bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irreversibility of the Defect in Glycogen Synthase Activity in Skeletal Muscle From Obese Patients With NIDDM Treated With Diet and Metformin
Authors: Damsbo Peter , Hermann Leif S , Vaag Allan , Hother-Nielsen Ole , Beck-Nielsen Henning 
Published: March 2007

OBJECTIVE
To assess the reversibility of the defect in glycogen synthase (GS) activity in skeletal muscle from obese patients with NIDDM treated with a hypocaloric diet and metformin.

RESEARCH DESIGN AND METHODS
Eighteen obese patients newly diagnosed with NIDDM were included in a randomized placebo-controlled double-blind parallel group trial and followed for 3 months. Euglycemic-hyperinsulinemic clamp including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus metformin or placebo. The patients were studied at basal, low, and high insulin concentrations.

RESULTS
The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia (for 8 h) or by chronic reduction of hyperglycemia by diet plus metformin. In both treatment groups, comparable effects on glycemic control and weight loss were found together with marked insulin suppression of nonesterified fatty acids and increased glucose oxidation. Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25% at high insulin level (259 ± 31 vs. 207 ± 21 mg · m−2 · min−1, P &lt; 0.05). An insignificant increase by 13% was found in the placebo group. There were no significant changes in nonoxidative glucose metabolism. GS activity and glucose utilization showed no significant differences between the two treatment groups when regression coefficients, expressed as incremental changes by increments of insulin, were compared.

CONCLUSIONS
Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia. Metformin and diet had no significant influence on GS activity. The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss.
Urinary Albumin Excretion Rate and Glomerular Filtration Rate in Single-Kidney Type 2 Diabetic Patients
Authors: Silveiro Sandra P , da Costa Luciana A , Beck Maristela O , Gross Jorge L 
Published: March 2007

OBJECTIVE
To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN).

RESEARCH DESIGN AND METHODS
Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 ± 9 years; diabetes duration 8.5 ± 7 years), 17 SKN (2 men, age 57 ± 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method.

RESULTS
SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 μg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER &gt;200 μg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 ± 21.4 ml · min−1 · 1.73 m−2) and SKD patients (73.0 ± 21.5 ml · min−1 · 1.73 m−2) were similar but higher than the one-kidney GFR (GFR ÷ 2) of the age-, sex-, and BMI-matched normal individuals (50.5 ± 9.0 ml · min−1 · 1.73 m−2) and normoalbuminuric type 2 diabetic patients (54.0 ± 11.6 ml · min−1 · 1.73 m−2).

CONCLUSIONS
Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.
Involvement of Peripheral Polymorphonuclear Leukocytes in Oxidative Stress and Inflammation in Type 2 Diabetic Patients
Authors: Shurtz-Swirski Revital , Sela Shifra , Herskovits Avraham T. , Shasha Shaul M. , Shapiro Galina , Nasser Lubna , Kristal Batya 
Published: March 2007

OBJECTIVE— To determine the extent to which peripheral polymorphonuclear leukocytes (PMNs) contributed to oxidative stress (OS) and inflammation in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS— PMNs and plasma were separated from blood withdrawn from 18 type 2 diabetic patients and 16 age- and sex-matched normal control subjects. The rate of superoxide release from phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs and the plasma glutathione (GSH) levels served as measures of OS. Inflammation was assessed by PMN recruitment, expressed by peripheral blood PMN counts, and the in vitro survival of PMNs, which reflects cell necrosis.
RESULTS— PMA-stimulated PMNs from diabetes released superoxide significantly faster, and plasma-reduced GSH was lower in diabetic patients than in normal control subjects. The rate of superoxide release from diabetic PMNs showed no correlation with the plasma glucose concentrations, whereas a positive linear correlation with HbAlc was found. The in vitro survival of diabetic PMNs was lower than normal control PMNs when each was incubated in its own serum. The in vitro survival of normal control PMNs was reduced when incubated with diabetic serum, whereas normal control sera promoted the survival of diabetic PMNs. Peripheral PMN counts were higher in diabetic patients than in normal control patients.
CONCLUSIONS— Type 2 diabetes is accompanied by a priming of PMNs, resulting in OS and increased self-necrosis. Necrosis starts a chain of inflammatory reactions that result in cell recruitment and in the long run,with OS, may result in endothelial dysfunction. Understanding the contribution of PMNs to OS and inflammation in diabetes may illuminate new mechanisms through which endothelial dysfunction evolves and causes angiopathy and atherosclerosis.
Early Detection of Microcirculatory Impairment in Diabetic Patients With Foot at Risk
Authors: Zimny Stefan , Dessel Frauke , Ehren Marianne , Pfohl Martin , Schatz Helmut 
Published: March 2007

OBJECTIVE—To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk.
RESEARCH DESIGN AND METHODS—This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPo2) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound.
RESULTS—In supine position, TcPo2 was significantly reduced (means ± SE) in diabetic patients with foot at risk (6.04 ± 0.52 kPa) compared with diabetic (7.14 ± 0.43 kPa, P = 0.035) and nondiabetic (8.10 ± 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPo2 difference was higher in diabetic subjects with foot at risk (3.13 ± 0.27 kPa) compared with both diabetic (2.00 ± 0.18, P = 0.004) and nondiabetic (1.77 ± 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 ± 0.12 in diabetic patients with foot at risk, 1.32 ± 0.04 in diabetic control subjects, and 1.25 ± 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPo2 ratio was negatively correlated with the heart rate variation coefficient at rest (r = −0.32, P = 0.044) and at deep respiration (r = −0.31, P = 0.046).
CONCLUSIONS—Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPo2 appears to be a useful tool in screening type 2 diabetic patients for foot at risk.
Insulin Resistance After Renal Transplantation
Authors: Hjelmesæth Jøran , Midtvedt Karsten , Jenssen Trond , Hartmann Anders 
Published: March 2007

OBJECTIVE—The purpose of the present study was to validate various surrogate estimates of insulin sensitivity (IS) in a renal transplant population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation.
RESEARCH DESIGN AND METHODS—A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 patients also underwent a euglycemic-hyperinsulinemic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinemic glucose clamp–derived IS index (ISICLAMP).
RESULTS—The OGTT-derived ISITX correlated closely with the ISICLAMP (r = 0.58, P &lt; 0.001). The other surrogate estimates of IS were also significantly but less well correlated with the ISICLAMP (Spearman’s correlation; r = −0.45 to 0.41, P = 0.003–0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or β-blockers were negatively associated with ISITX (P &lt; 0.05). After multiple regression analysis, BMI (P &lt; 0.001), daily prednisolone dose (P &lt; 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR.
CONCLUSIONS—The OGTT-derived ISITX may be a useful estimate of IS in Caucasian renal transplant recipients. Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of β-blockers and diuretics may also deteriorate IR in this group of patients.
Simple Screening Tests for Peripheral Neuropathy in the Diabetes Clinic
Authors: Perkins Bruce A. , Olaleye David , Zinman Bernard , Bril Vera 
Published: March 2007

OBJECTIVE— The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy.
RESEARCH DESIGN AND METHODS— We assessed four simple tests(the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test.
RESULTS— The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34,and 0.50, respectively. The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring ∼60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test.
CONCLUSIONS— Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.
The Impact of the Diabetes Control and Complications Trial and Humalog Insulin on Glycohemoglobin Levels and Severe Hypoglycemia in Type 1 Diabetes
Authors: Chase H. Peter , Lockspeiser Tai , Peery Ben , Shepherd Mark , MacKenzie Todd , Anderson James , Garg Satish K. 
Published: March 2007

OBJECTIVE—This study was performed to determine the effects of the Diabetes Control and Complications Trial (DCCT) report in 1993 and the introduction of Lispro (Humalog) insulin in 1996 on glycemic control and on the number of severe hypoglycemic episodes in type 1 diabetic patients of various ages.
RESEARCH DESIGN AND METHODS—Diabetes care parameters and HbA1c data from 884 subjects with type 1 diabetes were entered into our database at the time of clinic visits from 1993 through 1998. In addition, a questionnaire was sent to all patients to validate the number of insulin injections per day, the incidence of severe hypoglycemic episodes (as defined by the DCCT), and the use of Humalog insulin. Data were divided into four age-groups: &lt;5, 5–12, 13–18, and &gt;18 years of age.
RESULTS—Longitudinal HbA1c levels declined significantly after the DCCT report in 1993–1996 (P &lt; 0.001), but the number of severe hypoglycemic events increased (P &lt; 0.001). A second decline in HbA1c levels was observed after the introduction of Humalog insulin in 1996 (P &lt; 0.001). However, severe hypoglycemic episodes did not change (P = 0.26).
CONCLUSIONS—Administration of Humalog resulted in an additional reduction in HbA1c levels beyond the reduction in HbA1c values after the DCCT report. In contrast to the increase in severe hypoglycemic events after the DCCT results, the number of severe hypoglycemic episodes did not increase after the introduction of Humalog, despite a further decrease in HbA1c values.
Antiatherogenic Mitochondrial Genotype in Patients With Type 2 Diabetes
Authors: Matsunaga Hajime , Tanaka Yasushi , Tanaka Masashi , Gong Jian-Sheng , Zhang Jin , Nomiyama Takashi , Ogawa Osamu , Ogihara Takeshi , Yamada Yoshiji , Yagi Kunio , Kawamori Ryuzo 
Published: March 2007

OBJECTIVE—To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C → A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects.
RESEARCH DESIGN AND METHODS—Mt5178 typing was done by polymerase chain reaction–restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C.
RESULTS—The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mt5178A group than in the Mt5178C group (0.906 ± 0.018 vs. 0.995 ± 0.021 mm, mean ± SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis.
CONCLUSIONS—The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.
Na/Li Countertransport Abnormalities in Type 1 Diabetes With and Without Nephropathy Are Familial
Authors: Mead Paul A. , Wilkinson Robert , Thomas Trevor H. 
Published: March 2007

OBJECTIVE—To determine whether there is a familial abnormality in erythrocyte Na/Li countertransport (CT) kinetics in the approximate one-third of type 1 diabetic patients that succumb to a familial predisposition to nephropathy.
RESEARCH DESIGN AND METHODS—Erythrocyte Na/Li CT kinetics were measured in nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control subjects ( n = 25).
RESULTS—Increases in outside-site Na ion association rate constant and turnover rate of Na/Li countertransport (CT) in DNrels caused increases in Vmax/Km and Vmax, respectively. Thiol alkylation with N-ethylmaleimide (NEM) modifies these kinetic parameters abnormally in nephropathy. With Na ions at the outside site of the transporter, thiol alkylation causes a large decrease in Vmax; but in their absence, Vmax is decreased in normal control subjects, unchanged in DCrels, or increased in DNrels. The relationship between Vmax values after thiol alkylation with or without Na ions was different in DNrels (P &lt; 0.001). Kinetic parameters with and without thiol alkylation identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate assay of Na/Li CT did not give this discrimination, and its use may cause discrepancy between studies.
CONCLUSIONS—Clinically normal untreated DNrels have the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic syndrome with increased BMI and plasma triglycerides, but no elevation in blood pressure. Na/Li CT can detect those type 1 diabetic patients at risk of nephropathy who have a familial abnormality in a membrane thiol protein.
Epipen as an Alternative to Glucagon in the Treatment of Hypoglycemia in Children With Diabetes
Authors: Monsod Teresa P.C. , Tamborlane William V. , Coraluzzi Luisa , Bronson Mary , Yong-Zhan Ma Tony , Ahern Jo Ann 
Published: March 2007

OBJECTIVE—Fear of a severe hypoglycemic reaction is a major obstacle to achieving near-normal plasma glucose levels. Although parenteral glucagon is effective in treating these reactions, it is cumbersome to use, causes severe nausea, and is impractical in the school setting. Epinephrine is available as a premixed injection (Epipen) that may be used by all care providers. Using Epipen to treat hypoglycemia may be an effective, safe, and easy-to-use alternative to glucagon.
RESEARCH DESIGN AND METHODS—Ten children (age 11.7 ± 2.4 years) with type 1 diabetes were studied on two occasions. After an overnight equilibration period, hypoglycemia was induced via an insulin pump (1 mU · kg–1 · min–1). At a blood glucose level of 2.8 mmol/l, either glucagon (1 mg) or epinephrine (0.3 mg), in random order, was administered intramuscularly and responses were monitored.
RESULTS—Plasma free insulin concentrations were similar in both studies. Plasma glucose levels increased by 1.7 ± 0.2 mmol/l (mean ± SEM) in 10 min and by 2.6 ± 0.2 mmol/l in 15 min with administration of glucagon and were not consistently increased with administration of epinephrine (P &lt; 0.01). Peak glucagon concentrations after administration of glucagon were &gt;60-fold higher than basal concentrations. After administration of epinephrine, peak epinephrine levels were 20-fold higher than basal concentrations.
CONCLUSIONS—Epinephrine does not seem to be an adequate substitute for glucagon in the treatment of severe hypoglycemia. The effectiveness of glucagon in reversing hypoglycemia and its side effects of nausea and vomiting are likely related to the markedly supraphysiologic plasma levels achieved with the standard intramuscular dose.
Concordance for Type 1 Diabetes in Identical Twins Is Affected by Insulin Genotype
Authors: Metcalfe Karl A. , Hitman Graham A. , Rowe Rachel E. , Hawa Mohammed , Huang Xiaojian , Stewart Timothy , Leslie R. David G. 
Published: March 2007

OBJECTIVE—Monozygotic twins are usually discordant (only one twin affected) for type 1 diabetes. Discordance for disease between such twins implies a role for nongenetically determined factors but could also be influenced by a decreased load of diabetes susceptibility genes. The aim of this study was to determine whether two susceptibility genes were less prevalent in discordant twins compared with concordant twins.
RESEARCH DESIGN AND METHODS—We studied 77 monozygotic twin pairs (INS), 40 concordant and 37 discordant, for type 1 diabetes at polymorphism of the insulin gene region on chromosome 11p and HLA-DQBI.
RESULTS—The disease-associated INS genotype (Hph I) was identified in 87.5% of the concordant twins but only in 59.5% (P = 0.005) of the discordant twins. Neither DQB1*0201 nor DQB1*0302 was seen in 2 of 40 (5%) concordant twins compared with 8 of 37 (22%) discordant twins (P = 0.04). No statistical differences were seen between concordant and discordant twins at individual alleles of DQB1. Combining insulin and DQ data, 5% of concordant twins compared with 32.4% of discordant twins had neither DQB1*0201/DQB1*0302 nor the high-risk Hph I INS “++” genotype (P = 0.002).
CONCLUSIONS—We conclude that the possession of the high-risk Hph I insulin genotype increases the likelihood of identical twins being concordant for type 1 diabetes and that the “load” of both major histocompatibility complex (MHC) and non-MHC susceptibility genes has an impact on the disease penetrance of type 1 diabetes.