bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Trial of Continuous Subcutaneous Insulin Infusion and Intensive Injection Therapy in Type 1 Diabetes for Patients With Long-Standing Poor Glycemic Control
Authors: DeVries J. Hans , Snoek Frank J. , Kostense Piet J. , Masurel Nathalie , Heine Robert J. ,   On behalf of the Dutch Insulin Pump Study Group
Published: March 2007

OBJECTIVE—To assess in a randomized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-standing poor glycemic control.
RESEARCH DESIGN AND METHODS—A total of 79 patients in 11 Dutch centers were randomized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order. Glycemic control was assessed by HbA1c, self-reported hypoglycemic events, and blood glucose memory meter read outs. Changes in quality of life were assessed by self-report questionnaires administered at baseline and 16 weeks.
RESULTS—As the drop-out rate after crossover was high (17 of 79 patients [22%]), we analyzed the trial as a parallel clinical trial, using data of the first half of the crossover phase only. At 16 weeks, mean HbA1c was 0.84% (95% CI −1.31 to −0.36) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group (P = 0.002). Stability of blood glucose self-measurement values, expressed as SD of the nine-point blood glucose profiles, improved in the insulin pump group by 29.3 ± 41.1 vs. 8.2 ± 36.5% in the injection group (P = 0.039). The number of mild hypoglycemic episodes per patient-week was 0.99 (95% CI 0.11–1.87) higher in the insulin pump group (P = 0.028). Weight gain was similar in both groups. Scores on the Short-Form 36-Item subscales ‘general health’ and ‘mental health’ improved in the continuous subcutaneous insulin infusion group, compared with stable values in the injection group (P = 0.048 and 0.050, respectively).
CONCLUSIONS—Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control.
Effect of Combination Glipizide GITS/Metformin on Fibrinolytic and Metabolic Parameters in Poorly Controlled Type 2 Diabetic Subjects
Authors: Cefalu William T. , Schneider David J. , Carlson Harold E. , Migdal Phyllis , Gan Lim Leonil , Izon Meriam P. , Kapoor Anoop , Bell-Farrow Audrey , Terry James G. , Sobel Burton E. 
Published: March 2007

OBJECTIVE—Epidemiological studies have implicated increased plasminogen-activated inhibitor 1 (PAI-1) as a marker or predictor of accelerated coronary atherosclerotic disease in type 2 diabetes. We sought to determine whether metabolic control, independent of its oral mode of implementation, affects PAI-1 in patients with marked hyperglycemia.
RESEARCH DESIGN AND METHODS—A total of 91 subjects were screened, subjected to a 4-week drug washout, and randomized to daily treatment with glipizide GITS (maximum 20 mg, n = 46) or metformin (maximum 2,550 mg, n = 45) as monotherapy. After monotherapy, combination therapy was initiated by adding the second agent to the regimen. Plasma glucose (fasting and postprandial), HbA1c, fructosamine, and PAI-1 were assayed before and after randomization and sequentially thereafter in all subjects; hepatic glucose output (HGO) and abdominal fat distribution were each measured in a subset of subjects.
RESULTS—Glycemic control was markedly impaired at baseline (mean HbA1c 10.4 ± 0.2% glipizide GITS; 10.0 ± 0.2% metformin) but improved comparably with each agent as monotherapy and in combination (P &lt; 0.0001 vs. baseline), as assessed with meal tolerance studies, fructosamine values, and HGO. Body weight and abdominal fat distribution did not change significantly in either group. PAI-1 concentrations were extraordinarily high (5- to 10-fold more than normal) at baseline (202 ± 12 ng/ml glipizide GITS; 201 ± 13 ng/ml metformin) but declined comparably, and significantly, after treatment with either agent as monotherapy and decreased further with combination therapy.
CONCLUSIONS—When hyperglycemia is profound, increases in PAI-1 are also profound. Control of hyperglycemia with either glipizide GITS, an insulin secretagogue, or metformin as monotherapy comparably ameliorates elevated PAI-1.
Effect of Glimepiride on Insulin-Stimulated Glycogen Synthesis in Cultured Human Skeletal Muscle Cells
Authors: Haupt Axel , Kausch Christiana , Dahl Dominik , Bachmann Oliver , Stumvoll Michael , Häring Hans-U. , Matthaei Stephan 
Published: March 2007

OBJECTIVE—To examine the effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells in comparison with glibenclamide.
RESEARCH DESIGN AND METHODS—Myotubes derived from glucose-tolerant subjects were incubated with glimepiride or glibenclamide (0–100 μmol/l) for 4 h and with or without insulin (100 nmol/l) for 2 h, and subsequently glycogen synthesis was determined.
RESULTS—Glimepiride had no significant effect on basal glycogen synthesis; in contrast, glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis, with a maximal effect of 39.97 ± 8.4% (mean ± SEM, n = 4, P &lt; 0,02). The time course of this glimepiride effect on insulin-stimulated glycogen synthesis showed a peak after 12 h incubation with a half maximal effect after 4 h. Preincubation of the myotubes with wortmannin (100 nmol/l), an inhibitor of phosphatidylinositol (PI)- 3 kinase, caused an inhibition of this glimepiride effect on insulin-stimulated glycogen synthesis. In contrast to glimepiride, incubation of myotubes with glibenclamide (0–100nmol/l), a second generation sulfonylurea, had no significant effect on basal or insulin-stimulated glycogen synthesis.
CONCLUSIONS—Incubation of cultured human skeletal muscle cells derived from glucose-tolerant subjects with glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis using therapeutic glimepiride concentrations. This glimepiride effect seems to be mediated via the PI3 kinase pathway. In contrast to glimepiride, glibenclamide had no significant effect on basal or insulin-stimulated glycogen synthesis. These results suggest that glimepiride, beside its well-known effect to stimulate insulin secretion, possess an insulin-sensitizing action in cultured human skeletal muscle cells in support of the concept of an extrapancreatic action of glimepiride.
HbA1c Levels Among American Indian/Alaska Native Adults
Authors: Gilliland Susan S. , Carter Janette S. , Skipper Betty , Acton Kelly J. 
Published: March 2007

OBJECTIVE—Type 2 diabetes is a major public health problem among many American Indian/Alaska Native communities. Elevated levels of HbA1c have been observed in younger American Indian/Alaska Native adults. The objectives of this study were: 1) to determine whether HbA1c levels were elevated among younger American Indian/Alaska Native adults nationally and, if so, 2) to determine the relationship between HbA1c levels and age due to treatment type, BMI, renal disease, duration of diabetes, survival, or a poor diabetes health care index.
RESEARCH DESIGN AND METHODS—The national Indian Health Service Diabetes Care and Outcomes Audit was completed for a total of 11,419 American Indian/Alaska Native adults with type 2 diabetes from tribes across the U.S. in 1998. Glucose control was assessed by HbA1c. BMI, diabetes duration, treatment type, and proteinuria were assessed from the Diabetes Care and Outcomes Audit data. To assess diabetes quality of care, an index was developed from six standard of care Diabetes Care and Outcomes Audit variables.
RESULTS—We found HbA1c level decreased with increasing age. HbA1c levels were 9.2, 8.9, 8.8, 8.3, and 7.8 for ages 18–39, 40–49, 50–59, 60–69, and ≥70 years, respectively (P &lt; 0.0001). This inverse relationship was not accounted for by differences in BMI, diabetes duration, treatment type, proteinuria, or health care index.
CONCLUSIONS—Among American Indian/Alaska Native adults, HbA1c levels were highest in the youngest age-group. With increasing numbers of young American Indian/Alaska Native adults with diabetes, poorer glucose control is expected to bring concomitant increased morbidity and mortality unless more effective and efficient interventions are developed to improve glucose control among young American Indian/Alaska Native adults.
The Influence of Maternal BMI and Age in Twin Pregnancies on Insulin Resistance in the Offspring
Authors: Loos Ruth J.F. , Phillips David I.W. , Fagard Robert , Beunen Gaston , Derom Catherine , Mathieu Chantal , Verhaeghe Johan , Vlietinck Robert 
Published: March 2007

OBJECTIVE—There is strong evidence that low birth weight is associated with glucose intolerance and diabetes in adults. We have carried out a twin study to distinguish among maternal influences, which affect both twins; fetoplacental influences, which are unique to each twin; and the genetic factors that may underlie this association.
RESEARCH DESIGN AND METHODS—We identified a sample of 423 twin pairs (250 monozygotic and 173 dizygotic) from the East Flanders Prospective Twin Survey who were born between 1964 and 1982. Data collected in this study included the mother’s body composition and weight gain during pregnancy, the twins’ birth weights, and gestational age. The twins (aged 18–34 years) attended a research center for measurement of height, weight, and waist-to-hip ratio as well as fasting glucose, proinsulin, and insulin concentrations.
RESULTS—Among twin pairs discordant for birth weight, we found little evidence that the lighter twin had abnormal glucose-insulin metabolism in adult life. However, both a low prepregnancy maternal BMI and older maternal age at delivery were associated with hyperinsulinemia and evidence of insulin resistance in the offspring. Fasting insulin increased by 1.3% (95% CI 0.1–2.6%) per unit fall in maternal BMI and by 1.1% (0.02–2.0%) per year increase in maternal age. These associations were independent of the twins’ BMI and waist-to-hip ratio and their zygosity.
CONCLUSIONS—These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring.
Absorption and Metabolic Effect of Inhaled Insulin
Authors: Perera Ayesh D. , Kapitza Christoph , Nosek Leszek , Fishman Robert S. , Shapiro David A. , Heise Tim , Heinemann Lutz 
Published: March 2007

OBJECTIVE—To compare the intrapatient variability of the pharmacokinetic and pharmacodynamic responses to inhaled regular insulin (INH) delivered via the Aerodose Insulin Inhaler with that of subcutaneously injected regular insulin (SC) in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—A total of 15 patients with type 2 diabetes (nonsmokers, 10 men, aged 47–77 years) received two 240-unit doses of INH, delivered via a clinical Aerodose Insulin Inhaler and two 24-unit doses of SC under euglycemic clamp conditions on four separate study days. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. Comparisons of intrapatient coefficients of variation (CV) were used to assess the reproducibility of INH versus SC.
RESULTS—INH showed a bioavailability (0–8 h postdosing) of 16% and biopotency of 13% relative to SC. Comparison of the CVs (%) for area under the curve for serum insulin and GIR between INH and SC showed no significant differences between the treatments during 0–3 h (19% for INH versus 23% for SC) or 0–8 h (22% for INH versus 16% for SC). INH exhibited a shorter time to peak insulin concentration (Tmax [mean ± SD] 76 ± 51 vs. 193 ± 66 min) and shorter time to peak metabolic effect (TGIRmax 170 ± 53 vs. 244 ± 75 min) compared with SC (P &lt; 0.001). No adverse events were observed.
CONCLUSIONS—Comparable dosing reproducibility and shorter time to peak action of INH compared with SC suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes.
Deficit of Somatostatin-Like Immunoreactivity in the Vitreous Fluid of Diabetic Patients
Authors: Simó Rafael , Lecube Albert , Sararols Laura , García-Arumí José , Segura Rosa M. , Casamitjana Roser , Hernández Cristina 
Published: March 2007

OBJECTIVE—To evaluate the vitreous levels of somatostatin-like immunoreactivity (SLI) in patients with proliferative diabetic retinopathy (PDR).
RESEARCH DESIGN AND METHODS—A total of 14 diabetic patients with PDR, in whom a vitrectomy was performed, were included in the study. Sixteen nondiabetic patients, with other conditions requiring vitrectomy, served as a control group. Both venous blood and vitreous samples were collected at the time of vitreoretinal surgery. Patients in whom intravitreous hemoglobin was detectable were excluded. In addition, a correction for plasma levels of SLI and intravitreal proteins was performed. SLI was measured by radioimmunoassay and vitreous hemoglobin by spectrophotometry.
RESULTS—SLI in the vitreous fluid was significantly lower in diabetic patients than in the control group (68 ± 18.7 vs. 193.6 ± 30.8 pg/ml, P &lt; 0.01). The vitreous SLI-to-plasma SLI ratio was strikingly higher in nondiabetic subjects than in diabetic patients with PDR (5.3 [1.2–71.1] vs. 0.6 [0.03–4.1], P &lt; 0.01). After correcting for total vitreous protein concentration, SLI (pg/mg of proteins) remained significantly higher in nondiabetic control subjects than in diabetic patients with PDR (186 [51–463] vs. 7.5 [0.8–82], P &lt; 0.0001). Remarkably, intravitreous levels of SLI were higher than those obtained in plasma in nondiabetic control subjects (193.6 ± 30.8 vs. 43.5 ± 10.7 pg/ml, P &lt; 0.0001). Finally, a lack of relationship between plasma and vitreous levels of SLI was observed in both diabetic patients with PDR and nondiabetic control subjects.
CONCLUSIONS—The significantly higher SLI in the vitreous fluid than in plasma detected in nondiabetic control subjects supports the concept that somatostatin plays a relevant role in retinal homeostasis. In addition, the intravitreous deficit of SLI observed in diabetic patients with PDR suggests that it might contribute to the process of retinal neovascularization.
Insulin and Amylin Release Are Both Diminished in First-Degree Relatives of Subjects With Type 2 Diabetes
Authors: Knowles Negar G. , Landchild Melinda A. , Fujimoto Wilfred Y. , Kahn Steven E. 
Published: March 2007

OBJECTIVE—To determine whether first-degree relatives of individuals with type 2 diabetes, who are at high risk of subsequently developing hyperglycemia, manifest alterations in β-cell function including an alteration in the co-release of insulin and amylin.
RESEARCH DESIGN AND METHODS—In 30 first-degree relatives and 24 matched subjects with no family history of diabetes, β-cell function was measured as the intravenous glucose-induced acute insulin response (AIRg) and acute amylin response (AARg). The insulin sensitivity index (SI) was quantified and used to account for the role of insulin sensitivity to modulate β-cell function (SI × β-cell function).
RESULTS—Fasting plasma glucose (5.3 ± 0.1 vs. 5.1 ± 0.1 mmol/l; means ± SEM), immunoreactive insulin (IRI) (68 ± 7 vs. 57 ± 6 pmol/l) and amylin-like immunoreactivity (ALI) (5.5 ± 0.6 vs. 4.7 ± 0.7 pmol/l) were similar in relatives and control subjects, respectively. Relatives were insulin resistant compared with control subjects (SI: 4.86 ± 0.63 vs. 7.20 ± 0.78 × 10−5 min−1 · pmol−1 · l−1, P = 0.01), but their AIRg (392 ± 59 vs. 386 ± 50 pmol/l) and AARg (5.9 ± 0.9 vs. 6.1 ± 0.8 pmol/l) did not differ. When β-cell function was determined relative to insulin sensitivity, in the first-degree relatives, both AIRg (SI × AIRg: 1.60 ± 0.23 vs. 2.44 ± 0.31 × 10−2 min−1, P &lt; 0.05) and AARg (SI × AARg: 2.39 ± 0.35 vs. 4.06 ± 0.56 × 10−4 min−1, P &lt; 0.05) were reduced. The molar proportion of ALI to IRI was not altered in high-risk subjects (1.75 ± 0.16 vs. 1.71 ± 0.15%).
CONCLUSIONS—First-degree relatives of subjects with type 2 diabetes have diminished β-cell function at a time when they are not hyperglycemic, and this reduction affects insulin and amylin responses proportionally. Thus, an altered amylin-to-insulin ratio is not likely to identify individuals at high risk of developing type 2 diabetes.
Health Outcomes of Severely Obese Type 2 Diabetic Subjects 1 Year After Laparoscopic Adjustable Gastric Banding
Authors: Dixon John B. , O’Brien Paul E. 
Published: March 2007

OBJECTIVE—To prospectively examine the effect of weight loss 1 year after laparoscopic adjustable gastric band surgery on a broad range of health outcomes in 50 diabetic subjects.
RESEARCH DESIGN AND METHODS—A total of 50 (17 men, 33 women) of 51 patients with type 2 diabetes, from a total of 500 consecutive patients, were studied preoperatively and again 1 year after surgery.
RESULTS—Preoperative weight and BMI (means ± SD) were 137 ± 30 kg and 48.2 ± 8 kg/m2, respectively; at 1 year, weight and BMI were 110 ± 24 kg and 38.7 ± 6 kg/m2, respectively. There was significant improvement in all measures of glucose metabolism. Remission of diabetes occurred in 32 patients (64%), and major improvement of glucose control occurred in 13 patients (26%); glucose metabolism was unchanged in 5 patients (10%). HbA1c was 7.8 ± 3.2% preoperatively and 6.2 ± 2.7% at 1 year (P &lt; 0.001). Remission of diabetes was predicted by greater weight loss and a shorter history of diabetes (pseudo r2 = 0.44, P &lt; 0.001). Improvement in diabetes was related to increased insulin sensitivity and β-cell function. Weight loss was associated with significant improvements in fasting triglyceride level, HDL cholesterol level, hypertension, sleep, depression, appearance evaluation, and health-related quality of life. Early complications occurred in 6% of patients (wound infections in 4%, respiratory support in 2%), and late complications occurred in 30% of patients (gastric prolapse in 20%, band erosion in 6%, and tubing leaks in 4%). All late complications were successfully revised surgically.
CONCLUSIONS—Modern laparoscopic weight-loss surgery is effective in managing the broad range of health problems experienced by severely obese individuals with type 2 diabetes. Surgery should be considered as an early intervention.
Caffeine Can Decrease Insulin Sensitivity in Humans
Authors: Keijzers Gerben B. , De Galan Bastiaan E. , Tack Cees J. , Smits Paul 
Published: March 2007

OBJECTIVE—Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake.
RESEARCH DESIGN AND METHODS—Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects.
RESULTS—Caffeine decreased insulin sensitivity by 15% (P &lt; 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P &lt; 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P &lt; 0.0005), and smaller increases were recorded in plasma norepinephrine (P &lt; 0.02) and blood pressure (P &lt; 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P &lt; 0.01).
CONCLUSIONS—Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.
Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist, Rosiglitazone, Increases Plasma Levels of Adiponectin in Type 2 Diabetic Patients
Authors: Yang Wei-Shiung , Jeng Chi-Yuan , Wu Ta-Jen , Tanaka Sachiyo , Funahashi Tohru , Matsuzawa Yuji , Wang Jao-Ping , Chen Chi-Ling , Tai Tong-Yuan , Chuang Lee-Ming 
Published: March 2007

OBJECTIVE—Adiponectin, a plasma protein exclusively synthesized and secreted by adipose tissue, has recently been shown to have anti-inflammatory, antiatherogenic properties in vitro and beneficial metabolic effects in animals. Lower plasma levels of adiponectin have been documented in human subjects with metabolic syndrome and coronary artery disease. We investigated whether the level of this putative protective adipocytokine could be increased by treatment with a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in diabetic patients.
RESEARCH DESIGN AND METHODS—Type 2 diabetic patients (30 in the treatment group and 34 in the placebo group) were recruited for a randomized double-blind placebo-controlled trial for 6 months with the PPAR-γ agonist rosiglitazone. Blood samples were collected and metabolic variables and adiponectin levels were determined in all patients before initiation of the study.
RESULTS—In the rosiglitazone group, mean plasma adiponectin level was increased by more than twofold (P &lt; 0.0005), whereas no change was observed in the placebo group. Multivariate linear regression analysis showed that whether rosiglitazone was used was the single variable significantly related to the changes of plasma adiponectin. The amount of variance in changes of plasma adiponectin level explained by the treatment was ∼24% (r2 = 0.24) after adjusting for age, sex, and changes in fasting plasma glucose, HbA1c, insulin resistance index, and BMI.
CONCLUSIONS—Rosiglitazone increases plasma adiponectin levels in type 2 diabetic subjects. Whether this may contribute to the antihyperglycemic and putative antiatherogenic benefits of PPAR-γ agonists in type 2 diabetic patients warrants further investigation.
Progression of Retinopathy in Insulin-Treated Type 2 Diabetic Patients
Authors: Henricsson Marianne , Berntorp Kerstin , Fernlund Per , Sundkvist Göran 
Published: March 2007

OBJECTIVE—To study the progression of retinopathy 3 years after initiation of insulin therapy.
RESEARCH DESIGN AND METHODS—In a prospective, observational case-control study, 42 type 2 diabetic patients were examined at baseline and 1, 3, 6, 12, 24, and 36 months after change to insulin therapy. Retinopathy was graded based on fundus photographs using the Wisconsin scale; HbA1c and IGF-1 were measured.
RESULTS—During the observation period of 3 years, 26 patients progressed in the retinopathy scale; 11 patients progressed at least three levels. After 3 years of insulin therapy, HbA1c and IGF-1 were significantly lower than at baseline. Progression of retinopathy greater than or equal to three levels was related to high IGF-1 levels.
CONCLUSIONS—A relationship was found between high IGF-1 levels at 3 years and progression of retinopathy in type 2 diabetic patients.