bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dysfunction in Women With Type 1 Diabetes
Authors: Enzlin Paul , Mathieu Chantal , Van den Bruel Annick , Bosteels Jan , Vanderschueren Dirk , Demyttenaere Koen
Published: March 2007

OBJECTIVE—This study aimed to 1) examine the prevalence of sexual problems in women with type 1 diabetes, 2) compare this prevalence rate with that of an age-matched control group, 3) study the influence of diabetes-related somatic factors on female sexuality, and 4) study the influence of psychological variables on the sexual functioning of both groups.

RESEARCH DESIGN AND METHODS—A total of 120 women with diabetes visiting the outpatient diabetes clinic completed questionnaires evaluating psychological adjustment to diabetes, marital satisfaction, depression, and sexual functioning. Medical records were used to obtain data on HbA1c, use of medication, BMI, and early-onset microvascular complications. An age-matched control group of 180 healthy women attending an outpatient gynecological clinic for preventive routine gynecological assessment also completed the non–diabetes-related questionnaires.

RESULTS—More women with diabetes than control subjects reported sexual dysfunction (27 vs. 15%; P = 0.04), but a significant difference was found only for decreased lubrication. No association was found between sexual dysfunction and age, BMI, duration of diabetes, HbA1c, use of medication, menopausal status, or complications. Women with more complications, however, reported significantly more sexual dysfunctions, and the presence of complications altered treatment satisfaction. Both diabetic and control women with sexual dysfunction mentioned lower overall quality of the marital relation and more depressive symptoms than their respective counterparts without sexual problems. Depression was a significant predictor for sexual dysfunction in both women with diabetes and control subjects.

CONCLUSIONS—Sexual problems are frequent in women with diabetes. They affect the overall quality of life and deserve more attention in clinical practice and research.
Additional Lunchtime Basal Insulin During Insulin Lispro Intensive Therapy in a Randomized, Multicenter, Crossover Study in Adults
Authors: Stades Aline M.E. , Hoekstra Joost B.L. , van den Tweel Ingeborg , Erkelens D. Willem , Holleman Frits ,   STABILITY Study Group
Published: March 2007

OBJECTIVE—This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night.

RESEARCH DESIGN AND METHODS—The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 × NPH) or twice (2 × NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA1c levels <8.5%. Efficacy measures were HbA1c levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials.

RESULTS—In all, 104 patients completed the trial. The mean HbA1c level before randomization was 7.1 ± 0.85%. The HbA1c levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] −0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 × NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 × NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively.

CONCLUSIONS—Equal HbA1c levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 × NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.
The Rising Prevalence of Diabetes and Impaired Glucose Tolerance
Authors: Dunstan David W. , Zimmet Paul Z. , Welborn Timothy A. , de Courten Maximilian P. , Cameron Adrian J. , Sicree Richard A. , Dwyer Terry , Colagiuri Stephen , Jolley Damien , Knuiman Matthew , Atkins Robert , Shaw Jonathan E. ,   On Behalf of the AusDiab Steering Committee
Published: March 2007

OBJECTIVE—To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data.

RESEARCH DESIGN AND METHODS—A national sample involving 11,247 participants aged ≥25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance.

RESULTS—The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25–34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity.

CONCLUSIONS—Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.
Do Sensor Glucose Levels Accurately Predict Plasma Glucose Concentrations During Hypoglycemia and Hyperinsulinemia?
Authors: Monsod Teresa P. , Flanagan Daniel E. , Rife Fran , Saenz Rebecca , Caprio Sonia , Sherwin Robert S. , Tamborlane William V.
Published: March 2007

OBJECTIVE—The MiniMed Continuous Glucose Monitoring System (CGMS) measures subcutaneous interstitial glucose levels that are calibrated against three or more fingerstick glucose levels daily. The objective of the present study was to examine whether the relationship between plasma and interstitial fluid glucose is altered by changes in plasma glucose and insulin levels and how such alterations might influence CGMS performance.

RESEARCH DESIGN AND METHODS—Arterialized plasma glucose, sensor glucose, and interstitial fluid glucose were measured by microdialysis in 11 healthy subjects during a 1.0 mU · kg−1 · min−1 stepped euglycemic-hypoglycemic-hyperglycemic (plasma glucose ∼5, 3.1, and 8.6 mmol/l, respectively) insulin clamp that raised plasma insulin to ∼360–390 pmol/l.

RESULTS—When the CGMS was calibrated versus plasma glucose levels before insulin infusion, basal sensor and plasma glucose were similar (5.0 ± 0.3 vs. 5.2 ± 0.3 mmol/l, respectively); dialysate glucose was 3.3 ± 0.9 mmol/l. During the hyperinsulinemic-euglycemia study (plasma glucose 4.9 ± 0.3 mmol/l), dialysate glucose fell by 30–35%, accompanied by a significant reduction in sensor glucose (to 3.7 ± 0.6 mmol/l; P < 0.001 vs. plasma). Subsequently, sensor levels remained lower than plasma values during mild hypoglycemia (2.5 ± 0.6 vs. 3.1 ± 0.3 mmol/l; P < 0.01) and during recovery from hypoglycemia (7.3 ± 1.2 vs. 8.6 ± 0.6; P < 0.01). However, when the CGMS was calibrated against plasma glucose levels before and during each step of the clamp, sensor glucose levels increased throughout the study and did not differ from plasma glucose values during hypoglycemia.

CONCLUSIONS—Although hyperinsulinemia may contribute to modest discrepancies between plasma and sensor glucose levels, the CGMS is able to accurately track acute changes in plasma glucose when calibrated across a range of plasma glucose and insulin levels.
Impact of Simultaneous Pancreas and Kidney Transplantation on Progression of Coronary Atherosclerosis in Patients With End-Stage Renal Failure due to Type 1 Diabetes
Authors: Jukema J. Wouter , Smets Yves F. C. , van der Pijl Johan W. , Zwinderman Aeilko H. , Vliegen Hubert W. , Ringers Jan , Reiber Johan H. C. , Lemkes Herman H. P. J. , van der Wall Ernst E. , de Fijter Johan W.
Published: March 2007

OBJECTIVE—Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK.

RESEARCH DESIGN AND METHODS—We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis.

RESULTS—Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035).

CONCLUSIONS—Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.
Influence of Cardiac Autonomic Neuropathy on Heart Rate Dependence of Ventricular Repolarization in Diabetic Patients
Authors: Valensi Paul E. , Johnson Nicolas B. , Maison-Blanche Pierre , Extramania Fabrice , Motte Gilbert , Coumel Philippe
Published: March 2007

OBJECTIVE—Prolongation of the QT interval and increased QT dispersion are associated with a poor cardiac prognosis. The goal of this study was to assess the long-term influence of the autonomic nervous system on the heart rate dependence of ventricular repolarization in patients with diabetic autonomic neuropathy (DAN).

RESEARCH DESIGN AND METHODS—We studied 27 subjects (mean age 51.8 years) divided into three age- and sex-matched groups: nine control subjects, nine diabetic subjects with DAN (mostly at a mild stage; DAN+), and nine diabetic subjects without DAN (DAN−). DAN was assessed on heart rate variations during standard maneuvers (Valsalva, deep-breathing, and lying-to-standing maneuvers). No subject had coronary artery disease or left ventricular dysfunction or hypertrophy, and no subject was taking any drugs known to prolong the QT interval. All subjects underwent electrocardiogram and 24-h Holter recordings for heart rate variations (time and frequency domain) and QT analysis (selective beat averaging QT/RR relation, nocturnal QT lengthening).

RESULTS—Rate-corrected QT intervals (Bazett formula) did not differ significantly between the three groups. The diurnal and nocturnal levels of low frequency/high frequency, an index of sympathovagal balance, were significantly reduced in DAN+ subjects. Using the selective beat–averaging technique, a day-night modulation of the QT/RR relation was evidenced in control and DAN− subjects. This long-term modulation was significantly different in DAN+ subjects, with a reversed day-night pattern and an increased nocturnal QT rate dependence.

CONCLUSIONS—In diabetic patients with mild parasympathetic denervation, QT heart rate dependence was found to be impaired, as determined by noninvasive assessment using Holter data. Analysis of ventricular repolarization could represent a sensitive index of the progression of neuropathy. The potential prognostic impact of a reversed day-night pattern with steep nocturnal QT/RR relation still remains to be defined.
Impact of Diabetes Screening on Quality of Life
Authors: Edelman David , Olsen Maren K. , Dudley Tara K. , Harris Amy C. , Oddone Eugene Z.
Published: March 2007

OBJECTIVE—Diagnosis of a chronic illness can have a negative impact on patients’ perception of their well-being (“labeling” effect). We sought to determine the effects of a new diagnosis of diabetes, discovered by systematic screening, on patients’ health-related quality of life (HRQoL) 1 year after diagnosis.

RESEARCH DESIGN AND METHODS—We performed diabetes screening at the Durham Veterans Affairs Medical Center of 1,253 outpatients, aged 45–64 years, who did not report having diabetes. Our initial screen was a serum HbA1c measurement. All subjects with HbA1c ≥6.0% were invited for follow-up measurement of blood pressure and fasting plasma glucose. A case of unrecognized diabetes was defined as HbA1c ≥7.0% or fasting plasma glucose ≥7 mmol/dl. HRQoL was measured by Medical Outcomes Study Short Form 36 (SF-36) for all patients at baseline and 1 year after enrollment. Linear multivariable models were used to determine the independent effect of the new diagnosis of diabetes on HRQoL.

RESULTS—Mean SF-36 Physical Component Score (PCS) for all patients was 36.2, and mean Mental Component Score (MCS) was 49.6. A total of 56 patients (4.5%) were found to have diabetes at screening. Patients found to have diabetes at screening had mean PCS of 35.6, which was not different from a mean PCS of 36.3 for those patients found not to have diabetes (P = 0.67). After adjusting for baseline PCS values, PCS 1 year after screening was similar for patients with and without diabetes found at screening (P = 0.95). Similarly, patients found to have diabetes at screening had mean MCS of 48.8; those found not to have diabetes had MCS of 49.6 (P = 0.70). After adjusting for baseline MCS values, MCS 1 year after screening was also similar between the two groups (P = 0.77).

CONCLUSIONS—For patients with a new diagnosis of diabetes discovered through systematic screening, HRQoL is similar to patients found not to have diabetes. Furthermore, HRQoL scores remain stable over the year after screening. This suggests that screening for diabetes has minimal, if any, “labeling” effect with respect to HRQoL.
Use of a Novel Double-Antibody Technique to Describe the Pharmacokinetics of Rapid-Acting Insulin Analogs
Authors: Lindström Torbjörn , Hedman Christina A. , Arnqvist Hans J.
Published: March 2007

OBJECTIVE—To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 14 patients with type 1 diabetes, aged 35 ± 13 years (mean ± SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.

RESULTS—The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 ± 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 ± 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 ± 3 min and aspart at 55 ± 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.

CONCLUSIONS—The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.
Rapid Changes in Postprandial Blood Glucose Produce Concentration Differences at Finger, Forearm, and Thigh Sampling Sites
Authors: Ellison John M. , Stegmann Janet M. , Colner Sandra L. , Michael Ragui H. , Sharma Manoj K. , Ervin Kenneth R. , Horwitz David L.
Published: March 2007

OBJECTIVE—To compare pre- and postmeal capillary blood glucose concentrations measured at the finger, forearm, and thigh in adults with diabetes.

RESEARCH DESIGN AND METHODS—For phase 1, capillary blood glucose concentrations were measured at six time points (premeal and at ∼60, 90, 120, 150, and 180 min postmeal) using a blood glucose monitoring system and technician-obtained samples collected from finger, forearm, and thigh sites of 42 adults with diabetes. The finger samples were also tested with a laboratory instrument. For phase 2, ∼14 weeks later, the testing procedures were repeated with 38 subjects from the original study population.

RESULTS—Meter finger results were accurate at all time points. Alternate sites tended to produce lower glucose readings compared to finger readings at times when glucose was increasing rapidly (60 and 90 min postmeal). Forearm-to-finger differences correlated with rates of glucose change (r = 0.56, P < 0.001), as did the thigh-to-finger differences (r = 0.52, P < 0.001). Other factors, such as subject age, BMI, diabetes type, and insulin dependence did not have a significant impact on site differences. When the testing procedures were repeated with the same subjects, the pattern of site differences was consistent, although individual results were variable.

CONCLUSIONS—Changes in blood glucose immediately after a meal may be identified at finger sites before detection at forearm or thigh sites. Alternate site testing appears to be a useful option for routine self-monitoring before meals; however, patients and clinicians should recognize that results may be different from fingertip results when glucose levels are changing rapidly.
C-Reactive Protein, Diabetes, and Attendance at Religious Services
Authors: King Dana E. , Mainous Arch G. , Pearson William S.
Published: March 2007

OBJECTIVE—Previous studies have shown an association between attendance at religious services and health, particularly cardiovascular morbidity and mortality. People with diabetes have higher risk of cardiovascular mortality and higher C-reactive protein (CRP) levels than people without diabetes. The purpose of this study was to explore the relationship between religious attendance and CRP in people with diabetes.

RESEARCH DESIGN AND METHODS—This study used cross-sectional survey and examination of a nationally representative sample of noninstitutionalized U.S. adults aged ≥40 years, derived from the National Health and Nutrition Examination Survey III 1988–1994 (n = 10,059). There were 556 people with diabetes. The primary outcome measure was the presence of elevated CRP.

RESULTS—There were no differences between people with diabetes compared with people without diabetes in the percentage of those who attended religious services (62.29 vs. 62.0%, P = 0.36). Religious service nonattenders with diabetes were more likely than attenders to have an elevated CRP (odds ratio [OR] 2.17 [95% CI 1.15–4.09]). In people without diabetes, the association between attendance and CRP was not significant (P > 0.05). Among people with diabetes, after adjusting for demographic variables, health status, smoking, social support, mobility, and BMI, the association between religious attendance and CRP remained significant for respondents with diabetes (1.90 [1.03–3.51]).

CONCLUSIONS—These findings revealed that people with diabetes who have not attended religious services in the previous year are more likely to have elevated levels of CRP. Further research should be conducted to evaluate this association to improve our understanding of the psychological and religious factors that influence diabetes.
IA-2 Antibody-Negative Status Predicts Remission and Recovery of C-Peptide Levels in Type 1 Diabetic Patients Treated With Cyclosporin
Authors: Christie Michael R. , Mølvig Jens , Hawkes Charlotte J. , Carstensen Bendix , Mandrup-Poulsen Thomas ,   the Canadian-European Randomised Control Trial Group
Published: March 2007

OBJECTIVE—The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker.

RESEARCH DESIGN AND METHODS—IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry.

RESULTS—Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative.

CONCLUSIONS—The results demonstrate that IA-2 antibody analysis is valuable in identifying individuals for whom immunosuppressive treatment would be most effective.
Atorvastatin and Micronized Fenofibrate Alone and in Combination in Type 2 Diabetes With Combined Hyperlipidemia
Authors: Athyros Vasilios G. , Papageorgiou Athanasios A. , Athyrou Valasia V. , Demitriadis Dimokritos S. , Kontopoulos Athanasios G.
Published: March 2007

OBJECTIVE—This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile, in comparison to each drug alone, in patients with type 2 diabetes and combined hyperlipidemia (CHL).

RESEARCH DESIGN AND METHODS—A total of 120 consecutive patients, who were free of coronary artery disease (CAD) at entry, were studied for a period of 24 weeks. These patients were randomly assigned to atorvastatin (20 mg/day, n = 40), micronized fenofibrate (200 mg/day, n = 40), or a combination of both (atorvastatin 20 mg/day plus fenofibrate 200 mg/day, n = 40). The effect of treatment on LDL cholesterol, triglycerides (TGs), HDL cholesterol, apolipoprotein A-I and B, lipoprotein(a), and plasma fibrinogen (PF) was recorded. Moreover, the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated.

RESULTS—No patient was withdrawn from the study because of side effects. The atorvastatin-fenofibrate combination reduced total cholesterol by 37%, LDL cholesterol by 46%, TGs by 50%, and PF by 20%, whereas it increased HDL cholesterol by 22% (P < 0.0001 for all). These changes were significantly better than those of both monotherapies. Of the patients on drug combination, 97.5% reached the LDL cholesterol treatment goal of <100 mg/dl, 100% reached the desirable TG levels of <200 mg/dl, and 60% reached the optimal HDL cholesterol levels of >45 mg/dl. These rates were significantly higher than those of both monotherapies. Combined treatment reduced the 10-year probability for myocardial infarction from 21.6 to 4.2%.

CONCLUSIONS—The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL. It improved patients’ CAD risk status significantly more than each drug alone.
Total Sialic Acid and Associated Elements of the Metabolic Syndrome in Women With and Without Previous Gestational Diabetes
Authors: Sriharan Mohanaluxmi , Reichelt Angela J. , Opperman Maria Lúcia R. , Duncan Bruce B. , Mengue Sotero S. , Crook Martin A. , Schmidt Maria I.
Published: March 2007

OBJECTIVE—Inflammatory markers predict type 2 diabetes and relate to the metabolic syndrome. Gestational diabetes mellitus (GDM) predicts type 2 diabetes and may be part of this syndrome. To examine the association of inflammatory markers with GDM, we investigated total sialic acid (TSA) in women with and without previous GDM.

RESEARCH DESIGN AND METHODS—All women with GDM and a random sample of women from one center of the Brazilian Study of Gestational Diabetes were invited to return 7 years after their index pregnancy. After an interview, an oral glucose tolerance test and anthropometry were performed. A total of 46 women with and 50 women without previous GDM completed the protocol.

RESULTS—Mean TSA was significantly higher in women with (71.8 ± 11.1 mg/dl) than without (67.5 ± 9.8 mg/dl) previous GDM (P < 0.05). In a linear regression model, TSA was 4 mg/dl (P < 0.05) higher in women with previous GDM, after adjustment for BMI, fasting insulin sensitivity, and number of years spent in school. In a similar model, current 2-h plasma glucose levels were associated with higher TSA levels after adjustment for waist-to-hip ratio and the log of triglycerides. TSA was strongly correlated with individual components and aggregates (r = 0.55, P < 0.001) of the metabolic syndrome.

CONCLUSIONS—Increased TSA levels are associated with previous GDM and are strongly linked to the metabolic syndrome. These findings in young women suggest that a chronic mild systemic inflammatory response is an early feature of the metabolic syndrome and that GDM may be a window for its investigation.
Spurious Reporting of Nocturnal Hypoglycemia by CGMS in Patients With Tightly Controlled Type 1 Diabetes
Authors: McGowan Kilty , Thomas William , Moran Antoinette
Published: March 2007

OBJECTIVE—The Medtronic MiniMed Continuous Glucose Monitoring System (CGMS) is designed to continuously monitor interstitial fluid glucose levels within a range of 40–400 mg/dl. It is considered an important tool for overnight glucose monitoring. The goal of this study was to determine the accuracy of this system in individuals with tightly controlled diabetes.

RESEARCH DESIGN AND METHODS—Seven adolescents and young adults with HbA1c levels 6.6 ± 0.6% (range 5.7–7.1) were admitted to the Clinical Research Center. Simultaneous glucose measurements obtained by glucose analyzer, Accu-Check Advantage meter, and CGMS were compared. The analyzer levels were considered the standard.

RESULTS—The CGMS results were lower than analyzer readings in 74% of simultaneous pairs of tests performed during the 24-h period; the average correlation was 0.76. There was a trend for the poorest correlation to occur in patients with the narrowest range in daily glucose levels. When the lowest CGMS reading of the night was compared with the simultaneous analyzer reading, the CGMS level was lower in all cases by an average of 38 ± 15%. In six of seven patients, the discrepancy was believed to be clinically significant; in at least four patients, overnight glucose levels reported by CGMS were falsely low, in a range that might have resulted in inappropriate reduction of overnight insulin dose.

CONCLUSIONS—CGMS reports of asymptomatic nighttime hypoglycemia may be spurious and should be interpreted with caution in patients with tightly controlled diabetes.
Effect of Wheat Bran on Glycemic Control and Risk Factors for Cardiovascular Disease in Type 2 Diabetes
Authors: Jenkins David J. A. , Kendall Cyril W. C. , Augustin Livia S. A. , Martini Margaret C. , Axelsen Mette , Faulkner Dorothea , Vidgen Edward , Parker Tina , Lau Herb , Connelly Philip W. , Teitel Jerome , Singer William , Vandenbroucke Arthur C. , Leiter Lawrence A. , Josse Robert G.
Published: March 2007

OBJECTIVE—Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber).

RESULTS—Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA1c, serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 ± 5.4%, P < 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects).

CONCLUSIONS—High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.
Recent Trends in Hospitalization for Diabetic Ketoacidosis in Ontario Children
Authors: Curtis Jacqueline R. , To Teresa , Muirhead Sarah , Cummings Elizabeth , Daneman Denis
Published: March 2007

OBJECTIVE—To investigate trends and geographic variation in diabetic ketoacidosis (DKA) hospitalization rates among children in Ontario from 1991 to 1999.

RESEARCH DESIGN AND METHODS—Canadian Institute for Health Information (CIHI) data were used to identify 15,872 diabetes-related hospital admissions in children younger than 19 years in Ontario from 1991 to 1999. Of these, 5,008 admissions were because of DKA and 10,864 admissions were because of conditions other than DKA (non-DKA). Small area variation analysis was used to compare areas with high versus low DKA admission rates.

RESULTS—There was a 19% relative decrease in the overall diabetes admission rate over the study period. Non-DKA admissions decreased by 29%, whereas DKA admissions remained stable. Total days of care decreased by 393 days per year for non-DKA admissions and by 99 days per year for DKA admissions. The average length of hospital stay decreased from 4.9 to 3.5 days for non-DKA admissions and from 4.5 to 3.2 days for DKA admissions. The fatality rate was 0.19% for non-DKA admissions and 0.18% for DKA admissions. Variation across geographic areas remained stable for DKA over the study period (Kendall’s correlation coefficient 0.64, P = 0.017) with an average 3.7-fold difference between the lowest and highest regions.

CONCLUSIONS—Increased ambulatory care efforts for children with type 1 diabetes in Ontario have successfully reduced non-DKA admission rates. However, DKA admission rates have remained stable. Geographic variation for DKA admissions is low, but the observed 3.7-fold difference is clinically important for a preventable complication with a significant potential for long-term morbidity and mortality. Prevention strategies are needed, particularly in areas identified with the highest rates.
Intravenous Glargine and Regular Insulin Have Similar Effects on Endogenous Glucose Output and Peripheral Activation/Deactivation Kinetic Profiles
Authors: Mudaliar Sunder , Mohideen Pharis , Deutsch Reena , Ciaraldi Theodore P. , Armstrong Debra , Kim Bo , Sha Xue , Henry Robert R.
Published: March 2007

OBJECTIVE—To compare the effects of intravenously administered long-acting insulin analog glargine and regular human insulin on activation and deactivation of endogenous glucose output (EGO) and peripheral glucose uptake.

RESEARCH DESIGN AND METHODS—In this single-center, randomized, double-blind, crossover euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 ± 4 years, BMI 24.2 ± 0.7 kg/m2 [mean ± SE]) received a primed continuous intravenous infusion of 40 mU/m2 of insulin glargine or regular human insulin on 2 different study days in a randomized order. Euglycemia was maintained at 90 mg/dl using a simultaneous variable intravenous infusion of 20% dextrose containing d-[3-3H]glucose. EGO and peripheral glucose disposal kinetics were determined during a 4-h insulin infusion activation period and a 3-h deactivation period.

RESULTS—The results demonstrated no significant difference in activation or deactivation kinetics with respect to EGO and peripheral glucose disposal between insulin glargine and regular human insulin when given intravenously. The mean ± SE time required for 50% suppression of EGO after insulin infusion was 73 ± 23 min for regular insulin and 57 ± 20 min for insulin glargine (NS). The mean maximum rate of glucose disposal was 10.10 ± 0.77 and 9.90 ± 0.85 mg · kg−1 · min−1 for regular insulin and insulin glargine, respectively (NS). The mean time required for 50% suppression of incremental glucose disposal rate (GDR), defined as the time required for activation from the basal glucose disappearance rate (Rd) to half-maximum insulin-stimulated Rd, was 32 ± 5 and 42 ± 10 min for regular insulin and insulin glargine, respectively (NS). The time required for deactivation from maximum insulin-stimulated GDR to half-maximum GDR after cessation of insulin infusion was 63 ± 5 and 57 ± 4 min for regular insulin and insulin glargine, respectively (NS).

CONCLUSIONS—Activation and deactivation kinetics of EGO and peripheral glucose uptake as well as absolute disposal rate are similar between regular human insulin and insulin glargine when administered intravenously. Thus, the various biological actions of these insulin preparations when given subcutaneously are completely due to their different absorption kinetics.
Unique Effect of Visceral Fat on Insulin Sensitivity in Obese Hispanic Children With a Family History of Type 2 Diabetes
Authors: Cruz Martha L. , Bergman Richard N. , Goran Michael I.
Published: March 2007

OBJECTIVE—This study aimed to establish whether total fat or central fat was related to measures of insulin in obese Hispanic children with a family history of type 2 diabetes.

RESEARCH DESIGN AND METHODS—Subjects were 32 children aged 8–13 years. Visceral fat and subcutaneous abdominal fat were determined by magnetic resonance imaging at the umbilicus and total body fat was determined by dual-energy X-ray absorptiometry. Insulin sensitivity (Si) and acute insulin response (AIR) were determined by frequently sampled intravenous tolerance test with minimal modeling.

RESULTS—Mean fasting glucose and insulin, Si, and AIR (± SD) were 5.3 ± 0.3 mmol/l, 206 ± 105 pmol/l, 11.8 ± 5.7 [× 10−4 min−1/(pmol/l)], and 17,175 ± 9,695 (pmol/l × 10 min), respectively. In multivariate regression analysis, total fat mass was independently and positively related to fasting insulin (P < 0.01) and negatively related to Si (P < 0.05) but was not related to AIR. Visceral fat was independently and positively related to fasting insulin (P < 0.05) and AIR (P < 0.01) and negatively related to Si (P < 0.001).

CONCLUSIONS—These findings support the hypothesis that specific accumulation of visceral fat in addition to overall adiposity in Hispanic children increases the risk of type 2 diabetes.
Metformin as an Adjunct Therapy in Adolescents With Type 1 Diabetes and Insulin Resistance
Authors: Hamilton Jill , Cummings Elizabeth , Zdravkovic Vera , Finegood Diane , Daneman Denis
Published: March 2007

OBJECTIVE—To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.

RESEARCH DESIGN AND METHODS—This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit · kg−1 · day−1), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment.

RESULTS—At t = 0, HbA1c was 9.2 ± 0.9%, insulin dosage was 1.2 ± 0.2 units · kg−1 · day−1, fasting glucose was 10.6 ± 2.4 mmol/l, and BMI was 24.2 ± 3.9 kg/m2 (means ± SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group –0.14 ± 0.1 vs. placebo group 0.02 ± 0.2 units · kg−1 · day−1; P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 ± 0.8 vs. 0.9 ± 0.4 events · patient−1 · week−1; P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups.

CONCLUSIONS—Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.
The Relationship Between Dysglycemia and Atherosclerosis in South Asian, Chinese, and European Individuals in Canada
Authors: Gerstein Hertzel C. , Anand Sonia , Yi Qi Long , Vuksan Vladimir , Lonn Eva , Teo Koon , Malmberg Klas , McQueen Matthew , Yusuf Salim ,   For the SHARE Investigators*
Published: March 2007

OBJECTIVE—Raised glucose levels extending from normal into the diabetic range (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial.

RESEARCH DESIGN AND METHODS—Glucose tolerance, HbA1c, other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent.

RESULTS—The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA1c in all participants (P < 0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P < 0.0001) descent. This progressive curvilinear relationship was most apparent at HbA1c levels >5.7%. The HbA1c-AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P < 0.004). Both diabetes (P = 0.002) and HbA1c (P < 0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA1c (P < 0.0001) but not diabetes (P = 0.6) was a significant determinant.

CONCLUSIONS—The degree of AS is related to the level of HbA1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA1c and AS was observed within different ethnic groups.
Optimal Dose of Candesartan for Renoprotection in Type 2 Diabetic Patients With Nephropathy
Authors: Rossing Kasper , Christensen Per K. , Hansen Birgitte V. , Carstensen Bendix , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—We evaluated the optimal dose of the angiotensin II receptor antagonist candesartan cilexetil for renoprotection as reflected by short-term changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy.

RESEARCH DESIGN AND METHODS—A total of 23 hypertensive patients with type 2 diabetes and nephropathy were enrolled in this double-blind randomized cross-over trial with four treatment periods, each lasting 2 months. Each patient received placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive medication was discontinued before enrollment, except for long-acting furosemide, which all patients received throughout the study in median (range) doses of 40 (30–160) mg daily. End points were albuminuria (turbidimetry), 24-h blood pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (51Cr-labeled EDTA plasma clearance technique).

RESULTS—Values obtained during placebo treatment: albuminuria [geometric mean (95% CI)] 700 (486–1,007) mg/24-h, 24-h BP (mean ± SE) 147 ± 4/78 ± 2 mmHg, and GFR 84 ± 6 ml/min/1.73 m2. All three doses of candesartan significantly reduced albuminuria and 24-h BP compared with placebo. Mean (95% CI) reductions in albuminuria were 33% (21–43), 59% (52–65), and 52% (44–59) with increasing doses of candesartan. Albuminuria was reduced significantly more by the two highest doses than by the lowest dose (P < 0.01); 24-h systolic BP was reduced by 9 (2–16), 9 (2–16), and 13 (6–20) mmHg and 24-h diastolic BP was reduced by 5 (2–8), 4 (1–7), and 6 (3–9) mmHg with increasing doses of candesartan. There were no significant differences in the reductions in BP between the three doses. GFR was decreased by ∼6 ml/min/1.73 m2 by all three doses of candesartan (P < 0.05 versus placebo).

CONCLUSIONS—The optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by short-term reduction in albuminuria, in hypertensive type 2 diabetic patients with nephropathy.
Progression of Lower-Extremity Disability in Older Women With Diabetes
Authors: Volpato Stefano , Ferrucci Luigi , Blaum Caroline , Ostir Glenn , Cappola Anne , Fried Linda P. , Fellin Renato , Guralnik Jack M.
Published: March 2007

OBJECTIVE—Older patients with diabetes are more likely to have a higher prevalence of multiple risk factors for physical disability, as a result of diabetic complications. We evaluated the pace of decline in lower-extremity function and the risk for progression of disability in older women with diabetes.

RESEARCH DESIGN AND METHODS—We conducted a 3-year longitudinal cohort study of a random sample of 729 physically impaired older women (age ≥65 years) living in the community (Baltimore, MD). Diabetes was ascertained by standard criteria. Self-reported functional status and objective performance measures were assessed at baseline and over six semiannual follow-up visits.

RESULTS—The baseline prevalence of diabetes was 14.4%. After adjustment for age and compared with women without diabetes, those with diabetes had an RR of 1.8 (95% CI 1.3–2.5) for incident mobility disability and 1.6 (1.2–2.1) for incident activity of daily living disability. The increased incidence of new disability associated with diabetes was paralleled by a greater decline in objective measures of lower-extremity function. Adjustment for multiple risk factors for disability did not significantly attenuate the risk for disability associated with diabetes.

CONCLUSIONS—In older patients, impaired lower-extremity function is a long-term diabetic complication. Comprehensive assessment of older diabetic patients should include a standardized evaluation of lower-extremity performance.
Low Insulin Sensitivity (Si = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study
Authors: Haffner Steven M. , D’Agostino Ralph , Festa Andreas , Bergman Richard N. , Mykkänen Leena , Karter Andrew , Saad Mohammed F. , Wagenknecht Lynne E.
Published: March 2007

OBJECTIVE—To determine the meaning of Si = 0 derived from the frequently sampled intravenous glucose tolerance test.

RESEARCH DESIGN AND METHODS—The issue of assessing insulin resistance in large studies is important because the most definitive method (“gold standard”), the hyperinsulinemic-euglycemic clamp, is expensive and invasive. The frequently sampled intravenous glucose tolerance test (FSIGTT) has been widely used, but in insulin-resistant subjects (especially diabetic subjects), it yields considerable numbers of subjects whose Si is zero. The interpretation of an Si equaling zero is unknown.

RESULTS—To address this issue, we examined 1,482 subjects from the Insulin Resistance Atherosclerosis Study (IRAS) using an insulin-modified FSIGTT and minimal model calculation of Si. The proportion of insulin-resistant subjects (Si < 1.61 × 10−4 [min−1 · μU−1 · ml−1] based on the median of the nondiabetic population) was 38.6% in subjects with normal glucose tolerance (NGT), 74% in subjects with impaired glucose tolerance (IGT), and 92% in subjects with type 2 diabetes. The proportion of subjects with Si = 0 was 2.2% in subjects with NGT, 13.2% in subjects with IGT, and 35.7% in subjects with type 2 diabetes. In subjects with IGT, those with Si = 0 had significantly lower HDL cholesterol levels and higher BMI, waist circumference, fibrinogen, plasminogen-activator inhibitor 1 (PAI-1), C-reactive protein (CRP), and 2-h insulin levels than insulin-resistant subjects with Si > 0. In type 2 diabetes, subjects with Si = 0 had significantly greater BMI and waist circumference and higher triglyceride, PAI-1, CRP, fibrinogen, and fasting and 2-h insulin levels than insulin-resistant subjects with Si > 0. In addition, diabetic subjects with Si = 0 had more metabolic disorders related to the insulin resistance syndrome than diabetic insulin-resistant subjects with Si > 0.

CONCLUSIONS—We found very few subjects with Si = 0 among subjects with NGT and few subjects with Si = 0 among subjects with IGT. In contrast, Si = 0 was common in subjects with diabetes. Subjects with Si = 0 tended to have more features of the insulin resistance syndrome than other insulin-resistant subjects with Si > 0, as would be expected of subjects with almost no insulin-mediated glucose disposal, thus suggesting that subjects with Si = 0 are correctly classified as being very insulin resistant rather than having failed the minimal model program.