OBJECTIVE -To determine if children with type 1 diabetes have increased arterial stiffness by estimating augmentation index with the simple noninvasive technique of radial artery tonometry.RESEARCH DESIGN AND METHODS -We studied 98 type 1 diabetic children and 57 healthy control subjects, ages 10 -18 years, matched for age, sex, race, and BMI, generating 43 matched pairs. Radial artery tonometry was performed, and blood was collected for analysis of fasting lipids, HbA 1c , glucose, and cytokines in all children.RESULTS -Children with diabetes had a significantly higher augmentation index corrected to a heart rate of 75 (AI 75 ) than their matched control subjects. Mean AI 75 in type 1 diabetic subjects was 1.11 Ϯ 10.15 versus Ϫ3.32 Ϯ 10.36 in control subjects. The case-control difference was 5.20 Ϯ 11.02 (P ϭ 0.0031).CONCLUSIONS -Children with type 1 diabetes have increased arterial stiffness compared with healthy control subjects. Radial artery tonometry is a simple noninvasive technique that could be added to the armamentarium of tests used to provide cardiovascular risk stratification in children with type 1 diabetes. Many adult studies have demonstrated that the incidence of cardiovascular events can be lessened with reduction of plasma cholesterol and optimal management of hypertension. Unfortunately, the majority of patients who are being treated aggressively have already manifested cardiovascular complications. Because efficacy of intervention in children cannot be measured by cardiovascular event end points, surrogate markers must be used. Brachial artery reactivity is a technique that measures the endothelium-dependent dilation of the brachial artery in response to reactive hyperemia. In patients with endothelial dysfunction, the ability of the artery to dilate is impaired. Endothelial dysfunction, as measured by decreased brachial reactivity, has been shown to be an independent predictor of cardiovascular events (2). Impaired brachial reactivity has been demonstrated in adults and in a small group of children with type 1 diabetes (3,4). DiabetesRecent studies have demonstrated that endothelial function, as measured by brachial reactivity and carotid intimamedial thickness (IMT), are abnormal in children with type 1 diabetes (5); however, no one has yet demonstrated if radial tonometry can provide similar results. Because radial tonometry can be performed in nearly any clinic setting, is easy and affordable to perform, and provides the user with instant analysis of the patient's arterial stiffness, tonometry has a potential advantage over brachial reactivity and carotid IMT as a clinically useful tool.To test the utility of radial tonometry, we studied whether children with type 1 diabetes had increased arterial stiffness, as measured by augmentation index (AI), when compared with healthy control subjects. To gain further insight into their cardiovascular risk profiles, we obtained historical data on family history, exercise, and glycemic control and obtained blood for lipid, glucose, HbA 1c , and cyto...

OBJECTIVE-Antilymphocyte serum can reverse overt type 1 diabetes in NOD mice; yet, the therapeutic parameters and immunological mechanisms underlying the ability for this agent to modulate autoimmune responses against ␤-cells are unclear, forming the rationale for this investigation.RESEARCH DESIGN AND METHODS-A form of antilymphocyte serum, rabbit anti-mouse thymocyte globulin (mATG), was utilized in a variety of in vivo and in vitro settings, each for the purpose of defining the physiological, immunological, and metabolic activities of this agent, with particular focus on actions influencing development of type 1 diabetes.RESULTS-We observed that mATG attenuates type 1 diabetes development in an age-dependent fashion, only proving efficacious at disease onset or in the late pre-diabetic phase (12 weeks of age). When provided at 12 weeks of age, mATG reversed pancreatic insulitis, improved metabolic responses to glucose challenge, and rapidly increased frequency of antigen-presenting cells in spleen and pancreatic lymph nodes. Surprisingly, mATG therapy dramatically increased, in an age-dependent fashion, the frequency and the functional activity of CD4 ϩ CD25 ϩ regulatory T-cells. Adoptive transfer/cotransfer studies of type 1 diabetes also support the concept that mATG treatment induces a stable and transferable immunomodulatory repertoire in vivo.CONCLUSIONS-These findings indicate that an induction of immunoregulation, rather than simple lymphocyte depletion, contributes to the therapeutic efficacy of antithymocyte globulin and suggest that time-dependent windows for the ability to delay or reverse type 1 diabetes exist based on the capacity to enhance the functional activity of regulatory T-cells. Diabetes 57: [405][406][407][408][409][410][411][412][413][414] 2008

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