the role of amylin in bone metabolism

Conditions: Bone Diseases, Metabolic; Type 1 Diabetes

Summary: the clinical study aims to investigate the effect of the intravenously administrated amylin analogue (pramlintide) on the circulating levels of c-terminal telopeptide of type i collagen (ctx-1) (a marker of bone resorption) and n-terminal propeptide of type i procollagen (p1np) (a marker of bone formation) in individuals with type 1 diabetes and matched healthy controls during fasting euglycemic conditions.

using a randomised double blinded placebo-controlled crossover design the investigators will evaluate the effects of the intravenously administrated amylin analogue (pramlintide) on circulating levels of ctx-1 and p1np in ten individuals with type 1 diabetes and ten healthy controls matched for age, gender and body mass index (bmi) during fasting and euglycemic conditions. each participant will receive double-blinded infusions of pramlintide (3 pmol/kg/min) and saline on two separate study days performed in randomised order. the primary endpoints are the relative changes in the plasma levels of p1np and ctx-1. the changes in plasma concentrations will be assessed by the total and incremental (baseline-subtracted) area under the curve for plasma ctx-1 and p1np as well as %-changes from baseline including nadir. the secondary endpoints encompass changes in plasma concentrations of calcium, parathyroid hormone (pth), alkaline phosphatase, osteocalcin, glucagon, insulin, c-peptide, glucose, glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 and glucagon-like peptide 2.

Eligibility criteria:
inclusion criteria type 1 diabetes: * caucasian ethnicity * age between 18 and 60 years * bmi between 18.5 and 27 kg/m2 * type 1 diabetes (diagnosed according to the criteria of the world health organization) with hba1c \<69 mmol/mol (\<8.5%) and * type 1 diabetes duration of 2-20 years * c-peptide negative (stimulated c-peptide ≤30 pmol/l) * treatment with a stable basal-bolus or insulin pump regimen for ≥3 months * normal vitamin d (\>50 nmol/l) * informed consent exclusion criteria type 1 diabetes: * anaemia (haemoglobin below normal range) * liver disease (alat and/or asat \>2 times normal values) or history of hepatobiliary disorder * nephropathy (egfr \<60 ml/min/1,73m2 and/or microalbuminuria) * microvascular complications except non-proliferative retinopathy * treatment with anti-osteoporosis medication or glucocorticoids * fractures within the last 6 months * for women: currently perimenopausal or postmenopausal * diseases affecting calcium metabolism (e.g. hypoparathyroidism, hyperparathyroidism, osteoporosis, vitamin d deficiency and cancer) * pregnancy or breastfeeding * any physical or psychological condition that the investigator feels would interfere with trial participation * treatment with any glucose-lowering drugs beside insulin, treatment with medication against osteoporosis or treatment with any form of glucocorticoids inclusion criteria healthy controls: * caucasian ethnicity * age between 18 and 60 years * bmi between 18.5 and 27 kg/m2 * fasting plasma glucose ≤7.0 mmol/l and glycated haemoglobin (hba1c) \<48 mmol/mol * normal blood haemoglobin (8.3-10.5 mmol/l (males) and 7.3 - 9.5 mmol/l (females)) * normal plasma vitamin d (\>50 nmol/l) * informed consent exclusion criteria healthy controls: * any form of diabetes (according to world health organization criteria) * anaemia (haemoglobin below normal range) * nephropathy (egfr \<60 ml/min/1,73m2 and/or microalbuminuria) * known liver disease and/or alanine transaminase (alat) or aspartate transaminase (asat) \>2 × upper normal limit * any fractures within the last 6 months * for women: currently perimenopausal or postmenopausal * diseases affecting calcium metabolism (e.g. hypoparathyroidism, hyperparathyroidism, osteoporosis, vitamin d deficiency and cancer) * pregnancy or breastfeeding * any condition considered incompatible with participation by the investigators