bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes in urban African-Americans. XIX. Prediction of the need for pharmacological therapy.
Authors: Thaler L M , Ziemer D C , El-Kebbi I M , Gallina D L , Cook C B , Phillips L S
Published: March 2007

OBJECTIVE: To develop a prediction rule that will identify patients who will require pharmacological therapy within 6 months of first presentation to a diabetes clinic. RESEARCH DESIGN AND METHODS: Among the patients who came to the Grady Diabetes Clinic between 1991 and 1997, we randomized 557 frequent attenders to a development group and 520 frequent attenders to a validation group. Using multiple logistical regression, we derived a prediction rule in the development group to project whether patients would require pharmacological intervention to achieve HbA1c levels <7% after 6 months. The utility of the prediction rule was then confirmed in the validation group and tested prospectively on an additional group of 93 patients who presented from 1997 to 1998. Performance of the prediction rule was assessed using receiver operating characteristic (ROC) curves. RESULTS: The rule (-4.469 + 1.932 x sulfonylurea Rx + 1.334 x insulin Rx + 0.196 x duration + 0.468 x fasting glucose, where "Rx" indicates a prescription) predicted the need for pharmacological intervention in the development group (P < 0.0001). Use of insulin or sulfonylurea therapy at presentation, duration of diabetes, and fasting glucose levels were significant predictors of the future need for pharmacological management. The prediction rule also performed well in the validation group (positive predictive value 90%, correlation between predicted and observed need for medical management 0.99). ROC curves confirmed the value of the prediction rule (area under the curves was 0.91 for the development group, 0.85 for the validation group, and 0.81 for the prospective group). CONCLUSIONS: Early identification of individuals who will require pharmacological intervention to achieve national standards for glycemic control can be achieved with high probability, thus allowing for more efficient management of diabetes.
The summary of diabetes self-care activities measure: results from 7 studies and a revised scale.
Authors: Toobert D J , Hampson S E , Glasgow R E
Published: March 2007

OBJECTIVE: To review reliability, validity, and normative data from 7 different studies, involving a total of 1,988 people with diabetes, and provide a revised version of the Summary of Diabetes Self-Care Activities (SDSCA) measure. RESEARCH DESIGN AND METHODS: The SDSCA measure is a brief self-report questionnaire of diabetes self-management that includes items assessing the following aspects of the diabetes regimen: general diet, specific diet, exercise, blood-glucose testing, foot care, and smoking. Normative data (means and SD), inter-item and test-retest reliability, correlations between the SDSCA subscales and a range of criterion measures, and sensitivity to change scores are presented for the 7 different studies (5 randomized interventions and 2 observational studies). RESULTS: Participants were typically older patients, having type 2 diabetes for a number of years, with a slight preponderance of women. The average inter-item correlations within scales were high (mean = 0.47), with the exception of specific diet; test-retest correlations were moderate (mean = 0.40). Correlations with other measures of diet and exercise generally supported the validity of the SDSCA subscales (mean = 0.23). CONCLUSIONS: There are numerous benefits from standardization of measures across studies. The SDSCA questionnaire is a brief yet reliable and valid self-report measure of diabetes self-management that is useful both for research and practice. The revised version and its scoring are presented, and the inclusion of this measure in studies of diabetes self-management is recommended when appropriate.
Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.
Authors: Raskin P , Jovanovic L , Berger S , Schwartz S , Woo V , Ratner R
Published: March 2007

OBJECTIVE: This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured. RESULTS: The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups. CONCLUSIONS: Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.
Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans.
Authors: Shojaee-Moradie F , Powrie J K , Sundermann E , Spring M W , Schüttler A , Sönksen P H , Brandenburg D , Jones R H
Published: March 2007

OBJECTIVE: To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. RESEARCH DESIGN AND METHODS: Five normal human subjects received a subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. RESULTS: After subcutaneous administration, Bl-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (approximately 86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P < 0.05). CONCLUSIONS: When injected subcutaneously into normal human subjects, Bl-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma halflife. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used.
Thalidomide impairs insulin action on glucose uptake and glycogen synthesis in patients with type 2 diabetes.
Authors: Iqbal N , Zayed M , Boden G
Published: March 2007

OBJECTIVE: To investigate the effect of thalidomide on glucose turnover (glucose production and uptake), on intracellular pathways of glucose utilization (glycogen synthesis [GS], glycolysis [GLS], carbohydrate oxidation, and nonoxidative GLS), and on free fatty acid (FFA) turnover (lipolysis, FFA oxidation, and FFA reesterification). RESEARCH DESIGN AND METHODS: A total of 6 patients with type 2 diabetes were studied with 4-h isoglycemic-hyperinsulinemic clamps (approximately 8 mmol/l and 500-600 pmol/l, respectively) before treatment (Prestudy), after 3 weeks of thalidomide (150 mg orally at bedtime), and after 3 weeks of placebo. RESULTS: Thalidomide reduced insulin-stimulated glucose uptake by 31% (from 27.7 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 21% (from 24.2 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with placebo. Thalidomide also reduced insulin-stimulated GS by 48% (from 14.1 to 8.2 micromol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 40% (from 13.6 to 8.2 micromol x kg(-1) x min(-1), P < 0.5) compared with placebo. Thalidomide had no effect on rates of GLS, carbohydrate oxidation, nonoxidative GLS, lipolysis, FFA oxidation, and reesterification. CONCLUSIONS: We conclude that thalidomide increased insulin resistance in obese patients with type 2 diabetes by inhibiting insulin-stimulated GS and that patients taking thalidomide should be monitored for possible deterioration in their glucose tolerance.
Oxidative stress in families of type 1 diabetic patients.
Authors: Matteucci E , Giampietro O
Published: March 2007

OBJECTIVE: The link between hyperglycemia and the complications of diabetes is unknown. It is still discussed whether oxidative stress precedes or merely reflects diabetic complications. To search for a familial predisposition to oxidative stress, we investigated indexes of glucose and lipid metabolism, markers of plasma and cell lipid oxidation, a marker of oxidant-induced protein damage, and the effects of oxygen radicals on erythrocytes (or red blood cells [RBCs]) of patients with type 1 diabetes and their relatives. RESEARCH DESIGN AND METHODS: We recruited 30 type 1 diabetic subjects (10 without diabetic complications, 10 with retinopathy, and 10 with nephropathy), 36 nondiabetic siblings, 37 nondiabetic parents of type 1 diabetic subjects, and 3 control groups of healthy subjects without a family history of diabetes. Levels of blood creatinine, glucose, HbA(1c), cholesterol, triglycerides, lipoprotein(a) (Lp[a]), fibrinogen, malondialdehyde (MDA), and advanced oxidation protein products were determined. The RBC response to oxidative stress (3-h incubation at 37 degrees C with or without a radical generating system) was evaluated by measuring RBC glutathione (GSH), RBC-MDA, and hemolysis. RESULTS: Diabetic patients had higher levels of blood glucose (P < 0.001), HbA(1c) (P < 0.001), Lp(a) (P < 0.01), and fibrinogen (P < 0.05) than control subjects. Siblings of diabetic patients had higher Lp(a) levels (P < 0.001). Parents had higher levels of plasma glucose (P < 0.05) and Lp(a) (P < 0.01). Plasma and RBC-MDA were significantly elevated in diabetic subjects and relatives compared with control subjects. Basal RBC-GSH was lower in diabetic subjects (P < 0.01). In diabetic subjects, incubations of cells caused a decrease in RBC-GSH of a lesser degree than that in control subjects, but they caused a significant increase in hemolysis. Among relatives, hemolysis was increased both at baseline and after incubation. Plasma MDA levels were associated with blood glucose, creatinine, and fibrinogen levels (multiple r = 0.5, P < 0.001), and basal RBC-MDA levels were associated with plasma Lp(a), fibrinogen, and plasma MDA levels (r = 0.6, P < 0.001). Basal RBC-GSH content correlated with serum glucose and RBC-MDA production (r = 0.3, P < 0.01). CONCLUSIONS: Our study is the first to present evidence that markers of lipoprotein metabolism (Lp[a]), oxidative stress (plasma and RBC-MDA), and cellular fragility (hemolysis) are abnormal in nondiabetic relatives of type 1 diabetic subjects, thereby supporting the view that familial elements of diabetes even precede the onset of diabetes. It seems reasonable that the same biological markers considered major predictors of cardiovascular disease can also trace familial susceptibility to type 1 diabetes, just as they have been associated with the development of type 2 diabetes.
Secular trends in birth weight, BMI, and diabetes in the offspring of diabetic mothers.
Authors: Lindsay R S , Hanson R L , Bennett P H , Knowler W C
Published: March 2007

OBJECTIVE: The offspring of mothers who had diabetes during pregnancy experience increased risk later of diabetes and obesity later. We hypothesized that, in light of the historical improvements in the management of diabetes during pregnancy, these late consequences of the early environment might be diminishing with time. RESEARCH DESIGN AND METHODS: Birth weight and information on BMI and glucose tolerance have been collected as part of the epidemiological survey of the Gila River Indian Community in Arizona. We examined birth weight, BMI, and diabetes in offspring of mothers with type 2 diabetes during pregnancy born in four 10-year time intervals since 1955 compared with offspring whose mothers either had not developed diabetes or were prediabetic (i.e., developed diabetes after the index pregnancy). RESULTS: Offspring of diabetic mothers (ODM) were heavier at birth, had a higher BMI at all ages throughout childhood, and had an increased incidence rate of diabetes in childhood and early adulthood (7- to 20-fold, offspring of nondiabetic mothers [ONDM]; 3- to 5-fold, offspring of prediabetic mothers [OPDM]). Relative differences in birth weight and BMI between ODM and ONDM were greatest for those born before 1965. In those born after 1965, despite secular trends to higher BMI and diabetes incidence in the ONDM, differences in BMI and birth weight of ODM versus ONDM and OPDM appeared to have been maintained. CONCLUSIONS: With the possible exception of individuals born before 1965, the increased risk of diabetes and obesity experienced by ODM does not seem to be diminishing with time.
Proportion of type 2 diabetes cases resulting from impaired fetal growth.
Authors: Boyko E J
Published: March 2007

OBJECTIVE: During the past decade, several researchers have demonstrated a higher risk of type 2 diabetes in relation to lower birth weight. This theory, referred to as the "thrifty phenotype" hypothesis, postulates that impaired fetal growth predisposes individuals to the development of diabetes and other metabolic abnormalities. This article examines the importance of fetal growth in the etiology of diabetes by estimating the proportion of diabetes cases associated with this exposure. RESEARCH DESIGN AND METHODS: The importance of an exposure or its correlate as a potential cause of a disease can be assessed by estimating the proportion of cases that could be prevented if the exposure was eliminated from a defined population. This proportion is referred to as the population-attributable fraction (PAF). Published studies of the association between diabetes and birth weight were reviewed and selected for further analysis if data were presented that enabled PAF calculation. In addition, PAFs were calculated for higher birth weight cutoffs because researchers have postulated that the lowest birth weight category may not capture all cases of fetal growth retardation. Studies have shown that exposure classified in this broader manner can produce unbiased PAF estimates, even if many subjects are falsely classified as exposed. RESULTS: PAFs for the lowest birth weight category ranged from 0.01 to 0.25. In this analysis, PAFs for diabetes did not exceed 0.35. In contrast, >50% of diabetes cases in the First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study were attributable to excess adiposity as reflected by a BMI of > or =26 kg/m2 (PAF >0.50). CONCLUSIONS: Impaired fetal growth or its correlates account for a minority (<0.50) of type 2 diabetes cases.
Carotid intima-media thickness in Japanese type 2 diabetic subjects: predictors of progression and relationship with incident coronary heart disease.
Authors: Yamasaki Y , Kodama M , Nishizawa H , Sakamoto K , Matsuhisa M , Kajimoto Y , Kosugi K , Shimizu Y , Kawamori R , Hori M
Published: March 2007

OBJECTIVE: To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients. RESEARCH DESIGN AND METHODS: Carotid IMT of 287 subjects with type 2 diabetes (mean age 61.6 years) without CHD or cerebrovascular disease was examined at baseline and after a mean follow-up of 3.1 years. RESULTS: The annual progression of IMT (means +/- SEM) was 0.04+/-0.004 mm/year. Stepwise multivariate analysis demonstrated that independent risk factors for progress of IMT were the initial IMT (P<0.001), the average HbA1c level (P<0.001), and age (P = 0.001). Both the initial IMT (odds ratio [OR] 4.9, 95% CI 1.7-14.1) and a low average HDL cholesterol (OR 0.2, 0.1-0.8) were identified as predictors of incident nonfatal CHD (angina pectoris or nonfatal myocardial infarction; 3-year incidence 10.1%) after adjusting for age, sex, average HbA1c, and other risk factors. CONCLUSIONS: The predictors of the progression of carotid IMT in Japanese type 2 diabetic subjects were its baseline thickness and the average HbA1c during the follow-up. Baseline carotid IMT and low HDL cholesterol predicted the incidence of nonfatal CHD.
Sodium Sensitivity Related to Albuminuria Appearing Before Hypertension in Type 2 Diabetic Patients
Authors: Imanishi Masahito , Yoshioka Katsunobu , Okumura Michiaki , Konishi Yoshio , Okada Noriyuki , Morikawa Takashi , Sato Toshihiko , Tanaka Shiro , Fujii Satoru
Published: March 2007

OBJECTIVE— To find whether sodium sensitivity of blood pressure appears before hypertension and whether the sensitivity is related to diabetic nephropathy, we examined type 2 diabetic patients with normal levels of serum creatinine.

RESEARCH DESIGN AND METHODS— A total of 32 patients were divided into three age-matched groups: 11 patients had normoalbuminuria, 12 had microalbuminuria, and 9 had macroalbuminuria. Patients stayed on a diet with ordinary sodium levels for 1 week and a sodium-restricted diet for 1 week, in random order. Urinary excretion of sodium and albumin and systemic blood pressure were measured daily. A pressure-natriuresis curve was drawn by linkage of the two datum points obtained in the steady state during the different diets. We calculated the sodium sensitivity index as the reciprocal of the slope of this curve.

RESULTS— The median sodium sensitivity index and the mean blood pressure were higher in micro- and macroalbuminuric patients than in normoalbuminuric patients. Eighteen patients were without hypertension(<140/90 mmHg); of these, 10 had blood pressure readings <130/85 mmHg with ordinary sodium levels. Urinary albumin was correlated with the index but not with blood pressure. For these 10 patients, the index in those with albuminuria was higher than in those with normoalbuminuria. In such patients with albuminuria, sodium restriction decreased albuminuria and blood pressure.

CONCLUSIONS— In type 2 diabetic patients with albuminuria but normal levels of serum creatinine, sodium sensitivity of blood pressure appears before hypertension and is related to albuminuria; sodium restriction is one treatment for diabetic nephropathy, even without hypertension.
MICA Polymorphism Is Associated With Type 1 Diabetes in the Korean Population
Authors: Park Yongsoo , Lee Hongkyu , Sanjeevi Carani B. , Eisenbarth George S.
Published: March 2007

OBJECTIVE— Recent studies have demonstrated that MICA (major histocompatibility complex class I chain-related genes) on the short arm of the chromosome 6 are associated with susceptibility to various autoimmune diseases in Caucasians. The aim of our study was to investigate the role of MICA in type 1 diabetes susceptibility independent of the HLA DR-DQ polymorphism in genetically distinct Koreans.

RESEARCH DESIGN AND METHODS— A total of 119 patients selected from Korean Seoul type 1 diabetes registry and 134 nondiabetic unrelated control subjects were typed for exon 5 polymorphism of MICA in addition to HLA DR-DQ typing. A total of 52 simplex families of type 1 diabetes were also studied.

RESULTS— The MICA microsatellite allele consisting of six repetitions of GCT/AGC (A6) was present at a significantly lower frequency in the diabetic patient group (Pc < 0.01; Pc = P value after Bonferroni correction) than in the control population. The MICA microsatellite allele consisting of four repetitions (A4) was present at a higher frequency in diabetic patients(P < 0.05). This deviated distribution was not changed even after controlling for the HLA DRB1-DQB1 haplotype. Transmission/disequilibrium test revealed significant deviation of transmission for alleles at the A6 polymorphism within the MICA gene (P < 0.05).

CONCLUSIONS— We could assess that the MICA gene might be associated with type 1 diabetes transracially independent of the HLA gene.
How Cost-Effective Is the Treatment of Dyslipidemia in Patients With Diabetes but Without Cardiovascular Disease?
Authors: Grover Steven A. , Coupal Louis , Zowall Hanna , Alexander Charles M. , Weiss Thomas W. , Gomes Daniel R.J.
Published: March 2007

OBJECTIVE— Epidemiological studies have shown that the risk of myocardial infarction (MI) in diabetic patients without cardiovascular disease(CVD) is comparable to the risk of MI in patients with CVD. We used a validated Markov model to compare the long-term costs and benefits of treating dyslipidemia in diabetic patients without CVD versus treating CVD patients without diabetes in the U.S. The generalizability and robustness of these results were also compared across six other countries (Canada, France,Germany, Italy, Spain, and the U.K.).

RESEARCH DESIGN AND METHODS— With use of the Cardiovascular Disease Life Expectancy Model, cost effectiveness simulations of simvastatin treatment were performed for men and women who were 40-70 years of age and had dyslipidemia. We forecast the long-term risk reduction in CVD events after treatment. On the basis of the Scandinavian Simvastatin Survival Study results, we assumed a 35% reduction in LDL cholesterol and an 8% rise in HDL cholesterol.

RESULTS— In the U.S., treatment with simvastatin for CVD patients without diabetes was cost-effective, with estimates ranging from$8,799 to $21,628 per year of life saved (YOLS). Among diabetic individuals without CVD, lipid therapy also appeared to be cost-effective, with estimates ranging from $5,063 to $23,792 per YOLS. In the other countries studied, the cost effectiveness of treating diabetes in the absence of CVD was comparable to the cost effectiveness of treating CVD in the absence of diabetes.

CONCLUSIONS— Among diabetic men and women who do not have CVD,lipid therapy is likely to be as effective and cost-effective as treating nondiabetic individuals with CVD.
Potential Short-Term Economic Benefits of Improved Glycemic Control
Authors: Menzin Joseph , Langley-Hawthorne Clare , Friedman Mark , Boulanger Luke , Cavanaugh Robert
Published: March 2007

OBJECTIVE— There are limited data relating glycemic control to medical costs among patients with diabetes. The goal of this study was to examine the potential impact of improved glycemic control on selected short-term complications of diabetes and associated costs in a managed care setting.

RESEARCH DESIGN AND METHODS— Using a retrospective cohort design and automated databases from 1 January 1994 to 30 June 1998, adult members of the Fallon Clinic who were diagnosed with diabetes were identified and assigned to one of three study groups based on each patient's mean HbAlc level: good control (<8%), fair control (8-10%), and poor control (>10%) groups. Inpatient (hospital or skilled nursing facility)admissions for selected acute (short-term) complications, represented by selected infections, hyperglycemia, hypoglycemia, and electrolyte disturbances, and the associated medical charges were evaluated across the three HbAlc groups. Multivariate analyses were used to control for differences in several potential confounding factors among the study groups. All findings were expressed on a 3-year basis.

RESULTS— Of 2,394 patients with diabetes, ∼10% (251) had at least one inpatient stay for a short-term complication, accounting for 447 admissions. Over 3 years, the adjusted rate of inpatient treatment ranged from 13 per 100 patients with good glycemic control to 16 per 100 patients with fair glycemic control and 31 per 100 patients with poor glycemic control(P < 0.05). The corresponding mean adjusted charges were approximately $970, $1,380, and $3,040, respectively. Among the 30% of the study population with long-term diabetic complications, the results were more marked; the adjusted admissions per 100 patients (mean charges) were estimated to be 30 ($2,610), 38 ($3,810), and 74 ($8,320) over 3 years for patients with an HbAlc of <8, 8-10, and >10%, respectively.

CONCLUSIONS— In typical practice, better glycemic control is associated with a reduced rate of admission for selected short-term complications and, therefore, reduced medical charges for these complications over a 3-year period. The potential short-term economic benefits are important to consider when making decisions regarding the adoption and use of new interventions for the management of diabetes.
Interventions to Improve the Management of Diabetes in Primary Care, Outpatient, and Community Settings
Authors: Renders Carry M. , Valk Gerlof D. , Griffin Simon J. , Wagner Edward H. , Eijk van Jacques ThM. , Assendelft Willem J.J.
Published: March 2007

OBJECTIVE—To review the effectiveness of interventions targeted at health care professionals and/or the structure of care in order to improve the management of diabetes in primary care, outpatient, and community settings.

RESEARCH DESIGN AND METHODS—A systematic review of controlled trials evaluating the effectiveness of interventions targeted at health care professionals and aimed at improving the process of care or patient outcomes for patients with diabetes was performed. Standard search methods of the Cochrane Effective Practice and Organization of Care Group were used.

RESULTS—A total of 41 studies met the inclusion criteria. The studies identified were heterogeneous in terms of interventions, participants, settings, and reported outcomes. In all studies, the interventions were multifaceted. The interventions were targeted at health care professionals only in 12 studies, at the organization of care only in 9 studies, and at both in 20 studies. Complex professional interventions improved the process of care, but the effect on patient outcomes remained less clear because such outcomes were rarely assessed. Organizational interventions that facilitated the structured and regular review of patients also showed a favorable effect on process measures. Complex interventions in which patient education was added and/or the role of a nurse was enhanced led to improvements in patient outcomes as well as the process of care.

CONCLUSIONS—Multifaceted professional interventions and organizational interventions that facilitate structured and regular review of patients were effective in improving the process of care. The addition of patient education to these interventions and the enhancement of the role of nurses in diabetes care led to improvements in patient outcomes and the process of care.
Peak Expiratory Flow Rate: Relationship to Risk Variables and Mortality
Authors: Klein Barbara E.K. , Moss Scot E. , Klein Ronald , Cruickshanks Karen J.
Published: March 2007

OBJECTIVE—To examine correlates of peak expiratory flow rate in people with type 1 diabetes and to evaluate the relationship of peak expiratory flow rate to mortality.

RESEARCH DESIGN AND METHODS—A cohort study that was originally designed to determine the prevalence, incidence, and severity of diabetic retinopathy also provided the opportunity to measure peak expiratory flow rate. This was first measured at a 10-year follow-up and was evaluated in regard to risk factors for microvascular complications of diabetes. Mortality during 6 years of follow-up after the measurement was also ascertained.

RESULTS—In multivariable analysis, peak expiratory flow rate was associated with sex, age, height, BMI, history of cardiovascular disease, pulse rate, duration of diabetes, glycosylated hemoglobin, and end-stage renal disease. Peak expiratory flow rate was significantly associated with survival in categorical analyses. Even after considering age, sex, renal disease, history of cardiovascular disease, respiratory symptoms, duration of diabetes, cigarette smoking, and hypertension, peak expiratory flow rate was still significantly related to survival (hazard ratio 0.61 [95% CI 0.46–0.82]).

CONCLUSIONS—These data indicate that peak expiratory flow rate is associated with risk factors for other complications of diabetes. In addition, peak expiratory flow rate is a significant predictor of survival over even a relatively short period of time (6 years) in patients with younger-onset diabetes.
The Oregon Health Plan
Authors: Srinivasan Malathi , Przybylski Michael , Swigonski Nancy
Published: March 2007

OBJECTIVE— In 1994, the Oregon Health Plan (OHP) expanded basic Medicaid insurance to residents under the federal poverty limit, adopted a prioritized limited benefits package, and converted to managed care. The quality of care in predominantly Medicaid populations with diabetes has not been previously described. In OHP enrollees, we examined predictors of diabetes care based on American Diabetes Association guidelines and described OHP diabetes care compared with national benchmarks.

RESEARCH DESIGN AND METHODS— Chart abstraction and Medicaid data for 1995-1996 yielded 996 nonpregnant diabetic patients who were 18-64 years of age. Using HbAlc, lipid panel, and urine protein/microalbumin documentation ordered during the study year, we constructed a standard care (SC) index: SC for all three tests, mixed care(MC) for one to two tests, or no tests documented (NTD).

RESULTS— Our sample was predominantly white, 48 ± 11 years of age, 63% women, with 8 ± 5 provider visits. Providers ordered HbAlc (70%), urine microalbumin/protein (57%), and lipid panel(41%) tests. Patients distributed into SC (22%), MC (62%), or NTD (16%). Thirteen variables predicted SC. Patients had a higher likelihood of SC if they were 18-24 years of age, had more clinic visits, were on insulin daily,were in several comorbid groups, were enrolled in salaried or capitated health plans, or lived in counties with more hospital beds. Four studies were used as comparable national benchmarks.

CONCLUSIONS— Care provided to OHP patients with diabetes compares favorably with national benchmarks. Yet, most OHP patients with diabetes are still not achieving optimal care. Examining predictors of SC may play an important role in further policy development.
The Metabolic Syndrome in the West Bank Population
Authors: Abdul-Rahim Hanan F. , Husseini Abdullatif , Bjertness Espen , Giacaman Rita , Gordon Nahida H. , Jervell Jak
Published: March 2007

OBJECTIVE— To compare the prevalence of components of the metabolic syndrome, including hypertension, abnormal glucose metabolism,dyslipidemia, central obesity, and overall obesity, between a rural and an urban Palestinian West Bank community.

RESEARCH DESIGN AND METHODS— A total of 500 rural and 492 urban men and women aged 30-65 years participated in a community-based cross-sectional survey. Diabetes and impaired glucose tolerance were diagnosed using the oral glucose tolerance test. BMI, waist-to-hip ratio, and blood pressure were measured, and blood samples were taken from each subject. Sociodemographic characteristics were investigated using a questionnaire.

RESULTS— Hypertriglyceridemia, low HDL cholesterol, overall obesity, and smoking were significantly more prevalent in the urban population, whereas central obesity was more prevalent in the rural population. Prevalence of hypertension was not significantly different between the rural and urban populations (25.4 and 21.5%, respectively; P =0.15). The age-adjusted prevalences of diabetes were high: 11.3% (8.5-14.1 95%CI) and 13.9% (10.8-17.0) in the rural and urban populations, respectively,but not significantly different. In each community, the age-adjusted prevalence of the metabolic syndrome as defined by the World Health Organization was 17%.

CONCLUSIONS— Although no significant differences were found in the prevalences of hypertension and diabetes between the two populations,other components of the metabolic syndrome, namely elevated triglycerides, low HDL cholesterol, and overall obesity, were more prevalent in the urban population. Given the rapid urbanization of the Palestinian population, the implications for a rise in noncommunicable diseases should be a major public health concern.
Control of Vascular Cell Proliferation and Migration by PPAR-γ
Authors: Hsueh Willa A. , Jackson Simon , Law Ronald E.
Published: March 2007

Compared with nondiabetic subjects, type 2 diabetic individuals are at an increased risk for coronary artery disease and coronary restenosis after angioplasty or stenting. Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. Therefore, pharmaceutical interventions targeting proteins that regulate VSMC growth or movement are a promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator—activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily that, when activated by thiazolidinedione (TZD) insulin sensitizers, regulates a host of target genes. All of the major cells in the vasculature express PPAR-γ, including endothelial cells, VSMCs, and monocytes/macrophages. PPAR-γ is present in intimal macrophages and VSMCs in early human atheromas. In an animal model of vascular injury, PPAR-γ levels are substantially elevated in the neointima that forms after mechanical injury of the endothelium. Recent experimental studies provide evidence that PPAR-γ may function to protect the vasculature from injury. Cell culture studies have shown that TZD PPAR-γ ligands inhibit both the proliferation and migration of VSMCs. These antiatherogenic activities of PPAR-γ may also occur in vivo,because TZDs inhibit lesion formation in several animal models. PPAR-γligands may also protect the vasculature indirectly by normalizing metabolic abnormalities of the diabetic milieu that increase cardiovascular risk. Activation of PPAR-γ, newly defined in vascular cells, may be a useful approach to protect the vasculature in diabetes.
The High Prevalence of Autoantibodies to Tissue Transglutaminase in First-Degree Relatives of Patients With Type 1 Diabetes Is Not Associated With Islet Autoimmunity
Authors: Williams Alistair J. K. , Norcross Alastair J. , Lock Robert J. , Unsworth David J. , Gale Edwin A. M. , Bingley Polly J.
Published: March 2007

OBJECTIVE—To determine the extent of celiac autoimmunity in type 1 diabetic patients and the overlap between islet and celiac autoimmunity in their nondiabetic relatives.

RESEARCH DESIGN AND METHODS—IgA antibodies to tissue transglutaminase were determined in serum taken from 433 type 1 diabetic patients and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase antibodies above the 97.5th percentile of 347 schoolchildren were also assayed for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet cell antibodies and autoantibodies to insulin, glutamate decarboxylase, and protein tyrosine phosphatase IA-2) had previously been measured in all relatives.

RESULTS—In the absence of known celiac disease, the prevalence of transglutaminase antibody levels above the 97.5th percentile of the schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives. EMAs were found in addition to transglutaminase antibodies in 2.6% of probands and in 1.9% of first-degree relatives, but none of the schoolchildren. Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30 of 59 relatives with follow-up samples taken at least 2 years after the initial sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had transglutaminase antibodies.

CONCLUSIONS—We found a high prevalence of celiac autoimmunity in patients and first-degree relatives of children with type 1 diabetes, but we found limited overlap between islet and celiac autoimmunity in nondiabetic relatives. The high prevalence of celiac autoimmunity may be explained by shared genetic susceptibility and identifies a population within which screening for the disease may be justified.
Prevalence and Significance of Retinopathy in Subjects With Type 1 Diabetes of Less Than 5 Years’ Duration Screened for the Diabetes Control and Complications Trial
Authors: Malone John I. , Morrison Anthony D. , Pavan Peter R. , Cuthbertson David D.
Published: March 2007

OBJECTIVE—The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the progression of diabetic retinopathy. A large number of individuals (2,771) underwent stereoscopic color photography and fluorescein angiography as part of screening for participation in the DCCT. A subgroup of those individuals screened participated in the DCCT and underwent evaluation of their retinal vasculature semiannually for 4–9 years. These data were evaluated to determine how the 2000 American Diabetes Association position statement would apply to the DCCT experience. Specifically, the position statement indicates that the first dilated eye examination should be performed after 3–5 years’ duration of diabetes because vision-threatening retinopathy virtually never develops in patients with type 1 diabetes during that interval.

RESEARCH DESIGN AND METHODS—We examined the experience of the DCCT in evaluating retinal photographs in 1,613 patients with type 1 diabetes of <5 years’ duration and follow-up photographs every 6 months for 4–9 years in 855 members of that group.

RESULTS—Of 1,613 subjects with type 1 diabetes of <5 years’ duration screened for the DCCT, 716 (44.4%) had stereo-color photographic evidence of diabetic retinopathy, and 6 had preproliferative or worse pathology. Fluorescein angiography revealed retinopathy in 158 of 713 subjects with no evidence of retinopathy on color photographs. Thus, 874 (54.2%) of the original 1,613 subjects had retinopathy at baseline. DCCT follow-up identified 341 additional individuals in whom retinopathy was developing before 5 years; 1,083 of 1,613 (67.1%) individuals screened for the DCCT had retinopathy before 5 years’ duration of diabetes. Those with retinopathy before 5 years had more rapid three-step progression of vascular pathology than those with no retinopathy.

CONCLUSIONS—Dilated eye examinations and retinal photography should be included in the routine management of type 1 diabetes during the first 5 years to identify the individuals at greatest risk for vision-threatening problems.
Cardiovascular Drug Use and Hospitalizations Attributable to Type 2 Diabetes
Authors: Erkens Joëlle A. , Klungel Olaf H. , Stolk Ronald P. , Spoelstra José A. , Grobbee Diederick E. , Leufkens Hubert G.M.
Published: March 2007

OBJECTIVE—To investigate cardiovascular drug use and hospitalizations attributable to type 2 diabetes from 1 year before until 6 years after the start of oral antidiabetic therapy.

RESEARCH DESIGN AND METHODS—In this cohort study, 2,584 patients with type 2 diabetes were selected from the PHARMO Record Linkage System, comprising pharmacy records and hospitalizations for all 320,000 residents of six Dutch cities. Patients with type 2 diabetes were identified as incident oral antidiabetic drug users between 1992 and 1997. Nondiabetic subjects were 1:1–matched for age, sex, pharmacy, and index date and received no insulin, oral antidiabetic drugs, or glucose-testing supplies.

RESULTS—Patients with type 2 diabetes were more likely to use cardiovascular drugs (RR 1.28 [95% CI 1.23–1.34]) and to be hospitalized because of cardiovascular diseases (1.54 [1.33–1.78]) after the start of oral antidiabetic therapy than nondiabetic subjects. Differences between patients with type 2 diabetes and nondiabetic subjects lessened from 1 year before until 6 years after the start of oral antidiabetic therapy, reflected by decreasing attributable risks for diuretics, β-blockers, calcium channel blockers, and cardiac and antithrombotic drugs. The difference in use of angiotensin-converting enzyme inhibitors and lipid-lowering drugs increased. Cardiovascular hospitalizations attributable to type 2 diabetes were ∼50% in the years close to the start of oral antidiabetic treatment and decreased to ∼33% in the following years.

CONCLUSIONS—Although cardiovascular drug use and hospitalizations remained increased in patients with type 2 diabetes after the start of oral antidiabetic therapy, cardiovascular drug use attributable to type 2 diabetes decreased after the start of oral antidiabetic therapy, especially β-blockers, whereas cardiovascular hospitalizations first decreased and then stabilized.
Dietary Fat and Incidence of Type 2 Diabetes in Older Iowa Women
Authors: Meyer Katie A. , Kushi Lawrence H. , Jacobs David R. , Folsom Aaron R.
Published: March 2007

OBJECTIVE—To examine the associations between reported intakes of dietary fat and incident type 2 diabetes.

RESEARCH DESIGN AND METHODS—We studied the relation between dietary fatty acids and diabetes in a prospective cohort study of 35,988 older women who initially did not have diabetes. Diet was assessed with a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes occurred during 11 years of follow-up.

RESULTS—After adjusting for age, smoking, alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic factors, and dietary magnesium and cereal fiber, diabetes incidence was negatively associated with dietary polyunsaturated fatty acids, vegetable fat, and trans fatty acids and positively associated with ω-3 fatty acids, cholesterol, and the Keys score. After simultaneous adjustment for other dietary fat, only vegetable fat remained clearly related to diabetes risk. Relative risks across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated fatty acids for saturated fatty acids and positively correlated to the Keys dietary score.

CONCLUSIONS—These data support an inverse relation between incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty acids for saturated fatty acids and cholesterol.
Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg Polymorphism of the β3-Adrenergic Receptor Is Associated With Type 2 Diabetes and Obesity in a Large Japanese Sample
Authors: Oizumi Toshihide , Daimon Makoto , Saitoh Tamotsu , Kameda Wataru , Yamaguchi Hiroshi , Ohnuma Hiroshi , Igarashi Masahiko , Eguchi Hideyuki , Manaka Hideo , Tominaga Makoto , Kato Takeo
Published: March 2007

OBJECTIVE—Despite a large number of studies, no association of the Trp64Arg polymorphism of the β3-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample.

RESEARCH DESIGN AND METHODS—A total of 1,685 subjects (935 women and 750 men, aged 58.7 ± 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI ≥30 kg/m2 were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The χ2 test and analysis of variance were used for the association studies and to assess the differences in the traits’ values, respectively.

RESULTS—More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 ± 7.95 vs. 25.93 ± 7.21, P = 0.038) and BMI (25.07 ± 3.84 vs. 23.63 ± 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups.

CONCLUSIONS—Genotype Arg/Arg, but not Trp/Arg, of the β3-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.
Stress Echocardiography for Risk Stratification of Diabetic Patients With Known or Suspected Coronary Artery Disease
Authors: Bigi Riccardo , Desideri Alessandro , Cortigiani Lauro , Bax Jeroen J. , Celegon Leopoldo , Fiorentini Cesare
Published: March 2007

OBJECTIVE—Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetic patients; therefore, their risk stratification is a relevant issue. Because exercise tolerance is frequently impaired in these patients, pharmacological stress echocardiography (SE) has been suggested as a valuable alternative. Our aim was to evaluate the prognostic value of this technique in diabetic patients with known or suspected CAD.

RESEARCH DESIGN AND METHODS—A total of 259 consecutive diabetic patients underwent pharmacological SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up for 24 ± 22 months. A comparison between the prognostic value of SE and exercise electrocardiography (ECG) was made in a subgroup of 120 subjects.

RESULTS—A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during follow-up, and 58 patients were revascularized. Univariate predictors of outcome were known CAD, positive SE, rest and peak wall motion score index (WMSI), and peak/rest WMSI variation. Peak WMSI was the only significant and independent prognostic indicator (odds ratio 11; 95% CI 4–29, P < 0.0001) on multivariate Cox’s analysis. After adjustment for the most predictive clinical and exercise ECG variables, SE provided 43% additional prognostic information (gain in X2 = 7, P < 0.01). Moreover, positive SE was associated with a significantly lower event-free survival.

CONCLUSIONS—SE effectively predicts cardiac events in diabetic patients with known or suspected CAD and adds additional prognostic information as compared with exercise ECG.