The potential effect of metabolic alkalosis on insulin sensitivity in an adolescent with new-onset type 1 diabetes.

Metabolic alkalosis induced by ingestion of alkaline water may enhance insulin sensitivity in type 1 diabetes mellitus.

Increased systemic Th17 cytokines are associated with diastolic dysfunction in children and adolescents with diabetic ketoacidosis.

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6-12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.

An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment.

BACKGROUND: During the late 1900s, raised intracranial pressure (ICP) during treatment of pediatric diabetic ketoacidosis (DKA) surfaced as the most important cause of morbidity and mortality in pediatric DKA. The contribution of fluid and electrolyte therapy to neurologic deterioration during treatment remains controversial. METHODS: We proposed a physiologic approach to treatment of DKA, incorporating the principles of rehydration of hypertonic states. Consecutive episodes of pediatric DKA were managed using continuous intravenous insulin, an individualized assessment of the degree of dehydration, and rehydration solutions of tonicity approximating that of the patient. Gradual replacement of the volume of deficit after correction of shock, if present, was planned over 48 h with special attention to changes in effective osmolality along with intensive cardiorespiratory, neurologic, and biochemical monitoring. Mannitol was given for signs or symptoms of raised ICP. RESULTS: Six hundred and thirty-five consecutive episodes of pediatric DKA were treated from January 1988 to September 2005. Means +/- standard deviation (SD) for initial measured concentrations of total carbon dioxide, glucose, and urea nitrogen were 7.8 +/- 3.3 mmol/L, 602 +/- 271 mg/dL (33.4 +/- 15 mmol/L), and 21 +/- 1 mg/dL (7.4 +/- 3.6 mmol/L), respectively. Pretreatment blood gases were available for 477 episodes. The mean initial partial pressures of arterial and venous carbon dioxide +/- SD were 16.8 +/- 7 mmHg (kP(a)CO(2)= 2.24 +/- 0.93) for n = 308 and 26.6 +/- 7 mmHg (kP(v)CO(2)= 3.54 +/- 0.93) for n = 169, respectively. Although repair was planned to occur over 48 h, the mean time to achieve clinical rehydration and correction of DKA was 11.6 +/- 6.2 h. Mannitol was given in 35 (5.5%) episodes. There was no neurologic morbidity or mortality. CONCLUSION: Management of pediatric DKA using this multifaceted physiologic approach and the principles of rehydration described is safe and appears to minimize the risk of brain herniation during treatment.

Prehospital cardiac arrest in diabetic ketoacidemia: why brain swelling may lead to death before treatment.

An adolescent is reported with type 1 diabetes mellitus and diabetic ketoacidemia (DKA) who died from brain herniation prior to treatment with intravenous fluids and intravenous insulin. The pathophysiology of raised intracranial pressure (ICP) and water intoxication is discussed. As DKA evolves, water and electrolyte losses are replaced by very hypotonic fluids taken orally, leading to a physiologic excess of free water that would cause brain swelling prior to treatment. Central nervous system acidosis may interfere with normal compensatory mechanisms that help prevent small increases in ICP. The pathophysiology of pre-treatment brain swelling has important implications for rehydration with intravenous fluids and treatment with insulin. Prevention of DKA is paramount as well as complete postmortem evaluation of patients who die from this disease.