Sheela N. Magge

Type 1 Diabetes Mellitus and Cardiovascular Disease A Scientific Statement From the American Heart Association and American Diabetes Association

Despite the known higher risk of cardiovascular disease (CVD) in individuals with type 1 diabetes mellitus (T1DM), the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood. Management approaches to CVD reduction have been extrapolated in large part from experience in type 2 diabetes mellitus (T2DM), despite the longer duration of disease in T1DM than in T2DM and the important differences in the underlying pathophysiology. Furthermore, the phenotype of T1DM is changing. As a result of the findings of the Diabetes Control and Complications Trial (DCCT), which compared intensive glycemic control with usual care, and its follow-up observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), intensive management of diabetes mellitus (DM) has become the standard of care and has led to increasing longevity. However, our understanding of CVD in T1DM comes in large part from the previous era of less intensive glycemic control. More intensive glycemic control is associated with significant risk of weight gain, which may be magnified by the obesity epidemic. There is growing interest in better understanding the adverse effects of glycemia, the prevalence and type of lipid abnormalities in T1DM, the prognostic role of albuminuria and renal insufficiency, and the role of blood pressure (BP) in CVD. Obesity-associated metabolic abnormalities such as the proinflammatory state likely modify CVD risk in T1DM; however, the effect may be different from what is seen in T2DM. These concepts, and how they may affect management, have not been fully explored. The present review will focus on the importance of CVD in patients with T1DM. We will summarize recent observations of potential differences in the pathophysiology of T1DM compared with T2DM, particularly with regard to atherosclerosis. We will explore the implications of these concepts for treatment of CVD risk factors in patients with …

Long-Term Neuropsychological Effects of Sagittal Craniosynostosis on Child Development

The link between cranial deformity and “functional” disability is not obvious in single-suture sagittal craniosynostosis. Physicians have anecdotally reported that children with simple craniosynostosis often seem to have a higher proportion of learning disabilities and cognitive problems than their nonafflicted peers. These problems have not been systematically studied, however. This study examined the long-term neuropsychological effects of single-suture sagittal craniosynostosis on selected aspects of neurological development. It did so by going beyond global measures of mental function (intelligence quotient) in an attempt to assess the incidence of subtle neuropsychological sequelae. Retrospective inspection of the Yale Department of Neurosurgery records between 1980 and 1990 was used to identify study subjects born with nonsyndromic sagittal suture craniosynostosis who were between 6 and 16 years of age at the time of the study. Of the 16 study subjects born with sagittal synostosis, which is thought to be among the most benign of the single-suture craniosynostoses, this study found that 50% had a reading and/or spelling learning disability. Although children with single-suture sagittal craniosynostosis fall within the normal range for intelligence, there is a significantly higher incidence of learning disabilities in this group than in the general population.

Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association

Despite the known higher risk of cardiovascular disease (CVD) in individuals with type 1 diabetes mellitus (T1DM), the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood. Management approaches to CVD reduction have been extrapolated in large part from experience in type 2 diabetes mellitus (T2DM), despite the longer duration of disease in T1DM than in T2DM and the important differences in the underlying pathophysiology. Furthermore, the phenotype of T1DM is changing. As a result of the findings of the Diabetes Control and Complications Trial (DCCT), which compared intensive glycemic control with usual care, and its follow-up observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), intensive management of diabetes mellitus (DM) has become the standard of care and has led to increasing longevity. However, our understanding of CVD in T1DM comes in large part from the previous era of less intensive glycemic control. More intensive glycemic control is associated with significant risk of weight gain, which may be magnified by the obesity epidemic. There is growing interest in better understanding the adverse effects of glycemia, the prevalence and type of lipid abnormalities in T1DM, the prognostic role of albuminuria and renal insufficiency, and the role of blood pressure (BP) in CVD. Obesity-associated metabolic abnormalities such as the proinflammatory state likely modify CVD risk in T1DM; however, the effect may be different from what is seen in T2DM. These concepts, and how they may affect management, have not been fully explored. The present review will focus on the importance of CVD in patients with T1DM. We will summarize recent observations of potential differences in the pathophysiology of T1DM compared with T2DM, particularly with regard to atherosclerosis. We will explore the implications of these concepts for treatment of CVD risk factors in patients with …

Leptin Levels among Prepubertal Children with Down Syndrome Compared with Their Siblings

OBJECTIVES To compare levels of leptin and other obesity-related hormones in prepubertal children with Down syndrome (DS), a population at high obesity risk, and those in unaffected siblings to better understand the pathophysiology of obesity in children with DS. STUDY DESIGN This was a cross-sectional study of 35 children with DS and 33 control siblings, ages 4 to 10 years, with a fasting blood sample and anthropometric measurements to estimate body composition. Generalized estimating equations were used to account for the lack of independence between siblings. RESULTS In addition to having higher body mass index and percent body fat, children with DS had higher leptin levels than unaffected siblings, even after adjustment for age, sex, race, and ethnicity (difference, 5.8 ng/mL; 95% CI, 2.4-9.3; P = .001) and further adjustment for percent body fat (difference, 2.7 ng/mL; 95% CI, 0.08-5.40, P = .04). Leptin and percent body fat were positively associated in both groups (P < .0001), but with a significantly greater positive association in the DS group, suggesting a significant effect modification (P < .0001). CONCLUSIONS This group of children with DS had increased leptin levels for percent body fat than their unaffected siblings. This difference may contribute to the increased risk for obesity in children with DS.

Snacks, Sweetened Beverages, Added Sugars, and Schools

Concern over childhood obesity has generated a decade-long reformation of school nutrition policies. Food is available in school in 3 venues: federally sponsored school meal programs; items sold in competition to school meals, such as a la carte, vending machines, and school stores; and foods available in myriad informal settings, including packed meals and snacks, bake sales, fundraisers, sports booster sales, in-class parties, or other school celebrations. High-energy, low-nutrient beverages, in particular, contribute substantial calories, but little nutrient content, to a student’s diet. In 2004, the American Academy of Pediatrics recommended that sweetened drinks be replaced in school by water, white and flavored milks, or 100% fruit and vegetable beverages. Since then, school nutrition has undergone a significant transformation. Federal, state, and local regulations and policies, along with alternative products developed by industry, have helped decrease the availability of nutrient-poor foods and beverages in school. However, regular access to foods of high energy and low quality remains a school issue, much of it attributable to students, parents, and staff. Pediatricians, aligning with experts on child nutrition, are in a position to offer a perspective promoting nutrient-rich foods within calorie guidelines to improve those foods brought into or sold in schools. A positive emphasis on nutritional value, variety, appropriate portion, and encouragement for a steady improvement in quality will be a more effective approach for improving nutrition and health than simply advocating for the elimination of added sugars.

Consumption of raw or unpasteurized milk and milk products by pregnant women and children

Sales of raw or unpasteurized milk and milk products are still legal in at least 30 states in the United States. Raw milk and milk products from cows, goats, and sheep continue to be a source of bacterial infections attributable to a number of virulent pathogens, including Listeria monocytogenes, Campylobacter jejuni, Salmonella species, Brucella species, and Escherichia coli O157. These infections can occur in both healthy and immunocompromised individuals, including older adults, infants, young children, and pregnant women and their unborn fetuses, in whom life-threatening infections and fetal miscarriage can occur. Efforts to limit the sale of raw milk products have met with opposition from those who are proponents of the purported health benefits of consuming raw milk products, which contain natural or unprocessed factors not inactivated by pasteurization. However, the benefits of these natural factors have not been clearly demonstrated in evidence-based studies and, therefore, do not outweigh the risks of raw milk consumption. Substantial data suggest that pasteurized milk confers equivalent health benefits compared with raw milk, without the additional risk of bacterial infections. The purpose of this policy statement was to review the risks of raw milk consumption in the United States and to provide evidence of the risks of infectious complications associated with consumption of unpasteurized milk and milk products, especially among pregnant women, infants, and children.

Adiponectin Is Associated with Favorable Lipoprotein Profile, Independent of BMI and Insulin Resistance, in Adolescents

CONTEXT Children with obesity and insulin resistance (IR) have decreased adiponectin and have increased cardiovascular risk. Adiponectin has antiatherogenic effects, but its mechanism is unclear. OBJECTIVES Our objectives were 1) to compare lipoprotein subclass particles among obese and lean adolescents and delineate their relationships with IR and 2) to measure relationships between adiponectin and lipoproteins and their dependence on body mass index (BMI) and/or IR. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: This was a cross-sectional study of 57 obese and 38 lean pubertal adolescents, measuring lipoprotein subclass particles (nuclear magnetic resonance spectroscopy), lipids, adiponectin, and homeostasis model assessment of IR (HOMA-IR). RESULTS Obese had higher low-density lipoprotein (LDL) cholesterol (P = 0.018), higher small LDL particles (LDL-P) (P < 0.0005), smaller LDL-P size (P < 0.0005), smaller high-density lipoprotein particle (HDL-P) size (P < 0.0005), lower HDL cholesterol (HDL-C) (P < 0.0005), and higher small HDL-P (P = 0.009) compared with lean. HOMA-IR was higher in obese than lean (P < 0.0005) and positively associated with triglycerides, large very LDL-P, and small HDL-P and negatively with HDL-P size in obese. Adiponectin was lower in obese than lean (P < 0.0005) and was positively associated with LDL-P size, HDL-P size, and HDL-C and negatively with triglycerides, small LDL-P, large very LDL-P, and small HDL-P in obese. Using linear regression adjusting for demographics, Tanner stage, BMI, and HOMA-IR in all adolescents, adiponectin was positively associated with LDL-P size (P = 0.028), HDL-P size (P < 0.0005), and HDL-C (P = 0.042) and negatively with small LDL-P (P = 0.009) and small HDL-P (P = 0.004). CONCLUSIONS Obese adolescents have lower adiponectin levels than lean, and a more atherogenic lipoprotein profile, associated with increased IR. Adiponectin was inversely associated with atherogenic lipoproteins in adolescents, even after adjusting for obesity and IR. This is the first such report in children, and suggests a relationship between adiponectin and lipoproteins in adolescents independent of BMI and IR.

Glycemic Control in Youth with Type 2 Diabetes Declines as Early as Two Years after Diagnosis

OBJECTIVES To determine the course of glycemic decline in a pediatric cohort with type 2 diabetes mellitus (T2DM) by defining longitudinal changes in hemoglobin A1c (HbA1c) and insulin requirement. We also followed markers of insulin reserve (fasting C-peptide and IGFBP-1) over time. STUDY DESIGN Participants included two groups: (1) T2DM Nonacidotic (NA) (n = 46); and (2) T2DM diabetic ketoacidosis (n = 13). HbA1c, insulin dose, and fasting C-peptide and IGFBP-1 were obtained at baseline and every 6 months for 4 years. RESULTS At baseline, Mann Whitney tests demonstrated that the diabetic ketoacidosis group had higher HbA1c (P = .002), required more insulin (P = .036), and had lower C-peptide (P = .003) than the NA group. Baseline insulin dose (Spearman r = -0.424, P = .009) and baseline IGFBP-1 (Spearman r = -0.349, P = .046) correlated negatively with C-peptide. Over time, HbA1c, insulin dose, and C-peptide changed significantly in a complex manner, with group differences. HbA1c reached a nadir at 6 to 12 months and began to rise after 1.5 years. Insulin requirements reached a nadir at 1 year and began to rise after 2 years. CONCLUSIONS Unlike adults, children with T2DM require increasing insulin doses over a 4-year period, and diabetic ketoacidosis at diagnosis predicts greater β-cell decline over time.

Lipid Profiles of Children With Down Syndrome Compared With Their Siblings

OBJECTIVES: Our objective was to compare serum lipid profiles, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) between children with Down syndrome (DS) and their non-DS siblings. We hypothesized that the children with DS would have higher TC, LDL, and TG and lower HDL. The secondary aim was to explore if the difference in lipid profiles could be explained by differences in weight status. METHODS: This was a cross-sectional study. Fasting lipid profile was obtained from 27 children with DS and 31 siblings between 4 and 10 years of age with no severe comorbidities (heart disease, cancer, hypothyroidism, diabetes, or obesity). BMI was calculated and BMI z scores were used to account for differences in BMI throughout childhood. RESULTS: Children with DS had higher TC (difference, 11.2 mg/dL; 95% confidence interval: 2.5–19.9; P = .01), LDL (12.8 mg/dL; 7.2–18.4; P < .001), TG (33.6 mg/dL; 11.1–56.1; P = .003), and lower HDL (−7.6 mg/dL; −12.1 to −3.0; P = .001) after adjustment for race, gender, age, and ethnicity. Results remained significant after additional adjustment for BMI z score: TC (14.9 mg/dL; 4.9–24.9; P = .003), LDL (16.6 mg/dL; 10.1–23.2; P < .001), TG (32.7 mg/dL; 7.7–57.7; P = .01), and lower HDL (−6.4 mg/dL; −12.2 to −0.7; P = .03). CONCLUSIONS: Children with DS have less favorable lipid profiles than their siblings independent of weight status. These findings may have important implications for the screening and treatment of this large population at increased risk for ischemic heart disease.

An international surgical exchange program for children with cleft lip/cleft palate in Manaus, Brazil: patient and family expectations of outcome.

Increasingly, surgeons are traveling from the developed to the developing world to volunteer their services. They can often make an enormous difference in the lives of patients they serve, but they must understand that these patients exist in a sociocultural matrix in which the meaning of the condition they have and the future they face are determined by a host of factors over and above the specific surgery itself. This means that programs in which teams quickly go in and out of a country must take into account and plan for longer term follow-up by colleagues within that country as well as develop and target rehabilitation services and educational messages to ensure maximum benefits from the intervention performed. This study examines the long-term implications of a short-term surgical team intervention for pediatric patients with cleft lip/cleft palate and their families in the Amazon region of Brazil.