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.

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.

Atherosclerosis, Leukocyte Activation Disorder, Type 2 Diabetes Mellitus, Familial Combined Hyperlipidemia

Patients with type 2 diabetes mellitus, defined as having met the diagnostic criteria as outlined by the World Health Organization

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

Patients with familial hyperlipidemia, defined as having met the diagnostic criteria as outlined by the world Health Organization

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.

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.

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.

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

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.