bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of Treatment Protocols in the Diabetes Control and Complications Trial
Authors:   Diabetes Control and Complications Trial Research Group
Published: March 2007

OBJECTIVE
To describe the methods used to implement intensive and conventional therapies in the Diabetes Control and Complications Trial (DCCT) and the metabolic results that occurred with the different treatment regimens.

RESEARCH DESIGN AND METHODS
The DCCT was a controlled clinical trial that demonstrated the beneficial effect of intensive therapy on the long-term complications of insulin-dependent diabetes mellitus (IDDM). A total of 1,441 volunteers with IDDM, aged 13–39, from 29 centers in the U.S. and Canada, were randomly assigned to conventional or intensive diabetes therapy. Intensive therapy, which used multiple daily injections (MDI) of insulin (≥3 injections/day) or continuous subcutaneous insulin infusion (CSI1), was implemented by a team that included diabetes nurses, dietitians, behavioral experts, and diabetologists. Volunteers in the intensive treatment group could use MDI or CSII, based on patient and clinic preference, and could switch between therapies over the course of the study. The volunteers were followed for a mean of 6.5 years (range 3–9 years).

RESULTS
A detailed analysis of implementation of the two treatments indicates that intensive and conventional treatment subjects adhered to their respective insulin injection regimens &gt;97% of the time. Adherence to other elements of intensive treatment was similarly high and resulted in median HbAlc values between 6.7 and 7.2, compared with 8.7–9.2 with conventional therapy, over the course of the study. Severe hypoglycemia occurred three times more often in intensively treated subjects. Although subjects on intensive treatment were not randomly assigned to MDI or CSII, we compared those subjects who used either of these methods for &gt;90% of the study time. CSIIy-treated patients maintained a mean HbAlc of 6.8 vs. 7.0 in MDI-treated subjects during the trial (P &lt; 0.05). The frequency of hypoglycemia with coma and seizure and diabetic ketoacidosis was modestly higher with CSII than with MDI.

CONCLUSIONS
Intensive therapy was implemented successfully in the DCCT. The detailed description herein will serve to facilitate translation of the DCCT results to the clinical setting.
Glucokinase Gene Variants in Subjects With Late-Onset NIDDM and Impaired Glucose Tolerance
Authors: Laakso Markku , Malkki Mari , Kekäläinen Päivi , Kuusisto Johanna , Mykkänen Leena , Deeb Samir S 
Published: March 2007

OBJECTIVE
To investigate the frequency of variants of the glucokinase (GCK) gene in subjects with late-onset non-insulin-dependent diabetes mellitus (NIDDM) and in subjects with late-onset impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS
The study population included 36 Finnish patients with late-onset NIDDM who were treated with diet for &gt;8 years or who were newly diagnosed and 40 subjects with late-onset IGT who had low or normal insulin levels when tested by an oral glucose tolerance test. All exons, exon-intron junctions, and islet and liver promotor regions of the GCK gene were amplified with the polymerase chain reaction and screened for mutations using single-strand conformation polymorphism analysis.

RESULTS
A silent third-base substitution (TAC→TAT) in codon 215 of exon 6 was found in 2.8% of NIDDM patients and in 5.0% of IGT subjects. Polymorphisms were found in islet exon 1 at nucleotide 403 (C→G) in 16.7% of NIDDM patients and in 17.5% of IGT subjects and in the noncoding region of the islet promotor at nucleotide -30 (G→A) in 13.9% of NIDDM patients and in 25.0% of IGT subjects. Furthermore, in liver intron 1 a variant (C→T), 12 base pairs upstream from the splice acceptor site, was found in 5.6% of NIDDM patients and in 7.5% of IGT subjects.

CONCLUSIONS
These results indicate that the mutations in the coding region of the GCK gene are not likely to play a major role in the pathogenesis of late-onset NIDDM or IGT in the Finnish population.
Muscarinic Cholinergic Antagonism Does Not Enhance Recovery From Hypoglycemia in IDDM
Authors: Hvidberg Annemarie , Cryer Philip E 
Published: March 2007

OBJECTIVE
Because muscarinic cholinergic agonism in the absence of an increase in glucagon secretion inhibits hepatic glucose production, we tested the hypothesis that muscarinic cholinergic antagonism enhances glucose recovery from hypoglycemia in insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS
Eight (initially euglycemic) patients with IDDM received overnight infusions of insulin and were studied on three occasions in random order. Hypoglycemia was induced by low-dose insulin infusion (4.0 pmol·kg−1 min−1) from 0 through 80 min; observations were continued through 240 min. At 0 and 80 min, intravenous injections of atropine only (1.0 mg), placebo and then atropine, respectively, or placebo only were administered.

RESULTS
Increments in heart rate (P &lt; 0.001) and prevention of the pancreatic polypeptide response to hypoglycemia (P = 0.042) after atropine administration documented muscarinic cholinergic antagonism. The absent glucagon response to hypoglycemia was unaltered, but the epinephrine response was increased (P = 0.010). Nonetheless, rates of glucose production and utilization and plasma glucose concentrations were unaltered.

CONCLUSIONS
We conclude that muscarinic cholinergic antagonism does not enhance glucose recovery from hypoglycemia in patients with IDDM.
Early Involvement of Central Nervous System in type I Diabetic Patients
Authors: Bax Giuseppe , Lelli Stefania , Grandis Umberto , Cospite Anna Maria , Paolo Negrin , Fedele Domenico 
Published: March 2007

OBJECTIVE
To investigate whether the asymptomatic involvement of the central and peripheral nervous systems may be an early complication of diabetes.

RESEARCH DESIGN AND METHODS
We studied early impairment of the central and peripheral nervous system pathways in 15 type I diabetic patients with good metabolic control and short disease duration and in 10 healthy control subjects using a set of neurophysiological tests.

RESULTS
Results in diabetic subjects showed 1) impairment of motor (7% and somatosensory (13%) pathways of the central nervous system, 2) impairment of motor and sensory conduction velocities (40–60%), and 3) normal values of the vibration perception threshold and cardiovascular autonomic tests.

CONCLUSIONS
The damage is more evident in peripheral sites where hyperglycemia and aldose reductase pathways are more active. Instead, several episodes of hypoglycemia, which occur in type I diabetic patients in good metabolic control, may cause alterations of brain nervous cells.
Diabetes and Impaired Glucose Tolerance in Three American Indian Populations Aged 45-74 Years: The Strong Heart Study
Authors: Lee Elisa T , Howard Barbara V , Savage Peter J , Cowan Linda D , Fabsitz Richard R , Oopik Arvo J , Yeh Jeunliang , Go Oscar , Robbins David C , Welty Thomas K 
Published: March 2007

OBJECTIVE
To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry.

RESEARCH DESIGN AND METHODS
This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio.

RESULTS
A total of 4,549 eligible participants were examined, and diabetes status was determined for4,304(1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status.

CONCLUSIONS
Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs shoula be expanded to include those with IGT to improve glycemie control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.
A Comparison Between Alternative and Trade Name Glucose Test Strips
Authors: Lenhard M James , Cherney G Stephen De , Maser Raelene E , Patten Bernardine C , Kubik Jennifer 
Published: March 2007

OBJECTIVE
To determine the reliability of seven different alternative glucose test strips manufactured for use with three different glucose meters.

RESEARCH DESIGN AND METHODS
Venous blood samples were obtained from volunteers to test trade name glucose test strips on the manufacturers' glucose meters (One Touch II, Glucometer II, and Glucometer III), and the remainder of each sample was used for laboratory determination of blood glucose levels. In addition to the trade name test strips, Quick Check and First Choice test strips were tested on all meters, and Biotel test strips were also tested on the Glucometer III.

RESULTS
In linear regression analysis, the R2 ranged from 0.84 to 0.97 for the test strips compared with plasma glucose values. The test strips with the highest accuracy and precision at all ranges of blood glucose levels were the One Touch II and Glucometer III trade name strips and the Quick Check and First Choice alternative strips for the One Touch II glucose meter and the First Choice alternative strip for the Glucometer II. Subgroup analysis based on ranges of blood glucose values, however, revealed that the alternative strips were not as accurate as the trade name test strips, with the exception of the First Choice alternative test strip for the Glucometer II. All of the trade name test strips were more precise than the alternative test strips designed for the individual meters.

CONCLUSIONS
Alternative glucose test strips can be used to predict the actual laboratory blood glucose values but are generally not as accurate or precise as the trade name test strips.
Effects of Enalapril and Nitrendipine on the Excretion of Epidermal Growth Factor and Albumin in Hypertensive NIDDM Patients
Authors: Josefsberg Zeev , Ross Stuart A , Lev-Ran Arye , Hwang David L 
Published: March 2007

OBJECTIVE
To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects.

RESEARCH DESIGN AND METHODS
After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] &gt; 140 mmHg and/or diastolic blood pressure [dBP] &gt;90 mmHg) NIDDM patients with albuminuria (15-200 μg/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period.

RESULTS
A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP.

CONCLUSIONS
The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.
Prevalence and Associated Features of Albuminuria in Koreans with NIDDM
Authors: Lee Ki-Up , Park Joong Y , Kim Sang W , Lee Mee H , Kim Ghi S , Park Su-Kil , Park Jung-Sik 
Published: March 2007

OBJECTIVE
To determine the prevalence and the associated features of microalbuminuria and overt proteinuria in Korean subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic.

RESEARCH DESIGN AND METHODS
A total of 631 Korean outpatients with NIDDM were studied cross-sectionally for the presence of albuminuria and other micro- and macrovascular complications. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples. Subjects were divided into three groups: no nephropathy (AER &lt;20 μg/min), microalbuminuria (AER 20–200 μg/min), and overt proteinuria (AER &gt;200 μg/min).

RESULTS
Increased AER was present in 34% of our patients: 20% had microalbuminuria and 14% had overt proteinuria. Of patients with diabetes duration ≥ 15 years, 35% had overt proteinuria. Most (82%) patients with overt proteinuria had retinopathy. Although the prevalence of microalbuminuria as a whole did not differ according to diabetes duration, the prevalence of microalbuminuria in the patients with retinopathy increased with diabetes duration. The microalbuminuric patients without retinopathy (diabetes duration &lt; 5 years) were characterized by higher prevalence of hypertension and previous obesity, higher plasma triglyceride level, and lower plasma high-density lipoprotein cholesterol level.

CONCLUSIONS
The prevalence of overt proteinuria in Korean NIDDM patients with a long diabetes duration was higher than that reported in Caucasians. Our data also suggest that the clinical meaning of microalbuminuria may be different based on the presence or the absence of retinopathy. Microalbuminuria in patients with retinopathy most probably would reflect diabetic nephropathy. In contrast, some recent-onset NIDDM patients with microalbuminuria in the absence of retinopathy had features of syndrome X.
Local Reaction Secondary to Insulin Injection: A potential role for latex antigens in insulin vials and syringes
Authors: Towse Alison , O'Brien Maureen , Twarog Frank J , Braimon Jennifer , Moses Alan C 
Published: March 2007

OBJECTIVE
To evaluate the possibility that latex antigens (natural rubber) can contribute to or cause local sensitivity at insulin injection sites.

CASE
A subject with documented local cutaneous allergic reactions at the site of insulin injections and with systemic latex allergy manifested as anaphylaxis was tested with intradermal injections of insulin diluent from two manufacturers and with two brands of insulin syringes.

RESULTS
The subject had high titer anti-latex Ige and elevated total levels of IgE in serum. Anti-insulin IgG and IgE antibodies were absent. Erythema and wheals occurred at the sites of intradermal injection of insulin therapy components (insulin diluent and syringes) that contain natural latex rubber but not at the site of injection of insulin therapy components that do not contain natural latex rubber.

CONCLUSIONS
Small quantities of natural latex rubber antigens in insulin injection materials can be sufficient to produce local cutaneous reactions at the site of insulin injection in individuals highly allergic to natural latex rubber.
Effect of Pregnancy On Renal Function in Patients With Moderate-to-Severe Diabetic Renal Insufficiency
Authors: Purdy Lisa P , Hantsch Christina E , Molitch Mark E , Metzger Boyd E , Phelps Richard L , Dooley Sharon L , Hou Susan H 
Published: March 2007

OBJECTIVE
Previous studies of patients with diabetic nephropathy and mild renal impairment have suggested no determination in renal function as a result of pregnancy. The objective of this study was to determine whether pregnancy may permanently worsen renal function in women with diabetic nephropathy and moderate-to-severe renal insufficiency.

RESEARCH DESIGN AND METHODS
Eleven patients were identified with diabetic nephropathy and moderate-to-severe renal dysfunction (creatinine [Cr] ≥ 124 μmol/l [1.4 mg/dl]) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate were estimated by using linear regression of the reciprocal of Cr over time. An equal number of nonpregnant premenopausal type 1 diabetic women with similar degrees of renal dysfunction served as a comparison group for nonpregnant rate of decline of renal function and potential contributing factors.

RESULTS
Mean serum Cr rose from 159 μmol/l (1.8 mg/dl) prepregnancy to 221 μmol/l (2.5 mg/dl) in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia occurred in 73%. Seven patients progressed to dialysis 6–57 months postpartum, with 71% (five of seven) of these cases attributed to acceleration of disease during the pregnancy. Student's t tests and repeated-measures analysis of variance support a pregnancy-induced acceleration in the rate of decline of renal function.

CONCLUSIONS
In this series, patients with diabetic nephropathy and moderate-to-severe renal insufficiency were found to have a &gt; 40% chance of accelerated progression of their disease as a result of pregnancy.
The Efficacy of Tolrestat in the Treatment of Diabetic Peripheral Neuropathy: A meta-analysis of individual patient data
Authors: Nicolucci Antonio , Carinci Fabrizio , Graepel Jay G , Hohman Thomas C , Ferris Frederick , Lachin John M 
Published: March 2007

OBJECTIVE
The aim of this meta-analysis was to review the existent evidence on the effectiveness of tolrestat in the treatment of diabetic peripheral neuropathy.

RESEARCH DESIGN AND METHODS
Individual patient data on 738 subjects from the three randomized clinical trials published on this topic were analyzed using changes in motor nerve conduction velocities (NCVs) as endpoints. Nerves investigated included median, ulnar, tibial, and peroneal.

RESULTS
The pooled analysis of NCV taken as a continuous measurement showed a significant treatment effect, the magnitude of this benefit being approximately equal to 1 m/s for all the nerves investigated. When looking at the proportion of patients experiencing a loss of NCV of at least 1 or 2 m/s in at least two out of the four nerves investigated, it emerged that treatment reduced by &gt; 40% the risk of such outcomes after adjusting for patients' characteristics. The odds ratios relative to the placebo group were 1.82 (1.30–2.52) and 1.70 (1.15–2.48) for a decrease of 1 and 2 m/s, that is, placebo-treated patients have an 82 and 70% increased risk for a loss of nerve function of 1 and 2 m/s, respectively. No statistically significant difference in treatment effect emerged after stratification according to baseline motor NCV and glycated hemoglobin levels.

CONCLUSIONS
After a treatment duration ranging between 24–52 weeks, patients treated with tolrestat had a reduced risk for developing nerve function loss compared with placebo-treated patients. Future long-term trials are needed to evaluate the impact of the treatment on more clinically meaningful endpoints such as the development of foot complications.
Lipoprotein (a) Levels in African-Americans with NIDDM
Authors: Scheer W Douglas , Boudreau Donald A , Cook Curtiss B 
Published: March 2007

OBJECTIVE
The purpose of this study was to investigate possible relationships between lipoprotein (a) [Lp(a)] levels and NIDDM in African-Americans. The objectives were to identify associations between Lp(a) levels of subjects with and without NIDDM and to determine the influence of glycemic control, determined by GHb, and of mode of therapy on Lp(a) levels.

RESEARCH DESIGN AND METHODS
We studied 141 African-American subjects, 103 with NIDDM and 38 without NIDDM. Their Lp(a) levels, GHb levels, and apolipoprotein (a) [apo(a)] isoforms were determined. Clinical information, including mode of therapy (sulfonylurea, insulin, or no pharmacological therapy), date of diagnosis, and medical history, was obtained by chart review and patient interview.

RESULTS
There was no significant difference in median Lp(a) levels between the non-NIDDM (25.5 mg/dl) and NIDDM (24.0 mg/dl) study subjects. No statistically significant difference was found in Lp(a) levels when NIDDM patients with GHb &lt; 12.3% were compared to those with GHb ≥ 12.3% (P = 0.096). An inverse relationship was found between apo(a) root-mean-square isoform size and Lp(a) level (r2 = 0.091, P = 0.0035). Analysis of the cases by mode of therapy indicates that there is evidence of an increased median level of Lp(a) in African-Americans with NIDDM on insulin therapy relative to those on sulfonylurea (34.0 vs. 16.0 mg/dl; P = 0.013) and to nondiabetic subjects (34.0 vs. 25.5 mg/dl; P = 0.043).

CONCLUSIONS
We conclude that the level of plasma Lp(a) is higher in African-Americans with NIDDM who are being treated with insulin when compared to those on sulfonylurea therapy and to those who are non-NIDDM subjects, and this does not seem to be due to genetic variance or method bias.
Thrombolytic Therapy in Diabetic Patients with Acute Myocardial Infarction
Authors: Hansen Hans-Henrik T , Kjærgaard Søren C , Bülow Inge , Fog Lars , Christensen Per D 
Published: March 2007

OBJECTIVE
To compare the frequency of thrombolytic therapy in diabetic and nondiabetic patients with acute myocardial infarction (MI) and to examine why some diabetic patients do not receive thrombolytic therapy.

RESEARCH DESIGN AND METHODS
Retrospective study of all diabetic patients with acute MI admitted to the coronary care unit of Aalborg Hospital within a 3-year period.

RESULTS
Only 35% (43 of 123) of patients with diabetes compared with 47% (404 of 856) of patients without diabetes received thrombolytic therapy (P &lt; 0.002). There was no difference in the percentage of patients thrombolyzed among patients admitted to the hospital within 12 h after onset of symptoms. Of diabetic patients who were not thrombolyzed, 60% (48 of 80) arrived at the hospital later than 12 h after onset of symptoms. Among patients who arrived late, 63% (35 of 56) had Q wave infarction and 84% (47 of 56) had symptoms typical of acute MI. Mortality was 29% (16 of 56) in this group. Only one patient did not receive thrombolytic therapy due to diabetic retinopathy.

CONCLUSIONS
Significantly fewer diabetic patients received thrombolytic therapy compared with patients without diabetes. The main reason diabetic patients did not receive thrombolytic therapy was late arrival to the hospital.