bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Improves Alveolar-Capillary Membrane Gas Conductance in Type 2 Diabetes
Authors: Guazzi Marco , Oreglia Iacopo , Guazzi Maurizio D.
Published: March 2007

OBJECTIVE—In type 1 diabetes, lung diffusing capacity for carbon monoxide (DLCO) may be impaired, and insulin has been shown to be beneficial in cases in which near-normal metabolic control is achieved. An influence of insulin, per se, on the alveolar-capillary membrane conductance is unexplored. We aimed at testing this possibility.

RESEARCH DESIGN AND METHODS—We studied 19 life-long nonsmoking, asymptomatic patients with type 2 diabetes and normal cardiac function, whose GHb averaged 6.2 ± 0.3% with diet and hypoglycemic drugs. DLCO and its subcomponents (alveolar capillary membrane conductance [DM] and pulmonary capillary blood volume available for gas exchange [Vc]), vital capacity (VC), forced expiratory volume 1 s (FEV1), cardiac output (CO), ejection fraction (EF), pulmonary wedge pressure (WPP), and pulmonary arteriolar resistance (PAR) were determined before and within 60 min after infusion of 50 ml saline + 10 IU of regular insulin or after saline alone on 2 consecutive days (random block design). Glycemia was kept at baseline levels during experiments by dextrose infusion.

RESULTS—Percent of normal predicted DLCO averaged 84.2 ± 7.9% and in 14 patients was <100%. Insulin infusion, not saline alone, improved (P < 0.01) DLCO (12%) and DM (14%) and raised DLCO to 98% of the normal predicted value. There were no variations in VC, FEV1, CO, EF, WPP, or PAR, suggesting that the influences of the hormone on gas transfer were not mediated by changes in spirometry, volumes, and hemodynamics of the lung.

CONCLUSIONS—Several cases of type 2 diabetes present with increased impedance to gas transfer across the alveolar-capillary membrane, and hypoglycemic drugs do not prevent this inconvenience. Insulin, independently of the metabolic effects, acutely improves gas exchange, possibly through a facilitation of the alveolar-capillary interface conductance.
The Glucose Area Under the Profiles Obtained With Continuous Glucose Monitoring System Relationships With HbAlc in Pediatric Type 1 Diabetic Patients
Authors: Salardi Silvana , Zucchini Stefano , Santoni Roberta , Ragni Luca , Gualandi Stefano , Cicognani Alessandro , Cacciari Emanuele
Published: March 2007

OBJECTIVE—The purpose of this study was to determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) 1) is sufficiently representative of the overall metabolic control as assessed by HbA1c, 2) could be used to identify a particular blood glucose threshold value affecting hemoglobin glycation; and 3) is able to show any relationship between particular glycemic profiles and HbA1c levels.

RESEARCH DESIGN AND METHODS—Of 44 pediatric patients with type 1 diabetes who wore CGMS devices, 28 subjects were selected for the study. Criteria for inclusion were high levels of HbA1c (≥8%) for more than 1 year or a history of frequent hypoglycemic episodes and a complete CGMS registration for 72 h. Age of the subjects ranged from 5.7 to 24.8 years, the mean duration of disease was 7.63 ± 4.75 years, and the mean HbA1c value was 8.7 ± 1.3%. CGMS data were downloaded and glucose profiles were analyzed. The area under each glucose profile was calculated by means of a professional digital planimeter.

RESULTS—The glucose profiles showed a high frequency of prolonged hyperglycemic periods (80% of subjects) and a low frequency of postmeal glycemic peaks (29% of subjects). Postlunch values were significantly correlated with HbA1c levels, but the correlation disappeared when controlling for glucose area values. Glucose area values significantly correlated with HbA1c levels both when considered as a whole (40–400 mg/dl; r = 0.53, P = 0.002) and when considered fractioned (40–150, 40–200, 40–250, 40–300 mg/dl), apart from the 40–90 mg/dl partial area. HbA1c levels were significantly decreased 3 and 6 months after use of CGMS (P = 0.05 and 0.03, respectively, paired Student’s t test) .

CONCLUSIONS—HbA1c levels may be decreased by using the information obtained with the CGMS. Three-day glucose profiles are representative of the overall glucose control, because glucose area values correlate with HbA1c levels. The only glucose threshold below which there seems to be no correlation with HbA1c is 90 mg/dl. Only glucose area, and not postprandial glucose values, are directly and independently correlated with HbA1c. Therefore, to improve metabolic control, it is necessary to lower the whole mean 24-h glycemia and not just the postprandial glucose values.
Attributing Inpatient Medicare Costs to Diabetes Among the Texas Elderly
Authors: McCandless Roy R.
Published: March 2007

OBJECTIVE—This study compares alternative methods for attributing hospital utilization and costs to diabetes. Findings from five “numerator” methods, found in the literature and based on presence of certain diagnoses or combinations of diagnoses in the billing records, were compared to benchmark findings derived from attributable risk calculations.

RESEARCH DESIGN AND METHODS—Estimates of non-HMO, short-term, nonspecialized hospital stays, hospital days, and costs attributable to diabetes in Texas were derived from the 1995 Medicare inpatient database (MEDPAR) for persons aged at least 65 years at the end of 1994. Attributable risk calculations applied age-, sex-, and ethnicity-specific estimates of diabetes prevalence, based on the combined 1987–1994 National Health Interview Surveys, to 1995 Medicare non-HMO, Part A (hospital insurance) enrollment among the Texas elderly. Alternative prevalence estimates were based on the 1994–1996 Texas Behavioral Risk Factor Surveillance System.

RESULTS—The five numerator methods yielded cost estimates that were 10, 10, 75, 144, and 172% of the benchmark estimate.

CONCLUSIONS—This study documents great variation in diabetes cost estimates that might result from alternative methods for selecting diagnoses or combinations of diagnoses as criteria for attributing costs to diabetes. Whereas no method that ignores population prevalence yielded an accurate cost estimate, I suggest that further empirical study may be helpful in selecting those combinations of diagnoses that might, on average, reasonably estimate diabetes costs in situations where population denominators are unavailable or prevalence is unknown.
Neighborhood Characteristics and Components of the Insulin Resistance Syndrome in Young Adults
Authors: Diez Roux Ana V. , Jacobs David R. , Kiefe Catarina I.
Published: March 2007

OBJECTIVE—To examine associations of neighborhood characteristics with six components of the insulin resistance syndrome (IRS) in young adults.

RESEARCH DESIGN AND METHODS—Cross-sectional data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to examine associations of neighborhood characteristics with the IRS in 3,093 nondiabetic adults aged 28–40 years. Measures of BMI, fasting HDL cholesterol, triglycerides, insulin, glucose, and systolic blood pressure were combined into an IRS score. U.S. Census-derived neighborhood characteristics were summarized into a neighborhood socioeconomic score, with an increasing score signifying increasing socioeconomic advantage.

RESULTS—Among white men and women, the IRS score was inversely related to neighborhood socioeconomic score. Neighborhood characteristics remained associated with the IRS score after controlling for personal income and education (adjusted mean differences for 95th vs. 5th percentile of neighborhood score: −0.24 standard deviation units [SE = 0.12] in men and −0.56 standard deviation units [SE = 0.10] in women). Among black participants, neighborhood score was inversely associated with IRS score in persons of high income and education (mean differences 95th vs. 5th percentile −0.54 [SE 0.26] in men and −0.52 [SE 0.26] in women) but positively associated or not associated with IRS score in persons of low income and education (mean differences 0.60 [SE 0.21] in men and 0.00 [SE 0.16] in women).

CONCLUSIONS—The IRS score is associated with neighborhood characteristics as early as young adulthood. Features of residential environments may be related to the development of insulin resistance.
Personal Control and Disordered Eating in Female Adolescents With Type 1 Diabetes
Authors: Schwartz Stefanie A. , Weissberg-Benchell Jill , Perlmuter Lawrence C.
Published: March 2007

OBJECTIVE—The onset and subsequent management of diabetes can challenge one’s sense of control. Sense of control can also be affected by the biological changes accompanying normal pubertal development. The negative impact on one’s sense of control may be further exacerbated when both events (i.e., diabetes and puberty) occur in relatively close temporal proximity.

RESEARCH DESIGN AND METHODS—This study examined the relationship between sense of control and disordered eating and glycemic control in 45 female adolescents with type 1 diabetes.

RESULTS—A lower sense of overall control and a lower sense of bodily control were both directly related to more severe eating-disordered symptoms. However, a lower sense of overall control and lower bodily control were related to poorer metabolic control primarily when the diagnosis of diabetes occurred closer to the onset of puberty.

CONCLUSIONS—Clinicians should assess and monitor perceptions of control and also consider the temporal proximity of disease onset and onset of puberty when managing type 1 diabetes in female adolescents.
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 < 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 < 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 < 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 < 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 < 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 < 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 < 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 < 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 < 0.05) and AARg (SI × AARg: 2.39 ± 0.35 vs. 4.06 ± 0.56 × 10−4 min−1, P < 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 < 0.001). Remission of diabetes was predicted by greater weight loss and a shorter history of diabetes (pseudo r2 = 0.44, P < 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 < 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P < 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P < 0.0005), and smaller increases were recorded in plasma norepinephrine (P < 0.02) and blood pressure (P < 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P < 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 < 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.
Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes
Authors: Miyazaki Yoshinori , Matsuda Masafumi , DeFronzo Ralph A.
Published: March 2007

OBJECTIVE—To investigate the dose-response effects of pioglitazone on glycemic control, insulin sensitivity, and insulin secretion in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 58 diet-treated patients with type 2 diabetes (aged 54 ±1 years; 34 men and 24 women; BMI 31.5± 0.6 kg/m2) were randomly assigned to receive placebo (n=11) or 7.5 mg (n=13), 15 mg (n=12), 30 mg (n=11), or 45 mg (n=11) of pioglitazone per day for 26 weeks. Before and after 26 weeks, subjects underwent a 75-g oral glucose tolerance test (OGTT).

RESULTS—Patients treated with 7.5 or 15 mg/day of pioglitazone had no change in fasting plasma glucose (FPG) and fasting plasma insulin (FPI) concentrations or in plasma glucose (PG) and insulin concentrations during the OGTT. Patients treated with 30 and 45 mg/day of pioglitazone, respectively, had significant decreases from placebo in HbA1c (Δ=−2.0 and −2.9%), FPG (Δ=−66 and −97 mg/dl), and mean PG during OGTT (Δ=−84 and −107 mg/dl). Fasting plasma insulin decreased significantly in the 45-mg/day pioglitazone group, but the mean plasma insulin during the OGTT did not change. The insulinogenic index (Δ area under the curve [AUC] insulin/ΔAUC glucose) during the OGTT increased significantly in the 30- and 45-mg/day pioglitazone groups (0.13± 0.03 to 0.27± 0.05, P < 0.05). From the OGTT, we previously have derived a composite whole-body insulin sensitivity index (ISI) that correlates well with that measured directly with the insulin clamp technique. Whole-body ISI [ISI=10,000 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\sqrt{(FPG{\times}FPI){\times}(\overline{PG}{\times}\overline{PI})}\) \end{document}, where P̅G̅ and P̅I̅ equal mean plasma glucose and insulin concentrations during OGTT] increased significantly in patients treated with 30 mg (1.8± 0.3 to 2.5± 0.3, P < 0.05) or 45 mg (1.6± 0.2 to 2.7± 0.6, P < 0.05) per day of pioglitazone. In the basal state, the hepatic ISI [k/(FPG × FPI)[k/(FPG × FPI)], which agrees closely with that measured directly with tritiated glucose, increased in patients treated with 30 mg (0.13± 0.02 to 0.21± 0.03, P < 0.05) and 45 mg (0.11± 0.02 to 0.24± 0.06, P < 0.05) per day of pioglitazone. Significant correlations between the dose of pioglitazone and the changes in HbA1c (r=−0.58), FPG (r=−0.47), mean PG during the OGTT (r=−0.46), insulinogenic index (r=0.34), hepatic ISI (r=0.44), and whole-body ISI (r=0.36) were observed.

CONCLUSIONS—Pioglitazone improves glycemic control through the dose-dependent enhancement of β-cell function and improved whole-body and hepatic insulin sensitivity.
α-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients
Authors: Devaraj Sridevi , Chan Alberto V. Cabo , Jialal Ishwarlal
Published: March 2007

OBJECTIVE—Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. α-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses. The aim of the study was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator inhibitor-1 (PAI-1), and soluble P-selectin (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects.

RESEARCH DESIGN AND METHODS—The volunteers comprised type 2 diabetic patients with (n=23) and without (n=24) MVCs and matched control subjects (n=25). Plasma levels of PAI-1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase.

RESULTS—Both diabetic groups had significantly increased levels of PAI-1 compared with control subjects (P < 0.025), whereas only type 2 diabetic patients with MVCs had significantly elevated levels of sP-selectin compared with control subjects. AT supplementation significantly lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P=0.005).

CONCLUSIONS—Thus, AT therapy decreases markers of thrombosis in diabetic patients and control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.
Continuous Subcutaneous Insulin Infusion at 25 Years
Authors: Pickup John , Keen Harry
Published: March 2007

Continuous subcutaneous insulin infusion (CSII) is used in selected type 1 diabetic subjects to achieve strict blood glucose control. A quarter of a century after its introduction, world-wide use of CSII is increasing. We review the evidence base that justifies this increase, including effectiveness compared with modern intensified insulin injection regimens and concern about possible complications. Review of controlled trials shows that, in most patients, mean blood glucose concentrations and glycated hemoglobin percentages are either slightly lower or similar on CSII versus multiple insulin injections. However, hypoglycemia is markedly less frequent than during intensive injection therapy. Ketoacidosis occurs at the same rate. Nocturnal glycemic control is improved with insulin pumps, and automatic basal rate changes help to minimize a prebreakfast blood glucose increase (the “dawn phenomenon”) often seen with injection therapy. Patients with “brittle” diabetes characterized by recurrent ketoacidosis are often not improved by CSII, although there may be exceptions. We argue that explicit clinical indications for CSII are helpful; we suggest the principal indications for health service or health insurance–funded CSII should include frequent, unpredictable hypoglycemia or a marked dawn phenomenon, which persist after attempts to improve control with intensive insulin injection regimens. In any circumstances, candidates for CSII must be motivated, willing and able to undertake pump therapy, and adequately psychologically stable. Some diabetic patients with well-defined clinical problems are likely to benefit substantially from CSII and should not be denied a trial of the treatment. Their number is relatively small, as would therefore be the demand on funds set aside for this purpose.
Comorbidities and Impairments Explaining the Association Between Diabetes and Lower Extremity Disability
Authors: Volpato Stefano , Blaum Caroline , Resnick Helaine , Ferrucci Luigi , Fried Linda P. , Guralnik Jack M.
Published: March 2007

OBJECTIVE—To elucidate the role of diabetes-related impairments and comorbidities in the association between diabetes and physical disability, this study examined the association between diabetes and lower extremity function in a sample of disabled older women.

RESEARCH DESIGN AND METHODS—Cross-sectional analysis of 1,002 women (aged ≥65 years) enrolled in the Women’s Health and Aging Study (one-third most disabled of the total community-dwelling population). Diabetes and other medical conditions were ascertained by standard criteria that used multiple sources of information. Functional status was assessed using self-reported and objective performance measures.

RESULTS—Women with diabetes were significantly more likely to have cardiovascular diseases, peripheral nerve dysfunction, visual impairment, obesity, and depression. After adjustment for age, women with diabetes had a greater prevalence of mobility disability (odds ratio [OR] 1.85, 95% CI 1.12–3.06), activities of daily living disability (1.61, 1.06–2.43), and severe walking limitation (2.34, 1.56–3.50), and their summary mobility performance score (0–12 scale based on balance, gait speed, chair stands) was 1.4 points lower than in nondiabetic women (P < 0.001). Peripheral artery disease, peripheral nerve dysfunction, and depression were the main individual contributing factors; however, none of these conditions alone fully explained the association between diabetes and disability. Conversely, only after adjusting for all potential mediators was the relationship between diabetes and disability reduced to a large degree.

CONCLUSIONS—Even among physically impaired older women, diabetes is associated with a major burden of disability. A wide range of impairments and comorbidities explains the diabetes-disability relationship, suggesting that the mechanism for such an association is multifactorial.
A Prospective, Randomized Comparison of the Metabolic Effects of Pioglitazone or Rosiglitazone in Patients With Type 2 Diabetes Who Were Previously Treated With Troglitazone
Authors: Khan Mehmood A. , St. Peter John V. , Xue Jay L.
Published: March 2007

OBJECTIVE—To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone.

RESEARCH DESIGN AND METHODS—After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA1c, and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed.

RESULTS—A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA1c between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of ∼2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P < 0.005). Significant improvements in lipid profile were noted in the PIO group (P < 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of ∼20 mg/dl.

CONCLUSIONS—Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.
Control of Cardiovascular Risk Factors in Patients With Diabetes and Hypertension at Urban Academic Medical Centers
Authors: McFarlane Samy I. , Jacober Scott J. , Winer Nathaniel , Kaur Jasjeet , Castro Jonathan P. , Wui MaryLou A. , Gliwa Agnes , Von Gizycki Hans , Sowers James R.
Published: March 2007

OBJECTIVE—There are national mandates to reduce blood pressure (BP) to <130/85 mmHg, LDL cholesterol to <100 mg/dl, and HbA1c to <7% and to institute aspirin therapy in patients with diabetes. The objective of this study was to determine the proportion of patients in urban institutions with diabetes and hypertension who meet these treatment goals.

RESEARCH DESIGN AND METHODS—Using American Diabetes Association (ADA) guidelines, we evaluated the control of cardiovascular disease (CVD) risk factors in 1,372 patients receiving medical care at two major urban medical centers in Brooklyn and Detroit. Information was extracted from charts of outpatient clinics.

RESULTS—Of 1,372 active clinic patients with diabetes and hypertension, 1,247 (90.9%) had type 2 diabetes, and 26.7% met the target blood pressure of 130/85 mmHg. A total of 35.5% met the goal LDL cholesterol level of <100 mg/dl, 26.7% had an HbA1c <7%, and 45.6% were on antiplatelet therapy. Only 3.2% of patients met the combined ADA goal for BP, LDL cholesterol, and HbA1c.

CONCLUSIONS—Optimal control of CVD risk factors in adults with diabetes was achieved only in a minority of patients. Results reflect the inherent difficulties in achieving these complex guidelines in our present health care systems.
Interpersonal Predictors of HbA1c in Patients With Type 1 Diabetes
Authors: Ciechanowski Paul S. , Hirsch Irl B. , Katon Wayne J.
Published: March 2007

OBJECTIVE—Research suggests that increased collaboration and satisfaction in the patient-provider relationship is associated with better outcomes in patients with diabetes. In adults, an interpersonal style characterized by low trust of others and excessive self-reliance is known as “dismissing attachment style.” We hypothesized that diabetic patients with dismissing attachment style, due to a decreased ability to collaborate with providers and others, would have significantly higher HbA1c levels than patients with secure attachment style.

RESEARCH DESIGN AND METHODS—From 276 adult tertiary care patients with type 1 diabetes, we obtained mean HbA1c levels over the prior year and assessed patient attachment style, demographics, and clinical characteristics. We used χ2 tests and logistic regression to determine whether attachment style was associated with HbA1c levels.

RESULTS—We found that 62% of patients with dismissing attachment style had mean HbA1c levels ≥8% compared with 34% of patients with secure attachment style (P = 0.002). After adjusting for demographics, diabetes severity, medical comorbidity, and depression, dismissing attachment style remained significantly associated with HbA1c levels ≥8%, compared with secure attachment style (odds ratio 2.5, 95% CI 1.1–6.0).

CONCLUSIONS—We have found that dismissing attachment style is associated with a higher risk for poor glycemic control. This has relevance from a population-based perspective because ∼25% of the general population has a dismissing attachment style. Attachment style is easily measured using self-report instruments and may inform clinicians how to work with patients who are less engaged in the health care relationship.