Sowmya Krishnan

Sex differences in body composition early in life.

BACKGROUND Early development of the percentage of fat and muscle is rarely considered, but is important because excessive fat is related to the development of diabetes and other morbidities later in life. In pediatric medicine, there are few to no data comparing sex differences in body composition in the first months of life despite the fact that males are typically longer and weigh more than girls at birth. OBJECTIVE The purpose of this study was to determine whether observed sex differences in body composition at birth persist through the first 6 months of life. METHODS Participants were healthy, full-term, male and female newborns. Children throughout the Oklahoma City, Oklahoma, metropolitan area were enrolled. The inclusion criteria were: mothers aged 18 to 45 years at the time of delivery; a term pregnancy lasting >or=37 weeks of gestation (determined by mothers physician); weight adequate for gestational age; and a hospital stay for the infant of <3 days following delivery. The exclusion criteria were: maternal tobacco use or alcohol consumption (>1 drink per week) during pregnancy; gestational diabetes; preeclampsia; and infants with presumed or known congenital birth defects. Baseline assessment at birth included length and weight. Newborns had their body composition (percent fat [%fat], total fat, and fat-free mass) determined at approximately 1 month of age using whole body plethysmography. Mothers were invited to have their children take part in a 5-month extension that conducted additional body composition measurements at 3 and 6 months of age. RESULTS Sixty-four girls (mean [SD] age at time of testing, 20.9 [7.9] days; birth weight, 3500 [388] g; birth length, 49.9 [2.4] cm; white race, 73.4%) and 53 boys (mean age at time of testing, 20.2 [7.3] days; birth weight, 3353 [413] g; birth length, 51.0 [2.4] cm; white race, 69.8%) were assessed and included in the study. At birth, girls were significantly shorter and weighed more than boys (both, P < 0.05). At ~1 month of age, body composition revealed that girls had significantly greater %fat (15.1% vs 12.7%; P < 0.05) and less fat-free mass (3182 [303] vs 3454 [361] g; P < 0.001) than did boys. At 3 months of age, girls continued to have significantly less fat-free mass (4379 [347] vs 4787 [310] g; P < 0.01) than did boys; however, by 6 months of age, no significant sex difference was observed in any body composition variable studied. CONCLUSION In this small sample of healthy, full-term newborns, at ~1 month of age, statistically significant differences in %fat and fat-free mass existed between girls and boys; however, by 6 months of age, these differences no longer existed.

Prevalence and Significance of Cardiometabolic Risk Factors in Children With Type 1 Diabetes

Type 1 diabetes (T1D) is a common disease of childhood with a current prevalence of almost 2 cases per 1000 adolescents, according to the third National Health and Nutrition Examination Survey. Modern insulin treatment has resulted in improved quality of life for children with this chronic disorder. However, T1D continues to carry a long-term burden of increased microvascular and macrovascular complications and mortality risk. Compared to the nondiabetic population, patients with T1D are more likely to have >or=1 cardiovascular risk factor and often at an earlier age. Since the prevalence of cardiovascular risk factors increases with age in young persons with T1D, there is a clear need for early screening and counseling to prevent their occurrence and manage long-term health ramifications. The purpose of this review is to describe how traditional risk factors for cardiovascular disease such as an abnormal lipid profile, hypertension, obesity, and insulin resistance contribute to the accelerated atherosclerosis seen in young persons with T1D. A summary is given of the guidelines and recommendations published for clinical care for these patients.

A model of delivering multi-disciplinary care to people with 46 XY DSD

In 2006, a consensus statement was jointly produced by the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society of Paediatric Endocrinology (ESPE) concerning the management of disorders of sex development (DSD) [1]. A recommendation provided by this consensus was that evaluation and long-term care for people affected by DSD should be performed at medical centers with multi-disciplinary teams experienced in such conditions. Here we provide our teams interpretation of the 2006 consensus statement recommendations and its translation into a clinical protocol for individuals affected by 46 XY DSD with either female, or ambiguous, genitalia at birth. Options for medical and surgical management, transitioning of care, and the use of mental health services and peer support groups are discussed. Finally, we provide preliminary data to support the application of our model for delivering multi-disciplinary care and support to patients and their families.

An Evidence-Based Model of Multidisciplinary Care for Patients and Families Affected by Classical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

In 2002 a consensus statement pertaining to the management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency was jointly produced by the Lawson Wilkins Pediatric Endocrine Society and the European Society of Pediatric Endocrinology. One of the recommendations of this consensus was that centers should maintain multidisciplinary teams for providing care and support to these patients and their families. However, the specifics for how this should be accomplished were not addressed in the original consensus statement. Here we interpret and translate the 2002 consensus statement recommendations into medical, surgical and mental health protocols. Additionally, we provide preliminary evidence that such protocols result in improved care and support for patients and families.

Two new unrelated cases of hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia resulting from the same novel nonsense mutation in the vitamin D receptor gene.

ABSTRACT 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) an important regulator of bone homeostasis, mediates its actions by binding to the vitamin D receptor (VDR), a nuclear transcription factor. Mutations in the VDR cause the rare genetic disease hereditary vitamin D resistant rickets (HVDRR). In this study, we examined two unrelated young female patients who exhibited severe early onset rickets, hypocalcemia, and hypophosphatemia. Both patients had partial alopecia but with different unusual patterns of scant hair. Sequencing of the VDR gene showed that both patients harbored the same unique nonsense mutation that resulted in a premature stop codon (R50X). Skin fibroblasts from patient #1 were devoid of VDR protein and 1,25(OH)2D3 treatment of these cells failed to induce CYP24A1 gene expression, a marker of 1,25(OH)2D3 action. In conclusion, we identified a novel nonsense mutation in the VDR gene in two patients with HVDRR and alopecia. The mutation truncates the VDR protein and causes 1,25(OH)2D3 resistance.

Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat

BACKGROUND The treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis. OBJECTIVE To report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition. METHODS Serial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample. RESULTS The affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk. CONCLUSION The data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis.

Metabolic syndrome and daily ambulation in children, adolescents, and young adults.

PURPOSES To compare daily ambulatory measures in children, adolescents, and young adults with and without metabolic syndrome and to assess which metabolic syndrome components, demographic measures, and body composition measures are associated with daily ambulatory measures. METHODS Two-hundred fifty subjects between the ages of 10 and 30 yr were assessed on metabolic syndrome components, demographic and clinical measures, body fat percentage, and daily ambulatory strides, durations, and cadences during seven consecutive days. Of the 250 subjects, 45 had metabolic syndrome, as defined by the International Diabetes Federation. RESULTS Subjects with metabolic syndrome ambulated at a slower daily average cadence than those without metabolic syndrome (13.6 ± 2.2 vs 14.9 ± 3.2 strides per minute; P = 0.012), and they had slower cadences for continuous durations of 60 min (P = 0.006), 30 min (P = 0.005), 20 min (P = 0.003), 5 min (P = 0.002), and 1 min (P = 0.001). However, the total amount of time spent ambulating each day was not different (P = 0.077). After adjustment for metabolic syndrome status, average cadence is linearly associated with body fat percentage (P < 0.001) and fat mass (P < 0.01). Group difference in average cadence was no longer significant after adjusting for body fat percentage (P = 0.683) and fat mass (P = 0.973). CONCLUSIONS Children, adolescents, and young adults with metabolic syndrome ambulate more slowly and take fewer strides throughout the day than those without metabolic syndrome, although the total amount of time spent ambulating is not different. Furthermore, the detrimental influence of metabolic syndrome on ambulatory cadence is primarily a function of body fatness.

Sex differences in cardiovascular disease risk in adolescents with type 1 diabetes.

BACKGROUND Cardiovascular disease is seen at a younger age and at a higher prevalence in patients with type 1 diabetes than in the general population. It is well described that women with type 1 diabetes have a higher relative risk of cardiovascular disease than men with type 1 diabetes, unlike that seen in the general population. The pathophysiology behind this is unknown. OBJECTIVE We performed a cross-sectional study to examine sex differences in cardiovascular disease risk factors in adolescents with type 1 diabetes between ages 13 and 20 years, compared with children of a similar age without type 1 diabetes. METHODS All patients underwent a dual energy x-ray absorptiometry scan to measure body composition and a pulse wave test measure of arterial elasticity. Fasting serum lipid levels, apolipoprotein B, and apolipoprotein C-III levels were measured in each patient. Twenty-nine children with type 1 diabetes (10 girls, 19 boys) and 37 healthy children (18 girls, 19 boys) participated. RESULTS Although no sex differences for body mass index (P = 0.91) and glycosylated hemoglobin (P = 0.69) were seen, girls with type 1 diabetes had a significantly higher percent trunk fat compared with boys (P = 0.004). No sex differences were found (P > 0.05) for percent trunk fat in adolescents without diabetes. There was no sex difference among any other cardiovascular risk factors in either children with or without diabetes. CONCLUSIONS Female adolescents with type 1 diabetes have more centrally distributed fat, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden.

Impact of Type 1 Diabetes and Body Weight Status on Cardiovascular Risk Factors in Adolescent Children

Type 1 diabetes (T1D) is a risk factor for cardiovascular disease. However, it is unclear whether increased body weight amplifies that risk in T1D patients. This is a cross‐sectional study examining the presence of cardiovascular risk factors in normal and overweight children, both with and without T1D. Sixty‐six children (aged 16±2.2 years) were included in one of the following groups: (T1D and normal weight, T1D and overweight, healthy and normal weight, and healthy and overweight). A fasting blood sample was analyzed for lipid profile (triglyceride, cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol), apolipoprotein B (apoB), and apolipoprotein C‐III (apoC‐III) levels. Body composition was determined by dual energy x‐ray absorptiometry and vascular elasticity by HDI/Pulsewave CR‐2000 (Hypertension Diagnostics, Eagan, MN). Statistical analyses examined the effect of T1D and body weight status and their interactions on cardiovascular risk parameters. In this study, the authors were unable to demonstrate an additive effect of body weight status and T1D on cardiovascular risk profile. However, subgroup analysis of patients with T1D revealed higher apoC‐III levels in overweight patients with T1D (P=.0453) compared with normal‐weight diabetic children. Most notably, there was a direct relationship of small artery elasticity to body weight status. This seemingly paradoxical observation supports recent data and warrants further investigation.

Original researchSex Differences in Cardiovascular Disease Risk in Adolescents With Type 1 Diabetes

BACKGROUND Cardiovascular disease is seen at a younger age and at a higher prevalence in patients with type 1 diabetes than in the general population. It is well described that women with type 1 diabetes have a higher relative risk of cardiovascular disease than men with type 1 diabetes, unlike that seen in the general population. The pathophysiology behind this is unknown. OBJECTIVE We performed a cross-sectional study to examine sex differences in cardiovascular disease risk factors in adolescents with type 1 diabetes between ages 13 and 20 years, compared with children of a similar age without type 1 diabetes. METHODS All patients underwent a dual energy x-ray absorptiometry scan to measure body composition and a pulse wave test measure of arterial elasticity. Fasting serum lipid levels, apolipoprotein B, and apolipoprotein C-III levels were measured in each patient. Twenty-nine children with type 1 diabetes (10 girls, 19 boys) and 37 healthy children (18 girls, 19 boys) participated. RESULTS Although no sex differences for body mass index (P = 0.91) and glycosylated hemoglobin (P = 0.69) were seen, girls with type 1 diabetes had a significantly higher percent trunk fat compared with boys (P = 0.004). No sex differences were found (P > 0.05) for percent trunk fat in adolescents without diabetes. There was no sex difference among any other cardiovascular risk factors in either children with or without diabetes. CONCLUSIONS Female adolescents with type 1 diabetes have more centrally distributed fat, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden.