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Trevor J Orchard

Publications and source records attributed to Trevor J Orchard.

At least 19 recordsLinked to original sources
PubMed2006

Developing and validating a diabetes database in a large health system.

BACKGROUND: One component of clinical information systems is a registry of patients. Registries allow providers to identify gaps in care at the population level. Registries also allow for rapid cycle continuous quality improvement, targeted practice change and improved outcomes. Most registries are built based on membership with an insurer or other selection criteria. Little, if any data exist on registries representing demographically heterogeneous populations. METHODS: Administrative and clinical data for the period 1/1/2000-12/30/03 were examined. In total, 46,082,941 lab reports, 233,292,544 medical records, and 9,351,415 medical record abstracts, representing approximately 2 million unique patients were searched. The diabetes source population was identified by presence of any one of the following criteria: ICD-9 code 250 (diabetes) for inpatient, emergency room or outpatient visits; any hemoglobin A1c result; blood glucose >200mg/dl; or diabetes medication. A diagnosis of diabetes was verified by trained chart reviewers on a sample of patients. Single indicators and combinations were examined to determine optimal identification of these cases. RESULTS: In two separate validation studies, using two or more indicators or outpatient diagnosis maximized positive predictive value (PPV) (96 and 97%) and sensitivity (99 and 100%) and identified 55,807 individuals. When all patients with a single indicator of outpatient diagnosis (which had the highest single PPV of 94 and 95%) were included together with those having >or=2 indicators, the final sample size was 65,725. CONCLUSION: Two or more indicators or an out-patient-diagnosis identifies a sizeable and unselective diabetes database which can be used to track processes and outcomes.

Databases, Factual↗
PubMed2006

Identifying genetic susceptibilities to diabetes-related complications among individuals at low risk of complications: An application of tree-structured survival analysis.

The authors hypothesized that genetic predisposition to diabetes complications would be more evident among low-risk individuals and aimed to identify genes related to developing complications (confirmed distal symmetric polyneuropathy, overt nephropathy, or coronary artery disease) in low-risk groups. Participants in the Pittsburgh, Pennsylvania, Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes, first seen in 1986-1988 (mean age, 28 years; diabetes duration, 19 years), were reexamined biennially for 10 years. For each complication, subgroups with the lowest disease risk were identified by using tree-structured survival analysis, and 15 candidate genes were compared between subjects with and without complications. In the group with the lowest incidence of confirmed distal symmetric polyneuropathy (n = 123), confirmed distal symmetric polyneuropathy risk increased fivefold for those with the eNOS GG genotype (p < 0.05). In the group with the lowest risk of overt nephropathy (n = 340), the ACE D polymorphism increased overt nephropathy risk twofold (p = 0.05), whereas a protective effect was observed for the LIPC CC genotype (p < 0.05). In the group with the lowest incidence of coronary artery disease (n = 331), the MTHFR CC genotype increased coronary artery disease risk threefold (p < 0.05). Tree-structured survival analysis may help identify genetic predispositions among individuals who, despite low risk, develop diabetes-related complications.

Adult↗
PubMed2006

Modifications of coronary risk factors.

In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers.

Algorithms↗
PubMed2006

Hypotheses, design, and methods for the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) is a National Institutes of Health (NIH)-sponsored randomized clinical trial that evaluates treatment efficacy for patients with type 2 diabetes mellitus and angiographically documented stable coronary artery disease. Using a 2 x 2 factorial design, BARI 2D compares revascularization combined with aggressive medical treatment versus aggressive medical treatment alone; simultaneously, BARI 2D compares 2 glycemic control strategies, insulin sensitization versus insulin provision. All patients have goals of glycosylated hemoglobin values <7.0% and uniform control of hypertension, dyslipidemia, and obesity following recommended medical guidelines. The primary end point of BARI 2D is all-cause 5-year mortality analyzed by intention to treat, and the principal secondary end point is the combination of death, myocardial infarction, and stroke. A total of 2,368 patients have been enrolled at 49 clinical centers throughout North America, South America, and Europe. The study enrollment period was January 2001 through March 2005, and the patient treatment and follow-up phase is expected to extend at least through May 2007. Participants are treated at the local BARI 2D clinical sites on a monthly basis for the first 6 months and then every 3 months until the end of the study. Within BARI 2D, central management centers oversee the control of glycemia, plasma lipid levels, hypertension, and obesity. The randomized clinical trial collects data on patient symptoms, clinical measurements, medications, and clinical events as well as data from centralized evaluations of angiograms, electrocardiograms, nuclear stress tests, blood and urine specimens, and relative economic costs.

Angioplasty, Balloon, Coronary↗
PubMed2006

Lower-extremity arterial calcification as a correlate of coronary artery calcification.

Coronary artery calcification (CAC) has been used as a testing modality for coronary atherosclerosis burden. In diabetes, arterial calcification in the tunica media is common and predicts renal and cardiovascular mortality. It is unknown whether the 2 calcification processes are related. We identified risk factors associated with lower-extremity arterial calcification (LEAC) and determined its relationship to the presence of CAC 6 years later and the incidence of complications in type 1 diabetes mellitus. A random sample of 190 participants from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective cohort of childhood-onset type 1 diabetes mellitus, received radiographs of their ankles and feet at the 4-year follow-up examination (1990-1992) and was followed up for approximately 6 years. At the 10-year examination, 121 of these individuals received an electron beam tomography scan. Male sex (odds ratio [OR] = 12.72, P < .0001), diabetes duration (OR = 4.53, P < .0001), and autonomic neuropathy (AN; OR = 5.92, P = .007) independently increased the odds of LEAC. Controlling for other known risk factors (duration and high-density lipoprotein cholesterol), we found that LEAC correlated with the presence of CAC 6 years later (OR = 1.12, P = .03), although adjusting for neuropathy attenuated this relationship (P = .08). LEAC also independently predicted AN but not the onset of other diabetes complications. Although arterial calcification in the lower extremities and the heart share many of the same risk factors, LEAC is an independent correlate of the later presence of CAC and AN. Thus, factors related to the calcification process in addition to vascular risk factors may play a role in determining the extent of CAC.

Adult↗
PubMed2006

Influences on screening for chronic diabetes complications in type 1 diabetes.

Screening for the long-term complications of diabetes is a critical component of diabetes management; however, evidence demonstrates that screening rates in diabetes populations are suboptimal. Our objective was to determine the use and predictors of optimal screening behavior, defined as receiving a fasting lipid test, dilated eye exam, spot urine test, foot examination, blood pressure reading, and hemoglobin A1c (HbA1c) in the previous year in a representative cohort of subjects with type 1 diabetes. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective cohort study of subjects with childhood onset type 1 diabetes. Data from 325 participants who responded to a survey during 1999-2001 were included in analyses. Reported screening rates were as follows: 87.9% had at least one HbA1c measurement in the past year, 63% had a foot exam, 73.3% had a spot urine test, 81.9% had a dilated eye exam, 93.5% had a blood pressure reading and 68.7% received a fasting lipid profile. Within this group, 37.7% of subjects reported undergoing all five tests (optimal screening). Independent correlates of optimal screening were receiving care from a specialist provider (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.4-4.1) and blood glucose monitoring at least weekly (OR = 2.6; 95% CI: 1.1-6.2). These findings indicate that a large proportion of persons with type 1 diabetes are not being screened at the optimal level. Our data indicate that efforts to rectify this should focus on men and those who do not monitor blood glucose, and should involve primary care practitioners.

Adult↗
PubMed2006

The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience.

Declining incidences in Europe of overt nephropathy, proliferative retinopathy, and mortality in type 1 diabetes have recently been reported. However, comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking. These issues are addressed using the prospective observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Participants were stratified into five cohorts by diagnosis year: 1950-1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1980. Mortality, renal failure, and coronary artery disease (CAD) status were determined on the complete cohort (n = 906) at 20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination. There was a decreasing trend by diagnosis year for mortality, renal failure, and neuropathy across all time intervals (P < 0.05), with the 1950-1959 cohort having a fivefold higher mortality at 25 years than the 1970s' cohorts. Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no change at 25 years. CAD event rates, which were lower than the other complications, also showed no trend. Although some type 1 diabetes complications (mortality, renal failure, and neuropathy) are declining, others (CAD, overt nephropathy, and proliferative retinopathy) show less favorable changes by 30 years.

Age of Onset↗
PubMed2006

The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study.

The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at approximately 7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA(1c) (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT.

Adult↗
PubMed2006

Deficiencies of cardiovascular risk prediction models for type 1 diabetes.

OBJECTIVE: Cardiovascular risk prediction models are available for the general population (Framingham) and for type 2 diabetes (U.K. Prospective Diabetes Study [UKPDS] Risk Engine) but may not be appropriate in type 1 diabetes, as risk factors including younger age at diabetes onset and presence of diabetes complications are not considered. Therefore, our objective was to examine the accuracy of Framingham and UKPDS models for predicting coronary heart disease (CHD) in a type 1 diabetic cohort. RESEARCH DESIGN AND METHODS: Ten-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective cohort study of 658 subjects with childhood-onset type 1 diabetes diagnosed between 1950 and 1980 first seen in 1986-1988, were analyzed. EDC study data were used to calculate the 10-year probability of CHD (fatal CHD, nonfatal myocardial infarction, or Q-waves) applying to the Framingham and UKPDS equations. RESULTS: Mean age at CHD onset was 39 years. When fatal/nonfatal myocardial infarction and CHD death were modeled, both the UKPDS and Framingham models showed significant lack of calibration (P < 0.0001) but moderate discrimination (0.76 UKPDS, 0.77 Framingham men, and 0.88 Framingham women). Both the UKPDS and Framingham models underestimated probability of events in highest risk deciles. CONCLUSIONS: Currently available CHD models poorly predict events in type 1 diabetes. Future research should focus on determining the risk factors accounting for the lack of fit and developing prediction models specific to this high-risk group.

Adult↗
PubMed2006

Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women.

OBJECTIVE: To determine whether middle-aged premenopausal women with type 1 diabetes had more self-reported fractures and lower bone mineral density (BMD) compared with nondiabetic women. RESEARCH DESIGN AND METHODS: Participants were premenopausal women aged 35-55 years with type 1 diabetes (n = 67; 32.2 +/- 5.3 years duration) and without diabetes (n = 237). Total hip, femoral neck, whole-body, and spine BMD were measured by dual X-ray absorptiometry. Calcaneal broadband ultrasound attenuation (BUA) was assessed with quantitative ultrasound. RESULTS: Women with type 1 diabetes were more likely to report a fracture after age 20 years compared with nondiabetic women (33.3 vs. 22.6%; age-adjusted odds ratio 1.89 [95% CI 1.02-3.49]). Type 1 diabetes was associated with lower total hip BMD (0.890 vs. 0.961 g/cm2; P < 0.001), femoral neck BMD (0.797 vs. 0.847 g/cm2; P = 0.001), whole-body BMD (1.132 vs. 1.165 g/cm2; P < 0.01), and lower calcaneal BUA (71.6 vs. 84.9 dB/MHz; P < 0.001) after multivariate adjustment. BMD was 3-8% lower in type 1 diabetic compared with control women and calcaneal BUA was 15% lower. Spine BMD and biomarkers of bone remodeling were not significantly different between groups. In the type 1 diabetic women, reduced monofilament detection and blindness were both associated with lower BMD. CONCLUSIONS: Lower BMD in premenopausal women with type 1 diabetes may substantially increase their risk of developing osteoporosis after menopause. Type 1 diabetic women should be targeted for osteoporosis screening and possible fracture prevention as they transition through menopause.

Absorptiometry, Photon↗
PubMed2006

Lifestyle intervention is associated with lower prevalence of urinary incontinence: the Diabetes Prevention Program.

OBJECTIVE: Diabetes is associated with increased urinary incontinence risk. Weight loss improves incontinence, but exercise may worsen this condition. We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence. RESEARCH DESIGN AND METHODS: We analyzed data from the Diabetes Prevention Program, a randomized controlled trial in 27 U.S. centers. Of the 1,957 women included in this analysis, 660 (34%) were randomized to intensive lifestyle therapy, 636 (32%) to metformin, and 661 (34%) to placebo with standard lifestyle advice. The main outcome measure was incontinence symptoms by frequency and type by a validated questionnaire completed at the end-of-trial visit (mean 2.9 years). RESULTS: The prevalence of total (stress or urge) weekly incontinence was lower among women in the intensive lifestyle group (38.3%) than those randomized to metformin (48.1%) or placebo (45.7%). This difference was most apparent among women with stress incontinence (31.3% for intensive lifestyle group vs. 39.7% for metformin vs. 36.7% for placebo, P = 0.006). Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence. CONCLUSIONS: Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes.

Adult↗
PubMed2006

Translating the chronic care model into the community: results from a randomized controlled trial of a multifaceted diabetes care intervention.

OBJECTIVE: To determine whether using the chronic care model (CCM) in an underserved community leads to improved clinical and behavioral outcomes for people with diabetes. RESEARCH DESIGN AND METHODS: This multilevel, cluster-design, randomized controlled trial examined the effectiveness of a CCM-based intervention in an underserved urban community. Eleven primary care practices, along with their patients, were randomized to three groups: CCM intervention (n = 30 patients), provider education only (PROV group) (n = 38), and usual care (UC group) (n = 51). RESULTS: A marked decline in HbA(1c) was observed in the CCM group (-0.6%, P = 0.008) but not in the other groups. The magnitude of the association remained strong after adjustment for clustering (P = 0.01). The same pattern was observed for a decline in non-HDL cholesterol and for the proportion of participants who self-monitor blood glucose in the CCM group (non-HDL cholesterol: -10.4 mg/dl, P = 0.24; self-monitor blood glucose: +22.2%, P < 0.0001), with statistically significant between-group differences in improvement (non-HDL cholesterol: P = 0.05; self-monitor blood glucose: P = 0.03) after adjustment. The CCM group also showed improvement in HDL cholesterol (+5.5 mg/dl, P = 0.0004), diabetes knowledge test scores (+6.7%, P = 0.07), and empowerment scores (+2, P = 0.02). CONCLUSIONS: These results suggest that implementing the CCM in the community is effective in improving clinical and behavioral outcomes in patients with diabetes.

Aged↗
PubMed2006

A multinational assessment of complications in type 1 diabetes: the DiaMond substudy of complications (DiaComp) level 1.

The objectives of this study were to describe the global geographic variation of microvascular and macrovascular complications in childhood onset type 1 diabetes (T1D) and to relate any such variation to diabetes care activities such as self blood glucose monitoring and intensive insulin therapy. The DiaComp study is a multinational (17 countries) cross-sectional study of complications in T1D (n=2,657). All participants were diagnosed at < 15 years of age and had a diabetes duration of 5-24 years when surveyed. Complications were assessed by self-report of physician diagnosis. Twenty-two centres in 17 countries achieved at least a 67% response rate and are included in the analyses. Central European centres exhibited high rates of retinopathy (Lithuania=31.6%, Romania=24.2%), laser treatment (Lithuania=25.4%) and neuropathy (Lithuania=29.9%, Romania=12.4%) in those with short duration of diabetes (5-15 years), as did Cuba for neuropathy (15.4%). For retinopathy the geographic variation in the short-duration group was also pronounced, ranging from 1.6% in Italy to 41.6% in Lithuania, and from 0% in Brazil, Italy and Australia, to 29.9% in Lithuania for laser treatment. Variation was less dramatic for the prevalence of complications in the long-duration group (15-25 years). Hypertension and duration were strong consistent predictors of all complications, while women had higher prevalence for half the complications (retinopathy, laser treatment and renal disease). Intensive insulin therapy and self-monitoring of blood glucose showed little association with prevalence of complications. In conclusion, this first population-based account of the geographic variation of T1D complications has demonstrated substantial variation. However, the healthcare practice variables that were measured contributed little toward explaining this variation.

Adolescent↗
PubMed2005

Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes.

BACKGROUND: Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease. METHODS: The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee. RESULTS: During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or =0.05) after adjusting for these factors. CONCLUSIONS: Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.

Adolescent↗
PubMed2005

Novel predictors of overt nephropathy in subjects with type 1 diabetes. A nested case control study from the Pittsburgh Epidemiology of Diabetes Complications cohort.

BACKGROUND: Predictors of diabetic nephropathy are only partly known and traditional risk factors do not adequately explain disease risk. We thus examined novel risk factors for overt nephropathy (ON) in type 1 diabetes. METHODS: The EDC is a prospective study of childhood-onset type 1 diabetes. When first seen (1986-1988), mean age was 28 and diabetes duration 19 years. In the subsequent 10 years, 56 of 485 subjects without ON in 1986-88 developed ON. An age, duration (+/-3 years), and sex-matched control was identified for 47 cases. Forty-two matched pairs had available stored plasma samples obtained prior to ON onset in cases, and complete standard risk factor data. RESULTS: Cases had a higher baseline albumin excretion rate (AER), HbA1, pulse rate, non-HDL cholesterol, fibrinogen, small LDL and lower eGDR and LDL particle size compared to controls (all P values<0.05). Multiple measures of immune complexes were increased in cases (P<0.05), whereas borderline elevations were seen for total antioxidant reserve (P=0.06) and retinol (P=0.08). Multivariably, other than AER, LDL particle size and IgG-IC were predictive beyond the standard predictors. CONCLUSION: Besides AER, the immunecomplexes and lipoprotein subclasses may provide additional information in the assessment of ON risk in type 1 diabetes.

Adolescent↗
PubMed2005

Proteomic profiling of human urine using multi-dimensional protein identification technology.

Human urine samples are ideal for proteomic profiling and have tremendous potential as sources of biomarkers. Multi-dimensional protein identification technology (MudPIT) is an effective approach to analyzing human urine or other fluids dominated by diverse metabolites. MudPIT analysis was used to identify 87 proteins in just 15 ml of human urine. A high throughput, reproducible, and sensitive technology, MudPIT may soon be used for more proteomic analyses of metabolites.

Humans↗