Insulin Sensitivity/ResistanceISOSNCT02017210
Insulin-sensitive Obesity: Lessons From Longitudinal Data
An observational study of Insulin Sensitivity/Resistance and Obesity, run by Garvan Institute of Medical Research at 1 site in Australia.
Trial summary
People who are overweight and/or obese are at risk of insulin resistance and type 2 diabetes. However, research has shown that some overweight and/or obese individuals remain insulin-sensitive and metabolically healthy despite their unhealthy body weight. Read more about this study
- Who is it for?
- Ages 26 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity/Resistance, Obesity
- How many people
- 57 participants
- Where
- 1 siteAustralia
- Study dates
- Nov 2013to Feb 2016
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 26 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Participants of two previous separate studies performed at the Garvan Institute of Medical Research (Sydney, Australia) were contacted by postal mail to gauge interest in participating in this follow-up study. In the original studies, exclusion criteria included weight change greater than 2 kg in the preceding 6 months, self-reported regular exercise for periods longer than 60 min/week, treatment with medications known to affect insulin sensitivity or carbohydrate metabolism, known renal, cardiac, or liver disease and current cancer, planning pregnancy, consumption of more than 20 and 40 g/day alcohol for women and men, respectively, and smoking >10 cigarettes/day
Who may be able to join
- Participation in two previous studies conducted at the Garvan Institute of Medical Research Clinical Research Facility (described in the other publications 1-3).
- Willingness to give written informed consent and willingness to participate in the study.
Who cannot join
- Pregnant and/or lactating women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Insulin-sensitive Obesity: Prospective and Interventional Studies
People who are overweight and/or obese are at risk of insulin resistance and type 2 diabetes. However, research has shown that some overweight and/or obese individuals remain insulin-sensitive and metabolically healthy despite their unhealthy body weight.
The investigators hypothesise that overweight and/or obese people who were deemed insulin-sensitive in previous studies will maintain their insulin sensitivity and metabolic health over time. The investigators also hypothesise that the preservation of insulin sensitivity will be accompanied by key metabolic health markers.
Read the detailed description
While obesity is a risk factor for metabolic disease, sub cohorts with obesity not complicated by the metabolic syndrome have been described. These so called "metabolically healthy obese" may have reduced risk of type 2 diabetes, cardiovascular disease and all-cause mortality compared with individuals with obesity who present with components of the metabolic syndrome.
Longitudinal studies with diabetes and cardiovascular disease risk endpoints reported that individuals with obesity who are metabolically healthy (MHO) held an intermediate health status, such that they were still worse off than the healthy normal-weight individuals. While there have been studies evaluating the stability of the MHO phenotype over time, no study has reported the durability of insulin-sensitivity per se, as measured by the gold-standard hyperinsulinaemic-euglycaemic clamp. In the present study, we aimed to trace the change in insulin resistance/sensitivity, and to uncover predictors of insulin resistance in older age. The secondary aims were to trace the change in body composition, fat distribution and metabolic markers over time in a well-phenotyped cohort studied approximately 5-6 years apart.
- Conditions
- Insulin Sensitivity/Resistance, Obesity
- Keywords
- Hyperinsulinaemic-euglycaemic clamp, Body fat composition, Dual-energy x-ray absorptiometry, Obesity, Insulin resistance
- Medical subject headings
- Insulin Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Lean/normal weight | Individuals with body mass index (BMI)<25 kg/m^2 in the baseline study | |
| Overweight/Obese Insulin-Sensitive | Individuals with BMI>25kg/m^2 who were deemed insulin-sensitive by the hyperinsulinemic -euglycemic clamp (with M/I value above median for men and women separately) | |
| Overweight/Obese Insulin-Resistant | Individuals with BMI>25kg/m^2 who were deemed insulin-resistant by the hyperinsulinemic -euglycemic clamp (with M/I value under median for men and women separately) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
The change in insulin sensitivity (as measured by M-value normalised to insulin from hyperinsulinemic-euglycemic clamp) was determined "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Secondary outcomes (9)
Body Mass Index
Change in body mass index (BMI) was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Waist Circumference
Change in waist circumference was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Body Fat Mass
Body fat mass from dual-energy X-ray absorptiometry (DXA) change was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Body FFM
Body fat-free mass (FFM) from DXA change was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Visceral Fat Volume
Abdominal visceral fat volume from DXA change was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Systolic Blood Pressure
Change in Systolic Blood Pressure was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Diastolic Blood Pressure
Change in Diastolic Blood Pressure was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Fasting Blood Glucose
Change in fasting blood glucose was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Fasting Serum Insulin
Change in fasting serum insulin was determined as "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study startNov 2013
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Insulin Sensitivity/ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Garvan Institute of Medical Research
- Sponsor type
- University, hospital or other
- Collaborators
- The University of Hong Kong, Life for a Child Program, Diabetes Australia, The University of New South Wales, University of Sydney, St Vincent's Hospital, Sydney
- Responsible party
- Principal investigator, Dorit Samocha-Bonet, Garvan Institute of Medical Research
- Investigators
- Jerry R Greenfield, MBBS, PhD, Principal investigator, Garvan Institute of Medical ResearchDorit Samocha-Bonet, MSc, PhD, Principal investigator, Garvan Institute of Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02017210
- Sponsor's protocol ID
- ISOS (SVH 13/143)
- Acronym
- ISOS
- Status last verified
- Feb 2020
- First submitted
- 9 Dec 2013
- Last updated
- 24 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tonks KT, Ng Y, Miller S, Coster AC, Samocha-Bonet D, Iseli TJ, Xu A, Patrick E, Yang JY, Junutula JR, Modrusan Z, Kolumam G, Stockli J, Chisholm DJ, James DE, Greenfield JR. Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects. Diabetologia. 2013 Apr;56(4):875-85. doi: 10.1007/s00125-012-2811-y. Epub 2013 Jan 24.
PubMed 23344726Heilbronn LK, Campbell LV, Xu A, Samocha-Bonet D. Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans. PLoS One. 2013 Oct 18;8(10):e78864. doi: 10.1371/journal.pone.0078864. eCollection 2013.
PubMed 24205333Samocha-Bonet D, Campbell LV, Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK. A family history of type 2 diabetes increases risk factors associated with overfeeding. Diabetologia. 2010 Aug;53(8):1700-8. doi: 10.1007/s00125-010-1768-y. Epub 2010 May 12.
PubMed 20461357Tang A, Coster ACF, Tonks KT, Heilbronn LK, Pocock N, Purtell L, Govendir M, Blythe J, Zhang J, Xu A, Chisholm DJ, Johnson NA, Greenfield JR, Samocha-Bonet D. Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals. J Clin Med. 2019 May 8;8(5):623. doi: 10.3390/jcm8050623.
PubMed 31071971
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin-sensitive Obesity: Prospective and Interventional Studies
- ClinicalTrials.gov ID
- NCT02017210
- Acronym / sponsor ID
- ISOS / ISOS (SVH 13/143)
- Conditions
- Insulin Sensitivity/Resistance, Obesity
- Keywords
- Hyperinsulinaemic-euglycaemic clamp, Body fat composition, Dual-energy x-ray absorptiometry, Obesity, Insulin resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Garvan Institute of Medical ResearchUniversity, hospital or other
- Collaborators
- The University of Hong Kong, Life for a Child Program, Diabetes Australia, The University of New South Wales, University of Sydney, St Vincent's Hospital, Sydney
- Study start
- Nov 2013 (actual)
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 20 Dec 2013 (estimated)
- Results
- Posted 24 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People who are overweight and/or obese are at risk of insulin resistance and type 2 diabetes. However, research has shown that some overweight and/or obese individuals remain insulin-sensitive and metabolically healthy despite their unhealthy body weight.
The investigators hypothesise that overweight and/or obese people who were deemed insulin-sensitive in previous studies will maintain their insulin sensitivity and metabolic health over time. The investigators also hypothesise that the preservation of insulin sensitivity will be accompanied by key metabolic health markers.
Detailed description
While obesity is a risk factor for metabolic disease, sub cohorts with obesity not complicated by the metabolic syndrome have been described. These so called "metabolically healthy obese" may have reduced risk of type 2 diabetes, cardiovascular disease and all-cause mortality compared with individuals with obesity who present with components of the metabolic syndrome.
Longitudinal studies with diabetes and cardiovascular disease risk endpoints reported that individuals with obesity who are metabolically healthy (MHO) held an intermediate health status, such that they were still worse off than the healthy normal-weight individuals. While there have been studies evaluating the stability of the MHO phenotype over time, no study has reported the durability of insulin-sensitivity per se, as measured by the gold-standard hyperinsulinaemic-euglycaemic clamp. In the present study, we aimed to trace the change in insulin resistance/sensitivity, and to uncover predictors of insulin resistance in older age. The secondary aims were to trace the change in body composition, fat distribution and metabolic markers over time in a well-phenotyped cohort studied approximately 5-6 years apart.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lean/normal weight | – | –Individuals with body mass index (BMI)<25 kg/m^2 in the baseline study |
| Overweight/Obese Insulin-Sensitive | – | –Individuals with BMI>25kg/m^2 who were deemed insulin-sensitive by the hyperinsulinemic -euglycemic clamp (with M/I value above median for men and women separately) |
| Overweight/Obese Insulin-Resistant | – | –Individuals with BMI>25kg/m^2 who were deemed insulin-resistant by the hyperinsulinemic -euglycemic clamp (with M/I value under median for men and women separately) |
Who may qualify
- Ages
- 26 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Participants of two previous separate studies performed at the Garvan Institute of Medical Research (Sydney, Australia) were contacted by postal mail to gauge interest in participating in this follow-up study. In the original studies, exclusion criteria included weight change greater than 2 kg in the preceding 6 months, self-reported regular exercise for periods longer than 60 min/week, treatment with medications known to affect insulin sensitivity or carbohydrate metabolism, known renal, cardiac, or liver disease and current cancer, planning pregnancy, consumption of more than 20 and 40 g/day alcohol for women and men, respectively, and smoking >10 cigarettes/day
Key inclusion criteria (2 listed)
- Participation in two previous studies conducted at the Garvan Institute of Medical Research Clinical Research Facility (described in the other publications 1-3).
- Willingness to give written informed consent and willingness to participate in the study.
Key exclusion criteria (1 listed)
- Pregnant and/or lactating women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin Sensitivity
Time frame: 6 years
The change in insulin sensitivity (as measured by M-value normalised to insulin from hyperinsulinemic-euglycemic clamp) was determined "Follow-up Value - Baseline Value" /"Time between measurements". There were 2 time points 6 years apart
9 secondary outcomes
Body Mass Index
Time frame: 6 years
Waist Circumference
Time frame: 6 years
Body Fat Mass
Time frame: 6 years
Body FFM
Time frame: 6 years
Visceral Fat Volume
Time frame: 6 years
Systolic Blood Pressure
Time frame: 6 years
Diastolic Blood Pressure
Time frame: 6 years
Fasting Blood Glucose
Time frame: 6 years
Fasting Serum Insulin
Time frame: 6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23344726Tonks KT, Ng Y, Miller S, Coster AC, Samocha-Bonet D, Iseli TJ, Xu A, Patrick E, Yang JY, Junutula JR, Modrusan Z, Kolumam G, Stockli J, Chisholm DJ, James DE, Greenfield JR. Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects. Diabetologia. 2013 Apr;56(4):875-85. doi: 10.1007/s00125-012-2811-y. Epub 2013 Jan 24.
- Background: PubMed 24205333Heilbronn LK, Campbell LV, Xu A, Samocha-Bonet D. Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans. PLoS One. 2013 Oct 18;8(10):e78864. doi: 10.1371/journal.pone.0078864. eCollection 2013.
- Background: PubMed 20461357Samocha-Bonet D, Campbell LV, Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK. A family history of type 2 diabetes increases risk factors associated with overfeeding. Diabetologia. 2010 Aug;53(8):1700-8. doi: 10.1007/s00125-010-1768-y. Epub 2010 May 12.
- Results publication: PubMed 31071971Tang A, Coster ACF, Tonks KT, Heilbronn LK, Pocock N, Purtell L, Govendir M, Blythe J, Zhang J, Xu A, Chisholm DJ, Johnson NA, Greenfield JR, Samocha-Bonet D. Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals. J Clin Med. 2019 May 8;8(5):623. doi: 10.3390/jcm8050623.
- Individual participant dataSharing planned: No
Related trials for Insulin Sensitivity/Resistance
RecruitingObservational study
Study of the Effect of Innate on the Inflammatory Response to Endotoxin
Asthma, Atherosclerosis
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
RecruitingObservational study
Washed Microbiota Transplantation for Type 1 Diabetes Mellitus
Type 1 Diabetes
RecruitingPhase 2
Effects of Different Fish Oil Types on Type 2 Diabetes Risk Factors in High-Risk Adults
Type 2 Diabetes, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
Not yet recruiting
Whole-Food Magnesium for Mental and Cardiometabolic Health
Elevated Blood Glucose
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry R Greenfield, MBBS, PhD principal investigator
Garvan Institute of Medical Research
Dorit Samocha-Bonet, MSc, PhD principal investigator
Garvan Institute of Medical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Insulin Sensitivity/Resistance and Obesity, run by Garvan Institute of Medical Research at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Sensitivity (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02017210, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2020.