The Metabolic Effects of Acute Hyperglycemia in Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to characterize the changes in amino acid, lipid and glucose metabolism in patients with type 2 diabetes exposed to acute hyperglycemia. Moreover we wish to assess the effect of acute hyperglycemia on cardiac output.

Detailed Description
-----------------
Cardiovascular disease is the main cause of death in modern Western societies. Obesity, diabetes and the metabolic syndrome are the main risk factors for cardiovascular disease. People with type 2 diabetes and no history of heart disease have a risk of myocardial infarction similar to the risk in non-diabetic patients with known heart disease. However, the causal relationship between obesity, diabetes and cardiovascular disease is unclear. Insulin resistance leads to many metabolic abnormalities, including high circulating levels of free fatty acids (FFA). FFA induces insulin resistance and may lead to beta cell failure. In addition FFA may directly worsen the metabolic and electrochemical performance of the working heart. Moreover it is still unclear how acute hyperglycemia affects cardiac output. In this study our purpose is to characterize the changes in amino acid, lipid and glucose metabolism in patients with type 2 diabetes exposed to acute hyperglycemia (blood glucose between 18 and 20 mmol/L) compared to the amino acid, lipid and glucose metabolism at a normal glucose level (blood glucose between 5 and 7 mmol/L). The results from the patients with type 2 diabetes will be compared with results from healthy controls examined in a fasting basal state. The patients must not suffer from any kind of serious heart disease and should be treated with insulin. Moreover we wish to compare cardiac output at high and normal blood glucose levels, respectively. Cardiac output will primarily be assessed by doppler echocardiography.

Official Title
-----------------
The Effect of Acute Hyperglycemia on Cardiac Output, Amino Acid, Lipid and Glucose Metabolism in Patients With Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Actrapid (human insulin)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written consent Age 40-75 years old BMI between 22 and 35 Type 2 diabetes treated with insulin (< 60 IE/day) Exclusion Criteria: Severe disease Severe cardiac disease

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Euglycemic<br>The patients will be examined with a blood glucose at around 5-7 mmol/L. | Drug: Actrapid (human insulin)<br>* On day one the patients will receive glucose and insulin in order to reach a blood sugar around 18 and 20 mmol/L and on day two the patients will receive glucose and insulin in order to have a blood sugar around 5 and 7 mmol/L. On both days amino acid, lipid and glucose metabolism will be assessed by means of whole body isotope dilution.<br>|
| Experimental: Hyperglycemic<br>The patients will be examined with a blood glucose at around 18-20 mmol/L | Drug: Actrapid (human insulin)<br>* On day one the patients will receive glucose and insulin in order to reach a blood sugar around 18 and 20 mmol/L and on day two the patients will receive glucose and insulin in order to have a blood sugar around 5 and 7 mmol/L. On both days amino acid, lipid and glucose metabolism will be assessed by means of whole body isotope dilution.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic changes |  | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function |  | 6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 diabetes, Dysregulation, Metabolism, Cardiac output