Lysine Does Not Improve Insulin Sensitivity
Lysine Does Not Improve Insulin Sensitivity
Context Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. Objective: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m) individuals.
Methods We utilized a dual tracer technique (i.e., [6,6-H2] glucose primed constant infusion and 1-[C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios.
Results Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2 ± 0.1, 1.1 ± 0.1, 1.3 ± 0.1 mg•kg•min), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2 ± 0.1, 4.3 ± 0.2, and 4.5 ± 0.4 mg•kg•min), respectively.
Conclusions Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.
Cardiovascular disease (CVD) remains a leading cause of death among US adults. Elderly individuals are at high risk for negative cardiovascular outcomes due to age-related physiological changes that directly impact the anatomy and function of the cardiovascular system, as well as disease-related processes that are driven by poor nutritional status, physical inactivity, and other issues common at older ages. In addition, the accelerated loss of muscle mass (sarcopenia) that is typical among elderly adults, combined with the increasing prevalence of obesity in this population present additional difficulties when choosing an appropriate therapeutic course of action in this population.
Hyperglycemia is one important factor that directly influences vascular complications associated with CVD and represents a central therapeutic target for managing CVD-related outcomes in elderly adults. Although recent trials have demonstrated that intensive glucose control may be harmful compared to less-intensive standard treatment in older patients with advanced type 2 diabetes, tight glycemic control was associated with slowed progression of retinopathy and may especially reduce the risk of micro- and macrovascular disease when started earlier in the disease course. The ingestion of protein with glucose has been shown to augment insulin secretion and diminish the plasma glucose response in persons with type 2 diabetes. It has been recently reported that lysine (a readily abundant essential amino acid), when ingested with glucose, facilitates a reduction in the glucose area under the curve (AUC) by 44% without any change in plasma insulin, along with a reduction in plasma glucagon. Thus, lysine supplementation may represent a novel and cost-effective therapeutic intervention to reduce hyperglycemia and related CVD outcomes without potential complications associated with other nutritional, behavioral, or pharmacological interventions.
It is not known whether acute lysine supplementation in the previously mentioned study promoted improved glucose metabolism through 1) an increased suppression of endogenous glucose production (glucose Ra), 2) increased glucose disappearance (glucose Rd), or 3) both. Second, since almost all of the study subjects experienced some sort of mild gastrointestinal distress with higher doses of lysine, the efficacy of a lower dose of lysine requires investigation. In order to validate these preliminary studies and investigate the site of action, we propose to use a dual tracer technique ([1-C] glucose oral ingestion and [6,6-H2] glucose primed constant infusion) that will allow us to selectively delineate endogenous glucose Ra, exogenous glucose Ra, and endogenous glucose Rd. In this way, we will be able to determine the primary mechanism (increased suppression of glucose Ra, improved glucose Rd or both) responsible for the improvement in glucose AUC.
Therefore, the primary objective of this study was to determine the efficacy of acute lysine supplementation on glucose metabolism in older, overweight individuals. In addition, we incorporated the application of stable isotope tracer methodology coupled with an OGTT that allowed us to determine the site of action (hepatic and/or peripheral) that was influenced by lysine supplementation. To our knowledge, the influence of lysine supplementation on hepatic and peripheral glucose metabolism when given in combination with an OGTT has not been investigated. The practical implications of a readily available, efficacious nutrient that could be used to promote more effective glucose homeostasis have important implications.
Abstract and Introduction
Abstract
Context Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. Objective: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m) individuals.
Methods We utilized a dual tracer technique (i.e., [6,6-H2] glucose primed constant infusion and 1-[C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios.
Results Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2 ± 0.1, 1.1 ± 0.1, 1.3 ± 0.1 mg•kg•min), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2 ± 0.1, 4.3 ± 0.2, and 4.5 ± 0.4 mg•kg•min), respectively.
Conclusions Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.
Introduction
Cardiovascular disease (CVD) remains a leading cause of death among US adults. Elderly individuals are at high risk for negative cardiovascular outcomes due to age-related physiological changes that directly impact the anatomy and function of the cardiovascular system, as well as disease-related processes that are driven by poor nutritional status, physical inactivity, and other issues common at older ages. In addition, the accelerated loss of muscle mass (sarcopenia) that is typical among elderly adults, combined with the increasing prevalence of obesity in this population present additional difficulties when choosing an appropriate therapeutic course of action in this population.
Hyperglycemia is one important factor that directly influences vascular complications associated with CVD and represents a central therapeutic target for managing CVD-related outcomes in elderly adults. Although recent trials have demonstrated that intensive glucose control may be harmful compared to less-intensive standard treatment in older patients with advanced type 2 diabetes, tight glycemic control was associated with slowed progression of retinopathy and may especially reduce the risk of micro- and macrovascular disease when started earlier in the disease course. The ingestion of protein with glucose has been shown to augment insulin secretion and diminish the plasma glucose response in persons with type 2 diabetes. It has been recently reported that lysine (a readily abundant essential amino acid), when ingested with glucose, facilitates a reduction in the glucose area under the curve (AUC) by 44% without any change in plasma insulin, along with a reduction in plasma glucagon. Thus, lysine supplementation may represent a novel and cost-effective therapeutic intervention to reduce hyperglycemia and related CVD outcomes without potential complications associated with other nutritional, behavioral, or pharmacological interventions.
It is not known whether acute lysine supplementation in the previously mentioned study promoted improved glucose metabolism through 1) an increased suppression of endogenous glucose production (glucose Ra), 2) increased glucose disappearance (glucose Rd), or 3) both. Second, since almost all of the study subjects experienced some sort of mild gastrointestinal distress with higher doses of lysine, the efficacy of a lower dose of lysine requires investigation. In order to validate these preliminary studies and investigate the site of action, we propose to use a dual tracer technique ([1-C] glucose oral ingestion and [6,6-H2] glucose primed constant infusion) that will allow us to selectively delineate endogenous glucose Ra, exogenous glucose Ra, and endogenous glucose Rd. In this way, we will be able to determine the primary mechanism (increased suppression of glucose Ra, improved glucose Rd or both) responsible for the improvement in glucose AUC.
Therefore, the primary objective of this study was to determine the efficacy of acute lysine supplementation on glucose metabolism in older, overweight individuals. In addition, we incorporated the application of stable isotope tracer methodology coupled with an OGTT that allowed us to determine the site of action (hepatic and/or peripheral) that was influenced by lysine supplementation. To our knowledge, the influence of lysine supplementation on hepatic and peripheral glucose metabolism when given in combination with an OGTT has not been investigated. The practical implications of a readily available, efficacious nutrient that could be used to promote more effective glucose homeostasis have important implications.