Jacqueline Curtis

Impact of Renin Angiotensin System Modulation on the Hyperfiltration State in Type 1 Diabetes

The initial stages of diabetic nephropathy are characterized by glomerular hyperfiltration and hypertension, processes that have been linked to initiation and progression of renal disease. Renin angiotensin system (RAS) blockade is commonly used to modify the hyperfiltration state and delay progression of renal disease. Despite this therapy, many patients progress to ESRD, suggesting heterogeneity in the response to RAS modulation. The role of the RAS in the hyperfiltration state in adolescents with uncomplicated type 1 diabetes was examined, segregated on the basis of the presence of hyperfiltration. Baseline renal hemodynamic function was characterized in 22 patients. Eleven patients exhibited glomerular hyperfiltration (GFR>or=135 ml/min), and in the remaining 11 patients, the GFR was <130 ml/min. Renal hemodynamic function was assessed in response to a graded angiotensin II (AngII) infusion during euglycemic conditions and again after 21 d of angiotensin-converting enzyme (ACE) inhibition with enalapril. AngII infusion under euglycemic conditions resulted in a significant decline in GFR and renal plasma flow in the hyperfiltration group but not in the normofiltration group. After ACE inhibition, GFR fell but did not normalize in the hyperfiltration group; the normofiltration group showed no change. These data show significant differences in renal hemodynamic function between hyperfiltering and normofiltering adolescents with type 1 diabetes at baseline, after AngII infusion and ACE inhibition. The response to ACE inhibition and AngII in hyperfiltering patients suggests that vasodilation may complement RAS activation in causing the hyperfiltration state. The interaction between glomerular vasoconstrictors and vasodilators requires examination in future studies.

The Endocrine Outcome after Surgical Removal of Craniopharyngiomas

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (DKA)

Abstract: Cerebral edema is the primary cause of morbidity and mortality in children and adolescents with diabetic ketoacidosis (DKA). We report a case of an adolescent female with life‐threatening DKA‐related cerebral edema who responded to a combination of mannitol and hypertonic saline. This is the first report of the use of hypertonic saline in the treatment of cerebral edema due to DKA.

Impact of neighbourhood-level inequity on paediatric diabetes care

To evaluate the association between neighbourhood‐level inequity and glycaemic control in paediatric participants with Type 1 diabetes using the Neighbourhood Equity Index (NEI).

Assessing social determinants of health in a pediatric diabetes clinical research trial: Are recruited subjects representative of the larger clinical population?

Social determinants of health (SDH) impact clinical outcomes and are often poorly described in research trials. Using a validated tool, SDH dimensions were compared between adolescents enrolled and not enrolled into a large diabetes study. We observed that our study cohort reflected a SDH profile mirroring the eligible population.