Clinical trial NCT02017210: Insulin-sensitive Obesity: Lessons From Longitudinal Data
Official title: Insulin-sensitive Obesity: Prospective and Interventional Studies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Insulin Sensitivity/Resistance
Obesity
Keywords: Hyperinsulinaemic-euglycaemic clamp
Body fat composition
Dual-energy x-ray absorptiometry
Obesity
Insulin resistance
Lead sponsor: Garvan Institute of Medical Research
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong
name: Life for a Child Program, Diabetes Australia
name: The University of New South Wales
name: University of Sydney
name: St Vincent's Hospital, Sydney
First posted: 2013-12-20
Enrollment: 57
Sex: ALL
Minimum age (years): 26
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: 6 years
Secondary outcomes:
measure: Body Mass Index
timeFrame: 6 years
measure: Waist Circumference
timeFrame: 6 years
measure: Body Fat Mass
timeFrame: 6 years
measure: Body FFM
timeFrame: 6 years
measure: Visceral Fat Volume
timeFrame: 6 years
measure: Systolic Blood Pressure
timeFrame: 6 years
measure: Diastolic Blood Pressure
timeFrame: 6 years
measure: Fasting Blood Glucose
timeFrame: 6 years
measure: Fasting Serum Insulin
timeFrame: 6 years
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Dorit Samocha-Bonet
state: New South Wales
Study officials:
affiliation: Garvan Institute of Medical Research
name: Jerry R Greenfield, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Garvan Institute of Medical Research
name: Dorit Samocha-Bonet, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.