Ignite Creation Date:
2024-05-06 @ 10:28 AM
Last Modification Date:
2024-10-26 @ 12:30 PM
Study NCT ID:
NCT03264001
Status:
UNKNOWN
Last Update Posted:
2018-03-13
First Post:
2017-08-18
Brief Title:
Effects of Progressive Negative Energy Balance on Glucose Tolerance Insulin Sensitivity and Beta-cell Function
Sponsor:
Clinical Nutrition Research Centre Singapore
Organization:
Clinical Nutrition Research Centre Singapore
Study Overview
Official Title:
Effects of Progressive Negative Energy Balance Induced by Diet or Exercise on Glucose Tolerance Insulin Sensitivity and Beta-cell Function
Status:
UNKNOWN
Status Verified Date:
2018-03
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 ie 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 ie 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
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 ie 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
Detailed Description:
Metabolic dysfunction obesity and type 2 diabetes The incidence of overweight and obesity has been increasing during the past 2-3 decades in Singapore and is expected to rise further in the future By the year 2050 it is estimated that more than half of the population will be overweight or obese defined as having a body mass index BMI calculated as the weight in kilograms divided by the square of height in meters equal to or greater than 25 kgm2 This is likely responsible at least in part for the concomitant increase in obesity-related co-morbid conditions and particularly type 2 diabetes The relationship between BMI and the risk for type 2 diabetes in populations from the Asia-Pacific region is linear within a wide range of BMI values from 21 kgm2 to 34 kgm2 so that for every 2 kgm2 increase in BMI which corresponds to 6 kg for a normal-weight person of average stature the risk for developing type 2 diabetes rises by 27 In Singapore the prevalence of type 2 diabetes is expected to double from 73 in 1990 to 15 in 2050 predominantly as a result of the fattening of the population Remarkably however the prevalence of type 2 diabetes in Singapore is similar to that in the Unites States even though the prevalence of overweight and obesity BMI 25 kgm2 is approximately half This corroborates findings from many studies demonstrating that markers of metabolic dysfunction and particularly hyperglycemia hyperinsulinemia and insulin resistance are highly prevalent among Singaporean adults even among people who are not overweight or obese This likely results in increased risk for developing type 2 diabetes These observations underscore the importance of metabolic dysfunction independent of body weight per se
Metabolic effects of weight loss The pathogenesis of type 2 diabetes involves peripheral insulin resistance ie resistance of peripheral tissues and particularly skeletal muscle to the glucose uptake-promoting effect of insulin and inadequate secretion of insulin from the pancreatic beta-cells upon glucose stimulation leading to fasting and postprandial hyperglycemia Weight loss achieved as a result of chronic negative energy balance induced by a variety of ways calorie restriction exercise pharmacotherapy bariatric surgery improves metabolic function and is considered the cornerstone of diabetes prevention and management Part of the beneficial effect of weight loss could be due to the reduction in total body fat intra-abdominal fat and ectopic fat accumulation in metabolically active organs eg muscle pancreas and liver however acute perturbations in energy balance whether positive or negative for a period of 24-72 hours can affect insulin action beta-cell function and glycemic control even before any changes in body weight or body fat distribution occur For example one day of overfeeding disrupts 24-hr glucose homeostasis and two days of caloric restriction improves insulin action Likewise exercise can also lead to negative energy balance and is a very potent intervention that readily improves metabolic function and particularly insulin sensitivity even after just a single session Nevertheless the degree of negative energy balance that needs to be achieved by calorie restriction or exercise in order to improve insulin action and beta-cell function is not known and the dose-response relationship between negative energy balance and metabolic function remains elusive Furthermore the comparative efficacy of calorie restriction and exercise on improving the mechanisms regulating glucose homeostasis ie insulin sensitivity and beta-cell function has not been adequately studied One study found that for the same amount weight loss 8-9 of initial body weight induced by a low-calorie diet or endurance exercise exercise caused a greater reduction in fat mass a smaller decrease in muscle mass and led to a greater increase in insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp by 30 and a greater reduction in the total insulin response to an oral glucose tolerance test by 25-fold compared with matched diet-induced weight loss although these differences did not reach statistical significance These observations raise the possibility that for the same negative energy balance exercise may be more effective than calorie restriction in improving metabolic function however these findings are difficult to interpret in the face of the concomitant more favorable changes in body composition and fat distribution No study has directly assessed the effects of the same acute negative energy balance induced by calorie restriction or aerobic exercise on metabolic function
Accordingly a better understanding of the effects of calorie restriction and exercise on insulin sensitivity beta-cell function and daily glycemic control will have important implications for the design of effective lifestyle intervention targeted at preventing or managing type 2 diabetes To this end this study aims to test the following hypotheses
Hypothesis 1 It is hypothesized that a single day of negative energy balance induced by calorie restriction improves intravenous glucose tolerance because of improved beta-cell function without changes in insulin sensitivity The investigators further hypothesize that this effect requires 20 negative energy balance and does not improve further with greater energy restriction 40
Hypothesis 2 It is hypothesized that a single day of negative energy balance induced by aerobic exercise improves intravenous glucose tolerance because of improved insulin sensitivity without changes in beta-cell function The investigators further hypothesize this effect requires 20 negative energy balance and improves further with greater energy restriction 40
Hypothesis 3 It is hypothesized that at any given level of negative energy balance 20 or 40 calorie restriction has a greater effect than aerobic exercise on beta-cell function whereas aerobic exercise has a greater effect than calorie restriction on insulin sensitivity
Metabolic effects of weight loss The pathogenesis of type 2 diabetes involves peripheral insulin resistance ie resistance of peripheral tissues and particularly skeletal muscle to the glucose uptake-promoting effect of insulin and inadequate secretion of insulin from the pancreatic beta-cells upon glucose stimulation leading to fasting and postprandial hyperglycemia Weight loss achieved as a result of chronic negative energy balance induced by a variety of ways calorie restriction exercise pharmacotherapy bariatric surgery improves metabolic function and is considered the cornerstone of diabetes prevention and management Part of the beneficial effect of weight loss could be due to the reduction in total body fat intra-abdominal fat and ectopic fat accumulation in metabolically active organs eg muscle pancreas and liver however acute perturbations in energy balance whether positive or negative for a period of 24-72 hours can affect insulin action beta-cell function and glycemic control even before any changes in body weight or body fat distribution occur For example one day of overfeeding disrupts 24-hr glucose homeostasis and two days of caloric restriction improves insulin action Likewise exercise can also lead to negative energy balance and is a very potent intervention that readily improves metabolic function and particularly insulin sensitivity even after just a single session Nevertheless the degree of negative energy balance that needs to be achieved by calorie restriction or exercise in order to improve insulin action and beta-cell function is not known and the dose-response relationship between negative energy balance and metabolic function remains elusive Furthermore the comparative efficacy of calorie restriction and exercise on improving the mechanisms regulating glucose homeostasis ie insulin sensitivity and beta-cell function has not been adequately studied One study found that for the same amount weight loss 8-9 of initial body weight induced by a low-calorie diet or endurance exercise exercise caused a greater reduction in fat mass a smaller decrease in muscle mass and led to a greater increase in insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp by 30 and a greater reduction in the total insulin response to an oral glucose tolerance test by 25-fold compared with matched diet-induced weight loss although these differences did not reach statistical significance These observations raise the possibility that for the same negative energy balance exercise may be more effective than calorie restriction in improving metabolic function however these findings are difficult to interpret in the face of the concomitant more favorable changes in body composition and fat distribution No study has directly assessed the effects of the same acute negative energy balance induced by calorie restriction or aerobic exercise on metabolic function
Accordingly a better understanding of the effects of calorie restriction and exercise on insulin sensitivity beta-cell function and daily glycemic control will have important implications for the design of effective lifestyle intervention targeted at preventing or managing type 2 diabetes To this end this study aims to test the following hypotheses
Hypothesis 1 It is hypothesized that a single day of negative energy balance induced by calorie restriction improves intravenous glucose tolerance because of improved beta-cell function without changes in insulin sensitivity The investigators further hypothesize that this effect requires 20 negative energy balance and does not improve further with greater energy restriction 40
Hypothesis 2 It is hypothesized that a single day of negative energy balance induced by aerobic exercise improves intravenous glucose tolerance because of improved insulin sensitivity without changes in beta-cell function The investigators further hypothesize this effect requires 20 negative energy balance and improves further with greater energy restriction 40
Hypothesis 3 It is hypothesized that at any given level of negative energy balance 20 or 40 calorie restriction has a greater effect than aerobic exercise on beta-cell function whereas aerobic exercise has a greater effect than calorie restriction on insulin sensitivity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None