bluuebunny/crossref_metadata_2025 huggingface dataset:
The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid
Authors:   The SYDNEY Trial Authors, for the SYDNEY Trial Study Group:, Ametov Alexander S. , Barinov Alexei , Dyck Peter J. , Hermann Robert , Kozlova Natalia , Litchy William J. , Low Phillip A. , Nehrdich Detlef , Novosadova Maria , O’Brien Peter C. , Reljanovic Miroslav , Samigullin Rustem , Schuette Klemens , Strokov Igor , Tritschler Hans J. , Wessel Klaus , Yakhno Nikolai , Ziegler Dan
Published: March 2007

OBJECTIVE— Because α-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.

RESEARCH DESIGN AND METHODS— Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.

RESULTS— At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.

CONCLUSIONS— Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy.
Impact of Incident Diabetes and Incident Nonfatal Cardiovascular Disease on 18-Year Mortality
Authors: Eberly Lynn E. , Cohen Jerome D. , Prineas Ronald , Yang Lingfeng ,   For The Multiple Risk Factor Intervention Trial Research Group
Published: March 2007

OBJECTIVE— To report long-term risks for total, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality associated with incident diabetes (using current diagnostic criteria) and with incident nonfatal CVD (NF-CVD).

RESEARCH DESIGN AND METHODS— A total of 11,645 participants without diabetes or CVD at baseline from the Multiple Risk Factor Intervention Trial who survived to the end of the trial were grouped by during-trial incident diabetes and/or NF-CVD events: neither diabetes nor NF-CVD, diabetes only, NF-CVD only, or both diabetes and NF-CVD. Incident diabetes was defined by use of hypoglycemic agents or fasting glucose ≥126 mg/dl at any time over the 6 trial years. Proportional hazards models tested group differences in mortality over 18 post-trial years.

RESULTS— Among 3,859 total deaths were 1,846 from CVD and 1,277 from CHD, with death rates per 10,000 person-years of 203, 97, and 67, respectively. Multivariate-adjusted hazard ratios (HRs) for total mortality were 2.75 (P < 0.0001) for those with NF-CVD and diabetes both, 1.92 (P < 0.0001) for those with NF-CVD only, and 1.49 (P < 0.0001) for those with diabetes only, relative to neither diabetes nor NF-CVD. NF-CVD was associated with a higher hazard of death than diabetes for total (HR 1.29, P = 0.0004), CVD (HR 1.76, P < 0.0001), and CHD (HR 1.88, P < 0.0001) mortality. Only the subgroup of participants on hypoglycemic agents showed an equivalent risk of total mortality relative to participants with NF-CVD (HR 0.93, P = 0.54).

CONCLUSIONS— Current diabetes diagnostic criteria conferred significantly increased total, CVD, and CHD mortality risks independent of the impact of NF-CVD. NF-CVD was more strongly predictive of mortality.
Insulin Resistance, the Metabolic Syndrome, and Risk of Incident Cardiovascular Disease in Nondiabetic American Indians
Authors: Resnick Helaine E. , Jones Kristina , Ruotolo Giacomo , Jain Arvind K. , Henderson Jeffrey , Lu Weiquan , Howard Barbara V.
Published: March 2007

OBJECTIVE—Insulin resistance (IR) and the metabolic syndrome (MS) are associated with type 2 diabetes and adverse cardiovascular disease (CVD) risk factor profiles. Whether IR and MS predict CVD independently of diabetes and other CVD risk factors is not known. This study examines whether IR and/or presence of MS are independently associated with CVD in nondiabetic American Indians (AI).

RESEARCH DESIGN AND METHODS—We examined 2,283 nondiabetic AI who were free of CVD at the baseline examination of the Strong Heart Study (SHS). CVD risk factors were measured, IR was quantified using the homeostasis model assessment (HOMA), and MS as defined by the National Cholesterol Education Program Adult Treatment Panel (ATP III) was assessed for each participant. Incident CVD and diabetes were ascertained during follow-up.

RESULTS—MS was present in 798 individuals (35%), and 181 participants (7.9%) developed CVD over 7.6 ± 1.8 years of follow-up. Age, BMI, waist circumference, and triglyceride levels increased and HDL cholesterol decreased across tertiles of HOMA-IR. Risk of diabetes increased as a function of baseline HOMA-IR (6.3, 14.6, and 30.1%; P < 0.001) and MS (12.8 vs. 24.5%). In Cox models adjusted for CVD risk factors, risk of CVD did not increase either as a function of baseline HOMA-IR or MS, but individual CVD risk factors predicted subsequent CVD.

CONCLUSIONS—Among nondiabetic AI in the SHS, HOMA-IR and MS both predict diabetes, but neither predicts CVD independently of other established CVD risk factors.
Type 2 Diabetic Individuals Have Impaired Leg Blood Flow Responses to Exercise
Authors: Kingwell Bronwyn A. , Formosa Melissa , Muhlmann Michael , Bradley Scott J. , McConell Glenn K.
Published: March 2007

OBJECTIVE— Diabetic individuals have impaired endothelium-dependent forearm vasodilatory responses to ischemia, acetylcholine, and other endothelium-dependent agonists. The functional significance of impaired endothelium-dependent dilation in diabetic individuals is uncertain but is most likely to be manifest during leg muscle exercise and may have relevance to peripheral vascular disease and leg ischemia, which is prevalent in diabetic individuals. The current study aimed to determine the relationship between leg blood flow (LBF) responses to endothelium-dependent vasodilation and dynamic large muscle exercise.

RESEARCH DESIGN AND METHODS— LBF responses (thermodilution) to intrafemoral arterial infusions of an endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilator and a standardized 25-min cycling bout at 60% Vo2peak were compared in nine male type 2 diabetic subjects and nine age-, sex-, Vo2peak-, and weight-matched control subjects.

RESULTS— LBF responses to acetylcholine and exercise but not sodium nitroprusside were significantly (P < 0.05) attenuated in patients with diabetes compared with healthy control subjects. The percentage increase in LBF in response to exercise and acetylcholine were significantly correlated (r = 0.54, P = 0.02). Furthermore, resting plasma glucose was significantly related to the LBF response to exercise (r = −0.66, P = 0.003) independently of insulin, HbA1c, lipids, BMI, and blood pressure.

CONCLUSIONS— The increase in LBF during exercise is substantially attenuated in type 2 diabetic compared with matched control subjects. Impaired endothelium-dependent vasodilation secondary to elevated plasma glucose may underlie this observation. This mechanism may be of importance in determining the leg ischemic threshold in diabetic individuals with peripheral vascular disease.
Insulin Pump Therapy
Authors: Weissberg-Benchell Jill , Antisdel-Lomaglio Jeanne , Seshadri Roopa
Published: March 2007

OBJECTIVE—To conduct a meta-analysis of the metabolic and psychosocial impact of continuous subcutaneous insulin infusion (CSII) therapy on adults, adolescents, and children.

RESEARCH DESIGN AND METHODS—Studies were identified and data regarding study design, year of publication, sample size, patient’s age, diabetes duration, and duration of CSII therapy were collected. Means and SDs for glycohemoglobin, blood glucose, insulin dosages, and body weight for CSII and comparison conditions were subjected to meta-analytic procedures. Data regarding pump complications and psychosocial functioning were reviewed descriptively.

RESULTS—A total of 52 studies, consisting of 1,547 patients, were included in the meta-analysis. Results indicate that CSII therapy is associated with significant improvements in glycemic control (decreased glycohemoglobin and mean blood glucose). A descriptive review of potential complications of CSII use (e.g., hypoglycemia, diabetic ketoacidosis [DKA], pump malfunction, and site infections) suggests a decreased frequency of hypoglycemic episodes but an increased frequency of DKA in studies published before 1993.

CONCLUSIONS—CSII therapy is associated with improved glycemic control compared with traditional insulin therapies (conventional therapy and multiple daily injections) and does not appear to be associated with significant adverse outcomes. Additional studies are needed to further examine the relative risks of CSII therapy, including the potential psychosocial impact of this technologically advanced therapy.
International Comparison of Health Resource Utilization in Subjects With Diabetes
Authors: Klarenbach Scott W. , Jacobs Philip
Published: March 2007

OBJECTIVE—To compare health resource utilization in patients with diabetes between the U.S. and Canada.

RESEARCH DESIGN AND METHODS—We combined measures of health care utilization, personal, demographic, health status, functional status, and comorbid conditions from the current National Health Interview Survey (U.S.) and the National Public Health Survey (Canada). A binary logistic regression analysis was used to examine how country of residence influences the probability of accessing health care resources in adult Caucasian subjects after controlling for potential confounders.

RESULTS—Subjects from Canada (n = 521) were more likely to have contact with a general physician (odds ratio [OR] 4.01, 95% CI 2.26–7.14), eye specialists (1.46, 1.08–1. 98), and any physician (3.02, 1.03–8.84) in the past year than their American counterparts (n = 825) but were less likely to have had contact with other medical specialists (0.33, 0.24–0.46). Subjects in Canada were also more likely to have been hospitalized overnight (1.79, 1.17–2.75) or to have contact with a health care professional in the previous 12 months (3.35, 1.01–12.81).

CONCLUSIONS—Significant disparities exist in health service utilization for adult Caucasian individuals with diabetes in Canada versus the U.S. after controlling for various confounders. From what is known regarding optimal treatment of diabetes, those with diabetes in the U.S. have a greater chance of not receiving recommended care.
Long-Term Beneficial Effect of Islet Transplantation on Diabetic Macro-/Microangiopathy in Type 1 Diabetic Kidney-Transplanted Patients
Authors: Fiorina Paolo , Folli Franco , Bertuzzi Federico , Maffi Paola , Finzi Giovanna , Venturini Massimo , Socci Carlo , Davalli Alberto , Orsenigo Elena , Monti Lucilla , Falqui Luca , Uccella Silvia , La Rosa Stefano , Usellini Luciana , Properzi Giuliana , Di Carlo Valerio , Del Maschio Alessandro , Capella Carlo , Secchi Antonio
Published: March 2007

OBJECTIVE—Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients.

RESEARCH DESIGN AND METHODS—A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and d-dimer fragment (DDF)] were studied cross-sectionally.

RESULTS—The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, χ2 = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: Δ1–3 years −13 ± 30 μm vs. UI-K group: Δ1–3 years 245 ± 20 μm, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 ± 4.5% vs. UI-K 0.5 ± 2.7%, P = 0.02), higher basal NO (SI-K 42.9 ± 6.5 vs. UI-K 20.2 ± 6.8 μmol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 ± 15.3 vs. UI-K 180.6 ± 7.0%, P = 0.02) and DDF (SI-K 0.61 ± 0.22 vs. UI-K 3.07 ± 0.68 μg/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF.

CONCLUSIONS—Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patients.
Safety and Effectiveness of Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes
Authors: Plotnick Leslie P. , Clark Loretta M. , Brancati Frederick L. , Erlinger Thomas
Published: March 2007

OBJECTIVE—To evaluate the safety and effectiveness of insulin pump therapy in children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—All 95 patients who began insulin pump therapy at Johns Hopkins Hospital between January 1990 and December 2000 were included in the study. The mean age was 12.0 years (range 4–18), and 29% of the patients were <10 years old. Data were obtained by chart review beginning 6–12 months before pump start. The median duration of follow-up was 28 months.

RESULTS—There was a small but significant decrease in HbA1c at 3–6 months after pump start (7.7 vs. 7.5%; P = 0.03). HbA1c levels then gradually increased and remained elevated after 1 year of follow-up; however, this association was confounded by age and diabetes duration, both of which were associated with higher HbA1c levels. After adjusting for duration and age, mean HbA1c after pump start was significantly lower than before pump start (7.7 vs. 8.1%; P < 0.001). The number of medical complications (diabetic ketoacidosis, emergency department visits) was similar before and after pump start. There were fewer hypoglycemic events after pump start (12 vs. 17, rate ratio 0.46, 95% CI 0.21–1.01).

CONCLUSIONS—This study suggests that pump therapy is safe and effective in selected children and adolescents with type 1 diabetes.
Diabetes and Abnormal Glucose Tolerance in Women With Previous Gestational Diabetes
Authors: Albareda Mercè , Caballero Agueda , Badell Gemma , Piquer Sandra , Ortiz Angels , de Leiva Alberto , Corcoy Rosa
Published: March 2007

OBJECTIVE—In Spanish women with gestational diabetes mellitus (GDM), we aimed to study the progression to diabetes and abnormal glucose tolerance (AGT) and identify predictive factors.

RESEARCH DESIGN AND METHODS—In 696 women with GDM and 70 control women, glucose tolerance was evaluated postpartum and at 5-year intervals.

RESULTS—In the GDM group, the cumulative risk for diabetes and AGT was 13.8 and 42.4% after 11 years compared with 0 and 2.8% in control women, respectively (P < 0.05). Independent predictive factors for diabetes were previous hyperglycemia, four abnormal glucose values on the diagnostic oral glucose tolerance test (OGTT) or overt diabetes during pregnancy, 2-h blood glucose on the diagnostic OGTT ≥11.7 mmol/l, gestational age at diagnosis <24 weeks, and prepregnancy BMI ≥26.4 kg/m2. All of these factors (some with different cutoff points) in addition to fasting glycemia were predictors of AGT also. The risk was nonlinear. Four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy was the strongest predictive factor for diabetes (relative risk 3.92), and prepregnancy BMI was the predictive factor with the highest attributable fraction in the whole group (13.3%). When first postpartum OGTT data were included in the analysis, predictors changed, but the overall prediction was similar.

CONCLUSIONS—Spanish women with GDM have an increased risk of diabetes and AGT. Predictive factors display a nonlinear relationship. The strongest predictive factor for diabetes was four abnormal glucose values on the diagnostic OGTT or overt diabetes during pregnancy; the factor with the highest attributable fraction in the whole group was prepregnancy BMI.
Extrapancreatic Autoimmune Manifestations in Type 1 Diabetes Patients and Their First-Degree Relatives
Authors: Hanukoglu Aaron , Mizrachi Avraam , Dalal Ilan , Admoni Osnat , Rakover Yardena , Bistritzer Zvy , Levine Arie , Somekh Eli , Lehmann Dan , Tuval Myriam , Boaz Mona , Golander Avraham
Published: March 2007

OBJECTIVE—To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects.

RESEARCH DESIGN AND METHODS—The study population included 109 probands age 13 ± 4.9 years and 412 first-degree relatives age 28.7 ± 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 ± 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16–17 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations.

RESULTS—The prevalence of autoimmune thyroiditis determined by high TPO and/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P < 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P < 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P < 0.001) in families with a proband who had an additional autoimmune manifestation.

CONCLUSIONS—Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.
Effects of Withdrawal From Metformin on the Development of Diabetes in the Diabetes Prevention Program
Authors:   The Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—In the Diabetes Prevention Program (DPP), metformin significantly reduced the risk of diabetes in individuals with impaired glucose tolerance. Diabetes status was assessed by oral glucose tolerance tests (OGTTs) performed while participants were still taking metformin or placebo. To determine whether the observed benefit was a transient pharmacological effect or more sustained, we performed a repeat OGTT after a short “washout” period during which medications (metformin or placebo) were withheld.

RESEARCH DESIGN AND METHODS—All participants assigned to medication who had not developed diabetes at the end of the DPP were asked to have a repeat OGTT after discontinuing the study medication for 1–2 weeks. The predesignated outcome was the odds of diabetes in metformin versus placebo comparisons during the trial and washout combined

RESULTS—There were 1,274 participants who participated in the washout study and 529 who did not because they had already developed diabetes. Before the washout, the odds of diabetes in the metformin group was lower than that in the placebo group (odds ratio 0.66, 95% CI 0.54–0.82, P < 0.001). After the washout, diabetes was somewhat more frequently diagnosed in the metformin participants (1.49, 0.93–2.38, P = 0.098). Combining diabetes conversions during the DPP and during the washout, diabetes was diagnosed significantly less frequently in the metformin than the placebo group (0.75, 0.62–0.92, P = 0.005).

CONCLUSIONS—The primary analysis of the DPP demonstrated that metformin decreased the risk of diabetes by 31%. The washout study shows that 26% of this effect can be accounted for by a pharmacological effect of metformin that did not persist when the drug was stopped. After the washout the incidence of diabetes was still reduced by 25%.
Risk Factors for Diabetes in Familial Partial Lipodystrophy, Dunnigan Variety
Authors: Haque Wasim A. , Oral Elif Arioglu , Dietz Kelly , Bowcock Anne M. , Agarwal Anil K. , Garg Abhimanyu
Published: March 2007

OBJECTIVES—Familial partial lipodystrophy, Dunnigan variety (FPLD), is an autosomal dominant disorder due to missense mutations in the lamin A/C (LMNA) gene encoding nuclear lamina proteins. It is characterized by loss of subcutaneous fat from the extremities and trunk and accumulation of fat in the head and neck region beginning at puberty. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to identify risk factors for diabetes in patients with FPLD.

RESEARCH DESIGN AND METHODS—A cross-sectional study comparing clinical, biochemical, and anthropometric variables and LMNA genotypes in FPLD patients with and without diabetes.

RESULTS—We studied 52 women and 24 men with FPLD from 18 different families. Twenty-eight women (54%) but only four men (17%) had diabetes (P < 0.001); therefore further comparisons were mostly limited to women. Compared with women without diabetes, those with diabetes had higher BMI (median values 23 vs. 24 kg/m2, respectively; P = 0.03), increased chin skinfold thickness (10 vs. 20 mm; P = 0.001), lower rates of nulliparity (60% vs. 28%; P = 0.04), and higher levels of fasting serum triglycerides (2.4 vs. 3.5 mmol/l; P < 0.001) but similar serum leptin levels (3.4 vs. 3.6 ng/ml; P = 0.9). The prevalence of diabetes was not related to age, menopausal status, family history of type 2 diabetes in unaffected relatives, or LMNA genotype.

CONCLUSIONS—We conclude that increased adiposity as reflected by excess subcutaneous fat accumulation in the chin region and parity may predispose women with FPLD to develop diabetes.
Audit on Stillbirths in Women With Pregestational Type 1 Diabetes
Authors: Lauenborg Jeannet , Mathiesen Elisabeth , Ovesen Per , Westergaard Jes G. , Ekbom Pia , Mølsted-Pedersen Lars , Damm Peter
Published: March 2007

OBJECTIVE—To audit stillbirth cases in women with type 1 diabetes to search for specific characteristics in order to improve antenatal care and treatment

RESEARCH DESIGN AND METHODS—Retrospectively identified cases of stillbirths in women with type 1 diabetes during 1990–2000 were analyzed regarding characteristics of the mother, the pregnancy, glycemic control, and the stillborn. The cause of stillbirth was categorized as explainable, likely, or without obvious cause.

RESULTS—We found 22 women with 25 stillbirths among 1,361 singleton births by women with type 1 diabetes. In seven stillbirths the cause was categorized as explainable and in six as likely. In 12 cases no obvious cause was found; however, glycemic control was suboptimal in 9 of these cases. A total of 14 women reported daily smoking, and 10 of 19 with low education were unemployed.

CONCLUSIONS—Women experiencing stillbirth were characterized by a high incidence of suboptimal glycemic control, diabetic nephropathy, smoking, and low social status.
Stages of Change for Healthy Eating in Diabetes
Authors: Vallis Michael , Ruggiero Laurie , Greene Geoffrey , Jones Helen , Zinman Bernard , Rossi Susan , Edwards Lynn , Rossi Joseph S. , Prochaska James O.
Published: March 2007

OBJECTIVES—To identify diabetes-related characteristics of individuals at different stages of readiness to change to healthy, low-fat eating.

RESEARCH DESIGN AND METHODS—Stage-based differences in demographic, eating-related, health care utilization, and psychosocial factors were examined in a sample of 768 overweight (BMI >27 kg/m2) individuals with diabetes enrolled in a randomized behavioral intervention trial.

RESULTS—Stage-based differences occurred for type 1 diabetic participants on percent of calories from fat and number of daily vegetable servings. For type 2 diabetic participants, sex, disease-specific quality of life, percent calories from fat, and number of daily vegetables servings differed across stages. Those in action stages were more likely to be female and have a better quality of life and healthier eating habits. Type 2 diabetic insulin-requiring participants in action stages were more likely to be married. Social support was highest for those in the contemplation stage and lowest for those in the action stage. Type 2 diabetic participants on pills in the action stages were older, had a lower BMI, ate more fruit, were nonsmokers, recently attended diabetes education, had a better quality of life and social support, and had less stress. One anomalous finding for type 2 diabetic participants was that precontemplators scored similarly to those in action stages.

CONCLUSIONS—These data validate the Transtheoretical Model, where those in the action stages displayed healthier eating. They also indicate that demographic and psychosocial factors may mediate readiness to change diet. Precontemplators were a heterogeneous group and may need individually tailored interventions.
Evaluation of the Impact of Chiropodist Care in the Secondary Prevention of Foot Ulcerations in Diabetic Subjects
Authors: Plank Johannes , Haas Waltraud , Rakovac Ivo , Görzer Evelyn , Sommer Romana , Siebenhofer Andrea , Pieber Thomas R.
Published: March 2007

OBJECTIVE—To evaluate the influence of regular chiropodist care on the recurrence rate of diabetic foot ulcers within 1 year.

RESEARCH DESIGN AND METHODS—Ninety-one diabetic outpatients with healed foot ulcers (age 65 ± 11 years, 40 women and 51 men, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 ± 4.4, diabetes duration 16 ± 11 years, HbA1c 8.4 ± 1.6%) were randomized to a group that received monthly remunerated routine chiropodist care (n = 47) or a control group (n = 44).

RESULTS—Within a median follow-up of 386 days, ulceration recurred in 18 patients in the chiropodist group and 25 patients in the control group (hazard ratio [HR] 0.60; 95% CI, 0.32, 1.08; P = 0.09). Analysis of ulceration per foot demonstrated a significant reduction (20 vs. 32 ulcerations; Cox relative risk [Cox RR] 0.52; 95% CI, 0.30, 0.93; P = 0.03) in favor of chiropodist care. Per protocol, analysis of patients who actually underwent chiropodist foot care on a regular basis also indicates the beneficial influence of chiropodist care with ulceration in 13 vs. 30 patients (HR, 0.53; 95% CI, 0.30–1.01; P = 0.05) and in 15 vs. 37 feet (Cox RR, 0.46; 95% CI, 0.24–0.90; P = 0.02) for the intervention and control groups, respectively. Minor amputation was required in two patients in the intervention group and one patient in the control group. Four patients in the control group and two patients in the intervention group died during the trial.

CONCLUSIONS—These data suggest that secondary preventive measures by a chiropodist may reduce recurrence of foot ulcers in diabetic patients.
A Simple Meal Plan Emphasizing Healthy Food Choices Is as Effective as an Exchange-Based Meal Plan for Urban African Americans With Type 2 Diabetes
Authors: Ziemer David C. , Berkowitz Kathy J. , Panayioto Rita M. , El-Kebbi Imad M. , Musey Victoria C. , Anderson Lynda A. , Wanko Nancy S. , Fowke Margaret L. , Brazier Carol W. , Dunbar Virginia G. , Slocum Wrenn , Bacha Gael M. , Gallina Daniel L. , Cook Curtiss B. , Phillips Lawrence S.
Published: March 2007

OBJECTIVE—To compare a simple meal plan emphasizing healthy food choices with a traditional exchange-based meal plan in reducing HbA1c levels in urban African Americans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 648 patients with type 2 diabetes were randomized to receive instruction in either a healthy food choices meal plan (HFC) or an exchange-based meal plan (EXCH) to compare the impact on glycemic control, weight loss, serum lipids, and blood pressure at 6 months of follow-up. Dietary practices were assessed with food frequency questionnaires.

RESULTS—At presentation, the HFC and EXCH groups were comparable in age (52 years), sex (65% women), weight (94 kg), BMI (33.5), duration of diabetes (4.8 years), fasting plasma glucose (10.5 mmol/l), and HbA1c (9.4%). Improvements in glycemic control over 6 months were significant (P < 0.0001) but similar in both groups: HbA1c decreased from 9.7 to 7.8% with the HFC and from 9.6 to 7.7% with the EXCH. Improvements in HDL cholesterol and triglycerides were comparable in both groups, whereas other lipids and blood pressure were not altered. The HFC and EXCH groups exhibited similar improvement in dietary practices with respect to intake of fats and sugar sweetened foods. Among obese patients, average weight change, the percentage of patients losing weight, and the distribution of weight lost were comparable with the two approaches.

CONCLUSIONS—Medical nutrition therapy is effective in urban African Americans with type 2 diabetes. Either a meal plan emphasizing guidelines for healthy food choices or a low literacy exchange method is equally effective as a meal planning approach. Because the HFC meal plan may be easier to teach and easier for patients to understand, it may be preferable for low-literacy patient populations.
Two-Hour Insulin Determination Improves the Ability of Abdominal Fat Measurement to Identify Risk for the Metabolic Syndrome
Authors: Ribeiro-Filho Fernando F. , Faria Alessandra N. , Kohlmann Narcia E.B. , Zanella Maria-Teresa , Ferreira Sandra R.G.
Published: March 2007

OBJECTIVE—Visceral obesity is shown to be a predictor of morbidity and mortality. We evaluated the association of measurements of generalized adiposity and visceral fat area (VFA), with abnormalities of metabolic syndrome (MS).

RESEARCH DESIGN AND METHODS—Seventy-six women (47.9 ± 9.2 years) with BMI of 38.7 ± 5.4 kg/m2 underwent anthropometric measurements, laboratory procedures, bioeletrical impedance, and abdominal computed tomography (CT) scan. Diagnosis of MS was based on the presence of abdominal obesity and at least two of the following components: hypertension, dyslipidemia, and glucose intolerance and/or hyperinsulinemia.

RESULTS—BMI was correlated with both components of adipose tissue—subcutaneous (r = 0.66, P < 0.01) and VFA (r = 0.33, P < 0.02)—and leptin levels (r = 0.38, P < 0.01). In contrast, VFA was correlated with 2-h glucose and insulin levels (r = 0.32 and 0.35, P < 0.05, respectively), triglyceride, HDL cholesterol, and uric acid (r = 0.33, −0.34 and 0.24, P < 0.05, respectively). Subjects with high VFA, matched for BMI, showed greater plasma glucose area under the curve (621 ± 127 vs. 558 ± 129 mg · h−1 · dl−1, P < 0.05), 2-h insulin (804 ± 599 vs. 579 ± 347 pmol/l, P < 0.05), and uric acid levels (0.33 ± 0.07 vs. 0.26 ± 0.06 mmol/l, P < 0.05) than subjects with low VFA. In logistic regression analysis, waist circumference, VFA, and 2-h insulin were identified as independent predictors of MS. Receiver operating characteristic curve analysis pointed out the values of 104 cm for waist circumference (58.1% specificity, 84.1% sensitivity), 158.5 cm2 for VFA (78.1% specificity, 52.3% sensitivity), and 559.8 pmol/l for 2-h insulin (71.9% specificity, 69.8% sensitivity); the presence of at least two of the three variables resulted in a degree of concordance of 76%.

CONCLUSIONS—While BMI was unable to differentiate between obese people and those at higher risk for MS, abdominal fat was shown to be associated with its metabolic abnormalities. The usefulness of abdominal fat in the identification of high-risk subjects may be improved when combined with 2-h insulin determination.
Recent Antihyperglycemic Prescribing Trends for U.S. Privately Insured Patients With Type 2 Diabetes
Authors: Cohen Fredric J. , Neslusan Cheryl A. , Conklin Jonathan E. , Song Xue
Published: March 2007

OBJECTIVE—The mid-1990s witnessed the introduction of new classes of medications to treat hyperglycemia of type 2 diabetes. There is evidence that these newer classes have found a place in the therapeutic armamentarium, but details of their use patterns are not known. We sought to determine whether antihyperglycemic prescribing patterns changed concurrently with new drug introductions, and whether such changes were related to changes in the underlying patient population.

RESEARCH DESIGN AND METHODS—A sample of U.S. privately insured patients with suspected type 2 diabetes was identified from the MarketScan Research Database over the period of 1997–2000. Patients with type 2 diabetes were identified among those continuously enrolled in the database for at least 1 year. Drug therapy episodes were defined by sequential fulfillment of prescriptions implying a continuous supply of a particular drug (or combination) of at least 30 days duration. Univariate analyses were used to explore trends over time in drug prescriptions and patient characteristics. Multivariate logistic regressions were used to isolate the impact of year from other variables on the likelihood of receiving prescriptions for a specific therapy.

RESULTS—A total of 232,020 unique diabetic patients had an average of 1.91 diabetes drug therapy episodes between 1997 and 2000. Monotherapy with sulfonylureas decreased, but monotherapy with thiazolidinedione, metformin, and other oral antihyperglycemics increased over time. Combinations of sulfonylureas and metformin; sulfonylureas and thiazolidinedione; metformin and thiazolidinedione; and sulfonylureas, metformin, and thiazolidinedione each increased over the time interval. Insulin monotherapy decreased, as did insulin combination therapy with sulfonylureas. The combination of insulin and metformin increased, whereas insulin and thiazolidinedione was stable. The influence of year on prescribing patterns remained highly significant (P < 0.001) after adjusting for patient characteristics.

CONCLUSIONS—Antihyperglycemic prescription patterns in the U.S. have changed in recent years in parallel with, and probably as a direct result of, the introduction of different classes of medications to the marketplace. Overall, the prescribing trend has been away from monotherapy with insulins and sulfonylureas and toward combination therapies, presumably in attempts to reduce hypoglycemic symptoms and to achieve better glucose control.
Maternal and Fetal Outcomes if Gestational Impaired Glucose Tolerance Is Not Treated
Authors: Östlund Ingrid , Hanson Ulf , Björklund Anders , Hjertberg Ragnhild , Eva Nord , Nordlander Elisabeth , Marja-Liisa Swahn , Wager Jan
Published: March 2007

OBJECTIVE—To evaluate whether there is increased maternal or neonatal morbidity in connection with impaired glucose tolerance (IGT) during pregnancy when the condition is not treated.

RESEARCH DESIGN AND METHODS—During the study period of 1997–2001, in a defined geographical area in Sweden, the diagnostic criteria for gestational diabetes mellitus (GDM) were limited to the criteria for diabetes. Prospectively, 213 women who were identified with IGT during pregnancy were undiagnosed and untreated. Data on maternal and fetal outcome was collected from records. For each case subject, four control subjects were taken from the same delivery department.

RESULTS—The proportion of women who underwent cesarean section was significantly higher in the case subjects than in the control subjects and was independently associated with IGT. The adjusted odds ratio (OR) was 1.9 (95% CI 1.2–2.9). The proportion of infants who were large for gestational age (LGA), defined as birth weight >2 SDs greater than the mean for gestation and sex, was independently significantly associated with untreated IGT during pregnancy (OR 7.3, 95% CI 4.1–12.7). Admission to a neonatal intensive care unit (NICU) for 2 days or longer was more common (adjusted OR 2.0, 95% CI 1.1–3.8). However, 71.3% of the children in the IGT group and 87.3% of the control subjects had no neonatal complications.

CONCLUSIONS—There is increased independent association between cesarean section rate, prematurity, LGA, and macrosomic infants born to mothers with untreated IGT. Most of the children were healthy, but there is still increased morbidity. Therefore, to evaluate the effects of treatment, there is a need for a randomized study.
Spectrum of Autonomic Cardiovascular Neuropathy in Diabetes
Authors: Jacob Giris , Costa Fernando , Biaggioni Italo
Published: March 2007

OBJECTIVE—Diabetic patients with incapacitating orthostatic hypotension can have either a “hyperadrenergic” or “hypoadrenergic” presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction.

RESEARCH DESIGN AND METHODS—We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation.

RESULTS—Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 ± 15 mmHg, heart rate increased 20 ± 3 bpm, and plasma norepinephrine increased from 340 ± 80 to 910 ± 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 ± 5 mmHg, heart rate increased only 7 ± 3 bpm, and norepinephrine increased only from 130 ± 28 to 230 ± 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure.

CONCLUSIONS—Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients’ orthostatic hypotension.
Prevalences of Diabetes and Impaired Glucose Regulation in a Danish Population
Authors: Glümer Charlotte , Jørgensen Torben , Borch-Johnsen Knut
Published: March 2007

OBJECTIVE—To determine the age- and sex-specific prevalence of impaired fasting glycemia, impaired glucose tolerance, screen-detected diabetes, and known diabetes in a Danish population aged 30–60 years and to examine the phenotype and the cardiovascular risk profile in individuals with impaired glucose regulation.

RESEARCH DESIGN AND METHODS—In the Inter99 study, 13,016 inhabitants living in Copenhagen County were invited. All participants underwent anthropometric measurements, blood samples, and a 75-g standardized oral glucose tolerance test.

RESULTS—The age-specific prevalences in men were as follows: impaired fasting glycemia: 1.4–16.3%; impaired glucose tolerance: 6.9–17.8%; screen-detected diabetes: 0.7–9.7%; and known diabetes: 0–5.8%. The corresponding figures in women were 0–5.1, 10.5–17.3, 0.6–6.3, and 0.5–9%. The prevalence of impaired glucose regulation increased with age. Among individuals with diabetes, 65.6% were previously undiagnosed; this proportion was highest in the youngest age-group (82% among 45-year-old men vs. 63% among 60-year-old men, and 70% among 45-year-old women vs. 52% among 60-year-old women). Mean BMI, waist, HbA1c, systolic blood pressure, diastolic blood pressure, and total cholesterol were significantly higher (P < 0.0001) in the individuals with impaired glucose regulation compared with individuals with normal glucose tolerance.

CONCLUSIONS—This study revealed that the prevalence of type 2 diabetes is high and that still two out of three individuals are undiagnosed, indicating a need for more attention to the disease in society.
Low Incidence of End-Stage Renal Disease and Chronic Renal Failure in Type 2 Diabetes
Authors: Bruno Graziella , Biggeri Annibale , Merletti Franco , Bargero Giuseppe , Ferrero Stefania , Pagano Gianfranco , Perin Paolo Cavallo
Published: March 2007

OBJECTIVE—Data on the incidence of end-stage renal disease (ESRD) and chronic renal failure from population-based studies in Caucasian type 2 diabetic patients are lacking. To provide such data, a population-based cohort of type 2 diabetic patients was identified in Casale Monferrato, Italy, and prospectively examined from 1991 to 2001.

RESEARCH DESIGN AND METHODS—During the follow-up period, patients were regularly examined with centralized measurements of plasma creatinine and HbA1c. Independent predictors of progression to renal events were identified with multivariate Cox proportional hazards modeling, with sex, age, and individual follow-up time as confounders.

RESULTS—We followed 1,408 of 1,540 (91.4%) patients (average follow-up time 6.7 years, range 0.011–11.1); 10 new cases of ESRD and 72 of chronic renal failure (plasma values of creatinine ≥2.0 mg/dl) were identified, giving incidence rates/1,000 person-years of 1.04 (95% CI 0.56–1.94) and 7.63 (6.06–9.61), respectively. Cumulative risks for chronic renal failure adjusted for competing mortality were 6.1 and 9.3% after 20 and 30 years from diagnosis of diabetes, respectively. Incidence rates and cumulative risks of chronic renal failure defined by plasma creatinine values >1.5 mg/dl increased to 13.1/1,000 person-years, 8.6 and 14.8%, respectively. In Cox regression analysis, predictors of progression (after adjustment for confounders) were hypertension (P = 0.078), diastolic blood pressure (P = 0.034), BMI (P = 0.03), and albumin excretion rate (AER) (P < 0.0001).

CONCLUSIONS—We provide evidence that the individual risk of ESRD and chronic renal failure is low. AER and diastolic blood pressure are independent predictors of progression. These findings underline the relevance of primary prevention to reduce the number of diabetic patients with ESRD.
Effect on Glycemic Control of Exenatide (Synthetic Exendin-4) Additive to Existing Metformin and/or Sulfonylurea Treatment in Patients With Type 2 Diabetes
Authors: Fineman Mark S. , Bicsak Thomas A. , Shen Larry Z. , Taylor Kristin , Gaines Eling , Varns Amanda , Kim Dennis , Baron Alain D.
Published: March 2007

OBJECTIVE—AC2993 (synthetic exendin-4; exenatide) is a peptide that enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. AC2993 also promotes β-cell proliferation and neogenesis in vitro and in animal models. This study examines the activity and safety of subcutaneously injected AC2993 in patients with type 2 diabetes currently treated with diet and/or oral antidiabetic agents (OAAs).

RESEARCH DESIGN AND METHODS—A total of 109 patients treated with diet and a sulfonylurea and/or metformin were enrolled in a blinded study. Patients were randomly assigned to one of three subcutaneously (SC) injected regimens of AC2993 (0.08 μg/kg) or placebo for 28 days.

RESULTS—All three AC2993 regimens led to significant reductions in serum fructosamine relative to placebo (P ≤ 0.004). Mean reductions ranged from 39 to 46 μmol/l. All AC2993 groups had reductions in HbA1c ranging from 0.7 to 1.1% (P ≤ 0.006). An end-of-study HbA1c <7% was achieved by 15% of AC2993 patients versus 4% of placebo patients, confirming AC2993 effects on fasting and postprandial glycemia. On days 14 and 28, the β-cell index (homeostasis model assessment) for patients treated with AC2993 was 50–100% higher than baseline, contrasting with unchanged levels for placebo. The most common adverse event was transient mild-to-moderate nausea.

CONCLUSIONS—AC2993 is a promising therapeutic for patients with type 2 diabetes. In this study, it had significant effects on HbA1c levels in patients not currently achieving optimal glucose control with diet and/or OAAs.
Hyperbaric Oxygenation Accelerates the Healing Rate of Nonischemic Chronic Diabetic Foot Ulcers
Authors: Kessler Laurence , Bilbault Pascal , Ortéga Francoise , Grasso Claire , Passemard Raphael , Stephan Dominique , Pinget Michel , Schneider Francis
Published: March 2007

OBJECTIVE—To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers.

RESEARCH DESIGN AND METHODS—From 1999 to 2000, 28 patients (average age 60.2 ± 9.7 years, diabetes duration 18.2 ± 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I–III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.

RESULTS—HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPo2) measured on the dorsum of the feet of the patients was 45.6 ± 18.1 mmHg (room air). During HBO, the TcPo2 measured around the ulcer increased significantly from 21.9 ± 12.1 to 454.2 ± 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 ± 25.5 vs. 21.7 ± 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 ± 30.3 vs. 41.7 ± 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.

CONCLUSIONS—In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.