bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the CTLA-4 Gene 49 A/G Polymorphism With Type 1 Diabetes and Autoimmune Thyroid Disease in Japanese Children
Authors: Mochizuki Mie , Amemiya Shin , Kobayashi Kisho , Kobayashi Koji , Shimura Yoshie , Ishihara Toshihide , Nakagomi Yoshiko , Onigata Kazumichi , Tamai Shinya , Kasuga Akira , Nanazawa Shinpei
Published: March 2007

OBJECTIVE—To clarify the role of the T-lymphocyte–associated-4 (CTLA-4) polymorphism in the susceptibility to child-onset type 1 diabetes with regard to its clinical characteristics and complications with autoimmune thyroid disease (AITD) in the Japanese population.

RESEARCH DESIGN AND METHODS—The CTLA-4 49 A/G polymorphism was detected by the PCR-restriction fragment–length polymorphism (RFLP) method in 97 type 1 diabetic subjects and 20 patients with Graves’ disease, a cohort which included 4 patients who also had type 1 diabetes.

RESULTS—The genotypes and allele frequencies of this polymorphism did not differ between the type 1 diabetic subjects and the control subjects. The G allele frequency was 63.9% in the type 1 diabetic subjects. The G allele frequency in the subgroup of patients with a high titer of autoantibodies to the GAD antibody (Ab) was 72.9% (P = 0.0499 vs. control subjects); in the subgroup of patients without HLA DRB1*0405, it was 72.6% (P = 0.0271 vs. control subjects); and in the subgroup of patients with a residual β-cell function, it was 78.6% (P = 0.0391 vs. control subjects). The G allele frequency in the patients with Graves’ disease was also significantly higher at 78.1% (P = 0.0405 vs. control subjects). Furthermore, the frequency in our diabetic subjects complicated with Graves’ disease was even higher (87.5%).

CONCLUSIONS—We have demonstrated that a distinct association exists between the G allele of CTLA-4 and high values of GAD Ab, residual β-cell function, and the absence of HLA-DRB1*0405.
Ethnic and Racial Differences in Diabetes Care
Authors: Bonds Denise E. , Zaccaro Daniel J. , Karter Andrew J. , Selby Joe V. , Saad Mohammed , Goff David C.
Published: March 2007

OBJECTIVE—Diabetes and its complications disproportionately affect African Americans and Hispanics. Complications could be prevented with appropriate medical care. We compared five processes of care and three outcomes of care among African Americans, Hispanics, and non-Hispanic whites.

RESEARCH DESIGN AND METHODS—We used data from the Insulin Resistance Atherosclerosis Study (1993–1998) of participants with known diabetes. African Americans and Hispanics were compared with non-Hispanic whites from the same region. Five process measures (treatment of diabetes, hypertension, hyperlipidemia, albuminuria, and coronary artery disease) and three outcome measures (control of diabetes, hypertension, and hyperlipidemia) were evaluated.

RESULTS—Comparison groups were similar in baseline characteristics. African Americans and Hispanics were equally likely as their non-Hispanic white comparison group to receive treatment for diabetes, hypertension, hyperlipidemia, albuminuria, and coronary artery disease, although treatment rates for hyperlipidemia and albuminuria were poor for all groups. African Americans were more likely to have poorly controlled diabetes (HbA1c >8.0%: OR 2.23, 95% CI 1.26–3.94). Both African American and Hispanics were significantly more likely to have borderline or poorly controlled hypertension than non-Hispanic whites (blood pressure >130–140/85–90 or >140/90 mmHg: African American/non-Hispanic white OR 3.22, 95% CI 1.57–6.59; Hispanic/non-Hispanic white 3.14, 1.35–7.3).

CONCLUSIONS—The rates of treatment for diabetes and associated comorbidities are similar across all three ethnic groups. Few individuals in any ethnic group received treatment for hyperlipidemia and albuminuria. Ethnic disparities exist in control of diabetes and hypertension. Programs should be tested to improve overall quality of care and eliminate these disparities.
Mortality From Site-Specific Malignancies in Type 2 Diabetic Patients From Verona
Authors: Verlato Giuseppe , Zoppini Giacomo , Bonora Enzo , Muggeo Michele
Published: March 2007

OBJECTIVE— The aim of the present work was to compare mortality from site-specific malignancies in type 2 diabetic patients with those in the general population.

RESEARCH DESIGN AND METHODS— Mortality from site-specific cancers was assessed in a population-based cohort of 7,148 type 2 diabetic patients from Verona (Northern Italy) during a 10-year follow-up (1987–1996) by reviewing death certificates. Standardized mortality ratio (SMR) data were computed using as reference mortality rates in the general population of Verona.

RESULTS— During follow-up, 641 patients (378 men and 263 women) died of malignancies. The most common causes of death among site-specific malignancies were digestive tumors both in men (140 of 378, 37.0%) and women (105 of 263, 39.9%), respiratory tumors in men (103 of 378, 27.2%), and tumors of the reproductive system in women (79 of 263, 30.0%). A slight increase in the overall mortality from malignancies was observed in diabetic patients and achieved statistical significance in women (observed/expected = 1.16, 95% CI 1.02–1.30; P = 0.019) but not in men (observed/expected = 1.07, 0.97–1.19; P = 0.163). Excess mortality from hepatic cancer (SMR = 1.86, 1.44–2.38) was observed in both men and women. In addition, women with diabetes experienced a higher mortality from pancreatic tumors (observed/expected = 1.78, 1.13–2.67) and breast tumors (observed/expected = 1.40, 1.06–1.81). Excess mortality from breast cancer was confined to obese women with diabetes.

CONCLUSIONS— Mortality from site-specific malignancies is different in type 2 diabetic patients than in the general population. Better control of body weight seems necessary to prevent the excess mortality from breast cancer in women.
Utility of HbA1c Levels for Diabetes Case Finding in Hospitalized Patients With Hyperglycemia
Authors: Greci Laura S. , Kailasam Mala , Malkani Samir , Katz David L. , Hulinsky Ilja , Ahmadi Ramin , Nawaz Haq
Published: March 2007

OBJECTIVE—We evaluated the role of a single measurement of HbA1c in a diabetes case finding in hospitalized patients with random hyperglycemia at admission.

RESEARCH DESIGN AND METHODS—From 20 March to 31 July 2000, 508 patients admitted through the emergency department of one hospital were tested for random hyperglycemia (plasma glucose [PG] >125 mg/dl). Consenting patients with hyperglycemia (without preexisting diabetes or on corticosteroids) underwent testing for HbA1c levels, two fasting PG levels, and an outpatient oral glucose tolerance test (OGTT) if necessary.

RESULTS—Of the patients, 50 (9.8%) met the inclusion criteria. Of these, 70% (n = 35) completed the study, and 60% (n = 21) were diagnosed with diabetes. Patients with diabetes had higher HbA1c levels than subjects without diabetes (6.8 ± 0.4 vs. 5.3 ± 0.1%, P = 0.002). An HbA1c level >6.0% was 100% specific (14/14) and 57% sensitive (12/21) for the diagnosis of diabetes. When a lower cutoff value of HbA1c at 5.2% was used, specificity was 50% (10/21) and sensitivity was 100% (7/14).

CONCLUSIONS—In acutely ill patients with random hyperglycemia at hospital admission, an HbA1c >6.0% reliably diagnoses diabetes, and an HbA1c level <5.2% reliably excludes it (paralleling the operating characteristics of the standard fasting glucose measurements); however, the rapidity of the HbA1c level can be useful for diabetes case finding and treatment initiation early in the hospital course.
Effects of Postmenopausal Hormone Replacement Therapy on HbA1c Levels
Authors: Okada Mayumi , Nomura Seiji , Ikoma Yoko , Yamamoto Eiko , Ito Tomomi , Mitsui Takashi , Tamakoshi Koji , Mizutani Shigehiko
Published: March 2007

OBJECTIVE—Estrogen seems to contribute to glucose homeostasis in women. The objective of this study was to examine the effects of hormone replacement therapy (HRT) on HbA1c levels in Japanese postmenopausal women and to determine whether the effects varied with age.

RESEARCH DESIGN AND METHODS—We studied 99 postmenopausal women taking HRT (mean ± SD age 56.5 ± 6.9 years, BMI 21.5 ± 2.3 kg/m2) and 101 postmenopausal women not on HRT (51.4 ± 6.1 years, 21.3 ± 2.4 kg/m2). HRT consisted of continuous conjugated equine estrogen (CEE; 0.625 mg/day) and medroxyprogesterone acetate (MPA; 2.5 mg/day) for >2 years.

RESULTS—HbA1c levels are positively associated with age and BMI in women who use HRT as well as in those who do not use HRT. After adjusting for age and BMI, HRT showed no effects on HbA1c levels. However, HbA1c levels were significantly lower in postmenopausal women aged 40–49 years who were taking HRT than in women of similar age who were not taking HRT (mean ± SE 4.776 ± 0.092 vs. 5.096 ± 0.078%, P < 0.05). No differences in HbA1c levels between women who did and did not use HRT were observed in those older than 50 years.

CONCLUSIONS—Oral HRT involving CEE combined with MPA may decrease HbA1c levels in women aged 40–49 years and is likely to have no adverse effects on HbA1c levels in women older than 50 years.
Do Impotent Men With Diabetes Have More Severe Erectile Dysfunction and Worse Quality of Life Than the General Population of Impotent Patients?
Authors: Penson David F. , Latini David M. , Lubeck Deborah P. , Wallace Katrine L. , Henning James M. , Lue Tom F.
Published: March 2007

OBJECTIVE—Little is known regarding how diabetic men with erectile dysfunction (ED) differ from the general population of impotent men. The primary objective of this study was to compare disease-specific health-related quality of life (HRQOL) and severity of ED in impotent men with and without diabetes.

RESEARCH DESIGN AND METHODS—Validated functional and HRQOL questionnaires (including the International Index of Erectile Function, the Sexual Self-Efficacy Scale, and the Psychological Impact of Erectile Dysfunction scales) were administered to patients in an ED disease registry. Men with ED and a history of diabetes (n = 20) were compared with men with ED and no history of diabetes (n = 90) at baseline and at the 12-month follow-up.

RESULTS—Diabetic impotent men reported worse erectile function and intercourse satisfaction at baseline, and ED had a greater impact on their emotional life. Diabetic men with ED had significantly different trends over time in the Erectile Function (P < 0.001), Intercourse Satisfaction (P < 0.013), Sexual Desire (P < 0.016), Overall Satisfaction (P < 0.023), and the Sexual Experience-Psychological Impact domains (P < 0.002). In addition, there was a trend toward a difference over time in the Emotional Life-Psychological Impact domain (P < 0.067).

CONCLUSIONS—Impotent men with diabetes present with worse ED than nondiabetic men with ED, resulting in worse disease-specific HRQOL in the diabetic men. Although diabetic patients initially respond well to ED treatment, responses do not appear to be durable over time. Therefore, clinicians must provide longer-term follow-up when treating ED in diabetic patients.
The Impact of Severe Hypoglycemia and Impaired Awareness of Hypoglycemia on Relatives of Patients With Type 1 Diabetes
Authors: Jørgensen Hanne V. , Pedersen-Bjergaard Ulrik , Rasmussen Åse K. , Borch-Johnsen Knut
Published: March 2007

OBJECTIVE—Severe hypoglycemia is a major problem for patients with type 1 diabetes and their relatives. The aim of this study was to compare patients’ and relatives’ assessments of rates of severe hypoglycemia and state of awareness and to explore the influence on involvement and concern of relatives.

RESEARCH DESIGN AND METHODS—A cross-sectional paired questionnaire survey on hypoglycemia and the state of awareness was used in our study comprising 284 unselected adult patients with type 1 diabetes and their closest cohabitant. The cohabitant questionnaires also addressed involvement and concern.

RESULTS—The agreement between assessments of rates of severe hypoglycemia and state of awareness made by patients and cohabitants was weak (κ 0.404 and 0.442, respectively; P < 0.001). Cohabitants recalled more episodes of severe hypoglycemia than patients (2.7 vs. 1.6 episodes/patient-year; P < 0.001). Degree of involvement was positively related to the rate of severe hypoglycemia (P = 0.002) and negatively related to the state of awareness (P = 0.007) but not to level of HbA1c, duration of diabetes, or presence of late complications, except for peripheral neuropathy (P = 0.01).

CONCLUSIONS—Cohabitants of patients with type 1 diabetes recall significantly more episodes of severe hypoglycemia than the patients. The rate of severe hypoglycemia and state of hypoglycemic awareness are the principal determinants of degree of cohabitants’ involvement in their partners’ disease.
Blood Pressure in Young Adulthood and the Risk of Type 2 Diabetes in Middle Age
Authors: Golden Sherita Hill , Wang Nae-Yuh , Klag Michael J. , Meoni Lucy A. , Brancati Frederick L.
Published: March 2007

OBJECTIVE—Hypertension is known to accompany type 2 diabetes in middle age, but it is unknown how early in life blood pressure (BP) begins to rise among individuals who later develop diabetes. The objective of this study was to evaluate elevated BP as a long-term predictor of type 2 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a prospective cohort study of 1,152 white male medical students in The Johns Hopkins Precursors Study to longitudinally assess systolic BP (SBP) and diastolic BP (DBP) from young adulthood through middle age in men who went on to develop diabetes. Incident diabetes was identified by self-report through mailed questionnaires verified by medical record review.

RESULTS—During a median follow-up of 38 years, 77 cases of incident diabetes occurred. The mean age of diabetes diagnosis was 58 years. As early as age 30 years, mean SBP and DBP were significantly higher in men who developed diabetes during follow-up than in those who remained nondiabetic (SBP 122 vs. 119 mmHg, P = 0.009; DBP 78 vs. 75 mmHg, P = 0.0005). The rate of increase in SBP and DBP over time in men who developed diabetes was greater than the rate of increase in men who did not develop diabetes (SBP 0.49 vs. 0.27 mmHg/year, P < 0.00003; DBP 0.24 vs. 0.17 mmHg/year; P = 0.09). After adjustment for BMI and other risk factors for diabetes, SBP and DBP at age 30 years remained significantly higher in individuals who developed diabetes than in their nondiabetic counterparts; however, the difference in the rate of increase in SBP was no longer significant following multivariate adjustment.

CONCLUSIONS—BP elevations precede the development of type 2 diabetes in middle age by 20–25 years. Higher BP in the prediabetic state might contribute to the presence of vascular disease at the time of diagnosis of type 2 diabetes.
Thyroid Dysfunction in Patients With Type 1 Diabetes
Authors: Umpierrez Guillermo E. , Latif Kashif A. , Murphy Mary Beth , Lambeth Helen C. , Stentz Frankie , Bush Andrew , Kitabchi Abbas E.
Published: March 2007

OBJECTIVE—Cross-sectional studies have reported that the risk of thyroid dysfunction in patients with type 1 diabetes is two- to threefold higher than in the general population. However, longitudinal studies to determine the natural history of thyroid dysfunction in patients with type 1 diabetes are lacking.

RESEARCH DESIGN AND METHODS—We analyzed the incidence of thyroid dysfunction over time in a cohort of 58 patients (26 men and 32 women) enrolled in the Diabetes Control and Complications Trial at the University of Tennessee Health Science Center in 1983 and prospectively followed for 18 years. Patients underwent measurement of thyroid function tests (thyroid-stimulating hormone [TSH], thyroxine, and triiodothyronine) every year and thyroid peroxidase (TPO) antibodies at 4-year intervals.

RESULTS—A total of 18 patients had hypothyroidism, and 1 patient experienced transient hyperthyroidism. Two subjects developed hypothyroidism 7 and 18 years before the development of diabetes and were excluded from the analysis. The mean age of diagnosis was 19 ± 2 years for type 1 diabetes and 29 ± 3 years for hypothyroidism. Hypothyroidism was more common in female (41%) than in male (19%) subjects and in patients with positive TPO antibodies. Patients who were TPO positive were 17.91 times as likely to develop hypothyroidism as patients who were TPO negative (95% CI 3.89–82.54). There were no differences in BMI, lipid profile, and HbA1c between patients with and without thyroid dysfunction.

CONCLUSIONS—This longitudinal study confirms the association between autoimmune thyroid dysfunction and type 1 diabetes. Our results indicate that all subjects with type 1 diabetes should undergo annual screening by serum TSH measurement to detect asymptomatic thyroid dysfunction, particularly those with positive TPO antibodies.
Development of New Peripheral Arterial Occlusive Disease in Patients With Type 2 Diabetes During a Mean Follow-Up of 11 Years
Authors: Kallio Milla , Forsblom Carol , Groop Per-Henrik , Groop Leif , Lepäntalo Mauri
Published: March 2007

OBJECTIVE— To assess the occurrence and development of new peripheral arterial occlusive disease (PAOD), its risk factors, and the outcome in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS— A total of 130 type 2 diabetic patients (mean age 58 years) were examined at baseline and after a mean follow-up of 11 years (range 7–14). The ankle-brachial index (ABI) and toe-brachial index were used to detect PAOD. Blood and urine samples were taken at baseline, and a history of cardiovascular events was recorded during follow-up.

RESULTS— PAOD was diagnosed in 21 (16%) patients at baseline. During follow-up, 21 of 89 (24%) patients developed new PAOD. There were 29 patients who died, 21 (72%) of them from cardiovascular disease. Patients with PAOD suffered an excess mortality compared with patients without PAOD (58 vs. 16%; P < 0.001). Logistic regression analysis showed that PAOD at baseline was associated with age, duration of diabetes, smoking, and urinary albumin excretion rate. Patients who developed new PAOD during follow-up had higher serum LDL cholesterol concentrations and lower HDL cholesterol concentrations and were older than the patients who remained free of PAOD.

CONCLUSIONS— Objectively measured PAOD is frequent in type 2 diabetic patients. It presents the early clinical signs of atherosclerosis and is strongly associated with cardiovascular death. The risk factor pattern for PAOD was different at baseline and after a mean follow-up of 11 years. We consider routine ABI measurements and modification of risk factors necessary also in patients with asymptomatic PAOD.
Clinical Impact of Prandial State, Exercise, and Site Preparation on the Equivalence of Alternative-Site Blood Glucose Testing
Authors: Bina Dawn M. , Anderson Robyn L. , Johnson Mary L. , Bergenstal Richard M. , Kendall David M.
Published: March 2007

OBJECTIVE—To determine whether clinically significant differences exist in fasting blood glucose (BG) at the forearm, palm, and thigh relative to the fingertip; to assess the impact of prandial status by comparing BG between alternative sites and the fingertip at several time intervals after carbohydrate intake; to assess the effects of moderate brief exercise on site-to-site differences in BG; to evaluate the impact of site preparation by local rubbing on alternative-site testing (AST) equivalence; and to determine levels of perceived pain and satisfaction associated with AST.

RESEARCH DESIGN AND METHODS—Fasting BG was measured using the One Touch Ultra (LifeScan, Milpitas, CA) at the fingertip, palm, thigh, and each forearm (with local rubbing) in 86 patients with type 2 diabetes. A 40-g carbohydrate meal was consumed and BG was again measured from each site at 60, 90, and 120 min postmeal, with an additional forearm test at 90 min without local rubbing. Patients then exercised for 15 min with repeat BG at each site. Differences in BG between sites were assessed using repeated-measures ANOVA and regression analyses.

RESULTS—Significant differences in BG at alternative sites were found 60 min postmeal (P = 0.0003) and postexercise (P = 0.037). Specifically, clinically significant differences (expressed as percent difference from the fingertip) at 60 min include −8.8 ± 10.8% at the forearm and −13.7 ± 10.7% at the thigh, and postexercise +19.1 ± 19.1% at the forearm and +15.6 ± 22.6% at the thigh. However, no significant differences were observed between sites in either the fasting state or at 90 and 120 min postmeal. The dynamic results suggest a time lag in equilibration of forearm and thigh BG during periods of rapid glucose change. Palm and fingertip BG test results were similar at all time points.

CONCLUSIONS—AST results are consistent with fingertip BG results in both the fasting state and 2 h postmeal; no benefit from site preparation by local rubbing was noted. However, testing at sites other than the hand cannot be recommended 1 h postmeal or immediately after exercise. AST is equivalent and appropriate for use at testing times commonly used in clinical practice.
Nurse-Based Management in Patients With Gestational Diabetes
Authors: García-Patterson Apolonia , Martín Esther , Ubeda Justa , María Miguel A. , Adelantado Juan M. , Ginovart Gemma , de Leiva Alberto , Corcoy Rosa
Published: March 2007

OBJECTIVE—To compare the rate of insulin treatment and perinatal outcome in women with gestational diabetes mellitus (GDM) under endocrinologist-based versus diabetes nurse-based metabolic management.

RESEARCH DESIGN AND METHODS—In a retrospective analysis, maternal characteristics, rate of insulin treatment, and perinatal outcome of patients with GDM delivering between 1 January 1995 and 30 June 1997 (n = 244) receiving endocrinologist-based care were compared with those delivering between 1 July 1997 and 31 December 1999 (n = 283) who received diabetes nurse-based care. The diabetes nurse’s role was similar to that of an advanced practice nurse in the U.S. There were no changes in the metabolic goals and instruments or in obstetric and neonatal management. Quantitative data were compared with the Mann-Whitney U test and categorical data, with Fisher’s exact test.

RESULTS—Maternal characteristics (age, BMI, family history of diabetes, prior glucose intolerance, gestational age, and blood glucose at diagnosis of GDM) did not differ between groups treated during the two periods. Rates of insulin treatment and perinatal outcome (hypertension, preterm delivery, cesarean section, low Apgar score, macrosomia, small- and large-for-gestational-age newborns, obstetric trauma, major malformations, hypoglycemia, hypocalcemia, polycythemia, jaundice, respiratory distress, and mortality) were also similar in both groups.

CONCLUSIONS—Comparison of periods of endocrinologist-based and diabetes nurse-based metabolic management of women with GDM showed no differences in the rate of insulin treatment and perinatal outcome. This supports a more active role of nurses in the management of women with GDM.
The Significance of Impaired Fasting Glucose Versus Impaired Glucose Tolerance
Authors: Carnevale Schianca Gian Piero , Rossi Antonello , Sainaghi Pier Paolo , Maduli Elisabetta , Bartoli Ettore
Published: March 2007

OBJECTIVE—The American Diabetes Association recommended substituting 2hBS (glycemia at the second hour of an oral glucose tolerance test [OGTT]) for fasting blood glucose (FBS) in screening for glucose intolerance. It is debated whether these tests measure the same abnormality and relate to defective insulin secretion or resistance. This study examines the diagnostic effectiveness of FBS versus 2hBS and their relationship with insulin secretion and resistance.

RESEARCH DESIGN AND METHODS—Based on history or physical findings suggesting glucose intolerance, we enrolled 398 unselected subjects admitted to a general Internal Medicine ward. After 5 days of a weight-maintaining diet, FBS, 2hBS, and insulin were measured during OGTT. The homeostatic model assessment was used to assess β-cell function and insulin resistance.

RESULTS—Excluding 19 patients with diabetes (5%), we identified 284 subjects with normal glucose tolerance (NGT), 22 with isolated impaired fasting glucose (IFG), 59 with isolated impaired glucose tolerance (IGT), and 14 with associated IFG/IGT. The sensitivity of FBS in predicting 2hBS was 19%, specificity 93%. Positive and negative predictive values were 39% and 83%, respectively. Insulin resistance was absent in NGT and IFG and markedly elevated in IGT and IFG/IGT, whereas defective insulin release was significant only in isolated IFG.

CONCLUSIONS—In unselected patients, elevated FBS depends primarily on defective insulin secretion, and impaired 2hBS on insulin resistance. Because these tests measure different alterations, they are useful in combination.
Insulin Resistance–Related Factors, but not Glycemia, Predict Coronary Artery Disease in Type 1 Diabetes
Authors: Orchard Trevor J. , Olson Jon C. , Erbey John R. , Williams Katherine , Forrest Kimberly Y.-Z. , Smithline Kinder Leslie , Ellis Demetrius , Becker Dorothy J.
Published: March 2007

OBJECTIVE—To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation.

RESEARCH DESIGN AND METHODS—This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8–47) and 19 years (7–37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1–3, 5.1–3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis ≥50%, revascularization procedure, Q waves (MC 1.1–1.2), nonfatal myocardial infarction (MI), or CAD death.

RESULTS—A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or ≥50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA1 showed no association with subsequent CAD.

CONCLUSIONS—These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.
Polypharmacy and Medication Adherence in Patients With Type 2 Diabetes
Authors: Grant Richard W. , Devita Nicole G. , Singer Daniel E. , Meigs James B.
Published: March 2007

OBJECTIVE—To determine medication adherence and predictors of suboptimal adherence in a community cohort of patients with diabetes and to test the hypothesis that adherence decreases with increased number of medicines prescribed.

RESEARCH DESIGN AND METHODS—A total of 128 randomly selected patients with type 2 diabetes from a single community health center responded to a pharmacist-administered questionnaire regarding medication use. Survey data were linked to clinical data available from the electronic medical record. We assessed self-reported adherence rates for each diabetes-related medicine, barriers and attitudes regarding medication use, and HbA1c, total cholesterol, and blood pressure levels.

RESULTS—Patients were taking a mean of 4.1 (±1.9) diabetes-related medicines. The average 7-day adherence was 6.7 ± 1.1 days. Total number of medicines prescribed was not correlated with medication adherence. Adherence was significantly lower for medicines not felt to be improving current or future health (6.1 vs. 6.9 days out of 7, P < 0.001). Among patients on three or more medicines, 71% (15 of 21 patients) with suboptimal adherence were perfectly adherent with all but one medicine. Side effects were the most commonly reported problem with medication use. Of 29 medicines causing side effects that interfered with adherence, 24 (83%) did so for >1 month, and only 7 (24%) were reported to the patient’s primary care physician.

CONCLUSIONS—In this sample, patients reported very high medication adherence rates regardless of number of medicines prescribed. Among patients on multiple medicines, most patients with suboptimal adherence were perfectly adherent to all but one medicine. Unreported side effects and a lack of confidence in immediate or future benefits were significant predictors of suboptimal adherence. Physicians should not feel deterred from prescribing multiple agents in order to achieve adequate control of hyperglycemia, hypertension, and hyperlipidemia.
Visceral Adipose Tissue Cutoffs Associated With Metabolic Risk Factors for Coronary Heart Disease in Women
Authors: Nicklas Barbara J. , Penninx Brenda W.J.H. , Ryan Alice S. , Berman Dora M. , Lynch Nicole A. , Dennis Karen E.
Published: March 2007

OBJECTIVE—This study determined whether there is a critical level of visceral adipose tissue (VAT) associated with elevated coronary heart disease (CHD) risk factors in a cohort of women >45 years of age.

RESEARCH DESIGN AND METHODS—Measurements of body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography), fasting and 2-h postprandial (75-g) glucose concentrations, and fasting lipoprotein lipid and insulin concentrations were performed in 233 perimenopausal (9%) and postmenopausal women (age 59 ± 6 years, 79% Caucasian, 16% on hormone replacement therapy).

RESULTS—Women in the lowest VAT quintile (≤105 cm2) had higher concentrations of HDL and HDL2 cholesterol, lower LDL/HDL cholesterol ratios and triglyceride concentrations, and lower fasting glucose and insulin concentrations than women in the remaining four quintiles (P values <0.05–0.001). Women in the second lowest VAT quintile (106–139 cm2) had higher HDL and HDL2 cholesterol and lower LDL/HDL ratios than women with a VAT ≥163 cm2 (P < 0.05). Logistic regression analyses showed that women with a VAT of 106–162 cm2 are 2.5 times more likely to have a low HDL cholesterol (P < 0.05), while women with a VAT ≥163 cm2 are 5.5 times more likely to have a low HDL cholesterol (P < 0.01) and ∼4.0 times more likely to have a high LDL/HDL ratio (P < 0.05) compared with women with a VAT ≤105 cm2. Women with a VAT ≥163 cm2 are at a higher risk of having impaired glucose tolerance (P < 0.01).

CONCLUSIONS—A VAT ≥106 cm2 is associated with an elevated risk, and a VAT ≥163 cm2 with an even greater risk, for these metabolic CHD risk factors compared with women with a VAT ≤105 cm2. These values may prove useful for defining “visceral obesity” and for identifying women most likely to benefit from preventative interventions.
Multiple Hospitalizations for Patients With Diabetes
Authors: Jiang H. Joanna , Stryer Daniel , Friedman Bernard , Andrews Roxanne
Published: March 2007

OBJECTIVE—To describe the extent to which hospitalizations for patients with diabetes reflect multiple stays by the same individuals and to examine how multiple hospitalizations vary by patient demographic and socioeconomic characteristics.

RESEARCH DESIGN AND METHODS—Using the Healthcare Cost and Utilization Project complete discharge data for five states (California, Missouri, New York, Tennessee, and Virginia) in 1999, we identified 648,748 nonneonatal, nonmaternal patients who had one or more hospitalizations listing diabetes. Multiple hospitalizations were measured as percent of patients with multiple stays, percent of total stays represented by multiple stays, and average number of stays per patient. Total hospital costs were also examined. Stratified analysis and regression were performed to assess differences by age, sex, race/ethnicity, payer, location, and income.

RESULTS—Among patients with diabetes who had been hospitalized, 30% had two or more stays accounting for >50% of total hospitalizations and hospital costs. Controlled for patient age, sex, and clinical characteristics, the likelihood of having multiple hospitalizations was higher for Hispanics and non-Hispanic blacks compared with non-Hispanic whites, as well as for patients covered by Medicare or Medicaid and those living in low-income areas. The prevalence of diabetes complications and multiple conditions differed by age, race/ethnicity, and payer among patients with multiple stays.

CONCLUSIONS—Multiple hospitalizations are common among patients with diabetes but vary by age, race/ethnicity, payer, and income, with those populations traditionally considered to be more vulnerable experiencing higher likelihoods of multiple stays. Significant opportunities exist to reduce the proportion of multiple hospitalizations for patients with diabetes. Clinical and policy interventions to improve the quality of care and outcomes for these patients should be designed accordingly and have the potential to pay major dividends.
Low IGF-I and Elevated Testosterone During Puberty in Subjects With Type 1 Diabetes Developing Microalbuminuria in Comparison to Normoalbuminuric Control Subjects
Authors: Amin Rakesh , Schultz Carl , Ong Ken , Frystyk Jan , Dalton R. Neil , Perry Les , Ørskov Hans , Dunger David B.
Published: March 2007

OBJECTIVE—To describe longitudinal variations in pubertal hormonal variables in subjects with and without microalbuminuria (MA).

RESEARCH DESIGN AND METHODS—Blood samples collected annually from subjects recruited at diagnosis of type 1 diabetes and followed prospectively through puberty (median follow-up 9.3 years, range 4.7–12.8) were analyzed for total and free IGF-I, IGF binding protein-1, testosterone, sex hormone-binding globulin, and HbA1c. A total of 55 subjects who developed MA (MA+ group) were compared with 55 age-, sex-, and duration-matched control subjects who did not develop MA (MA− group).

RESULTS—For female subjects, total IGF-I (MA+ 1.2 mU/l vs. MA− 1.4 mU/l, P = 0.03) and free IGF-I levels (MA+ 1,767 ng/l vs. MA− 2010 ng/l, P = 0.002) were lower, whereas the free androgen index (MA+ 2.4 vs. MA− 2.0, P = 0.03) was higher in those with MA. These changes were less pronounced in male subjects. For both sexes, in a Cox model after adjusting for puberty, the presence of MA was associated with lower free IGF-I levels, higher testosterone standard deviation score (SDS), and poor glycemic control. We found that 22 of 55 case subjects (40%) developed persistent MA, whereas 33 (60%) had transient MA. In the persistent MA group compared with the transient and control groups, total IGF-I levels were lower (1.1 vs. 1.3 vs. 1.4 mU/l, P = 0.002) as were free IGF-I levels (1,370.9 vs. 1,907.3 vs. 1,886.7 ng/l, P < 0.001), whereas HbA1c levels were higher (11.8 vs. 10.3 vs. 9.9%, P < 0.001).

CONCLUSIONS—Poor glycemic control and differences in IGF-I levels and androgens, particularly in female subjects, accompany development of MA at puberty. These differences may in part account for the sexual dimorphism in MA risk during puberty and could relate to disease progression.
Modem Transmission of Glucose Values Reduces the Costs and Need for Clinic Visits
Authors: Chase H. Peter , Pearson Jerusha A. , Wightman Clare , Roberts Mary D. , Oderberg Adam D. , Garg Satish K.
Published: March 2007

OBJECTIVE—To determine whether modem technology allows for effective management of type 1 diabetes when used in lieu of a clinic visit.

RESEARCH DESIGN AND METHODS—A total of 70 adolescent patients with diabetes were prospectively randomized to either a control group or a modem group. Control group patients continued the standard of care of quarterly clinic visits, and modem group patients were instructed to transmit blood glucose data every 2 weeks for 6 months instead of a usual quarterly clinic visit. Health care providers analyzed the data received by modem and contacted patients to discuss diabetes treatment changes. GHbA1c levels were determined at 0 and 6 months, and the number of high and low blood glucose levels and adverse events were tracked. Clinic visit costs, patient expenses, and health care provider times were tracked for cost analysis for both groups.

RESULTS—A total of 63 patients (33 control, 30 modem) completed the 6-month study. The GHbA1c values significantly decreased in both groups, with no statistically significant difference between groups (P = 0.96). The occurrence of mild-to-moderate hypoglycemic events were similar in the two groups, and there were no severe hypoglycemic events. The average cost of care for a clinic visit was $305.00, whereas the cost for 6 months of modem transmission was $163.00.

CONCLUSIONS—This study shows that electronic transmission of blood glucose levels and other diabetes data every 2 weeks—in lieu of a clinic visit—results in a similar level of glucose control and incidence of acute diabetes complications when compared with current standard care.
Effects of an Automated Electronic Reminder in Changing the Antiplatelet Drug–Prescribing Behavior Among Italian General Practitioners in Diabetic Patients
Authors: Filippi Alessandro , Sabatini Andrea , Badioli Letizia , Samani Fabio , Mazzaglia Giampiero , Catapano Alberico , Cricelli Claudio
Published: March 2007

OBJECTIVE—To evaluate whether an electronic reminder integrated into a routine computer system increases the use of antiplatelet drugs for diabetic patients among Italian general practitioners (GPs).

RESEARCH DESIGN AND METHODS—A randomized controlled trial was carried out among 300 GPs and their patients selected from the Health Search Database. Among these, 150 GPs (intervention group) received instructions to activate an electronic reminder plus a letter summarizing the beneficial effects of antiplatelet drugs in diabetic patients with at least one additional cardiovascular risk factor (“high risk”), whereas the other 150 GPs (control group) received only the letter. The electronic reminder, integrated into a standard software system for the management of the daily clinical practice, was displayed when every participating GP opened the medical record of diabetic patients aged ≥30 years. Only high-risk diabetic patients were included in the analysis. Patients were considered under antiplatelet treatment if they received two or more prescriptions at baseline and during the follow-up.

RESULTS—We selected 15,343 high-risk diabetic patients, 7,313 belonging to GPs of the control group and 8,030 belonging to GPs of the intervention group. Overall, 1,672 patients (22.9%) of the control group and 1,886 (23.5%) patients of the intervention group received antiplatelet drugs at baseline (P = N.S.). At the end of the follow-up, the number of treated patients was significantly increased in the intervention group (odds ratio 1.99, 95% CI 1.79–2.22) versus the control group. The effect of the electronic reminder was more relevant among those patients with one or more cardiovascular risk factors but without previous cardiovascular diseases (CVDs), compared with those with CVDs.

CONCLUSIONS—These findings provide evidence for the effect of an electronic reminder in affecting the prescriptive behavior of GPs.
Evaluation of Urinary 8-Hydroxydeoxy-Guanosine as a Novel Biomarker of Macrovascular Complications in Type 2 Diabetes
Authors: Nishikawa Takeshi , Sasahara Takayuki , Kiritoshi Shinsuke , Sonoda Kazuhiro , Senokuchi Takahumi , Matsuo Tomoko , Kukidome Daisuke , Wake Nakayasu , Matsumura Takeshi , Miyamura Nobuhiro , Sakakida Michiharu , Kishikawa Hideki , Araki Eiichi
Published: March 2007

OBJECTIVE—To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications.

RESEARCH DESIGN AND METHODS—The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21–B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion.

RESULTS—The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA1c than in those with normal HbA1c (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01).

CONCLUSIONS—Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.
Diabetes and Coronary Artery Bypass Surgery
Authors: McAlister Finlay A. , Man Jeremy , Bistritz Lana , Amad Hani , Tandon Puneeta
Published: March 2007

OBJECTIVE—To determine the adequacy of perioperative glycemic control in diabetic patients undergoing coronary artery bypass grafting (CABG) and to explore the association between glycemic control and in-hospital morbidity/mortality.

RESEARCH DESIGN AND METHODS—Retrospective cohort study of consecutive patients with diabetes undergoing CABG between April 2000 and March 2001 who survived at least 24 h postoperatively.

RESULTS—Of the 291 patients in this study, 95% had type 2 diabetes and 40% had retinopathy, nephropathy, or neuropathy at baseline. During hospitalization (median 7 days), 78 (27%) of these patients suffered a nonfatal stroke or myocardial infarction, septic complication, or died (“adverse outcomes”). Glycemic control was suboptimal (average glucose on first postoperative day was 11.4 [11.2–11.6] mmol/l) and was significantly associated with adverse outcomes post-CABG (P = 0.03). Patients whose average glucose level was in the highest quartile on postoperative day 1 had higher risk of adverse outcomes after the first postoperative day than those with glucose in the lowest quartile (odds ratio 2.5 [1.1–5.3]). Even after adjustment for other clinical and operative factors, average blood glucose level on the first postoperative day remained significantly associated with subsequent adverse outcomes: for each 1-mmol/l increase above 6.1 mmol/l, risk increased by 17%.

CONCLUSIONS—Perioperative glycemic control in our cohort of diabetic patients undergoing CABG in a tertiary care facility was suboptimal. We believe closure of this care gap is imperative, because hyperglycemia in the first postoperative day was associated with subsequent adverse outcomes in our study patients.
C-Reactive Protein and Glycemic Control in Adults With Diabetes
Authors: King Dana E. , Mainous Arch G. , Buchanan Thomas A. , Pearson William S.
Published: March 2007

OBJECTIVE—Recent evidence suggests that poor glycemic control is significantly associated with the development of macrovascular complications of diabetes. Studies have indicated that C-reactive protein (CRP) is an important risk factor for cardiovascular disease. The purpose of this study was to determine the relation between CRP and HbA1c in a large national sample of individuals with diabetes.

RESEARCH DESIGN AND METHODS—A nationally representative sample of noninstitutionalized U.S. adults aged 17 years and over with nongestational diabetes was derived from the National Health and Nutrition Examination Survey III (1988–1994) (n = 1,018). Respondents with diabetes were stratified by HbA1c level. The main outcome measure was elevated (>0.30 mg/dl) CRP.

RESULTS—In unadjusted analyses, respondents with diabetes who had elevated HbA1c levels (≥9.0%) had a significantly higher percent of elevated CRP than people with low (<7%) HbA1c levels (P < 0.001). In adjusted regression analysis, after controlling for age, race, sex, smoking, length of time with diabetes, insulin, and BMI, HbA1c was significantly associated with an increased likelihood of elevated CRP for HbA1c >9.0% (OR 2.15, 95% CI 1.07–4.32) and for HbA1c >11.0% (4.40, 1.87–10.38). Higher HbA1c also predicted elevated CRP in the regression model when HbA1c was analyzed as a continuous variable (1.20, 1.07–1.34).

CONCLUSIONS—In this study, the likelihood of elevated CRP concentrations increased with increasing HbA1c levels. These findings suggest an association between glycemic control and systemic inflammation in people with established diabetes.
Antihyperglycemic Effect of Oolong Tea in Type 2 Diabetes
Authors: Hosoda Kazuaki , Wang Ming-Fu , Liao Mei-Ling , Chuang Chin-Kuang , Iha Miyuki , Clevidence Beverly , Yamamoto Shigeru
Published: March 2007

OBJECTIVE—To determine the efficacy of oolong tea for lowering plasma glucose in type 2 diabetic patients in Miaoli, Taiwan.

RESEARCH DESIGN AND METHODS—A total of 20 free-living subjects who had type 2 diabetes and took hyperglycemic drugs as prescribed were enrolled in the present study. Subjects consumed oolong tea (1,500 ml) or water for 30 days each in a randomized crossover design. Tea was not consumed for 14 days prior to treatments.

RESULTS—Relative to initial concentrations, oolong tea markedly lowered concentrations of plasma glucose (from 229 ± 53.9 to 162.2 ± 29.7 mg/dl, P < 0.001) and fructosamine (from 409.9 ± 96.1 to 323.3 ± 56.4 μmol/l, P < 0.01), whereas the water control group had not changed (208.7 ± 61.0 vs. 232.3 ± 63.1 mg/dl for glucose and from 368.4 ± 85.0 to 340.0 ± 76.1 μmol/l for fructosamine).

CONCLUSIONS—Oolong tea may be an effective adjunct to oral hypoglycemic agents in the treatment of type 2 diabetes.
Type 2 Diabetes and Subsequent Incidence of Breast Cancer in the Nurses’ Health Study
Authors: Michels Karin B. , Solomon Caren G. , Hu Frank B. , Rosner Bernard A. , Hankinson Susan E. , Colditz Graham A. , Manson JoAnn E.
Published: March 2007

OBJECTIVE—Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses’ Health Study.

RESEARCH DESIGN AND METHODS—A total of 116,488 female nurses who were 30–55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports.

RESULTS—During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01–1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98–1.62) but not premenopausal women (0.83; 0.48–1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01–1.47).

CONCLUSIONS—Women with type 2 diabetes may have a slightly increased risk of breast cancer.