bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Lower-Extremity Amputation in American Indians
Authors: Resnick Helaine E. , Carter Elizabeth A. , Sosenko Jay M. , Henly Susan J. , Fabsitz Richard R. , Ness Frederick K. , Welty Thomas K. , Lee Elisa T. , Howard Barbara V.
Published: March 2007

OBJECTIVE—To define incidence and predictors of nontraumatic lower-extremity amputation (LEA) in a diverse cohort of American Indians with diabetes.

RESEARCH DESIGN AND METHODS—The Strong Heart Study is a study of cardiovascular disease and its risk factors in 13 American-Indian communities. Data on the presence/absence of amputations were collected at each of three serial examinations (1989–1992, 1993–1995, and 1997–1999) by direct examination of the lower extremity. The logistic regression model was used to quantify the relationship between risk of LEA and potential risk factors, including diabetes duration, HbA1c, peripheral arterial disease, and renal function.

RESULTS—Of the 1,974 individuals with diabetes and without prevalent LEA at baseline, 87 (4.4%) experienced an LEA during 8 years of follow-up, and a total of 157 anatomical sites were amputated among these individuals. Amputation of toes was most common, followed by below-the-knee and above-the-knee amputations. Age-adjusted odds of LEA were higher among individuals with unfavorable combinations of risk factors, such as albuminuria and elevated HbA1c. Multivariable modeling indicated that male sex, renal dysfunction, high ankle-brachial index, longer duration of diabetes, less than a high school education, increasing systolic blood pressure, and HbA1c predicted LEA risk.

CONCLUSIONS—The 8-year cumulative incidence of LEA in American Indians with diabetes is 4.4%, with marked differences in risk by sex, educational attainment, renal function, and glycemic control.
Male Sex Increases the Risk of Autoimmunity but not Type 1 Diabetes
Authors: Krischer Jeffrey P. , Cuthbertson David D. , Greenbaum Carla ,   the Diabetes Prevention Trial-Type 1 Study Group
Published: March 2007

OBJECTIVE—The goal of this study was to explore the role of sex on the prevalence of autoantibodies, protective genetic subtypes, β-cell function, and the incidence of type 1 diabetes in a population of first- and second-degree relatives of patients with type 1 diabetes (probands). We examined both the effect of the sex of the individual screened as well as the effect of the sex of the individual’s proband on diabetes risk variables tested.

RESEARCH DESIGN AND METHODS—The Diabetes Prevention Trial-Type 1 has screened 93,188 relatives of type 1 diabetic patients from February 1994 to January 2002. After observing that more men than women were islet cell autoantibody (ICA) positive for the group as a whole, we further explored the role of sex by detailed analysis of variables in this population.

RESULTS—Our data suggest only an influence of sex on the type 1 diabetes disease process. After adjustment for race, age, and relationship to proband, male sex was associated with the appearance of autoimmunity, i.e., the presence of ICA and having two or more antibodies. There was no effect of sex on the presence of other autoantibodies, insulin secretion, results of oral glucose tolerance test, or development of diabetes.

CONCLUSIONS—Our finding that male sex conveys an independent increased risk for development of ICA and multiple antibodies, while at the same time finding no difference with respect to the development of diabetes, suggests that male relatives with the known risk factor of ICA are less likely than comparable female relatives to progress to overt disease, that the pathogenesis of type 1 diabetes among men is slower compared with women, or that women develop diabetes manifesting different antibody responses.
Impact of Degree of Obesity on Surrogate Estimates of Insulin Resistance
Authors: Kim Sun H. , Abbasi Fahim , Reaven Gerald M.
Published: March 2007

OBJECTIVE—To evaluate the role of adiposity in the relationship between specific and surrogate estimates of insulin-mediated glucose uptake (IMGU) in a large nondiabetic population.

RESEARCH DESIGN AND METHODS—Healthy volunteers were classified by BMI into normal weight (<25.0 kg/m2, n = 208), overweight (25.0–29.9 kg/m2, n = 168), and obese (≥30.0 kg/m2, n = 109) groups. We then assessed how differences in BMI affect the correlation between steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide, glucose, and insulin (a specific measure of IMGU) and five surrogate estimates: fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and area under the curve for insulin in response to oral glucose (I-AUC).

RESULTS—Correlation coefficients (r values) between SSPG and surrogate measures of IMGU were all significant (P < 0.05), but the magnitude varied between BMI groups: normal weight: fasting plasma glucose 0.20, fasting plasma insulin 0.33, HOMA-IR 0.36, QUICKI −0.33, and I-AUC 0.69; overweight: fasting plasma glucose 0.19, fasting plasma insulin 0.55, HOMA-IR 0.55, QUICKI −0.54, and I-AUC 0.72; and obese: fasting plasma glucose 0.40, fasting plasma insulin 0.56, HOMA-IR 0.60, QUICKI −0.61, and I-AUC 0.69.

CONCLUSIONS—The relationship between direct and surrogate estimates of IMGU varies with BMI, with the weakest correlations seen in the normal-weight group and the strongest in the obese group. In general, I-AUC is the most useful surrogate estimate of IMGU in all weight groups. Fasting plasma insulin, HOMA-IR, and QUICKI provide comparable information about IMGU. Surrogate estimates of IMGU based on fasting insulin and glucose account for no more than 13% of the variability in insulin action in the normal-weight group, 30% in the overweight group, and 37% in the obese group.
Adiponectin and Leptin Concentrations May Aid in Discriminating Disease Forms in Children and Adolescents With Type 1 and Type 2 Diabetes
Authors: Morales Alba , Wasserfall Clive , Brusko Todd , Carter Carolyn , Schatz Desmond , Silverstein Janet , Ellis Tamir , Atkinson Mark
Published: March 2007

OBJECTIVE—The incidence of pediatric type 2 diabetes has recently seen an alarming increase. To improve our understanding of pediatric type 2 diabetes and identify markers that discriminate these subjects from those with type 1 diabetes, we performed a multivariant analysis associating serum adiponectin and leptin levels with anthropometrical parameters and disease state.

RESEARCH DESIGN AND METHODS—Samples from children and adolescents with type 1 diabetes (n = 41) and type 2 diabetes (n = 17) and from nondiabetic individuals of similar age from the general population (n = 43) were investigated. An analysis included the parameters of matching for BMI and Tanner stage. Receiver-operator characteristic (ROC) curves were established to assess these analytes’ association with disease.

RESULTS—Contrary to studies of adult type 1 diabetes, adiponectin levels in our pediatric type 1 diabetic subjects (10.2 μg/ml [95% CI 8.6–11.7]) did not differ from those of healthy control subjects (10.6 μg/ml [9.2–12.0]; P = NS). Children with type 2 diabetes (5.5 μg/ml [4.8–6.2]) had significantly lower adiponectin levels than both of those groups. Conversely, type 2 diabetic subjects showed marked elevations in serum leptin concentrations (24.3 ng/ml [17.1–31.5]) compared with healthy control subjects (2.7 ng/ml [1.3–4.1]; P < 0.001) and type 1 diabetic subjects (5.1 ng/ml [3.5–6.7]; P < 0.001). Importantly, each of the properties ascribed to pediatric type 2 diabetes was present when the comparison was restricted to healthy children or type 1 diabetic patients whose BMI was >85th percentile or who had Tanner stage 4 and 5. The evaluation of adiponectin-to-leptin ratios revealed a striking difference between children with type 1 diabetes (6.3 [3.8–8.8]) and type 2 diabetes (0.3 [0.2–0.5]; P < 0.001).

CONCLUSIONS—In pediatric diabetes, where diagnosis of disease is often difficult, these studies suggest that the adiponectin-to-leptin ratio may provide additional help in the discrimination between type 1 and type 2 diabetes.
A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women
Authors: Song Yiqing , Manson JoAnn E. , Buring Julie E. , Liu Simin
Published: March 2007

OBJECTIVE—The aim of this study was to prospectively assess the relation between red meat intake and incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—Over an average of 8.8 years, we evaluated 37,309 participants in the Women’s Health Study aged ≥45 years who were free of cardiovascular disease, cancer, and type 2 diabetes and completed validated semiquantitative food frequency questionnaires in 1993.

RESULTS—During 326,876 person-years of follow-up, we documented 1,558 incident cases of type 2 diabetes. After adjusting for age, BMI, total energy intake, exercise, alcohol intake, cigarette smoking, and family history of diabetes, we found positive associations between intakes of red meat and processed meat and risk of type 2 diabetes. Comparing women in the highest quintile with those in the lowest quintile, the multivariate-adjusted relative risks (RRs) of type 2 diabetes were 1.28 for red meat (95% CI 1.07–1.53, P < 0.001 for trend) and 1.23 for processed meat intake (1.05–1.45, P = 0.001 for trend). Furthermore, the significantly increased diabetes risk appeared to be most pronounced for frequent consumption of total processed meat (RR 1.43, 95% CI 1.17–1.75 for ≥5/week vs. <1/month, P < 0.001 for trend) and two major subtypes, which were bacon (1.21, 1.06–1.39 for ≥2/week vs. <1/week, P = 0.004 for trend) and hot dogs (1.28, 1.09–1.50 for ≥2/week vs. <1/week, P = 0.003 for trend). These results remained significant after further adjustment for intakes of dietary fiber, magnesium, glycemic load, and total fat. Intakes of total cholesterol, animal protein, and heme iron were also significantly associated with a higher risk of type 2 diabetes.

CONCLUSIONS—Our data indicate that higher consumption of total red meat, especially various processed meats, may increase risk of developing type 2 diabetes in women.
Oral Antihyperglycemic Medication Nonadherence and Subsequent Hospitalization Among Individuals With Type 2 Diabetes
Authors: Lau Denys T. , Nau David P.
Published: March 2007

OBJECTIVE—This study examines the association between oral antihyperglycemic medication nonadherence and subsequent hospitalization among individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Using administrative claims data (2000–2001) from a managed care organization in the Midwestern U.S., this study analyzed 900 enrollees, aged 18 years and over, with type 2 diabetes who were taking oral antihyperglycemic agents both years but who did not use insulin. Nonadherence was defined as a medication possession ratio (MPR) <80%. Multivariate logistic regression analyses were performed where hospitalization in 2001 was regressed on nonadherence to the oral antihyperglycemic drug regimen in 2000, while controlling for nonadherence to drugs for hypertension and dyslipidemia and for hospitalization in 2000, age, sex, intensity of the diabetes drug regimen, and comorbidities.

RESULTS—The proportion of enrollees who were nonadherent to the antihyperglycemic drug regimen in 2001 was 28.9%, whereas 18.8 and 26.9% were nonadherent to antihypertensive and lipid-modifying drugs, respectively. The increase in the hospitalization rate for 2001 was most apparent where the antihyperglycemic MPR for 2000 dropped to <80%. Enrollees who were nonadherent to oral diabetes medications in 2000 were at higher risk of hospitalization in 2001 (odds ratio 2.53; 95% CI 1.38–4.64), whereas nonadherence to drugs for hypertension and dyslipidemia were not significantly associated with hospitalization.

CONCLUSIONS—Patients with type 2 diabetes who do not obtain at least 80% of their oral antihyperglycemic medications across 1 year are at a higher risk of hospitalization in the following year.
Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects
Authors: Manning Patrick J. , Sutherland Wayne H.F. , Walker Robert J. , Williams Sheila M. , de Jong Sylvia A. , Ryalls Anne R. , Berry Elizabeth A.
Published: March 2007

OBJECTIVE—Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals.

RESEARCH DESIGN AND METHODS—Eighty overweight individuals (BMI >27 kg/m2) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months.

RESULTS—Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period.

CONCLUSIONS—In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient.
Temporary Preservation of β-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes
Authors: Örtqvist Eva , Björk Elisabeth , Wallensteen Måna , Ludvigsson Johnny , Åman Jan , Johansson Calle , Forsander Gun , Lindgren Fredrik , Berglund Lars , Bengtsson Mats , Berne Christian , Persson Bengt , Karlsson F. Anders
Published: March 2007

OBJECTIVE—We examined the effect of diazoxide, an ATP-sensitive K+ channel opener and inhibitor of insulin secretion, on β-cell function and remission in children at clinical onset of type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 56 subjects (21 girls and 35 boys, age 7–17 years) were randomized to 3 months of active treatment (diazoxide 5–7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years.

RESULTS—Diazoxide decreased circulating C-peptide concentrations by ∼50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 ± 0.22 vs. 0.31 ± 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (−0.05 ± 0.24 vs. −0.18 ± 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 ± 0.20 and 0.20 ± 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent.

CONCLUSIONS—This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of β-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
Diabetes Is the Strongest Risk Factor for Lower-Extremity Amputation in New Hemodialysis Patients
Authors: Speckman Rebecca A. , Frankenfield Diane L. , Roman Sheila H. , Eggers Paul W. , Bedinger Marjorie R. , Rocco Michael V. , McClellan William M.
Published: March 2007

OBJECTIVE—End-stage renal disease (ESRD) patients, especially those with diabetes, have an increased risk of nontraumatic lower-extremity amputation (LEA). The present study aims to examine the association of demographic and clinical variables with the risk of hospitalization for LEA among incident hemodialysis patients.

RESEARCH DESIGN AND METHODS—The study population consisted of incident hemodialysis patients from the study years 1996–1999 of the ESRD Core Indicator/Clinical Performance Measures (CPM) Project. Cox proportional hazard modeling was used to identify factors associated with LEA.

RESULTS—Four percent (116 of 3,272) of noncensored incident patients had an LEA during the 12-month follow-up period. Factors associated with LEA included diabetes as the cause of ESRD or preexisting comorbidity (hazard ratio 6.4, 95% CI 3.4–12.0), cardiovascular comorbidity (1.8, 1.2–2.8), hemodialysis inadequacy (urea reduction ratio [URR] <58.5% (1.9, 1.1–3.3), and lower serum albumin level (1.6, 1.1–2.3). Among patients with diabetes, hemodialysis inadequacy and cardiovascular comorbidity were risk factors for LEA (2.6, 1.4–4.8, and 1.7, 1.1–2.6, respectively).

CONCLUSIONS—These data suggest that diabetes is a potent risk factor for LEA in new hemodialysis patients. In ESRD patients with diabetes, a multipronged approach may reduce the rate of LEA. Potentially beneficial strategies include adherence to hemodialysis adequacy guidelines, aggressive treatment of cardiovascular comorbidities, and the utilization of LEA prevention strategies recommended for the general population of patients with diabetes.
Possible Impairment of Transcardiac Utilization of Adiponectin in Patients With Type 2 Diabetes
Authors: Furuhashi Masato , Ura Nobuyuki , Moniwa Norihito , Shinshi Yasuyuki , Kouzu Hidemichi , Nishihara Masahiro , Kokubu Nobuaki , Takahashi Toru , Sakamoto Ken-ichi , Hayashi Manabu , Satoh Naotoshi , Nishitani Takahiro , Shikano Yasukuni , Shimamoto Kazuaki
Published: March 2007

OBJECTIVE—Adiponectin, an adipocyte-derived protein, has been suggested to enhance insulin sensitivity and prevent atherosclerosis. Circulating adiponecin levels are reduced in states of insulin resistance such as type 2 diabetes. We examined transcardiac utilization of adiponectin in patients with and without type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 17 male type 2 diabetic patients and 17 male nondiabetic patients were investigated. Venous blood samples were taken to measure glucose and lipid variables. Blood samples for the measurement of adiponectin were collected simultaneously from the aortic root and coronary sinus. Angiographic semiquantitative stenosis score of coronary artery was also evaluated.

RESULTS—The adiponectin levels in both the aortic root and coronary sinus in the diabetic patients were significantly lower than those in the nondiabetic patients. The adiponectin level was significantly lower in the coronary sinus than in the aortic root in the nondiabetic patients, but there was no significant difference between adiponectin levels in the aortic root and coronary sinus in the diabetic patients. The total stenosis score, as an index of severity of coronary artery stenosis, was significantly higher in the diabetic patients than in the nondiabetic patients. The stenosis score was correlated with the degree of transcardiac utilization of adiponectin from the aortic root to coronary sinus in the nondiabetic patients but not in the diabetic patients.

CONCLUSIONS—Diabetic patients not only have a decreased adiponectin level in the basal state compared with nondiabetic patients but also have impaired utilization of adiponectin in the coronary artery and/or the heart, which may promote the development of atherosclerosis.
The Burden of Diabetes-Associated Cardiovascular Hospitalizations in Veterans Administration (VA) and Non-VA Medical Facilities
Authors: Smith Nicholas L. , Maynard Charles
Published: March 2007

OBJECTIVE—This study examines the relative burden of cardiovascular disease in diabetic and nondiabetic admissions to Veterans Administration (VA) and non-VA hospitals.

RESEARCH DESIGN AND METHODS—Calendar year 1997 hospitalization data were collected from the VA Patient Treatment File and the National Hospital Discharge Survey, National Center for Health Statistics. Discharge diagnoses based on ICD-9 codes were used to classify cardiovascular events and procedures and diabetes. Proportionate hospitalization ratios (PHRs) were calculated based on the number of cardiovascular hospitalizations from among all hospitalizations.

RESULTS—We identified 119,653 VA hospitalizations (19.1%) and 3,765,696 non-VA hospitalizations (16.8%) that coded diabetes among the discharge diagnoses. Cardiovascular hospitalizations, primarily coronary in origin, accounted for nearly 50% of all hospitalizations of persons with diabetes within VA and non-VA medical care systems. Coronary events and procedures (PHR = 1.85 and 1.68) and, to a lesser extent, cerebrovascular events and procedures (PHR = 1.55 and 1.33) were more common in VA hospitalizations where diabetes was listed as a comorbidity than in VA hospitalizations where diabetes was not listed. The burden of coronary hospitalizations was larger in VA than non-VA facilities for men (PHR = 1.82 vs. 1.66) and smaller in VA than non-VA facilities for women (PHR = 3.11 vs. 3.44) in age and race-standardized analyses. The burden of coronary hospitalization was higher for whites and blacks in VA facilities (PHR = 1.83 and 2.01) when compared with non-VA facilities (PHR = 1.68 and 1.84).

CONCLUSIONS—The burden of cardiovascular hospitalizations is not equally borne across hospitalizations with and without diabetes and across VA and non-VA facilities.
Quality Improvement Initiatives
Authors: Hayward Rodney A. , Hofer Timothy P. , Kerr Eve A. , Krein Sarah L.
Published: March 2007

OBJECTIVE—To outline the principles that direct the Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) dedicated to diabetes quality improvement (QUERI-DM).

RESEARCH DESIGN AND METHODS—We discuss the VA initiatives aimed at improving diabetes care for veterans as well as general issues that should be considered in quality improvement initiatives. We specifically describe some of the epidemiological, statistical, and organizational issues that have guided our quality improvement (QI) programs.

RESULTS—The five principles that have guided the QUERI-DM process are: 1) treating clinical guidelines and goals distinct from quality standards and quality improvement priorities; 2) targeting high-risk patients and high-impact quality issues; 3) profiling processes over outcomes; 4) targeting processes that will improve patient outcomes; and 5) paying attention to the loci of practice variation.

CONCLUSIONS—The authors recommend that all five principles be considered when moving from practice guidelines to performance measures and QI initiatives. Targeting high-priority problems and high-risk groups can greatly improve the effectiveness and efficiency of QI interventions.
Diabetes Quality Improvement in Department of Veterans Affairs Ambulatory Care Clinics
Authors: Reiber Gayle E. , Au David , McDonell Mary , Fihn Stephan D.
Published: March 2007

OBJECTIVE— To conduct a group-randomized clinical trial to determine whether regular feedback to primary care providers of synthesized information on patients’ health, function, and satisfaction would demonstrate improved outcomes for their patients with diabetes.

RESEARCH DESIGN AND METHODS—Patients in General Internal Medicine Clinics Department of Veterans Affairs (VA) Medical Centers were randomized into seven intervention or control firms. Patient self-reported information was collected by mail on general health, diabetes, and up to five other chronic conditions. Patients with diabetes received the Seattle Diabetes Questionnaire, the 36-item Medical Outcomes Study short form (SF-36), and a validated patient satisfaction questionnaire at regular intervals. Data from self-report, clinical, pharmacy, and laboratory sources were synthesized into patient-specific feedback reports that intervention providers received before patients’ visits.

RESULTS—The timely delivery to primary care providers of state-of-the-art patient-feedback reports that identified patient issues and areas for improvement did not result in significant improvements in patient outcomes between the intervention and control firms.

CONCLUSIONS—Outcomes in diabetic patients whose providers received synthesized patient data before visits were no better than in those receiving care from control firms. Future studies may benefit from substantial involvement in patients discussing, problem solving, and goal setting in addition to use of timely synthesized patient data.
Diabetes Process and Outcome Measures in the Department of Veterans Affairs
Authors: Sawin Clark T. , Walder Debby J. , Bross Dean S. , Pogach Leonard M.
Published: March 2007

OBJECTIVE—To evaluate performance of process and outcome measures in the care of patients with diabetes seen in Department of Veterans Affairs (VA) facilities.

RESEARCH DESIGN AND METHODS—Retrospective audits of records and databases were conducted on randomly selected patients with diabetes over 5 years (1995 [baseline] and 1997–2000) in 22 VA networks. Performance on diabetes-specific and preventive processes was measured.

RESULTS—Nationally, significant improvements over time were observed for all measures (P < 0.001). For example, the percentage of patients receiving a dilated retinal examination rose from 44% in 1995 to 67% in 2000. The percentage of patients who received a urinary protein test rose from 23% in 1997 to 54% in 2000. Those who received influenza vaccination rose from 34% in 1995 to 78% in 2000. However, there was significant regional variation among all measures.

CONCLUSIONS—Adherence to diabetes-specific and preventive care measures in the VA improved from 1997 to 2000 compared with a 1995 baseline. The improvement occurred in a setting of the provision of guidelines, the contractual setting of specific targets, and the timely feedback of results to medical center and network directors. Future studies are needed to determine whether adherence to these measures will decrease the rates of complications in VA patients with diabetes.
Metabolic Syndrome Variables at Low Levels in Childhood Are Beneficially Associated With Adulthood Cardiovascular Risk
Authors: Chen Wei , Srinivasan Sathanur R. , Li Shengxu , Xu Jihua , Berenson Gerald S.
Published: March 2007

OBJECTIVE—Most epidemiologic studies have focused on the adverse impact of the metabolic syndrome on cardiovascular (CV) disease. However, information on the relationship between the clustering of metabolic syndrome variables at favorable levels in childhood and the measures of CV risk in adulthood is not known.

RESEARCH DESIGN AND METHODS—The study cohort included 1,474 individuals (552 blacks and 922 whites) who were examined for CV risk factors in childhood (aged 4–17 years) and again in adulthood (aged 19–41 years) in Bogalusa, Louisiana, during 1982–2003, with an average follow-up period of 15.8 years.

RESULTS—In childhood, 9.0% of the cohort displayed clustering of three- or four-criterion risk variables at the bottom quartiles of BMI, homeostasis model assessment of insulin resistance, systolic blood pressure, and total–to–HDL cholesterol ratio. The clustering was significantly higher than expected by chance alone (P < 0.01). These children, compared with those having clustering of less than three risk variables at the bottom quartiles, had a lower prevalence of metabolic syndrome in adulthood (clustering at top quartiles) (3.8 vs. 14.6%, P < 0.001). A higher prevalence of clustering of risk variables at low levels in childhood was associated with negative parental histories of coronary heart disease (9.4 vs. 5.0%, P = 0.024) and hypertension (10.5 vs. 6.6%, P = 0.012). Mean values of carotid intima-media thickness in adulthood decreased with an increasing number of risk variables clustering at the bottom quartiles in childhood (P for trend = 0.013).

CONCLUSIONS—The constellation of metabolic syndrome variables at low levels in childhood is associated with lower measures of CV risk in adulthood.
Antidiabetic Drugs and Heart Failure Risk in Patients With Type 2 Diabetes in the U.K. Primary Care Setting
Authors: Maru Shoko , Koch Gary G. , Stender Monika , Clark Douglas , Gibowski Laura , Petri Hans , White Alice D. , Simpson Ross J.
Published: March 2007

OBJECTIVE—To assess the effects of antidiabetic drugs on the risk of heart failure in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a retrospective cohort study with a newly diagnosed diabetes cohort of 25,690 patients registered in the U.K. General Practice Research Database, 1988–1999. We categorized person-time drug exposures to monotherapies in insulin, sulfonylureas (SUs), metformins, and other oral hypoglycemic agents (i.e., acarbose, guar gum) and combination therapy including insulin, combination therapy without insulin, and triple combination therapy with or without insulin. A drug-free time interval served as a reference category. Cox interval-wise (piece-wise) regression analyses were used. The main outcome was incident heart failure.

RESULTS—Among 43,390 drug exposure intervals for 25,690 patients who had a mean follow-up period of 2.5 years, 1,409 patients developed heart failure. Heart failure occurred most frequently in SU monotherapy exposure. After adjusting for duration of diabetes, the timing and order of treatments received, and known risk factors for heart failure, we found no differential effects among type-specific therapies. Patients with any drug use within the first year after diabetes diagnosis had a 4.75-fold higher risk (hazard ratio) for heart failure than those with drug-free status but had no increased risk during subsequent years.

CONCLUSIONS—In conclusion, the use of any pharmacological therapy for type 2 diabetes appears to be associated with an increased risk of heart failure. This risk does not persist beyond the first year after diagnosis of diabetes and does not appear to differ among the types of drug therapy examined. This observation suggests that the severity of diabetes or the preclinical duration of diabetes and the need for drug therapy, and not the therapy itself, is an explanation for heart failure in patients with type 2 diabetes.
Randomized Effectiveness Trial of a Computer-Assisted Intervention to Improve Diabetes Care
Authors: Glasgow Russell E. , Nutting Paul A. , King Diane K. , Nelson Candace C. , Cutter Gary , Gaglio Bridget , Rahm Alanna Kulchak , Whitesides Holly
Published: March 2007

OBJECTIVE—There is a well-documented gap between diabetes care guidelines and the services received by patients in most health care settings. This report presents 12-month follow-up results from a computer-assisted, patient-centered intervention to improve the level of recommended services patients received from a variety of primary care settings.

RESEARCH DESIGN AND METHODS—A total of 886 patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program. Physicians were stratified and randomized to intervention or control conditions and evaluated on two primary outcomes: number of recommended laboratory screenings and recommended patient-centered care activities completed from the National Committee on Quality Assurance/American Diabetes Association Provider Recognition Program (PRP). Secondary outcomes were evaluated using the Problem Areas in Diabetes 2 quality of life scale, lipid and HbA1c levels, and the Patient Health Questionnaire-9 depression scale.

RESULTS—The program was well implemented and significantly improved both the number of laboratory assays and patient-centered aspects of diabetes care patients received compared with those in the control condition. There was overall improvement on secondary outcomes of lipids, HbA1c, quality of life, and depression scores; between-condition differences were not significant.

CONCLUSIONS—Staff in small, mixed-payer primary care offices can consistently implement a patient-centered intervention to improve PRP measures of quality of diabetes care. Alternative explanations for why these process improvements did not lead to improved outcomes, and suggested directions for future research are discussed.
Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition
Authors: Cheung N. Wah , Napier Brett , Zaccaria Cathy , Fletcher John P.
Published: March 2007

OBJECTIVE—Hyperglycemia is associated with poor clinical outcomes and mortality in myocardial infarction, stroke, and general hospital patients. However, there are few data regarding the effect of hyperglycemia on outcomes in patients receiving total parenteral nutrition (TPN), a therapy that predisposes patients to hyperglycemia. The aim of this study was to determine whether elevated blood glucose levels are associated with adverse outcomes in patients receiving TPN.

RESEARCH DESIGN AND METHODS—A retrospective analysis was undertaken from the medical records of 111 patients (122 treatment episodes) receiving TPN. All patients had blood drawn daily for the measurement of blood glucose levels. Outcome measures were assessed as a function of mean daily blood glucose levels while receiving TPN.

RESULTS—Increased blood glucose levels were associated with an increased risk of cardiac complications (odds ratio 1.61, 95% CI 1.09–2.37, P = 0.02), infection (1.4, 1.08–1.82, P = 0.01), systemic sepsis (1.36, 1.00–1.86, P = 0.05), acute renal failure (1.47, 1.00–2.17, P = 0.05), and death (1.77, 1.23–2.52, P < 0.01). When the data were examined by quartiles of blood glucose levels, the mortality of subjects in the highest quartile was 10.9 times (95% CI 2.0–60.5, P < 0.01) that of subjects in the lowest quartile, and the risk of developing any complication was 4.3 times higher (1.4–13.1, P < 0.01). These effects were independent of age, sex, or prior diabetes status.

CONCLUSIONS—Hyperglycemia is a predictor of poor outcomes in patients receiving TPN. The confirmation of a relation between blood glucose levels and adverse outcomes provides support for tight glycemic control in these patients.
Frequency and Timing of Severe Hypoglycemia Affects Spatial Memory in Children With Type 1 Diabetes
Authors: Hershey Tamara , Perantie Dana C. , Warren Stacie L. , Zimmerman Emily C. , Sadler Michelle , White Neil H.
Published: March 2007

OBJECTIVE—Repeated severe hypoglycemia has been reported to reduce long-term spatial memory in children with type 1 diabetes. Early exposure to hypoglycemia may be more damaging to cognitive function than later exposure. Our goal was to determine whether the age at which severe hypoglycemia occurs modulates the impact of severe hypoglycemia frequency on long-term spatial memory.

RESEARCH DESIGN AND METHODS—We combined data from three independent studies to obtain a sample of children aged 6–18 years with type 1 diabetes (n = 103) and nondiabetic control subjects (n = 60). Each study evaluated previous severe hypoglycemia and tested short (5 s)- and long (60 s)-delay spatial memory with the spatial delayed response task. Type 1 diabetic participants were categorized as having zero, one to two, or three or more severe hypoglycemic episodes and as having their first severe hypoglycemic episode before or after 5 years of age. Information on chronic hyperglycemia (HbA1c values) was also collected.

RESULTS—We found that repeated severe hypoglycemia (more than three episodes) reduced long-delay spatial delayed response performance, particularly when severe hypoglycemic episodes began before the age of 5 years. Age of type 1 diabetes onset and estimates of chronic hyperglycemia did not influence performance.

CONCLUSIONS—High frequency of and early exposure to severe hypoglycemia during development negatively affects spatial long-term memory performance.
Dose Response of Inhaled Dry-Powder Insulin and Dose Equivalence to Subcutaneous Insulin Lispro
Authors: Rave Klaus M. , Nosek Leszek , de la Peña Amparo , Seger Mary , Ernest Charles S. , Heinemann Lutz , Batycky Richard P. , Muchmore Douglas B.
Published: March 2007

OBJECTIVE—To determine the pharmacokinetic (PK) and glucodynamic (GD) dose response of human insulin inhalation powder (HIIP) delivered via AIR particle technology and dose equivalence to subcutaneous (SC) insulin lispro.

RESEARCH DESIGN AND METHODS—Twenty healthy, nonsmoking, male or female subjects (aged 29.6 ± 6.9 years, BMI 23.2 ± 2.3 kg/m2, means ± SD) with normal forced vital capacity and forced expiratory volume were enrolled in an open-label, randomized, seven-period, euglycemic glucose clamp, cross-over trial. Each subject received up to four single doses of HIIP (2.6, 3.6, 5.2, or 7.8 mg) and three doses of SC lispro (6, 12, or 18 units) from 5 to 18 days apart.

RESULTS—HIIP demonstrated a similar rapid onset but an extended time exposure and a prolonged duration of effect (late t50% 412 vs. 236 min, P < 0.001) compared with SC lispro. The HIIP versus SC lispro doses of 2.6 mg vs. 6 units, 5.2 mg vs. 12 units, and 7.8 mg vs. 18 units achieved similar PK area under the serum immunoreactive insulin (IRI) concentration-versus-time curve from time zero until the serum IRI concentrations returned to the predose baseline value [AUC(0-t′)] and GD (Gtot) responses. The median insulin (tmax) was not different between HIIP and SC lispro (45 min for both), although the median time of return to baseline for PK was apparently longer for HIIP compared with SC lispro (480 vs. 360 min). Relative bioavailability and relative biopotency of HIIP were consistent across doses (8 and 9%).

CONCLUSIONS—While the time-action profile was longer for HIIP than for SC lispro, both treatments showed rapid initial absorption and similar overall PK exposure and GD effect. HIIP was as well tolerated as SC lispro, thereby offering a promising alternative to injectable insulin therapy.
Evaluating the Clinical Accuracy of Two Continuous Glucose Sensors Using Continuous Glucose–Error Grid Analysis
Authors: Clarke William L. , Anderson Stacey , Farhy Leon , Breton Marc , Gonder-Frederick Linda , Cox Daniel , Kovatchev Boris
Published: March 2007

OBJECTIVE—To compare the clinical accuracy of two different continuous glucose sensors (CGS) during euglycemia and hypoglycemia using continuous glucose–error grid analysis (CG-EGA).

RESEARCH DESIGN AND METHODS—FreeStyle Navigator (Abbott Laboratories, Alameda, CA) and MiniMed CGMS (Medtronic, Northridge, CA) CGSs were applied to the abdomens of 16 type 1 diabetic subjects (age 42 ± 3 years) 12 h before the initiation of the study. Each system was calibrated according to the manufacturer’s recommendations. Each subject underwent a hyperinsulinemic-euglycemic clamp (blood glucose goal 110 mg/dl) for 70–210 min followed by a 1–mg · dl−1 · min−1 controlled reduction in blood glucose toward a nadir of 40 mg/dl. Arterialized blood glucose was determined every 5 min using a Beckman Glucose Analyzer (Fullerton, CA). CGS glucose recordings were matched to the reference blood glucose with 30-s precision, and rates of glucose change were calculated for 5-min intervals. CG-EGA was used to quantify the clinical accuracy of both systems by estimating combined point and rate accuracy of each system in the euglycemic (70−180 mg/dl) and hypoglycemic (<70 mg/dl) ranges.

RESULTS—A total of 1,104 data pairs were recorded in the euglycemic range and 250 data pairs in the hypoglycemic range. Overall correlation between CGS and reference glucose was similar for both systems (Navigator, r = 0.84; CGMS, r = 0.79, NS). During euglycemia, both CGS systems had similar clinical accuracy (Navigator zones A + B, 88.8%; CGMS zones A + B, 89.3%, NS). However, during hypoglycemia, the Navigator was significantly more clinically accurate than the CGMS (zones A + B = 82.4 vs. 61.6%, Navigator and CGMS, respectively, P < 0.0005).

CONCLUSIONS—CG-EGA is a helpful tool for evaluating and comparing the clinical accuracy of CGS systems in different blood glucose ranges. CG-EGA provides accuracy details beyond other methods of evaluation, including correlational analysis and the original EGA.
Longitudinal Predictors of Reduced Mobility and Physical Disability in Patients With Type 2 Diabetes
Authors: Bruce David G. , Davis Wendy A. , Davis Timothy M.E.
Published: March 2007

OBJECTIVE—The purpose of this study was to determine longitudinal predictors of impaired mobility and physical disability in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We studied patients with type 2 diabetes who participated in a prospective, community-based study. A wide range of baseline variables were examined to determine whether they predicted future difficulties with 1) mobility and 2) basic activities of daily living (ADLs) in patients free of ADLs difficulty at baseline. To study mobility impairment, subjects with baseline mobility problems were also excluded.

RESULTS—After an average 4.6 ± 2.3 and 4.8 ± 2.3 years of follow-up in 818 and 934 patients, respectively, 28.5% of subjects had developed new mobility impairment and 18.1% had developed new ADL disability. In Cox proportional hazards models, the risk of mobility impairment was significantly increased by older age (6%/year), peripheral neuropathy (40% increase), stroke history (123%), insulin treatment (117%), albuminuria, and arthritis (82%); taking exercise and being married lowered the risk (by 39 and 32%, respectively). The risk of new ADL disability was increased by baseline mobility problems (222% increase), stroke (92%), claudication (67%), and depression (41%) and was also influenced by age, smoking, lack of exercise, nonfluency in English, and indigenous Australian ethnicity.

CONCLUSIONS—Both mobility impairment and ADL disability in type 2 diabetes have multiple causes that are due to diabetes complications and common comorbidities. The specific causes of each functional problem are largely distinct, and different approaches may be required to prevent their onset or progression.
Relation of Characteristics of Metabolic Syndrome to Short-Term Prognosis and Effects of Intensive Statin Therapy After Acute Coronary Syndrome
Authors: Schwartz Gregory G. , Olsson Anders G. , Szarek Michael , Sasiela William J.
Published: March 2007

OBJECTIVE—We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome.

RESEARCH DESIGN AND METHODS—A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure ≥130/≥85, BMI >30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides ≥150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome.

RESULTS—A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% CI 1.24–1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome.

CONCLUSIONS—Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome.
Urinary Albumin Excretion and Its Relation With C-Reactive Protein and the Metabolic Syndrome in the Prediction of Type 2 Diabetes
Authors: Brantsma Auke H. , Bakker Stephan J.L. , Hillege Hans L. , de Zeeuw Dick , de Jong Paul E. , Gansevoort Ronald T. ,   the PREVEND Study Group
Published: March 2007

OBJECTIVE—To investigate urinary albumin excretion (UAE) and its relation with C-reactive protein (CRP) and the metabolic syndrome in the prediction of the development of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We used data from the Prevention of Renal and Vascular End Stage Disease (PREVEND) study, an ongoing, community-based, prospective cohort study initiated in 1997 in the Netherlands. The initial cohort consisted of 8,592 subjects. After 4 years, 6,894 subjects participated in a follow-up survey. Subjects with diabetes at baseline or missing data on fasting glucose were excluded, leaving 5,654 subjects for analysis. The development of type 2 diabetes, defined as a fasting glucose ≥7.0 mmol/l and/or the use of antidiabetic medication, was used as the outcome measure. UAE was calculated as the mean UAE from two consecutive 24-h urine collections. Logistic regression models were used, with the development of type 2 diabetes as the dependent variable.

RESULTS—Of the 5,654 subjects for whom data were analyzed, 185 (3.3%) developed type 2 diabetes during a mean follow-up period of 4.2 years. UAE, CRP, and the presence of the metabolic syndrome at baseline were significantly associated with the incidence of type 2 diabetes (P < 0.001 for all variables). In a univariate model, the odds ratio (OR) for UAE was 1.59 (95% CI 1.42–1.79). In our full model, adjusted for age, sex, number of criteria of metabolic syndrome, and other known risk factors for the development of type 2 diabetes (including fasting insulin), the association between UAE and type 2 diabetes remained significant (OR 1.53, 95% CI 1.25–1.88, P < 0.001). There was a significant interaction between UAE and CRP (P = 0.002). After CRP was stratified into tertiles, the ORs for the association between baseline UAE and the development of type 2 diabetes were 2.2 (1.47–3.3), 1.33 (0.96–1.84), and 1.04 (0.83–1.31) for the lowest to highest tertiles, respectively.

CONCLUSIONS—UAE predicts type 2 diabetes independent of the metabolic syndrome and other known risk markers of development of type 2 diabetes. The predictive value of UAE was modified by the level of CRP.
Effect of a High-Carbohydrate Versus a High—cis-Monounsaturated Fat Diet on Blood Pressure in Patients With Type 2 Diabetes
Authors: Shah Meena , Adams-Huet Beverley , Bantle John P. , Henry Robert R. , Griver Kay A. , Raatz Susan K. , Brinkley Linda J. , Reaven Gerald M. , Garg Abhimanyu
Published: March 2007

OBJECTIVE—To investigate whether blood pressure is different in type 2 diabetic patients on a diet rich in carbohydrates versus a diet rich in cis-monounsaturated fatty acids. Data on the dietary effects on these diets’ glucose and lipid metabolism have been previously published.

RESEARCH DESIGN AND METHODS—The study compared the effect of feeding 42 type 2 diabetic patients a carefully controlled isoenergic high-carbohydrate (high-carb; 55% energy as carbohydrate, 30% as fat, and 10% as monounsaturated fat) and high−monounsaturated fat (high-mono; 45% energy as fat, 25% as monounsaturated fat, and 40% as carbohydrate) diet for 6 weeks each in a four-center, randomized, cross-over study on blood pressure. Twenty-one patients continued the diet they received during the second phase for an additional 8 weeks.

RESULTS—According to repeated-measures ANOVA, blood pressure during the last 3 days of each phase was similar after 6 weeks of the high-carb and high-mono diets (systolic blood pressure: 128 ± 16 vs. 127 ± 15 mmHg, P = 0.9; diastolic blood pressure: 75 ± 7 vs. 75 ± 8 mmHg, P = 0.7). However, after 14 weeks of the high-carb diet (n = 13), there was a significant increase in blood pressure compared with 6 weeks of the high-mono diet (systolic blood pressure: 132 ± 13 vs. 126 ± 11 mmHg, P = 0.04; diastolic blood pressure: 83 ± 6 vs. 76 ± 7 mmHg, P = 0.002). After 14 weeks of the high-mono diet (n = 8), the reduction in blood pressure was not significant compared with 6 weeks of the high-carb diet (systolic blood pressure: 118 ± 14 vs. 121 ± 16 mmHg, P = 0.4; diastolic blood pressure: 71 ± 8 vs. 75 ± 10 mmHg, P = 0.3).

CONCLUSION—Although the exchange of carbohydrates with monounsaturated fats may not affect blood pressure in the short term, long-term consumption of a high-carbohydrate diet may modestly raise blood pressure in type 2 diabetic patients.