Diabetes Mellitus, Hypertension, Ischemic Heart Disease, Stroke
Conditions
Keywords
Insulin resistance, Diabetes mellitus, Adipositas
Brief summary
The purpose of this study is to identify risk factors for insulin resistance and to investigate the influence of insulin sensitivity on development of cardiovascular risk markers like blood pressure, heart rate, body build (weight, BMI, waist-hip ratio, skinfold thickness), reduced insulin sensitivity, diabetes mellitus, dyslipidaemia, and sympathoadrenal activity or manifest cardiovascular disease among young men during 10-20 years.
Detailed description
In 1988 Reaven described a syndrome designed syndrome X based on the clustering of resistance to insulin-stimulated glucose uptake, hyperinsulinaemia, hyperglycaemia, increased triglycerides, decreased high-density lipoprotein (HDL) cholesterol and high blood pressure and proposed insulin resistance as the common feature and the aetiology of the syndrome. Later obesity and the sympathetic nervous system have been proposed as pathogenic factors of the metabolic syndrome, and still major controversy exists regarding its precise aetiology and different definitions of metabolic syndrome are also discussed. Insulin resistance is a growing epidemic concern in both industrialized and developing countries. It is one of the components of the metabolic syndrome, and plays an important role in the pathogenesis of type 2 diabetes. In view of the predicted increase in the number of diabetic patients during the coming decades, further information about risk factors and pathophysiology of diabetes are of utmost importance for early detection and possible prevention and early treatment from both a medical and a financial perspective. Our research group has for decades studied the pathophysiology of insulin resistance, hypertension, sympathoadrenal hyperreactivity and dyslipidaemia. We have also recently finished a long-term follow up study of subjects based on their cardiovascular and sympathetic responses to mental stress. During 1991-2002 healthy young men recruited from the military enlistments in the Oslo/Akershus area were examined at Center of Cardiovascular and Renal Research, Division of Medicine, Oslo University Hospital, Ullevål. Young, healthy men, mean age of 21, were examined using the hyperinsulinaemic isoglycaemic glucose clamp technique, which is the gold standard to assess insulin sensitivity. The present study aims to re-examine these subjects in order to investigate the influence of insulin sensitivity on development of cardiovascular risk factors and diabetes. We therefore have a unique opportunity to perform a true, long-term follow-up study of a homogenous sample of subjects of same race and gender which may provide new insights into various pathophysiological mechanisms in diabetes and cardiovascular disease including elucidating the connections between insulin resistance, changes in parameters of body build, blood pressure and sympathetic over-activity. Clarifying these mechanisms are of direct importance for the entire population. There has to our knowledge not been any previous long-term follow-up on subjects based on their insulin resistance measured with this gold standard technique. We now want to re-examine the same subject to investigate the influence of insulin sensitivity on development of cardiovascular risk factors like blood pressure, heart rate, body build (weight, BMI, waist-hip ration, skinfold thickness), reduced insulin sensitivity, diabetes mellitus, dyslipidaemia, and sympathoadrenal activity or manifest cardiovascular disease among young men during 10-20 years of follow-up.
Interventions
None listed
Sponsors
Oslo University Hospital
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
MALE
Age
30 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Completed hyperinsulinemic glucose clamp
Exclusion criteria
* Missing agreement * No contact information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exploring Insulin Sensitivity After 10-20 Years of Follow-up | One-day visit and the analyses will be done when all patients are examined in the period 2012-2013 | The primary outcome is insulin sensitivity measured as the glucose disposal rate (GDR) (mg/kg/min), calculated from the average glucose infusion rate during the last 20 minutes of a 120 minutes hyperinsulinaemic isoglycaemic glucose clamp. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sympathoadrenal Activity During Rest and Stress Tests | One-day visit and analyses will be done during 2012-2013 | A mental arithmetic stress test will be announced and performed immediately after the glucose clamp, to assess the effects of increased adrenaline and noradrenaline when hepatic glucose production is suppressed by hyperinsulinaemia. Blood pressure, heart rate and catecholamine blood-levels are measured at pre-defined intervals. |
| Echocardiography | One-day visit, final analyses 2012-2013 | Transthoracic echocardiography will be performed using a VIVID E9 (or VIVID 7) echocardiographic scanner (GE Vingmed, Horten) with 1,7-MHz probe in second harmonic mode and optimal gain and contrast.Left ventricular (LV) internal dimension, intraventricular septal thickness and LV posterior wall thickness will be measured as well as epicardial adipose tissue. We will also evaluate biplane Simpson ejection fraction and valvular incompetence |
| Ultrasound Abdomen | One-day visit. Final analyses of the whole cohort during 2012-2013 | Ultrasound quantification of abdominal adipose tissue |
Countries
Norway
Participant flow
Recruitment details
During 1991-96 men from the military enlistments were examined at Center of Cardiovascular and Renal Research, Division of Medicine, Oslo University Hospital, Ullevål, using hyperinsulinaemic isoglycaemic glucose clamp technique to assess insulin sensitivity. They were re-invited to participate in the presented study during 2012-13.
Pre-assignment details
103 consented to participation.
Participants by arm
| Arm | Count |
|---|---|
| Longitudinal Insulin Sensitivity The participants were examined using the hyperinsulinaemic isoglycaemic glucose clamp technique which is the gold standard to assess insulin sensitivity. | 103 |
| Total | 103 |
Baseline characteristics
| Characteristic | Longitudinal Insulin Sensitivity |
|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 4 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 103 |
| other Total, other adverse events | 0 / 103 |
| serious Total, serious adverse events | 0 / 103 |
Outcome results
Primary
Exploring Insulin Sensitivity After 10-20 Years of Follow-up
The primary outcome is insulin sensitivity measured as the glucose disposal rate (GDR) (mg/kg/min), calculated from the average glucose infusion rate during the last 20 minutes of a 120 minutes hyperinsulinaemic isoglycaemic glucose clamp.
Time frame: One-day visit and the analyses will be done when all patients are examined in the period 2012-2013
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Longitudinal Insulin Sensitivity | Exploring Insulin Sensitivity After 10-20 Years of Follow-up | 7 mg/kg/min | Standard Deviation 2 |
Comparison: Only an observational follow-up studyp-value: <0.05Spearman
Primary
Exploring Insulin Sensitivity After 10-20 Years of Follow-up
The primary outcome is insulin sensitivity measured as the glucose disposal rate (GDR) (mg/kg/min), calculated from the average glucose infusion rate during the last 20 minutes of a 120 minutes hyperinsulinaemic isoglycaemic glucose clamp.
Time frame: 20 years
Secondary
Echocardiography
Transthoracic echocardiography will be performed using a VIVID E9 (or VIVID 7) echocardiographic scanner (GE Vingmed, Horten) with 1,7-MHz probe in second harmonic mode and optimal gain and contrast.Left ventricular (LV) internal dimension, intraventricular septal thickness and LV posterior wall thickness will be measured as well as epicardial adipose tissue. We will also evaluate biplane Simpson ejection fraction and valvular incompetence
Time frame: One-day visit, final analyses 2012-2013
Secondary
Sympathoadrenal Activity During Rest and Stress Tests
A mental arithmetic stress test will be announced and performed immediately after the glucose clamp, to assess the effects of increased adrenaline and noradrenaline when hepatic glucose production is suppressed by hyperinsulinaemia. Blood pressure, heart rate and catecholamine blood-levels are measured at pre-defined intervals.
Time frame: One-day visit and analyses will be done during 2012-2013
Secondary
Ultrasound Abdomen
Ultrasound quantification of abdominal adipose tissue
Time frame: One-day visit. Final analyses of the whole cohort during 2012-2013