Severe complications after initial management of hyperglycemic hyperosmolar syndrome and diabetic ketoacidosis with a standard diabetic ketoacidosis protocol.

Hyperglycemic hyperosmolar syndrome (HHS) is a clinical entity not identical to diabetic ketoacidosis (DKA), and with a markedly higher mortality. Children with HHS can also present with concomitant DKA. Patients with HHS (with or without DKA) are profoundly dehydrated but often receive inadequate fluid resuscitation as well as intravenous insulin therapy based on traditional DKA protocols, and this can lead to devastating consequences.

Hypocalcemic cardiomyopathy as initial presentation of primary hypoparathyroidism.

Cardiomyopathy is a rare but life-threatening condition in children. Myocarditis is the leading cause of dilated cardiomyopathy (DCM) and prognosis is generally poor without heart transplantation. We report a rare case of hypocalcemic DCM due to primary hypoparathyroidism in a male infant.

Overweight and obesity in children and adolescents.

Obesity among children, adolescents and adults has emerged as one of the most serious public health concerns in the 21st century. The worldwide prevalence of childhood obesity has increased remarkably over the past 3 decades. The growing prevalence of childhood obesity has also led to appearance of obesity-related comorbid disease entities at an early age.

Decreased cystathionine-γ-lyase (CSE) activity in livers of type 1 diabetic rats and peripheral blood mononuclear cells (PBMC) of type 1 diabetic patients.

The liver plays a major role in the formation of H2S, a novel signaling molecule. Diabetes is associated with lower blood levels of H2S. This study investigated the activities of cystathionine-γ-lyase (CSE, the enzyme that catalyzes H2S formation) in livers of type 1 diabetic (T1D) animals and in peripheral blood mononuclear cells (PBMC) isolated from T1D patients.

SDF-1-CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1-SLIT2 interactions in mice.

Aims/hypothesis: We had previously reported that stromal cell-derived factor 1 (SDF-1) mediates chemorepulsion of diabetogenic T cell adhesion to islet microvascular endothelium through unknown mechanisms in NOD mice. Here we report that SDF-1-mediated chemorepulsion occurs through slit homologue (SLIT)2-roundabout, axon guidance receptor, homologue 1 (Drosophila) (ROBO1) interactions.

Methods: C-X-C receptor (CXCR)4 and ROBO1 protein expression was measured in mouse and human T cells.

Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes.

Objective: To compare indices of insulin secretion, insulin sensitivity (IS), and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab(-)) versus those with T2DM and positive autoantibodies (Ab(+)) to examine whether differences in β-cell function can be detected between the 2 groups.

Study Design: Twenty-seven youth with Ab(-) and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal-derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [ΔI(30)/ΔG(30)] and C-peptide [ΔC(30)/ΔG(30)]), and oDI were calculated.

Progressive deterioration of β-cell function in obese youth with type 2 diabetes.

Objective: In adults, type 2 diabetes (T2DM) is characterized with progressive deterioration in insulin secretion. Data are scanty in youth. We investigated prospectively the change in β-cell function and in insulin sensitivity in youth with T2DM.

Type 2 diabetes mellitus in a young girl: ominous presentation and atypical course.

Objective: To report a 7-year-old young girl who was found unresponsive and found to be in severe diabetic ketoacidosis (DKA). Presence of obesity, acanthosis nigricans, and strong family history of type 2 diabetes mellitus (T2DM) along with negative pancreatic autoimmune antibody evaluation suggested T2DM as the culprit.

Methods: We present clinical findings, laboratory test results, and imaging reports as well as follow-up on this unique presentation of T2DM.

Type 2 diabetes in youth: are there racial differences in β-cell responsiveness relative to insulin sensitivity?

Objective: Non-diabetic African American (AA) youth have an upregulated insulin secretion relative to insulin sensitivity (IS) compared with their American White (AW) peers. We investigated if similar racial differences exist in youth with T2DM.

Research Design And Methods: Fourteen AAs and 14 AWs T2DM adolescents underwent evaluation of IS and clearance (hyperinsulinemic-euglycemic clamp), first- and second-phase insulin and C-peptide secretion (hyperglycemic clamp); body composition (DEXA); and abdominal adiposity (CT).

Declining β-cell function relative to insulin sensitivity with escalating OGTT 2-h glucose concentrations in the nondiabetic through the diabetic range in overweight youth.

Objective: Overweight in youth is associated with the risk of developing type 2 diabetes. We hypothesized that β-cell function relative to insulin sensitivity decreases with increasing 2-h glucose levels based on an oral glucose tolerance test (OGTT) in overweight youth. RESEARCH DESIGN AND METHODS A total of 147 overweight (BMI ≥85th percentile for age and sex) youth, aged 8 to <20 years, undertook three tests: 1) a 3-h hyperinsulinemic-euglycemic clamp; 2) a 2-h hyperglycemic clamp; and 3) a 2-h OGTT.

From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation.

Objective: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered pre-diabetes states. There are limited data in pediatrics in regard to their pathophysiology. We investigated differences in insulin sensitivity and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.

Islet cell antibody-positive versus -negative phenotypic type 2 diabetes in youth: does the oral glucose tolerance test distinguish between the two?

OBJECTIVE Using the clamp technique, youths with a clinical diagnosis of type 2 diabetes (CDx-type 2 diabetes) and positive pancreatic autoantibodies (Ab(+)) were shown to have severe impairment in insulin secretion and less insulin resistance than their peers with negative antibodies (Ab(-)). In this study, we investigated whether oral glucose tolerance test (OGTT)-derived indexes of insulin secretion and sensitivity could distinguish between these two groups. RESEARCH DESIGN AND METHODS A total of 25 Ab(-), 11 Ab(+) CDx-type 2 diabetic, and 21 obese control youths had an OGTT.

Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients.

Objective: Some obese youth with a clinical diagnosis of type 2 diabetes have evidence of islet cell autoimmunity with positive autoantibodies. In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab-) and -positive (Ab+) youth with clinically diagnosed type 2 diabetes in comparison with control subjects.

Research Design And Methods: Sixteen Ab- and 26 Ab+ clinically diagnosed type 2 diabetic patients and 39 obese control youth underwent evaluation of insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp), substrate oxidation (indirect calorimetry), first- and second-phase insulin secretion (2-h hyperglycemic clamp), body composition and abdominal adiposity (dual energy X-ray absorptiometry and computed tomography scan, respectively), and glucose disposition index (first-phase insulin secretion x insulin sensitivity).

In vivo insulin sensitivity and secretion in obese youth: what are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?

Objective: Impaired glucose tolerance (IGT) represents a pre-diabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes.

Measures of beta-cell function during the oral glucose tolerance test, liquid mixed-meal test, and hyperglycemic clamp test.

Objective: To evaluate clinically useful measures of beta-cell function derived from the oral glucose tolerance test (OGTT) or mixed-meal (ie, Boost) tolerance test to assess insulin secretion in comparison with the gold standard, the hyperglycemic clamp (Hyper-C) test.

Study Design: We hypothesized that OGTT/Boost-derived measures are useful estimates of beta-cell function and correlate well with insulin secretion measured by the Hyper-C test. This study was designed to assess the correlation between the ratio of the early incremental insulin/glucose responses at 15 and 30 minutes (DeltaI(15)/DeltaG(15) and DeltaI(30)/DeltaG(30)) of the OGTT and the Boost test with insulin secretion measured during the Hyper-C test (225 mg/dL).

Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers.

Objectives: To examine the prevalence of the metabolic syndrome using different pediatric definitions reported in the literature and its relationship to abdominal adipose tissue (AT), in vivo insulin resistance, and inflammatory biomarkers in children and adolescents, as well as the utility of fasting insulin and adiponectin as predictors of the metabolic syndrome.

Study Design: Cross-sectional measurements were obtained from 122 African Americans and 129 Caucasians age 8 to 19 years. Insulin sensitivity (IS) was measured by a 3-h hyperinsulinemic-euglycemic clamp.

Insulin resistance: link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth.

Objective: We examined the relationship of in vivo insulin sensitivity to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth.

Research Design And Methods: Subjects included 216 youths (8-19 years of age) who participated in a 3-h hyperinsulinemic-euglycemic clamp.

Results: Independent of race, the frequencies of central obesity, high triglycerides, low HDL, high blood pressure, impaired fasting glucose, and impaired glucose tolerance were significantly higher (P < 0.

Cardiorespiratory fitness in youth: relationship to insulin sensitivity and beta-cell function.

Objective: We examined whether the relationship between cardiorespiratory fitness (CRF) and insulin sensitivity (IS)/secretion is independent of adiposity in healthy African-American (n = 65) and white (n = 57) youth.

Research Methods And Procedures: IS and beta-cell function were evaluated by a 3-hour hyperinsulinemic-euglycemic and a 2-hour hyperglycemic (12.5 mM) clamp, respectively.

Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents?

Objective: Obesity is often associated with insulin resistance and the components of the metabolic syndrome. However, wide variations in insulin sensitivity are noted in obese youth. It is not clear if greater insulin resistance confers a higher risk of cardiovascular comorbidities and risk for type 2 diabetes.

Waist circumference is an independent predictor of insulin resistance in black and white youths.

Objectives: We examined how well waist circumference (WC) reflects total and abdominal fat and whether WC predicts insulin resistance independent of body mass index (BMI) percentile in youths.

Study Design: Body composition was measured by dual-energy x-ray absorptiometry and abdominal adiposity by computed tomography. Insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp.

Racial differences in adiponectin in youth: relationship to visceral fat and insulin sensitivity.

Objective: The purpose of this study was to investigate 1) whether adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in African-American and Caucasian youth and 2) whether adiponectin is associated with racial differences in insulin sensitivity.

Research Design And Methods: Total body fat was measured by dual-energy X-ray absorptiometry and abdominal adipose tissue with computed tomography. Insulin sensitivity was measured by a 3-h hyperinsulinemic-euglycemic clamp.

Type 2 diabetes mellitus in youth: the complete picture to date.

Type 2 diabetes mellitus is a heterogeneous condition in which the clinical manifestation of hyperglycemia is a reflection of the impaired balance between insulin sensitivity and insulin secretion. Clinical experience and research in youth type 2 diabetes mellitus are in an early stage because of the relative novelty of the condition in pediatrics. This article discusses the amassed information in type 2 diabetes mellitus of youth to date with respect to the epidemiology, pathophysiology, risk factors, clinical presentation, screening, and management strategies.

Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of African-American children?

Adiponectin is an adipocytokine with antidiabetogenic properties. The present study investigated: (i) the effect of race on adiponectin levels and (ii) the relationship of adiponectin levels in children to insulin sensitivity and secretion. Fasting adiponectin levels were determined in 22 healthy prepubertal black compared with 22 white children of similar body composition.

Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates.

The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and relative insulin deficiency in at-risk youth. We-report longitudinal changes in insulin sensitivity and secretion in a high-risk African-American youth with obesity and polycystic ovary syndrome who progressed from normal glucose tolerance to impaired glucose tolerance to T2DM within 5 yr. This report demonstrates that in our patient: (i) insulin resistance was the pre-existing abnormality, but it was the marked decline in insulin secretion which led to T2DM and (ii) surrogate estimates of insulin sensitivity using fasting glucose and insulin concentrations were not reliable indices in reflecting the changes in in vivo insulin sensitivity in this case.