Inflammatory Aspects of Glucose in Hyperlipidemia and Diabetes (INFORM)

In this study, we will investigate both inflammatory systems in healthy volunteers and patients with T2DM on insulin therapy and hyperlipidemia (both familial hyperlipidemia (FH) and familial combined hyperlipidemia (FCH)) during an OGTT.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Atherosclerosis; Leukocyte Activation Disorder; Familial Combined Hyperlipidemia
• Intervention / Treatment: Dietary supplement: OGTT

Detailed Description

Cardiovascular disease (CVD) is number one killer in the Netherlands. Insulin resistance and dyslipideima are the main causes of CVD. Recently, we have shown that there is an acute leukocyte activation after an oral glucose tolerance test (OGTT) in patients with newly-diagnosed diabets mellitus type 2 (T2DM). Leukocyte activation is an important and obligatory aspect in the process of atherosclerosis. Complement system is another important inflammatory component in atherosclerosis, which becomes activated in the postprandial phase.

In this study, we will investigate both inflammatory systems in healthy volunteers and patients with T2DM on insulin therapy and hyperlipidemia (both familial hyperlipidemia (FH) and familial combined hyperlipidemia (FCH)) during an OGTT.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide written informed consent
• Aged 45-65 years
• BMI < 35 kg/m2

Exclusion Criteria:

• Emotionally and intellectually not capable to decide about participation in the study and the consequences of participation. Subjects who are not able to understand the patient information
• Diabetes mellitus treated with oral antidiabetic medicine
• Type 1 diabetes mellitus
• Peripheral artery and/or coronary disease
• Untreated hypertension
• Alcohol use > 2 units/day
• Aberrations in kidney, liver and thyroid function
• Use of any experimental medication within 6 months of the study
• The use of immunosuppressive drugs

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: T2DM; Patients with type 2 diabetes mellitus, defined as having met the diagnostic criteria as outlined by the World Health Organization	Dietary supplement: OGTT; Oral glucose tolerance test (OGTT) with 75 g of oral anhydrous glucose
Active Comparator: FCH; Patients with familial combined hyperlipidemia, defined as familial hyperlipidemia with a dominant inheritance pattern, elevated plasma apolipoprotein (apo) B concentrations (>1.2 g/L) and elevated triglyceride (TG) levels (>1.7 mmol/L) at the time of diagnosis	Dietary supplement: OGTT; Oral glucose tolerance test (OGTT) with 75 g of oral anhydrous glucose
Active Comparator: FH; Patients with familial hyperlipidemia, defined as having met the diagnostic criteria as outlined by the world Health Organization	Dietary supplement: OGTT; Oral glucose tolerance test (OGTT) with 75 g of oral anhydrous glucose
Active Comparator: Healthy controls	Dietary supplement: OGTT; Oral glucose tolerance test (OGTT) with 75 g of oral anhydrous glucose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial change in leukocyte activation	Leukocyte activation is determined by flow cytometry, using fluorescent labelled antibodies: FITC-conjugated anti-CD66b and PE-conjugated anti-CD11b, expressed in mean fluorescence intensity in arbitrary units. The difference in postprandial response, expressed as area under the curve, between patients with T2DM, FCH and healthy controls is determined using ANOVA.	area under the curve during 2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between chronic glycemia and leukocyte activation	To assess whether chronic hyperglycemia (HbA1c) correlates with postprandial leukocyte activation, correlation between HbA1c and postprandial leukocyte activation (area under the curve) will be determined for the total study group.	area under the curve during 2 hours
Correlation between acute glycemia and leukocyte activation	To assess whether acute hyperglycemia correlates with postprandial leukocyte activation, correlation between fasting glucose levels and postprandial leukocyte activation (area under the curve) will be determined for the total study group.	area under the curve during 2 hours

Collaborators and Investigators

• Sponsor: Sint Franciscus Gasthuis
• Investigators: Study Chair: Manuel Castro Cabezas, MD, PhD, Sint Franciscus Gasthuis

Publications and helpful links

General Publications

• de Vries MA, Alipour A, Klop B, van de Geijn GJ, Janssen HW, Njo TL, van der Meulen N, Rietveld AP, Liem AH, Westerman EM, de Herder WW, Cabezas MC. Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls. Metabolism. 2015 Feb;64(2):213-7. doi: 10.1016/j.metabol.2014.10.011. Epub 2014 Oct 16.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: April 21, 2014
• First Submitted That Met QC Criteria: May 1, 2014
• First Posted (Estimate): May 5, 2014

Study Record Updates

• Last Update Posted (Estimate): May 5, 2014
• Last Update Submitted That Met QC Criteria: May 1, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Diabetes Mellitus; Diabetes Mellitus, Type 2; Atherosclerosis; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipidemia, Familial Combined
• Other Study ID Numbers: NL17100.101.07