The Effects of Weight Loss on Neuroadrenergic Function

NCT ID: NCT01771042

Last Updated: 2013-01-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-04-30

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.

Conditions

Obesity; Type 2 Diabetes; Metabolic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Normal glucose tolerant

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.

Group Type: EXPERIMENTAL

Dietary weight loss at 25% energy deficit

Intervention Type: OTHER

Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.

Impaired glucose tolerant

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

Group Type: EXPERIMENTAL

Dietary weight loss at 25% energy deficit

Intervention Type: OTHER

Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.

Type 2 diabetic hyperinsulinemic

Weight loss using 25% caloric restriction.

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

Group Type: EXPERIMENTAL

Dietary weight loss at 25% energy deficit

Intervention Type: OTHER

Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.

Type 2 diabetic hypoinsulinemic

Weight loss via 25% caloric restriction.

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

Group Type: EXPERIMENTAL

Dietary weight loss at 25% energy deficit

Intervention Type: OTHER

Dietary weight loss at 25% energy deficit. Dietary macronutrient content will comprise 25% protein, 30% fat and 45% carbohydrate.

Interventions

Dietary 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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baker Heart Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Nora E. Straznicky

Group Leader/Senior Research Officer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr Nora E Straznicky, PhD MPH

Role: PRINCIPAL_INVESTIGATOR

Baker IDI Heart & Diabetes Institute

Locations

Baker IDI Heart & Diabetes Institute

Melbourne, Victoria, Australia

Countries

Australia

Central Contacts

Dr Nora E Straznicky, PhD MPH

Role: CONTACT

nora.straznicky@bakeridi.edu.au

61 3 8532 1371

Ms Mariee T Grima, BNutr MDiet

Role: CONTACT

mariee.grima@bakeridi.edu.au

61 3 8532 1523

Facility Contacts

Nora E Straznicky, PhD MPH

Role: primary

nora.straznicky@bakeridi.edu.au

61 3 8532 1371

References

Straznicky NE, Grima MT, Sari CI, Lambert EA, Phillips SE, Eikelis N, Kobayashi D, Hering D, Mariani JA, Dixon JB, Nestel PJ, Karapanagiotidis S, Schlaich MP, Lambert GW. Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss. Cardiovasc Diabetol. 2015 Aug 22;14:113. doi: 10.1186/s12933-015-0276-2.

Reference Type: DERIVED

PMID: 26297500 (View on PubMed)

Straznicky NE, Grima MT, Lambert EA, Sari CI, Eikelis N, Nestel PJ, Phillips SE, Hering D, Karapanagiotidis S, Dixon JB, Schlaich MP, Lambert GW. Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome. J Clin Endocrinol Metab. 2015 Apr;100(4):1544-50. doi: 10.1210/jc.2014-3796. Epub 2015 Jan 15.

Reference Type: DERIVED

PMID: 25590214 (View on PubMed)

Other Identifiers

1/13

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1/13

Identifier Type: -

Identifier Source: org_study_id