bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Obstructive Pulmonary Disease, Asthma, and Risk of Type 2 Diabetes in Women
Authors: Rana Jamal S. , Mittleman Murray A. , Sheikh Javed , Hu Frank B. , Manson JoAnn E. , Colditz Graham A. , Speizer Frank E. , Barr R. Graham , Camargo Carlos A.
Published: March 2007

OBJECTIVE—Inflammation plays a key role in chronic obstructive pulmonary disease (COPD) and asthma. Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD and asthma with the development of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Nurses’ Health Study is a prospective cohort study. From 1988–1996, 103,614 female nurses were asked biennially about a physician diagnosis of emphysema, chronic bronchitis, asthma, and diabetes.

RESULTS—During 8 years of follow-up, we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2 diabetes was significantly higher for patients with COPD than those without (multivariate relative risk 1.8, 95% CI 1.1–2.8). By contrast, the risk of type 2 diabetes among asthmatic patients was not increased (1.0, 0.8–1.2). The asthma results remained nonsignificant even when we evaluated diabetes risk by duration of asthma exposure.

CONCLUSIONS—Our findings suggest that COPD may be a risk factor for developing type 2 diabetes. Differences in the inflammation and cytokine profile between COPD and asthma might explain why COPD, but not asthma, is associated with increased risk of type 2 diabetes.
Induction of Long-term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients Is Associated With Improvement of β-Cell Function
Authors: Li Yanbing , Xu Wen , Liao Zhihong , Yao Bin , Chen Xiahua , Huang Zhimin , Hu Guoliang , Weng JianPing
Published: March 2007

OBJECTIVE—To investigate whether long-term optimal glycemic control can be achieved without medication by transient continuous subcutaneous insulin infusion (CSII) and the possible mechanisms responsible for this remission.

RESEARCH DESIGN AND METHODS—Newly diagnosed type 2 diabetic patients (n = 138, fasting glucose >11.1mmol/l) were hospitalized and treated with CSII for 2 weeks. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, HbA1c, lipid profiles, proinsulin, insulin, and C-peptide were measured before and after CSII. Patients were followed longitudinally on diet alone after withdrawal of insulin.

RESULTS—Optimal glycemic control was achieved within 6.3 ± 3.9 days by CSII in 126 patients. The remission rates (percentages maintaining near euglycemia) at the third, sixth, twelfth, and twenty-fourth month were 72.6, 67.0, 47.1, and 42.3%, respectively. Patients who maintained glycemic control >12 months (remission group) had greater recovery of β-cell function than those who did not (nonremission group) when assessed immediately after CSII. Homeostasis model assessment of β-cell function (HOMA-B) and the area under the curve (AUC) of insulin during IVGTT were higher in the remission group (145.4 ± 89.6 vs. 78.5 ± 68.5, P = 0.002, and 1,423.4 ± 523.2 vs. 1,159.5 ± 476.8 pmol · l−1 · min−1, P = 0.044). Change in acute insulin response was also greater in the remission group than that in the nonremission group (621.8 ± 430.4 vs. 387.3 ± 428.8 pmol · l−1 · min−1, P = 0.033).

CONCLUSIONS—Short-term intensive insulin therapy can induce long-term glycemic control in newly diagnosed type 2 diabetic patients with severe hyperglycemia. The improvement of β-cell function, especially the restoration of first-phase insulin secretion, could be responsible for the remission.
Diabetes Is the Main Factor Accounting for the High Ferritin Levels Detected in Chronic Hepatitis C Virus Infection
Authors: Lecube Albert , Hernández Cristina , Genescà Joan , Esteban Joan I. , Jardí Rosend , García Lydia , Simó Rafael
Published: March 2007

OBJECTIVE—A high prevalence of diabetes has been reported in patients with hepatitis C virus (HCV) infection. Both diabetes and HCV infection are associated with high serum ferritin levels. Although HCV infection could be the main factor responsible for the high ferritin levels, it is also possible that diabetes rather than HCV infection might be a major contributor to the high ferritin levels observed in patients with HCV infection. The aim of this study was to investigate the contribution of diabetes to the high ferritin levels observed in HCV-infected patients with chronic hepatitis.

RESEARCH DESIGN AND METHODS—A total of 634 noncirrhotic individuals were prospectively recruited at a university hospital. According to the HCV antibody status and the presence of diabetes, the subjects were divided into four groups: group A (anti–HCV-positive diabetic patients, n = 53), group B (anti–HCV-negative diabetic patients, n = 242), group C (anti–HCV-positive nondiabetic patients, n = 191), and group D (anti–HCV-negative nondiabetic control subjects, n = 148). Multiple regression analyses were used to explore the variables independently related to ferritin levels.

RESULTS—Serum ferritin levels in group A were significantly higher than in the other groups (A > B, P < 0.01; A > C, P < 0.001; A > D, P < 0.001). Ferritin levels were higher in group B than in group D (P = 0.001). However, group C has ferritin values similar to those of group D. In multivariate analyses, diabetes but not HCV infection was independently related to serum ferritin concentrations.

CONCLUSIONS—Diabetes rather than HCV infection itself is the main factor associated with the increased ferritin levels detected in patients with HCV infection. Therefore, the presence of diabetes should be taken into account when iron metabolism is evaluated in HCV-infected patients.
Diagnosis of Type 2 Diabetes at an Older Age
Authors: Tan Hwee H. , McAlpine Ritchie R. , James Peter , Thompson Philip , McMurdo Marion E.T. , Morris Andrew D. , Evans Josie M.M. ,   DARTS/MEMO Collaboration
Published: March 2007

OBJECTIVE—To compare the mortality of people who were diagnosed with type 2 diabetes over 65 years of age with that of nondiabetic individuals.

RESEARCH DESIGN AND METHODS—Using a population-based diabetes information system for an observational cohort study in Tayside, Scotland, people who were diagnosed with type 2 diabetes over the age of 65 years between 1993 and 2002 were identified. Nondiabetic comparators, matched for age and sex, were identified from the nondiabetic population. The two cohorts were followed up for mortality and cardiovascular mortality according to death certification records.

RESULTS—There were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators identified in the study. Over a mean follow-up period of 4.6 ± 2.9 years for 3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The adjusted relative risk for mortality in the diabetic cohort compared with the nondiabetic cohort was 1.06 (95% CI 0.94–1.19) for men and 1.29 (1.15–1.45) for women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and 45.2% in those without diabetes (adjusted relative risk 1.01 [0.93–1.10]).

CONCLUSIONS—Men diagnosed with type 2 diabetes over the age of 65 years have no excess mortality compared with their nondiabetic counterparts, a finding that was not replicated for women.
Clinical Outcomes and Adherence to Medications Measured by Claims Data in Patients With Diabetes
Authors: Pladevall Manel , Williams L. Keoki , Potts Lisa Ann , Divine George , Xi Hugo , Elston Lafata Jennifer
Published: March 2007

OBJECTIVE—Although poor medication adherence may contribute to inadequate diabetes control, ways to feasibly measure adherence in routine clinical practice have yet to be established. The present study was conducted to determine whether pharmacy claims-based measures of medication adherence are associated with clinical outcomes in patients with diabetes.

RESEARCH DESIGN AND METHODS—The study setting was a large, integrated delivery and financial system serving the residents of southeastern Michigan. The study population consisted of 677 randomly selected patients aged ≥18 years with a diagnosis of diabetes, hypercholesterolemia, and hypertension and who filled at least one prescription for either an antidiabetic, lipid-lowering, or antihypertensive drug in each of the 3 study years (1999–2001). The main outcome measures were HbA1c, LDL cholesterol levels, and blood pressure.

RESULTS—Nonadherent patients had both statistically and clinically worse outcomes than adherent patients. Even after adjusting for demographic and clinical characteristics, nonadherence was significantly associated with HbA1c and LDL cholesterol levels. A 10% increase in nonadherence to metformin and statins was associated with an increase of 0.14% in HbA1c and an increase of 4.9 mg/dl in LDL cholesterol levels. Nonadherence to ACE inhibitors was not significantly associated with blood pressure.

CONCLUSIONS—Claims-based measures of medication adherence are associated with clinical outcomes in patients with diabetes and may therefore prove to be useful in clinical practice. More research is needed on methods to introduce claims-based adherence measurements into routine clinical practice and how to use these measurements to effectively improve adherence and health outcomes in chronic care management.
Factors Associated With Preterm Delivery in Women With Type 1 Diabetes
Authors: Lepercq Jacques , Coste Joel , Theau Anne , Dubois-Laforgue Daniele , Timsit Jose
Published: March 2007

OBJECTIVE—The reported rate of preterm delivery in women with type 1 diabetes ranges from 22 to 45%, but the reasons are unclear. The purpose of this study was to identify factors associated with preterm delivery in these women.

RESEARCH DESIGN AND METHODS—We studied the influence of maternal and diabetes-related factors on the occurrence of preterm delivery in 168 single pregnancies occurring in 127 women with type 1 diabetes. Women with spontaneous or indicated preterm delivery were compared with those who delivered after 37 weeks of gestation using polytomous logistic regression.

RESULTS—The overall rate of preterm delivery was 24%, fivefold higher than the French prematurity rate in single pregnancy. Preterm delivery was spontaneous in 9% and indicated in 15%. HbA1c ≥7% at delivery was associated with spontaneous preterm delivery (odds ratio [OR] 5.3 [95% CI 1.1–26.8]). Nulliparity (12.0 [2.3–64.1]), progression of nephropathy (7.7 [1.3–46.9]), preeclampsia (12.0 [3.1–47.1]), and HbA1c ≥7% (7.5 [1.5–37.9]) at delivery were all associated with indicated preterm delivery. Preterm delivery was associated with significant neonatal morbidity as the risks for neonatal hypoglycemia and respiratory distress syndrome were increased by three- to sixfold compared with the reference group.

CONCLUSIONS—The rate of preterm delivery remains high in women with type 1 diabetes. Different factors were associated with spontaneous and indicated preterm delivery, respectively. Because poor glycemic control was a risk factor for both outcomes, part of preterm delivery might be preventable.
Peripheral Arterial Disease, Diabetes, and Mortality
Authors: Leibson Cynthia L. , Ransom Jeanine E. , Olson Wayne , Zimmerman Bruce R. , O’Fallon W. Michael , Palumbo Pasquale J.
Published: March 2007

OBJECTIVE—The aims of this study were to provide estimates of 1) the risk of mortality for individuals with both diabetes and peripheral arterial disease (PAD) relative to that for individuals with either condition alone and 2) the association between PAD progression and mortality for individuals with diabetes, PAD, and both conditions.

RESEARCH DESIGN AND METHODS—This longitudinal cohort study was conducted in Rochester, Minnesota. Local residents age 50–70 years with a prior diagnosis of PAD and/or diabetes were identified from the Mayo Clinic diagnostic registry and invited to a baseline examination (1977–1978). Those who met inclusion criteria were assessed for PAD progression at 2 and 4 years and followed for vital status through 31 December 1999.

RESULTS—The numbers who met criteria for PAD, diabetes, and both conditions at baseline were 149, 238, and 186, respectively. Within each group, observed survival was less than expected (P < 0.001). The adjusted risk of death for both conditions was 2.2 times that for PAD alone. Among the 449 who returned at 4 years, the risk of subsequent death was greater for those whose PAD had progressed; among individuals with diabetes alone at baseline, 100% (17 of 17) who met criteria for PAD progression were dead by 31 December 1999 compared with 62% (111 of 178) of those who had not met criteria (adjusted relative hazard 2.29 [95% CI 1.30–4.02], P = 0.004). The increased mortality associated with PAD progression was significant only for individuals with diabetes (alone or with PAD).

CONCLUSIONS—Diabetes is a risk factor for both PAD and PAD-associated mortality, emphasizing the critical need to detect and monitor PAD in diabetic patients.
Family and Disease Management in African-American Patients With Type 2 Diabetes
Authors: Chesla Catherine A. , Fisher Lawrence , Mullan Joseph T. , Skaff Marilyn M. , Gardiner Phillip , Chun Kevin , Kanter Richard
Published: March 2007

OBJECTIVE—The aim of this project is to specify features of family life that are associated with disease management in African Americans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 159 African-American patients with type 2 diabetes were assessed on three domains of family life (structure/organization, world view, and emotion management) and three key dimensions of disease management (morale, management behaviors, and glucose regulation). Analyses assessed the associations of family factors with disease management.

RESULTS—Multivariate tests for the main effects of three family variables were significantly related to the block of disease management variables for morale (F = 3.82; df = 12,363; P < 0.0001) and behavior (2.12; 9,329; P < 0.03). Structural togetherness in families was positively related to diabetes quality of life (DQOL)–Satisfaction (P < 0.01). High family coherence, a world view that life is meaningful and manageable, was positively associated with general health (P < 0.05) and DQOL-Impact (P < 0.05) and negatively associated with depressive symptoms (P < 0.001). Emotion management, marked by unresolved family conflict about diabetes, was related to more depressive symptoms (P < 0.001), lower DQOL-Satisfaction (P < 0.01), and lower DQOL-Impact (P < 0.001). No family measures were related to HbA1c levels.

CONCLUSIONS—The family domain of emotion management demonstrates the strongest associations with diabetes management in African-American patients, followed by family beliefs. Patient morale is the aspect of disease management that seems most related to family context.
The Impact of the Micro-Lightguide O2C for the Quantification of Tissue Ischemia in Diabetic Foot Ulcers
Authors: Beckert Stefan , Witte Maria B. , Königsrainer Alfred , Coerper Stephan
Published: March 2007

OBJECTIVE—Tissue oxygen supply is crucial for wound healing. Especially in diabetic foot lesions, the chances for healing are mainly dependent on the presence or absence of ischemia. This study investigates the impact of the tissue O2 analysis system “O2C” for noninvasive quantification of tissue oxygenation in diabetic foot ulcer patients.

RESEARCH DESIGN AND METHODS—O2C assessed relative blood flow (flow), flow velocity (velo), and hemoglobin concentration (rHb) and hemoglobin oxygenation (SO2) at 2 and 6 mm depth (means ± SE). 1) Measurements were performed on intact skin of the forefoot and forearm of 20 healthy volunteers on 2 consecutive days. 2) Parameters were assessed on intact skin of the forefoot of diabetic foot ulcer patients (n = 14). 3) Measurements were performed directly at the wound site in diabetic patients (n = 14).

RESULTS—1) Flow, velo, rHb, and SO2 at 2 and 6 mm depth were not significantly different when measured at 2 consecutive days. 2) There were no significant differences between diabetic subjects and healthy volunteers. Only flow in 6 mm depth was significantly higher in diabetic subjects (75 ± 13 vs. 51 ± 0.4 arbitrary units [AU], P < 0.05). When diabetic foot ulcer patients were split into healers and nonhealers, initial readings of SO2 at 2 mm (32 ± 6 vs. 44 ± 3%, P < 0.05) and flow in 6 mm (28 ± 1 vs. 51 ± 0.6 AU, P < 0.05) were significantly reduced in nonhealers compared with control subjects, whereas in healers flow in 6 mm (70 ± 0.6 vs. 51 ± 0.6 AU, P < 0.05) was significantly higher than that in control subjects. 3) Initial SO2, rHb, flow, and velo were significantly lower in nonhealing compared with healing wounds.

CONCLUSIONS—O2C is a new reliable and valid method for noninvasive measurement of tissue oxygenation and microvascular blood flow in patients with diabetic foot ulcers.
Continuous Glucose Monitoring and the Reality of Metabolic Control in Preschool Children With Type 1 Diabetes
Authors: Jeha George S. , Karaviti Lefkothea P. , Anderson Barbara , O’Brian Smith E. , Donaldson Susan , McGirk Toniean S. , Haymond Morey W.
Published: March 2007

OBJECTIVE—To determine using the MiniMed continuous glucose monitoring system (CGMS) 1) whether twice-daily insulin injection therapy achieves adequate control in preschool children with type 1 diabetes and 2) whether the CGMS is more informative than self-monitoring of blood glucose (SMBG) regarding glucose control and well tolerated by preschool children and their families.

RESEARCH DESIGN AND METHODS—Ten children <6 years of age with type 1 diabetes were monitored twice using the CGMS. The distribution of glucose values was analyzed, particularly the frequency, duration, and distribution of hypoglycemia. We analyzed the accuracy of the CGMS in detecting hypoglycemia as well as the clinical relevance of the difference between CGMS and SMBG values.

RESULTS—Although hypoglycemia was more frequent during the night (0.8 nighttime episodes · subject–1 · 24 h–1 vs. 0.3 daytime episodes · subject–1 · 24 h–1), the difference did not reach statistical significance (P = 0.07). However, nighttime episodes lasted longer than daytime episodes (1.2 vs. 0.2 h · subject–1 · 24 h–1, P = 0.006). Hypoglycemia accounted for 7% and normoglycemia for 24%, while hyperglycemia occurred 64% of the time, with postprandial hyperglycemia being an almost universal feature (94 ± 7% of all postmeal values). The CGMS correlated well with SMBG without significant clinical discrepancy. The CGMS sensitivity to detect hypoglycemia was 70% with a specificity of 99%; however, the CGMS detected twice as many total episodes as SMBG (82 vs. 40).

CONCLUSIONS—Twice-daily insulin injection rarely achieves control in preschool children with type 1 diabetes. The CGMS is well tolerated by patients and has the advantage of revealing daily glucose trends missed by SMBG.
Two-Year Statin Therapy Does Not Alter the Progression of Intima-Media Thickness in Patients With Type 2 Diabetes Without Manifest Cardiovascular Disease
Authors: Beishuizen Edith D. , van de Ree Marcel A. , Jukema J. Wouter , Tamsma Jouke T. , van der Vijver J. Carel M. , Meinders A. Edo , Putter Hein , Huisman Menno V.
Published: March 2007

OBJECTIVE—Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD.

RESEARCH DESIGN AND METHODS—A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years.

RESULTS—Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P < 0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P = 0.006).

CONCLUSIONS—There was no effect of 2 years’ statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group.
Plasma Vascular Endothelial Growth Factor, Angiopoietin-1, and Angiopoietin-2 in Diabetes
Authors: Lim Hoong Sern , Blann Andrew D. , Chong Aun Yeong , Freestone Bethan , Lip Gregory Y.H.
Published: March 2007

OBJECTIVE—Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 are mediators of angiogenesis. More recent data suggest that the balance between these growth factors may affect vascular endothelial integrity. Because diabetes is closely associated with endothelial perturbation, we studied plasma levels of these angiogenic growth factors in patients with diabetes; their relationship with glycemia, inflammation, and endothelial damage/dysfunction; and the effect of intensified cardiovascular risk management.

RESEARCH DESIGN AND METHODS—We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von Willebrand factor (vWf) and urine albumin–to–creatinine ratio (marking endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with overt cardiovascular disease [CVD]) with diabetes and 34 normal control subjects.

RESULTS—Plasma vWf (P = 0.009), IL-6 (P < 0.001), VEGF (P = 0.001), and Ang-2 (P = 0.001), but not Ang-1 (P = 0.635), were higher in diabetic patients with and without CVD than in control subjects. On multivariate analysis, HbA1c was an independent predictor of plasma VEGF (P = 0.032) and Ang-2 (P = 0.015). Of the 94 patients, a subgroup of 33 patients with and 31 patients without CVD participated in a year of intensified cardiovascular risk management. HbA1c and LDL cholesterol reduced significantly with treatment, along with associated reductions in plasma vWf and VEGF in both groups (P < 0.001). Ang-2 decreased (P < 0.001) only in patients without CVD. There were no significant changes in plasma IL-6 levels in both groups.

CONCLUSIONS—Plasma Ang-2 (but not Ang-1), like VEGF levels, are selectively elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction, regardless of vascular disease. Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment.
Autonomic Symptoms and Diabetic Neuropathy
Authors: Low Phillip A. , Benrud-Larson Lisa M. , Sletten David M. , Opfer-Gehrking Tonette L. , Weigand Stephen D. , O’Brien Peter C. , Suarez Guillermo A. , Dyck Peter J.
Published: March 2007

OBJECTIVE—The prevalence of autonomic symptoms and deficits in certain systems is known, but a comprehensive autonomic symptom profile in diabetes is not available. We aimed to estimate this using a laboratory evaluation of autonomic function and a validated self-report measure of autonomic symptoms in patients and matched control subjects from the population-based Rochester Diabetic Neuropathy Study.

RESEARCH DESIGN AND METHODS—Participants included 231 patients with diabetes (type 1, n = 83; type 2, n = 148) and 245 healthy age-matched control subjects. We assessed symptoms using a validated self-report instrument (Autonomic Symptom Profile) and evaluated the severity and distribution of autonomic deficits (cardiovagal, sudomotor, adrenergic) with the objective, laboratory-based Composite Autonomic Severity Score (CASS).

RESULTS—Autonomic symptoms were present more commonly in type 1 than in type 2 diabetes, with symptoms of orthostatic intolerance, secretomotor, urinary control, diarrhea, and sleep disturbance and pupillomotor, vasomotor, and erectile dysfunction significantly increased over healthy control subjects in type 2 diabetic patients. The prevalence of autonomic impairment was 54% in type 1 and 73% in type 2 diabetic patients. Severity of autonomic failure was mild overall (mean CASS 2.3; maximum 10), with orthostatic hypotension occurring in 8.4 and 7.4% of type 1 and 2 diabetic patients, respectively. Fourteen percent of patients had a CASS ≥5, indicating moderate to severe generalized autonomic failure. The correlation of symptoms with autonomic deficits (CASS) was better in type 1 than type 2 diabetic subjects and was weak overall.

CONCLUSIONS—These findings indicate that autonomic symptoms and deficits are common in diabetes, but mild in severity, and that the correlation between symptom scores and deficits is overall weak in mild diabetic neuropathy, emphasizing the need to separately evaluate autonomic symptoms.
Sex-Related Differences Between Adiponectin and Insulin Resistance in Schoolchildren
Authors: Tsou Pei-Ling , Jiang Yi-Der , Chang Ching-Chung , Wei Jung-Nan , Sung Fung-Chang , Lin Chau-Ching , Chiang Chuan-Chi , Tai Tong-Yuan , Chuang Lee-Ming
Published: March 2007

OBJECTIVE—To study the effect of body composition and adiponectin on insulin resistance and β-cell function in schoolchildren during puberty.

RESEARCH DESIGN AND METHODS—Plasma adiponectin level and its relationships with insulin sensitivity and β-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6–18 years in a national survey program for diabetes in 1999. Insulin resistance and β-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay.

RESULTS—Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in β-cell function during this period. A transient drop of adiponectin level with a trough at 10–12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = −0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15–18 years and in girls aged 11–14 years. No association was observed between adiponectin levels and β-cell function by HOMA.

CONCLUSIONS—There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.
Low Cardiorespiratory Fitness Is Associated With Elevated C-Reactive Protein Levels in Women With Type 2 Diabetes
Authors: McGavock Jonathan M. , Mandic Sandra , Vonder Muhll Isabelle , Lewanczuk Richard Z. , Quinney H. Arthur , Taylor Dylan A. , Welsh Robert C. , Haykowsky Mark
Published: March 2007

OBJECTIVE—The purpose of this study was to examine differences in novel markers of cardiovascular disease (CVD) in women with type 2 diabetes stratified according to cardiorespiratory fitness.

RESEARCH DESIGN AND METHODS—A total of 28 women (mean age 57 ± 6 years) with type 2 diabetes who were free from overt CVD were placed into low cardiorespiratory fitness (LCF) or average cardiorespiratory fitness (ACF) groups based on a graded exercise test to exhaustion. A group of eight women without type 2 diabetes were also examined and served as healthy control subjects. The median V˙o2peak value was used as a cutoff for group determination. We assessed both conventional CVD risk factors, including blood pressure, BMI, and lipid profile, as well as novel CVD risk factors, such as left ventricular filling dynamics, arterial stiffness, fasting insulin, and C-reactive protein (CRP).

RESULTS—V˙o2peak values were 69 ± 14 and 91 ± 24% of predicted values for sedentary age-matched healthy individuals in the LCF and ACF groups, respectively. BMI was significantly greater in the LCF group (P < 0.05); however, no differences were observed in age, lipid profile, or resting hemodynamics. CRP was 3.3-fold higher in the LCF group (6.3 ± 41. vs. 1.9 ± 1.7 mg/l, P < 0.05), whereas other novel markers of CVD were not significantly different between the groups. Significant negative relationships were observed between V˙o2peak and both CRP (r = −0.49) and the homeostasis model assessment index (r = −0.48) (P < 0.05).

CONCLUSIONS—The novel finding of this investigation is that low cardiorespiratory fitness is associated with elevated CRP and reduced fasting glucose control in women with type 2 diabetes.
Ethnic Differences in Insulin Sensitivity and β-Cell Function in Premenopausal or Early Perimenopausal Women Without Diabetes
Authors: Torréns Javier I. , Skurnick Joan , Davidow Amy L. , Korenman Stanley G. , Santoro Nanette , Soto-Greene Maria , Lasser Norman , Weiss Gerson
Published: March 2007

OBJECTIVE—To assess differences in insulin sensitivity and β-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non–Mexican-American Latino women.

RESEARCH DESIGN AND METHODS—Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and β-cell function (HOMA%β) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%β between non-Hispanic whites and each of the four ethnic groups.

RESULTS—HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non–Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%β than non-Hispanic whites, whereas African Americans had higher HOMA%β than non-Hispanic whites after correcting for confounders. HOMA%β was similar between non–Mexican-American Latinos and non-Hispanic whites.

CONCLUSIONS—These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and β-cell function. Previous studies of Mexican-American populations may not apply to non–Mexican-American Latino women.
Cardiac Abnormalities in Diabetic Patients With Neuropathy
Authors: Johnson Brian F. , Nesto Richard W. , Pfeifer Michael A. , Slater William R. , Vinik Aaron I. , Chyun Deborah A. , Law Gordon , Wackers Frans J.Th. , Young Lawrence H.
Published: March 2007

OBJECTIVE—The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy.

RESEARCH DESIGN AND METHODS—Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year.

RESULTS—After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group.

CONCLUSIONS—Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.
Nondipping and Its Relation to Glomerulopathy and Hyperfiltration in Adolescents With Type 1 Diabetes
Authors: Torbjörnsdotter Torun B. , Jaremko Georg A. , Berg Ulla B.
Published: March 2007

OBJECTIVE—To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a <7%, diastolic nondippers as a <14%, and mean arterial blood pressure (MAP) nondippers as a <12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA1c were measured.

RESULTS—MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA1c than dippers.

CONCLUSIONS—Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.
Predictors of the Incident Metabolic Syndrome in Adults
Authors: Palaniappan Latha , Carnethon Mercedes R. , Wang Yun , Hanley Anthony J.G. , Fortmann Stephen P. , Haffner Stephen M. , Wagenknecht Lynne
Published: March 2007

OBJECTIVE—To prospectively investigate predictors of the incident metabolic syndrome in nondiabetic adults.

RESEARCH DESIGN AND METHODS—This analysis included 714 white, black, and Hispanic participants in the Insulin Resistance Atherosclerosis Study (IRAS) who were free of the metabolic syndrome at baseline; 139 of these developed the metabolic syndrome in the subsequent 5 years. We examined measures of glucose (fasting and 2 h), insulin (fasting and 2 h, acute insulin response, insulin sensitivity [Si], and proinsulin), lipids (HDL and triglycerides), blood pressure (systolic and diastolic), waist circumference, and baseline physical activity (total energy expenditure) as predictors of the metabolic syndrome. Logistic regression models were adjusted for age, sex, study site, ethnicity, and impaired glucose tolerance. Signal detection analysis was used to identify the characteristics of the highest risk group.

RESULTS—The best predictors of incident metabolic syndrome were waist circumference (odds ratio [OR] 1.7 [1.3–2.0] per 11 cm), HDL cholesterol (0.6 [0.4–0.7] per 15 mg/dl), and proinsulin (1.7 [1.4–2.0] per 3.3 pmol/l). Signal detection analysis identified waist circumference (>89 cm in women, >102 cm in men) as the optimal predictor.

CONCLUSIONS—These findings suggest that obesity may precede the development of other metabolic syndrome components. Interventions that address obesity and reduce waist circumference may reduce the incidence of the metabolic syndrome in nondiabetic adults.
Preclinical Atherosclerosis and Inflammation in 61-Year-Old Men With Newly Diagnosed Diabetes and Established Diabetes
Authors: Sigurdardottir Vilborg , Fagerberg Björn , Hulthe Johannes
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the occurrence of subclinical atherosclerosis and underlying mechanisms in men with newly diagnosed diabetes and established diabetes compared with healthy control subjects.

RESEARCH DESIGN AND METHODS—In a population-based study of 61-year-old Caucasian men (n = 271) with established diabetes (n = 50) and newly diagnosed diabetes (n = 24) and healthy control subjects (n = 197), standard risk factors and highly sensitive (hs) C-reactive protein (CRP) were measured. Ultrasound measurements of intima-media thickness (IMT) were performed bilaterally in the common carotid artery, and a composite measure was calculated from common carotid and carotid bulb IMT (composite IMT). The plaque status was assessed.

RESULTS—Composite IMT and carotid plaque size increased gradually among the healthy control subjects, newly diagnosed diabetic patients, and established diabetic patients (P for trend ≤0.001, respectively). CRP was higher in newly and established diabetes (NS between diabetes groups) compared with healthy control subjects (P < 0.001). Total cholesterol levels were lower in newly diagnosed diabetes (5.51 ± 1.13 mmol/l, P < 0.05) and established diabetes (5.45 ± 1.15 mmol/l, P < 0.01) compared with those of healthy control subjects (5.77 ± 1.03 mmol/l). In men with diabetes (n = 74), diabetes onset status (newly diagnosed versus established), waist-to-hip ratio (WHR), and serum triglycerides, but not CRP, explained 16% of the variance in composite IMT.

CONCLUSIONS—This is the first study to show increased preclinical atherosclerotic changes (IMT and plaque size) and increased inflammation (hs-CRP) in men with newly diagnosed diabetes as well as in patients with established diabetes compared with healthy control subjects. WHR, diabetes onset status (newly diagnosed versus established), and triglycerides, but not CRP, were independent correlates of carotid artery IMT in men with diabetes.
Role of Simvastatin as an Immunomodulator in Type 2 Diabetes
Authors: Lopes-Virella Maria F. , Mironova Marina , Stephan Elias , Durazo-Arvizu Ramon , Virella Gabriel
Published: March 2007

OBJECTIVE—To test the hypothesis that simvastatin reduces the levels of circulating immune complexes (ICs) containing modified lipoproteins (mLDLs; mLDL-ICs), which may represent an additional mechanism for the reduced incidence of cardiovascular events in patients treated with simvastatin.

RESEARCH DESIGN AND METHODS—A total of 26 patients with type 2 diabetes and triglyceride levels <400 mg/dl who were not receiving lipid-lowering medications or CYP 3A4 inhibitors were enrolled in the study. After 2 weeks on a lipid-lowering diet and exercise, the patients were started on simvastatin 20 mg/day. The dose of simvastatin was adjusted until the levels of LDL cholesterol were ≤100 mg/dl. Blood was collected at baseline, 3 and 6 months after LDL cholesterol levels reached target, and 3 months after stopping simvastatin to measure advanced glycation end product LDL and oxidized LDL antibodies, mLDL-IC, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, metalloproteinase-1 (MMP-1), lipid profile, liver function tests, creatinine kinase, glucose, and HbA1c.

RESULTS—Twenty-one patients completed the study. Their HbA1c remained within 1% of baseline levels. There was a highly significant decrease in mLDL-IC levels after 3 and 6 months of treatment with simvastatin, with a return to near baseline levels after discontinuation.

CONCLUSIONS—Simvastatin significantly reduced the concentration of mLDL-IC, probably as a consequence of both a decrease in the formation of mLDL and to a reduction in the titers of mLDL antibodies. This effect is likely to have a beneficial impact in the inflammatory reaction associated with atherosclerosis.
Telecare for Patients With Type 1 Diabetes and Inadequate Glycemic Control
Authors: Montori Victor M. , Helgemoe Pamela K. , Guyatt Gordon H. , Dean Diana S. , Leung Teresa W. , Smith Steven A. , Kudva Yogish C.
Published: March 2007

OBJECTIVE—To determine the efficacy of telecare (modem transmission of glucometer data and clinician feedback) to support intensive insulin therapy in patients with type 1 diabetes and inadequate glycemic control.

RESEARCH DESIGN AND METHODS—Thirty-one patients with type 1 diabetes on intensive insulin therapy and with HbA1c >7.8% were randomized to telecare (glucometer transmission with feedback) or control (glucometer transmission without feedback) for 6 months. The primary end point was 6-month HbA1c. To place our findings in context, we pooled HbA1c change from baseline reported in randomized trials of telecare identified in a systematic review of the literature.

RESULTS—Compared with the control group, telecare patients had a significantly lower 6-month HbA1c (8.2 vs. 7.8%, P = 0.03, after accounting for HbA1c at baseline) and a nonsignificant fourfold greater chance of achieving 6-month HbA1c ≤7% (29 vs. 7%; risk difference 21.9%, 95% CI −4.7 to 50.5). Nurses spent 50 more min/patient giving feedback on the phone with telecare patients than with control patients. Meta-analysis of seven randomized trials of adult patients with type 1 diabetes found a 0.4% difference (95% CI 0–0.8) in HbA1c mean change from baseline between the telecare and control groups.

CONCLUSIONS—Telecare is associated with small effects on glycemic control in patients with type 1 diabetes on intensive insulin therapy but with inadequate glycemic control.
Contrasting Diabetes Phenotypes Associated With Hepatocyte Nuclear Factor-1α and -1β Mutations
Authors: Pearson Ewan R. , Badman Michael K. , Lockwood Christopher R. , Clark Penelope M. , Ellard Sian , Bingham Coralie , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—Mutations in the highly homologous transcription factors hepatocyte nuclear factor (HNF)-1α and -1β cause maturity-onset diabetes of the young types 3 and 5, respectively. Diabetes due to HNF-1α mutations is well characterized. However, physiological assessment of the HNF-1β phenotype is limited. We aimed to test the hypothesis that the diabetes phenotype due to HNF-1β mutations is similar to that in HNF-1α.

RESEARCH DESIGN AND METHODS—Fasting biochemistry and a tolbutamide-modified intravenous glucose tolerance test (IVGTT) were compared in matched HNF-1β, HNF-1α, type 2 diabetic, and control subjects. Homeostasis model assessment indexes were determined from fasting insulin and glucose. The peak measures for the insulin increment after tolbutamide and for the insulin increment after glucose were determined from the IVGTT.

RESULTS—The HNF-1β patients showed a 2.4-fold reduction in insulin sensitivity compared with the HNF-1α patients (P = 0.001) with fasting insulin concentrations 2.7-fold higher (P = 0.004). HNF-1β patients had lower HDL cholesterol (1.17 vs. 1.46 mmol/l; P = 0.009) and higher triglyceride (2.2 vs. 1.35 mmol/l; P = 0.015) levels than HNF-1α patients. The HNF-1β patients had similar β-cell responses to tolbutamide and glucose as the type 2 diabetic patients, but in the HNF-1α patients, the tolbutamide response was considerably increased relative to the response to glucose (P = 0.002).

CONCLUSIONS—HNF-1β patients have a different diabetes phenotype than HNF-1α patients. Those with HNF-1β mutations have hyperinsulinemia and associated dyslipidemia consistent with insulin resistance and may have a different β-cell defect. This suggests that despite considerable homology and a shared binding site, HNF-1α and HNF-1β have a different role in maintaining normal glucose homeostasis. This result suggests a new etiological pathway for insulin resistance involving HNF-1β.
Influence of Caffeine on Heart Rate Variability in Patients With Long-Standing Type 1 Diabetes
Authors: Richardson Tristan , Rozkovec Adrian , Thomas Peter , Ryder Jacqueline , Meckes Candy , Kerr David
Published: March 2007

OBJECTIVE—The effect of caffeine on cardiovascular health remains controversial. Patients with long-standing type 1 diabetes are at risk of autonomic failure and sudden cardiac death. We investigated the effects of caffeine on autonomic dysfunction (as assessed by heart rate variability [HRV]) in this high-risk group and in a control population.

RESEARCH DESIGN AND METHODS—Using a randomized blinded, placebo-controlled, crossover design trial, we examined 2 weeks of caffeine consumption (250 mg twice daily) on HRV in 20 type 1 diabetic patients and 10 matched healthy volunteers.

RESULTS—Baseline HRV was blunted in the diabetic patients (P < 0.0005 vs. control subjects) and markedly increased by caffeine in both groups (+103% in the group with diabetes [P = 0.009] and +38% in control subjects [P = 0.002]). The caffeine-associated increase in HRV was not statistically different between the control and the type 1 diabetes groups (P = 0.16).

CONCLUSIONS—Modest amounts of caffeine improved autonomic function in diabetic patients and healthy volunteers. For individuals with abnormal HRV, regular caffeine use may have the potential to reduce the risk of cardiovascular events.
Risk of Community-Acquired Pneumococcal Bacteremia in Patients With Diabetes
Authors: Wernich Thomsen Reimar , Holmager Hundborg Heidi , Lervang Hans-Henrik , Paaske Johnsen Søren , Schønheyder Henrik Carl , Toft Sørensen Henrik
Published: March 2007

OBJECTIVE—We conducted this population-based case-control study to examine whether diabetes is associated with an increased risk of community-acquired pneumococcal bacteremia.

RESEARCH DESIGN AND METHODS—We included 598 cases in the North Jutland County Bacteremia Registry, Denmark, with residence in the county and a first hospitalization for community-acquired pneumococcal bacteremia from 1992 through 2001. Ten sex- and age-matched population control subjects per case were selected, using a unique personal identifier. Diabetes was determined by record linkage with the County Prescription Database (for prescriptions for antidiabetic drugs) and the Hospital Discharge Registry (for previous hospitalizations with diabetes or diabetic complications). We performed conditional logistic regression to estimate odds ratios (ORs) for pneumococcal bacteremia among diabetic and nondiabetic persons, with adjustment for a range of comorbid diseases considered to be risk factors for pneumococcal infection.

RESULTS—The crude OR for pneumococcal bacteremia in persons with diabetes was 1.9 (95% CI 1.4–2.6). After adjustment for comorbidity, the OR decreased to 1.5 (95% CI 1.1–2.0). The impact of diabetes on the risk for pneumococcal bacteremia was most pronounced in adults aged 40 years and younger (adjusted OR 4.2, 95% CI 1.1–16.7) and in persons without any other coexisting morbidity (adjusted OR 2.3, 95% CI 1.3–3.9). Under the assumptions that the association was causal and that there is a 5% overall prevalence of diabetes in our study population, 24 of 1,000 admissions with incident pneumococcal bacteremia may be attributed to diabetes.

CONCLUSIONS—Diabetes seems to be a risk factor for community-acquired pneumococcal bacteremia.