Diabetes After Total Pancreatectomy
Conditions
Keywords
glucagon
Brief summary
The overall objective of this study is to investigate whether hypoglycaemia (the most potent stimulus of pancreatic glucagon secretion) affects the secretion of gut-derived glucagon in totally pancreatectomized patients.
Detailed description
The investigators want to assess the plasma glucagon response to insulin-induced hypoglycaemia in totally pancreatectomised patients and at the same time evaluate whether hypoglycaemia affects a range of other products from endocrine cells in the gastrointestinal tract including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon-like peptide-2 (GLP-2), oxyntomodulin and peptide YY (PYY). Furthermore the investigators will evaluate how hypoglycaemia in these patients affects other counter-regulatory mechanisms including plasma responses of the hormones adrenaline, noradrenaline, growth hormone and cortisol as well as the rate of gastric emptying rate (which under normal circumstances accelerates during hypoglycaemia) during an oral glucose tolerance test (OGTT).
Interventions
OTHEROral glucose tolerance test
50 grams OGTT
OTHERClamp experiment
insulin-induced hypoglycaemic clamp followed by an 50 grams OGTT
Sponsors
University of Copenhagen
University Hospital, Gentofte, Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
12 totally pancreatectomized patients and 12 healthy control subjects
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Pancreatectomised patients * Caucasian above 30 years of age who have undergone total pancreatectomy * Blood haemoglobin \>7.0 mmol/l for males and \>6.5 mmol/l for females Non-diabetic control subjects * Normal fasting plasma glucose and normal HbA1c (according to the World Health Organization (WHO) criteria) * Normal blood haemoglobin * Caucasian above 30 years of age * BMI (body mass index) 17-30 * Informed consent
Exclusion criteria
Pancreatectomised patients * Pancreatectomy within the last 3 months * Ongoing chemotherapy or chemotherapy within the last 3 months * Previous or ongoing treatment with GLP-1 receptor agonists or dipeptidyl peptidase 4 (DPP-4) inhibitors * Inflammatory bowel disease * Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy * Nephropathy (eGFR\<60 and/or albuminuria) * Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>3 × normal values) * Severe lung disease * Pregnancy and/or breastfeeding * Age above 85 years * Uncontrolled hypertension and/or significant cardiovascular disease * Any condition that the investigator feels would interfere with trial participation Non-diabetic control subjects * Diabetes or prediabetes (according to WHO criteria) * First-degree relatives with diabetes * Inflammatory bowel disease * Gastrointestinal resection and/or ostomy * Nephropathy (serum creatinine \>150 µmol/l and/or albuminuria) * Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum ALAT and/or serum ASAT \>3 × normal values) * Severe lung disease * Pregnancy and/or breastfeeding * Age above 85 years * Uncontrolled hypertension and/or significant cardiovascular disease * Any condition that the investigator feels would interfere with trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| p-glucagon | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes | Plasma glucagon excursions measured as incremental area under the curve (iAUC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| p-glucose | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes | plasma glucose excursions measured as incremental area under the curve (iAUC) |
| GIP, GLP-1, GLP-2, GIP, oxyntomodulin, ghrelin, peptide YY, gastrin | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes | excursions in Gut hormones measured as incremental area under the curve (iAUC) |
| catecholamines | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes | p-adrenaline and p-noradrenaline, excursions measured as incremental area under the curve (iAUC) |
| cortisol | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes | p-cortisol excursions measured as incremental area under the curve (iAUC) |
| growth hormone | -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes | p-growth hormone excursions measured as incremental area under the curve (iAUC) |
Countries
Denmark
Outcome results
None listed