bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Exercise Training on Glucose Homeostasis
Authors: Boulé Normand G. , Weisnagel S. John , Lakka Timo A. , Tremblay Angelo , Bergman Richard N. , Rankinen Tuomo , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D.C. , Bouchard Claude 
Published: March 2007

OBJECTIVE—To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (IVGTT).
RESEARCH DESIGN AND METHODS—An IVGTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% Vo2max for 30 min per session to 75% Vo2max for 50 min per session.
RESULTS—Mean insulin sensitivity increased by 10% (P &lt; 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P &lt; 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P &lt; 0.001). The glucose area below fasting levels during the IVGTT was reduced by 7% (P = 0.02).
CONCLUSIONS—Although the effects of structured regular exercise were highly variable, there were improvements in virtually all IVGTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.
Improved Clinical Outcomes Associated With Metformin in Patients With Diabetes and Heart Failure
Authors: Eurich Dean T. , Majumdar Sumit R. , McAlister Finlay A. , Tsuyuki Ross T. , Johnson Jeffrey A. 
Published: March 2007

OBJECTIVE—Metformin is considered contraindicated in patients with heart failure because of concerns over lactic acidosis, despite increasing evidence of potential benefit. The aim of this study was to evaluate the association between metformin and clinical outcomes in patients with heart failure and type 2 diabetes.
RESEARCH DESIGN AND METHODS—Using the Saskatchewan Health databases, 12,272 new users of oral antidiabetic agents were identified between the years 1991 and 1996. Subjects with incident heart failure (n = 1,833) were identified through administrative records based on ICD-9 code 428 and grouped according to antidiabetic therapy: metformin monotherapy (n = 208), sulfonylurea monotherapy (n = 773), or combination therapy (n = 852). Multivariate Cox proportional hazards models were used to assess differences in all-cause mortality, all-cause hospitalization, and the combination (i.e., all-cause hospitalization or mortality).
RESULTS—Average age of subjects was 72 years, 57% were male, and average follow-up was 2.5 ± 2.0 (SD) years. Compared with sulfonylurea therapy, fewer deaths occurred in subjects receiving metformin: 404 (52%) for sulfonylurea monotherapy versus 69 (33%) for metformin monotherapy (hazard ratio [HR] 0.70 [95% CI 0.54–0.91]) and 263 (31%) for combination therapy (0.61 [0.52–0.72]). A reduction in deaths or hospitalizations was also observed: 658 (85%) for sulfonylurea monotherapy versus 160 (77%) for metformin monotherapy (0.83 [0.70–0.99]) and 681 (80%) for combination therapy (0.86 [0.77–0.96]). There was no difference in time to first hospitalization between study groups.
CONCLUSIONS—Metformin, alone or in combination, in subjects with heart failure and type 2 diabetes was associated with lower morbidity and mortality compared with sulfonylurea monotherapy.
Comparative Outcomes Study of Metformin Intervention Versus Conventional Approach The COSMIC Approach Study
Authors: Cryer Dennis R. , Nicholas Savian P. , Henry David H. , Mills Donna J. , Stadel Bruce V. 
Published: March 2007

OBJECTIVE—Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions.
RESEARCH DESIGN AND METHODS—The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization.
RESULTS—SAEs occurred in 10.3% (95% CI 9.6–11.1%) of the metformin group and in 11.0% (9.5–12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9–1.4%] vs. 1.3% [0.8–2.0%], P = 0.596) and hospitalization (9.4% [8.8–10.1%] vs. 10.4% [8.9–12.1%], P = 0.229) were similar between groups.
CONCLUSIONS—The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases.
β-Cell Response During a Meal Test
Authors: Cozma Lawrence S. , Luzio Stephen D. , Dunseath Gareth J. , Underwood Paul M. , Owens David R. 
Published: March 2007

OBJECTIVE—To assess the effects of incremental doses of repaglinide on postprandial insulin and glucose profiles after a standard 500-kcal test meal.
RESEARCH DESIGN AND METHODS—Sixteen diet-treated Caucasians with type 2 diabetes (mean HbA1c 8.4%) were enrolled in this randomized, open-label, crossover trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1 week apart.
RESULTS—The insulinogenic index (ΔI30/ΔG30) and insulin area under the curve (AUC) from 0 to 30 min (AUC0–30) were higher with the 4-mg drug dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On subgroup analysis, the incremental insulin responses were apparent only in the fasting plasma glucose (FPG) &lt;9-mmol/l subgroup of subjects and not in the FPG &gt;9-mmol/l subgroup. There was a significant dose-related increase in the late postprandial insulin secretion (insulin AUC120–240), which resulted in hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg) were more effective than the 0.5- and 1-mg doses.
CONCLUSIONS—Significant dose-related increases in early insulin secretion were found only in less advanced diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg) was significant compared with placebo. Better proinsulin-to-insulin processing was noted with increasing drug doses.
Anemia and Diabetes in the Absence of Nephropathy
Authors: Craig Kathrine J. , Williams John D. , Riley Stephen G. , Smith Hilary , Owens David R. , Worthing Debbie , Cavill Ivor , Phillips Aled O. 
Published: March 2007

OBJECTIVE—Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy.
RESEARCH DESIGN AND METHODS—The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA1c, and glomerular filtration rate.
RESULTS—In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb &lt;13g/dl and &lt;11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb ≤11.5) to that with the highest (Hb ≥14.5) Hb values, with a median Epo value of 37 (interquartile range 24–42) vs. 13 (9–15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from 44 (38–57) to 76.5 (56–83) in the lowest and highest Hb groups, respectively.
CONCLUSIONS—Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response.
Work Disability Among Individuals With Diabetes
Authors: Von Korff Michael , Katon Wayne , Lin Elizabeth H.B. , Simon Gregory , Ciechanowski Paul , Ludman Evette , Oliver Malia , Rutter Carolyn , Young Bessie 
Published: March 2007

OBJECTIVE—Diabetes is rapidly increasing in prevalence among working-age adults, but little is known about the clinical characteristics that predict work disability in this population. This study assessed clinical predictors of work disability among working-age individuals with diabetes.
RESEARCH DESIGN AND METHODS—In a cohort of diabetic individuals (n = 1,642) enrolled in a large health maintenance organization, excluding homemakers and retirees, we assessed the relation of diabetes severity, chronic disease comorbidity, depressive illness, and behavioral risk factors with work disability. Three indicators of work disability were assessed: being unable to work or otherwise being unemployed; missing ≥5 days from work in the prior month; and having severe difficulty with work tasks.
RESULTS—In the study population, 19% had significant work disability: 12% were unemployed, 7% of employed subjects had missed ≥5 days from work in the prior month, and 4% of employed subjects reported having had severe difficulty with work tasks. Depressive illness, chronic disease comorbidity, and diabetes symptoms were associated with all three types of work disability. Diabetes complications predicted unemployment and overall work disability status, whereas obesity and sedentary lifestyle did not predict work disability. Among subjects experiencing both major depression and three or more diabetes complications, &gt;50% were unemployed; of those with significant work disability, half met the criteria for major or minor depression.
CONCLUSIONS—Depressive illness was strongly associated with unemployment and problems with work performance. Disease severity indicators, including complications and chronic disease comorbidity, were associated with unemployment and overall work disability status. Effective management of work disability among diabetic patients may need to address both physical and psychological impairments.
The Beneficial Effects of Pancreas Transplant Alone on Diabetic Nephropathy
Authors: Coppelli Alberto , Giannarelli Rosa , Vistoli Fabio , Del Prato Stefano , Rizzo Gaetano , Mosca Franco , Boggi Ugo , Marchetti Piero 
Published: March 2007

OBJECTIVE—Pancreas transplant alone can be effective in significantly improving the quality of life of type 1 diabetic patients, and it can also eliminate acute diabetes complications, such as hypoglycemic and/or hyperglycemic episodes. The effects of pancreas transplant alone on long-term complications of diabetes, including nephropathy, are still not settled. We evaluated whether restoration of long-lasting normoglycemia by pancreas transplant alone might have beneficial action on diabetic nephropathy.
RESEARCH DESIGN AND METHODS—A total of 32 type 1 diabetic patients were evaluated before and 1 year after successful pancreas transplant alone, together with 30 matched nontransplanted type 1 diabetic subjects. Several metabolic and kidney function parameters were measured, including plasma glucose, glycohemoglobin (A1C), C-peptide, plasma lipids, blood pressure, creatinine, creatinine clearance, and urinary protein excretion.
RESULTS—Pancreas transplant alone restored sustained normoglycemia, without exogenous insulin administration, and improved plasma lipid levels. Blood pressure decreased significantly. Creatinine concentrations and clearances did not differ before and after transplantation. Urinary protein excretion decreased significantly after pancreas transplant alone, with four microalbuminuric and three macroalbuminuric patients who became normoalbuminuric. None of these changes occurred in the nontransplanted group.
CONCLUSIONS—Successful pancreas transplant alone, through restoration of sustained normoglycemia, improves diabetic nephropathy in type 1 diabetic patients.
Effects of Irbesartan on Intracellular Antioxidant Enzyme Expression and Activity in Adolescents and Young Adults With Early Diabetic Angiopathy
Authors: Chiarelli Francesco , Di Marzio Daniele , Santilli Francesca , Mohn Angelika , Blasetti Annalisa , Cipollone Francesco , Mezzetti Andrea , Verrotti Alberto 
Published: March 2007

OBJECTIVE—Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy.
RESEARCH DESIGN AND METHODS—This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14–21 years), 11 type 1 diabetic patients without angiopathy (ages 12–22 years), and 10 healthy volunteers (ages 16–22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco’s modified Eagle’s medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l).
RESULTS—At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 ± 0.21 units/mg protein, 4.4 ± 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 ± 0.04 units/mg protein, 0.08 ± 0.07 mRNA), CAT (0.32 ± 0.08 units/mg protein, 4.8 ± 1.3 mRNA), and GPX (0.53 ± 0.09 units/mg protein, 2.2 ± 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 ± 0.26 units/mg protein, 9.4 ± 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 ± 0.09 units/mg protein and 5.0 ± 1.4 mRNA; 0.54 ± 0.10 units/mg protein and 2.3 ± 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F2α) were significantly reduced after treatment with irbesartan.
CONCLUSIONS—Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.
Acute Psychological Stress Affects Glucose Concentrations in Patients With Type 1 Diabetes Following Food Intake but not in the Fasting State
Authors: Wiesli Peter , Schmid Christoph , Kerwer Oranna , Nigg-Koch Christel , Klaghofer Richard , Seifert Burkhardt , Spinas Giatgen A. , Schwegler Kyrill 
Published: March 2007

OBJECTIVE—To compare the effect of acute psychosocial stress on glucose concentrations in the fasting state and following food intake in patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS—In study 1, 20 patients were exposed to moderate psychosocial stress by means of the Trier Social Stress Test (TSST) in the fasting state. In study 2, the TSST was applied to 20 additional patients 75 min after intake of a standard meal. Glucose concentrations (by continuous glucose monitoring system), blood pressure, and heart rate were monitored on the control day and on the stress testing day.
RESULTS—In both studies, blood pressure increased in response to TSST from 122/77 ± 14/9 mmHg at baseline to a maximum of 152/93 ± 21/13 mmHg (P &lt; 0.001), and heart rate increased from 80 ± 11 to 99 ± 19 bpm (P &lt; 0.001). In the fasting state (study 1), glucose concentrations remained unchanged during the control day as well as during the stress testing day. In study 2, glucose concentrations were similar on both days before and up to 75 min after the intake of the standard meal. However, a significant delay (of 45 min) in the decrease of glucose concentrations was induced by psychological stress. A two-factor repeated-measures ANOVA revealed a significant difference of glucose concentrations over time (F = 646.65/P &lt; 0.001).
CONCLUSIONS—In the postprandial period, acute psychological stress induced a significantly delayed decrease of glucose concentrations, whereas in the fasting state, no effect on poststress glucose concentrations was observed.
Somatostatin Molecular Variants in the Vitreous Fluid
Authors: Hernández Cristina , Carrasco Esther , Casamitjana Roser , Deulofeu Ramon , García-Arumí José , Simó Rafael 
Published: March 2007

OBJECTIVE—There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured.
RESERCH DESIGN AND METHODS—Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14.
RESULTS—The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102–837] vs. 78 [24–32] pg/ml; patients with PDR: 187 [87–998] vs. 62 [24–472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 ± 32 vs. 595 ± 66 pg/ml; P = 0.004).
CONCLUSIONS—Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment.
PRESERVE-β
Authors: Gerich John , Raskin Philip , Jean-Louis Lisa , Purkayastha Das , Baron Michelle A. 
Published: March 2007

OBJECTIVE—To compare long-term efficacy and safety of initial combination therapy with nateglinide/metformin versus glyburide/metformin.
RESEARCH DESIGN AND METHODS—We conducted a randomized, multicenter, double-masked, 2-year study of 428 drug-naïve patients with type 2 diabetes. Patients received 120 mg a.c. nateglinide or 1.25 mg q.d. glyburide plus 500 mg q.d. open-label metformin for the initial 4 weeks. During a subsequent 12-week titration period, glyburide and metformin were increased by 1.25- and 500-mg increments to maximum daily doses of 10 and 2,000 mg, respectively, if biweekly fasting plasma glucose (FPG) ≥6.7 mmol/l. Nateglinide was not titrated. Blinding was maintained by use of matching placebo for nateglinide and glyburide. An 88-week monitoring period followed, during which HbA1c (A1C), FPG, and postprandial glucose excursions (PPGEs) during an oral glucose tolerance test were measured.
RESULTS—In nateglinide/metformin-treated patients, mean A1C was 8.4% at baseline and 6.9% at week 104. In glyburide/metformin-treated patients, mean A1C was 8.3% at baseline and 6.8% at week 104 (P &lt; 0.0001 vs. baseline for both treatments, NS between treatments). The ΔPPGE averaged −96 ± 19 (P &lt; 0.0001) and −57 ± 22 mmol · l−1 · min−1 (P &lt; 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas ΔFPG was –1.6 ± 0.2 (P &lt; 0.0001) and −2.4 ± 0.2 mmol/l (P &lt; 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P &lt; 0.01 between groups). Thus, the two treatments achieved similar efficacy with differential effects on FPG versus PPGE. Hypoglycemia occurred in 8.2 and 17.7% of patients receiving nateglinide/metformin and glyburide/metformin, respectively.
CONCLUSIONS—Similar good glycemic control can be maintained for 2 years with either treatment regimen, but nateglinide/metformin may represent a safer approach to initial combination therapy.
Targeting Plasma Glucose: Preprandial Versus Postprandial
Authors: Schrot Richard J. 
Published: March 2007

IN BRIEF
Considering there are potentially seven points within a 24-hour glucose profile (pre-meals, post-meals, and at bedtime), the question of which of these values to target is important to both patients and busy practitioners. Appropriate targeting of plasma glucose may lead to less expense and less unnecessary testing for patients and may help patients and practitioners achieve glucose goals more expeditiously. This article suggests that targeting fasting plasma glucose is more beneficial when hemoglobin A1c (A1C)results are very high, whereas targeting postprandial glucose is more effective when A1C results are lower.