Search

Objective: To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.Research Design and Methods: SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.Results: Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.Conclusions: The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes.Research Design and Methods: Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71-93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years.Results: A total of approximately 66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement.Conclusions: The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies. [ABSTRACT FROM AUTHOR]

Studies of metabolic processes have been enhanced by our understanding of the relationships among obesity, body fat distribution, insulin sensitivity and islet beta-cell function. Thus, we have learned that although insulin resistance is usually associated with obesity, even lean subjects can be insulin resistant due to the accumulation of visceral fat. Insulin sensitivity and beta-cell function are also intimately linked. The hyperbolic relationship between these two parameters explains why insulin-resistant individuals have markedly enhanced insulin responses, whereas subjects who are insulin sensitive exhibit very low responses. Failure to take into account this relationship will lead to erroneous conclusions. By accounting for this important interaction, it has been clearly demonstrated that subjects at high risk of developing type 2 diabetes (older individuals, women with a history of gestational diabetes or polycystic ovary syndrome, subjects with impaired glucose tolerance and first-degree relatives of individuals with type 2 diabetes) have impaired beta-cell function. Furthermore, the progression from normal glucose tolerance to impaired glucose tolerance and type 2 diabetes is associated with declining insulin secretion. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men. DESIGN: Prospective observational study. SUBJECTS: Second-generation Japanese-American males enrolled in a community-based population study. MEASUREMENTS: At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutanous fat areas (SCF). RESULTS: After 7.5y, IAF increased by a mean of 8.0cm² (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r=-0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/I] = -107.13, P = 0.003). CONCLUSIONS: In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, Iow levels of testosterone may increase the risk of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the relationship of percentage of indigenous ancestry with body mass index (BMI) and waist to hip ratio (WHR) among Native Hawaiians. DESIGN: A cross-sectional, observational study among 567 rural native Hawaiian men and women, aged 30 or older, enrolled between 1993-96. MEASUREMENTS: Ancestry was assessed by self-report, and was verified with a brief genealogical interview. Anthropometric measurements, as well as dietary and physical activity histories were also obtained. RESULTS: Percentage Hawaiian ancestry was significantly associated with increased body mass index (BMI), waist to hip ratio (WHR), and age. The association between percentage Hawaiian ancestry and both anthropometric measures persisted after adjusting for age, leisure time physical activity and total dietary energy intake. CONCLUSION: Obesity and central adiposity were highly prevalent among Hawaiians participating in this study. The association between BMI and WHR with percentage Hawaiian ancestry, unexplained by differences in diet and physical activity, suggests genetic factors play an important role in the high prevalence of obesity observed among Native Hawaiians. [ABSTRACT FROM AUTHOR]

In June 1994, the National Heart, Lung, and Blood Institute held a workshop entitled 'Epidemiology of Hypertension in Hispanic Americans, Native Americans, and Asian/Pacific Islander Americans.' The studies that served as the basis for the workshop along with a summary of two workshop panel discussions are being published as a supplement by Public Health Reports. In this article, the authors present graphs that compare results across these studies with data for non-Hispanic whites, blacks, and Hispanics from the Third National Health and Nutrition Examination Survey. The graphs indicate differences in mean blood pressure levels within and among these three population groups; such differences are also apparent in comparisons of these groups with the U.S. white and black populations. Although they appear modest, these differences are sufficient to result in increased mortality rates in populations with higher levels of hypertension. Environmental influences appear to underlie most of these differences. In all of these populations, blood pressure control rates are poor. Based on these studies, hypertension prevention and control programs should be undertaken. Special emphasis should be placed on the underserved minority populations that were the focus of the workshop. [ABSTRACT FROM AUTHOR]

Bak (bcl-2 homologous antagonist/killer) is a proapoptotic member of the ever-expanding bcl-2 gene family, a recently described category of oncogenes that is critical for the regulation of programmed cell death. We investigated the expression of bak in several inflammatory and neoplastic skin diseases in comparison with normal skin. Immunohistochemical analysis revealed positive bak staining in epidermal keratinocytes of normal skin, with the granular layer being stained slightly more strongly than the basal and spinous layers, and in psoriasis vulgaris, lichen planus, actinic keratosis, keratoacanthoma and squamous cell carcinoma. We demonstrated the expression of bak in the follicular infundibulum in contrast to the outer rout sheath of the lower follicle, which showed only negative to weak bak expression. Seventeen of 20 basal cell carcinomas examined showed negative immunostaining for bak, and the remaining three basal cell carcinomas showed only partial weak positivity, mainly in the palisading layers of some tumour formations. Immunoblot analysis using cultured normal human epidermal keratinocytes revealed the presence of bak protein in both undifferentiated and differentiated keratinocytes. The results of our study suggest that the loss of bak expression, in conjunction with the previously reported overexpression of bcl-2, might contribute to the pathogenesis of basal cell carcinoma. [ABSTRACT FROM AUTHOR]