A Novel Generalized Lipodystrophy-Associated Progeroid Syndrome Due to Recurrent Heterozygous LMNA p.T10I Mutation.

Background: Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported patients with APS harbored a recurrent de novo heterozygous LMNA p.T10I mutation. All five had generalized lipodystrophy, as well as similar metabolic and clinical features, suggesting a distinct progeroid syndrome. Methods: We report nine new patients and follow-up of two previously reported patients with the heterozygous LMNA p.T10I mutation and compare their clinical and metabolic features with other patients with APS. Results: Compared with other patients with APS, those with the heterozygous LMNA p.T10I mutation were younger in age but had increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly, together with higher fasting serum insulin and triglyceride levels and lower serum leptin and high-density lipoprotein cholesterol levels. Prominent clinical features included mottled skin pigmentation, joint contractures, and cardiomyopathy resulting in cardiac transplants in three patients at ages 13, 33, and 47 years. Seven patients received metreleptin therapy for 0.5 to 16 years with all, except one noncompliant patient, showing marked improvement in metabolic complications. Conclusions: Patients with the heterozygous LMNA p.T10I mutation have distinct clinical features and significantly worse metabolic complications compared with other patients with APS as well as patients with Hutchinson-Gilford progeria syndrome. We propose that they be recognized as having generalized lipodystrophy-associated progeroid syndrome. Patients with generalized lipodystrophy-associated progeroid syndrome should undergo careful multisystem assessment at onset and yearly metabolic and cardiac evaluation, as hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy are the major contributors to morbidity and mortality.

Intima-media thickness at different arterial segments in pediatric type 1 diabetes patients and its relationship with advanced glycation end products.

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) are at risk for premature atherosclerosis (AS), which has its origin in childhood. Carotid intima-media thickness (IMT) is an established surrogate marker for subclinical AS in adults. The first macroscopically detectable AS changes, however, begin in the abdominal aorta. Advanced glycation end products (AGE) predict microvascular complications in diabetes. OBJECTIVES: To assess the sensitivity for early macrovascular changes of brachial, femoral, and aortic IMT compared to conventional carotid IMT in pediatric T1DM patients ; and the relationship of IMT with AGE. METHODS: Using high-resolution external ultrasound, carotid, brachial, femoral, and aortic IMT were prospectively analyzed in children and adolescents with established T1DM and in controls (Ctrls). AGE were estimated by skin intrinsic fluorescence (SIF). Other established cardiovascular risk factors were excluded. RESULTS: Seventy-six subjects (T1DM = 38; Ctrls = 38) with a mean age of 13.1 ± 4.0 years (6-19, median 13) qualified for analysis. Carotid, brachial, femoral, and aortic IMT analyses were feasible in 100%, 74%, 84%, and 92% of subjects, respectively. Aortic and femoral IMT were increased in T1DM patients (0.60 ± 0.11 vs 0.52 ± 0.10 mm, P < .001; and 0.41 ± 0.07 vs 0.36 ± 0.07 mm, P < .01, respectively) while carotid and brachial IMT were not. AGE levels were elevated in T1DM patients and correlated with aortic IMT only. The influence of AGE on aIMT did not remain significant after adjusting for T1DM and age in our small population. CONCLUSION: We found aortic IMT-and to a lesser degree femoral IMT-to be more sensitive than carotid and brachial IMT for detecting early macrovascular changes in pediatric T1DM patients.

The Healer's Art: Remembering Our Professional Lineage in Community through the Cultivation of Individual Core Values.

This article was migrated. The article was marked as recommended. Introduction: There is both patient and provider dissatisfaction with the climate of healthcare delivery. Upon review, this is found to be at least in part attributable to the mechanization of health care, which often involves more computer interaction than hands-on care. Despite rising costs, the physical exam is replaced by lab tests and radiologic studies, generating more cost. The time-honored respect for a carefully obtained history from the patient is replaced by a computer check-box template. The humanity of both physician and patient are marginalized, with increased potential for both diagnostic and therapeutic compromise. Though access to medical information about disease is possible with bioinformatics, artificial intelligence cannot substitute for analysis by an informed, attentive, and properly educated physician. The process of healing must begin with the first patient visit - and the presence of an informed, compassionate, and fully attentive physician. Objective: To describe the history of medical educators' grappling with this problem through 3 landmark articles over a 100-year period. To illustrate the challenges of the climate of medical education. To offer some educational strategies (with examples of successful programs) to teach physicians using the Humanities. To illustrate that the art and science of medicine are synergistic, not dichotomous. Methods: Two educational theories ripe for use: Chickering and the Discovery Model, and Osler's recommended bedside reading list, exemplary programs that are being used currently (and over the last 25-plus years) to emphasize the importance of both the science and the practice of medicine in an effort to optimize the medical climate. Conclusion: The problem of physician burnout and patient dissatisfaction is being addressed in the medical literature, by regulatory societies devoted to physician wellness and by medical educators. This is nevertheless a challenge given the current electronic climate (with bioinformatics and artificial intelligence) and revenue-focused agendas of practice management business people. Results: With an awareness of the need for emphasis on the humanities coupled with an historical perspective over the last 100 years, a spirit of hope can be provided to both physician and patient from the lineage of the medical profession, which also is a legacy for our medical students.

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

BACKGROUND: 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. OBJECTIVE: Test the hypothesis that neighborhood disadvantage is associated with inflammation and poor metabolic control in a racially mixed population of pediatric type 1 diabetes patients. METHODS: Patients (n = 86, 53 white, 33 black) were recruited from diabetes clinics. Self-monitored mean blood glucose (MBG) was downloaded from patient glucose meters. Blood was collected for analysis of HbA1c and C-reactive protein (CRP). Patient addresses and census data were used to calculate a concentrated disadvantage index (CDI). High CDI reflects characteristics of disadvantaged neighborhoods. RESULTS: HbA1c and MBG were higher (p < 0.0001) in blacks [10.4% (90.3 mmol/mol), 255 mg/dL] than whites [8.9% (73.9 mmol/mol), 198 mg/dL). CDI was higher in blacks (p < 0.0001) and positively correlated with HbA1c (r = 0.40, p = 0.0002) and MBG (r = 0.35, p = 0.0011) unless controlled for race. CDI was positively associated with CRP by linear regression within racial groups. CRP was not different between racial groups, and was not correlated with MBG, but was positively correlated with HbA1c when controlled for race (p = 0.04). CONCLUSIONS: Neighborhood disadvantage was associated with inflammation and poor metabolic control in pediatric type 1 diabetes patients. Marked racial differences in potential confounding factors precluded differentiation between genetic and environmental effects. Future studies should recruit patients matched for neighborhood characteristics and treatment regimen to more comprehensively assess racial variation in HbA1c.

Family functioning and children's response to primary care treatment for overweight: a preliminary study.

OBJECTIVE: The aim of this study was to assess the relation between family functioning and children's response to treatment for overweight in a primary care setting. METHODS: Sixty predominantly African American (72%) parents of children who are overweight were recruited from a pediatric outpatient clinic to provide information about family functioning. Children's success in treatment was tracked through medical chart review. RESULTS: Parents' baseline self-report of family adaptability was associated with child body mass index z-scores (zBMI) at 3-month follow-up, although this association was no longer significant once baseline child zBMI was taken into account. CONCLUSIONS: Families with greater ability to adopt/implement changes may have children who do better in weight loss treatment. This preliminary study provides a model for integrating family systems ideas into pediatric overweight research and offers heuristic value as well as directions for future research in primary care settings.

Adolescent self-efficacy and resilience in participants attending A diabetes camp.

Adolescents with type 1 diabetes mellitus (T1DM) often speak of the importance of attending a diabetes camp. In an effort to identify the effect of a diabetes camp on participants, a descriptive comparative pilot study was undertaken. Adolescents 10 to 16 years of age with T1DM attending a residential diabetes camp (N = 81) were recruited to explore the concept of self-efficacy and resilience, two possible mediators influenced by attending camp. Overall, self-efficacy and resilience scores were moderately high. No differences were detected in outcome measures for gender or mode of insulin therapy; however, African Americans scored significantly higher for diabetes self-efficacy and resilience. Subjects living with one parent had poorer glycosylated hemoglobin (HgbA1C) but scored better in resilience. No association for years of camp attendance and study outcomes were identified. Diabetes camp is an important experience for adolescents living with T1DM, and continued exploration of the influence of diabetes camp is warranted.