bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormone Replacement Therapy, Insulin Sensitivity, and Abdominal Obesity in Postmenopausal Women
Authors: Ryan Alice S. , Nicklas Barbara J. , Berman Dora M.
Published: March 2007

OBJECTIVE—The purpose of this study was to determine whether insulin sensitivity differs between postmenopausal women taking estradiol, women on estrogen plus progesterone hormone replacement therapy (HRT), and women not on HRT and whether differences are explained by the differences in total and/or abdominal adiposity and fat deposition in the muscle.

RESEARCH DESIGN AND METHODS—We studied 28 obese, sedentary postmenopausal Caucasian women. Women taking oral estrogen (n = 6) were matched for age (57 ± 3 vs. 58 ± 2 years), weight (87.9 ± 6.0 vs. 83.0 ± 3.9 kg), and BMI (33.9 ± 1.7 vs. 33.9 ± 1.9 kg/m2) with women not on HRT (n = 6). Eight women taking oral estrogen plus progesterone were matched with eight different women not on HRT for age (59 ± 2 vs. 60 ± 2 years), weight (82.8 ± 3.7 vs. 83.7 ± 4.1 kg), and BMI (30.7 ± 1.0 vs. 29.9 ± 1.3 kg/m2).

RESULTS—Vo2max (maximal aerobic capacity), percentage of fat, total body fat mass, and fat-free mass (FFM) were similar between groups. Visceral fat, subcutaneous abdominal fat, sagittal diameter, and mid-thigh low-density lean tissue (intramuscular fat) did not differ by hormone status. Basal carbohydrate and fat utilization was not different among groups. Fasting plasma glucose and insulin did not differ by hormone use. Glucose utilization (M) was measured during the last 30 min of a 3-h hyperinsulinemic-euglycemic clamp (40 mU · m2 · min−1). Postmenopausal women taking oral estrogen had a 31% lower M than women not on HRT (42.7 ± 4.0 vs. 61.7 ± 4.7 μmol · kgFFM · min−1, P < 0.05). M was 26% lower in women taking estrogen plus progesterone (44.0 ± 3.5 vs. 59.7 ± 6.2 μmol · kgFFM · min−1, P < 0.05) than women not on HRT. M/I, the amount of glucose metabolized per unit of plasma insulin (I), an index of insulin sensitivity, was 36% lower in women taking estrogen compared with matched women not on HRT (P < 0.05) and 28% lower in women taking estrogen plus progesterone compared with matched women not on HRT (P < 0.05).

CONCLUSIONS—Postmenopausal women taking oral estrogen or those taking a combination of estrogen and HRT are more insulin-resistant than women not on HRT, even when women are of comparable total and abdominal adiposity.
High-Intensity Resistance Training Improves Glycemic Control in Older Patients With Type 2 Diabetes
Authors: Dunstan David W. , Daly Robin M. , Owen Neville , Jolley Damien , de Courten Maximilian , Shaw Jonathan , Zimmet Paul
Published: March 2007

OBJECTIVE—To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Sedentary, overweight men and women with type 2 diabetes, aged 60–80 years (n = 36), were randomized to high-intensity progressive resistance training plus moderate weight loss (RT & WL group) or moderate weight loss plus a control program (WL group). Clinical and laboratory measurements were assessed at 0, 3, and 6 months.

RESULTS—HbA1c fell significantly more in RT & WL than WL at 3 months (0.6 ± 0.7 vs. 0.07 ± 0.8%, P < 0.05) and 6 months (1.2 ± 1.0 vs. 0.4 ± 0.8%, P < 0.05). Similar reductions in body weight (RT & WL 2.5 ± 2.9 vs. WL 3.1 ± 2.1 kg) and fat mass (RT & WL 2.4 ± 2.7 vs. WL 2.7 ± 2.5 kg) were observed after 6 months. In contrast, lean body mass (LBM) increased in the RT & WL group (0.5 ± 1.1 kg) and decreased in the WL group (0.4 ± 1.0) after 6 months (P < 0.05). There were no between-group differences for fasting glucose, insulin, serum lipids and lipoproteins, or resting blood pressure.

CONCLUSIONS—High-intensity progressive resistance training, in combination with moderate weight loss, was effective in improving glycemic control in older patients with type 2 diabetes. Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes.
Barriers to Blood Glucose Monitoring in a Multiethnic Community
Authors: Zgibor Janice C. , Simmons David
Published: March 2007

OBJECTIVE—We studied a multiethnic community to determine factors associated with blood glucose monitoring (BGM) and to determine the independent association between barriers to diabetes care and BGM.

RESEARCH DESIGN AND METHODS—A total of 323 participants (35.6% European, 32.2% Maori, and 32.2% Pacific Islander) from the South Auckland Diabetes Project (free of major complications by self-report) completed a qualitative survey to determine barriers to diabetes care. Five barriers to diabetes care categories were generated including internal psychological (self efficacy/health beliefs), external psychological (psychosocial environment), internal physical (comorbidities/side effects of treatment), external physical (finance/access to care), and educational (knowledge of diabetes/services) barriers.

RESULTS—Characteristics associated with BGM greater than or equal to twice weekly were female sex, HbA1c >8%, higher diabetes knowledge scores, and insulin use. Multivariate analyses demonstrated that those reporting external physical barriers (OR 0.47, 95% CI 0.26–0.84), external psychological barriers (0.55, 0.30–1.0), and internal psychological barriers (0.56, 0.32–1.0) were less likely to perform BGM independent of ethnicity, insulin use, age, sex, diabetes knowledge, and glycemic control. Further multivariate analyses demonstrated that those reporting external physical barriers, particularly related to personal finance, were less likely to perform BGM.

CONCLUSIONS—These data demonstrate that patient-reported barriers to diabetes care are associated with BGM, particularly in relation to financial, psychosocial, and self-efficacy issues. Understanding these barriers and overcoming them within the context of the patient’s ethnic environment may lead to increased participation in self-care.
A Comparison of the Effects of Rosiglitazone and Glyburide on Cardiovascular Function and Glycemic Control in Patients With Type 2 Diabetes
Authors: St. John Sutton Martin , Rendell Marc , Dandona Paresh , Dole Jo F. , Murphy Karen , Patwardhan Rita , Patel Jai , Freed Martin ,   For the Rosiglitazone Clinical Trials Study Group
Published: March 2007

OBJECTIVE—This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA1c.

RESULTS—Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA1c and FPG.

CONCLUSIONS—A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.
Adherence to American Diabetes Association Standards of Care by Rural Health Care Providers
Authors: Coon Patricia , Zulkowski Karen
Published: March 2007

OBJECTIVE—To determine whether rural health care providers are compliant with American Diabetes Association (ADA) clinical practice guidelines for glycemic, blood pressure, lipid management, and preventative services.

RESEARCH DESIGN AND METHODS—This study was performed using a retrospective chart review of 399 patients 45 years of age and older, with a definitive diagnosis of diabetes seen for primary diabetes care at four rural health facilities in Montana between 1 January 1999 and 1 August 2000.

RESULTS—Glycemic testing was adequate (85%), and glycemic control (HbA1c 7.43 ± 1.7%) was above the national average. Comorbid conditions of hypertension and dyslipidemia were not as well managed. Mean systolic blood pressure (SBP) was 139 ± 18.8 mmHg and LDL was 119 ± 33 mg/dl. Of 399 patients, 11 were considered as needing no additional treatment based on ADA guidelines of an HbA1c level <7%, a BP <130/85 mmHg, and a LDL level <100 mg/dl. Monofilament testing and dilated eye examinations were poorly documented, as were immunizations. There were few referrals for diabetic education.

CONCLUSIONS—Rural health care practitioners are not adequately following the ADA standards for comprehensive management of their patients with diabetes. Glycemic testing is being ordered, but HbA1c values indicate that patients do not have their diabetes under optimal control. The comorbid conditions of hypertension and dyslipidemia are not optimally managed according to the ADA guidelines.
A Health Economic Model to Assess the Long-Term Effects and Cost-Effectiveness of Orlistat in Obese Type 2 Diabetic Patients
Authors: Lamotte Mark , Annemans Lieven , Lefever Aurelia , Nechelput Myriam , Masure Johan
Published: March 2007

OBJECTIVES—Obesity is a common condition in type 2 diabetic patients. Treating obesity may enhance hypoglycemic treatment and contribute to the reduction of long-term microvascular and macrovascular complications. Orlistat reduces cardiovascular risk factors in obese type 2 diabetic patients. The objectives of this study were to estimate the long-term clinical consequences of this weight loss and the resulting cost-effectiveness of treating obese type 2 diabetic patients with orlistat.

RESEARCH DESIGN AND METHODS—A Markov model was developed to predict, over a 10-year period, the complication rates and mortality with and without a 2-year orlistat treatment, assuming a 5-year catch-up period after treatment. A stepwise approach was used to obtain the clinical data. First, the impact of weight loss with orlistat on HbA1c, blood pressure, and cholesterol was assessed; then, the impact on mortality and micro- and macrovascular complications of decreasing these risk factors was applied. Four subgroups were studied based on the presence of risk factors.

RESULTS—Cost-effectiveness varies between 3,462 Euro/life-year gained (LYG) for obese diabetic patients with hypertension and hypercholesterolemia and 19,986 Euro/LYG for obese diabetic patients without other risk factors. The latter result is not robust according to sensitivity analyses.

CONCLUSIONS—Our results suggest that orlistat is cost-effective in the management of obese type 2 diabetic patients, especially in those with the presence of hypercholesterolemia and/or hypertension. Evidence on longer-term benefits of orlistat (>2 years) will be of importance for future decision-making.
Continuous Subcutaneous Glucose Monitoring in Diabetic Patients
Authors: Maran Alberto , Crepaldi Cristina , Tiengo Antonio , Grassi Giorgio , Vitali Emanuela , Pagano Gianfranco , Bistoni Sergio , Calabrese Giuseppe , Santeusanio Fausto , Leonetti Frida , Ribaudo Maria , Di Mario Umberto , Annuzzi Giovanni , Genovese Salvatore , Riccardi Gabriele , Previti Marcello , Cucinotta Domenico , Giorgino Francesco , Bellomo Aurelia , Giorgino Riccardo , Poscia Alessandro , Varalli Maurizio
Published: March 2007

OBJECTIVE—To evaluate the accuracy of a new subcutaneous glucose sensor (Glucoday; A. Menarini Diagnostics) compared with venous blood glucose measurement in type 1 and type 2 diabetic patients.

RESEARCH DESIGN—A multicenter study was performed in 70 diabetic patients. A microdialysis fiber was inserted subcutaneously into the periumbelical region and perfused with a buffer solution. Glucose concentrations in the dialysate were then measured every 3 min by the glucose sensor over a 24-h period, during which nine venous blood samples were also collected throughout the day.

RESULTS—Both the insertion of the fiber and the wearing of the device were well tolerated by the patients. Subcutaneous glucose levels were well correlated with venous glucose measurements (r = 0.9, P < 0.001) over a wide range (40–400 mg/dl) for up to 24 h, with a single-point calibration. An analysis of 381 data pairs showed a linear relationship between the GlucoDay and serial venous blood glucose levels, and 97% of the data fell in the A and B regions of the error grid analysis. Percentage bias between the GlucoDay and the blood venous levels was −2.0% in the hypoglycemic range (<70 mg/dl), 6.9% in the euglycemic range (70–180 mg/dl), and 11.2% in the hyperglycemic range (>180 mg/dl).

CONCLUSIONS—The GlucoDay system demonstrated high reliability and reported values that closely agreed with venous blood glucose measurements. The system was well tolerated and thus constitutes a relatively easy method to monitor glucose excursions in diabetic patients.
Foot Ulceration and Lower Limb Amputation in Type 2 Diabetic Patients in Dutch Primary Health Care
Authors: Muller Ilona Statius , de Grauw Wim J.C. , van Gerwen Willem H.E.M. , Bartelink Marie Louise , van den Hoogen Henk J.M. , Rutten Guy E.H.M.
Published: March 2007

OBJECTIVE— To determine the incidence of foot ulceration and lower limb amputation in type 2 diabetic patients in primary health care.

RESEARCH DESIGN AND METHODS— Data on type 2 diabetes were collected by the Nijmegen Monitoring Project between 1993 and 1998 as part of a study of chronic diseases. The records of all patients recorded as having diabetic foot problems and those who died, moved to a nursing home, or were under specialist care were included. The annual incidence of foot ulceration was defined as the number of type 2 diabetic patients per patient-year who developed a new foot ulcer. Incidence of lower limb amputation was similarly defined. Additional information was collected on treatment of foot ulcers.

RESULTS— The study population of type 2 diabetic patients increased from 511 patient-years in 1993 to 665 in 1998. The annual incidence of foot ulceration varied between 1.2 and 3.0% (mean 2.1) per year; 25% of the patients had recurrent episodes. The annual incidence of lower limb amputation varied between 0.5 and 0.8% (mean 0.6). Ten of the 15 amputees died, and 12 of 52 (23%) patients with ulceration had a subsequent amputation or a previous history of amputation. In 35 of the 73 (48%) episodes of ulceration, only the family physician provided treatment. Patients with foot problems were older and had more cardiovascular disease, retinopathy, and absent peripheral pulses.

CONCLUSIONS— The incidence of foot ulceration and lower limb amputation in type 2 diabetes is low; nevertheless, recurrence rates of ulceration and risk of amputation are high, with high mortality.
Impact of Diabetes on Coronary Stenosis and Coronary Artery Calcification Detected by Electron-Beam Computed Tomography in Symptomatic Patients
Authors: Hosoi Masayuki , Sato Toshihiko , Yamagami Keiko , Hasegawa Takanori , Yamakita Tetsuya , Miyamoto Masafumi , Yoshioka Katsunobu , Yamamoto Tsunehiko , Ishii Tomofusa , Tanaka Shiro , Itoh Akira , Haze Kazuo , Fujii Satoru
Published: March 2007

OBJECTIVE—Ischemic heart disease is a pivotal complication for diabetic patients. Electron-beam computed tomography (EBCT) represents the only noninvasive method that allows for accurate quantification of coronary artery calcification that reflects underlying atherosclerotic disease. Although coronary calcium score (CCS) cut points that predict the presence of angiographic stenosis have been established in nondiabetic individuals, it is not known whether coronary calcifications in diabetic patients are associated with the presence of significant coronary stenoses. In this study, we evaluated the relationship between coronary calcifications and angiographic stenosis in symptomatic patients with or without type 2 diabetes.

RESEARCH DESIGN AND METHODS—In this study, 282 patients (204 men and 78 women) with chest pain, including 101 diabetic patients and 181 nondiabetic patients (mean age 63 ± 9.6 years), underwent coronary angiography and EBCT with determination of CCS using Agatston’s method. Luminal stenosis ≥ 50% was defined as significant coronary stenosis.

RESULTS—Angiography identified 205 patients with significant stenoses (89 of 101 diabetic patients, 114 of 181 nondiabetic patients). The sensitivity and specificity of EBCT to detect significant coronary stenosis were not significantly different between diabetic and nondiabetic patients. In diabetic patients, a CCS ≥90 was associated with 75% sensitivity and 75% specificity, whereas a CCS ≥200 was associated with 64% sensitivity and 83% specificity.

CONCLUSIONS—We demonstrated that calcification of the coronary arteries in symptomatic diabetic patients is well associated with severity of coronary stenosis, as in nondiabetic patients.
Improved Postprandial Glycemic Control With Biphasic Insulin Aspart Relative to Biphasic Insulin Lispro and Biphasic Human Insulin in Patients With Type 2 Diabetes
Authors: Hermansen Kjeld , Colombo Michele , Storgaard Heidi , Østergaard Anette , Kølendorf Klaus , Madsbad Sten
Published: March 2007

OBJECTIVE—The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations. This trial compared the postprandial serum glucose control of biphasic insulin aspart 30 (BIAsp 30: 30% aspart, 70% protaminated aspart) with that of biphasic insulin lispro 25 (Mix25: 25% lispro, 75% protaminated lispro) and biphasic human insulin 30 (BHI 30: 30% regular insulin, 70% NPH insulin) in insulin-treated subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This was an open-labeled, randomized, single-dose, three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications. BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal, and BHI 30 was injected 15 min before a test meal. The primary target of analysis was serum glucose excursion 0–5 h after a meal.

RESULTS—The postprandial glycemic control with BIAsp 30, as assessed by the 5-h postmeal serum glucose excursion, was superior to that with both BHI 30 and Mix25 (16.6 ± 4.5 vs. 20.1 ± 4.9 and 18.9 ± 6.1 mmol/l per hour, respectively; P < 0.001 and P < 0.05). For BIAsp 30 versus BHI 30, this was supported by a reduced maximum glucose concentration [Cmax(SG)] (−5%; P < 0.05) occurring earlier (−13 min; P < 0.01). Furthermore, BIAsp 30 displayed a higher maximum serum insulin concentration (+101%; P < 0.001) occurring earlier (−55 min; P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter time to Cmax(SG) (−11 min; P < 0.05) after treatment with BIAsp 30.

CONCLUSIONS—This trial demonstrates that BIAsp 30 improves postprandial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.
Use of Stress Echocardiography to Predict Mortality in Patients With Diabetes and Known or Suspected Coronary Artery Disease
Authors: Marwick Thomas H. , Case Colin , Sawada Stephen , Vasey Charles , Short Leanne , Lauer Michael
Published: March 2007

OBJECTIVE—This study sought to determine whether stress echocardiography using exercise (when feasible) or dobutamine echo could be used to predict mortality in patients with diabetes.

RESEARCH DESIGN AND METHODS—Stress echo was performed in 937 patients with diabetes (aged 59 ± 13 years, 529 men) for symptom evaluation (42%) and follow-up of known coronary artery disease (CAD) (58%). Stress echocardiography using exercise was performed in 333 patients able to exercise maximally, and dobutamine echo using a standard dobutamine stress was used in 604 patients. Patients were followed for ≤9 years (mean 3.9 ± 2.3) for all-cause mortality.

RESULTS—Normal studies were obtained in 567 (60%) patients; 29% had resting left ventricular (LV) dysfunction, and 25% had ischemia. Abnormalities were confined to one territory in 183 (20%) patients and to multiple territories in 187 (20%) patients. Death (in 275 [29%] patients) was predicted by referral for pharmacologic stress (hazard ratio [HR] 3.94, P < 0.0001), ischemia (1.77, P < 0.0001), age (1.02, P = 0.002), and heart failure (1.54, P = 0.01). The risk of death in patients with a normal scan was 4% per year, and this was associated with age and selection for pharmacologic stress testing. In stepwise models replicating the sequence of clinical evaluation, the predictive power of independent clinical predictors (age, selection for pharmacologic stress, previous infarction, and heart failure; model χ2 = 104.8) was significantly enhanced by addition of stress echo data (model χ2 = 122.9).

CONCLUSIONS—The results of stress echo are independent predictors of death in diabetic patients with known or suspected CAD. Ischemia adds risk that is incremental to clinical risks and LV dysfunction.
Albuminuria in Recent-Onset Type 2 Diabetes
Authors: Sosenko Jay M. , Hu Dongsheng , Welty Tom , Howard Barbara V. , Lee Elisa , Robbins David C.
Published: March 2007

OBJECTIVE—It is not known how frequently abnormal albumin excretion occurs in the initial years after the onset of type 2 diabetes and to what extent its occurrence is related to the severity of diabetes. We have used a prospective cohort study to examine this.

RESEARCH DESIGN AND METHODS—A total of 782 participants from the Strong Heart Study who had normal glucose tolerance and normal albumin excretion (albumin-to-creatinine ratio <30 mg albumin/g creatinine) at baseline were assessed for diabetes and abnormal albumin excretion at a follow-up visit (interval 3.91 ± 0.95 years, mean ± SD). Logistic regression models were used to examine the associations.

RESULTS—Abnormal albumin excretion was detected in 52 (6.6%) and diabetes was determined to be present in 105 (13.4%) of the participants at the follow-up visit. In univariate analyses, abnormal albumin excretion was statistically significantly related to the baseline albumin-to-creatinine ratio, diastolic blood pressure, fasting insulin, and extent of American Indian heritage. Abnormal albumin excretion was much more prevalent in those with recent onset diabetes at the follow-up visit (18 vs. 5%, P < 0.001). In a logistic regression analysis, abnormal albumin excretion and diabetes remained strongly related (odds ratio 3.45, P < 0.001), and associations of abnormal albumin excretion with baseline albumin-to-creatinine ratio, blood pressure, and American Indian heritage also remained significant in a separate logistic regression analysis, including only those who developed diabetes. There was a strong association between abnormal albumin excretion and fasting glucose levels (<0.01) at the follow-up visit.

CONCLUSIONS—These data suggest that an appreciable percentage of individuals develop abnormal albumin excretion within the first few years after the onset of type 2 diabetes. Also, the severity of diabetes at onset appears to be a key risk factor for the early development of abnormal albumin excretion.
Relation of Drinking Alcohol to Atherosclerotic Risk in Type 2 Diabetes
Authors: Wakabayashi Ichiro , Kobaba-Wakabayashi Rie , Masuda Hiroshi
Published: March 2007

OBJECTIVE—The effects of drinking alcohol on atherosclerotic risks were investigated in 194 type 2 diabetic patients to determine whether drinking alcohol influences risk of atherosclerosis in diabetic subjects.

RESEARCH DESIGN AND METHODS—The subjects were divided by the degree of their average weekly alcohol consumption into three groups: nondrinkers, light drinkers (ethanol consumption <210 g/week), and heavy drinkers (ethanol consumption ≥210 g/week). The degree of atherosclerotic progression was evaluated using aortic pulse wave velocity (a-PWV), and possible atherosclerotic risks were evaluated using known atherosclerotic risk factors.

RESULTS—a-PWV was significantly lower in light drinkers than in nondrinkers and heavy drinkers, but there was no significant difference in a-PWV between nondrinkers and heavy drinkers. Systolic blood pressure, HDL cholesterol, and triglyceride levels were significantly higher in heavy drinkers than in nondrinkers and light drinkers, whereas there was no significant difference in these levels between nondrinkers and light drinkers. The mean levels of BMI and blood HbA1c, uric acid, and fibrinogen were not different between the three groups. There were significant positive correlations of a-PWV with age and systolic blood pressure and weak but significant negative correlations of a-PWV with alcohol consumption and HDL cholesterol level.

CONCLUSIONS—Light drinking, but not heavy drinking, has preventive effects on atherosclerosis in type 2 diabetic subjects. The known beneficial effects of drinking alcohol on blood lipids and fibrinogen may not be involved in the preventive effect of light drinking on atherosclerosis in diabetic subjects.
Coronary Artery Calcification in Type 2 Diabetes and Insulin Resistance
Authors: Meigs James B. , Larson Martin G. , D’Agostino Ralph B. , Levy Daniel , Clouse Melvin E. , Nathan David M. , Wilson Peter W. F. , O’Donnell Christopher J.
Published: March 2007

OBJECTIVE—To assess risk for subclinical coronary atherosclerosis using electron beam- computed tomography in subjects with or without insulin resistance and with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT/impaired fasting glucose [IFG]) or type 2 diabetes.

RESEARCH DESIGN AND METHODS—We categorized glucose tolerance by type 2 diabetes therapy (diagnosed diabetes) or with an oral glucose tolerance test (OGTT) (IFG, IGT, and OGTT-detected diabetes) and insulin resistance as an elevated fasting insulin level, in subjects attending the fifth examination (1991–1995) of the Framingham Offspring Study. A representative subset of subjects without clinical atherosclerosis was selected for electron beam computed tomography in 1998–1999 from age- and sex-stratified quintiles of the Framingham risk score. The presence of subclinical atherosclerosis was defined as the upper quartile of the Agatston score distribution (score > 170). We assessed risk for subclinical atherosclerosis using multivariable logistic regression.

RESULTS—Of 325 subjects aged 31–73 years, 51% were men, 11.2% had IFG/IGT, and 9.9% had diabetes (2.8% with diagnosed diabetes); 14.5% had insulin resistance. Compared with NGT, subjects with IFG/IGT tended to be more likely (adjusted odds ratio 1.5, 95% CI 0.7–3.4) and those with diabetes were significantly more likely (2.7, 1.2–6.1) to have subclinical coronary atherosclerosis. In age- and sex-adjusted models, subjects with insulin resistance were more likely to have subclinical atherosclerosis than those without insulin resistance (2.1, 1.01–4.2), but further risk factor adjustment weakened this association. In adjusted models including insulin resistance, diabetes remained associated with risk for subclinical atherosclerosis (2.8, 1.2–6.7); diagnosed diabetes (6.0, 1.4–25.2) had a larger effect than OGTT-detected diabetes (2.1, 0.8–5.5).

CONCLUSIONS—Individuals with diabetes have an elevated burden of subclinical coronary atherosclerosis. Aggressive clinical atherosclerosis prevention is warranted, especially in diagnosed diabetes.
Detection of GAD65-Reactive T-Cells in Type 1 Diabetes by Immunoglobulin-Free ELISPOT Assays
Authors: Kotani Reiko , Nagata Masao , Moriyama Hiroaki , Nakayama Maki , Yamada Katsumi , Chowdhury Shahead Ali , Chakrabarty Sagarika , Jin Zhenzi , Yasuda Hisafumi , Yokono Koichi
Published: March 2007

OBJECTIVE—To investigate the prevalence of β-cell autoantigen-reactive peripheral T-cells in type 1 diabetes, we developed an immunoglobulin-free enzyme-linked immunospot (ELISPOT) assay and assessed its usefulness for diagnosing this disease.

RESEARCH DESIGN AND METHODS—Cellular immune responses to β -cell autoantigens were studied both by immunoglobulin-free proliferation assays and ELISPOT assays in 33 patients with type 1 diabetes and 15 patients with type 2 diabetes, compared with 23 healthy control subjects. Autoantibodies against GAD65 and IA-2 were measured by radioimmunoassay.

RESULTS—Significant proliferative responses to GAD65 were observed in 10 of 31 (32.3%) type 1 diabetic patients (P < 0.05), whereas GAD65-reactive γ-interferon (IFN-γ)-secreting cells were detected in 22 of 33 patients (66.7%) by ELISPOT assay (P < 0.001). Of patients negative for both GAD65 and IA-2, five of six (83.3%) showed IFN-γ positivity in ELISPOT and two of five (40.0%) showed significant proliferation against GAD65.

CONCLUSIONS—Using a newly developed ELISPOT assay, GAD-reactive T-helper 1 cells in PBMC of type 1 diabetic patients could be identified at a higher frequency than by the proliferation assay. Therefore, the immunoglobulin-free ELISPOT assay is an excellent tool for detecting T-cell reactivity to autoantigens with greater specificity and, in combination with β-cell autoantibody determination, will improve the diagnosis of type 1 diabetes.
Adherence of Type 1-Fimbriated Escherichia coli to Uroepithelial Cells
Authors: Geerlings Suzanne E. , Meiland Ruby , van Lith Emiel C. , Brouwer Ellen C. , Gaastra Wim , Hoepelman Andy I.M.
Published: March 2007

OBJECTIVE—Women with diabetes have bacteriuria more often than women without diabetes. Because Escherichia coli adhere better to vaginal cells of nondiabetic patients with recurrent urinary tract infections (UTIs) than to those obtained from healthy control subjects, it was hypothesized that E. coli adhere more to the uroepithelial cells of diabetic women, either because of substances excreted in the urine (e.g., albumin, glucose, and Tamm Horsfall protein) or because of a difference in the uroepithelial cells.

RESEARCH DESIGN AND METHODS—A T24 bladder cell line and uroepithelial cells of 25 diabetic women and 19 control subjects were incubated with three different E. coli strains.

RESULTS—The mean numbers of type 1-fimbriated E. coli that adhered to diabetic and control cells were 12.9 and 6.1 (P = 0.001), respectively, whereas those of P-fimbriated E. coli were 8.8 and 8.1 (P = 0.8), and those of nonfimbriated E. coli were 2.7 and 3.4 (P = 0.4). The addition of various substances did not influence the adherence of E. coli to a T24 bladder cell line.

CONCLUSIONS—Type 1-fimbriated E. coli adhere more to diabetic than to control uroepithelial cells.
Are Lower Fasting Plasma Glucose Levels at Diagnosis of Type 2 Diabetes Associated With Improved Outcomes?
Authors: Colagiuri Stephen , Cull Carole A. , Holman Rury R. ,   For the UKPDS Group
Published: March 2007

OBJECTIVE—Type 2 diabetes may be present for several years before diagnosis, by which time many patients have already developed diabetic complications. Earlier detection and treatment may reduce this burden, but evidence to support this approach is lacking.

RESEARCH DESIGN AND METHODS—Glycemic control and clinical and surrogate outcomes were compared for 5,088 of 5,102 U.K. Diabetes Prospective Study participants according to whether they had low (<140 mg/dl [<7.8 mmol/l]), intermediate (140 to <180 mg/dl [7.8 to <10.0 mmol/l]), or high (≥180 mg/dl [≥10 mmol/l]) fasting plasma glucose (FPG) levels at diagnosis. Individuals who presented with and without diabetic symptoms were also compared.

RESULTS—Fewer people with FPG in the lowest category had retinopathy, abnormal biothesiometer measurements, or reported erectile dysfunction. The rate of increase in FPG and HbA1c during the study was identical in all three groups, although absolute differences persisted. Individuals in the low FPG group had a significantly reduced risk for each predefined clinical outcome except stroke, whereas those in the intermediate group had significantly reduced risk for each outcome except stroke and myocardial infarction. The low and intermediate FPG groups had a significantly reduced risk for progression of retinopathy, reduction in vibration sensory threshold, or development of microalbuminuria.

CONCLUSIONS—People presenting with type 2 diabetes with lower initial glycemia who may be earlier in the course of their disease had fewer adverse clinical outcomes despite similar glycemic progression. Since most such people are asymptomatic at diagnosis, active case detection programs would be required to identify them.
Influence of Health Care Providers on the Development of Diabetes Complications
Authors: Zgibor Janice C. , Songer Thomas J. , Kelsey Sheryl F. , Drash Allan L. , Orchard Trevor J.
Published: March 2007

OBJECTIVE—To quantify total diabetes care received (generalist or specialist) from diagnosis onward and its association with the incidence of diabetes complications in a representative cohort of patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 429 subjects from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective follow-up study of childhood-onset type 1 diabetic subjects first seen between 1986 and 1988 (mean age 28 years, mean duration 19 years), followed biennially for up to 10 years were studied. Specialist care was defined as care received from a board-certified endocrinologist, diabetologist, or diabetes clinic and quantified as the percent of diabetes duration spent in specialist care.

RESULTS—There was a significant trend for a higher incidence of neuropathy, overt nephropathy, and coronary artery disease with lower use of specialist care. Multivariate analyses controlling for diabetes duration, demographic characteristics, health care practices, and physiological risk factors demonstrated that higher past use of specialist care was found to be significantly protective against the development of overt nephropathy (risk ratio 0.43, 95% CI 0.21–0.88) and neuropathy (0.54, 0.35–0.83) and weakly protective against coronary artery disease (0.65, 0.37–1.1).

CONCLUSIONS—A higher proportion of diabetes duration spent in specialist care may result in delayed development of certain diabetes complications independent of other risk factors. This study thus supports the concept that the benefits of specialist care should be available to all patients with type 1 diabetes.
Evaluation of Conventional Blood Glucose Monitoring as an Indicator of Integrated Glucose Values Using a Continuous Subcutaneous Sensor
Authors: Zavalkoff Samara R. , Polychronakos Constantin
Published: March 2007

OBJECTIVE—To use a portable continuous glucose monitoring system (CGMS) to evaluate how well the customary intermittent self-monitoring of blood glucose (SMBG) correlates with integrated values during the surrounding time periods in ambulatory patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—In the study, 18 young patients with type 1 diabetes were monitored with CGMS for up to 72 h, during which they continued to perform the four standard SMBG tests (preprandial and bedtime). Correlations were examined between each of the four standard SMBG tests and the mean CGMS values from defined periods that preceded and followed. We also tested how well a low bedtime SMBG predicted nocturnal hypoglycemia.

RESULTS—Strong correlations were found between 1) SMBG at breakfast and the mean CGMS value for the preceding 8 h (r = 0.7514), 2) SMBG at dinner and the CGMS from lunch to dinner (r = 0.7538), 3) SMBG at bedtime and the CGMS from dinner to bedtime (r = 0.8145), and 4) SMBG at bedtime and the CGMS from bedtime to breakfast (r = 0.6463). The remaining correlations were weak and not statistically significant. These correlations seem independent of insulin-delivery method as virtually identical results were obtained when data from patients on conventional versus intensive regimes were separately analyzed. A bedtime SMBG <7 mmol/l did not predict nocturnal hypoglycemia (defined as at least one CGMS value <3).

CONCLUSIONS—The breakfast and dinnertime SMBG values are good indicators of integrated glucose values in the time period preceding them, while the bedtime test correlates well with the integrated values both preceding and following it. This information should aid in the meaningful use of SMBG to evaluate glycemic control and make insulin dose adjustments.
Prevalence of Diabetes Is Higher Among Female than Male Zuni Indians
Authors: Scavini Marina , Stidley Christine A. , Shah Vallabh O. , Narva Andrew S. , Tentori Francesca , Kessler David S. , Bobelu Arlene , Albert Carleton P. , Bobelu Jeanette , Jamon Eunice , Natachu Kathy , Neha Donica , Waikaniwa Mildred , Welty Thomas K. , MacCluer Jean W. , Zager Philip G.
Published: March 2007

OBJECTIVE—Test the hypothesis that diabetes and related risk factors are more common among female than male Zuni Indians.

RESEARCH DESIGN AND METHODS—We conducted a population-based, cross-sectional survey of the Zuni Indians aged ≥5 years. We used households within neighborhood clusters as the sampling frame. We administered a questionnaire, collected blood and urine, and measured height and weight. Self-reported diabetes was used to assess previously diagnosed diabetes. Participants without a prior history of diabetes were classified as having newly diagnosed diabetes if they had HbA1c >7.0% or random glucose ≥11.1 mmol/l during the survey.

RESULTS—The prevalence of previously diagnosed diabetes among Zuni Indians aged ≥5 years (n = 1,503) was higher among female Zuni Indians (16.7% [95% CI 14.1–19.3]) than male Zuni Indians (9.7% [7.4–12.1]) (P < 0.001). The prevalence of newly diagnosed diabetes was similar among female Zuni Indians (2.4% [1.4–3.4]) and male Zuni Indians (2.4% [1.2–3.6]). The prevalence of previously and newly diagnosed diabetes was higher among female Zuni Indians (19.1% [16.4–21.9]) than male Zuni Indians (12.2% [9.5–14.8]) (P < 0.001). The prevalence of obesity was higher among female Zuni Indians (34.3% [30.9–37.7]) than male Zuni Indians (21.5% [18.4–24.7]) (P < 0.001). Obesity was associated with diabetes among female and male Zuni Indians. Physical inactivity was more common among female Zuni Indians (44.2% [40.7–47.8]) than male Zuni Indians (35.1% [31.5–38.7]) (P < 0.001). However, physical inactivity was not associated with diabetes among either female or male Zuni Indians. Gestational diabetes was a risk factor among female Zuni Indians.

CONCLUSIONS—Among the Zuni Indians, the prevalence of diabetes was 57% higher among female than male members of the population. Culture, tradition, and lifestyle differences may contribute to the higher prevalence of diabetes and obesity among female Zuni Indians.
Alcohol Consumption and the Incidence of Type 2 Diabetes
Authors: Carlsson Sofia , Hammar Niklas , Grill Valdemar , Kaprio Jaakko
Published: March 2007

OBJECTIVE—The aim of this study was to investigate alcohol consumption in relation to the incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The study population consisted of 22,778 twins of the Finnish Twin Cohort. This cohort was compiled in 1975 and includes all same-sexed twins born in Finland before 1958. Information on alcohol, smoking, diet, physical activity, medical, and social conditions was obtained by questionnaires administered in 1975, 1981, and 1990. By record linkage to national registers of hospital discharge and prescribed medication, 580 incident cases of type 2 diabetes were identified during 20 years of follow-up.

RESULTS—Moderate alcohol consumption (5–29.9 g/day in men and 5–19.9 g/day in women) tended to be associated with a reduced incidence of type 2 diabetes compared with low consumption (<5 g/day). The estimates were lower in overweight (BMI ≥25.0 kg/m2) subjects (relative risk 0.7, 95% CI 0.5–1.0 [men]; 0.6, 0.3–1.1 [women]). High alcohol consumption (≥20 g/day) was associated with an increased incidence of type 2 diabetes in lean women (2.9, 1.1–7.5) but not in overweight women or in men. In women, binge drinking was associated with an increased incidence of type 2 diabetes (2.1, 1.0–4.4). Analyses of alcohol-discordant twin pairs supported a reduced risk in moderate consuming twins compared with their low-consuming cotwins (odds ratio 0.5, 95% CI 0.2–1.5).

CONCLUSIONS—The results of this study suggested that moderate alcohol consumption may reduce the risk of type 2 diabetes. On the other hand, binge drinking and high alcohol consumption may increase the risk of type 2 diabetes in women.
Signs of Nephropathy May Occur Early in Young Adults With Diabetes Despite Modern Diabetes Management
Authors: Svensson Maria , Sundkvist Göran , Arnqvist Hans J. , Björk Elisabeth , Blohmé Göran , Bolinder Jan , Henricsson Marianne , Nyström Lennarth , Torffvit Ole , Waernbaum Ingeborg , Östman Jan , Eriksson Jan W.
Published: March 2007

OBJECTIVE—To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure.

RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15–34 years. In 1987–1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186).

RESULTS—During the follow-up time, median 9 years (range 6–12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA1c during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure.

CONCLUSIONS—Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA1c, high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.
Diabetes Is Associated With Subclinical Functional Limitation in Nondisabled Older Individuals
Authors: de Rekeneire Nathalie , Resnick Helaine E. , Schwartz Ann V. , Shorr Ronald I. , Kuller Lewis H. , Simonsick Eleanor M. , Vellas Bruno , Harris Tamara B.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the role of comorbid conditions and body composition in the association between diabetes and subclinical functional limitation, an indication of early functional decline, in well-functioning older individuals.

RESEARCH DESIGN AND METHODS—This was a cross-sectional analysis of 3,075 well-functioning black and white men and women aged 70–79 years, enrolled in the Health, Aging, and Body Composition study. Diabetes was defined by self-report and/or hypoglycemic medication use or fasting glucose ≥126 mg/dl. Subclinical functional limitation was defined using self-report of capacity and objective performance measures. Comorbid conditions were identified by self-reported diagnoses, medication use, and clinical measures. Body composition measures included anthropometry and total fat (dual X-ray absorptiometry).

RESULTS—Of 2,926 participants, 1,252 (42.8%) had subclinical functional limitation at baseline. Among 2,370 individuals without diabetes, 40% had subclinical functional limitation, whereas the prevalence was 53% among the 556 diabetic participants with an age/sex/race-adjusted odds ratio (OR) 1.70 (95% CI 1.40–2.06). This association remained significant when adjusted for body composition measures (OR 1.54 [1.26–1.88]), diabetes-related comorbidities, and other potential confounders (OR 1.40 [1.14–1.73]). In the fully adjusted model, consideration of HbA1c (< or ≥7%) and diabetes duration showed that poor glycemic control in diabetic individuals explained the association with subclinical functional limitation.

CONCLUSIONS—In a well-functioning older population, diabetes is associated with early indicators of functional decline, even after accounting for body composition and diabetes-related comorbidities. Poor glycemic control contributes to this relationship. Whether improvement in glycemic control in older people with diabetes would change this association should be tested.
Atorvastatin Dose-Dependently Decreases Hepatic Lipase Activity in Type 2 Diabetes
Authors: Berk-Planken Ingrid I.L. , Hoogerbrugge Nicoline , Stolk Ronald P. , Bootsma Aart H. , Jansen Hans ,   on behalf of the DALI study group
Published: March 2007

OBJECTIVE—Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the hepatic lipase gene, the LIPC promoter variant in type 2 diabetes. Therefore, we studied the effect of atorvastatin 10 mg (A10) and 80 mg (A80) on HL activity in 198 patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Patients (aged 45–75 years, without manifest coronary artery disease, total cholesterol 4.0–8.0 mmol/l, and fasting triglycerides [TG] 1.5–6.0 mmol/l) were included in a double-blind, randomized, placebo-controlled trial for 30 weeks (Diabetes Atorvastatin Lipid Intervention study).

RESULTS—HL activity at baseline was significantly higher in our population compared with an age-matched control group without type 2 diabetes (406 ± 150 vs. 357 ± 118 units/l). HL activity in men versus women (443 ± 158 vs. 358 ± 127 units/l), in carriers of the LIPC C/C allele versus carriers of the T/T allele (444 ± 142 vs. 227 ± 96 units/l), and in Caucasians versus blacks (415 ± 150 vs. 260 ± 127 units/l) all differed significantly (P < 0.001). Atorvastatin dose-dependently decreased HL (A10, −11%; A80, −22%; both P < 0.001). Neither sex nor the LIPC C→T variation influenced the effect of atorvastatin on HL activity.

CONCLUSIONS—Sex, LIPC promoter variant, and ethnicity significantly contribute to the baseline variance in HL activity. Atorvastatin treatment in diabetic dyslipidemia results in a significant dose-dependent decrease in HL activity, regardless of sex or the LIPC promoter variant.