Postprandial Dysmetabolism (PPDysMet)

Postprandial Dysmetabolism - The Effects of Monounsaturated vs. Saturated Lipids on Lipid and Carbohydrate Metabolism and Inflammation in Healthy 1st Degree Relatives of Patients With Type 2 Diabetes.

Type 2 diabetes (T2D) is a common disease associated with multiple complications and an increased risk of cardiovascular morbidity and mortality. Also, it is a heavy economical burden on society. 1st degree relatives of patients with T2D have an increased risk of developing T2D. This risk can be modified by the ingested diet: a traditional north European diet rich in saturated fat increases the risk, while a Mediterranean diet rich in monounsaturated fat protects from development of T2D and cardiovascular disease.

T2D is a part of the metabolic syndrome consisting of T2D, hypertension, adipositas, dyslipidemia and steatosis. The pathogenesis of the metabolic syndrome is partly explained by fasting dyslipidemia, postprandial dysmetabolism (derangement of lipid and carbohydrate metabolism) and impaired metabolic flexibility. Partly, it can be explained by a chronic low-grade inflammation in peripheral tissue. The dysmetabolism and the inflammation are correlating entities exerting their influence through common biochemical pathways. This is established in patients with T2D, but sparsely studied in healthy relatives of patients with T2D.

In this project, the investigators will study postprandial dysmetabolism, inflammation, oxidative stress, adipocytokines, incretins, appetite regulating hormones and the expression of the genes involved in above mentioned. We will compare healthy 1st degree relatives of patients with T2D with healthy controls with no family history of T2D and look into differences in the response to meal stimulation with respectively saturated and monounsaturated fat. The subjects will be thoroughly examined with a hyperinsulinaemic euglycaemic clamp and a DEXA scan. Before and after the meal stimulation, we will perform calorimetry (in order to determine the metabolic rates), take blood samples and perform muscle and fat tissue biopsies. The biopsies will be used for studies of a vast number of genes.

The project will give us new valuable knowledge about the interaction between the intermediate metabolism and the innate immune system and the early pre-diabetic changes in the 1st degree relatives of patients with T2D. In the long run, the project will contribute to improving our guidance and treatment of persons at risk of developing T2D.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Meal challenge; Dietary supplement: Meal challenge

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relatives: Minimum 2 1st degree relatives with type 2 diabetes or 1 one 1st degree relative with type 2 diabetes and history of gestational diabetes.
• Controls: No family history of type 2 diabetes and fasting blood glucose <6.0 mM.

Exclusion Criteria:

• Cardiovascular, renal or endocrine disease.
• Treatment with steroids.
• Psychiatric history.
• Abuse of alcohol or narcotics.
• Smoking.
• Pregnancy or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Relatives to patients with type 2 diabetes.	Dietary supplement: Meal challenge; Meal challenge with a test meal rich on saturated fat.; Dietary supplement: Meal challenge; Meal challenge with a test meal rich on monounsaturated fat
ACTIVE_COMPARATOR: 2; Controls with no family history of type 2 diabetes.	Dietary supplement: Meal challenge; Meal challenge with a test meal rich on saturated fat.; Dietary supplement: Meal challenge; Meal challenge with a test meal rich on monounsaturated fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incremental AUC og the triglyceride response	6 hrs

Secondary Outcome Measures

Outcome Measure	Time Frame
Gene expression of genes involved in lipid metabolism and inflammation	6 hrs

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Diabetesforeningen

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ANTICIPATED): August 1, 2011

Study Registration Dates

• First Submitted: December 19, 2008
• First Submitted That Met QC Criteria: December 19, 2008
• First Posted (ESTIMATE): December 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 8, 2011
• Last Update Submitted That Met QC Criteria: March 7, 2011
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Relatives; Postprandial inflammation; Meal challenge; Postprandial dysmetabolism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CERN-PPDysMet-AP