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Inflammatory Aspects of Glucose in Hyperlipidemia and Diabetes

Not Applicable
Completed
Conditions
Atherosclerosis
Leukocyte Activation Disorder
Type 2 Diabetes Mellitus
Familial Combined Hyperlipidemia
Interventions
Dietary Supplement: OGTT
Registration Number
NCT02130505
Lead Sponsor
Sint Franciscus Gasthuis
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
51
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
T2DMOGTTPatients with type 2 diabetes mellitus, defined as having met the diagnostic criteria as outlined by the World Health Organization
FCHOGTTPatients 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
FHOGTTPatients with familial hyperlipidemia, defined as having met the diagnostic criteria as outlined by the world Health Organization
Healthy controlsOGTTHealthy controls
Primary Outcome Measures
NameTimeMethod
Postprandial change in leukocyte activationarea under the curve during 2 hours

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.

Secondary Outcome Measures
NameTimeMethod
Correlation between chronic glycemia and leukocyte activationarea under the curve during 2 hours

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.

Correlation between acute glycemia and leukocyte activationarea under the curve during 2 hours

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.

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