The Effects of Weight Loss on Neuroadrenergic Function

Baker Heart Research Institute

Status: Unknown

Conditions: Obesity; Type 2 Diabetes; Metabolic Syndrome

Treatments: Other: Dietary weight loss at 25% energy deficit

Study type: Interventional

Funder types: Other

Identifiers

NCT01771042

1/13 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 45 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 4 patient groups

Normal glucose tolerant

Experimental group

Description:

Weight loss attained by 25% caloric restriction. This arm will be both a glycemic and time control. Initially they will undergo a 4-month weight maintenance phase (acting as time control), followed by 4 month weight loss.

Treatment:

Other: Dietary weight loss at 25% energy deficit

Impaired glucose tolerant

Experimental group

Description:

Weight loss using 25% caloric restriction. Impaired glucose tolerant subjects will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Treatment:

Other: Dietary weight loss at 25% energy deficit

Type 2 diabetic hyperinsulinemic

Experimental group

Description:

Weight loss using 25% caloric restriction. This group will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Treatment:

Other: Dietary weight loss at 25% energy deficit

Type 2 diabetic hypoinsulinemic

Experimental group

Description:

Weight loss via 25% caloric restriction. This group will undergo 4 months weight loss (25% caloric deficit) followed by 3 months weight loss maintenance

Treatment:

Other: Dietary weight loss at 25% energy deficit