bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous Insulin Absorption Explained by Insulin's Physicochemical Properties: Evidence From Absorption Studies of Soluble Human Insulin and Insulin Analogues in Humans
Authors: Kang Steven , Brange Jens , Burch Anna , Vølund Aage , Owens David R 
Published: March 2007

Objective
To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans.

Research Design and Methods
Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external γ-counting.

Results
The mean ± SE initial fractional disappearance rates for the four preparations were 20.7 ± 1.9 (hexameric soluble human insulin), 44.4 ± 2.5 (dimeric analogue AspB10), 50.6 ± 3.9 (analogue AspB28), and 67.4 ± 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P &lt; 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P &lt; 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = −0.98, P &lt; 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 ± 6.8; dimer 44.4 ± 2.5 from 0 to 2 h and 68.9 ± 3.5 from 2.5 h onward; and hexameric insulin 20.7 ± 1.9 from 0 to 2 h, 45.6 ± 5.0 from 2.5 to 5 h, and 70.6 ± 6.3 from 5 h onward.

Conclusions
Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.
Effect of Antecedent Glucose Control on Cerebral Function During Hypoglycemia
Authors: Amiel Stephanie A , Pottinger Richard C , Archibald Helen R , Chusney Gary , Cunnah David TF , Prior Pamela F , Gale Edwin AM 
Published: March 2007

Objective
The incidence of both severe and asymptomatic hypoglycemia is increased threefold in intensively treated diabetic patients. To examine whether this reflects cerebral adaptation to low blood glucose levels, we investigated the effect of preceding glycemic experience on hormonal, EEG, and evoked potential responses to experimentally induced hypoglycemia with the slow-fall clamp.

Research Design and Methods
Three groups were examined: well-controlled diabetic patients and patients with insulinoma (group 1), poorly controlled diabetic patients (group 2), and nondiabetic subjects (group 3).

Results
The glucose threshold for epinephrine release was lower in group 1 (2.3 ± 0.1 vs. 3.0 ± 0.3 and 3.1 ± 0.1 mM, P &lt; 0.02), and the peak epinephrine response was reduced (1.29 ± 0.36 vs. 5.48 ± 1 and 5.62 ± 1.2 nM, P &lt; 0.01) compared with groups 2 and 3, whereas symptoms were not perceived until a lower blood glucose level had been reached (2.0 ± 0.2 vs. 3.3 ± 0.4 and 2.6 ± 0.2 mM, P &lt; 0.01). Other counterregulatory responses were similarly delayed and diminished. In contrast, EEG changes that were compatible with hypoglycemia were detected in all subjects in group 1 (blood glucose 1.9 ± 0.1 mM) but in only two in group 2 and none in group 3, despite similar blood glucose nadirs.

Conclusions
The glycemic threshold for hormonal responses to hypoglycemia falls in individuals with intensively treated diabetes or insulinomas, but these patients are more likely to develop EEG abnormalities during hypoglycemia. This disparity helps explain the increased vulnerability of intensively treated patients to severe hypoglycemia.
Color Discrimination and Accuracy of Blood Glucose Self-Monitoring in Type I Diabetic Patients
Authors: Sawicki Peter T , Karschny Lothar , Stolpe Verena , Wolf Elmar , Berger Michael 
Published: March 2007

Objective
To determine the importance of color discrimination ability regarding accuracy in the self-monitoring of blood glucose.

Research Design and Methods
Two hundred two insulin-dependent (type I) diabetic patients performed the Fansworth-Munsell 100-hue test and a second group of 159 type I diabetic patients performed a new Düsseldorf 26-hue test. Error scores in both tests were compared with error scores of patients' self-monitoring of blood glucose measurements with Chemstrip Haemoglucotest 20'800 strips.

Results
Color discrimination ability decreased with age, diabetes duration, and presence of retinopathy. It was independent of the degree of glycemia and accuracy of self-monitoring of blood glucose.

Conclusions
Impaired color vision by itself is no reason to abandon self-monitoring of blood glucose with visually read strips.
Abdominal Obesity and Physical Inactivity as Risk Factors for NIDDM and Impaired Glucose Tolerance in Indian, Creole, and Chinese Mauritians
Authors: Dowse Gary K , Zimmet Paul Z , Gareeboo Hassam , Alberti K George M M , Tuomilehto Jaakko , Finch Caroline F , Chitson Pierrot , Tulsidas Harish 
Published: March 2007

Objective
We wanted to determine whether obesity, abdominal fat distribution, and physical inactivity act similarly and independently as risk factors for noninsulin- dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in Hindu and Muslim Asian Indians, African-origin Creoles, and Chinese Mauritians.

Research Design and Methods
We examined a population-based random cluster sample of 5080 adult subjects from the Indian Ocean island of Mauritius. Glucose tolerance was assessed with a 75-g oral glucose tolerance test and World Health Organization criteria.

Results
Univariate data and multiple logistic regression models indicated that age, family history of diabetes, body mass index (BMI), waisthip ratio (WHR), and physical inactivity conveyed similar risk for NIDDM (and IGT) in each ethnic group. After adjusting for all other factors, Hindu ethnicity conferred additional risk for NIDDM (but not IGT) in men, but in women there were no clear ethnic differences. Although BMI and WHR were independently significant risk factors, WHR conveyed relatively stronger risk for NIDDM than BMI in women, whereas the converse was true in men. For ethnic groups combined, the independent odds ratios for IGT associated with moderate and low physical activity scores (relative to high) were 1.56 and 1.71 (P &lt; 0.05), respectively, in men and 1.32 and 1.69 (P &lt; 0.05) in women. In subjects with asymptomatic NIDDM diagnosed during the survey, the independent odds ratios were 1.96 and 2.00 (P &lt; 0.05) in men and 1.73 and 2.70 (P &lt; 0.05) in women.

Conclusions
These data indicate that BMI, abdominally distributed fat, and physical inactivity are important independent risk factors for both IGT and NIDDM in diverse ethnic groups. Attributable risk fractions for Mauritius suggest that populationwide modification of levels of these risk factors could potentially result in substantially lower occurrence of NIDDM (and IGT). Such interventions should be attempted in high-risk populations.
Epidemiology and Prevention of Periodontal Disease in Individuals With Diabetes
Authors: Katz Patricia P , Wirthlin M Robert , Szpunar Susan M , Selby Joseph V , Sepe Stephen J , Showstack Jonathan A 
Published: March 2007

Objective
This article reviews the epidemiological evidence of the relationship between diabetes and periodontal disease, possible physiological mechanisms for the association, and effects of interventions on the occurrence and severity of periodontal disease among individuals with diabetes.

Research Design And Methods
A comprehensive qualitative review of published literature in the area was performed.

Results
Much of the research in this area was found to contain methodological problems, such as failing to specify the type of diabetes, small sample sizes, and inadequate control of covariates such as age or duration of diabetes.

Conclusions
Trends indicate that periodontal disease is more prevalent and more severe among individuals with diabetes. This trend may be modified by factors such as oral hygiene, duration of diabetes, age, and degree of metabolic control of diabetes. Generally, poor oral hygiene, a long history of diabetes, greater age, and poor metabolic control are associated with more severe periodontal disease. The association of diabetes and periodontal disease may be due to numerous physiological phenomena found in diabetes, such as impaired resistance, vascular changes, altered oral microflora, and abnormal collagen metabolism. With some modifications, the same prevention and treatment procedures for periodontal disease recommended for the general population are appropriate for those with diabetes. People with diabetes who appear to be particularly susceptible to periodontal disease include those who do not maintain good oral hygiene or good metabolic control of their diabetes, those with diabetes of long duration or with other complications of diabetes, and teenagers and pregnant women.
Relationship Between First-Phase Insulin Secretion and Age, HLA, Islet Cell Antibody Status, and Development of Type I Diabetes in 220 Juvenile First-Degree Relatives of Diabetic Patients
Authors: Robert Jean-J , Deschamps Ingeborg , Chevenne Didier , Roger Marc , Mogenet Agnès , Boitard Christian 
Published: March 2007

Objective
To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes.

Research Design and Methods
Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3–29 yr) of diabetic patients; 75 underwent two or more tests.

Results
At the first test, insulin responses correlated with age in ICA− children ≤ 11 yr old (r = 0.46, P &lt; 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children &lt; 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA− subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA− subjects displayed distinct changes; the mean ± SE insulin response increased in ICA− subjects from 619.2 ± 40.8 to 716.4 ± 50.4 pM (P &lt; 0.001) but declined in ICA+ subjects from 403.2 ± 91.8 to 313.8 ± 67.2 pM (P &lt; 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA− subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response.

Conclusions
Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
Effects of Human Insulin on Insulin Binding Antibody Production in Nondiabetic Subjects
Authors: Davis Stephen N , Thompson Christopher J , Peak Matthew , Brown Mavis D , Alberti K George M M 
Published: March 2007

Objective
—To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production.

Research Design and Methods
—Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone.

Results
—Mean ± SE basal insulin antibody levels (1.2 ± 0.2 μg/L) increased to a maximal level of 4.5 ± 0.8 μg/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 ± 0.3 μg/L. This represented a highly significant overall increase (P &lt; 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 ± 0.7–2.7 ± 0.6 μg/L).

Conclusions
—These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.
Standardization of IVGTT to Predict IDDM
Authors: Bingley Polly J , Colman Peter , Eisenbarth George S , Jackson Richard A , McCulloch David K , Riley William J , Gale Edwin A 
Published: March 2007

OBJECTIVE
To review current practice in centers that use the IVGTT for prediction of IDDM. To establish consensus protocol for performance of the test.

RESEARCH DESIGN AND METHODS
Postal questionnaires were delivered to 12 centers.

RESULTS
Eleven centers used a glucose dose of 0.5 g/kg and 1 used 0.3 g/kg; the dosage in adults was limited to a maximum of 25–50 g in some centers but others applied no upper limit. The glucose concentration of the infusate varied between 20 and 66%. Eight centers injected glucose manually, two used a syringe pump, and two used gravity infusion. The period of infusion ranged from 30 ± 10 s to 4 ± 2 min, and time zero was taken as the start (1 center), middle (1 center), or end (10 centers) of the infusion. The potential range in timing of the + 1-min sample varied between 1 and 7 min from the start of the infusion. Quality-assurance standards for the insulin assays used were not always appropriate for the fasting and low stimulated range of insulin levels.

CONCLUSIONS
The first-phase insulin response to the IVGTT is widely measured as an index of risk of progression to IDDM. We established that methodology varies widely. Because of this, a new standard protocol for use in prediction of IDDM was agreed by an ICARUS working group and is described herein.
Residual Left Ventricular Pump Function After Acute Myocardial Infarction in NIDDM Patients
Authors: Iwasaka T , Takahashi N , Nakamura S , Sugiura T , Tarumi N , Kimura Y , Okubo N , Taniguchi H , Matsui Y , Inada M 
Published: March 2007

OBJECTIVE
Left ventricular remodeling occurs immediately after MI, involving structural changes in noninfarcted segment. However, the residual left ventricular pump function in NIDDM patients after acute MI has not been clarified. The purpose of this study was to evaluate the difference in the process of left ventricular remodeling between NIDDM and nondiabetic patients.

RESEARCH DESIGN AND METHODS
Left ventricular regional EF images obtained by radionuclide angiography were investigated in 20 NIDDM and 29 nondiabetic patients the 3rd wk after acute MI.

RESULTS
Regional EF of the noninfarcted area and P/V had a significant hyperbolic relation with left ventricular EDV in both groups of patients. Despite no difference in the extent of myocardial necrosis and the number of coronary vessels diseased between NIDDM and nondiabetic patients, regional EF of the noninfarcted area and P/V were significantly lower when left ventricular EDV increased in NIDDM patients compared with nondiabetic patients.

CONCLUSIONS
Pathogenetic changes of the residual myocardium associated with NIDDM may adversely influence the process of left ventricular remodeling after MI, especially in patients with increased left ventricular EDV.
Mexiletine in the Treatment of Diabetic Neuropathy
Authors: Stracke Hilmar , Meyer Ulrike E , Schumacher Helmut E , Federlin Konrad 
Published: March 2007

OBJECTIVE
To prove the efficacy of mexiletine in painful diabetic neuropathy.

RESEARCH DESIGN AND METHODS
Treatment was provided in three dosages. For pain measurements, a VAS and McGill's verbal rating scale were chosen. Ninety-five patients were included in the study.

RESULTS
A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo. The total evaluation (PRIT) of the McGill scale fell just below the level of significance. More specific exploratory evaluations of subclasses of the McGill scale, representing different degrees of pain, gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items. In special subgroups, which were formed according to types and courses of complaints compiled at the beginning of this evaluation, the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale.

CONCLUSIONS
Evidence strongly indicates that, in particular, those patients with stabbing or burning pain, heat sensations, or formication will benefit most by mexiletine therapy. Concerning the dosage, a medium regimen of 450 mg/day seems to be appropriate. With an increase in the antiarryhthmic dosage level, the efficacy does not rise proportionally. Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range, even &lt; placebo; and remarkably, no cardiovascular side effects were noted. Further studies should avoid global assessments and pay more attention to the variety of complaints and quality of life.
Interaction of Insulin and Exercise on Glucose Transport in Muscle
Authors: Rodnick Kenneth J , Piper Robert C , Slot Jan W , James David E 
Published: March 2007

Glucose transport is the rate-limiting step for glucose utilization in muscle. In muscle and adipose tissue, glucose transport is acutely regulated by such factors as insulin and exercise. Translocation of glucose transporters (GLUT4) from an intracellular domain to the cell surface is the major mechanism for this regulation. Using immunocytochemistry, the intracellular distribution of GLUT4 under resting conditions is similar in adipocytes and myocytes. GLUT4 is concentrated in tubulovesicular structures either in the trans-Golgi region or in the cytosol, often close to the cell surface but not on the cell surface. After stimulation, cell surface GLUT4 labeling is increased by as much as 40-fold.
GLUT4 is chronically regulated by altered gene expression. Neural and/or contractile activity regulates GLUT4 expression in muscle: 1) GLUT4 levels differ among muscles of different fiber type; 2) GLUT4 levels in muscle are increased with exercise training and decreased with denervation; and 3) cultured muscle cells, which lack an intact nerve supply, express very low levels of GLUT4. GLUT4 expression appears to be regulated in parallel with many oxidative enzymes in muscle, suggesting that there may be a unified developmental program that determines the overall metabolic properties of a particular muscle. Preliminary evidence suggests that impaired GLUT4 expression in muscle is not the primary defect associated with insulin resistance. Nevertheless, it is conceivable that the adaptive increase in muscle GLUT4 that is found with exercise training may have beneficial effects in insulin-resistant states such as non-insulin-dependent diabetes.
Glycemic Control and Peripheral Nerve Conduction in Children and Young Adults After 5–6 Mo of IDDM
Authors: Allen Catherine , Duck Stephen C , Robert L Sufit , Swick Herbert M , D'alessio Donn J ,   for the Wisconsin Diabetes Registry
Published: March 2007

Objective
A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies.

Research Design and Methods
Unselected cases with IDDM, who were 6–29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort.

Results
Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P &lt;0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3–11 mo) were not consistently related to nerve conduction parameters after controlling for age and height.

Conclusions
These findings suggest that as early as 5–6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.