Insulin-sensitive Obesity: Lessons From Longitudinal Data (ISOS)

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Insulin Sensitivity/Resistance

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 Type: Observational
• Enrollment (Actual): 57

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Dorit Samocha-Bonet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Pregnant and/or lactating women.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	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	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	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	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	6 years

Collaborators and Investigators

• Sponsor: Garvan Institute of Medical Research
• Collaborators: The University of Hong Kong; University of Sydney; The University of New South Wales; St Vincent's Hospital, Sydney; Diabetes Australia
• Investigators: Principal Investigator: Jerry R Greenfield, MBBS, PhD, Garvan Institute of Medical Research; Principal Investigator: Dorit Samocha-Bonet, MSc, PhD, Garvan Institute of Medical Research

Publications and helpful links

General 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.
• Heilbronn 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.
• Samocha-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.
• Tang 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2013
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: December 9, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (ESTIMATE): December 20, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; Insulin resistance; Dual-energy x-ray absorptiometry; Body fat composition; Hyperinsulinaemic-euglycaemic clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Insulin Resistance
• Other Study ID Numbers: ISOS (SVH 13/143)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No