Progressive decrease in N-acetylaspartate/Creatine ratio in a teenager with type 1 diabetes and repeated episodes of ketoacidosis without clinically apparent cerebral edema: Evidence for permanent brain injury.

Recent data suggest that DKA may contribute to cognitive impairment in children with type 1 DM. We measured the NAA/Cr ratio in a teenager during and following 2 separate episodes of DKA without clinically apparent cerebral edema. The NAA/Cr ratio decreased during DKA and improved following recovery. However, the NAA/Cr value was lower after the second episode of DKA (1.76) than after the first (1.97). These findings provide support for the hypothesis that neuronal injury may result from DKA.

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis.

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes.

Acid-base homeostasis in children with growth hormone deficiency.

BACKGROUND: Although the primary use of growth hormone (GH) is to promote linear growth, it is also known to affect many metabolic processes and to influence renal function. In laboratory animals, growth hormone deficiency (GHD) causes a mild metabolic acidosis that is corrected by GH treatment. We observed a patient with GHD who initially presented with acidosis of unclear etiology and corrected the acidosis with GH treatment. OBJECTIVES: To determine: 1) whether children with GHD have lower mean serum bicarbonate concentrations than do children with short stature because of other causes; and 2) whether the presence of a low serum bicarbonate concentration increases the probability of GHD among children with short stature. METHODS: We collected data from the medical records of 143 children with short stature who had serum electrolyte concentrations measured as part of their initial evaluations, 66 with GHD and 77 with short stature as a result of other causes. We compared mean serum bicarbonate concentrations and bicarbonate standard deviation scores (SDS) between these two groups and determined the probability of GHD for patients according to bicarbonate SDS. RESULTS: The mean serum bicarbonate concentration was significantly lower in patients with GHD (mean standard deviation [SD]; 23.9 [0.4] mEq/L vs 25.2 [0.3] mEq/L) as was the bicarbonate SDS (-0.12 [0.14] SD vs 0.38 [0.10] SD). Twelve (75%) of 16 patients with bicarbonate SDS 1 SD. Patients with bicarbonate SDS between -1 SD and 1 SD had an intermediate probability of GHD, 46/102 (45%), similar to the overall prevalence of GHD in the study population (46%). Mean bicarbonate concentrations and bicarbonate SDS increased significantly in 9 patients who had repeat electrolyte measurements during treatment with GH (mean bicarbonate; 21.7 [1.1] mEq/L vs 26.9 [0.59] mEq/L, mean bicarbonate SDS; -1.24 [0.43] SD vs 0.55 [0.27] SD). CONCLUSIONS: Serum bicarbonate concentrations are lower in patients with GHD than in patients with short stature as a result of other causes. In addition, serum bicarbonate concentrations rise with GH treatment in patients with GHD. The probability of GHD is increased for patients with bicarbonate SDS 1 SD. These findings indicate a role for GH in maintaining normal acid-base homeostasis and suggest that GHD should be considered in children whose growth failure is attributed to other causes of acidosis.

Non-insulin dependent diabetes mellitus in Mexican-American children.

To define the clinical and metabolic characteristics of children with non-insulin-dependent diabetes mellitus (NIDDM), we reviewed the medical records of 18 children and adolescents who met either or both of the following criteria for the diagnosis of the disease: evidence of continued endogenous secretion of insulin beyond that expected in insulin-dependent diabetes mellitus and satisfactory glycemic control with diet alone or in combination with an oral hypoglycemic agent more than 2 years from the time of diagnosis. Patients who met these criteria but had islet cell antibodies or insulin autoantibodies were eliminated from the study group. Patients with NIDDM constituted 8% of all patients with diabetes seen in our pediatric clinics and 19% of diabetic patients of Central or South American ancestry. Of the 18 patients, 12 (67%) were Mexican American. The mean age of onset was 12.8 years (range, 5 to 17). Obesity (n = 9) and acanthosis nigricans (n = 12) were common findings. Ketonuria was present at diagnosis in 5 (33%) of 15 patients and acidosis in 2 of 14 (14%). Challenge with a nutritional supplement (Sustacal, Mead Johnson Nutritionals) (n = 10) showed a mean fasting serum C-peptide concentration of 1.19 nmol per liter (3.6 ng per ml). A family history of NIDDM was present in 13 (87%) of 15 patients, with 7 (47%) having 3 or more generations affected. Children with NIDDM are an important subset of those with diabetes, and this disease should be suspected in diabetic children presenting without ketoacidosis and with acanthosis nigricans, obesity, and a strong family history, particularly among those of Mexican-American ethnicity. Children with these characteristics should undergo testing of endogenous insulin secretion for appropriate therapeutic intervention.

Variation in the management of pediatric diabetic ketoacidosis by specialty training.

OBJECTIVE: To compare management strategies for pediatric diabetic ketoacidosis (DKA) among physicians with different specialty training. METHODS: We conducted a mail survey of 1000 randomly selected physicians, including 200 pediatric endocrinologists, 200 general emergency physicians, 200 pediatric emergency physicians, 200 pediatric intensivists, and 200 pediatric chief residents. We posed questions regarding a hypothetical 10-year-old patient with new onset of diabetes mellitus who is approximately 10% dehydrated but alert, with venous pH of 7.1 and serum glucose concentration of 34.7 mmol/L (625 mg/dL). Questions involved the rate of rehydration, content of intravenous fluids, insulin therapy, potassium replacement, use of sodium bicarbonate, and adjustments in therapy for decreasing serum glucose concentration. We compared responses of physicians in each specialty and used multiple regression analysis to adjust for potential confounding variables, including number of years in practice, number of children with DKA seen per month, and practice setting. RESULTS: Five hundred eighty-one physicians (58.1%) completed the survey, with responses demonstrating significant, consistent differences between specialties. Extremes of responses included the following: (1) 59% of endocrinologists vs 11% of general emergency physicians would give an initial fluid bolus of less than 20 mL/kg (odds ratio [OR], 11.7; 95% confidence interval [CI], 5.0-27.7) (P < .001); (2) 83.5% of general emergency physicians vs 42.5% of pediatric intensivists would administer an initial insulin bolus (OR, 4.1; 95% CI, 2.0-8.7) (P < .001); (3) 58.2% of pediatric intensivists vs 9% of general emergency physicians would replace fluids over a period of greater than 24 hours (OR, 14.1; 95% CI, 5.5-37.5) (P < .001); and (4) 54.3% of general emergency physicians vs 7.3% of pediatric intensivists would use potassium chloride alone for potassium replacement (OR, 10.8; 95% CI, 5.0-23.8) (P < .001). All of these differences persisted after adjusting for the potential confounding variables. CONCLUSIONS: Substantial differences exist in the management of pediatric DKA among physicians of different specialties, presumably due to differences in specialty training. These differences obscure our ability to evaluate the treatment of DKA and highlight the necessity for further studies comparing the outcomes of different treatment strategies.

Predictors of early remission of hyperthyroidism in children.

Children with hyperthyroidism often require prolonged courses of antithyroid medication to achieve remission, and long-term compliance is problematic. To determine which clinical and laboratory features predict early remission, we reviewed the records of 191 patients less than 19 yr old with Graves' disease. We compared patients achieving remission within 2 yr (group 1, n = 27) with those who completed more than 2 yr of medical therapy but did not achieve a remission (group 2, n = 79). Patients who were in neither of the above categories (n = 85) were excluded from the statistical analysis. Variables that were measurable at the time of diagnosis, recorded in more than 50% of the study population and associated with early remission in the univariate analysis (P < or = 0.05), were entered into a stepwise multiple logistic regression analysis. Variables retaining a significant association with early remission (P < 0.05) were considered independent predictors of early remission. Patients achieving early remission were older (mean, 12.5 vs. 10.9 yr, P = 0.039) and had higher body mass indexes (BMI, 19.0 vs. 16.6, P = 0.002), higher BMI SD scores (-0.03 vs. -0.60, P = 0.004), lower heart rates (110 vs. 121, P = 0.023), smaller goiters (group 1: 60% with moderate/large goiter; group 2: 83%, P = 0.050), lower platelet counts (272 vs. 339 K/microL, P = 0.006), lower serum T4 and T3 concentrations at presentation (T4: 18.3 vs. 22.5 microg/dL, P = 0.015; T3: 439 vs. 613 ng/dL, P = 0.008), and were less likely to have a positive test for thyroid stimulating Igs (group 1: 50% vs. group 2: 93%, P = 0.008). Regression analysis identified BMI SD score and goiter size as independent predictors of early remission (P < 0.05). Eighty-six percent of patients with BMI SD score above -0.5 SD and minimal/small goiters achieved early remission, compared with 13% of those with BMI SD score below -0.5 SD and moderate/large goiters. We conclude that, of multiple clinical and laboratory variables associated with early remission, BMI SD score and goiter size are independent predictors. Algorithms employing these two variables can be used to facilitate counseling of patients and expedite therapeutic decisions.

Non-insulin-dependent diabetes mellitus in childhood and adolescence.

NIDDM in children and adolescents represents a heterogeneous group of disorders with different underlying pathophysiologic mechanisms. Most subtypes of NIDDM that occur in childhood are uncommon, but some, such as early onset of "classic" NIDDM, seem to be increasing in prevalence. This observed increase is thought to be caused by societal factors that lead to sedentary lifestyles and an increased prevalence of obesity. In adults, hyperglycemia frequently exists for years before a diagnosis of NIDDM is made and treatment is begun. Microvascular complications, such as retinopathy, are often already present at the time of diagnosis. Children are frequently asymptomatic at the time of diagnosis, so screening for this disorder in high-risk populations is important. Screening should be considered for children of high-risk ethnic populations with a strong family history of NIDDM with obesity or signs of hyperinsulinism, such as acanthosis nigricans. Even for children in these high-risk groups who do not yet manifest hyperglycemia, primary care providers can have an important role in encouraging lifestyle modifications that might delay or prevent onset of NIDDM.