Impact of INsulin Sensitivity on Cardiovascular Risk Markers During 10-20 Years of FOllow up (INFO)

Impact of INsulin Sensitivity on Cardiovascular Risk Markers During 10-20 Years of FOllow-up

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Hypertension; Diabetes Mellitus; Ischemic Heart Disease

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.

• Study Type: Observational
• Enrollment (Actual): 103

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0407
    • Section of Cardiovascular and Renal Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

103 men previously examined with hyperinsulinemic glucose clamp, measuring insulin sensitivity, at Center of Cardiovascular and Renal Research, Division of Medicine, Oslo University Hospital, Ullevål.

Description

Inclusion Criteria:

• Completed hyperinsulinemic glucose clamp

Exclusion Criteria:

• Missing agreement
• No contact information

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Longitudinal Insulin Sensitivity; The participants were examined using the hyperinsulinaemic isoglycaemic glucose clamp technique which is the gold standard to assess insulin sensitivity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One-day visit and the analyses will be done when all patients are examined in the period 2012-2013
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.	20 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One-day visit and analyses will be done during 2012-2013
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	One-day visit, final analyses 2012-2013
Ultrasound Abdomen	Ultrasound quantification of abdominal adipose tissue	One-day visit. Final analyses of the whole cohort during 2012-2013

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Study Director: Sverre E Kjeldsen, PhD, Oslo Univeristy Hospital

Publications and helpful links

General Publications

• Akra S, Aksnes TA, Flaa A, Eggesbo HB, Opstad TB, Njerve IU, Seljeflot I. Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men. Sci Rep. 2020 Aug 20;10(1):14055. doi: 10.1038/s41598-020-71109-4.
• Skarn SN, Eggesbo HB, Flaa A, Kjeldsen SE, Rostrup M, Brunborg C, Reims HM, Aksnes TA. Predictors of abdominal adipose tissue compartments: 18-year follow-up of young men with and without family history of diabetes. Eur J Intern Med. 2016 Apr;29:26-31. doi: 10.1016/j.ejim.2015.11.027. Epub 2015 Dec 23.

Helpful Links

• Homepage for Section of Cardiovascular and Renal Research

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: July 22, 2011
• First Submitted That Met QC Criteria: August 8, 2011
• First Posted (Estimate): August 9, 2011

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Insulin resistance; Diabetes mellitus; Adipositas
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Hyperinsulinism; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Diabetes Mellitus; Insulin Resistance
• Other Study ID Numbers: 2010/3339