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Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

Information source: University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non-alcoholic Fatty Liver Disease

Intervention: Liver biopsy (Procedure); Pancreatic clamp (Other)

Phase: N/A

Status: Recruiting

Sponsored by: University Hospital, Gentofte, Copenhagen

Overall contact:
Filip K Knop, MD, PhD, Phone: +45 2683 0161, Email: filipknop@dadlnet.dk


The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.

Clinical Details

Official title: Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

Study design: Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome:

Urea synthesis

Endogenous glucose production

Plasma glucose level

Secondary outcome: Degree of steatosis

Detailed description: Hyperglucagonemia is a common condition in obesity, prediabetes and type 2 diabetes. It increases the hepatic glucose production, thus contributing to type 2-diabetic hyperglycemia. In the current study we wish to examine whether non-alcoholic fatty disease (NAFLD) results in hepatic glucagon resistance. This could result in hyperglucagonemia through a feedback mechanism acting on the level of pancreatic alpha cells. Cirrhosis and type 1 diabetes, respectively, has previously been shown to be associated with hepatic glucagon resistance but it has not been examined in relation to NAFLD in humans so far.


Minimum age: 25 Years. Maximum age: 80 Years. Gender(s): Both.


Inclusion Criteria:

- Normal fasting plasma glucose and HbA1c < 6. 0%

- Between 18. 5 and 25 kg/m2 or between 30 and 40 kg/m2

- Normal haemoglobin

- Normal coagulation factor II, VII and X, INR and thrombocytes

- Age above 25 years

- Informed consent

Exclusion Criteria:

- Diabetes

- Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)

- First-degree relatives with diabetes

- Nephropathy (eGFR < 60ml/min and/or albuminuria)

- Liver disease (ALAT and/or serum ASAT >2x normal values)

- Use of anticoagulative medicine like Clopidogrel og Warfarin

- Pregnancy and/or breastfeeding

- Age above 80 years

- Any condition that the investigator feels would interfere with trial participation

Locations and Contacts

Filip K Knop, MD, PhD, Phone: +45 2683 0161, Email: filipknop@dadlnet.dk

Center for Diabetes Research, Gentofte 2900, Denmark; Recruiting
Filip K Knop, MD, PhD, Phone: +45 2683 0161, Email: filipknop@dadlnet.dk
Malte Suppli, BSc, Phone: +45 3867 2463, Email: maltepalm@gmail.com
Additional Information

Related publications:

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Gromada J, Franklin I, Wollheim CB. Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007 Feb;28(1):84-116. Epub 2007 Jan 16. Review.

Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012 Jun;14(6):500-10. doi: 10.1111/j.1463-1326.2011.01549.x. Epub 2012 Jan 17.

Færch K, Pilgaard K, Knop FK, Hansen T, Pedersen O, Jørgensen T, Holst JJ. Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele. Diabetes Obes Metab. 2013 Jan;15(1):91-5. doi: 10.1111/j.1463-1326.2012.01675.x. Epub 2012 Sep 9.

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Starting date: January 2015
Last updated: January 12, 2015

Page last updated: August 23, 2015

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