Ignite Creation Date:
2024-05-06 @ 2:56 AM
Last Modification Date:
2024-10-26 @ 11:26 AM
Study NCT ID:
NCT02169518
Status:
RECRUITING
Last Update Posted:
2023-04-12
First Post:
2014-06-19
Brief Title:
Paraoxonase and HDL Qualities in Glycaemia and Inflammation
Sponsor:
Manchester University NHS Foundation Trust
Organization:
Manchester University NHS Foundation Trust
Study Overview
Official Title:
Changes in Paraoxonase Activity HDL Properties Inflammatory Markers and Corneal Innervation in Post-bariatric Surgery Patients Type 1 Diabetics With and Without Nephropathy Type 2 Diabetics and During an Oral Glucose Tolerance Test
Status:
RECRUITING
Status Verified Date:
2023-04
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:
PON1
Brief Summary:
The incidence of coronary heart disease CHD is significant in the super-obese and diabetics
Inflammation is believed to play an important part in the development of CHD and the large collection of abdominal fat in the obese person is a vast source of inflammation Diabetics have abnormal glucose and cholesterol metabolism which ultimately compromise their bodies circulatory system and nerve function
Cholesterol plays a vital role in CHD Low-density lipoprotein LDL particles carry cholesterol and deposit it in blood vessel walls which become damaged as a result When LDL particles undergo changes chemically called oxidation or as a result of high circulating blood glucose called glycation they become more harmful to the body High-density lipoprotein HDL particles have a protective function in CHD Not only do they transport cholesterol away from the blood vessels to the liver to be broken down they have properties against oxidation and inflammation These properties are related to the activity of an enzyme on HDL called paraoxonase 1PON1
Super-obese patients are increasingly treated by weight-reducing surgery bariatric surgery In this study we examine whether weight loss following bariatric surgery results in reduced inflammatory state improved HDL function higher PON1 activity better control of blood glucose and less nerve damage
We will study PON1 activity inflammation and glucose control in patients with type 1 diabetes with and without kidney damage and type 2 diabetes We will also study the effects of rapidly rising blood glucose levels on PON1 and glycated LDL in patients undergoing oral glucose tolerance test
Inflammation is believed to play an important part in the development of CHD and the large collection of abdominal fat in the obese person is a vast source of inflammation Diabetics have abnormal glucose and cholesterol metabolism which ultimately compromise their bodies circulatory system and nerve function
Cholesterol plays a vital role in CHD Low-density lipoprotein LDL particles carry cholesterol and deposit it in blood vessel walls which become damaged as a result When LDL particles undergo changes chemically called oxidation or as a result of high circulating blood glucose called glycation they become more harmful to the body High-density lipoprotein HDL particles have a protective function in CHD Not only do they transport cholesterol away from the blood vessels to the liver to be broken down they have properties against oxidation and inflammation These properties are related to the activity of an enzyme on HDL called paraoxonase 1PON1
Super-obese patients are increasingly treated by weight-reducing surgery bariatric surgery In this study we examine whether weight loss following bariatric surgery results in reduced inflammatory state improved HDL function higher PON1 activity better control of blood glucose and less nerve damage
We will study PON1 activity inflammation and glucose control in patients with type 1 diabetes with and without kidney damage and type 2 diabetes We will also study the effects of rapidly rising blood glucose levels on PON1 and glycated LDL in patients undergoing oral glucose tolerance test
Detailed Description:
High-density lipoprotein HDL is known to have a protective role in cardiovascular disease Apart from transporting cholesterol from peripheral blood vessels back to the liver where it is processed HDL has the ability to inhibit chemical changes called oxidation to low-density lipoprotein LDL which would make the latter more toxic to the body HDL can also stop inflammatory particles from damaging the vessel walls The anti-oxidation and anti-inflammatory properties of HDL are associated with an enzyme on HDL called paraoxonase 1 PON1 It is not the level of measured HDL but the level of PON1 activity that is important in preventing cardiovascular disease PON1 activity determines the quality of HDL and the effect against vascular disease
Obese patients accumulate most of the fat within their abdomen termed visceral fat It is known that visceral fat produces large quantities of inflammatory particles so that obese patients have increased systemic inflammation and thus higher risk of vascular disease The impact of heightened inflammatory status on HDL functions and PON1 activity is not known Weight-reducing bariatric surgery can result in significant weight loss in obese patients It is unclear whether the weight loss is associated with improvement in HDL functions possible reversal of lipoprotein abnormalities and other physiological parameters We plan to study a population of obese patients scheduled to have bariatric surgery before and after the surgery and compare the results with a matching population of healthy control patients
Diabetic patients are at increased risk of developing cardiovascular disease HDL in diabetic patients is often dysfunctional Even though HDL levels are normal PON1 activity may be reduced LDL is able to interact with raised levels of blood glucose called glycation and become more harmful to the body Glycation of lipoproteins associated with PON1 may affect PON1 activity We plan to study glycated lipoproteins and PON1 activity in a population of diabetic patients who have either type 1 or type 2 diabetes Some of the type 1 diabetics will have diabetic kidney disease these patients are known to be particularly at high risk of cardiovascular complications We also plan to recruit a cohort of patients who do not have diabetes but who have had an abnormal blood glucose test These patients will be having an oral glucose tolerance test OGTT which establishes whether they have diabetes During the OGTT patients are given an oral glucose load which results in a rapid rise in blood glucose We will see if this accelerated change in blood glucose level has any effects on the glycation of lipoproteins
Obese patients accumulate most of the fat within their abdomen termed visceral fat It is known that visceral fat produces large quantities of inflammatory particles so that obese patients have increased systemic inflammation and thus higher risk of vascular disease The impact of heightened inflammatory status on HDL functions and PON1 activity is not known Weight-reducing bariatric surgery can result in significant weight loss in obese patients It is unclear whether the weight loss is associated with improvement in HDL functions possible reversal of lipoprotein abnormalities and other physiological parameters We plan to study a population of obese patients scheduled to have bariatric surgery before and after the surgery and compare the results with a matching population of healthy control patients
Diabetic patients are at increased risk of developing cardiovascular disease HDL in diabetic patients is often dysfunctional Even though HDL levels are normal PON1 activity may be reduced LDL is able to interact with raised levels of blood glucose called glycation and become more harmful to the body Glycation of lipoproteins associated with PON1 may affect PON1 activity We plan to study glycated lipoproteins and PON1 activity in a population of diabetic patients who have either type 1 or type 2 diabetes Some of the type 1 diabetics will have diabetic kidney disease these patients are known to be particularly at high risk of cardiovascular complications We also plan to recruit a cohort of patients who do not have diabetes but who have had an abnormal blood glucose test These patients will be having an oral glucose tolerance test OGTT which establishes whether they have diabetes During the OGTT patients are given an oral glucose load which results in a rapid rise in blood glucose We will see if this accelerated change in blood glucose level has any effects on the glycation of lipoproteins
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None