Metabolic Syndrome, Obesity, Type 2 Diabetes
Conditions
Keywords
weight loss, metabolic syndrome, sympathetic nervous system, insulin resistance, glucose tolerance
Brief summary
Elevated subconscious nervous system activity is a characteristic of the obese state and contributes importantly to the risk of heart disease and diabetes. This project will compare sympathetic nervous system activity and function in a group of obese persons with differing levels of sugar tolerance (normal, impaired and type 2 diabetic). Inter-relationships with insulin action, blood pressure, heart and kidney function will be determined before and after a 4-month weight loss and 3-month weight loss maintenance program. It is hypothesized that the transition from normal sugar tolerance to impaired sugar tolerance to type 2 diabetes will be accompanied by escalating sympathetic nervous system dysfunction. Furthermore, that weight loss will favorably improve sympathetic function, with greatest benefits occurring in those subjects who are insulin resistant with high blood insulin concentration.
Detailed description
The twin epidemics of obesity and diabetes represent a major public health problem worldwide. There is a growing body of evidence to suggest that autonomic dysfunction, comprising elevated sympathetic nervous system (SNS) activity and blunted sympathetic neural responsiveness plays a role in both the pathogenesis and target organ complications of obesity and diabetes. The proposed project will undertake a detailed comparative analysis of neuroadrenergic function along the diabetes continuum, its inter-relationship with insulin sensitivity and secretion, and target organ function, and the benefits of active weight loss and weight loss maintenance within different strata of metabolic risk.
Interventions
OTHERDietary weight loss at 25% energy deficit
Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.
Sponsors
Baker Heart Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Men and postmenopausal women (n=120), untreated, weight-stable, non-smoking, aged 45-65 years, BMI 27-45 kg/m2, will be recruited. Glucose tolerance status will be determined by a 75-g oral glucose tolerance test (OGTT), using WHO criteria (53): normal glucose tolerance, fasting plasma glucose \< 7.0 mmol/L and 2-h plasma glucose \< 7.8 mmol/L; IGT, fasting plasma glucose \< 7.0 mmol/L and 2-h plasma glucose \> 7.8 and \< 11.1 mmol/L; T2D, fasting plasma glucose \> 7.0 mmol/L or 2-h plasma glucose \> 11.1 mmol/L. Hyper-insulinemia will be defined as an insulin area under the curve during OGTT \> 8000 mU/L ∙ min-1 and hypo-insulinemia as \< 8000 mU/L ∙ min-1.
Exclusion criteria
Prior history of cardiovascular disease (previous myocardial infarction, angina, stroke, heart failure, secondary hypertension), renal (serum creatinine \>0.12 mmol/L or estimated GFR \<60 ml/min/1.73 m2) or hepatic disease or diseases which may affect measured parameters (e.g. thyroid disease); severe hypertension; a history of surgical weight loss; CPAP therapy; and \>4 alcoholic drinks/day. T2D individuals with moderate hyperglycemia (HbA1c \>9%) will be excluded so that hypoglycaemic pharmacotherapy may be instituted (54). Participants will be sought through newspaper advertising and poster displays in primary health care centres (General Practices). Newly diagnosed T2D subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in whole-body norepinephrine kinetics | 4 months and 7 months | The study will examine the dynamic processes of norepinephrine spillover into and removal from the central plasma compartment using the isotope dilution technique.Measurements will be made at baseline, after 4 months active weight loss, and again after 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on sympathetic neural parameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in muscle sympathetic nerve activity | 4 months and 7 months | Muscle sympathetic nerve firing will be quantified by the technique of mirconeurography at baseline and after 4 months active weight loss and 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on sympathetic nerve firing and pattern. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin sensitivity | 4 months and 7 months | Insulin sensitivity will be assessed by the gold standard euglycemic hyperinsulinemic clamp method at baseline and after 4 months active weight loss and 3 months weight loss maintenance. The weight loss maintenance phase will permit differentiation of the effects of active weight loss (incorporating both negative energy balance and weight loss per se) and stable lower body weight on insulin sensitivity. |
Countries
Australia
Contacts
Primary ContactDr Nora E Straznicky, PhD MPH
Backup ContactMs Mariee T Grima, BNutr MDiet
Outcome results
None listed