Incretins and Metabolism

The Extrapancreatic Metabolic Effects of Incretin Hormones

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01607944

Enrollment

Registered

2012-05-30

Start date

2012-04-30

Completion date

2014-12-31

Last updated

2014-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes

Brief summary

Incretin hormones (GLP-1 and GIP) have insulin secretory effects on the pancreas that are glucose dependent. Extrapancreatic effects of incretin hormones are reported, however the glucose dependency of these effects have not been examined. In type 2 diabetes, pancreatic endocrine function and incretin metabolism are impaired. The investigators hypothesize that extrapancreatic effects of incretin hormones are glucose depedent and dysregulated in subjects with type 2 diabetes. Healthy control subjects and type 2 diabetics will undergo pancreatic clamps. In brief, somatostatin will be infused to inhibit pancreatic endocrine function and basal levels of insulin, glucagon, and growth hormone will be replace via infusion. Metabolic flux will be studied during euglycemic and hyperglycemic stages of the pancreatic clamp. Each subject will undergo 3 trials involving the co-infusion of either saline(Control Trial), GLP-1, or GIP. Glucose metabolism will be assessed using 13C-glucose stable isotope methodology combined with indirect calorimetry and expired breath isotope ratio analysis. Blood flow and flow-mediated dilation will be measured using ultrasound Doppler. Skeletal muscle and abdominal adipose biopsies will be taken to examine intracellular signalling.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

MALE

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* age 18-60 years * BMI 18-35 kg/m2 * NGT or T2DM as classified by ADA criteria

Exclusion criteria

* Insulin dependency * Smokers * History of or presentation with cardiovascular disease, cancer, and chronic hematological, renal, hepatic, pulmonary disease * Weight loss (\>2 kg in previous 6 months) * Physical activity (\>150 mins/week)

Design outcomes

Primary

Measure	Time frame	Description
Glucose turnover	0, 1, 2, 3, 4 hours	Rates of appearance and disappearance (g/min) will be measured by examining \[6,6-2H2\]glucose enrichment in plasma.

Secondary

Measure	Time frame	Description
Blood flow and flow-mediated dilation	0, 1, 2, 3, 4 hours	—
Palmitate turnover and oxidation	0, 1, 2, 3, 4 hours	Rates of appearance and disappearance (g/min) will be measured by examining \[U13C\]palmitate enrichment in plasma. Rate of oxidation (g/min) will also be measured by examining 13C incorporation into CO2 in expired breath.

Countries

Denmark

Outcome results