The Effects of Weight Loss on Neuroadrenergic Function

NCT01771042 | Unknown

• 1 other identifier: 1/13
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Type 2 Diabetes; Metabolic Syndrome

Keywords

weight loss; metabolic syndrome; sympathetic nervous system; insulin resistance; glucose tolerance

Outcome Measures

Primary Outcomes (1)

• Change in whole-body norepinephrine kinetics

  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.

  4 months and 7 months

Secondary Outcomes (1)

• Change in muscle sympathetic nerve activity

  4 months and 7 months

Other Outcomes (1)

• Change in insulin sensitivity

  4 months and 7 months

Study Arms (4)

Normal glucose tolerant

EXPERIMENTAL

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.

Other: Dietary weight loss at 25% energy deficit

Impaired glucose tolerant

EXPERIMENTAL

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

Other: Dietary weight loss at 25% energy deficit

Type 2 diabetic hyperinsulinemic

EXPERIMENTAL

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

Other: Dietary weight loss at 25% energy deficit

Type 2 diabetic hypoinsulinemic

EXPERIMENTAL

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

Other: Dietary weight loss at 25% energy deficit

Interventions

Dietary weight loss at 25% energy deficit OTHER

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

Impaired glucose tolerant; Normal glucose tolerant; Type 2 diabetic hyperinsulinemic; Type 2 diabetic hypoinsulinemic

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Baker Heart Research Institute: lead

Study Sites (1)

Baker IDI Heart & Diabetes Institute

Melbourne, Victoria, 8008, Australia

Location

Related Publications (2)

• 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.

  PMID: 26297500 DERIVED

• 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.

  PMID: 25590214 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2; Metabolic Syndrome; Weight Loss; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Body Weight Changes

Study Officials

• Dr Nora E Straznicky, PhD MPH

  Baker IDI Heart & Diabetes Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Nora E Straznicky, PhD MPH

CONTACT

61 3 8532 1371; nora.straznicky@bakeridi.edu.au

Ms Mariee T Grima, BNutr MDiet

CONTACT

61 3 8532 1523; mariee.grima@bakeridi.edu.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Group Leader/Senior Research Officer

Study Record Dates

• First Submitted: January 15, 2013
• First Posted: January 18, 2013
• Study Start: April 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: January 18, 2013

Record last verified: 2013-01

Locations

AU (1)