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Type 1 Diabetes
Inflammation in Pediatric Patients with Type 1 Diabetes—
An Early Predictor of Complications?
Janet K Snell-Bergeon, PhD, MPH
1
and Dana Dabelea, MD, PhD
2
1. Assistant Professor of Pediatrics, Barbara Davis Center for Childhood Diabetes;
2. Associate Professor, Colorado School of Public Health, University of Colorado Denver
Abstract
Type 1 diabetes is an autoimmune disease caused by the destruction of the pancreatic beta cells, and common complications include both
microvascular (kidney disease, retinopathy, neuropathy) and macrovascular (peripheral arterial disease, coronary artery disease, stroke) disease.
Hyperglycemia is a well-known risk factor for microvascular as well as macrovascular complications. However, even when glycemic control is
improved, complications are not completely avoided, which has resulted in a theory of a ‘metabolic memory.’ Systemic inflammation is a common
finding in patients with type 1 diabetes, and increased inflammatory markers appear even among children who have been recently diagnosed.
Increased inflammatory cytokines have been found to be associated with later development of cardiovascular disease, diabetic nephropathy,
retinopathy, and diabetic neuropathy, and may therefore act as a ‘second hit’ to hyperglycemia in the development of complications. Here we
review the evidence for associations between inflammation and complications among children and youth with type 1 diabetes.
Keywords
Type 1 diabetes, coronary artery disease, atherosclerosis, diabetic nephropathy, retinopathy, diabetic neuropathy, inflammation, fibrinolysis
Disclosure: The authors have no conflicts of interest to declare.
Acknowledgements: This work was supported by American Diabetes Association Post-Doctoral Fellowship #7-09-CVD-06.
Received: September 7, 2009 Accepted: November 19, 2009
Correspondence: Janet K Snell-Bergeon, PhD, MPH, Assistant Professor of Pediatrics, University of Colorado Denver, Barbara Davis Center for Childhood Diabetes,
1775 Aurora Court, Room 2306, PO Box 6511, Mail Stop A140, Aurora, CO 80045. E: Janet.Snell-Bergeon@ucdenver.edu
Type 1 diabetes is characterized by the loss of beta-cell function in the responsible for 25% of cases of end-stage renal disease in the US,
13
and
pancreas due to an autoimmune reaction. The incidence of type 1 diabetes diabetic retinopathy is the leading cause of blindness.
14
Microvascular
peaks during childhood (six to nine years of age) and adolescence (12–15 complications do not usually develop until after puberty in pediatric
years of age).
1,2
Over the past few decades, an increase in the incidence of patients with type 1 diabetes,
15
but the development of these
type 1 diabetes has been noted worldwide,
3–7
and there is some evidence complications may likely be predicted by factors that occur earlier in the
that the age at diagnosis has been decreasing. Complications of type 1 course of the disease.
diabetes include microvascular (kidney disease, retinopathy, and
neuropathy) and macrovascular (peripheral arterial disease, coronary Role of Hyperglycemia in Microvascular and
artery disease [CAD], and stroke) disease. Macrovascular Complications
The Diabetes Control and Complications Trial (DCCT) established the
The majority of deaths among patients with type 1 diabetes are importance of glycemic control in reducing the microvascular
attributed to cardiovascular disease,
8,9
which occurs at younger ages
9
complications of type 1 diabetes.
16
The follow-up Epidemiology of
and is more often fatal in adults with type 1 diabetes than in the general Diabetes Interventions and Complications (EDIC) study demonstrated
population.
10
While clinical events typically do not occur until the third that improved glycated hemoglobin (HbA
1c
) during the period of the
decade of life, evidence that the process of atheroslerosis begins in DCCT study contributed to lower complication rates years later, even
childhood has been established by several large studies, including the when glycemic control in the intensively treated and control groups
Bogalusa Heart Study
11
and the Pathobiological Determinants of converged following the DCCT.
17,18
As a result, it appears that there is a
Atherosclerosis in Youth (PDAY) study.
12
As a result, the identification ‘metabolic memory’ of prior glycemic control that continues to affect
of risk markers during childhood is critical for primary prevention of the rate of development of complications. It has been hypothesized
cardiovascular complications of type 1 diabetes. that the accumulation of advanced glycation end-products (AGEs)
during periods of chronic hyperglycemia may continue to contribute to
Microvascular complications also contribute to increased mortality and tissue damage and complications even after improvement of
morbidity in patients with type 1 diabetes, as diabetic nephropathy is hyperglycemia, as the degradation of AGEs occurs slowly.
17
© TOUCH BRIEFINGS 2009 85
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