NCT06065930RecruitingNot Applicable
Mechanistic Studies in Human Subcutaneous Adipose Tissue
Vastra Gotaland Region1 site in 1 country45 target enrollmentStarted: May 5, 2023Last updated:
Conditions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Fasting galectin-1 concentration in subcutaneous interstitial fluid
Study Overview
Brief Summary
The investigator recently showed that the glycan-binding adipokine galectin-1 increased during overfeeding and that galectin-1 independently could predict type 2 diabetes. Further, the molecules that induce insulin release in the fasting state when blood glucose is normal remain elusive. It is possible that galectin-1 is involved in adaptive mechanisms in adipose tissue in obese subjects.
Detailed Description
The investigator will define adaptive mechanisms in adipose tissue associated with galectin-1 in obese insulin-sensitive (Ob-IS) subjects compared with obese insulin-resistant (Ob-IR) subjects and lean healthy controls. Further, the investigator will study molecules secreted from adipose tissue that might trigger insulin secretion when blood glucose is normal.
The investigator hypothesizes that Ob-IS subjects keep fatty acid levels normal through an adaptive response in adipose tissue that involves up-regulation of galectin-1 for dampening of immune cell activity and stimulation of lipolysis.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 40 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and women of age: 40.0 - 70.0 years
- •BMI: 18.0 - 25.0 kg/m2 (lean subjects) and BMI 30.0 - 38.0 kg/m2 (Ob-IS and Ob-IR)
- •Fasting insulin < 9.0 mU/l (lean and Ob-IS subjects) and fasting insulin > 9.0 mU/l (Ob-IR)
- •Fasting glucose < 6.1 mmol/l
- •Body temperature < 37.5°C
- •First-degree relative with known T2D in Ob-IR
- •Weight stable ± 5 kg < 3 months before screening
- •Fluent in Swedish and can follow given instructions
- •Consent given to participate
Exclusion Criteria
- •First-degree relative with known T2D in lean or Ob-IS subjects
- •Alcohol intake > 10 units/week or known high alcohol intake < 10 years back in time
- •Daily use of cigarettes or daily frequent use of smokeless tobacco not enabling the participant to suspend nicotine during a visit at the research center without getting abstinent
- •Regular physical activity corresponding to Saltin-Gimby level 4
- •Special diet eg Atkins or 5:2 for weight reduction. Vegetarian food accepted if duration > 1 year
- •Impaired fasting glucose (IFG) (venous fasting plasma glucose 6.1-6.9 mmol/l)
- •Type 2 diabetes according to ADA criteria
- •Ongoing or previous ischemic heart disease, eg angina pectoris, unstable angina or previous myocardial infarction treated with platelet inhibitors or non vitamin-K oral anticoagulants
- •Heart failure (NYHA II-IV) or cardiac arrhytmia that needs medical treatment
- •Previous cerebral infarction or transitory ischemic episodes (TIA) treated with platelet inhibitors or other anticoagulants
- •Peripheral arterial insufficiency eg claudication
- •Hypertension >170/105 mmHg at screening or more than one class of drugs for treatment of known hypertension
- •Lipid disorder defined as fasting serum triglycerides > 5.0 mmol/l or serum cholesterol > 7.5 mmol/l
- •Hematologic diseases such as anemia not being substituted (Hb < 130 g/l in males and Hv < 120 g/l in females) or disease causing bleeding disorder
- •Renal failure defined as absolute estimated glomerular filtration rate (eGFRcreatinine) < 60 ml/min/1.73 m2
- •Hypothyroidism defined as TSH > 4.0 mIE/l and symptoms
- •Liver disease e.g. hepatitis B, cirrhosis or conditions where AST or ALT are > 2 times UNL
- •Systemic inflammatory disease e.g. rheumatoid arthritis, ulcerative cholitis or Chrons disease. Celiac disease, dyspepsia or IBS are excepted
- •Chronic bronchitis or chronic obstructive pulmonary with disease symptoms
- •Previous pancreatitis or other disease in pancreas that needs treatment
- •Migraine elicited by stress
- •Spinal insufficiency causing inconvenience lying in supine position during the study day
- •Drug addiction interfering with the study procedures
- •Psychiatric insufficiency interfering with the study procedures
- •Medication with potential to affect adipose tissue metabolism that can not be stopped 10 days before the study days
- •Treatment with beta-blockers
- •Less than three months from previous use of antibiotics
- •Cancer disease < 5 years since diagnosis
- •Physical examination or laboratory results indicating that participation in the study is inappropriate
- •Pregnancy or intention to be pregnant during the study
- •Shift work > 1 time per week that might interfere with the circadian rhytm
- •Other reasons that causes the PI to believe that participation is inappropriate
Outcomes
Primary Outcomes
Fasting galectin-1 concentration in subcutaneous interstitial fluid
Time Frame: Three weeks
Comparison between eligible Ob-IS and Ob-IR subjects \< 3 weeks after enrolment
Fasting Neuropilin-1 concentration in subcutaneous interstitial fluid
Time Frame: Three weeks
Comparison between eligible Ob-IS and Ob-IR subjects \< 3 weeks after enrolment
Secondary Outcomes
- Fasting serum galectin-1 concentrations(Three weeks)
- Fasting plasma fatty acid concentrations(Three weeks)
- RNA sequencing results of subcutaneous adipose cells(Six weeks)
- Fasting fatty acid levels in subcutaneous dialysates(Three weeks)
- Messenger RNA expression in whole adipose tissue(Six weeks)
- Fasting amino acid profile in subcutaneous dialysates(Three weeks)
- Circulating lipidome including lipid derivatives measured by Mass Spectrometry(Three weeks)
- Ectopic lipid accumulation assessed by magnetic resonance imaging in relative measures(Nine weeks)
- Function of microvascular endothelial cells in subcutaneous stromal vascular fraction(Six weeks)
- Fasting serum neuropilin-1 concentrations(Three weeks)
- Fasting serum amino acid concentrations(Three weeks)
- Peptides identified by Mass Spectrometry in subcutaneous dialysates(Three weeks)
- Function of immune cells in subcutaneous stromal vascular fraction characterized by Fluorescence Activated Cell Sorting (FACS)(Six weeks)
- Activation of insulin signaling proteins in adipose cells assessed by Western blot(Six weeks)
- Circulating metabolome including lipoprotein-related parameters measured by Mass Spectrometry(Three weeks)
- Metabolites in urine including acylcarnitines measured by Mass Spectrometry(Three weeks)
- Dysbiosis in faeces assessed by 16S rRNA gene sequencing(Six weeks)
Investigators
Study Sites (1)
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