Hepatic Metabolic Changes in Response to Glucagon Infusion

Steno Diabetes Centers

Status

Completed

Conditions

Total Pancreatectomy

Diabetes Mellitus

Non-Alcoholic Fatty Liver Disease

Treatments

Drug: Glucagon

Drug: Saline

Study type

Interventional

Funder types

Other

Identifiers

NCT03526445

H-18003696

Details and patient eligibility

About

The objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure.

Full description

Most research has focused on the role of the pancreatic hormone, insulin, and insulin signalling (or lack of) in the development of NAFLD. However, increasing evidence suggest that the other major gluco-regulatory pancreatic hormone glucagon is also implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This, combined with observations of increased degree of hepatic steatosis in patients after total pancreatectomy, who are devoid of pancreatic glucagon and typically are lean and peripherally insulin sensitive, suggests that glucagon may play a hitherto unrecognised role in the pathophysiology of NAFLD.

The hypothesis of the study is that exogenously delivered glucagon will drive hepatic metabolism in a lipolytic direction and increase resting energy expenditure without affecting appetite and food intake.

The acute effects of exogeneous glucagon infusion on hepatic lipid metabolism will be evaluated in patients after total pancreatectomy (no endogenous pancreatic hormones), in patients with type 1 diabetes (no endogenous insulin production) and in healthy controls (preserved endogenous pancreatic hormones).

Enrollment

27 patients

Sex

All

Ages

30 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Pancreatectomised patients

Patients who have undergone total pancreatectomy
Caucasian between 30-80
Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
Informed consent

Patients with type 1 diabetes

Patients with C-peptide negative type 1 diabetes
Caucasian between 30-80
Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
Informed consent

Healthy controls

Normal fasting plasma glucose (< 7 mmol/l) and normal HbA1c (< 6.5 %) (30,31)
Normal blood haemoglobin (>8.3 mmol/l for males and >7.3 mmol/l for females)
Caucasian between 30-80
Informed consent

Exclusion criteria

All subjects

Inflammatory bowel disease
Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
Known liver disease (excluding non-alcoholic fatty liver disease)
Severe lung disease
Pregnancy and/or breastfeeding
Uncontrolled hypertension and/or significant cardiovascular disease
Treatment with drugs with potential steatogenic side-effects within three months prior to inclusion
Alcohol consumption above 21 units/week for men and 14 units/week for women
Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject.