylin structure–function relationships and receptor pharmacology: implications for amylin mimetic drug development

Beyond HbA1c: using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision‐making

Contact Info

Product

Resources

About

Beyond HbA_1c: using continuous glucose monitoring metrics to enhance interpretation of treatment effect and improve clinical decision‐making