bluuebunny/crossref_metadata_2025 huggingface dataset:
Age- and Sex-Specific Prevalence of Diabetes and Impaired Glucose Regulation in 11 Asian Cohorts
Authors:   the DECODA Study Group
Published: March 2007

OBJECTIVE—To report the age- and sex-specific prevalence of diabetes and impaired glucose regulation (IGR) according to revised World Health Organization criteria for diabetes in Asian populations.

RESEARCH DESIGN AND METHODS—We performed 11 studies of 4 countries, comprising 24,335 subjects (10,851 men and 13,484 women) aged 30–89 years who attended the 2-h oral glucose tolerance test and met the inclusion criteria for data analysis.

RESULTS—The prevalence of diabetes increased with age and reached the peak at 70–89 years of age in Chinese and Japanese subjects but peaked at 60–69 years of age followed by a decline at the 70 years of age in Indian subjects. At 30–79 years of age, the 10-year age-specific prevalence of diabetes was higher in Indian than in Chinese and Japanese subjects. Indian subjects also had a higher prevalence of IGR in the younger age-groups (30–49 years) compared with that for Chinese and Japanese subjects. Impaired glucose tolerance was more prevalent than impaired fasting glycemia in all Asian populations studied for all age-groups.

CONCLUSIONS—Indians had the highest prevalence of diabetes among Asian countries. The age at which the peak prevalence of diabetes was reached was ∼10 years younger in Indian compared with Chinese and Japanese subjects. Diabetes and IGR will be underestimated in Asians based on the fasting glucose testing alone.
The Health Care Costs of Diabetic Peripheral Neuropathy in the U.S.
Authors: Gordois Adam , Scuffham Paul , Shearer Arran , Oglesby Alan , Tobian Janet Ash
Published: March 2007

OBJECTIVE—Peripheral neuropathy is common among people with diabetes and can result in foot ulceration and amputation. The aim of this study was to quantify the annual medical costs of peripheral neuropathy and its complications among people with type 1 and type 2 diabetes in the U.S.

RESEARCH DESIGN AND METHODS—A cost-of-illness model was used to estimate the numbers of diabetic individuals in the U.S. who have diabetic peripheral neuropathy (DPN) and/or neuropathic foot ulcers (both those with no deep infection and those accompanied by cellulitis or osteomyelitis) at a given point in time, and/or a toe, foot, or leg amputation during a year. Prevalence and incidence rates were estimated from published studies and applied to the general U.S. population. All costs were estimated in 2001 U.S. dollars. In a sensitivity analysis, we varied the rates of complications to assess the robustness of the cost estimates.

RESULTS—The annual costs of DPN and its complications in the U.S. were $0.8 billion (type 1 diabetes), $10.1 billion (type 2 diabetes), and $10.9 billion (total). After allowing for uncertainty in the point estimates of complication rates, the range of costs were between $0.3 and $1.0 billion (type 1 diabetes), $4.3b and $12.7 billion (type 2 diabetes), and $4.6 and $13.7 billion (type 1 and type 2 diabetes).

CONCLUSIONS—The total annual cost of DPN and its complications in the U.S. was estimated to be between $4.6 and $13.7 billion. Up to 27% of the direct medical cost of diabetes may be attributed to DPN.
Cost Effectiveness of Statin Therapy for the Primary Prevention of Major Coronary Events in Individuals With Type 2 Diabetes
Authors: Brandle Michael , Davidson Mayer B. , Schriger David L. , Lorber Brett , Herman William H.
Published: March 2007

OBJECTIVE—To assess the cost and cost effectiveness of hydroxymethylglutaryl (HMG)-CoA reductase inhibitor (statin) therapy for the primary prevention of major coronary events in the U.S. population with diabetes and LDL cholesterol levels ≥100 mg/dl, especially in the population with LDL cholesterol levels 100–129 mg/dl.

RESEARCH DESIGN AND METHODS—Analyses were performed using population estimates from National Health and Nutrition Examination Survey (NHANES)-III, cost estimates from a health system perspective, statin LDL-lowering effectiveness from pivotal clinical trials, and treatment effectiveness from the diabetic subgroup analysis of the Heart Protection Study.

RESULTS—There are ∼8.2 million Americans with diabetes, LDL cholesterol levels ≥100 mg/dl, and no clinical evidence of cardiovascular disease. Each year, statin therapy could prevent ∼71,000 major coronary events in this population. In the subgroup with LDL cholesterol levels 100–129 mg/dl, the annual cost of statin treatment ranges from $600 to $1,000 per subject. In the population with LDL cholesterol levels ≥130 mg/dl, the annual cost ranges from $700 to $2,100. Annual incremental cost per subject, defined as the cost of statin treatment plus the cost of major coronary events with statin treatment minus the cost of major coronary events without statin treatment, ranges from $480 to $950 in the subgroup with LDL cholesterol levels 100–129 mg/dl and from $590 to $1,920 in the population with LDL cholesterol levels ≥130 mg/dl.

CONCLUSIONS—Statin therapy for the primary prevention of major coronary events in subjects with type 2 diabetes and LDL cholesterol levels 100–129 mg/dl is affordable and cost effective relative to statin therapy in subjects with higher LDL cholesterol levels.
On the Association Between Diabetes and Mental Disorders in a Community Sample
Authors: Kruse Johannes , Schmitz Norbert , Thefeld Wolfgang
Published: March 2007

OBJECTIVE—To determine the relationship between mental disorders and diabetes in a representative community sample.

RESEARCH DESIGN AND METHODS—This was a cross-sectional study. Data on diabetes and HbA1c values were obtained by structured questionnaires and by laboratory assessments. Current psychiatric disorders were diagnosed by a modified version of the Composite International Diagnostic Interview (CIDI).

RESULTS—People with diabetes (PWD) were not more likely to meet Diagnostic and Statistical Manual of Psychiatric Disorders, 4th edition (DSM-IV) criteria for at least one mental disorder than were individuals without diabetes. However, a different diagnostic pattern occurred compared with the general population: odds ratios (ORs) for anxiety disorders in PWD were higher (OR 1.93, 95% CI 1.19–3.14). Although PWD had higher prevalence rates of affective disorders, the relationship between diabetes and affective disorders was not statistically significant after controlling for age, sex, marital status, and socioeconomic status. In contrast, the relationship between diabetes and anxiety disorders remained significant after controlling for these variables. In contrast to individuals without mental disorders, PWD with affective or anxiety disorders more frequently had adequate glycemic control.

CONCLUSIONS—Diabetes was associated with an increased likelihood of anxiety disorders. The association between mental disorders, diabetes, and glycemic control should be evaluated carefully in terms of potentially confounding sociodemographic variables, sample characteristics, and definitions of the disorders.
Rapid Increase in the Use of Oral Antidiabetic Drugs in the United States, 1990–2001
Authors: Wysowski Diane K. , Armstrong George , Governale Laura
Published: March 2007

OBJECTIVE—To describe the use of oral antidiabetic drugs for management of type 2 diabetes in the U.S. from 1990 through 2001.

RESEARCH DESIGN AND METHODS—Data on oral antidiabetic drugs were derived from two pharmaceutical marketing databases from IMS Health, the National Prescription Audit Plus and the National Disease and Therapeutic Index.

RESULTS—In 1990, 23.4 million outpatient prescriptions of oral antidiabetic agents were dispensed. By 2001, this number had increased 3.9-fold, to 91.8 million prescriptions. Glipizide and glyburide, two sulfonylurea medications, accounted for ∼77% of prescriptions of oral antidiabetic drugs in 1990 and 35.5% of prescriptions in 2001. By 2001, the biguanide metformin (approved in 1995) had captured ∼33% of prescriptions, and the thiazolidinedione insulin sensitizers (rosiglitazone and pioglitazone marketed beginning in 1999) accounted for ∼17% of market share. Compared with patients treated in 1990, those in 2001 were proportionately younger and they more often used oral antidiabetic drugs and insulin in combination. Internists and general and family practitioners were the primary prescribers of this class of drugs.

CONCLUSIONS—Consistent with the reported increase in the prevalence of type 2 diabetes, the number of dispensed outpatient prescriptions of oral antidiabetic drugs increased rapidly between 1990 and 2001. This period was marked by an increase in the treatment of younger people and the use of oral antidiabetic drugs in combination. With the approval in the last decade of several new types of oral antidiabetic medications with different mechanisms of action, options for management of type 2 diabetes have expanded.
Effects of the Early ACE Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction
Authors: Borghi Claudio , Bacchelli Stefano , Esposti Daniela Degli , Ambrosioni Ettore ,   on behalf of the SMILE Study Investigators
Published: March 2007

OBJECTIVE—The aim of the present study was to evaluate the clinical efficacy of the ACE inhibitor zofenopril in a cohort of diabetic patients with nonthrombolyzed anterior acute myocardial infarction who were enrolled in the Survival of Myocardial Infarction Long-Term Evaluation (SMILE) trial.

RESEARCH DESIGN AND METHODS—Among the overall population of 1,512 patients, 303 (20.0%) had diabetes. The primary end point of this study was the effect of treatment on the 6-week combined occurrence of death and severe congestive heart failure (CHF). Secondary end points included the evaluation of the 6-week rate of major cardiovascular events as well as the 1-year survival rate.

RESULTS—After 6 weeks of double-blind treatment, zofenopril significantly reduced both the incidence of the primary end point (8.6 vs. 18.3%; P = 0.019) and the 6-week incidence of severe CHF (0 vs. 7.3%; P = 0.001) in diabetic patients, and the effect was greater than that observed in nondiabetic patients. Conversely, 1-year mortality was significantly reduced among nondiabetic patients (9.1 vs. 13.8%; P = 0.010), whereas in the diabetic population, the decrease did not reach statistical significance (13.7 vs. 16.5%; P = 0.52).

CONCLUSIONS—The present data suggest that the clinical outcome of patients with diabetes and myocardial infarction can be significantly improved by early treatment with zofenopril. The lesser effect on 1-year mortality seems to suggest that long-term treatment is probably needed to maintain the benefits of the early ACE inhibition in patients with diabetes.
Relation Between Serum 3-Deoxyglucosone and Development of Diabetic Microangiopathy
Authors: Kusunoki Hitomi , Miyata Satoshi , Ohara Takeshi , Liu Bing-Fen , Uriuhara Atsuko , Kojima Hiroshi , Suzuki Kotaro , Miyazaki Hiroyuki , Yamashita Yumiko , Inaba Kayo , Kasuga Masato
Published: March 2007

OBJECTIVE—3-Deoxyglucosone (3-DG), a highly reactive intermediate of the glycation reaction, has been suggested to contribute to the development of diabetes complications. To verify this hypothesis, we assessed the relation between serum 3-DG concentrations and the severity of diabetic microangiopathy in diabetic patients.

RESEARCH DESIGN AND METHODS—We conducted a high-performance liquid chromatography assay to determine the serum 3-DG concentrations of 110 diabetic patients with different degrees of severity of diabetic microangiopathy and 57 age-matched control subjects.

RESULTS—The fasting serum 3-DG level in diabetic patients was significantly (P < 0.001) higher than that in control subjects (353 ± 110 vs. 199 ± 53 nmol/l). The 3-DG levels were significantly (P < 0.001) elevated even in the diabetic patients showing normoalbuminuria (n = 62, 322 ± 79 nmol/l) compared with control subjects. The 3-DG levels were further elevated in the patients with microalbuminuria (n = 30, 383 ± 146 nmol/l) and overt proteinuria (n = 18, 410 ± 100 nmol/l) (P = 0.027 and P < 0.001 vs. normoalbuminuria group, respectively). This phenomenon was basically reproduced in a category of retinopathy. Furthermore, the diabetic patients with low nerve conduction velocity showed a tendency to display higher 3-DG levels.

CONCLUSIONS—The present results show that the fasting serum 3-DG level is elevated in diabetic patients and that the patients with relatively higher 3-DG levels were prone to suffer from more severe complications, indicating a possible association of 3-DG with diabetic microangiopathy.
Left Ventricular Systolic and Diastolic Function in Normotensive Type 1 Diabetic Patients With or Without Autonomic Neuropathy
Authors: Didangelos Triantaffilos P. , Arsos Georgios A. , Karamitsos Dimitrios T. , Athyros Vasilios G. , Karatzas Nikolaos D.
Published: March 2007

OBJECTIVE—To investigate the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 57 type 1 diabetic patients free of coronary artery disease and arterial hypertension were studied. Diagnosis of DAN was established by autonomic nervous function (ANF) tests, and LV systolic and diastolic functions were assessed by radionuclide ventriculography at rest.

RESULTS—There were 24 patients who had definite DAN, established by the presence of two or more abnormal ANF tests, and 33 subjects were without DAN. DAN patients had impaired LV filling pattern, obvious by a reduced peak filling rate (3.1 ± 1.1 vs. 3.7 ± 0.7 end-diastolic volume [EDV]/s, P = 0.011) and first third filling fraction (35.3 ± 19.5 vs. 50.8 ± 16%, P = 0.002) as well as an increased time to peak filling (159.4 ± 45.1 vs. 134.2 ± 33.4 ms, P = 0.02) after correction for age and heart rate. There were no differences between the two groups with regard to ejection fraction, cardiac output, and cardiac index, whereas the peak emptying rate was greater in DAN patients (4.1 ± 0.8 vs. 3.6 ± 0.8 EDV/s, P = 0.019), suggesting LV hypercontractility. DAN patients had an increased heart rate (83.4 ± 11.9 vs. 72.7 ± 9.3 bpm, P = 0.001) and slightly higher systolic blood pressure. As a result, LV working load at rest was higher in DAN patients (11,109 vs. 9,096 bpm × mmHg, P < 0.001). Moreover, a correlation was found between abnormal LV systolic and diastolic indexes and the number of abnormal ANF tests.

CONCLUSIONS—At rest, DAN patients have impaired LV filling pattern, slightly increased LV systolic function, and a higher LV working load, in comparison to non-DAN type 1 diabetic patients.
Carbohydrate-Induced Memory Impairment in Adults With Type 2 Diabetes
Authors: Greenwood Carol E. , Kaplan Randall J. , Hebblethwaite Stacey , Jenkins David J.A.
Published: March 2007

OBJECTIVE—Memory impairment is observed in adults with type 2 diabetes. The focus of this study was to determine whether acute carbohydrate consumption contributes to or exacerbates memory dysfunction.

RESEARCH DESIGN AND METHODS—The impact of consuming 50 g of rapidly absorbed carbohydrate (one half bagel and white grape juice) at breakfast was examined in 19 adults with type 2 diabetes. Subjects (mean age 63 ± 9 years, mean BMI 26.1 ± 4.5 kg/m2) were tested, under fed and fasted conditions, on verbal declarative memory using both word list and paragraph recall tests (immediate and delayed [7-min] recall), Trails Test Part B as a measure of general brain function, and mood (subjectively monitoring global vigor and affect).

RESULTS—Under baseline (fasting) conditions, elevated blood HbA1c was negatively associated with immediate and delayed paragraph recall performance (R2 = 0.30; P = 0.024) and higher fasting blood glucose trended toward poorer word list recall (R2 = 0.09; P = 0.102). Carbohydrate ingestion influenced measures of delayed, but not immediate, recall in a time-dependent fashion (time × food) (word list, P = 0.046; paragraph, P = 0.044) such that delayed recall was improved at 15 min postingestion but was impaired at 30 min. Neither Trails Test scores (P = 0.17) nor mood (affect, P = 0.68 and vigor, P = 0.45) were influenced by food ingestion.

CONCLUSIONS—In adults with type 2 diabetes, poorer glycemic control is associated with lower performance on tests of declarative memory. Acute ingestion of high glycemic index carbohydrate foods further contributes to the underlying memory impairment.
Population Health Significance of Gestational Diabetes
Authors: Cheung N. Wah , Byth Karen
Published: March 2007

OBJECTIVE—Women who have had gestational diabetes mellitus (GDM) have a high risk of subsequently developing diabetes. However, the contribution of GDM toward the total population of people with diabetes, or its population health impact, has not been examined. Therefore, the aim of this study is to determine the population health significance of GDM by estimating the proportion of cases of diabetes in women that would have been preceded by a pregnancy complicated by GDM.

RESEARCH DESIGN AND METHODS—A MEDLINE search was conducted to identify controlled follow-up studies of women with GDM. Meta-analysis of these studies, using the Mantel-Haenszel method for pooling relative risks (RRs), provided an overall RR for the development of diabetes in women with GDM versus control women who had been pregnant without GDM. Recent large studies examining the prevalence of GDM were also reviewed. This enabled the calculation of the population-attributable risk (PAR) for these populations. In this case, the PAR represents the proportion of cases of diabetes among parous women that were associated with previous GDM.

RESULTS—From six controlled follow-up studies, the overall RR for developing diabetes after GDM was calculated to be 6.0 (95% CI 4.1–8.8). Applying this to the studies of GDM prevalence, the PAR for GDM ranged from 0.10 to 0.31 (i.e., 10–31% of parous women with diabetes would have experienced a GDM pregnancy earlier).

CONCLUSIONS—In some populations, women who have had GDM comprise a substantial proportion of subjects who ultimately develop diabetes. Effective measures to prevent women with GDM from progressing to frank diabetes could therefore have a significant population health impact.
Characteristics of Patients With Type 2 Diabetes in México
Authors: Aguilar-Salinas Carlos A. , Monroy Oscar Velazquez , Gómez-Pérez Francisco J. , Chávez Antonio Gonzalez , Esqueda Agustin Lara , Cuevas Virginia Molina , Rull-Rodrigo Juan A. , Conyer Roberto Tapia ,   for the ENSA (Encuesta Nacional de Salud) 2000 Group
Published: March 2007

OBJECTIVE—To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México.

RESEARCH DESIGN AND METHODS—In 2000, information was obtained from 42,886 subjects aged ≥20 years using a multistage sampling procedure. Standardized questionnaires were used. Anthropometric measurements, blood pressure, and capillary glucose concentrations were taken.

RESULTS—Type 2 diabetes was found in 3,597 subjects (age-adjusted prevalence 8.18%), of which 2,878 (80%) had previously been diagnosed. The average age of the diabetic participants was 55.2 ± 13.5 years; 13% were <40 years of age. Nine percent had been diagnosed for >10 years. The average BMI was 29.2 ± 5.7 kg/m2; three-quarters of the cases had BMI >25 kg/m2. The average waist circumference was 102 ± 13.4 cm, and increased waist circumference was more common among women. Arterial hypertension was found in half of the cases and, of those on treatment, only one-third had a blood pressure <140/90 mmHg. Smoking was reported in 34% of the diabetic group, a higher rate than in the nondiabetic subjects. There was at least one modifiable coronary risk factor in 67.6% of the cases. Very few followed an exercise or dietary regimen and a small percentage used insulin.

CONCLUSIONS—Diabetes affects a large proportion of Mexican adults (8.18%). This figure may be underestimated. The majority of the subjects had modifiable risk factors for the chronic complications of diabetes. Only a few achieved adequate blood pressure control and other treatment goals.
Evaluating Concordance to American Diabetes Association Standards of Care for Type 2 Diabetes Through Group Visits in an Uninsured or Inadequately Insured Patient Population
Authors: Clancy Dawn E. , Cope Dennis W. , Magruder Kathryn Marley , Huang Peng , Wolfman Tamara E.
Published: March 2007

OBJECTIVE—To evaluate the effectiveness of a managed care approach to health care delivery, group visits, in the management of uninsured or inadequately insured patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 120 patients with uncontrolled type 2 diabetes were randomly assigned to receive their care in group visits or usual care for 6 months. After 6 months, concordance with 10 process-of-care indicators recommended by the American Diabetes Association (ADA) standards of care was evaluated through chart abstraction. The 10 items evaluated were up-to-date HbA1c levels and lipid profiles, urine for microalbumin, appropriate use of ACE inhibitor or angiotensin receptor blockers, use of lipid-lowering agents where indicated, daily aspirin use, annual foot examinations, annual referrals for retinal examinations, and immunizations against streptococcal pneumonia and influenza.

RESULTS—Patients who received care in group visits showed statistically significant improvement in concordance with these 10 process-of-care indicators (P < 0.001). Of the patients, 76% who received care in group visits had at least 9 of these 10 items up to date, as compared with 23% of control patients; 86% of patients in group visits had at least 8 of the 10 indicators compared with 47% of control patients.

CONCLUSIONS—Group visits proved more effective in promoting concordance with ADA standards of care than usual care in the treatment of uninsured or inadequately insured patients with type 2 diabetes.
Long-Term Mortality in Nationwide Cohorts of Childhood-Onset Type 1 Diabetes in Japan and Finland
Authors: Asao Keiko , Sarti Cinzia , Forsen Tom , Hyttinen Valma , Nishimura Rimei , Matsushima Masato , Reunanen Antti , Tuomilehto Jaakko , Tajima Naoko ,   for the Diabetes Epidemiology Research International (DERI) Mortality Study Group
Published: March 2007

OBJECTIVE—This study compares mortality from type 1 diabetes in Japan and Finland and examines the effects of sex, age at diagnosis, and calendar time period of diagnosis on mortality.

RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes from Japan (n = 1,408) and Finland (n = 5,126), diagnosed from 1965 through 1979, at age <18 years, were followed until 1994. Mortality was estimated with and without adjustment for that of the general population to assess absolute and relative mortality using Cox proportional hazard models.

RESULTS—Overall mortality rates in Japan and Finland were 607 (95% CI 510–718) and 352 (315–393), respectively, per 100,000 person-years; standardized mortality ratios were 12.9 (10.8–15.3) and 3.7 (3.3–4.1), respectively. Absolute mortality was higher for men than for women in Finland, but relative mortality was higher for women than for men in both cohorts. Absolute mortality was higher in both cohorts among those whose diabetes was diagnosed during puberty, but relative mortality did not show any significant difference by age at diagnosis in either cohort. In Japan, both absolute and relative mortality were higher among those whose diagnosis was in the 1960s rather than the 1970s.

CONCLUSIONS—Mortality from type 1 diabetes was higher in Japan compared with Finland. The increased risk of death from type 1 diabetes seems to vary by sex, age at diagnosis, and calendar time period of diagnosis. Further investigation, especially on cause-specific mortality, is warranted in the two countries.
Self-Management Competence as a Predictor of Outcomes of Intensive Therapy or Usual Care in Youth With Type 1 Diabetes
Authors: Wysocki Tim , Harris Michael A. , Wilkinson Karen , Sadler Michelle , Mauras Nelly , White Neil H.
Published: March 2007

OBJECTIVE—This article evaluates prediction of HbA1c during an 18-month randomized trial of intensive therapy (IT) versus usual care (UC) for type 1 diabetes in 142 youth.

RESEARCH DESIGN AND METHODS—Patients received a composite score for self-management competence (SMC) that combined standardized scores on baseline measures of diabetes knowledge, treatment adherence, and quality of health care interactions. They were categorized by tertiles split into low, moderate, and high SMC levels.

RESULTS—IT yielded very similar mean HbA1c levels in all three SMC groups. However, in UC patients, HbA1c increased markedly for low-SMC youth but not for moderate- and high-SMC youth during the trial. Compared with the mean HbA1c of their UC counterparts, low-SMC patients realized greater glycemic benefit from IT than did the moderate- or high-SMC youth. Baseline SMC was more strongly correlated with HbA1c for UC than IT.

CONCLUSIONS—All three SMC groups realized similar glycemic benefits from IT. The mean HbA1c levels of low-SMC patients in the UC group increased markedly over 18 months, whereas HbA1c levels of low-SMC patients in the IT group did not differ significantly from that of moderate- and high-SMC patients. Relative to their UC counterparts, low-SMC patients derived greater glycemic benefit from IT than did moderate- or high-SMC youth. SMC may be more critical to the success of UC than IT. Perhaps more importantly, patients should not be denied access to IT on the basis of limited competence in diabetes self-management.
Non-HDL Cholesterol and Apolipoprotein B in the Dyslipidemic Classification of Type 2 Diabetic Patients
Authors: Wägner Ana Maria , Pérez Antonio , Zapico Edgar , Ordóñez-Llanos Jordi
Published: March 2007

OBJECTIVE—To compare non-HDL cholesterol (HDLc) and apolipoprotein B (apoB) in the identification of nonconventional high-risk dyslipidemic phenotypes in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Total cholesterol and triglycerides, HDLc, LDL cholesterol, non-HDLc, apolipoprotein B (apoB), and LDL size were determined in 122 type 2 diabetic patients (68% male, aged 59.6 ± 9.7 years, and HbA1c 7.5% [range 5.2–16.0]). They were then classified as normo- and hypertriglyceridemic if their triglyceride concentrations were below/above 2.25 mmol/l, as normo/hyper-non-HDLc if non-HDLc concentrations were below/above 4.13 mmol/l, and as normo- and hyperapoB if apoB concentrations were below/above 0.97 g/l. Both classifications were compared (concordance assessed with the κ index), and low HDLc and LDL phenotype B were identified in each category.

RESULTS—A total of 26 patients were hypertriglyceridemic and 96 were normotriglyceridemic. All hypertriglyceridemic subjects had increased non-HDLc, whereas 24 had increased apoB (κ= 0.95). In the normotriglyceridemic group, 44 had increased non-HDLc, 68 had increased apoB, and 25 of the 52 patients with normal non-HDLc had increased apoB (κ= 0.587). Low HDLc and LDL phenotype B were similarly distributed into the equivalent categories.

CONCLUSIONS—Non-HDLc and apoB are equivalent risk markers in hypertriglyceridemic patients, but apoB identifies additional patients with high-risk dyslipidemic phenotypes in normotriglyceridemic type 2 diabetic patients.
Heart Rate Recovery Following Maximal Exercise Testing as a Predictor of Cardiovascular Disease and All-Cause Mortality in Men With Diabetes
Authors: Cheng Yiling J. , Lauer Michael S. , Earnest Conrad P. , Church Timothy S. , Kampert James B. , Gibbons Larry W. , Blair Steven N.
Published: March 2007

OBJECTIVE—Heart rate recovery (HRR) is an independent prognostic indicator for cardiovascular disease (CVD) and all-cause mortality in healthy men. We examined the association of HRR to CVD-related and all-cause mortality in men with diabetes.

RESEARCH DESIGN AND METHODS—In this cohort study we examined 2,333 men with documented diabetes (mean age 49.4 years) that had baseline 5-min HRR measurement following maximal exercise (heart ratepeak − heart rate5 min of recovery) at The Cooper Clinic, Dallas, TX. We identified HRR quartiles as quartile 1 <55, quartile 2 55–66, quartile 3 67–75, and quartile 4 >75 bpm. Hazard ratios (HRs) for cardiovascular and all-cause death were adjusted for age, cardiorespiratory fitness, resting heart rate, fasting blood glucose, BMI, smoking habit, alcohol consumption, total cholesterol, triglyceride, and history of CVD at baseline.

RESULTS—During a median of 14.9 years follow-up, there were 142 deaths that were considered CVD related and 287 total deaths. Compared with men in the highest quartile of HRR, adjusted HRs in the first, second, and third quartiles were 2.0 (95% CI 1.1–3.8), 1.5 (0.8–2.7), and 1.5 (0.9–2.8), respectively, for cardiovascular death (P for trend < 0.001). Similarly, for all-cause death, adjusted HRs in the first, second, and third quartiles were 2.0 (1.3–3.2), 1.5 (1.0–2.3), and 1.5 (1.1–2.3) (P for trend < 0.001).

CONCLUSIONS—Among men with diabetes, a decreased HRR, even measured as long as 5 min after recovery, was independently predictive of cardiovascular and all-cause death.
Vascular Risk Factors and Markers of Endothelial Function as Determinants of Inflammatory Markers in Type 1 Diabetes
Authors: Schram Miranda T. , Chaturvedi Nish , Schalkwijk Casper , Giorgino Francesco , Ebeling Pertti , Fuller John H. , Stehouwer Coen D. ,   the EURODIAB Prospective Complications Study Group
Published: March 2007

OBJECTIVE—Inflammatory activity is increased in type 1 diabetes and may predispose to vascular disease. Its origin is not clear. We therefore investigated determinants of inflammation in type 1 diabetes.

RESEARCH DESIGN AND METHODS—We performed a nested case-control study from the EURODIAB Prospective Complications Study of 543 European individuals having type 1 diabetes (278 men), diagnosed at <36 years of age. Case subjects (n = 348) were those with one or more complications of diabetes; control subjects (n = 195) were all those with no evidence of any complication. We determined levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α, combined them in a “general score of inflammatory markers,” and investigated their associations with vascular risk factors and markers of endothelial dysfunction by use of multiple linear regression analysis.

RESULTS—Measures of inflammation were associated with sex, diabetes duration, glycemic control, the advanced glycation end product pentosidine, BMI, HDL cholesterol, triglycerides, and systolic blood pressure (standardized βs with the general score of inflammatory markers 0.15 [P = 0.002], 0.15 [P = 0.006], 0.18 [P < 0.0001], 0.12 [P = 0.005], 0.10 [P = 0.057], −0.15 [P = 0.001], 0.16 [P < 0.0001], and 0.09 [P = 0.042], respectively). In addition, measures of inflammation were strongly associated with markers of endothelial dysfunction, soluble vascular cell adhesion molecule-1, and soluble E-selectin (standardized βs with the general score of inflammatory markers 0.28 [P < 0.0001] and 0.19 [P < 0.0001]).

CONCLUSIONS—We have shown that conventional risk factors for vascular disease and endothelial adhesion molecules are important determinants of inflammation in type 1 diabetic individuals, suggesting that strategies to decrease inflammatory activity in type 1 diabetes should focus not only on control of conventional risk factors, but also on improvement of endothelial function.
Insulin 70/30 Mix Plus Metformin Versus Triple Oral Therapy in the Treatment of Type 2 Diabetes After Failure of Two Oral Drugs
Authors: Schwartz Sherwyn , Sievers Richard , Strange Poul , Lyness William H. , Hollander Priscilla ,   For The INS-2061 Study Team
Published: March 2007

OBJECTIVE—Subjects (n = 188) with type 2 diabetes and inadequate response to two oral medications (A1C >8.0%) were randomly assigned to treatment with either a third oral medication or an insulin 70/30 mix b.i.d. plus metformin for a comparison of efficacy, safety, and cost.

RESEARCH DESIGN AND METHODS—The protocol called for aggressive dose titration to achieve target values of fasting blood glucose (80–120 mg/dl), postprandial glucose (<160 mg/dl), and A1C (<7%). These efficacy parameters were evaluated at weeks 2, 6, 12, and 24 of therapy. If dose adjustments failed to achieve targeted glycemic control, subjects were switched to an alternate therapy.

RESULTS—At the end of study (week 24 of therapy), A1C and fasting plasma glucose (FPG) values showed comparable decreases in the two treatment groups. Only 31% (oral therapy) and 32% (insulin plus metformin) of subjects achieved target values of A1C (<7%). A total of 10 of the 98 subjects randomized to triple oral therapy (10.2%) who failed to improve sufficiently were switched to insulin therapy. An additional four subjects dropped out of the oral treatment group due to adverse events felt to be potentially drug related. Only two of the subjects randomized to insulin plus metformin had to be switched to basal-bolus regimens (regular insulin and NPH insulin). Cost analysis determined that insulin plus metformin (mean cost $3.20/day) provided efficacy equal to that of a triple oral drug regimen ($10.40/day).

CONCLUSIONS—Insulin 70/30 mix plus metformin was as effective as triple oral therapy in lowering A1C and FPG values. The triple oral regimen was not as cost effective, and a high percentage of subjects (total of 16.3%) did not complete this regimen due to lack of efficacy or side effects.
Low–Glycemic Index Diets in the Management of Diabetes
Authors: Brand-Miller Jennie , Hayne Susan , Petocz Peter , Colagiuri Stephen
Published: March 2007

OBJECTIVE—The use of diets with low glycemic index (GI) in the management of diabetes is controversial, with contrasting recommendations around the world. We performed a meta-analysis of randomized controlled trials to determine whether low-GI diets, compared with conventional or high-GI diets, improved overall glycemic control in individuals with diabetes, as assessed by reduced HbA1c or fructosamine levels.

RESEARCH DESIGN AND METHODS—Literature searches identified 14 studies, comprising 356 subjects, that met strict inclusion criteria. All were randomized crossover or parallel experimental design of 12 days’ to 12 months’ duration (mean 10 weeks) with modification of at least two meals per day. Only 10 studies documented differences in postprandial glycemia on the two types of diet.

RESULTS—Low-GI diets reduced HbA1c by 0.43% points (CI 0.72–0.13) over and above that produced by high-GI diets. Taking both HbA1c and fructosamine data together and adjusting for baseline differences, glycated proteins were reduced 7.4% (8.8–6.0) more on the low-GI diet than on the high-GI diet. This result was stable and changed little if the data were unadjusted for baseline levels or excluded studies of short duration. Systematically taking out each study from the meta-analysis did not change the CIs.

CONCLUSIONS—Choosing low-GI foods in place of conventional or high-GI foods has a small but clinically useful effect on medium-term glycemic control in patients with diabetes. The incremental benefit is similar to that offered by pharmacological agents that also target postprandial hyperglycemia.
Renoprotective Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended Doses of ACE Inhibitor in Diabetic Nephropathy
Authors: Rossing Kasper , Jacobsen Peter , Pietraszek Lotte , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy.

RESEARCH DESIGN AND METHODS—A total of 20 patients (17 men and 3 women) with type 2 diabetes along with hypertension and nephropathy were enrolled in this double-blind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the 51Cr-EDTA plasma-clearance technique.

RESULTS—During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349−1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 ± 3/72 ± 2 mmHg (mean ± SE); and GFR was 77 ± 6 ml · min−1 · 1.73 m−2 (mean ± SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17−38) compared with ACEI alone (P < 0.001). There was a modest reduction in systolic/diastolic 24-h ABP of 3/2 mmHg (−2 to 8 systolic, −2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (−1 to 9) ml · min−1 · 1.73 m−2.

CONCLUSIONS—Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy.
Increased Visceral Fat and Serum Levels of Triglyceride Are Associated With Insulin Resistance in Japanese Metabolically Obese, Normal Weight Subjects With Normal Glucose Tolerance
Authors: Katsuki Akira , Sumida Yasuhiro , Urakawa Hideki , Gabazza Esteban C. , Murashima Shuichi , Maruyama Noriko , Morioka Kohei , Nakatani Kaname , Yano Yutaka , Adachi Yukihiko
Published: March 2007

OBJECTIVE—The purpose of this study was to investigate the association between visceral adiposity or triglyceride (TG) metabolism and insulin resistance in metabolically obese, normal weight (MONW) Japanese individuals with normal glucose tolerance.

RESEARCH DESIGN AND METHODS—We evaluated body fat areas, lipid profiles, and the glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp study in 20 MONW subjects (BMI <25 kg/m2and visceral fat areas 100 cm2) with normal glucose tolerance. Body fat areas were measured by computed tomography scans. Control data were obtained from 20 normal subjects (BMI <25 kg/m2 and visceral fat areas <100 cm2).

RESULTS—MONW subjects showed a significant increase in fasting serum levels of TG (P < 0.01) and a decrease in GIR (P < 0.01) compared with normal subjects. There were significant correlations between visceral fat areas (r = −0.563, P < 0.01) or serum levels of TG (r = −0.474, P < 0.05) and GIR in MONW subjects. Multiple regression analyses showed that visceral fat areas (F = 7.702, P < 0.02) and serum levels of TG (F = 7.114, P < 0.05) were significantly associated with GIR in all (MONW and normal) subjects.

CONCLUSIONS—Increased visceral fat and serum levels of TG are associated with insulin resistance in Japanese MONW subjects with normal glucose tolerance. Excess visceral fat and elevated TG levels may play important roles in the development of insulin resistance in Japanese MONW subjects with normal glucose tolerance.
Does Low Bone Mineral Density Start in Post-Teenage Years in Women With Type 1 Diabetes?
Authors: Liu Emily Y. , Wactawski-Wende Jean , Donahue Richard P. , Dmochowski Jacek , Hovey Kathleen M. , Quattrin Teresa
Published: March 2007

OBJECTIVE—Type 1 diabetes has been associated with decreased bone mineral density (BMD). However, the natural history and etiopathogenesis of osteoporosis in type 1 diabetes are not clear. The aims of this study were to assess BMD in a cohort of young women with type 1 diabetes compared with nondiabetic control subjects and to evaluate the possible association of BMD with diabetes duration, HbA1c, and biomarkers of bone metabolism.

RESEARCH DESIGN AND METHODS—BMD was measured by dual-energy X-ray absortiometry scan in 39 teenage (age 13–19 years) and 33 post-teenage females (age 20–37 years) with type 1 diabetes and 91 female age-matched control subjects. Serum osteocalcin, IGF-I, IGF binding protein-3 (IGFBP-3), HbA1c, and urine N-telopeptides were measured.

RESULTS—After adjustment for age and BMI, BMD values were significantly lower at the femoral neck and lateral spine in women with type 1 diabetes older than age 20 years compared with control subjects but not in the case subjects younger than age 20 years, nor at the anterio-posterior spine, wrist, or whole body. No association was found between BMD and diabetes duration or glycemic control. IGF-I, IGFBP-3, osteocalcin, and N-telopeptides were similar in diabetic subjects and control subjects.

CONCLUSIONS—This study indicates that women with type 1 diabetes exhibit BMD differences early in life with significant differences already present in the post-teenage years. Lower hip BMD in these young women may explain, in part, the higher incidence of hip fracture experienced in postmenopausal women with type 1 diabetes.
Microalbuminuria and Mortality in Long-Duration Type 1 Diabetes
Authors: Allen Kate V. , Walker James D.
Published: March 2007

OBJECTIVE—Microalbuminuria is a recognized risk factor for increased mortality and renal failure in type 1 diabetes. Whether it remains a powerful predictor in patients with a long duration of type 1 diabetes is not known. We ascertained the prognostic significance of abnormal urinary albumin excretion in a cohort of patients with at least 30 years of type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 190 patients with a disease duration of type 1 diabetes of at least 30 years with baseline and 5 years of follow-up.

RESULTS—At baseline 66% were normoalbuminuric, and at 5 years 11% of this cohort had died. Of the 22% who were microalbuminuric at baseline, 26% had died, and of the 8% with persistent proteinuria at baseline, 44% had died. Of the 4% with end-stage renal failure at baseline, 71% had died within 5 years. Death was attributable to a cardiovascular cause in two-thirds of the cases in all groups.

CONCLUSIONS—Even in those with a long duration of type 1 diabetes, the presence of abnormal urinary excretion remains a powerful predictor of increased mortality.
APOE Polymorphism and the Progression of Diabetic Nephropathy in Japanese Subjects With Type 2 Diabetes
Authors: Araki Shin-ichi , Koya Daisuke , Makiishi Tetsuya , Sugimoto Toshiro , Isono Motohide , Kikkawa Ryuichi , Kashiwagi Atsunori , Haneda Masakazu
Published: March 2007

OBJECTIVE—The aim of this study is to clarify the conflicting results of the ε2/ε3/ε4 APOE polymorphism as a risk factor on diabetic nephropathy by a cohort study.

RESEARCH DESIGN AND METHODS—A total of 429 Japanese subjects with type 2 diabetes and with normoalbuminuria (n = 299) or with microalbuminuria (n = 130) were enrolled in a prospective observational follow-up study during 1995–1998 and followed until 2001 (for at least 3 years). The endpoint was the occurrence of a renal event defined as the progression to a higher stage of diabetic nephropathy.

RESULTS—During the study (the mean follow-up period: 4.4 ± 1.0 years), 31 of 429 subjects progressed: 21 from normoalbuminuria to microalbuminuria and 10 from microalbuminuria to overt proteinuria. The allele frequency of the APOE polymorphism was significantly different between the progressors and the nonprogressors. Eight of 42 ε2 carriers (19%) progressed, whereas 23 of 387 noncarriers (6%) progressed with a relative risk of 3.2 (95% CI 1.5–6.7). When subjects were stratified by renal status at baseline, each relative risk for the progression in the ε2 carriers was 2.7 (0.99–7.4) in those with normoalbuminuria and 4.2 (1.3–13.3) in those with microalbuminuria. Furthermore, when analyzed only in subjects with normoalbuminuria and short duration of diabetes (<15 years) at baseline, the risk in the ε2 carriers became higher to 3.2 (1.2–8.8).

CONCLUSIONS—Our follow-up study indicates that the ε2 allele of the APOE polymorphism is a prognostic risk factor for both the onset and the progression of diabetic nephropathy in Japanese type 2 diabetes.
Heart Failure
Authors: Bell David S.H.
Published: March 2007

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of β-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. β-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with β-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation β-blocker. Prophylactic utilization of ACE inhibitors and β-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.
Effects of Clinical Nutrition Education and Educator Discipline on Glycemic Control Outcomes in the Indian Health Service
Authors: Wilson Charlton , Brown Tammy , Acton Kelly , Gilliland Susan
Published: March 2007

OBJECTIVE—We used the Indian Health Service (IHS) Diabetes Care and Outcomes Audit to assess the effectiveness of clinical nutrition education in reducing HbA1c levels and to test the relative effectiveness of clinical nutrition education when it was delivered by a registered dietitian (RD) compared with an educator from another discipline (non-RD).

RESEARCH DESIGN AND METHODS—We examined clinical care data collected by the IHS Diabetes Care and Outcomes Audit of 7,490 medical records during 2001. Glycemic control was assessed by using the difference between the two most recent HbA1c levels during 2001. Age, BMI, duration of diabetes, type of treatment, proteinuria, and facility were included as covariates. Clinical nutrition education was defined as documentation in the record of any diet instruction and educator discipline classified as RD or non-RD. ANCOVA methods were used to assess the effects of diet education and educator discipline on differences between the two HbA1c measurements and to adjust for differences in the distribution of covariates among the education groups.

RESULTS—After adjustment for age, sex, type of treatment, duration of diabetes, BMI, initial HbA1c level, and clinical facility, clinical nutrition education and educator discipline were each associated with changes in HbA1c levels (P < 0.001). Those receiving clinical nutrition education from an RD or from an RD as well as a non-RD had the largest improvements in HbA1c levels (−0.26 and −0.32, respectively) compared with those receiving either only non-RD or no clinical nutrition education (−0.19 and −0.10, respectively).

CONCLUSIONS—Clinical nutrition education in the IHS is associated with favorable trends in glycemic control. To be effective, clinical nutrition education should be delivered by an RD or a team that includes an RD.