Insulin Sensitivity/Resistance, Obesity
Conditions
Keywords
Hyperinsulinaemic-euglycaemic clamp, Body fat composition, Dual-energy x-ray absorptiometry, Obesity, Insulin resistance
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.
Interventions
None listed
Sponsors
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
Garvan Institute of Medical Research
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
26 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Waist Circumference | 6 years | Change in waist circumference was determined as Follow-up Value - Baseline Value /Time between measurements. There were 2 time points 6 years apart |
| Body Fat Mass | 6 years | 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 |
| Body FFM | 6 years | 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 |
| Visceral Fat Volume | 6 years | 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 |
| Body Mass Index | 6 years | 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 |
| Diastolic Blood Pressure | 6 years | Change in Diastolic Blood Pressure was determined as Follow-up Value - Baseline Value /Time between measurements. There were 2 time points 6 years apart |
| Fasting Blood Glucose | 6 years | Change in fasting blood glucose was determined as Follow-up Value - Baseline Value /Time between measurements. There were 2 time points 6 years apart |
| Fasting Serum Insulin | 6 years | Change in fasting serum insulin was determined as Follow-up Value - Baseline Value /Time between measurements. There were 2 time points 6 years apart |
| Systolic Blood Pressure | 6 years | Change in Systolic Blood Pressure was determined as Follow-up Value - Baseline Value /Time between measurements. There were 2 time points 6 years apart |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lean/Normal Weight Individuals with body mass index (BMI)\<25 kg/m\^2 in the baseline study | 17 |
| Overweight/Obese Insulin-Sensitive Individuals with BMI\>25 kg/m\^2 who were deemed insulin-sensitive at the baseline study | 20 |
| Overweight/Obese Insulin-Resistant Individuals with BMI\>25 kg/m\^2 who were deemed insulin-resistant at the baseline study | 20 |
| Total | 57 |
Baseline characteristics
| Characteristic | Lean/Normal Weight | Total | Overweight/Obese Insulin-Resistant | Overweight/Obese Insulin-Sensitive |
|---|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 11.1 | 57.5 years STANDARD_DEVIATION 11.6 | 63.4 years STANDARD_DEVIATION 10.7 | 54.2 years STANDARD_DEVIATION 10.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 54 Participants | 19 Participants | 19 Participants |
| Region of Enrollment Australia | 17 Participants | 99 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Female | 6 Participants | 27 Participants | 12 Participants | 9 Participants |
| Sex: Female, Male Male | 11 Participants | 30 Participants | 8 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
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
Time frame: 6 years
Population: The hyperinsulinemic-euglycemic clamp was performed in a sub-cohort of n=9, 10 and 16 participants who were normal-weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant, respectively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Insulin Sensitivity | 0.0105 micro mol/min/Kg/mU/L/year |
| Overweight/Obese Insulin-Sensitive | Insulin Sensitivity | -0.0076 micro mol/min/Kg/mU/L/year |
| Overweight/Obese Insulin-Resistant | Insulin Sensitivity | 0.0041 micro mol/min/Kg/mU/L/year |
Secondary
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
Time frame: 6 years
Population: DXA was performed in a sub-cohort of n=11, 11 and 19 in normal weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant participants, respectively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Body Fat Mass | 0.2281 % of total body mass/year |
| Overweight/Obese Insulin-Sensitive | Body Fat Mass | 0.3696 % of total body mass/year |
| Overweight/Obese Insulin-Resistant | Body Fat Mass | 0.3478 % of total body mass/year |
Secondary
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
Time frame: 6 years
Population: DXA was performed in a sub-cohort of n=11, 11 and 19 in normal weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant participants, respectively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Body FFM | -0.0382 kg/year |
| Overweight/Obese Insulin-Sensitive | Body FFM | -0.1786 kg/year |
| Overweight/Obese Insulin-Resistant | Body FFM | -0.4017 kg/year |
Secondary
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
Time frame: 6 years
Population: All individuals who were followed up after 6 years were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Body Mass Index | 0.0526 kg/m^2/year |
| Overweight/Obese Insulin-Sensitive | Body Mass Index | 0.0941 kg/m^2/year |
| Overweight/Obese Insulin-Resistant | Body Mass Index | 0.0088 kg/m^2/year |
Secondary
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
Time frame: 6 years
Population: All individuals who were followed up after 6 years were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Diastolic Blood Pressure | 1.1290 mmHg/year |
| Overweight/Obese Insulin-Sensitive | Diastolic Blood Pressure | 0.4117 mmHg/year |
| Overweight/Obese Insulin-Resistant | Diastolic Blood Pressure | 0.5662 mmHg/year |
Secondary
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
Time frame: 6 years
Population: Fasting blood glucose concentration measure was available in a sub-cohort of n=16, 18 and 19 in normal weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant participants, respectively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Fasting Blood Glucose | -0.0151 mmol/L/year |
| Overweight/Obese Insulin-Sensitive | Fasting Blood Glucose | 0.0062 mmol/L/year |
| Overweight/Obese Insulin-Resistant | Fasting Blood Glucose | -0.0254 mmol/L/year |
Secondary
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
Time frame: 6 years
Population: Fasting serum insulin measurement was available in a sub-cohort of n=16, 18 and 19 in normal weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant participants, respectively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Fasting Serum Insulin | 0.2223 mU/L/year |
| Overweight/Obese Insulin-Sensitive | Fasting Serum Insulin | 0.0855 mU/L/year |
| Overweight/Obese Insulin-Resistant | Fasting Serum Insulin | -0.2370 mU/L/year |
Secondary
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
Time frame: 6 years
Population: All individuals who were followed up after 6 years were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Systolic Blood Pressure | 0.3704 mmHg/year |
| Overweight/Obese Insulin-Sensitive | Systolic Blood Pressure | 0.9483 mmHg/year |
| Overweight/Obese Insulin-Resistant | Systolic Blood Pressure | 1.3593 mmHg/year |
Secondary
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
Time frame: 6 years
Population: Visceral fat volume was available in n=11, 10 and 18 normal weight, overweight/obese insulin-sensitive and overweight/obese insulin-resistant participants who undergone a DXA measure due to technical reasons
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Visceral Fat Volume | 13.3962 cm^3/year |
| Overweight/Obese Insulin-Sensitive | Visceral Fat Volume | 47.3351 cm^3/year |
| Overweight/Obese Insulin-Resistant | Visceral Fat Volume | 46.2974 cm^3/year |
Secondary
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
Time frame: 6 years
Population: All individuals who were followed up after 6 years were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lean/Normal Weight | Waist Circumference | 0.5263 cm/year |
| Overweight/Obese Insulin-Sensitive | Waist Circumference | 0.4894 cm/year |
| Overweight/Obese Insulin-Resistant | Waist Circumference | 0.0000 cm/year |