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Aspects of inflammation and oxidative stress in pediatric obesity and type 1 diabetes: an overview of ten years of studies.

Tran B, Oliver S, Rosa J, Galassetti P - Exp Diabetes Res (2012)

Bottom Line: In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear.Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field.This paper offers a concise overview of the salient results from this decade-long research effort.

View Article: PubMed Central - PubMed

Affiliation: Insitute for Clinical and Translational Science, University of California, 843 Health Science Road, Irvine, CA 92697, USA.

ABSTRACT
Obesity and type 1 diabetes (T1DM) are the two most common conditions of altered metabolism in children and adolescents. In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear. Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field. Interestingly, while obese and type 1 diabetic children often differed in the specific type and magnitude of molecular alterations, in both groups a clear exaggeration of inflammatory and oxidative activation was detected when compared to healthy, age-matched controls. Our main findings include definition of resting and exercise-induced cytokine patterns and leukocyte profiles, patterns of activation of immune cells in vitro, and correlation of the magnitude of observed alterations with severity of obesity and quality of glycemic control. Further, we have identified a series of alterations in growth factor profiles during exercise that parallel inflammatory changes in obese children. This paper offers a concise overview of the salient results from this decade-long research effort.

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Related in: MedlinePlus

Plasma interleukin-6 (IL-6) in 47 children with type 1 diabetes before, at the end of, and 30 min after a standardized 30 minute intermittent exercise challenge (a) and exercise-induced IL-6 increments (b). While all children exercised in euglycemic conditions (and had been euglycemic for at least the two hours preceding exercise), they differed in average glycemic control during the previous three days and were therefore subdivided in four groups (11-12 subjects each) with increasing mean prior 3-day glycemia. Children in the group with the lowest mean glycemia (<8 mM, only slightly greater than comparable healthy controls) displayed the lowest IL-6 values at all time points; with greater mean prior glycemia, IL-6 values became progressively higher. Data are group means ± SE. *P < 0.05 <8.0 mM group I.
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fig1: Plasma interleukin-6 (IL-6) in 47 children with type 1 diabetes before, at the end of, and 30 min after a standardized 30 minute intermittent exercise challenge (a) and exercise-induced IL-6 increments (b). While all children exercised in euglycemic conditions (and had been euglycemic for at least the two hours preceding exercise), they differed in average glycemic control during the previous three days and were therefore subdivided in four groups (11-12 subjects each) with increasing mean prior 3-day glycemia. Children in the group with the lowest mean glycemia (<8 mM, only slightly greater than comparable healthy controls) displayed the lowest IL-6 values at all time points; with greater mean prior glycemia, IL-6 values became progressively higher. Data are group means ± SE. *P < 0.05 <8.0 mM group I.

Mentions: A logical extension of the above experiments became the characterization of the nature of the hyperglycemic states (severity, durations, or distance in the past) that led to subsequent sustained inflammation. In a previous study, we divided 29 T1DM children in to 4 subgroups, based on their spontaneous morning glycemic level; we then normalized blood glucose in all subjects, kept them euglycemic for at least 2 hours, and then measured plasma IL-6. Not surprisingly, we observed that the group with the highest prior morning plasma glucose (>300 mg/dL) also had the highest IL-6 concentrations; the other three groups (prior glycemia of 200–300, 150–200, and <150 mg/dL, resp.) displayed progressively lower IL-6 levels, the lowest being identical to healthy controls. A subsequent study expanded these findings by incorporating the effect of prior hyperglycemia not only in the morning of the measurements, but also for the full previous three days. Participants wore a continuous glucose monitoring system recording glycemia every 5 minutes for a 3-day period while continuing their normal insulin regimen and conducting normal life activities (Figure 1). This allowed us to obtain additional information, including depth, duration, and repetition pattern of each hyperglycemic episode, as well as total time spent above arbitrary hyperglycrmic thresholds (i.e., 11 mM, the clinical definition of postprandial hyperglycemia). Among these variables, the average glycemia over the whole 3-day period correlated best with IL-6 levels at the end of the continuous measurements, after all subjects' glycemia had again been normalized for several hours. Again, children with the highest mean prior 3-day glycemia had the highest IL-6 levels and progressively lower IL-6 as their prior glycemia approached the physiological profile. Within subjects with similar mean 3-day glycemia, a greater proinflammatory effect was observed in those with the highest hyperglycemic peaks, indicating that optimal management strategies in these patients must be aimed not only at limiting the overall occurrence of hyperglycemia, but also at preventing its most dangerous characteristics (for example, the same overall amount of postprandial hyperglycemia can be achieved without a very high hyperglycemic peak if insulin administration is timed carefully and carbohydrate ingestion is spaced over a longer time).


Aspects of inflammation and oxidative stress in pediatric obesity and type 1 diabetes: an overview of ten years of studies.

Tran B, Oliver S, Rosa J, Galassetti P - Exp Diabetes Res (2012)

Plasma interleukin-6 (IL-6) in 47 children with type 1 diabetes before, at the end of, and 30 min after a standardized 30 minute intermittent exercise challenge (a) and exercise-induced IL-6 increments (b). While all children exercised in euglycemic conditions (and had been euglycemic for at least the two hours preceding exercise), they differed in average glycemic control during the previous three days and were therefore subdivided in four groups (11-12 subjects each) with increasing mean prior 3-day glycemia. Children in the group with the lowest mean glycemia (<8 mM, only slightly greater than comparable healthy controls) displayed the lowest IL-6 values at all time points; with greater mean prior glycemia, IL-6 values became progressively higher. Data are group means ± SE. *P < 0.05 <8.0 mM group I.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475317&req=5

fig1: Plasma interleukin-6 (IL-6) in 47 children with type 1 diabetes before, at the end of, and 30 min after a standardized 30 minute intermittent exercise challenge (a) and exercise-induced IL-6 increments (b). While all children exercised in euglycemic conditions (and had been euglycemic for at least the two hours preceding exercise), they differed in average glycemic control during the previous three days and were therefore subdivided in four groups (11-12 subjects each) with increasing mean prior 3-day glycemia. Children in the group with the lowest mean glycemia (<8 mM, only slightly greater than comparable healthy controls) displayed the lowest IL-6 values at all time points; with greater mean prior glycemia, IL-6 values became progressively higher. Data are group means ± SE. *P < 0.05 <8.0 mM group I.
Mentions: A logical extension of the above experiments became the characterization of the nature of the hyperglycemic states (severity, durations, or distance in the past) that led to subsequent sustained inflammation. In a previous study, we divided 29 T1DM children in to 4 subgroups, based on their spontaneous morning glycemic level; we then normalized blood glucose in all subjects, kept them euglycemic for at least 2 hours, and then measured plasma IL-6. Not surprisingly, we observed that the group with the highest prior morning plasma glucose (>300 mg/dL) also had the highest IL-6 concentrations; the other three groups (prior glycemia of 200–300, 150–200, and <150 mg/dL, resp.) displayed progressively lower IL-6 levels, the lowest being identical to healthy controls. A subsequent study expanded these findings by incorporating the effect of prior hyperglycemia not only in the morning of the measurements, but also for the full previous three days. Participants wore a continuous glucose monitoring system recording glycemia every 5 minutes for a 3-day period while continuing their normal insulin regimen and conducting normal life activities (Figure 1). This allowed us to obtain additional information, including depth, duration, and repetition pattern of each hyperglycemic episode, as well as total time spent above arbitrary hyperglycrmic thresholds (i.e., 11 mM, the clinical definition of postprandial hyperglycemia). Among these variables, the average glycemia over the whole 3-day period correlated best with IL-6 levels at the end of the continuous measurements, after all subjects' glycemia had again been normalized for several hours. Again, children with the highest mean prior 3-day glycemia had the highest IL-6 levels and progressively lower IL-6 as their prior glycemia approached the physiological profile. Within subjects with similar mean 3-day glycemia, a greater proinflammatory effect was observed in those with the highest hyperglycemic peaks, indicating that optimal management strategies in these patients must be aimed not only at limiting the overall occurrence of hyperglycemia, but also at preventing its most dangerous characteristics (for example, the same overall amount of postprandial hyperglycemia can be achieved without a very high hyperglycemic peak if insulin administration is timed carefully and carbohydrate ingestion is spaced over a longer time).

Bottom Line: In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear.Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field.This paper offers a concise overview of the salient results from this decade-long research effort.

View Article: PubMed Central - PubMed

Affiliation: Insitute for Clinical and Translational Science, University of California, 843 Health Science Road, Irvine, CA 92697, USA.

ABSTRACT
Obesity and type 1 diabetes (T1DM) are the two most common conditions of altered metabolism in children and adolescents. In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear. Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field. Interestingly, while obese and type 1 diabetic children often differed in the specific type and magnitude of molecular alterations, in both groups a clear exaggeration of inflammatory and oxidative activation was detected when compared to healthy, age-matched controls. Our main findings include definition of resting and exercise-induced cytokine patterns and leukocyte profiles, patterns of activation of immune cells in vitro, and correlation of the magnitude of observed alterations with severity of obesity and quality of glycemic control. Further, we have identified a series of alterations in growth factor profiles during exercise that parallel inflammatory changes in obese children. This paper offers a concise overview of the salient results from this decade-long research effort.

Show MeSH
Related in: MedlinePlus