Glucose-dependent Asprosin Dynamics

NCT ID: NCT03358121

Last Updated: 2017-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

10 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-07-11

Study Completion Date

2017-10-13

Brief Summary

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The study entitled " Asprosin Dynamics relating to serum Glucose levels under controlled alterations" investigates the dynamics of Asprosin in relation to glucose levels under controlled conditions in diabetic patients.

Detailed Description

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The Pilot study entitled Asprosin Dynamics relating to serum Glucose levels under controlled alterations is designed to date the asprosin kinetics at various metabolic states relating to serum glucose and the correlation between asprosin and the known glucose regulating hormones. Asprosin is the C-terminal cleavage product of profibrilln. This new hormone is encoded by FBN1 Gen (Amino acid residues 2732 to 2871, molecular weight 30 kDa), which also encodes fibrillin. The hormone was initially discovered during the analysis of the genome of patients with the extremely rare Wiedemann Rautenstrauch syndrome. According to the data so far, asprosin is a fast induced protein hormone that acts on the liver through cell membrane receptors, where it activates the G protein cAMP PKA pathway, leading to a rapid release of glucose into the circulation and to compensatory insulin production. The above seems to match the constellation found in overweight type 2 diabetes patients or patients with metabolic syndrome (insulin resistance). Diabetic mice were able to normalize their glucose and insulin levels by asprosin-binding antibodies. According to a recent study, asprosin had no influence on the serum concentration of glucagon, epinephrine, norepinephrine and cortisol in mice. In humans it is known that asprosin increases during fasting.

The liver related glucose release into the blood circulation is crucial for the brain function and overall survival during fasting. In addition, a compensatory rise in asprosin is expected during a hypoglycemic episode. In this pilot study, the asprosin concentration is measured both in participants with type 1 Diabetes mellitus, with or without hypoglycemia unawareness during a hypoglycemic phase. These relevant measurements are compared in the two subgroups, consisting of 5 persons each. By correlating asprosin values with other regulating hormones, there is hope to better understand the pathomechanism of hypoglycemia unawareness. Recently discovered is that the recombinant asprosin administration in mice allows both the blood glucose and the insulin to rise. It is therefore very likely that further studying of asprosin could provide new insights into the (patho) physiology of the intermediary metabolism disorder.

According to the above, the following hypotheses arise:

Asprosin dynamics relating to serum Glucose levels under controlled alteration:

Asprosin, as fast induced protein hormone, increases serum levels in type 1 diabetics with or without diabetes late complications during a hypoglycemic phase. Asprosin increases serum levels more significantly in diabetics without hypoglycemia unawareness compared to diabetics with hypoglycemia unawareness. There is probably no correlation between asprosin and the previous known regulating hormones. In order to investigate these hypotheses, study participants will be initially profoundly examined in our Clinical Study Center regarding both their glycemic metabolical responses and the clinical findings relating to their possible micro- and macrovascular complications. In addition to this quality of life, well being, depression and neuropathic pain is going to be taken into account. This is to be the first study of its kind, in which plasma levels of asprosin is determined and Type 1 diabetics with and without hypoglycemia unawareness are thoroughly examined in order to identify possible differences and similarities for the better determination of the new hormone utilizing the framework of hyperinsulinemic Clamp Tests. The intention behind is to better understand the (patho) physiology of the hypoglycaemia unawareness, as well as to better characterize the physiological properties of asprosin

Conditions

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Diabetes Mellitus

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Diabetics without hypoglycemia awareness

Diabetic patients without impaired hypoglycemia awareness. No interventions were performed, the study is purely observational.

Clamp study

Intervention Type DIAGNOSTIC_TEST

Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.

Diabetics with hypoglycemia awareness

Diabetic patients with impaired hypoglycemia awareness. No interventions were performed, the study is purely observational.

Clamp study

Intervention Type DIAGNOSTIC_TEST

Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.

Interventions

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Clamp study

Clamp study to achieve high, normal, and lower glucose levels to study the dynamics of Asprosin.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Age between 18 and 75 years
* BMI between 20 und 35 kg per m2
* Persons with manifest diabetes mellitus type 1 and diagnosis according to according to DDG guidelines 2011 oGTT, HbA1c more than 6.5 percent in the absence of adulteration of the HbA1c, over 200 mg per dl in the 2 hour value of the oGTT, fasting glucose more than 126 mg per dl, spontaneous glucose more than 200 mg per dl at least twice.


* Persons who are not aware of hypoglycemia symptoms at glucose levels above 50 mg per dl
* Age between 18 and 75 years
* BMI between 20 und 35 kg per m2
* Persons with manifest diabetes mellitus type 1 and diagnosis according to DDG guidelines 2011 oGTT, HbA1c more than 6.5 percent in the absence of adulteration of the HbA1c, over 200 mg per dl in the 2 hour value of the oGTT, fasting glucose more than 126 mg per dl, spontaneous glucose more than 200 mg per dl at least twice.

Exclusion Criteria

* Current pregnancy
* Acute infections or fever Immune-suppressant therapy
* Severe psychiatric diseases requiring treatment (for example personality disorders, schizophrenia, depression)
* Known alcohol or drug dependency
* Severe heart, kidney, or liver insufficiency NYHA stadium IV
* Non-diabetic liver disease (for example PBC, PSC, Wilson's disease, hemochromatosis, autoimmune hepatitis)
* severe peripheral artery disease (stadium IV)
* non-diabetic glomerulopathy
* Cancer or other malignant diseases within the last 5 years
* Infectious diseases like hepatitis B, C, E, or HIV
* Other severe autoimmune diseases
* Current participation in an interventional study
* Past history of deep vein thrombosis or pulmonary embolism
* Routine laboratory test results less than 80 percent below lower reference value: Ferritin, iron, leucocytes, haemoglobin, hematocrit, RBC, platelets, blood alcohol levels.


* measurement Pacemaker or ICD
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Heidelberg University

OTHER

Sponsor Role lead

Responsible Party

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Stefan Kopf MD

Head of the Clinical Study Center for Diabetes Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stef Kopf, MD

Role: PRINCIPAL_INVESTIGATOR

Head of the Clinical Study Center for Diabetes Research

Locations

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Medizinische Klinik, University Hospital

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Countries

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Germany

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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S-550/2016

Identifier Type: -

Identifier Source: org_study_id