Effects of Progressive Negative Energy Balance on Glucose Tolerance, Insulin Sensitivity, and Beta-cell Function

NCT03264001 | Unknown

• 1 other identifier: NEB
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes results from a combination of peripheral insulin resistance and beta-cell dysfunction, and manifests as fasting and postprandial hyperglycemia. In Singapore, despite the relatively low prevalence of overweight and obesity, the prevalence of type 2 diabetes is disproportionately high and is expected to double in the near future. This indicates that insulin resistance and beta-cell dysfunction are widely prevalent even among individuals who are not overweight or obese. Still, weight loss induced by a variety of ways (calorie restriction, exercise, surgery, etc.) is considered the cornerstone of diabetes treatment. This underscores the importance of negative energy balance in improving metabolic function. In fact, negative energy balance induced by calorie restriction can improve metabolic function acutely, i.e. within 1-2 days and before any weight loss occurs. Likewise, negative energy balance induced by a single session of aerobic exercise improves metabolic function over the next few days. However, the magnitude of negative energy balance that needs to be achieved in order to improve metabolic function, as well as possible dose-response relationships, are not known. Furthermore, the comparative efficacy of calorie restriction vs. exercise in improving metabolic function has never been directly assessed. Accordingly, a better understanding of the effects of acute negative energy balance induced by calorie restriction or aerobic exercise on insulin sensitivity and beta-cell function will have important implications for public health, by facilitating the design of effective lifestyle (diet and physical activity) interventions to prevent or treat type 2 diabetes. To test these hypotheses, whole-body insulin sensitivity, the acute insulin response to glucose, and the disposition index (i.e. beta-cell function), will be determined the morning after a single day of progressively increasing negative energy balance (equivalent to 20% or 40% of total daily energy needs for weight maintenance) induced by calorie restriction or aerobic exercise. Results from this project are expected to result in the better understanding of the effects of negative energy balance induced by diet and exercise on metabolic function. Therefore, this project may help in the design of effective lifestyle intervention programs for the prevention and treatment of type 2 diabetes.

Conditions

Insulin Sensitivity; Glucose Intolerance; Insulin Resistance; Energy Supply; Deficiency

Outcome Measures

Primary Outcomes (2)

• Insulin sensitivity

  Insulin sensitivity index (i.e. Si) will be determined by using minimal modeling analysis of the IVGTT data.

  4-6 weeks

• Beta-cell function

  Beta-cell function will be determined as the disposition index (i.e. product of acute insulin response \[AIR\] and Si) using minimal modeling analysis of the IVGTT data.

  4-6 weeks

Study Arms (2)

Diet-induced negative energy balance

EXPERIMENTAL

For the diet-induced negative energy balance arm, the three trials will include one control trial (isocaloric diet; zero energy balance) and two trials of progressively increasing negative energy balance induced by calorie restriction (20% and 40% reduction of daily energy needs for weight maintenance). With respect to physical activity, all diet trials will be performed under resting conditions.

Behavioral: Negative energy balance

Exercise-induced negative energy balance

EXPERIMENTAL

For the exercise-induced negative energy balance arm, the three trials will include one control trial (rest; zero energy balance) and two trials of progressively increasing negative energy balance induced by aerobic exercise (20% and 40% reduction of daily energy needs for weight maintenance); with respect to caloric intake, all exercise trials will be performed under isocaloric conditions.

Behavioral: Negative energy balance

Interventions

Negative energy balance BEHAVIORAL

20% and 40% reduction of daily energy needs for weight maintenance

Diet-induced negative energy balance; Exercise-induced negative energy balance

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males and females
• Age between 21-65 years
• BMI from ≥18 to \<30 kg/m2 (BMI is equal to body weight in kilograms divided by height in metres squared)

You may not qualify if:

• Persons with metabolic diseases that require use of medications (e.g. diabetes, heart disease, hypertension, etc.)
• Persons using tobacco products (smokes daily or occasionally)
• Persons who regularly consume alcohol (≥1 drink/day)
• Women on oral contraceptives or hormone replacement therapy
• Pregnant or breastfeeding women
• Persons who have had recent weight loss or gain (≥5% over the past 6 months)
• Persons with contraindication to calorie restriction (e.g. anemia) or exercise (e.g. asthma)

Sponsors & Collaborators

• Singapore Institute of Food and Biotechnology Innovation: lead

Study Sites (1)

Clinical Nutrition Research Centre

Singapore, 117609, Singapore

Location

Related Publications (29)

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  PMID: 33718425 DERIVED

• Ding C, Chooi YUC, Chan Z, Lo J, Choo J, Ding BTK, Leow MK, Magkos F. Dose-Dependent Effects of Exercise and Diet on Insulin Sensitivity and Secretion. Med Sci Sports Exerc. 2019 Oct;51(10):2109-2116. doi: 10.1249/MSS.0000000000002020.

  PMID: 31033904 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Glucose Intolerance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia

Study Officials

• Faidon Magkos, PhD

  Clinical Nutrition Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 28, 2017
• Study Start: April 4, 2017
• Primary Completion: July 31, 2018
• Study Completion: December 31, 2018
• Last Updated: March 13, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)