Ignite Creation Date:
2024-05-06 @ 2:21 AM
Last Modification Date:
2024-10-26 @ 11:17 AM
Study NCT ID:
NCT02023489
Status:
UNKNOWN
Last Update Posted:
2017-03-23
First Post:
2013-12-18
Brief Title:
Lipid and Glycogen Metabolism in Patients With Impaired Glucose Tolerance and Calcium Sensing Receptor Mutations
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Myocardial Lipid and Glycogen Metabolism Cardiac Function in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus and Calcium Sensing Receptor Mutations - A Cross Sectional Magnetic Resonance Spectroscopy and Imaging Study
Status:
UNKNOWN
Status Verified Date:
2017-03
Last Known Status:
RECRUITING
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:
RISC_7T
Brief Summary:
Background
Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure in part due to diabetic cardiomyopathy However the association between intracellular lipid accumulation and myocardial functional impairment is likely more complex than originally imagined Recent studies suggest that not fat per se but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction
In addition skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing
Hypothesis
In addition to total ectopic lipid deposition in the myocardium myocardial lipid composition ie the relative abundance of saturated and unsaturated fatty acids and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy
Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene FHH
Aims
Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy
Characterization of the metabolic interplay between the myocardium skeletal muscle liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation
Methods
1H13C and 31P magnetic resonance spectroscopy and imaging for measurements of myocardial skeletal and liver lipid and glycogen content abdominal adipose tissue distribution and composition ATP synthesis and myocardial functional parameters
Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues myocardium skeletal muscle liver adipose tissue
Hyperinsulinemic-hyperglycemic glucose clamp HHC with enrichment of the infused glucose with the stable isotope 1-13Cglucose to trace the incorporation of circulating glucose into myocardial glycogen
in healthy insulin sensitive volunteers prediabetic insulin resistant volunteers with impaired glucose tolerance healthy subjects patients suffering from type 2 diabetes mellitus patients suffering from type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor
Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure in part due to diabetic cardiomyopathy However the association between intracellular lipid accumulation and myocardial functional impairment is likely more complex than originally imagined Recent studies suggest that not fat per se but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction
In addition skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing
Hypothesis
In addition to total ectopic lipid deposition in the myocardium myocardial lipid composition ie the relative abundance of saturated and unsaturated fatty acids and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy
Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene FHH
Aims
Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy
Characterization of the metabolic interplay between the myocardium skeletal muscle liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation
Methods
1H13C and 31P magnetic resonance spectroscopy and imaging for measurements of myocardial skeletal and liver lipid and glycogen content abdominal adipose tissue distribution and composition ATP synthesis and myocardial functional parameters
Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues myocardium skeletal muscle liver adipose tissue
Hyperinsulinemic-hyperglycemic glucose clamp HHC with enrichment of the infused glucose with the stable isotope 1-13Cglucose to trace the incorporation of circulating glucose into myocardial glycogen
in healthy insulin sensitive volunteers prediabetic insulin resistant volunteers with impaired glucose tolerance healthy subjects patients suffering from type 2 diabetes mellitus patients suffering from type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor
Detailed Description:
Background
1 Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure in part due to diabetic cardiomyopathy Ectopic intracellular lipid accumulation and impaired glycogen metabolism in skeletal muscle and liver and are closely associated with metabolic impairment in insulin resistant subjects and patients with diabetes mellitus Recent evidence suggests that increased myocardial lipid accumulation might contribute to the development of myocardial dysfunction by direct toxic effects lipotoxicity However the association between intracellular lipid accumulation and myocardial functional impairment is likely more complex than originally imagined Recent studies suggest that not fat per se but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction
In addition carbohydrates stored as glycogen in muscle cells serve as readily available energy supply for contracting muscle Skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing
2 Heterozygote inherited inactivating mutations in Calcium Sensing Receptor CaSR-gene leads to familiar hypocalciuric hypercalcemia FHH specified by mildly elevated plasma Ca and parathyroid hormone concentrations whereas urine Ca excretion is inadequately low However in addition to the parathyroid gland CaSR is expressed in various tissues including the endocrine pancreas and the heart So far it is unknown whether the endocrine function of the pancreas or myocardial morphology andor function is altered in patients with FHH
3 Altered hepatic energy metabolism might play an important role in the development of type 2 diabetes Additionally the lack of insulin delivery to the liver via the portal vein in type 1 diabetes might alter liver ATP synthesis Therefore we aim to investigate hepatic energy metabolism non invasively with MRS
Hypothesis
In addition to total ectopic lipid deposition in the myocardium myocardial lipid composition ie the relative abundance of saturated and unsaturated fatty acids and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy
Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene FHH
Hepatic and cardiac lipid and energy metabolism is altered in T1DM
Aims
Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy
Characterization of the metabolic interplay between the myocardium skeletal muscle liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation
Methods
1H13C and 31P magnetic resonance spectroscopy MRS and imaging MRI for measurements of myocardial skeletal and liver lipid and glycogen content abdominal adipose tissue distribution and composition ATP synthesis and myocardial functional parameters
Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues myocardium skeletal muscle liver adipose tissue
Hyperinsulinemic-hyperglycemic glucose clamp HHC with enrichment of the infused glucose with the stable isotope 1-13Cglucose to trace the incorporation of circulating glucose into myocardial glycogen
in healthy insulin sensitive volunteers prediabetic insulin resistant volunteers with impaired glucose tolerance healthy subjects patients suffering from type 2 diabetes mellitus type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor
Relevance
Despite intensive treatment of cardiovascular risk factors heart diseases are still the main cause of death in diabetic patients Thus elucidation of mechanisms that link impaired lipid andor glycogen metabolism and energy homeostasis to the development of heart failure appears to be crucial for the development of novel treatment strategies Additionally hepatic steatosis plays a challenging emerging role in the treatment of liver disease wherefore further insight in hepatic energy metabolism in various endocrine disease is urgently needed
1 Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure in part due to diabetic cardiomyopathy Ectopic intracellular lipid accumulation and impaired glycogen metabolism in skeletal muscle and liver and are closely associated with metabolic impairment in insulin resistant subjects and patients with diabetes mellitus Recent evidence suggests that increased myocardial lipid accumulation might contribute to the development of myocardial dysfunction by direct toxic effects lipotoxicity However the association between intracellular lipid accumulation and myocardial functional impairment is likely more complex than originally imagined Recent studies suggest that not fat per se but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction
In addition carbohydrates stored as glycogen in muscle cells serve as readily available energy supply for contracting muscle Skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing
2 Heterozygote inherited inactivating mutations in Calcium Sensing Receptor CaSR-gene leads to familiar hypocalciuric hypercalcemia FHH specified by mildly elevated plasma Ca and parathyroid hormone concentrations whereas urine Ca excretion is inadequately low However in addition to the parathyroid gland CaSR is expressed in various tissues including the endocrine pancreas and the heart So far it is unknown whether the endocrine function of the pancreas or myocardial morphology andor function is altered in patients with FHH
3 Altered hepatic energy metabolism might play an important role in the development of type 2 diabetes Additionally the lack of insulin delivery to the liver via the portal vein in type 1 diabetes might alter liver ATP synthesis Therefore we aim to investigate hepatic energy metabolism non invasively with MRS
Hypothesis
In addition to total ectopic lipid deposition in the myocardium myocardial lipid composition ie the relative abundance of saturated and unsaturated fatty acids and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy
Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene FHH
Hepatic and cardiac lipid and energy metabolism is altered in T1DM
Aims
Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy
Characterization of the metabolic interplay between the myocardium skeletal muscle liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation
Methods
1H13C and 31P magnetic resonance spectroscopy MRS and imaging MRI for measurements of myocardial skeletal and liver lipid and glycogen content abdominal adipose tissue distribution and composition ATP synthesis and myocardial functional parameters
Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues myocardium skeletal muscle liver adipose tissue
Hyperinsulinemic-hyperglycemic glucose clamp HHC with enrichment of the infused glucose with the stable isotope 1-13Cglucose to trace the incorporation of circulating glucose into myocardial glycogen
in healthy insulin sensitive volunteers prediabetic insulin resistant volunteers with impaired glucose tolerance healthy subjects patients suffering from type 2 diabetes mellitus type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor
Relevance
Despite intensive treatment of cardiovascular risk factors heart diseases are still the main cause of death in diabetic patients Thus elucidation of mechanisms that link impaired lipid andor glycogen metabolism and energy homeostasis to the development of heart failure appears to be crucial for the development of novel treatment strategies Additionally hepatic steatosis plays a challenging emerging role in the treatment of liver disease wherefore further insight in hepatic energy metabolism in various endocrine disease is urgently needed
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