bluuebunny/crossref_metadata_2025 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 < 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 < 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 < 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) <9-mmol/l subgroup of subjects and not in the FPG >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 <13g/dl and <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, >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 < 0.001), and heart rate increased from 80 ± 11 to 99 ± 19 bpm (P < 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 < 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 < 0.0001 vs. baseline for both treatments, NS between treatments). The ΔPPGE averaged −96 ± 19 (P < 0.0001) and −57 ± 22 mmol · l−1 · min−1 (P < 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas ΔFPG was –1.6 ± 0.2 (P < 0.0001) and −2.4 ± 0.2 mmol/l (P < 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P < 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.
Patient-Determined Glycosylated Hemoglobin Measurements: An Aid to Patient Education
Authors: McDermott K , Cooks M , Peterson C M
Published: March 2007

The feasibility of patient determination of fast fraction hemoglobin (HbA1) was evaluated. In the laboratory, the fast fraction method correlated well with known mixed standards of between 0 and 40% hemoglobin A1c (r2 = 0.97, slope 1.19) and reasonably well with radioimmunoassay (r2 = 0.78, slope 1.09), although prepackaged columns performed poorly about 18% of the time. Sixteen patients practicing home blood monitoring performed the determination of HbA1 on their own blood obtained from fingerstick. Two hours of patient training were required for the procedure. The correlation of patient determination of HbA1 with the results obtained by the laboratory on venous blood was reasonable (r2 – 0.81 with a slope of 0.88). Patient performance of HbA1 was useful in (1) providing enhanced reinforcement for self-monitoring programs, (2) engaging patients in groups in the monitoring process, and (3) providing an educational tool with which to teach pathophysiologic principles involved in diabetes mellitus.
Evaluation of a New Reflectance Photometer For Use in Home Blood Glucose Monitoring
Authors: Clarke William L , Melton Terry W , Sachse Marti , Schneider Jack M , Schneider Kathy D , Yarborough Margaret C
Published: March 2007

A new reflectance photometer (Glucometer, Ames Division, Miles Laboratories, Elkhart, Indiana) has been developed for use with the Dextrostix reagent strip. The device measures 8 × 17 cm, weighs 330 g, uses AA batteries, and requires no warm-up. High (330 mg/dl) and low (50 mg/dl) calibrations are stored in memory and need be repeated only when: (1) a control solution (100 mg/dl) reading is in error, (2) ambient temperature changes by more than 5°C, (3) a new bottle of Dextrostix is used, and (4) batteries are changed. A 60-s timer with alarm helps make timing of the procedure consistent. Nineteen insulin-dependent and one non-insulin-dependent diabetic subjects each performed a minimum of 20 blood glucose determinations over a 3-mo period in the investigators' laboratories. Simultaneous capillary blood samples were obtained for plasma glucose analysis by a comparative method. A total of 602 patient-determined glucose values ranging from 30 to 400 mg/dl were compared with simultaneous laboratory values. These values correlated significantly (r = 0.96, P < 0.0001, y = 2.6 + 0.92x). The Glucometer-Dextrostix System is an accurate and convenient method for home blood glucose monitoring by diabetic patients.
Implanting the Glucose Enzyme Electrode: Problems, Progress, and Alternative Solutions
Authors: Updike Stuart J , Shults Mark , Ekman Bo
Published: March 2007

An implantable glucose sensor is needed before a reliable artificial pancreas can be realized. The principles and current status of one such device, the glucose enzyme electrode, is presented and discussed. While monitoring glucose this enzyme sensor consumes enough oxygen to become oxygen-limited. This problem has been solved by developing hydrophobic membranes that are more permeable to oxygen than to glucose. Two types of membranes with this property made from (1) cross-linked albumin and (2) sebacyl chloride (nylon) are described. Placing these membranes over the glucose enzyme electrode solves the problem of oxygen limitation. Furthermore, the addition of this type of membrane increases the linear response range of the electrode to glucose to include the entire clinical range of interest (0-400 mg/dl). Other problems in developing an implantable glucose sensor are discussed. Competing strategies to achieve an implantable artificial pancreas without using electronic or mechanical components are presented and evaluated.
Dyschromatopsia in Diabetes Mellitus and its Relation to Metabolic Control
Authors: Muntoni Sergio , Serra Antonina , Mascia Chiara , Songini Marco
Published: March 2007

In 102 insulin-dependent diabetic patients without retinopathy and with visual acuity 20/20, the Farnsworth-Munsell 100-Hue test was performed, and glycosylated hemoglobin (GlHb) levels were determined. In 70% of the patients, a dyschromatopsia in the yellow-blue axis (tritanopia) was found. No correlation existed between duration of diabetes and tritanopia. On the other hand, the degree of this visual defect was positively correlated with GlHb levels. Thus, dyschromatopsia might be associated with poor metabolic control. It is suggested that dyschromatopsia is a consequence of hypoxia at the neuroepithelial level. The high levels of GlHb could be a contributory cause of hypoxia by reduction of both oxygen release capacity and erythrocyte deformability.
Treatment of Severe Lactic Acidosis with Dichloroacetate
Authors: Blackshear Perry J , Fang Leslie S-T , Axelrod Lloyd
Published: March 2007

Four patients with severe lactic acidosis associated with septic shock were treated with sodium dichloroacetate (DCA) (50 mg/kg body wt), an activator of pyruvate dehydrogenase. All patients were in a group with an expected mortality rate of 90–100%, based on previous studies. In one patient, treatment with DCA was associated with a decrease in blood lactate levels from 11.2 mM before treatment to 0.8 mM 16 h later. Markedly elevated blood pyruvate and alanine levels also decreased to normal. After treatment, the arterial blood pH rose to 7.53, and vasopressor agents were no longer needed to support blood pressure. Some degree of biochemical improvement was also noted in the other cases in whom the blood lactate levels before treatment were 15, 17, and 31 mM. However, all three patients eventually died of refractory acidosis.
Comparison of Plateau Insulin Levels Achieved by Intravenous or Subcutaneous Insulin Infusion: Evidence for Low Rates of Subcutaneous Degradation
Authors: Kraegen Edward W , Chisholm Donald J , Hewett Margot J
Published: March 2007

Continuous insulin infusion via the subcutaneous (s.c.) route is attractive for diabetes therapy because of its simplicity compared with other routes. Some insulin will be degraded locally before systemic absorption, although the magnitude of this degradation hasnot been established. We have performed in five normal subjects s.c. and intravenous (i.v.) insulin infusions (2.4 U/h) of sufficient duration to compare steady-state systemic appearance rates of exogenous insulin. A steady state was produced after 60–90 min (i.v.) and 6–8 h (s.c). Blood glucose fell to approximately 2.7 mmol/L in both studies and a fall in C-peptide indicated suppression of endogenous insulin secretion. Plateau insulin levels attributable to systemic entry of exogenous insulin were 36 ± 2.0 mU/L (i.v. route) and 29 ± 1.8 mU/L (s.c. route). These indicate a rate of s.c.degradation of insulin of 19 ± 5% in the steady state. We conclude that there is a low rate of degradation of insulin during continuous s.c. infusion.
The Prevalence of Diabetic Retinopathy: Effect of Sex, Age, Duration of Disease, and Mode of Therapy
Authors: Segal Pesach , Treister Giora , Yalon Moshe , Sandak Ruth , Berezin Meir , Modan Michaela
Published: March 2007

Studying 445 diabetic patients, we investigated the effects of sex, age, duration of disease, and mode of diabetes therapy on the prevalence of diabetic retinopathy. Of the study participants, 193 were treated with insulin injections, 164 took oral antidiabetic medications, and 88 were managed on diet alone. The prevalence of diabetic retinopathy washighest among insulin-treated patients (64%), while in the oral medication and diet groups, it was 36% and 12%, respectively. Diabetic retinopathy was more prevalent among patients with prolonged duration of disease. Sex and age did not seem to affect the prevalence of diabetic retinopathy when adjustments were made for the duration of disease.
Glycemic Response to Wheat Products: Reduced Response to Pasta but No Effect of Fiber
Authors: Jenkins David J A , Wolever Thomas M S , Jenkins Alexandra L , Lee Randolph , Wong Gerald S , Josse Robert
Published: March 2007

The blood glucose response to feeding 50-g carbohydrate portions of white and wholemeal bread and white spaghetti was studied in a group of nine diabetic subjects. Blood glucose rises after white and wholemeal bread were identical, but the response after spaghetti was markedly reduced. These results emphasize that food form rather than fiber may be important in determining the glycemic response and that pasta may be a useful source of carbohydrate in the diabetic diet.
Effect of Acute Blood Loss on Glycosylated Hemoglobin Determinations in Normal Subjects
Authors: Starkman Harold S , Wacks Marilyn , Soeldner J Stuart , Kim Agnes
Published: March 2007

Nondiabetic adult subjects (N = 12) were studied to determine the effect of an approximately 450-ml acute blood loss upon glycosylated hemoglobin measurements. After blood loss, the hematocrit significantly decreased by week 1 (P < 0.001) and the reticulocyte count peaked by week 2. All glycosylated hemoglobins measured showed significant decreases post blood loss. The nadir was at week 4 for total A1, A1c, and irreversible A1c by high-pressure liquid chromatography (HPLC), and at week 6 for irreversible A1 by HPLC and A1 by electrophoresis. The mean percent decrease in glycosylated hemoglobins ranged from 4.6% (irreversible A1 by HPLC) to 8.6% (total A1c by HPLC).
Referral Bias in Diabetes Research
Authors: Melton L Joseph , Ochi James W , Palumbo Pasquale J , Chu Chu Pin
Published: March 2007

Of all the known diabetic individuals residing in the community of Rochester, Minnesota, only about one-half would have been recognized through a review of the medical records of 1 yr. Only one-fifth of the diabetic residents were hospitalized during the index year and a similarly small proportion were attended in a diabetes clinic. This selective process produced distortion in the apparent clinical spectrum of diabetes observed at different levels in the medical care system. Notable was overestimation of the relative importance of insulin-dependent diabetes and of the vascular complications of diabetes among hospital and diabetes clinic patients. Referral bias should be taken into account when differences are noted in the epidemiologic features of diabetes as reported from different types of medical care settings.
Liver Function Tests in Diabetic Patients
Authors: Salmela Pasi I , Sotaniemi Eero A , Niemi Marja , Mäentausta Olli
Published: March 2007

Nine different liver function tests (LFT) were assessed in 175 unselected diabetic outpatients stabilized on diet, insulin, or oral hypoglycemic drugs. In another group of 72 diabetic inpatients having diagnostic liver biopsy, relationships between LFT and histologic changes in the liver were investigated. Abnormalities in at least one of the tests were noted in 57% of the outpatients, and two tests gave pathologic results in 27%. The non-insulin-dependent diabetic patients more often had abnormal LFT results than did the insulin-dependent diabetic patients. Serum chenodeoxycholic acid concentrations were increased in 27%, γ-glutamyl transpeptidase (gGT) activities in 19%, and alanine aminotransferase (Alt) activities in 17% of the outpatients, but the increases were rarely more than twice the upper limit of normal. In multivariate analysis, outpatients who were overweight, showed poor diabetes control during a short duration of diabetes controlled by treatment with diet or oral agents, and had a mature age at onset of diabetes displayed the most significant clinical explanatory variables associated with abnormal Alt. In the inpatients, the percentages of abnormal Alt and gGT results were augmented, along with increasing severity of histologic changes, but the mean values of Alt and gGT did not differ significantly between the various histologic groups. In addition, the diabetic patients with nonspecific inflammatory changes or increase in liver fibrosis often showed normal or only minor elevations in these test values.
Significance of Spontaneous Ketonuria and Serum C-Peptide Levels in Obese Type II Diabetic Patients
Authors: Osei Kwame , Falko James M , O'Dorisio Thomas M , Adam David R , Cataland Samuel
Published: March 2007

Patients with type II diabetes mellitus (type II DM patients) are characteristically obese, hyperinsulinemic, and non-ketosis prone. Recently, we have encountered several obese type II DM patients with either diabetic ketoacidosis or significant ketonuria after insulin withdrawal. There was no evidence of infection, stress, or starvation to explain their ketonuria. Therefore, we assessed serum connecting peptide (C-peptide) response to oral glucose in 14 obese, insulin-treated type II DM patients: 6 with and 8 without episodes of spontaneous ketonuria. The group presenting with ketonuria had low to absent basal and stimulated serum C-peptide responses. The nonketonuric group had higher basal C-peptide (P < 0.01) concentrations that increased significantly (P < 0.001) after oral glucose compared with those of the ketonuric group. Clinical characteristics and biochemical control were similar in both groups. Our findings confirm that obese type II diabetes mellitus is a heterogeneous disease with variable fasting and stimulated C-peptide responses. Spontaneous ketonuria could be a feature in the clinical presentation of the patients especially in the presence of both low fasting and stimulated C-peptide levels. The significance of these findings is unclear but suggests individualization in the management of type II DM patients and cautious withdrawal of insulin therapy in such patients. Furthermore, serum C-peptide levels alone cannot be recommended to classify patients into either type I or type II diabetes mellitus.
Effect of Protein Ingestion on the Glucose and Insulin Response to a Standardized Oral Glucose Load
Authors: Nuttall Frank Q , Mooradian Arshag D , Gannon Mary C , Billington Charles , Krezowski Phillip
Published: March 2007

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 ± 35, 83 ± 19 µU · h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 ± 33 µU · h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.
Epidemiology and Treatment of Diabetic Ketoacidosis in a Community Population
Authors: Ellemann K , Soerensen J Noertved , Pedersen L , Edsberg B , Andersen O Ortved
Published: March 2007

We evaluated the epidemiology of diabetic ketoacidosis in the period 1960–1979. In Frederiksborg County, Denmark, the incidence of ketoacidosis at the county hospital increased from 60 per 100,000 in the period 1943–1963 to 120 per 100,000 in the period 1960–1979. In the investigation period we found an increasing incidence confined to urban areas. Precipitating factors were not somatic in 53% of the cases. Patients in the lowest social class (V) were in a higher risk group, experiencing ketoacidosis more often and having a higher frequency of severe acidosis. Forty-nine percent of the patients have had a diabetes duration of more than 5 yr. The lethality rate decreased from the period 1943–1963 and was 4.7% in the investigation period 1960–1979.
Retinopathy in Young-onset Diabetic Patients
Authors: Klein Ronald , Klein Barbara E , Moss Scot E , Davis Matthew D , DeMets David L
Published: March 2007

The relative importance of duration of diabetes before and after 13 yr of age as a risk factor for retinopathy was investigated using data from 200 persons who were younger than 26 yr of age. These persons were identified in a population-based study of diabetic retinopathy in southern Wisconsin in 1980–1982. Retinopathy was found in 9% of persons who were younger than 13 yr and in 34% of persons who were 13 yr or older and had been diagnosed at or after 13 yr. Presence of retinopathy was more strongly associated with the duration of diabetes after 13 yr of age than before it.
Blood Glucose Control by Intermittent Loop Closure in the Basal Mode: Computer Simulation Studies with a Diabetic Model
Authors: Furler Stuart M , Biomed E M , Kraegen Edward W , Smallwood Robert H , Chisholm Donald J
Published: March 2007

A semiclosed loop, bedside insulin infusion system using a simple basal infusion algorithm consisting of a linear transition between two insulin delivery rates as blood glucose (BG) increases has been developed. A theoretical study using computer simulation has now been undertaken to examine the effect of BG sampling frequency and algorithm parameters on BG control. A model for BG control by exogenous insulin in the individual with diabetes was developed from a model for healthy subjects and from clinical data in the literature. Results of computer simulation using this model showed a decrease in BG stability as the sampling interval increased from 1 to 4 h. Simulations also showed a decrease in BG stability as the sensitivity of the control algorithm increased. Choice of an appropriate basal control algorithm involved a compromise between stability, sampling interval, and metabolic control. We conclude that satisfactory metabolic control can be obtained using intermittent BG sampling in the basal state; sampling at intervals of 3 h combined with a basal control algorithm whereby insulin delivery rate increases linearly from 0.5 to 2.5 U/h over the BG range 2–12 mmol/L appears suitable for most diabetic persons. Three-hour sampling offers a good compromise between degree of metabolic control and clinical effort involved.
Reagent Strip Glucose Monitoring Methods in Chronic Hemodialysis
Authors: Wason Candace J , Green Jacqueline , Miller Clara , Roxe David M
Published: March 2007

Reagent strip blood glucose testing methods have not been extensively validated in dialysis patients, a serious omission as thousands of diabetic patients are now entering dialysis. Severe anemia and uremia are potentially confounding variables that might impair those testing methods. Various methods were tested pre- and postdialysis, and compared with standard laboratory results. In general, strip methods (SM) underestimated laboratory results by approximately 15%. Extremes of blood urea nitrogen, hematocrit, or blood glucose levels did not affect this reliability. Such methods appear to be suitable for use in chronic hemodialysis patients.
Hypoglycemia and Counterregulation in Insulin-Dependent Diabetic Patients: A Comparison of Continuous Subcutaneous Insulin Infusion and Conventional Insulin Injection Therapy
Authors: Ng Tang Fui S , Pickup J C , Bending J J , Collins Andrea C G , Keen H , Dalton N
Published: March 2007

Eleven insulin-dependent diabetic patients were treated in random order by 2-mo continuous subcutaneous insulin infusion (CSII) or 2-mo conventional injection treatment (CIT)with crossover to the alternative regimen. Mean plasma glucose concentrations throughout the day were significantly lower during CSII than during CIT, but the percentage of plasma glucose values <2.5 mmol/L, obtained from outpatient self-collected diurnal profiles, was similar for both treatments (CSII vs. CIT: 5.9 and 4.8%, respectively). Reported symptomatic hypoglycemia at home was not significantly different in the whole group of patients treated by CSII or CIT but was reduced by a mean of 57% (P < .02) in the five patients on CSII who experienced frequent symptomatic hypoglycemic episodes (>4/2 mo) during CIT. Neither the plasma glucose concentration at which the patients recognizedinduced hypoglycemia nor the glycemic or counterregulatory hormone responses for 60 min thereafter were changed by CSII treatment.
Telemetry Glucose Monitoring Device With Needle-Type Glucose Sensor: A Useful Tool for Blood Glucose Monitoring in Diabetic Individuals
Authors: Shichiri Motoaki , Asakawa Nobuyuki , Yamasaki Yoshimitsu , Kawamori Ryuzo , Abe Hiroshi
Published: March 2007

For continuous monitoring of glucose concentration in ambulant diabetic patients, a telemetry glucose monitoring system with a needle-type glucose sensor has been developed. The system consists of a sensor transmitter (4 × 6 × 2 cm, 50 g) that converts current signals generated in a needle-type glucose sensor to high-frequency audio signals and a receiver that continuously calculates glucose concentrations from the received audio signals. The noise range of a monitoring record with the telemetry system (0.3 ± 0.04%, mean ± SEM) was significantly smaller than that with a wire-connected system, the wearable artificial endocrine pancreas (2.5 ± 0.3%). Postprandial tissue glucose concentration responded well to the plasma glucose concentration, with a time lag of 5 min. Continuous glucose monitoring of five diabetic subjects for 77 ± 22 h revealed that a significant correlation existed between the subcutaneous tissue glucose concentration and the plasma glucose concentration measured simultaneously in each patient. These data indicate the usefulness of the telemetry glucose monitoring system in strict glycemic control of diabetic individuals.
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.
Alteration of distal tarsal subchondral bone thickness pattern in horses with tarsal pain
Authors: BRANCH M. V. , MURRAY R. C. , DYSON S. J. , GOODSHIP A. E.
Published: March 2007

Reasons for performing study: Understanding of the development of pathology and source of pain in distal tarsal osteoarthritis is poorly understood. Magnetic resonance imaging is often used in the analysis of human osteoarthritis (OA) because it is sensitive to early changes.

Hypothesis: In association with distal tarsal joint (DTJ) pain, there will be an alteration in the characteristic subchondral bone (SCB) thickness pattern of horses with no history of pain when subjected to low‐level exercise.

Methods: Sixteen cadaver tarsal joints were collected from 9 mature horses with a history of tarsal pain and radiographic evidence of OA; 3 cadaver tarsi were collected from 2 mature horses with a history of tarsal pain and no radiographic abnormality. Magnetic resonance images were acquired using high‐resolution sagittal 3D T1 weighted spoiled gradient echo sequence. Subchondral bone thickness was measured on sagittal images at dorsal and plantar locations on the proximal and distal aspects of the central (CT) and third (T3) tarsal bones and proximal aspect of the third metatarsal bone (MT3).

Results: In tarsi with radiographic evidence of OA medial and lateral SCB thicknesses were greater than midline on the proximal and distal aspects of CT and T3. Lateral SCB thickness was greater than medial on the proximal aspect of MT3. There was an increase in SCB thickness at the majority of sites compared with normal horses. There were too few joints in the group without radiographic changes to analyse statistically. In painful tarsi SCB thickness was greater medially than laterally at all sites. In horses without tarsal pain all lateral sites had greater SCB thickness, except the proximal aspect of CT.

Conclusions: There is alteration of normal SCB thickness patterns in painful tarsi. Different thickness patterns could represent different types of pathological processes.

Potential clinical relevance: Further work is required to elucidate the pathological processes leading to OA of the DTJs.