Endothelial Function in Patients With Type 2 Diabetes Versus Healthy Subjects (EndoPat)

Effect of Hyperinsulinemia and Postprandial Metabolic Changes on Endothelial Function in Patients With Type 2 Diabetes Versus Healthy Subjects

The aim of the study is to evaluate the effect of hyperinsulinemia and postprandial changes in plasma glucose and lipids concentrations on the endothelial function together with other metabolic parameters in patients with type 2 diabetes (T2D) and in healthy subjects.

Hypothesis:

Different changes in endothelial function to acute in vivo induced hyperinsulinemia and after the meal test will be found in patients with T2D compared to healthy subjects.

A significant relationships between insulin sensitivity, selected adipokines intramyocellular fat content, hepatic fat content and high energy phosphates in soleus muscle will be documented in both groups.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance; Type 2 Diabetes
• Intervention / Treatment: Other: mixed meal; Other: Acute in vivo induced hyperinsulinemia

Detailed Description

30 patients with T2D and 30 healthy control subjects will be examined on an outpatient basis. The following examination will be carried out in each subject after 12 hrs fasting:

• Hyperinsulinaemic euglycemic clamp study lasting 4 hours combined with indirect calorimetry and biopsy of subcutaneous adipose tissue and muscle aspiration biopsy
• Meal test:Plasma glucose, immunoreactive insulin, plasma lipids, oxidative stress markers and gastrointestinal peptides measured in response to a standard meal(at times 0´,30´,60´,120´,180´)
• At the beginning and after 120 minutes during the meal test and clamp peripheral microvascular endothelial function will be measured using EndoPat(Itamar Medical)
• Proton and phosphorus magnetic resonance spectroscopy(MRS).
• Dual Energy X-ray Absorptiometry(DXA) scanning to measure body composition.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czech Republic
  • Prague, Czech Republic, 140 21
    • Diabetes Center, Institute of Clinical and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Patients with T2D:

Inclusion criteria -

1. Men and women aged 30-65 years
2. Body Mass Index in the range of 25 - 45(kg/m2)
3. Type 2 diabetes mellitus for at least one year
4. Treatment of T2D: diet or oral antidiabetic agents (stable drug therapy at least 3 months before the trial

5. The presence of metabolic syndrome - any three of the following symptoms:

   1. Abdominal obesity - waist circumference in men >102 cm, in women >88 cm
   2. Diagnosis and treatment of type 2 diabetes
   3. Raised blood pressure (BP): systolic BP > 130 mm Hg or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension
   4. Reduced HDL cholesterol in men < 1 mmol/l, in women < 1,3 mmol/l (or treatment)
   5. Raised triglycerides > 1,7 mmol/l (or treatment)

4. HbA1c ≥ 42 a ≤100 mmol/mol

Exclusion criteria -

1. Type 1 diabetes mellitus
2. Unstable drug therapy at least 3 month before the trial
3. Pregnancy, breast feeding or trying to become pregnant
4. Alcoholism or drug use
5. Presence of other medical condition, which occurs during physical examination, laboratory tests, including pulmonary, neurological or inflammatory disease, which would be considered by the examiner to distort the consistency of data

Healthy subjects:

Inclusion criteria -

1. Men and women aged 30-65 years
2. Body Mass Index 25-45 (kg/m2)

3. Absence of metabolic syndrome - not more than any two of the following symptoms:

   1. Abdominal obesity - waist circumference in men >102 cm, in women >88 cm
   2. Diagnosis and treatment of type 2 diabetes or raised fasting plasma glucose level (FPG >5,6 mmol/l)
   3. Raised blood pressure (BP): systolic BP >130 mm Hg or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension
   4. Reduced HDL cholesterol in men <1 mmol/l, in women <1,3 mmol/l(or treatment)
   5. Raised triglycerides > 1,7 mmol/l (or treatment)

Exclusion criteria -

1. Diabetes or impaired glucose tolerance (HbA1c ≥40 mmol/mol and/or FPG >5,6 mmol/l), diagnosed diabetes in first-line relatives
2. Pregnancy, breast feeding or trying to become pregnant
3. Alcoholism or drug use
4. Presence of other medical condition, which occurs during physical examination, laboratory tests, including pulmonary, neurological or inflammatory disease, which would be considered by the examiner to distort the consistency of data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with type 2 diabetes; 30 individuals with type 2 diabetes Intervention: mixed meal, acute in vivo induced hyperinsulinemia	Other: mixed meal; Baguette Cheese Gourmet (Crocodile: 180g, energy 452.8 Kcal, composition: carbohydrates 49,2 g (44,55%), proteins 18,5 g (16,74%), lipids 18,8 g (38,7%), of which saturated 6,8 g, monounsaturated 6,0 g, polyunsaturated 5,0 g.; Other: Acute in vivo induced hyperinsulinemia; Hyperinsulinemic (1mU/kg/min) euglycemic clamp 3 hours long
Active Comparator: Healthy subjects; 30 healthy men and women with no metabolic syndrome Intervention: mixed meal, acute in vivo induced hyperinsulinemia	Other: mixed meal; Baguette Cheese Gourmet (Crocodile: 180g, energy 452.8 Kcal, composition: carbohydrates 49,2 g (44,55%), proteins 18,5 g (16,74%), lipids 18,8 g (38,7%), of which saturated 6,8 g, monounsaturated 6,0 g, polyunsaturated 5,0 g.; Other: Acute in vivo induced hyperinsulinemia; Hyperinsulinemic (1mU/kg/min) euglycemic clamp 3 hours long

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of endothelial function (measured by EndoPat)	at 0 and after 120 minutes during the clamp and 120 minutes after meal ingestion	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gastrointestinal peptides concentrations	0, 30, 60, 120, 180 minutes after meal ingestion	180 minutes
Changes in oxidative stress markers	at 0 and after 120 minutes after meal ingestion	120 minutes
Insulin sensitivity measured as glucose disposal during clamp		4 hours

Collaborators and Investigators

• Sponsor: Institute for Clinical and Experimental Medicine
• Investigators: Principal Investigator: Terezie Pelikanova, Prof, MD, Diabetes Center, Institute of Clinical and Experimental Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 16, 2013
• First Posted (Estimate): September 19, 2013

Study Record Updates

• Last Update Posted (Estimate): March 7, 2016
• Last Update Submitted That Met QC Criteria: March 3, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Oxidative stress; Insulin Resistance; Endothelial function; Hyperglycemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: G981