bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Pulsatile Versus Continuous Insulin Administration on Hepatic Glucose Production and Glucose Utilization in Type I Diabetic Humans
Authors: Bratusch-Marrain P R , Komjati M , Waldhäusl W K 
Published: September 2013

To evaluate the role of pulsatile insulin administration, hepatic glucose production (HGP) and utilization were studied in type I diabetic patients in the fasting state and during a euglycemic insulin (1 mU · kg−1 · min−1 i.v.) clamp with continuous and pulsatile insulin administration. In the latter study, insulin was infused at twice the continuous rate with 3-min-on/7-min-off intervals, thereby reducing total insulin delivery by 40%. The restraining effect of pulsatile insulin on basal HGP (1.91 ± 0.35 mg · kg−1 · min−1) was equipotent to continuous insulin exposure (1.80 ± 0.17 mg · kg−1 min−1). During the insulin-clamp studies, HGP was equally suppressed by pulsed (0.62 ± 0.12 mg · kg−1 min−1) as by continuous insulin infusion (0.63 ± 0.12 mg · kg−1 · min−1). Insulin-stimulated glucose utilization was not significantly altered in either study (2.55 ± 0.27 vs. 2.92 ± 0.23 mg · kg−1 min−1). When in further studies the total insulin dose given during the pulsatile study was infused continuously (0.6 mU · kg−1 · min−1), HGP in the basal state and residual HGP during the insulin-clamp study were 25–30% higher than in the pulsatile experiments, whereas glucose utilization was not significantly different.
In conclusion, by reducing total hormone delivery by up to 40%, but given in a pulsatile fashion, insulin is equally potent in controlling HGP as continuous insulin administration. This greater efficacy of pulsatile exposure in suppressing HGP is accompanied by an equipotent effect on glucose utilization. Application of pulsatile insulin substitution in intravenous-pump users may reduce systemic hyperinsulinemia and, in the long run, insulin resistance by reversing downregulation of insulin receptors.
Effects of Weight Loss on Mechanisms of Hyperglycemia in Obese Non-Insulin-Dependent Diabetes Mellitus
Authors: Henry R R , Wallace P , Olefsky J M 
Published: September 2013

To quantitate the effects of weight loss on the mechanisms responsible for hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), eight obese subjects with NIDDM were studied before and after weight reduction with posttreatment assessment after 3 wks of isocaloric (weight maintenance) refeeding.
After weight loss of 16.8 ± 2.7 kg (mean ± SE), the fasting plasma glucose level decreased 55% from 277 ± 21 to 123 ± 8 mg/dl. The individual fasting glucose levels were highly correlated with the elevated basal rates of hepatic glucose output (HGO) (r = 0.91, P &lt; .001), which fell from 138 ± 11 to 87 ± 5 mg · m2 · min1 after weight loss. The change in fasting plasma glucose also correlated significantly with the change in the basal rates of HGO (r = 0.74, P &lt; .05). This was associated with reduced fasting serum levels of glucagon (from 229 ± 15 to 141 ± 12 pg/ml), reduced free fatty acids (from 791 ± 87 to 379 ± 35 μeq/L), and unchanged basal insulin levels (17 ± 4 to 15 ± 2 fill/ml).
Peripheral glucose disposal, assessed by the euglycemic glucose-clamp technique, at insulin infusion rates of 120 and 1200 mU · m2 · min1 increased between 135 and 165%, from 128 ± 17 to 288 ± 24 mg · m2 · min1 during the 120-mU · m2 · min1 studies and from 159 ± 19 to 318 ± 24 mg · m2 · min1 during the 1200-mU · m2 · min1 clamp studies, despite comparable steady-state serum insulin levels at each infusion rate before and after weight loss. HGO during the 120-mU · m2 · min1 clamp studies increased from 85% to complete (100%) suppression after treatment. Adipocyte size was reduced 44% (851 ± 91 to 475 ± 48 pi), whereas surface area decreased by 32% (4.30 × 104 to 2.92 × 104 μm2cell). Insulin binding to isolated adipocytes was unchanged, whereas basal in vitro rates of 3-O-methylglucose transport increased from 0.21 ± 0.13 to 0.53 ± 0.24 pmol/(2 × 109 μm2) × (10 s−1) and maximal glucose transport rates increased from 0.64 ± 0.29 to 1.18 ± 0.48 pmol/(2 × 105 cells) × (10 s−1) and 0.42 ± 0.20 to 1.04 ± 0.30 pmol/(2 × 109 μm2) × (10 s−1).
Finally, absolute serum insulin levels during oral glucose-tolerance tests and meal-tolerance tests were unchanged by weight reduction, whereas plasma glucose levels were markedly reduced.
We conclude that in obese NIDDM, weight loss results in improved glucose homeostasis with 1) reducedbasal HGO predominently responsible for the lowering of fasting glucose levels; 2) improved postprandial glucose excursions with marked amelioration of peripheral insulin resistance due to improved postreceptor insulin action, which is at least partly due to enhanced glucose transport system activity; and 3) unchanged absolute insulin levels in the face of markedly reduced glycemia, indicative of enhanced p-cell sensitivity to insulinogenic stimuli.
Trapped Immunoglobulins on Peripheral Nerve Myelin From Patients With Diabetes Mellitus
Authors: Brownlee M , Vlassara H , Cerami A 
Published: September 2013

Diabetic peripheral neuropathy is characterized by endoneurial capillary closure and by segmental demyelination and axonal degeneration in a spatial pattern consistent with ischemic damage. The increased permeability of human diabetic endoneurial capillaries to plasma proteins may contribute to the pathogenesis of these structural changes in peripheral nerve by further accelerating the rate at which plasma proteins are trapped by reactive nonenzymatic glycosylation products on long-lived proteins such as myelin.
We have measured trapped immunoglobins (Ig)G and M on peripheral nerve myelin from diabetic and nondiabetic patients by an enzyme-linked immunosorbent assay to determine whether plasma proteins accumulate on nerves as they do in the glomerular matrix of diabetics. The amount of trapped IgG on brain myelin from these subjects was also determined.
Peripheral nerve myelin from diabetics had on average &gt;14 times the amount of trapped IgM found in identically prepared samples from nondiabetics (0.90 ± 0.2 vs. 0.06 ± 0.004 OD/μ.g myelin protein) and &gt;4 times the amount of trapped IgG (6.40 ± 1.92 vs. 1.5 ± 0.25 OD/μg myelin protein). In contrast, no significant trapping of IgG was detected in any samples of brain myelin. This most likely reflects effective exclusion of IgG by the blood-brain barrier.
These data suggest that excessive trapping of Igs and other plasma proteins by diabetic peripheral nerve myelin may contribute to the development of peripheral nerve damage, whereas the lack of such trapping by brain myelin may partly explain the rarity of diabetic central neuropathy.
Effect of Aldose Reductase Inhibitor ONO 2235 on Reduced Sympathetic Nervous System Activity and Peripheral Nerve Disorders in STZ-lnduced Diabetic Rats
Authors: Yoshida Toshihide , Nishioka Hitoshi , Yoshioka Keiji , Nakanoa Koji , Kondo Motoharu , Terashima Hiroshi 
Published: September 2013

To test the hypothesis that inhibitors of aldose reductase, a key enzyme for polyol synthesis, prevent the decrease of sympathetic nervous system (SNS) activity and improve motor nerve conduction velocity (MNCV) through the reduction of sorbitol accumulation in streptozocin (STZ)-induced diabetic rats, norepinephrine (NE) turnover (reliable indicator of SNS activity in the interscapular brown adipose tissue (IBAT), heart, and pancreas), and MNCV were measured in untreated STZ-induced diabetic rats, STZ-induced diabetic rats treated with an aldose reductase inhibitor (ARI) (ONO 2235, 50 mg · kg−1 · day−1, orally), STZ-induced diabetic rats treated with insulin therapy, control rats, and control rats treated with ARI. As expected, results from studies with the inhibition of NE biosynthesis with α-methyl-p-tyrosine or radiolabeled NE to measure NE turnover demonstrated significant reductions in SNS activity in IBAT, heart, and pancreas of untreated STZinduced diabetic rats, compared with those in control rats. MNCV determined with the tail nerve was significantly reduced in untreated STZ-induced diabetic rats, compared with that of the controls. Both daily ARI treatment and insulin therapy in STZ-induced diabetic rats prevented partially but significantly the decrease of NE turnover in IBAT, heart, and pancreas, ameliorated MNCV, and reduced sorbitol accumulation in the nerve tissue and red blood cells. ARI treatment in control rats had no effect on NE turnover, MNCV, or sorbitol content.
These results suggest that STZ-induced diabetic rats had not only motor neuropathy but also sympathetic nervous dysfunction and that ARI treatment might prevent these as well as insulin therapy does through the reduction of sorbitol accumulation.
Effect of Glyburide on Glycemic Control, Insulin Requirement, and Glucose Metabolism in Insulin-Treated Diabetic Patients
Authors: Simonson Donald C , Delprato Stefano , Castellino Pietro , Groop Leif , DeFronzo Ralph A 
Published: September 2013

Glycemic control and glucose metabolism were examined in 5 patients with insulin-dependent diabetes mellitus (IDDM) and 8 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients before and after 2 mo of therapy with glyburide (20 mg/day). Glycemic control was assessed by daily insulin requirement, 24-h plasma glucose profile, glucosuria, and glycosylated hemoglobin. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, and insulin sensitivity was determined by a two-step euglycemic insulin clamp (1 and 10 mU ·kg−1 · min−1) performed with indirect calorimetry and [3−3H]glucose.
In the IDDM patients, the addition of glyburide produced no change in daily insulin dose (54 ± 8 vs. 53 ± 7 U/day), mean 24-h glucose level (177 ± 20 vs. 174 ± 29 mg/dl), glucosuria (20 ± 6 vs. 35 ± 12 g/day) or glycosylated hemoglobin (10.1 ± 1.0 vs. 9.5 ± 0.7%). Furthermore, there was no improvement in basal hepatic glucose production (2.1 ± 0.2 vs. 2.4 ± 0.1 mg · kg−1 · min−1), suppression of hepatic glucose production by low- and high-dose insulin infusion, or in any measure of total, oxidative, or nonoxidative glucose metabolism in the basal state or during insulin infusion. C-peptide levels were undetectable (&lt;0.01 pmol/ml) in the basal state and after glucagon infusion and remained undetectable after glyburide therapy.
In contrast to the IDDM patients, the insulin-treated NIDDM subjects exhibited significant reductions in daily insulin requirement (72 ± 6 vs. 58 ± 9 U/day), mean 24-h plasma glucose concentration (153 ± 10 vs. 131 ± 5 mg/dl), glucosuria (14 ± 5 vs. 4 ± 1 g/day), and glycosylated hemoglobin (10.3 ± 0.7 vs. 8.0 ± 0.4 %) after glyburide treatment (all P ≤ .05). However, there was no change in basal hepatic glucose produc-tion (1.7 ± 0.1 vs. 1.7 ± 0.1 mg kg−1 min−1), suppression of hepatic glucose production by insulin, or insulin sensitivity during the two-step insulin-clamp study. Both basal (0.14 ± 0.05 vs. 0.32 ± 0.05 pmol/ ml, P &lt; .05) and glucagon-stimulated (0.24 ± 0.07 vs. 0.44 ± 0.09 pmol/ml) C-peptide levels rose after 2 mo of glyburide therapy and both were correlated with the decrease in insulin requirement (basal: r = .65, P = .08; glucagon stimulated: r = .93, P &lt; .001).
These data indicate that in IDDM subjects, the addition of glyburide to insulin does not affect insulin requirement, glycemic control, or insulin sensitivity. In contrast, in insulin-treatedNIDDM patients, glyburide produces a modest decrease in insulin dose and improves glycemic control without altering insulin sensitivity. This improvement in glucose metabolism primarily reflectsan increase in endogenous insulin secretion.
Plasma Insulin Response Among Nauruans: Prediction of Deterioration in Glucose Tolerance Over 6 Yr
Authors: Sicree Richard A , Zimmet Paul Z , King Hilary O M , Coventry Janice S 
Published: September 2013

A longitudinal study of 266 randomly selected nondiabetic Nauruans [215 with normal tolerance and 51 with impaired glucose tolerance (IGT)] over 6 yr showed that deterioration in glucose tolerance status had occurred in 61 subjects. Of the subjects with initially normal tolerance, 34 (16%) progressed to IGT and 14 (6.5%) progressed to diabetes. Thirteen of the subjects with IGT (25%) progressed to diabetes.
Subjects were examined in 1975 through 1976, and follow-up examinations were performed in 1982. After age, a high 2-h plasma insulin response to a glucose load was the factor most predictiveof progression from normal tolerance to both diabetes (P &lt; .001) and IGT (P &lt; .01). Both a high 2-h glucose level and greater obesity independently predicted progression from IGT, and a diminished 2-h insulin response just failed to significantly improve the model (P &lt; .06). The negative parameter of the insulin response associated with deterioration from IGT differed significantly (P &lt; .01) from the positive-parameter estimate of the response associated with progression to diabetes from normal tolerance (P &lt; .01), implying a qualitative difference between these nondiabetic subgroups. The use of a glucose-insulin interaction term to predict (P &lt; .01) progression to diabetes for all nondiabetic subjects confirmed this difference; this term's addition improved the model (P &lt; .01), and progression to diabetes was associated with a high insulin response for 2-h glucose &lt;7.8 mM but a low response for 2-h glucose &gt;7.8 mM.
Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance Among Second-Generation Japanese-American Men
Authors: Fujimoto Wilfred Y , Leonetti Donna L , Kinyoun James L , Newell-Morris Laura , Shuman William P , Stolov Walter C , Wahl Patricia W 
Published: September 2013

We describe the initial findings from a multidisciplinary, epidemiologic study of diabetes mellitus conducted in a population of secondgeneration Japanese-American (Nisei) men born between 1910 and 1939 who reside in King County, Washington (n = 1746). From this study population, 487 volunteered, and 229 were enrolled to comprise the study sample. A random sample of Nisei men was also drawn from the population to develop a reference sample of 189 men.
All subjects participated in a 75-g oral glucose tolerance test; the National Diabetes Data Group (NDDG) and World Health Organization (WHO) diagnostic criteria as well as a modification of the WHO criteria were used to classify individuals with normal glucose tolerance, impaired glucose tolerance (IGT), or diabetes. Within the study sample, 79 men were found to have normal glucose tolerance, 72 had IGT, and 78 had type II diabetes. The mean age of the study sample was 61.4 yr. Based on comparison of the study sample to the reference sample, the study sample was ascertained to be representative of Nisei men in King County.
Extrapolating from our observations in the reference sample and in the study sample, we have estimated that ∼56% of Nisei men in the study population have abnormal glucose tolerance. Much of this is undiagnosed because only ∼13% of the reference sample of Nisei men reported a prior diagnosis of diabetes. Of the men who enrolled in the study as nondiabetic subjects, 11.1% had diabetes and 39.2% had IGT; i.e., 50.3% had previously unknown abnormalities in glucose tolerance. We estimate that ∼20% of Nisei men have diabetes (both previously diagnosed and undiagnosed) and ∼36% have IGT.
Prevalence of Complications Among Second-Generation Japanese-American Men With Diabetes, Impaired Glucose Tolerance, or Normal Glucose Tolerance
Authors: Fujimoto Wilfred Y , Leonetti Donna L , Kinyoun James L , Shuman William P , Stolov Walter C , Wahl Patricia W 
Published: September 2013

In a study sample of 229 second-generation Japanese- American (Nisei) men, 79 with normal glucose tolerance, 72 with impaired glucose tolerance (IGT), and 78 with non-insulin-dependent diabetes, we have determined prevalence rates for certain conditions (ischemic heart disease, peripheral vascular disease, hypertension, retinopathy, neuropathy, and nephropathy) associated with diabetes. All subjects participated in a 75-g oral glucose tolerance test. World Health Organization (WHO) diagnostic criteria and information from the subject's medical history and personal physician were used to classify the subjects.
Retinopathy was observed only in diabetic men in the study sample (11.5% of diabetic men). Furthermore, it was observed only in men who were receiving drug treatment for diabetes—40.0% of insulin-treated and 17.2% of sulfonylurea-treated men. Electrophysiologic evidence of peripheral neuropathy was observed in 46.2% of diabetic men and in 4.0% of nondiabetic (normal and IGT) men. For diabetic men with fasting serum glucose ≥140 mg/dl, 63.8% had peripheral neuropathy and 19.1% had retinopathy, whereas for diabetic men with fasting serum glucose &lt;140 mg/dl, 19.4% had neuropathy and none had retinopathy. For diabetic men with a diabetes duration of 2:10 yr, 72.7% had neuropathy and 31.8% had retinopathy; with a diabetes duration of 5-9 yr, 70.6% had neuropathy and 11.8% had retinopathy; and with a diabetes duration of &lt;5 yr, 20.5% had neuropathy and none had retinopathy. Nephropathy was distinctly uncommon, and among the measurements of kidney function, only proteinuria was clearly abnormal with diabetes. Prevalence rates of hypertension, peripheral vascular disease, and ischemic heart disease were highest in Nisei men with diabetes, lowest in men with normal glucose tolerance, and intermediate in men with IGT. None of these conditions appeared to be strongly related to the degree of fasting hyperglycemia. Hypertension occurred in 53.8% of diabetic men, 51.4% of men with IGT, and 29.1% of men with normal glucose tolerance (blood pressure &gt; 140/90 and/or treatment with medication for hypertension). Arteriosclerosis obliterans of the lower leg vessels was determined by Doppler technique to occur in 24.4% of diabetic men, 16.7% of men with IGT, and 8.9% of men with normal glucose tolerance. Ischemic heart disease, as determined from a resting electrocardiogram and the Minnesota Code criteria for ischemic heart disease, occurred in 29.5% of diabetic men, 23.6% of men with IGT, and only 6.3% of men with normal glucose tolerance.
Nonenzymatic Glycosylation of Serum IgG and Its Effect on Antibody Activity in Patients With Diabetes Mellitus
Authors: Kaneshige Hideaki 
Published: September 2013

Susceptibility to infection is assumed to be increased in diabetic patients, although its mechanism is unknown. The purpose of this study was to determine whether glycosylation of circulating immunoglobulins is related to the decrease of antibody activity in diabetic patients. Thirty-five patients with type II (non-insulin-dependent) diabetes and 14 age-matched normal controls were examined. Nonenzymatic glycosylation of serum immunoglobulin G (IgG) in vivo was measured by two different techniques, colorimetry and affinity chromatography. The levels of glycosylated IgG were significantly higher in diabetic patients than in normal controls.
To evaluate the antibody activity of glycosylated IgG, anti-streptolysin O (ASO) titers after in vitro glycosylation of IgG and antibody titers before and after in vivo immunization with influenza vaccine were determined. IgG specific for streptolysin O purified by affinity chromatography decreased ASO titers after in vitro glycosylation. In diabetic patients, serum titers of hemagglutinin-inhibiting antibody against influenza viruses 4 wk after initial immunization were significantly lower than those in normal controls. These results indicate that serum IgG in diabetic patients was nonenzymaticaliy glycosylated, and this modification in vivo might be associated with its functional alteration.
Alterations in Free Radical Tissue-Defense Mechanisms in Streptozocin-Induced Diabetes in Rat: Effects of Insulin Treatment
Authors: Wohaieb Saleh A , Godin David V 
Published: September 2013

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9–12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status.
Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
Detection of Potentially Reversible Diabetic Albuminuria: A Three-drop Agglutination Test for Urinary Albumin at Low Concentration
Authors: Viberti G C , Vergani D 
Published: September 2013

Subclinical elevation of urinary albumin excretion early in the course of insulin-dependent diabetes has been shown to predict later clinical proteinuria. An agglutination test (Three-drop Albutest) to detect these lesser degrees of albuminuria has been developed. Rabbit anti-human albumin antiserum is immobilized on latex beads. In the presence of human albumin and additional antiserum in solution, a visible precipitate appears. Concentrations of solid and liquid phase antiserum have been adjusted to detect urinary albumin concentrations ranging between 2.5 and 17 mg/dl, undetectable by a standard clinical method (Albustix, Ames Company, Miles Laboratories Ltd, Stoke Poges, Slough, Bucks, England). The test is specific for albumin, failing to cross-react with other plasma proteins present in urine or with bovine serum albumin. It is simple to perform and is read within 5 min.
This test should find a place in the early detection of diabetics with subclinical albuminuria and in monitoring the success of attempts to reverse this risk factorfor clinical diabetic nephropathy.