Older age of childhood type 1 diabetes onset is associated with islet autoantibody positivity >30 years later: the Pittsburgh Epidemiology of Diabetes Complications Study.

AIMS: To examine the association between islet autoantibody positivity and clinical characteristics, residual ß-cell function (C-peptide) and prevalence of complications in a childhood-onset (age <17 years), long-duration (≥32 years) type 1 diabetes cohort. METHODS: Islet autoantibodies (glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter-8 antibodies) were measured in the serum of participants who attended the 2011-2013 Pittsburgh Epidemiology of Diabetes Complications study follow-up examination (n=177, mean age 51 years, diabetes duration 43 years). RESULTS: Prevalences of islet autoantibodies were: glutamic acid decarboxylase, 32%; insulinoma-associated protein 2, 22%; and zinc transporter-8, 4%. Positivity for each islet autoantibody was associated with older age at diabetes onset (glutamic acid decarboxylase antibodies, P=0.03; insulinoma-associated protein 2 antibodies, P=0.001; zinc transporter-8 antibodies, P<0.0001). Older age at onset was also associated with an increasing number of autoantibodies (P = 0.001). Glutamic acid decarboxylase antibody positivity was also associated with lower HbA1c (P = 0.02), insulinoma-associated protein 2 antibody positivity was associated with lower prevalence of severe hypoglycaemic episodes (P=0.02) and both distal and autonomic neuropathy (P=0.04 for both), and zinc transporter-8 antibody positivity was associated with higher total and LDL cholesterol (P=0.01). No association between autoantibody positivity and C-peptide was observed. CONCLUSIONS: The strong association between islet autoantibody positivity and older age at type 1 diabetes onset supports the hypothesis of a less aggressive, and thus more persistent, immune process in those with older age at onset. This observation suggests that there may be long-term persistence of heterogeneity in the underlying autoimmune process.

The emergence of vampire bat rabies in Uruguay within a historical context.

Pathogen spillover from wildlife to humans or domestic animals requires a series of conditions to align with space and time. Comparing these conditions between times and locations where spillover does and does not occur presents opportunities to understand the factors that shape spillover risk. Bovine rabies transmitted by vampire bats was first confirmed in 1911 and has since been detected across the distribution of vampire bats. However, Uruguay is an exception. Uruguay was free of bovine rabies until 2007, despite high-cattle densities, the presence of vampire bats and a strong surveillance system. To explore why Uruguay was free of bovine rabies until recently, we review the historic literature and reconstruct the conditions that would allow rabies invasion into Uruguay. We used available historical records on the abundance of livestock and wildlife, the vampire bat distribution and occurrence of rabies outbreaks, as well as environmental modifications, to propose four alternative hypotheses to explain rabies virus emergence and spillover: bat movement, viral invasion, surveillance failure and environmental changes. While future statistical modelling efforts will be required to disentangle these hypotheses, we here show how a detailed historical analysis can be used to generate testable predictions for the conditions leading to pathogen spillover.

Novel hemotropic mycoplasmas are widespread and genetically diverse in vampire bats.

Bats (Order: Chiroptera) have been widely studied as reservoir hosts for viruses of concern for human and animal health. However, whether bats are equally competent hosts of non-viral pathogens such as bacteria remains an important open question. Here, we surveyed blood and saliva samples of vampire bats from Peru and Belize for hemotropic Mycoplasma spp. (hemoplasmas), bacteria that can cause inapparent infection or anemia in hosts. 16S rRNA gene amplification of blood showed 67% (150/223) of common vampire bats (Desmodus rotundus) were infected by hemoplasmas. Sequencing of the 16S rRNA gene amplicons revealed three novel genotypes that were phylogenetically related but not identical to hemoplasmas described from other (non-vampire) bat species, rodents, humans, and non-human primates. Hemoplasma prevalence in vampire bats was highest in non-reproductive and young individuals, did not differ by country, and was relatively stable over time (i.e., endemic). Metagenomics from pooled D. rotundus saliva from Peru detected non-hemotropic Mycoplasma species and hemoplasma genotypes phylogenetically similar to those identified in blood, providing indirect evidence for potential direct transmission of hemoplasmas through biting or social contacts. This study demonstrates vampire bats host several novel hemoplasmas and sheds light on risk factors for infection and basic transmission routes. Given the high frequency of direct contacts that arise when vampire bats feed on humans, domestic animals, and wildlife, the potential of these bacteria to be transmitted between species should be investigated in future work.

The effects of state-level expenditures for home- and community-based services on the risk of becoming a long-stay nursing home resident after hip fracture.

SUMMARY: This study measures the effect of spending policies for long-term care services on the risk of becoming a long-stay nursing home resident after a hip fracture. Relative spending on community-based services may reduce the risk of long-term nursing home residence. Policies favoring alternative sources of care may provide opportunities for older adults to remain community-bound. INTRODUCTION: This study aims to understand how long-term care policies affect outcomes by investigating the effect of state-level spending for home- and community-based services (HCBSs) on the likelihood of an individual's nursing home placement following hip fracture. METHODS: This study uses data from the 5% sample of Medicare beneficiaries from 2005 to 2010 to identify incident hip fractures among dual-eligibility, community-dwelling adults aged at least 65 years. A multilevel generalized estimating equation (GEE) model estimated the association between an individual's risk of nursing home residence within 1 year and the percent of states' Medicaid long-term support service (LTSS) budget allocated to HCBS. Other covariates included expenditures for Title III services and individual demographic and health status characteristics. RESULTS: States vary considerably in HCBS spending, ranging from 17.7 to 83.8% of the Medicaid LTSS budget in 2009. Hip fractures were observed from claims among 7778 beneficiaries; 34% were admitted to a nursing home and 25% died within 1 year. HCBS spending was associated with a decreased risk of nursing home residence by 0.17 percentage points (p 0.056). CONCLUSIONS: Consistent with other studies, our findings suggest that state policies favoring an emphasis on HCBS may reduce nursing home residence among low-income older adults with hip fracture who are at high risk for institutionalization.

Prevalence and incidence of clinically recognized cases of Type 1 diabetes in children and adolescents in Rwanda, Africa.

AIMS: To determine prevalence and incidence estimates for clinically recognized cases of Type 1 diabetes from the Life For a Child Program (LFAC) with onset < 26 years in six representative districts, and the capital, of Rwanda. METHODS: Cases were identified from the LFAC registry and visits to district hospitals. Denominators were calculated from district-level population surveys. Period prevalence data were collected from 1 August 2011 to 31 July 2012 and annual incidence rates were calculated, retrospectively, for 2004-2011. Ninety-five per cent confidence intervals (95% CI) were calculated using a Poisson distribution. RESULTS: The prevalence of known Type 1 diabetes in seven districts in Rwanda for ages < 26 years was 16.4 [95% CI 14.6-18.4]/100 000 and for < 15 years was 4.8 [3.5-6.4]/100 000. Prevalence was higher in females (18.5 [15.8-21.4]/100 000) than males (14.1 [11.8-16.7]/100 000; P = 0.01) and rates increased with age. The annual incidence rate for those < 26 years was stable between 2007 and 2011 with a mean incidence over that time of 2.7 [2.0-3.7]/100 000 ( < 15 years = 1.2 [0.5-2.0]/100 000). Incidence rates were higher in females than males and peaked in males at ages 17 and 22 years and in females at age 18 years. CONCLUSIONS: Our report of known Type 1 diabetes cases shows lower incidence and prevalence rates in Rwanda than previously reported in the USA and most African countries. Incidence of recognized cases has increased over time, but has recently stabilized. However, the likelihood of missed cases due to death before diagnosis and misdiagnosis is high and therefore more definitive studies are needed.

Characterizing the transition from paediatric to adult care among emerging adults with Type 1 diabetes.

AIMS: The goals of the study were to describe the transition of youth with Type 1 diabetes from paediatric to adult healthcare services, examine the link of this transition with self care and glycaemic control, and distinguish youth who received medical treatment from different physicians in terms of demographic and parent relationship variables. METHODS: Youth with Type 1 diabetes (n = 118) were enrolled in a prospective study that examined the transition from the paediatric to adult healthcare systems and were evaluated during their senior year of high school (time 1) and 1 year later (time 2). Data on self care, glycaemic control and parent relationship were collected. RESULTS: The majority of youth saw a paediatric endocrinologist at both assessments (n = 64); others saw an adult care physician at both assessments (n = 26) or transitioned from a paediatric endocrinologist to an adult care physician (n = 19). Nine youth saw no physician between time 1 and time 2. There were group differences in demographic and parent relationship variables and self-care behaviour and glycaemic control related to the transition of care. Youth who remained in the paediatric healthcare system had the best self care and did not experience declines in glycaemic control over time. CONCLUSIONS: Early transition from the paediatric healthcare system to the adult healthcare system is associated with psychosocial variables and worse glycaemic control. Future research should identify factors that determine optimal timing and strategies to avoid deterioration of care and control during this transition.

Songbird preen oil odour reflects haemosporidian parasite load.

Investigating the impact of parasitism on host phenotype is key to understanding parasite transmission ecology, host behavioural ecology and host-parasite coevolution. Previous studies have provided evidence that avian odour is one such phenotypic trait, as mosquitoes that vector the haemosporidian blood parasite Plasmodium tend to prefer birds that are already infected. Preen oil is a major source of avian odour, yet studies to date have not identified differences in preen oil odour based on the presence or absence of haemosporidian infection. Because preen oil can vary with physiological dynamics, we predicted that the composition of preen oil odours might vary according to parasite load, rather than solely by the presence or absence of infection. We used gas chromatography-mass spectrometry to characterize the composition of volatile compounds in preen oil taken from female dark-eyed juncos, Junco hyemalis carolinensis, and asked whether their composition varied with relative haemosporidian parasite load, which we assessed using quantitative PCR. We identified a subset of volatile compounds (a 'blend') and two specific compounds that varied with increasing parasite load. Importantly, the quantity of these compounds did not vary based on parasite presence or absence, suggesting that birds with low parasite loads might be phenotypically indistinguishable from uninfected birds. The volatile blend associated with parasite load also varied with sampling date, suggesting a possible seasonal relapse of chronic infections triggered by shifts in junco host reproductive state. Furthermore, we found a positive relationship between parasite load and a volatile blend shown in a previous study to predict reproductive success in juncos. This is the first study to demonstrate quantitative differences in avian host odour based on haemosporidian parasite load. Our findings highlight the importance of focusing on parasite load, rather than solely presence or absence, in investigating host-parasite interactions.

Clinical and demographic factors associated with fractures among older Americans.

UNLABELLED: Medicare claims data were used to investigate associations between history of previous fractures, chronic conditions, and demographic characteristics and occurrence of fractures at six anatomic sites. The study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures. INTRODUCTION: This study investigates the associations of a history of fracture, comorbid chronic conditions, and demographic characteristics with incident fractures among Medicare beneficiaries. The majority of fracture incidence studies have focused on the hip and on white females. This study examines a greater variety of fracture sites and more population subgroups than prior studies. METHODS: We used Medicare claims data to examine the incidence of fracture at six anatomic sites in a random 5% sample of Medicare beneficiaries during the time period 2000 through 2005. RESULTS: For each type of incident fracture, women had a higher rate than men, and there was a positive association with age and an inverse association with income. Whites had a higher rate than nonwhites. Rates were lowest among African-Americans for all sites except ankle and tibia/fibula, which were lowest among Asian-Americans. Rates of hip and spine fracture were highest in the South, and fractures of other sites were highest in the Northeast. Fall-related conditions and depressive illnesses were associated with each type of incident fracture, conditions treated with glucocorticoids with hip and spine fractures and diabetes with ankle and humerus fractures. Histories of hip and spine fractures were associated positively with each site of incident fracture except ankle; histories of nonhip, nonspine fractures were associated with most types of incident fracture. CONCLUSIONS: This study confirmed previously established associations for hip and spine fractures and identified several new associations of interest for nonhip, nonspine fractures.

Characterizing sudden death and dead-in-bed syndrome in Type 1 diabetes: analysis from two childhood-onset Type 1 diabetes registries.

AIMS: Type 1 diabetes mellitus increases the risk for sudden unexplained death, generating concern that diabetes processes and/or treatments underlie these deaths. Young (< 50 years) and otherwise healthy patients who are found dead in bed have been classified as experiencing 'dead-in-bed' syndrome. METHODS: We thus identified all unwitnessed deaths in two related registries (the Children's Hospital of Pittsburgh and Allegheny County) yielding 1319 persons with childhood-onset (age < 18 years) Type 1 diabetes diagnosed between 1965 and 1979. Cause of death was determined by a Mortality Classification Committee (MCC) of at least two physician epidemiologists, based on the death certificate and additional records surrounding the death. RESULTS: Of the 329 participants who had died, the Mortality Classification Committee has so far reviewed and assigned a final cause of death to 255 (78%). Nineteen (8%) of these were sudden unexplained deaths (13 male) and seven met dead-in-bed criteria. The Mortality Classification Committee adjudicated cause of death in the seven dead-in-bed persons as: diabetic coma (n =4), unknown (n=2) and cardiomyopathy (n=1, found on autopsy). The three dead-in-bed individuals who participated in a clinical study had higher HbA(1c) , lower BMI and higher daily insulin dose compared with both those dying from other causes and those surviving. CONCLUSIONS: Sudden unexplained death in Type 1 diabetes seems to be increased 10-fold and associated with male sex, while dead-in-bed individuals have a high HbA(1c) and insulin dose and low BMI. Although sample size is too small for definitive conclusions, these results suggest specific sex and metabolic factors predispose to sudden unexplained death and dead-in-bed death.

The geographic availability and associated utilization of dual-energy X-ray absorptiometry (DXA) testing among older persons in the United States.

UNLABELLED: Using national Medicare data from 1999-2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices. INTRODUCTION: Medicare reimbursement for DXAs performed in non-facility settings (e.g., physician offices) decreased in 2007. With declining reimbursement, some DXA providers may cease providing this service, which would increase travel distance for some people. The impact of travel distance on access to DXA is unclear. METHODS: Using national Medicare data, we identified claims for DXA to evaluate trends in the number and locations of DXAs performed. Travel distance was the distance from beneficiaries' residence and the nearest DXA provider. Binomial regression evaluated the relationship between travel distance and receipt of DXA. RESULTS: In 2006, 2.9 million DXAs were performed, a 103% increase since 1999. In 2005-2006, 8.0% of persons were tested at non-facility sites versus 4.2% at facility sites. The remainder (88%) had no DXA. Persons traveling 5-9, 10-24, 25-39, and 40-54, and > or = 55 miles were less likely to receive DXA (adjusted risk ratios = 0.92, 0.79, 0.43, 0.32, and 0.26, respectively, < 5 miles referent). Rural residents were more dependent than urban residents on the availability of DXA from non-facility providers. CONCLUSION: Approximately two-thirds of DXAs in 2005-2006 were performed in non-facility settings (e.g., physician offices). Rural residents would have preferentially reduced access to DXA if there were fewer non-facility sites.

"Pathologic" fractures: should these be included in epidemiologic studies of osteoporotic fractures?

UNLABELLED: Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy. INTRODUCTION: Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined "pathologic" fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy. METHODS: We studied US Medicare beneficiaries age > or =65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture. RESULTS: We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a "pathologic" vertebral fracture ICD-9 code, but 66% of persons with a "pathologic" hip fracture, there was evidence of a possible cancer diagnosis. CONCLUSION: Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.

Leukocyte adhesion deficiency type II.

Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persistent leukocytosis, and severe mental and growth retardation. LAD II neutrophils are deficient in expression of selectin ligand activity, and exhibit a correspondingly diminished ability to roll on endothelium and to traffic to inflammatory sites in vivo. LAD II patients exhibit a deficiency in the expression of cell surface fucosylated glycan structures that include the H and Lewis blood group determinants and the sialyl Lewis x epitope, yet the corresponding fucosyltransferase activities responsible for synthesis of these structures are expressed at normal levels. The molecular defect in LAD II has been localized to the pathway that synthesizes GDP-fucose from GDP-mannose. However, the two known component enzymes in this GDP-fucose biosynthetic pathway are normal in sequence and in expression levels in LAD II cells. The genetic lesion in LAD II that accounts for the generalized fucosylation defect in LAD II patients remains to be determined.

Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women.

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.

Hypertension as a risk factor for diabetic neuropathy: a prospective study.

The pathogeneses of diabetic neuropathy is still unclear. This study prospectively investigated the risk factors for distal symmetrical polyneuropathy (DSP) in a cohort of childhood-onset IDDM patients. Subjects from the Epidemiology of Diabetes Complications (EDC) Study were clinically examined at baseline and then biennially. DSP was diagnosed by a combination of clinical criteria, symptoms and signs (Diabetes Control and Complications Trial [DCCT] exam), and quantitative sensory threshold (QST). Among the 463 (70.4%) subjects who were free of DSP at baseline, 453 (97.8%) participated in at least one biennial reexamination during the first 6 years of follow-up and were included in the current analysis. A total of 68 (15.0%) subjects developed DSP in 6 years, giving a cumulative probability of 0.29. The Cox proportional hazards model shows that longer IDDM duration, hypertension, poor glycemic control, height, and smoking were all independent predictors of the incidence of DSP (all P < 0.0001, except for smoking for which P = 0.03). Hypertension showed the greatest impact on the development of DSP for individuals with either short or long IDDM duration. This study confirms some risk factors for DSP found in cross-sectional studies and suggests a strong relationship between hypertension and DSP. The results indicate that in addition to good glycemic control, avoidance of smoking and good blood pressure control may be helpful in preventing or delaying the onset of DSP in IDDM patients.

Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II.

The prevalence of and interrelationships among all four major complications of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a large epidemiologic study of IDDM subjects diagnosed in childhood. This article focuses on the baseline prevalence of complications in the 657 subjects diagnosed between 1950 and 1980 and currently aged 8-48 yr, with a mean duration of 20 yr. In addition to background retinopathy being virtually universal after 20 yr of diabetes, proliferative retinopathy affects 70% of IDDM subjects after 30 yr duration. As with overt nephropathy, prevalence of proliferative retinopathy is marginally higher in females than in males at short durations; the previously reported male excess is limited to the subjects with IDDM of longer duration (greater than or equal to 25 yr). Somewhat different patterns of microalbuminuria are also seen by sex. Males show a threefold increase in prevalence from 10 to 25 yr duration, whereas females show a more constant prevalence across these durations. A further rise in microalbuminuria is seen in males but not females at greater than or equal to 30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at greater than or equal to 30 yr duration of 84% (males) and 59% (females). Distal symmetrical polyneuropathy shows a constant rise with duration and is only marginally higher in men. Prevalence of cardiovascular (coronary and cerebral) disease shows no sex difference, whereas peripheral vascular disease is particularly common in women after 30 yr duration (greater than 30%) compared with men (11%) when determined by ankle/arm blood pressure ratio less than 0.8 at rest or after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of insulin antibodies in newly diagnosed children with insulin-dependent diabetes before insulin therapy.

Insulin antibodies, as measured by plasma radiolabeled insulin-binding capacity, were determined in 124 newly diagnosed insulin-dependent diabetic (IDDM) children before and after 1, 3, and 5 days of insulin therapy. Controls were 35 nondiabetic children with plasma insulin binding capacity of 1.0 +/- 0.7%. The patients were divided into three groups according to their plasma insulin-binding capacity. Group 1 (N = 79) had binding within two standard deviations (SD) of the control mean, group 2 (N = 20) had insulin binding 2-6 SD above controls, and group 3 (N = 25) showed insulin-binding capacity of more than 6 SD above the control mean. After exogenous insulin therapy, plasma 125I-insulin-binding capacity dropped significantly in both groups 2 and 3, concurrent with significant increases in plasma insulin levels. The three groups differed from each other in that patients in group 3 were significantly younger than in the other groups and clinically seemed to be more severely dehydrated, as reflected in their higher levels of serum urea nitrogen, plasma glucose, potassium, and elevated pulse rate. The three groups did not differ in respect to sex, HLA-DR antigens, Coxsackie-B antibody titers, islet cell cytoplasmic antibodies, immunoglobulin level, and C-peptide levels. Only two of 446 siblings of IDDM children showed elevated insulin binding, one of whom developed IDDM 6 wk later. The presence of an insulin-binding substance probably representing insulin antibodies in some cases of newly diagnosed IDDM suggests that autoimmunity in this disorder is not limited to the B-cell membrane and cytoplasm and lends further support to the heterogeneity of IDDM.

The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study. Mortality results.

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Children's Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U.S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

Antibodies to oxidized LDL predict coronary artery disease in type 1 diabetes: a nested case-control study from the Pittsburgh Epidemiology of Diabetes Complications Study.

The pathogenesis of excess cardiovascular risk in type 1 diabetes is unclear. LDL cholesterol is only weakly predictive, and its concentration is often normal in type 1 diabetes. We therefore examined whether markers of LDL oxidation such as antibodies to oxidized LDL (Ab-OxLDL) and LDL-containing immune complexes, rather than LDL concentration, were predictive of coronary artery disease (CAD) in type 1 diabetes. This nested case-control study from an epidemiologic cohort study included 49 incident cases of myocardial infarction (MI), angina, or CAD death and 49 age-, sex-, and duration-matched control subjects. Ab-OxLDL was measured by enzyme immunoassay and the apolipoprotein B (ApoB) content of immune complexes (ApoB-IC) precipitated by polyethylene glycol by immunoelectrophoresis in baseline stored samples. Ab-OxLDL was inversely, and ApoB-IC directly, related to subsequent CAD. In multivariate analyses, Ab-OxLDL remained a significant independent predictor along with previously recognized predictors, hypertension and Beck depression score. In conclusion, oxidation of LDL and the immune response it elicits may play a role in predicting the development of CAD in type 1 diabetes and explain at least some of the enhanced CAD risk in type I diabetes.

Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study.

The natural history of diabetic neuropathy and its risk factors are not well understood, apart from the recognition that prevalence increases with duration and, in many studies, degree of glycemia. The role of potential risk factors was therefore evaluated in a cross-sectional analysis from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study. We present results from the first 400 subjects seen at baseline examination. Neuropathy was determined by a trained internist with a standardized examination and was defined as the presence of at least two of three criteria: abnormal sensory or motor signs, symptoms consistent with neuropathy, and decreased tendon reflexes. The prevalence of neuropathy in this cohort was 34% (18%, 18-29 yr old, 58% greater than or equal to 30 yr old) with no difference by sex. By focusing on subjects greater than or equal to 18 yr old, all significant univariate variables (e.g., duration, glycosylated hemoglobin [HbA1]) were analyzed in 3 multiple logistic regression models: all subjects greater than or equal to 18 yr old and separating the same subjects into two groups based on age (18-29 and greater than or equal to 30 yr). Duration, HbA1, smoking status, and high-density lipoprotein cholesterol were found to be associated with neuropathy in the models for the greater than or equal to 18-yr-old group and the greater than or equal to 30-yr-old group. In the 18- to 29-yr-old group, duration, HbA1, and hypertension status were found to be significantly associated with neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA heterogeneity of insulin-dependent diabetes mellitus at diagnosis. The Pittsburgh IDDM study.

Although some previous studies have suggested that insulin-dependent diabetes mellitus (IDDM) is a heterogeneous condition with variant forms being associated with HLA-DR types, the evidence, thus far, is conflicting. To address this issue, we have examined the presenting characteristics of a consecutive admission series of 200 newly diagnosed cases of IDDM from the Children's Hospital of Pittsburgh. Because HLA-DR frequencies vary by race, data are presented only for the 172 white cases with complete HLA-DR typing. HLA-DR3 was found more frequently among male cases and DR4 among female cases (P less than 0.005). Generally, patients with DR4 presented with a severer clinical picture, being more likely to have impaired consciousness and significant dehydration. In addition, patients with DR4 were more likely to be acidotic, ketotic, and to more frequently report a recent viral infection. This latter finding was supported by a greater frequency of antibodies to Coxsackie-B viruses in the DR4 cases at presentation. These results therefore suggest that there is considerable heterogeneity in IDDM, at least in presenting characteristics, according to HLA-DR type.