Ignite Creation Date:
2025-12-24 @ 12:37 PM
Ignite Modification Date:
2025-12-30 @ 7:53 PM
Study NCT ID:
NCT04334161
Status:
COMPLETED
Last Update Posted:
2021-08-10
First Post:
2020-03-30
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluation of the Neuro-endocrine Response to Post-prandial Hyperinsulinaemic Hypoglycaemia.
Sponsor:
Lia Bally
Organization:
Study Overview
Official Title:
Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery Part 1 B: Evaluation of the Neuro-endocrine Response to Hypoglycaemia.
Status:
COMPLETED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEEP1B
Brief Summary:
The primary objective of this study is to assess the neuro-endocrine response to hypoglycaemia in PHH vs. non-PHH post-gastric bypass individuals.
Detailed Description:
Obesity is a major global public health concern, for which the most effective therapy is bariatric surgery. Beyond weight loss, bariatric surgery exerts powerful effects on glucose metabolism, achieving complete type 2 diabetes remission in up to 70% of cases. An exaggeration of these effects, however, can result in an increasingly recognized metabolic complication known as postprandial hyperinsulinaemic hypoglycaemia (PHH). The condition manifests 1-3 years after surgery with hypoglycaemic episodes after meals. Emerging data suggest that PHH is more frequent than previously thought and affects approximately 30% of postoperative patients, more commonly after gastric bypass than sleeve gastrectomy . Despite such frequency, the underlying pathophysiology of PHH remains incompletely understood.
A striking finding in PHH patients is the observed lack of insulin suppression and inadequate glucagon response to the sharply falling glucose levels. The blunted glucagon response to hypoglycaemia may result from altered alpha-cell function (acute or chronic) and an interaction with gut hormones (e.g. glucagon-like peptide 1 (GLP-1) that is known to exert glucagon-inhibitory effects) or altered brain signalling. It is conceivable that, both, lack of endogenous insulin suppression in response to falling postprandial blood glucose levels and impaired glucagon secretion contribute to PHH.
Further neuroendocrine regulatory processes to counteract hypoglycaemia involve catecholamines, cortisol, growth hormone and autonomic nervous system activity. Two previous studies examined counter-regulatory hormones during experimentally induced hypoglycaemia in patients after gastric bypass surgery and found lower levels than before surgery, suggesting that bariatric surgery per se influences counter-regulation to hypoglycaemia. Underlying mechanisms remain speculative. Of note, impaired neuroendocrine counter-regulation to hypoglycaemia is further supported by the high proportion of asymptomatic patients, which may be reflective of impaired hypoglycaemia awareness. The role of counter-regulatory hormones in PHH patients remains not fully understood.
Apart from the neuroendocrine milieu, effectiveness of hypoglycaemia counter-regulation depends on the capacity to provide glucose from the liver, also known as endogenous glucose production. In healthy humans, approximately 85% of the glucose produced by the liver during the initial 60-90min of hypoglycaemia is derived from liver glycogen. Postprandial hepatic glycogen stores, in turn, depend heavily on the hepatic glucose uptake following a meal. Postprandial hepatic glucose disposal and mobilization of hepatic glucose during hypoglycaemia in PHH patients remain unexplored to date.
There is currently no evidence, that increased insulin sensitivity is implicated in the pathophysiology of PHH. Conversely, previous studies suggested increased non-insulin dependent whole body glucose uptake in PHH compared to non-PHH in the light of similar or even decreased insulin sensitivity.
The primary objective of this study is to assess the neuro-endocrine response to hypoglycaemia in PHH vs. non-PHH post-gastric bypass individuals. The investigators hypothesize that the glucagon response to standardized and controlled hypoglycaemia is significantly diminished in PHH vs. non-PHH post-gastric bypass individuals. Involvement of non-surgical non-PHH controls and sleeve-gastrectomy non-PHH controls will allow to explore effects of bariatric surgery on counter-regulatory mechanisms to hypoglycaemia, including differences between procedures (gastric bypass vs. sleeve gastrectomy).
A striking finding in PHH patients is the observed lack of insulin suppression and inadequate glucagon response to the sharply falling glucose levels. The blunted glucagon response to hypoglycaemia may result from altered alpha-cell function (acute or chronic) and an interaction with gut hormones (e.g. glucagon-like peptide 1 (GLP-1) that is known to exert glucagon-inhibitory effects) or altered brain signalling. It is conceivable that, both, lack of endogenous insulin suppression in response to falling postprandial blood glucose levels and impaired glucagon secretion contribute to PHH.
Further neuroendocrine regulatory processes to counteract hypoglycaemia involve catecholamines, cortisol, growth hormone and autonomic nervous system activity. Two previous studies examined counter-regulatory hormones during experimentally induced hypoglycaemia in patients after gastric bypass surgery and found lower levels than before surgery, suggesting that bariatric surgery per se influences counter-regulation to hypoglycaemia. Underlying mechanisms remain speculative. Of note, impaired neuroendocrine counter-regulation to hypoglycaemia is further supported by the high proportion of asymptomatic patients, which may be reflective of impaired hypoglycaemia awareness. The role of counter-regulatory hormones in PHH patients remains not fully understood.
Apart from the neuroendocrine milieu, effectiveness of hypoglycaemia counter-regulation depends on the capacity to provide glucose from the liver, also known as endogenous glucose production. In healthy humans, approximately 85% of the glucose produced by the liver during the initial 60-90min of hypoglycaemia is derived from liver glycogen. Postprandial hepatic glycogen stores, in turn, depend heavily on the hepatic glucose uptake following a meal. Postprandial hepatic glucose disposal and mobilization of hepatic glucose during hypoglycaemia in PHH patients remain unexplored to date.
There is currently no evidence, that increased insulin sensitivity is implicated in the pathophysiology of PHH. Conversely, previous studies suggested increased non-insulin dependent whole body glucose uptake in PHH compared to non-PHH in the light of similar or even decreased insulin sensitivity.
The primary objective of this study is to assess the neuro-endocrine response to hypoglycaemia in PHH vs. non-PHH post-gastric bypass individuals. The investigators hypothesize that the glucagon response to standardized and controlled hypoglycaemia is significantly diminished in PHH vs. non-PHH post-gastric bypass individuals. Involvement of non-surgical non-PHH controls and sleeve-gastrectomy non-PHH controls will allow to explore effects of bariatric surgery on counter-regulatory mechanisms to hypoglycaemia, including differences between procedures (gastric bypass vs. sleeve gastrectomy).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: