Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes, incretin, beta-cell function, glucolipotoxicity, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide
Brief summary
Elevations of blood glucose and lipid are thought to be deleterious to the insulin secretory function of the pancreas. This is known as glucolipotoxicity. However, few studies have examined this in detail. This investigation will examine pancreatic insulin secretory function in physiological models of glucolipotoxicity such as obese and type 2 diabetic individuals. Furthermore, healthy subjects will undergo 24 hour infusion of glucose or Intralipid to induce experimental models of glucolipotoxicity. Insulin secretion in response to intravenous infusions of glucose, GLP-1, GIP, and arginine and in response to meal ingestion, will be examined. the investigators hypothesize that experimental glucolipotoxicity will impairs pancreatic insulin secretory function to levels akin to that seen in type 2 diabetics.
Interventions
PROCEDUREGlucotoxicity
Glucose will be infused intravenously for a 24 hour period to raise blood glucose concentrations 5 mM above basal.
PROCEDURELipotoxicity
Intralipid and heparin will be infused intravenously for a 24 hour period to raise blood free fatty acid concentrations to approximately 1 mM.
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* normal glucose tolerance based on screening OGTT or * diagnosed type 2 diabetic (confirmed with OGTT)
Exclusion criteria
* insulin dependent diabetes * age \<18 or \>65 years * BMI \<20 or \> 35 kg/m2 * evidence of hematological, pulmonary, hepatic, renal, or cardiovascular disease * actively undergoing weight-loss (\>2kg change in last 6 months) * bariatric surgery (gastric by-pass or banding) * pregnancy * smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Secretion | 24 hours | Insulin secretion will be assessed in response to intravenous infusions of glucose, GLP-1, GIP, and arginine, and in response to meal ingestion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 24 hours | Glucose kinetics will be assesed using \[6,6-2H2\]glucose. Rate of glucose disappearance during glucose infusion will be quantified per unit of plasma insulin to derive an estimate of insulin sensitivity. |
| Plasma Cytokines (IL-6, TNF, IL-1beta, IL-1ra) | 24 hours | Cytokines will be measured in plasma: IL-6, TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-8, IL-10, Interferon gamma. Peripheral blood mononuclear cells will be isolated. |
Countries
Denmark
Outcome results
None listed