Rebecca B. Lipton

Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index.

BACKGROUND. The early onset of puberty may be related to obesity, so there is a need to know the prevalence of early pubertal milestones in nonoverweight children. OBJECTIVE. We compared attainment of stage 2 breasts, stage 3 (sexual) pubic hair, and menarche in the Third National Health and Nutrition Examination Survey sample of children with normal BMI with those with excessive BMI (≥85th percentile). DESIGN/METHODS. The ages at which 5%, 50%, and 95% of youth had attained key pubertal stages were estimated by probit models. Logit models were then fit to compare attainment of these milestones in children of excessive and normal BMI. RESULTS. Pubertal signs occurred before 8.0 years of age in <5% of the normal-BMI general and non-Hispanic white female population. However, pubertal milestones generally appeared earlier in normal-BMI non-Hispanic black and Mexican American girls; thelarche occurred before age 8.0 in 12% to 19% of these groups, and the 5th percentile for menarche was 0.8 years earlier for non-Hispanic black than non-Hispanic white subjects. Pubarche was found in ≤3% of 8.0-year-old girls with normal BMI of all of these ethnic groups but was significantly earlier in minority groups. Pubarche appeared before 10.0 years in <2% of normal-BMI boys. Girls with excessive BMI had a significantly higher prevalence of breast appearance from ages 8.0 through 9.6 years and pubarche from ages 8.0 through 10.2 years than those with normal BMI. Menarche was also significantly more likely to occur in preteen girls with an elevated BMI. CONCLUSIONS. Prevalence estimates are given for the key pubertal milestones in children with normal BMI. Breast and sexual pubic hair development are premature before 8 years of age in girls with normal BMI in the general population. Adiposity and non-Hispanic black and Mexican American ethnicity are independently associated with earlier pubertal development in girls.

Insulin gene mutations as a cause of permanent neonatal diabetes

We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with β cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially β cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of β cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder.

The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease

OBJECTIVES We sought to examine the age and gender distribution of coronary artery calcium (CAC) by diabetes status in a large cohort of asymptomatic individuals. BACKGROUND Among individuals with diabetes, coronary artery disease (CAD) is a major cause of morbidity and mortality. Electron-beam tomography (EBT) quantifies CAC, a marker for atherosclerosis. METHODS Screening for CAC by EBT was performed in 30,904 asymptomatic individuals stratified by their self-reported diabetes status, gender, and age. The distribution of CAC across the strata and the association between diabetes and CAC were examined. RESULTS Compared with nondiabetic individuals (n = 29,829), those with diabetes (n = 1,075) had higher median CAC scores across all but two age groups (women 40 to 44 years old and men and women > or =70 years old). Overall, the likelihood of having a CAC score in the highest age/gender quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. CONCLUSIONS Younger diabetic individuals appear to have calcified plaque burden comparable to that of older individuals without diabetes. These findings call for future research to determine if EBT-CAC screening has an incremental value over the current CAD risk assessment of individuals with diabetes.

Diagnosis and treatment of neonatal diabetes: an United States experience

Background/objective:  Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age.

Attitudes and Issues in Treating Latino Patients With Type 2 Diabetes: Views of Healthcare Providers

The purpose of this study was to explore the concerns Of Latino patients with Type 2 diabetes. Focus groups were conducted with healthcare practitioners to chart their perceptions of the issues faced by their Latino patients. One group consisted of professionals working among Mexican American clients in an inner-city clinic; another group was held at an inner-city hospital serving mostly Puerto Rican Americans; and a third group involved providers practicing with more affluent, suburban Mexican Americans. Practitioners agreed that communication with patients was hindered by low reading levels, lack of proficiency in English, and an excessive respect for physicians. Emotional barriers to adequate treatment were often more important than financial concerns, even among low-income patients. Fear of insulin therapy was expressed in Hispanic communities, and folk remedies were commonly used. Because family needs were considered most important, adhering to a treatment regimen might be viewed as self-indulgent. Yet families provided valuable reinforcement and emotional support. Important questions facing Latinos with diabetes were effectively identified using focus groups of healthcare providers.

Incidence and onset features of diabetes in African-American and Latino children in Chicago, 1985-1994.

The study aimed to describe the epidemiology of diabetes in minority children residing in Chicago, IL, USA, and to compare the demographic and clinical characteristics of those with type 1 to those with youth‐onset type 2 diabetes.

Ethnic differences in mortality from insulin-dependent diabetes mellitus among people less than 25 years of age.

Objective. To determine whether the risk of death from type 1 insulin-dependent diabetes mellitus (IDDM) was similar among young non-Hispanic black, non-Hispanic white, and Hispanic patients. Design. Retrospective study of death certificates for Chicago residents between 1 and 24 years of age with any mention of diabetes during 1987 through 1994. Prevalence was estimated by an ongoing incidence registry in the city, the 1990 US Census, and published studies. Autopsy reports and/or medical records were examined to determine more clearly the circumstances of death. Case-fatality rates for IDDM in non-Hispanic black, non-Hispanic white, and Hispanic patients were calculated. Deaths in those with diabetes were compared with the mortality experience of the underlying population using race-specific standardized mortality ratios. Results. A total of 30 diabetes-related deaths occurred in the 8-year interval: 23 among non-Hispanic black, 5 among Hispanic, and 2 among non-Hispanic white paients. The average annual case-fatality rate for all ethnic groups combined was 247.2/105 (95% CI: 166.9–353.5). Race-specific rates were 447.8/105(283.9–671.7) for non-Hispanic black patients, 175.6/105(56.9–409.2) for Hispanic patients, and 48.2/105(5.8–174.0) for non-Hispanic white patients; there were no gender differences in risk. A total of 8 individuals died at the onset of disease (7 non-Hispanic black patients and 1 Hispanic patient). Compared with the underlying population, ethnic-specific standardized mortality ratios were elevated significantly for non-Hispanic black and Hispanic patients but not for non-Hispanic white patients. Conclusions. Short-term mortality is elevated substantially among non-Hispanic black and Hispanic youth with IDDM. The ninefold greater risk of death for non-Hispanic black compared with non-Hispanic white youth with diabetes may indicate gaps in access to comprehensive diabetes care.

The Cost-Effectiveness of Personalized Genetic Medicine The case of genetic testing in neonatal diabetes

OBJECTIVE Neonatal diabetes mellitus is a rare form of diabetes diagnosed in infancy. Nearly half of patients with permanent neonatal diabetes have mutations in the genes for the ATP-sensitive potassium channel (KCNJ11 and ABCC8) that allow switching from insulin to sulfonylurea therapy. Although treatment conversion has dramatic benefits, the cost-effectiveness of routine genetic testing is unknown. RESEARCH DESIGN AND METHODS We conducted a societal cost-utility analysis comparing a policy of routine genetic testing to no testing among children with permanent neonatal diabetes. We used a simulation model of type 1 diabetic complications, with the outcome of interest being the incremental cost-effectiveness ratio (ICER,

Obesity at the Onset of Diabetes in an Ethnically Diverse Population of Children: What Does It Mean for Epidemiologists and Clinicians?

/quality-adjusted life-year [QALY] gained) over 30 years of follow-up. RESULTS In the base case, the testing policy dominated the no-testing policy. The testing policy was projected to bring about quality-of-life benefits that enlarged over time (0.32 QALYs at 10 years, 0.70 at 30 years) and produced savings in total costs that were present as early as 10 years (

Incidence of childhood type I and non-type 1 diabetes mellitus in a diverse population: the Chicago Childhood Diabetes Registry, 1994 to 2003.

12,528 at 10 years,