Insulin-sensitive Obesity: Lessons From Longitudinal Data

Study Overview
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Brief Summary
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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
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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.

Official Title
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Insulin-sensitive Obesity: Prospective and Interventional Studies

Conditions
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Obesity, Insulin Sensitivity/Resistance

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lean/normal weight<br>Individuals with body mass index (BMI)<25 kg/m^2 in the baseline study | |
| Overweight/Obese Insulin-Sensitive<br>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<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperinsulinaemic-euglycaemic clamp, Body fat composition, Dual-energy x-ray absorptiometry, Obesity, Insulin resistance