Alfonso Vargas

Weight loss and growth velocity in obese children after very low calorie diet, exercise, and behavior modification

The prevalence of obesity in American youth is increasing and treatment of the condition is difficult. We have developed a multi‐disciplinary weight reduction program that extends over 1 y and includes a very low‐calorie diet (VLCD) followed by a hypocaloric diet, exercise, and behavior modification. Based on data collected at baseline, at the end of the acute intervention phase (10–20 wk), and at 1‐y evaluation, we assessed the efficacy of this outpatient weight reduction program in treating obese children and adolescents in a follow‐up of a series of cases. Furthermore, we examined the impact of the approach on growth velocity and maintenance of weight loss at 1 y. Fifty‐six overweight children (aged 7–17 y) were recruited during a period of 18 mo to participate in the weight management program; 52 (93%) completed the acute phase of treatment and 35 (62.5%) successfully completed the I‐y program. There was a significant decrease in body weight and body fat, as assessed by weight determinations and skinfold measurements 0, < 0.0001; results not corrected for age). The body mass index for the 35 individuals who completed the 1‐y program decreased significantly from 32.7 on entry to 28.72 at 1 y (p < 0.0001; results not corrected for age).

Oral Insulin Therapy to Prevent Progression of Immune‐Mediated (Type 1) Diabetes

Abstract: Repeated ingestion of insulin has been suggested as an immune tolerization therapy to prevent immune‐mediated (type 1) diabetes. We performed a placebo‐controlled, two‐dose, oral insulin tolerance trial in newly diagnosed (< 2 years) diabetic patients who had required insulin replacement for less than 4 weeks and were found to have cytoplasmic islet cell autoantibodies (ICAs). No oral hypoglycemic agents were permitted during the trial. Endogenous insulin reserves were estimated at six‐month intervals by plasma C‐peptide responses to a mixed meal. Positive ICAs were found in 262 (31%) of the 846 patients screened. Of the 197 who agreed to participate, 187 could be followed for 6 to 36 months. Endogenous insulin retention was dependent upon initial stimulated C‐peptide response, age at diabetes onset, and numbers of specific islet cell autoantibodies found. Oral insulin improved plasma C‐peptide responses in patients diagnosed at ages greater than 20 years, best seen at the low (1 mg/day) over the high (10 mg/day) insulin dose (P= .003 and P= .01, respectively). In patients diagnosed before age 20 years, the 1 mg dose was ineffective, whereas the 10 mg dose actually accelerated C‐peptide loss (P= .003). There were no adverse effects. If confirmed, these findings suggest that diabetic patients over age 20 years with ICA evidence of late‐onset immune‐mediated diabetes should be considered for oral insulin at 1 mg/day to better retain endogenous insulin secretion.

Predictors of glycemic control in children with Type 1 diabetes : the importance of race

Diabetes is a common cause of kidney failure and blindness among young adults, particularly of African-American descent. Since glycemic control is a predictor of diabetes complications, we evaluated the impact of multiple factors including a special multidisciplinary management program on glycosylated hemoglobin in children with Type 1 diabetes. Data was collected from pediatric diabetes clinics in New Orleans, LA and Baltimore, MD. In New Orleans, hemoglobin A(1c) was higher in African-American patients 12. 5+/-3.3% (n=71) vs. 10.7+/-2.1% (n=80) in Caucasian children, p<0. 0001. Longer duration of diabetes was also associated with higher hemoglobin A(1c) in both races. The effect of race on hemoglobin A(1c) was independent of the influence of sex, insurance status, body mass index (BMI) z-score, and number of clinic visits. Covariate analysis with mean blood glucose levels indicated that higher hemoglobin A(1c) was attributable to higher mean blood glucose levels in African-American children. From the Baltimore data, a multidisciplinary intervention program led to improved total glycosylated hemoglobin for Caucasian patients but not for African-American children. Poorer glycemic control of African-American children is likely to predispose them to a higher likelihood of developing microvascular complications as they mature. Standard hospital-based multidisciplinary programming for diabetes management may have limited effectiveness in improving glycemic control of African-American children with diabetes. Innovative intervention programs are needed for these high-risk patients.

Recent Advances in the Treatment of Childhood Obesity

The multidisciplinary, four-phase approach, which includes PSMF, BEM, and MPE is successful in treating mild, moderate, and severe degrees of childhood and adolescent obesity. The MPE program is appropriate for use with PSMF and BEM due to its progressive nature, variety of options, and moderate intensity level. In addition, the MPE program is of sufficient intensity, duration, and frequency to promote a significant increase in estimated aerobic capacity (VO2max) and to promote the maintenance of lean body mass and resting energy expenditure. The short-term intervention of PSMF, BEM, and MPE also results in an improvement in body composition, lipid profiles, and IGF-1 and T3 levels. The 1200-calorie balanced diet, MPE, and BEM also provide a successful method of weight maintenance in children and adolescents, as indicated by further improvement in body composition at the 26-week measure. Additional studies are needed to assess the contribution of exercise to the maintenance of lean body mass and resting energy expenditure in obese children and adolescents. In addition, it will be important to assess long-term weight maintenance in obese adolescents who effectively lose weight in this multidisciplinary program.

Helicobacter pylori infection and insulin requirement among children with type 1 diabetes mellitus.

Objective. Helicobacter pylori induces gastric inflammation and the production of cytokines in infected individuals. Theoretically, this increased production of cytokines could be deleterious for the control of the glycemia of patients with diabetes. This study aimed to describe the insulin requirement among patients with type 1 diabetes and H pylori infection compared with uninfected counterparts. Methods. Cross-sectional design. Demographic information (age, gender, race, annual family income, and number of individuals per room in the household) and clinical information (age at diagnosis of diabetes, duration of illness, weight, height, compliance with clinical appointments, daily insulin units per kilogram of body weight [IU/kg/d], and glycosylated hemoglobin A level) was obtained from children and adolescents with diagnosis of type 1 diabetes mellitus who were seen at Childrens Hospital in New Orleans. A total of 2 mL of blood was also collected and sera were tested forH pylori-specific immunoglobulin G antibodies using an enzyme immunoassay. The daily insulin requirement among infected and uninfected children was compared, and the effect of other variables was evaluated with multiple linear regression. Results. Of the 71 subjects who were evaluated (median age: 11 years), 11 (15.5%) were found to be infected. H pylori infection was more frequent among subjects who were older, who had a lower family income, and who were black. Infected children were found to require more insulin (1.2 vs 0.9 IU/Kg/d) and their glycosylated hemoglobin A level was higher (14.9 vs 11.8) than the level found in uninfected subjects. Multiple linear regression analysis identified H pylori infection duration of illness, race (black), body mass index, and gender (female), to be associated independently with increased daily insulin requirement (IU/kg/d). Conclusion. In our study population, children with type 1 diabetes and H pylori infection had an increased daily insulin requirement compared with the requirement of their uninfected peers. The reason for this association requires additional investigation.

Poor glycemic control is associated with increased diastolic blood pressure and heart rate in children with Type 1 diabetes

Although higher levels of hemoglobin A1c (HbA1c) and blood pressure precede the development of nephropathy in Type 1 diabetes (T1DM), the relationship between glycemic control and cardiovascular factors early in the course of diabetes is not clear. We conducted a retrospective study from clinic data for a 1-year period in 148 children with T1DM aged 12.5+/-4.4 years who had average diabetes duration of 4.5+/-3.3 years. The influence of HbA1c and reported insulin dose on blood pressure and heart rate were analyzed in multivariate linear regression models, statistically adjusted for the effect of race, sex, age, body mass index, and duration of diabetes. There was a significant positive correlation of mean HbA1c with mean diastolic blood pressure (P<.025) and mean heart rate (P<.0004). Higher diastolic blood pressure and heart rate were associated with higher HbA1c. Increased insulin doses were also associated with increased diastolic blood pressure (P<.009) and heart rate (P<.013). Insulin dose and HbA1c were also significantly correlated (P<.001). There was no correlation between mean HbA1c and mean systolic blood pressure. Increased levels of HbA1c and insulin dose are associated with increased diastolic blood pressure and heart rate. Although within the normal range, early increases of diastolic blood pressure and heart may indicate early cardiovascular changes in response to diabetes and potentially contribute to a greater proclivity for later development of nephropathy.

Effects of Physical Activity on Diabetes Management and Lowering Risk for Type 2 Diabetes

Abstract Physical activity is a proven form of diabetes management and is considered a cornerstone in the prevention of diabetes. In children with diabetes, physical activity may improve insulin sensitivity and glucose uptake in skeletal muscle. Aerobic-based physical activity lasting 40-60 minutes daily for a minimum of four months is shown to enhance insulin sensitivity, and may reduce the risk for type 2 diabetes. An important adjunct to aerobic-based physical activity for diabetes prevention is resistance training. The American Academy of Pediatrics supports properly supervised strength/resistance training as a safe method for strength development in preadolescent children. Resistance training may increase skeletal muscle mass, therefore increasing whole-body glucose disposal capacity. In addition to immediate health benefits during childhood, increased physical activity in children and adolescents is likely to contribute to the establishment of healthy leisure habits over a lifetime and improved adult cardiovascular health. Large-scale intervention studies, however, are needed to determine the most effective physical activity strategies for prevention and management of type 2 diabetes in children and adolescents.

Racial differences in neighborhood disadvantage, inflammation and metabolic control in black and white pediatric type 1 diabetes patients

Racial variation in the relationship between blood glucose and hemoglobin A1c (HbA1c) complicates diabetes diagnosis and management in racially mixed populations. Understanding why HbA1c is persistently higher in blacks than whites could help reduce racial disparity in diabetes outcomes.

Association between Helicobacter felis—Induced Gastritis and Elevated Glycated Hemoglobin Levels in a Mouse Model of Type 1 Diabetes

Helicobacter pylori infection has been described in association with increases in glycated hemoglobin (HbA(1c)) levels in patients with type 1 diabetes. The purpose of the present study was to use an animal model of Helicobacter infection to test, under controlled conditions, the hypothesis that infection is associated with high HbA(1c) levels. Diabetes was induced in C57BL/6 mice by administration of streptozotocin, and the mice were orally inoculated with H. felis. Six weeks after inoculation, infected mice (n=10) showed gastritis scores significantly greater (P=.01) than those of uninfected mice (n=10). HbA(1c) levels were significantly higher in infected mice with gastritis (11.6%; n=6) than in infected mice without gastritis (8.4%; n=4) or uninfected mice (7.6%; n=10). It was concluded that gastritis induced by H. felis is associated with increased HbA(1c) levels in the mouse model of streptozotocin-induced diabetes.

Further evidence that variants in PPP1CB cause a rasopathy similar to Noonan syndrome with loose anagen hair.

Further Evidence That Variants in PPP1CB Cause a Rasopathy Similar to Noonan Syndrome with Loose Anagen Hair Regina M. Zambrano,* Michael Marble, Stuart A. Chalew, Christian Lilje, Alfonso Vargas, and Yves Lacassie* Division of Genetics, Department of Pediatrics, Louisiana State University Health Sciences Center School of Medicine, and Children’s Hospital, New Orleans, Louisiana Division of Endocrinology, Department of Pediatrics, Louisiana State University Health Sciences Center School of Medicine, and Children’s Hospital, New Orleans, Louisiana Division of Cardiology, Department of Pediatrics, Louisiana State University Health Sciences Center School of Medicine, and Children’s Hospital, New Orleans, Louisiana