Brief Summary
Type 2 diabetes is a chronic condition that affects the ability of the body to regulate glucose (sugar). When glucose levels are low, the liver can make glucose to increase levels in the body. This important process is called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to coordinate this process by communicating with the liver through potassium channels. Control of EGP can be impaired in people with type 2 diabetes, which may contribute to the high levels of glucose seen in these individuals.
The purpose of this study is to understand how activating these potassium channels in the control centers of the brain with a medication called diazoxide might inhibit the amount of glucose made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn causes hyperglycemia (high levels of sugar in the blood) that leads to diabetes complications.
The purpose of this study is to understand how activating these potassium channels in the control centers of the brain with a medication called diazoxide might inhibit the amount of glucose made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn causes hyperglycemia (high levels of sugar in the blood) that leads to diabetes complications.
Brief Title
Central Mechanisms That Regulate Glucose Metabolism in Humans
Detailed Description
In this study, the investigators will study healthy participants through a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Endogenous glucose production (the production of sugar by the liver) will be measured in patients given diazoxide (a medication that activates potassium channels in the brain that may affect glucose production in the liver through brain-liver signaling), compared with when a placebo is given.
All experiments will consist of 240 min insulin/somatostatin (250 μg/hr) infusions with replacement of glucoregulatory hormones (glucagon 1 ng/kg·min; growth hormone 3 ng/kg·min). Throughout the study, the plasma glucose concentration will be maintained at basal levels ( \~90 mg/dl). This will be attained by infusion of insulin at adequate rates to maintain normoglycemia without requiring glucose infusion. Primed continuous infusions of High-performance liquid chromatography-purified \[3-3H\]-glucose will be initiated at t=0 (21.6 μCi bolus, then 0.15 μCi/min), to measure glucose fluxes. All infusions will be stopped at t=240 min. From t=0 to t=240 min, blood samples will be obtained for determinations of plasma glucose, insulin, glucagon, C-peptide, cortisol, growth hormone, free fatty acids (FFA), glycerol, and lactate, and for 3-3H-glucose determinations.
This registration is exclusive to Aim 1 of the study protocol, which determined the effect of diazoxide on hepatic glucose production in nondiabetic, healthy, young individuals under fixed hormonal conditions. Euglycemic (90 mg/dl x 4 hours) pancreatic clamp studies (n= 10), with either saline or diazoxide infusion.
All experiments will consist of 240 min insulin/somatostatin (250 μg/hr) infusions with replacement of glucoregulatory hormones (glucagon 1 ng/kg·min; growth hormone 3 ng/kg·min). Throughout the study, the plasma glucose concentration will be maintained at basal levels ( \~90 mg/dl). This will be attained by infusion of insulin at adequate rates to maintain normoglycemia without requiring glucose infusion. Primed continuous infusions of High-performance liquid chromatography-purified \[3-3H\]-glucose will be initiated at t=0 (21.6 μCi bolus, then 0.15 μCi/min), to measure glucose fluxes. All infusions will be stopped at t=240 min. From t=0 to t=240 min, blood samples will be obtained for determinations of plasma glucose, insulin, glucagon, C-peptide, cortisol, growth hormone, free fatty acids (FFA), glycerol, and lactate, and for 3-3H-glucose determinations.
This registration is exclusive to Aim 1 of the study protocol, which determined the effect of diazoxide on hepatic glucose production in nondiabetic, healthy, young individuals under fixed hormonal conditions. Euglycemic (90 mg/dl x 4 hours) pancreatic clamp studies (n= 10), with either saline or diazoxide infusion.
Completion Date
Completion Date Type
Actual
Conditions
Type 2 Diabetes
Glucose Metabolism Disorders
Glucose, High Blood
Eligibility Criteria
Inclusion Criteria:
* Healthy volunteers
* Be no more than 140% of body weight
* No concurrent illnesses
Exclusion Criteria:
* No clinical history or laboratory evidence of hyperlipidemia (LDL cholesterol \< 160 mg/dL)
* Clinical history of Hypertension
* Clinical history of Heart disease
* Clinical history of Cerebrovascular disease
* Clinical history of Seizures
* Clinical history of Bleeding disorders
* Clinical history of Muscle disease
* Smokers
* Mentally disabled persons
* Prisoners
* Pregnancy
* Clinical history of ethanol or drug or toxin exposure which could be associated with neuropathy
* Subjects incapable of giving voluntary informed consent
* History of bleeding disorder
* Clinical history of prolonged Prothrombin Time (PT) or Partial Thromboplastin Time
* Healthy volunteers
* Be no more than 140% of body weight
* No concurrent illnesses
Exclusion Criteria:
* No clinical history or laboratory evidence of hyperlipidemia (LDL cholesterol \< 160 mg/dL)
* Clinical history of Hypertension
* Clinical history of Heart disease
* Clinical history of Cerebrovascular disease
* Clinical history of Seizures
* Clinical history of Bleeding disorders
* Clinical history of Muscle disease
* Smokers
* Mentally disabled persons
* Prisoners
* Pregnancy
* Clinical history of ethanol or drug or toxin exposure which could be associated with neuropathy
* Subjects incapable of giving voluntary informed consent
* History of bleeding disorder
* Clinical history of prolonged Prothrombin Time (PT) or Partial Thromboplastin Time
Inclusion Criteria
Inclusion Criteria:
* Healthy volunteers
* Be no more than 140% of body weight
* No concurrent illnesses
* Healthy volunteers
* Be no more than 140% of body weight
* No concurrent illnesses
Gender
All
Gender Based
false
Keywords
Type 2 Diabetes
Diabetes
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
45 Years
Minimum Age
21 Years
NCT Id
NCT01028846
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2006-414
Overall Status
Terminated
Phases
Phase 4
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Central Mechanisms That Regulate Glucose Metabolism in Humans
Primary Outcomes
Outcome Description
Rate of EGP (a measure of the body's production of sugar) was measured using analysis of blood samples taken throughout the pancreatic clamp procedure under various treatment conditions (e.g., diazoxide or placebo) by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar). Rates were summarized by treatment (Diazoxide or Placebo) in mg/kg/min sing basic descriptive statistics.
Outcome Measure
Rate of Endogenous Glucose Production (EGP)
Outcome Time Frame
Final 60 minutes (t=180-240 minutes) of the pancreatic clamp, 6-7 hours after dosing
Secondary Ids
Secondary Id
R01DK069861
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
45
Minimum Age Number (converted to Years and rounded down)
21
Investigators
Investigator Type
Principal Investigator
Investigator Name
Meredith Hawkins
Investigator Email
meredith.hawkins@einsteinmed.org
Investigator Phone
718-430-3186