Full Accounting of Diabetes and Pre-Diabetes in the U.S. Population in 1988�C1994 and 2005�C2006

OBJECTIVE—We examined the prevalences of diagnosed diabetes, and undiagnosed diabetes and pre-diabetes using fasting and 2-h oral glucose tolerance test values, in the U.S. during 2005–2006. We then compared the prevalences of these conditions with those in 1988–1994.RESEARCH DESIGN AND METHODS—In 2005–2006, the National Health and Nutrition Examination Survey included a probability sample of 7,267 people aged ≥12 years. Participants were classified according to glycemic status by interview for diagnosed diabetes and by fasting and 2-h glucoses measured in subsamples.RESULTS—In 2005–2006, the crude prevalence of total diabetes in people aged ≥20 years was 12.9%, of which ∼40% was undiagnosed. In people aged ≥20 years, the crude prevalence of impaired fasting glucose was 25.7% and of impaired glucose tolerance was 13.8%, with almost 30% having either. Over 40% of individuals had diabetes or pre-diabetes. Almost one-third of the elderly had diabetes, and three-quarters had diabetes or pre-diabetes. Compared with non-Hispanic whites, age- and sex-standardized prevalence of diagnosed diabetes was approximately twice as high in non-Hispanic blacks (P < 0.0001) and Mexican Americans (P = 0.0001), whereas undiagnosed diabetes was not higher. Crude prevalence of diagnosed diabetes in people aged ≥20 years rose from 5.1% in 1988–1994 to 7.7% in 2005–2006 (P = 0.0001); this was significant after accounting for differences in age and sex, particularly in non-Hispanic blacks. Prevalences of undiagnosed diabetes and pre-diabetes were generally stable, although the proportion of total diabetes that was undiagnosed decreased in Mexican Americans.CONCLUSIONS—Over 40% of people aged ≥20 years have hyperglycemic conditions, and prevalence is higher in minorities. Diagnosed diabetes has increased over time, but other conditions have been relatively stable.Diabetes and its complications remain major causes of morbidity and mortality in the U.S. (1). Estimated economic costs of diabetes in medical expenditures and lost productivity total $174 billion in the U.S. in 2007 (2). In 1999–2002, the crude prevalence of diabetes (diagnosed and undiagnosed) in the U.S. was 9.3%, of which 30% was undiagnosed based on fasting plasma glucose (FPG) (3). A further 26% had impaired fasting glucose (IFG). IFG increases the risk of diabetes (4), and both undiagnosed diabetes and IFG are associated with diabetes complications and risk factors (4,5). These prevalence data came from the National Health and Nutrition Examination Survey (NHANES), the only national survey that captures information on diabetes and pre-diabetes from an interview and FPG.In 2005–2006, an oral glucose tolerance test (OGTT) was added to NHANES, which had not been performed since NHANES 1988–1994. Whereas elevated FPG is determined more by impaired hepatic insulin resistance, elevated 2-h plasma glucose from an OGTT is determined predominantly by peripheral insulin resistance (4,6). The OGTT aids in detecting the total burden of diabetes and also impaired glucose tolerance (IGT). Two-hour plasma glucose values are more sensitive in the elderly (7), an increasing proportion of the U.S. population. IGT also predicts diabetes and is more commonly associated with cardiovascular disease risk factors and events than IFG (4,8).In this report, we analyze the prevalence of diagnosed diabetes, undiagnosed diabetes based on fasting and 2-h plasma glucose from an OGTT, and pre-diabetes (IFG or IGT) in people aged ≥12 years using data from NHANES 2005–2006. Results are presented by age, sex, and race/ethnicity. We compare these estimates with those from NHANES 1988–1994.The addition of the OGTT also allowed assessment of the agreement between diagnostic categories defined by fasting and 2-h plasma glucose. Although this was examined in NHANES 1988–1994 in those aged 40–74 years (9), a reexamination is appropriate given 1) the measurements in a wider age range in NHANES 2005–2006, 2) the change in criteria for IFG (lowered from 110 to 100 mg/dl) since that report (8), and 3) the rising prevalence of glucose abnormalities (3) and obesity (10).     

Trends in Diabetes Prevalence and Diabetes-Related Complications in Older Mexican Americans From 1993�C1994 to 2004�C2005

OBJECTIVE

Evidence has shown that Mexican Americans have a higher prevalence of diabetes and a greater risk for diabetes-related complications than non-Hispanic whites. However, no studies have described the changes in prevalence among older Mexican Americans. The purpose of this study was to expand on the current literature by examining the trends in diabetes prevalence and diabetes-related complications in Mexican Americans aged ≥75 years from 1993–1994 to 2004–2005.

RESEARCH DESIGN AND METHODS

The prevalences of self-reported diabetes and diabetes-related complications were estimated in the original cohort (1993–1994) and the new cohort (2004–2005) of the Hispanic Established Population for the Epidemiologic Study of the Elderly (Hispanic EPESE) and were compared across the two surveys.

RESULTS

The prevalence of diabetes among Mexican Americans aged ≥75 years has nearly doubled between 1993–1994 and 2004–2005 from 20.3 to 37.2%, respectively (P < 0.001). The increase in the prevalence of diabetes was similar across all sociodemographic factors. Diabetes complications did not change significantly between the two cohorts. However, the prevalence of having any lower-extremity function disability did increase between the two cohorts.

CONCLUSIONS

The prevalence of diabetes in older Mexican Americans has increased dramatically. At the same time, there has been no improvement in diabetes-related complications as has been found in the general older population. These findings heighten the urgency for more effective public health interventions targeted to this population. As diabetes and obesity become more prevalent in older adults, physicians should encourage appropriate management in older patients, including early detection and glycemic control.Diabetes is the seventh leading cause of death in the U.S., affecting 16.8 million Americans in 2006 (1). The prevalence of diabetes among individuals aged ≥75 years is projected to increase 336% by 2050 (2). This upward trend is attributed mainly to the aging of the population, an increase in obesity, and lifestyle changes (3–5). Simultaneously, there has been a decrease in the prevalence of several diabetes-related complications as a result of advancements in diabetes management (6).Older Hispanics are a rapidly growing segment of the U.S. population (7). During 1999 and 2002, diabetes was diagnosed in 24.9% of older Mexican Americans (aged ≥65 years) compared with only 14.3% of non-Hispanic white adults of the same age (8). Mexican Americans also have an increased risk and prevalence of diabetes-related complications and a higher disability rate compared with non-Hispanic whites (9,10). As overall life expectancy has increased, many Mexican Americans are living longer with more comorbidities including diabetes (9). Although several studies have examined the national trends of diabetes over the previous decades, no studies have examined the trends in diabetes prevalence and diabetes-related complications among older Mexican Americans. Hence, the purpose of this study was to expand on the current literature by examining the trends in diabetes prevalence and diabetes-related complications over the period 1993–1994 to 2004–2005, comparing two separate representative samples from the Hispanic Established Population for the Epidemiologic Study of the Elderly (Hispanic EPESE), a community-based study of older Mexican Americans (aged ≥65 years) residing in five southwestern states. This analysis builds on earlier work with the baseline data from this study, which showed high rates of diabetes and diabetes complications in older Mexican Americans in 1993–1994 (11–14).     

Leben retten �C sterben zulassen

Background

Emergency missions can also be necessary for patients in the terminal phase of a progressive incurable disease. The emergency physician, accustomed to acting under strict procedures and whose training focuses on the restoration and stabilization of acutely threatened vital functions, can face severe difficulties when treating incurably ill patients in the terminal phase. This study investigates the number of such cases, patient symptoms and the events occurring during life-threatening emergencies of terminally ill patients.

Method

All cases of emergency events involving terminally ill patients were analyzed prospectively. In addition to the standardized protocol (following DIVI/Mind?2) an enquiry sheet was used, which contained an 8-item checklist specifically for terminally ill patients, to be filled out by the responding physician.

Results

The total number of patients in the terminal phase identified by the emergency physician was 55 (0.72% of total cases) and of these patients 30 (55%) were tumor patients. The most frequent complaint observed was dyspnea (30?patients, 55%), followed by relatives of the patients experiencing the stress of caring for a terminally ill person (19?patients, 35%). The leading symptom of 6?patients (11%) was pain. Only 17?cases (30.9%) required transport of the patient to hospital for further treatment.

Conclusion

Every emergency physician can be confronted with an emergency involving a patient with a progressive incurable disease. The condition of each patient must be assessed for each medical decision. Not only medical, but also psychosocial, ethical and legal aspects have to be considered.     

Age at Development of Type 1 Diabetes�C and Celiac Disease�CAssociated Antibodies and Clinical Disease in Genetically Susceptible Children Observed From Birth

OBJECTIVE

To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with an HLA-conferred susceptibility to both diseases.

RESEARCH DESIGN AND METHODS

We observed 2,052 children carrying genetic risks for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease–associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by World Health Organization criteria and celiac disease by duodenal biopsies.

RESULTS

Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease–associated antibody at the median ages of 3.0 and 1.5 years, respectively (P < 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease–associated antibodies, 3 progressed to both diabetes and celiac disease.

CONCLUSIONS

Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease–associated antibodies mostly at a younger age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.The incidences of type 1 diabetes and celiac disease are increasing rapidly (1). These autoimmune diseases often occur together, as ∼4.5% of subjects with recent-onset type 1 diabetes also have celiac disease, and the coexistence is even more common in subjects with long-standing type 1 diabetes (2,3). Shared susceptibility alleles in the HLA region probably contribute to this coexistence (4). Although appearance of diabetes- and celiac disease–specific antibodies strongly indicates commencement of autoimmunity (5), antibodies also predict progression to the respective clinical diseases. However, in the case of diabetes, in particular, the time from autoimmunity to overt disease may vary from months to years. Interestingly, clinical type 1 diabetes is usually diagnosed first and celiac disease within the following few years (6,7). The order is rarely reversed (8).Although coexistence of type 1 diabetes and celiac disease has been studied mainly in clinical patients, Williams et al. (9) showed in a cross-sectional study that 5.4% of nondiabetic first-degree relatives of type 1 diabetic patients who were positive for diabetes-associated autoantibodies were positive also for tissue transglutaminase autoantibody (TGA). However, the findings of the Diabetes Autoimmunity Study in the Young (DAISY) indicated that the two types of antibodies rarely appeared simultaneously (10), whereas the German BabyDiab study suggested that celiac disease–associated antibodies invariably develop later than diabetes-associated autoantibodies (11,12).Here we report the age and order in which the diabetes- and celiac disease–associated antibodies and the two clinical diseases developed in children who carried genetic type 1 diabetes and celiac disease susceptibility and participated in the type 1 Diabetes Prediction and Prevention (DIPP) study.     

Evolution of Percutaneous Coronary Intervention in Patients with Diabetes: A report from the National Heart, Lung, and Blood Institute�Csponsored PTCA (1985�C1986) and Dynamic (1997�C2006) Registries

OBJECTIVE

To evaluate the association of successive percutaneous coronary intervention (PCI) modalities with balloon angioplasty (BA), bare-metal stent (BMS), drug-eluting stents (DES), and pharmacotherapy over the last 3 decades with outcomes among patients with diabetes in routine clinical practice.

RESEARCH DESIGN AND METHODS

We examined outcomes in 1,846 patients with diabetes undergoing de novo PCI in the multicenter, National Heart, Lung, and Blood Institute–sponsored 1985–1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry and 1997–2006 Dynamic Registry. Multivariable Cox regression models were used to estimate the adjusted risk of events (death/myocardial infarction [MI], repeat revascularization) over 1 year.

RESULTS

Cumulative event rates for postdischarge (31–365 days) death/MI were 8% by BA, 7% by BMS, and 7% by DES use (P = 0.76) and for repeat revascularization were 19, 13, and 9% (P < 0.001), respectively. Multivariable analysis showed a significantly lower risk of repeat revascularization with DES use when compared with the use of BA (hazard ratio [HR] 0.41 [95% CI 0.29–0.58]) and BMS (HR 0.55 [95% CI 0.39–0.76]). After further adjustment for discharge medications, the lower risk for death/MI was not statistically significant for DES when compared with BA.

CONCLUSIONS

In patients with diabetes undergoing PCI, the use of DES is associated with a reduced need for repeat revascularization when compared with BA or BMS use. The associated death/MI benefit observed with the DES versus the BA group may well be due to greater use of pharmacotherapy.The practice of percutaneous coronary intervention (PCI) has evolved rapidly in the past 3 decades, with technological advancements from balloon angioplasty (BA) to bare-metal stents (BMS) and the more recent drug-eluting stents (DES) (1). Comparisons of device-specific outcomes have yielded similar results, with a recent meta-analysis reporting a significant reduction in the rate of target lesion revascularization, but not mortality, with DES use compared with BMS use (2).Coronary angioplasty in patients with diabetes has been shown to have a higher rate of infarction and a greater need for additional revascularization procedures (3). In a large consecutive series of patients treated by elective stent implantation, patients with diabetes were at higher risk for in-hospital mortality and subsequent revascularization, which ultimately resulted in a significantly lower cardiac event-free survival rate (4). Yet, the benefit of DES over BMS remains unclear. A pooled analysis (5) reported a significant difference in survival in favor of BMS over the DES, whereas no significant difference in mortality was observed in another analysis of 14 randomized controlled trials (6). Given these inconsistent findings and the growing percentage of diabetic patients undergoing PCI, the impact of advances in PCI technology and adjunct improvement in pharmacotherapy on outcomes in patients with diabetes needs to be assessed.We, therefore, investigated the effectiveness of PCI in patients with diabetes by comparing 1-year rates of death/myocardial infarction (MI) and repeat revascularization across the three device modalities: BA, BMS, and DES. Data from the multicenter, National Heart, Lung, and Blood Institute (NHLBI)-sponsored 1985–1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry and the 1997–2006 Dynamic Registry were used for this purpose.     

Prevalence and Management of Diabetes in Korean Adults: Korea National Health and Nutrition Examination Surveys 1998�C2005

OBJECTIVE

This research investigated recent changes in the prevalence and management status of diabetes among Korean adults.

RESEARCH DESIGN AND METHODS

The Korea National Health and Nutrition Examination Survey (KNHANES), a nationwide survey examining the general health and nutrition status of the Korean people, was conducted in 1998, 2001, and 2005. Using the first (1998; n = 5,645), second (2001; n = 4,154), and third (2005; n = 4,628) KNHANES datasets, in the present study, we estimated the prevalence of diabetes among Korean adults (aged ≥30 years), the proportions of known cases of diabetes, and the proportions of well-controlled cases of diabetes, as defined by either the American Diabetes Association (A1C <7%) or the International Diabetes Federation guidelines (A1C <6.5%).

RESULTS

In 2005, the prevalence of diabetes was estimated to be 9.1% (∼2.58 million people: 10.2% of men and 7.9% of women), including 6.2% with known diabetes and 2.9% with newly diagnosed diabetes. The prevalence of impaired fasting glucose was 17.4% (∼4.94 million people). The proportion of known cases of diabetes drastically increased from 23.2% in 1998 to 41.2% in 2001 and 68.0% in 2005 (P < 0.0001). Among known diabetic patients in 2005, 43.5 and 22.9% had A1C levels <7.0 and <6.5%, respectively.

CONCLUSIONS

The overall prevalence of diabetes in Korea has not changed significantly between 1998 and 2005. Physician diagnosis and treatment rates of diabetes have significantly improved during this period, but glycemic control was still poorer than that in other developed countries.Diabetes has emerged as an important social issue worldwide, particularly in some Asian countries (1–4). The increased prevalence is probably attributable to rapid economic development, improved living standards, an aging population, and a Westernized lifestyle (3,4). In Korea, diabetes and its complications have become a major cause of morbidity and mortality. For example, the mortality rate due to diabetes has doubled during the last decade, increasing from 17.2 per 100,000 persons in 1995 to 24.5 per 100,000 persons in 2005 (5). The prevalence of diabetes also increased rapidly in Korea. Estimated at <1% in 1970 (6) and ∼7.2% in the early 1990s (7), the prevalence rose to 7.6% of the adult population according to an analysis of the 2001 Korea National Health and Nutrition Examination Survey (KNHANES) (8). Considering the impact of suboptimal diabetes control on public health, the management status of diabetes is as relevant as its prevalence. Rapid economic growth over the past 3 decades has brought many changes in Korea, such as better education, frequent oversea travels and international exchange, and the world''s fastest Internet connections, enabling easy access to information nationwide and worldwide (9). These changes made Koreans more interested in a healthy life and forced the government to pay more attention to the issues of health and social welfare. The increasing attention to health and welfare is expected to improve management and control of diabetes in Korea. However, recent changes in the management status of diabetes have not been adequately studied at the national level. Thus, we investigated recent changes in the prevalence, diagnosis, treatment, and control rates of diabetes among Korean adults based on the 1998, 2001, and 2005 KNHANES data.     

Association Between Iron Deficiency and A1C Levels Among Adults Without Diabetes in the National Health and Nutrition Examination Survey, 1999�C2006

OBJECTIVE

Iron deficiency has been reported to elevate A1C levels apart from glycemia. We examined the influence of iron deficiency on A1C distribution among adults without diabetes.

RESEARCH DESIGN AND METHODS

Participants included adults without self-reported diabetes or chronic kidney disease in the National Health and Nutrition Examination Survey 1999–2006 who were aged ≥18 years of age and had complete blood counts, iron studies, and A1C levels. Iron deficiency was defined as at least two abnormalities including free erythrocyte protoporphyrin >70 μg/dl erythrocytes, transferrin saturation <16%, or serum ferritin ≤15 μg/l. Anemia was defined as hemoglobin <13.5 g/dl in men and <12.0 g/dl in women.

RESULTS

Among women (n = 6,666), 13.7% had iron deficiency and 4.0% had iron deficiency anemia. Whereas 316 women with iron deficiency had A1C ≥5.5%, only 32 women with iron deficiency had A1C ≥6.5%. Among men (n = 3,869), only 13 had iron deficiency and A1C ≥5.5%, and only 1 had iron deficiency and A1C ≥6.5%. Among women, iron deficiency was associated with a greater odds of A1C ≥5.5% (odds ratio 1.39 [95% CI 1.11–1.73]) after adjustment for age, race/ethnicity, and waist circumference but not with a greater odds of A1C ≥6.5% (0.79 [0.33–1.85]).

CONCLUSIONS

Iron deficiency is common among women and is associated with shifts in A1C distribution from <5.5 to ≥5.5%. Further research is needed to examine whether iron deficiency is associated with shifts at higher A1C levels.A1C is formed by the glycation of the terminal valine of the β-chain of hemoglobin. It is used commonly as a screening test for diabetes in clinical practice (1). A1C may be less susceptible than other measures of glycemia to temporary fluctuations caused by diet, physical activity, or illness as well as differences in local testing standards; as a result, an expert committee has recently endorsed an A1C ≥6.5% as diagnostic for diabetes (1).Previous studies have reported that depletion of iron stores may alter the glycation rate of hemoglobin and elevate A1C concentrations, independent of glycemia (2). Iron deficiency may be present without associated anemia (3). Although iron deficiency is the most common nutritional deficiency (3), the clinical relevance of iron deficiency on the use of A1C as a screening test for diabetes has not been studied. Reproductive-age women are particularly vulnerable to iron deficiency, reflecting iron loss through menstruation and pregnancy. In the Third National Health and Nutrition Examination Survey (NHANES) 1988–1994 and later NHANES waves, >11% of women had iron deficiency (3,4).Using a recent population-based sample of U.S. adults, we examined the distribution of A1C by iron deficiency status among adults without known diabetes. We hypothesized that adults with iron deficiency would be more likely to have elevated A1C levels, even after consideration of fasting plasma glucose. We also hypothesized that any differences would persist after adjustment for other factors associated with A1C and iron deficiency, including age, race/ethnicity, and waist circumference.     

Environmental-Enrichment�CRelated Variations in Behavioral, Biochemical, and Physiologic Responses of Sprague�CDawley and Long Evans Rats

The behavioral, biochemical, and physiologic consequences of 6 wk of environmental enrichment were evaluated in male Long Evans and Sprague–Dawley rats and compared with those of rats in standard single-housing conditions. Standard housing provided little or no social or physical stimulation whereas environmental enrichment comprised group housing for 8 h daily in a 3-story cage equipped with novel stimuli. Dependent measures included performance in the forced swim test, thresholds for brain-stimulation reward, sucrose intake and preference, determination of corticosterone levels before and after brief restraint stress, and rate of weight gain. In forced swimming tests, active behaviors (diving, swimming with struggling, and climbing) tended to dominate over passive behaviors (sinking, floating) in both groups and outbred rat stocks (especially in enriched groups) on the first day. These behaviors were replaced with maintenance behaviors such as grooming and swimming without struggling on the second exposure, with enriched Long Evans rats showing the largest decline in activity. Baseline plasma corticosterone levels were elevated in both rat stocks after 6 wk of enrichment. After restraint stress, hormone levels in enriched animals tended to peak earlier and approach or exceed baseline values more quickly than was observed in the comparable control groups. Rate of body weight gain was greater in enriched Long Evans rats than Sprague–Dawley or control rats. Our observations indicate that stock- and group-associated differences in several indices occur in association with enrichment. The data support the claim that environmental enrichment may render animals more resilient to challenges.Abbreviation: BSR, brain-stimulation reward; EE, environmental enrichment; FST, forced swim testEnvironmental enrichment (EE) paradigms are designed to enhance laboratory animals’ surroundings to encourage natural behaviors. Some enrichment paradigms also include a social component, based on the social interactions typical of the genus and species. For example, wild mice and rats generally live in colonies, whereas hamsters are known to be social with unfamiliar animals only during mating.²¹Adverse environmental conditions have been shown to affect the susceptibility of animals exposed to diverse stress regimes, reflected in their behavioral,^7,34 physiologic,^{8,25,29,36,56} and biochemical^6,8,16 responses in a strain-dependent manner.^7,8,16 Therefore, a diverse environment might be expected to alter their response to such stressors. A review of the literature reveals few behavioral investigations of the effects of EE on response to a stressor, and the results of biochemical studies in this context have generally been inconsistent. For example, some laboratories have reported no difference in corticosterone levels between EE- and standard-housed animals after exposure to a stressor,^22,33,46 whereas others have observed a reduction in the corticosterone levels of Sprague–Dawley rats⁴ or even elevated levels of plasma corticosterone in enriched Wistar rats.³² These differences may be due to length of EE exposure or in-strain responsivity to stress. Therefore, the first aim of the present set of experiments was to investigate whether rat strain influences the behavioral and physiologic measures typically used to assess stress responses.Behaviors observed during the forced swim test (FST) and sucrose intake values are known to be affected by environmental conditions.^7,15,28,37 Historically, the FST has been used to assess behavioral despair, as indexed by the degree of immobility in an inescapable environment. After antidepressant administration, immobility typically is replaced by more active behaviors.^41-44 EE attenuated behavioral despair in male Sprague–Dawley rats during the FST.⁹ In our hands, exposure to 5 min of FST generally results in more active or escape behaviors (mostly frantic swimming with struggling and climbing) and in the second 5-min test, less vigorous swimming (without struggling). This pattern is not as prominent in stressed male rats.⁷ In the present study, we evaluated the effects of EE on behaviors exhibited in the FST, hypothesizing that animals with experience in an enriched environment would demonstrate less swimming with struggling in the second test compared with rats living in standard housing conditions.In the context of stress research, the presence of an anhedonic state typically is evaluated by using behavioral measures such as thresholds for brain-stimulation reward^2,7,34 and sucrose intake and preference.^28,37,55 The recent finding that EE also alters the behavioral profile of animals with respect to sucrose intake⁹ prompted us to include this measure in our study to determine the general hedonic status of animals in an enriched environment. We also evaluated rate of weight gain and corticosterone levels after 6 wk of EE, because these 2 measures are used frequently as indices of environmental challenges.^3,10,58 In chronic mild stress studies, 3 to 6 wk of administration is a fairly standard regime.^{7,8,19,26,28,50}In summary, we conducted 2 studies using male Sprague–Dawley and Long Evans rats. In the first, we assessed weight gain and plasma corticosterone levels after 6 wk of EE. In addition to these physiologic measures, we administered weekly sucrose intake and preference tests. In the second study, thresholds for brain-stimulation reward were collected biweekly, and exposure to the FST was evaluated after 6 wk of EE.     

Pneumatosis coli �C an underrecognized lesion mimicking neoplastic disease

Pneumatosis (cystoides) intestinalis is defined as the presence of gas in the bowel wall and can be found anywhere in the gastrointestinal tract. It may be harmless or life-threatening, depending on the etiology which includes infectious and drug-induced colitis, bowel ischemia and necrotizing enterocolitis. The lesion has additionally been described following endoscopy. We report two cases of asymptomatic pneumatosis coli mimicking polyposis syndrome or malignancy. Both cases were verified histologically after snare polypectomy or hemicolectomy. The differential diagnosis and the clinical significance of the disease are discussed. Accurate diagnosis, which is mainly based upon endoscopy, computed tomography and histology, is crucial for optimal patient management thus avoiding unnecessary surgical procedures.     

Awareness and knowledge of child abuse amongst physicians �C a descriptive study by a sample of rural Austria

This study with a selected sample of physicians was conducted to assess their awareness and knowledge of child abuse. Two thirds (66.7%) of all participants confirmed contact with obviously abused children in the course of their professional life, whereas 87.3% did not report any prior education or training in that field. In relation to general practitioners, pediatricians had significantly more contacts with abused children (p = 0.021) and more prior education (p = 0.012). Results indicate that physicians in rural regions of Austria possess basic knowledge. Better training and further specialization is needed to facilitate diagnosing, enhance reporting, strengthen cooperation with experts and reduce fears when handling abuse victims. Austria is a rich country with excellent health care and competitive research structures. However, child abuse research in Austria still has to fill gaps in order to keep up with international developments.     

Prevalence of Diabetes and High Risk for Diabetes Using A1C Criteria in the U.S. Population in 1988�C2006

OBJECTIVE

We examined prevalences of previously diagnosed diabetes and undiagnosed diabetes and high risk for diabetes using recently suggested A1C criteria in the U.S. during 2003–2006. We compared these prevalences to those in earlier surveys and those using glucose criteria.

RESEARCH DESIGN AND METHODS

In 2003–2006, the National Health and Nutrition Examination Survey included a probability sample of 14,611 individuals aged ≥12 years. Participants were classified on glycemic status by interview for diagnosed diabetes and by A1C, fasting, and 2-h glucose challenge values measured in subsamples.

RESULTS

Using A1C criteria, the crude prevalence of total diabetes in adults aged ≥20 years was 9.6% (20.4 million), of which 19.0% was undiagnosed (7.8% diagnosed, 1.8% undiagnosed using A1C ≥6.5%). Another 3.5% of adults (7.4 million) were at high risk for diabetes (A1C 6.0 to <6.5%). Prevalences were disproportionately high in the elderly. Age-/sex-standardized prevalence was more than two times higher in non-Hispanic blacks and Mexican Americans versus non-Hispanic whites for diagnosed, undiagnosed, and total diabetes (P < 0.003); standardized prevalence at high risk for diabetes was more than two times higher in non-Hispanic blacks versus non-Hispanic whites and Mexican Americans (P < 0.00001). Since 1988–1994, diagnosed diabetes generally increased, while the percent of diabetes that was undiagnosed and the percent at high risk of diabetes generally decreased. Using A1C criteria, prevalences of undiagnosed diabetes and high risk of diabetes were one-third that and one-tenth that, respectively, using glucose criteria.

CONCLUSIONS

Although A1C detects much lower prevalences than glucose criteria, hyperglycemic conditions remain high in the U.S., and elderly and minority groups are disproportionately affected.The A1C test has recently been recommended for diagnosing diabetes, based on a detailed analysis of its attributes by an international expert committee (1). Laboratory-measured A1C is now as accurate and precise as glucose assays due to improvements in instrumentation and standardization. A1C samples can be obtained at any time, require no patient preparation, and are relatively stable at room temperature after collection. A1C has substantially less biologic variability and is unaffected by acute effects of stress or illness. As a measure of long-term glycemic exposure, A1C has been shown to be better and more consistently correlated with retinopathy in the setting of observational studies and clinical trials in type 1 and type 2 diabetic patients, which have established widely accepted A1C treatment goals for diabetes. A cut point of ≥6.5% for the diagnosis of diabetes was recommended by the committee as optimal for detecting a level of retinopathy thought to be diabetes specific and not due to other conditions (e.g., hypertension). A limitation of A1C for diagnosis is that the committee could not define a specific intermediate threshold at which increased risk for diabetes clearly begins. While there is a continuum of risk even at values into the normal range, the committee suggested the range of ≥6.0 to <6.5% to represent the highest risk for progression to diabetes and one at which preventive measures might be implemented, with additional consideration of prevention efforts at lower levels in the presence of other risk factors. The committee hoped that its report would serve as a stimulus to the scientific community and professional organizations for considering the A1C assay for diagnosis of diabetes.A change in diagnostic criteria has important public health implications pertaining to the magnitude of the population with diabetes or at high risk of diabetes. This report examines the prevalence of diagnosed and undiagnosed diabetes and high risk of diabetes based on self-report and A1C criteria in the U.S. population during 2003–2006. Prevalences are compared with those using the A1C criteria in 1988–1994 and 1999–2002. Finally, we compare the concordance in prevalence of undiagnosed diabetes using the new A1C criteria to criteria based on fasting plasma glucose and 2-h plasma glucose from an oral glucose tolerance test (OGTT).     

Conditions for Tumor-free and Dopamine Neuron�Cenriched Grafts After Transplanting Human ES Cell�Cderived Neural Precursor Cells

We have previously demonstrated derivation of neural precursor (NP) cells of a midbrain-type from human embryonic stem (hES) cells to yield an enriched population of dopamine (DA) neurons. These hES-derived NPs can be expanded in vitro through multiple passages without altering their DA neurogenic potential. Here, we studied two aspects of these hES-NP cells that are critical issues in cell therapeutic approaches for Parkinson''s disease (PD): cell survival and tumorigenic potential. Neuroepithelial rosettes, a potentially tumorigenic structure, disappeared during hES-NP cell expansion in vitro. Although a minor population of cells positive for Oct3/4, a marker specific for undifferentiated hES cells, persisted in culture during hES-NP cell expansion, they could be completely eliminated by subculturing hES-NPs under differentiation-inducing conditions. Consistently, no tumors/teratomas are formed in rats grafted with multipassaged hES-NPs. However, extensively expanded hES-NP cells easily underwent cell death during differentiation in vitro and after transplantation in vivo. Transgenic expression of Bcl-XL and sonic hedgehog (SHH) completely overcame the cell survival problems without increasing tumor formation. These findings indicate that hES-NP cell expansion in conjunction with Bcl-XL+SHH transgene expression may provide a renewable and safe source of DA neurons for transplantation in PD.     

Flicker Light�CInduced Retinal Vasodilation in Diabetes and Diabetic Retinopathy

OBJECTIVE

Flicker light–induced retinal vasodilation may reflect endothelial function in the retinal circulation. We investigated flicker light–induced vasodilation in individuals with diabetes and diabetic retinopathy.

RESEARCH DESIGN AND METHODS

Participants consisted of 224 individuals with diabetes and 103 nondiabetic control subjects. Flicker light–induced retinal vasodilation (percentage increase over baseline diameter) was measured using the Dynamic Vessel Analyzer. Diabetic retinopathy was graded from retinal photographs.

RESULTS

Mean ± SD age was 56.5 ± 11.8 years for those with diabetes and 48.0 ± 16.3 years for control subjects. Mean arteriolar and venular dilation after flicker light stimulation were reduced in participants with diabetes compared with those in control subjects (1.43 ± 2.10 vs. 3.46 ± 2.36%, P < 0.001 for arteriolar and 2.83 ± 2.10 vs. 3.98 ± 1.84%, P < 0.001 for venular dilation). After adjustment for age, sex, diabetes duration, fasting glucose, cholesterol and triglyceride levels, current smoking status, systolic blood pressure, and use of antihypertensive and lipid-lowering medications, participants with reduced flicker light–induced vasodilation were more likely to have diabetes (odds ratio 19.7 [95% CI 6.5–59.1], P < 0.001 and 8.14 [3.1–21.4], P < 0.001, comparing lowest vs. highest tertile of arteriolar and venular dilation, respectively). Diabetic participants with reduced flicker light–induced vasodilation were more likely to have diabetic retinopathy (2.2 [1.2–4.0], P = 0.01 for arteriolar dilation and 2.5 [1.3–4.5], P = 0.004 for venular dilation).

CONCLUSIONS

Reduced retinal vasodilation after flicker light stimulation is independently associated with diabetes status and, in individuals with diabetes, with diabetic retinopathy. Our findings may therefore support endothelial dysfunction as a pathophysiological mechanism underlying diabetes and its microvascular manifestations.Diabetes affects more than 240 million individuals worldwide, and diabetic retinopathy is the leading cause of blindness in the working-age population in most developed countries (1). There is increasing recognition that early endothelial dysfunction plays a key role in the pathogenesis of diabetes (2) and the development of subsequent microvascular complications (3). In support of endothelial dysfunction in diabetic retinopathy (4) are studies showing relationships of diabetic retinopathy with cardiovascular diseases, including stroke, coronary heart disease, and heart failure, independent of traditional risk factors (5–7). Diabetic retinopathy has also been linked with subclinical manifestations of vascular diseases such as coronary artery calcification and cardiac remodeling (5). However, clinical and epidemiological studies have not found consistent associations of serum markers of endothelial dysfunction (e.g., soluble vascular adhesion molecule-1) with diabetic retinopathy, with some reporting positive associations (8,9), but others not finding any (10,11).The response of retinal vessels to diffuse luminance flicker can be measured noninvasively (12) and may reflect endothelial function of the retinal circulation because it has been demonstrated that nitric oxide is released in the retinal vasculature when it is stimulated by flicker light (13). One recent study showed that individuals with diabetes and diabetic retinopathy have reduced flicker-induced retinal vasodilation but did not control for concomitant risk factors including hyperglycemia, hypertension, and diabetes duration (14). In our current study, we sought to clarify whether flicker light–induced vasodilation is impaired in patients with diabetes and in those with diabetic retinopathy, signs independent of major risk factors.     

Serum HER2/ECD value in stage I and II early breast cancer �C need of a lower cut-off?

BACKGROUND: HER2 overexpression is well-established risk factor of worse prognosis in metastatic and early breast cancer. HER2 positivity can be determined from tumor tissue by immunohistochemical staining or by fluorescent in situ hybridization, or from serum by measuring concentration of HER2 receptor extracellular domain (HER2/ECD). HER2/ECD correlates well with worse prognosis in metastatic and locally advanced (stage III) disease if serum concentration is >15 ng/ml, but there are no consistent data for patients with early breast cancer. METHODS AND RESULTS: 41 patients with stage I and II breast cancer and 52 healthy controls were included into the study. HER2/ECD was determined before surgery and correlated with HER2/neu overexpression, Ki67, hormone receptor status and disease stage, and compared with value in healthy controls. Mean serum HER2/ECD concentration in patients was 8.62 ng/ml and 5.78 ng/ml in controls, and the difference was statistically significant (p = 0.000061). The best diagnostic cut-off value was 7.7 ng/ml, with 76.92% sensitivity and 72.92% specificity. Positive predictive value of the test was 69.77% and negative predictive value was 79.55%, with 74.71% of patients correctly classified. Serum HER2/ECD correlated with hormone receptors status, and no correlation with histological overexpression has been observed. CONCLUSION. Serum HER2/ECD concentration of ≥7.7 ng/ml has possible diagnostic value in stage I and II breast cancer. It should not be used as a determinant of HER2 positivity. Prognostic significance of HER2/ECD in early breast cancer, its correlation with hormone receptor status, and interconnection between hormone receptors and HER2 receptor signaling should be further analyzed, since it may have therapeutic implications.     

Prophylaxe und Therapie der Glukokortikoid-induzierten Osteoporose �C rezente Leitlinien im ��berblick

Several international guidelines for treatment and prophylaxis of glucocorticoid-induced osteoporosis (GIO) have been published. Consistent with the development of new therapeutic agents, a different approach to treatment can be recognized depending on the year of publication. Also, new insights for the postmenopausal osteoporosis leave their marks on recent guidelines. The working committee on Osteology of the Austrian Society for Rheumatology and Rehabilitation (?GR) sifted through actual guidelines and recent literature on the topic to develop recommendations for the prophylaxis and treatment of the GIO.