bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial Changes in the Prevalence of Islet Cell Antibodies and Islet Cell Antibody Titer in Children With IDDM of Abrupt or Slow Onset
Authors: Urakami Tatsuhiko , Miyamoto Yukinobu , Matsunaga Hiroko , Owada Misao , Kitagawa Teruo 
Published: March 2007

OBJECTIVE
To elucidate the significance of clinical and immunogenic heterogeneity in Japanese children with insulin-dependent diabetes mellitus (IDDM).

RESEARCH DESIGN AND METHODS
Serial changes in the prevalence of islet cell antibodies (ICAs) and in ICA titer were monitored for 10 years after diagnosis in 34 IDDM children, 17 with abrupt onset and 17 with slow onset, whose durations of disease were &gt; 5 years.

RESULTS
In slow-onset IDDM children, enough β-cell function was maintained in the early phase of the disease within 2 years after diagnosis. There was a high prevalence of ICAs in children with both forms of IDDM at the time of diagnosis (abrupt onset 94% slow onset 82%). However, the decline in the frequency of ICAs in slow-onset IDDM seemed less marked than in abrupt-onset IDDM after a duration of ≥ 1 year (47 vs. 82%, 1–3 years; 24 vs. 47%, 3–5 years; 24 vs. 47%, 5–7 years; 18 vs. 53%, 7–10 years, P &lt; 0.05). In terms of changes in ICA titer, abrupt-onset IDDM children initially had high ICA levels of 160–320 Juvenile Diabetes Foundation units (JDF U), but these titers decreased rapidly after the 1st year. On the other hand, slow-onset IDDM children tended to continue to be ICA+ for a relatively long period with low titers of 20–40 JDF U. Among 12 children who remained ICA+ for &gt; 5 years, slow onset was noted in 67% while abrupt onset was seen in only 33%.

CONCLUSIONS
From these results, we speculated that changes in ICA titer reflect the slow autoimmune destruction of pancreatic β-cells. It may be probable that immunogenic factors as well as environmental factors could affect the clinical features in the early phase of IDDM in children.
Severe Islet Amyloidosis in Congenital Generalized Lipodystrophy
Authors: Garg Abhimanyu , Chandalia Manisha , Vuitch Frank 
Published: March 2007

OBJECTIVE
Islet amyloidosis may be one mechanism for pancreatic islet β-cell loss that is associated with the development of NIDDM. However, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (IAPP) secretion in states of insulin resistance could lead to formation of islet amyloidosis and hence NIDDM in some patients. We studied pancreatic islet pathology in congenital generalized lipodystrophy, a genetic syndrome of extreme insulin resistance that may provide some clues.

RESEARCH DESIGN AND METHODS
Our patient was a 24-year-old African-American woman with congenital generalized lipodystrophy. Severe acanthosis nigricans was noted in her since age 6. At ages 12 and 16, normal and impaired glucose tolerances, respectively, were noted on oral glucose tolerance tests but were accompanied by extreme fasting and post-prandial hyperinsulnemia. Overt diabetes developed at age 18 and she required ∼180 U of insulin daily. Immediately after an accidental death at age 24, an autopsy was performed. Pancreatic histology was studied in detail using routine methods and immunohistochemical techniques.

RESULTS
Some scarring of the pancreas as a result of previous episodes of acute pancreatitis was observed. Severe amyloidosis was noted in 89% of the islets, sparing those that were rich in pancreatic polypeptide-secreting cells. Amyloid deposits stained intensely on immunostaining with antibodies against amylin. Marked paucity of β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio ∼ 4:1).

CONCLUSIONS
These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.
The Effects of High- and Medium-Dose Metformin Therapy on Cardiovascular Risk Factors in Patients With Type II Diabetes
Authors: Grant Peter J 
Published: March 2007

OBJECTIVE
To study the dose response to metformin in type II diabetic patients.

RESEARCH DESIGN AND METHODS
Type II diabetic patients with a BMI &gt; 25 were treated with 3,000 mg/day (n = 27), 1,500 mg/day (n = 25), or placebo (n = 23) for 6 months. Venous blood samples were taken at each visit for plasma glucose and insulin, HbA1c, triglyceride and cholesterol, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (TPA), and euglobulin clot lysis time (ECLT). Blood pressure was recorded at each visit.

RESULTS
There were no changes in BMI or blood pressure. Blood glucose fell (mean) by 3.6 mmol/l in the high-dose and 0.5 mmol/l in the low-dose group over the 6-month study (P &lt; 0.001 and NS compared with placebo). HbA1c and plasma insulin fell in both treatment groups (HbA1c, P &lt; 0.001; insulin, P &lt; 0.003 and 0.03). There was a fall in triglyceride (P &lt; 0.05) and cholesterol (P &lt; 0.008) with high-dose metformin. PAI-1 antigen and activity fell by ∼ 20% of baseline in both treatment groups (PAI-1 antigen high dose, P &lt; 0.01; PAI-1 antigen low dose, P &lt; 0.002: PAI-1 activity high and low dose, P &lt; 0.003). There were significant falls in total tPA in both groups (P &lt; 0.004), but the overall effect was a fall in ECLT (P &lt; 0.03).

CONCLUSIONS
The results indicate that metformin has favorable effects on cardiovascular risk factors associated with type II diabetes. The effects on glycemic control and lipids are dose-dependent, while the enhanced fibrinolytic response is independent of the doses used.
Elevated Plasma Levels of Transforming Growth Factor-β1 in NIDDM
Authors: Pfeiffer Andreas , Middelberg-Bisping Kristina , Drewes Cordula , Schatz Helmut 
Published: March 2007

OBJECTIVE
Transforming growth factor-β (TGF-β) is a potent inducer of extracellular matrix production and of fibrogenesis and has been associated with the occurrence of diabetic micro- and macrovascular complications. Our aim was to determine whether circulating levels of TGF-β1 are altered in NIDDM and, if so, whether they are correlated with blood glucose and show an association with diabetic complications.

RESEARCH DESIGN AND METHODS
Plasma levels of TGF-β1 were determined by enzyme-linked immunosorbent assay in 44 NIDDM patients and 28 control subjects of comparable age and weight and were correlated with parameters of metabolic control and the occurrence of micro- and macrovascular complications.

RESULTS
TGF-β1 was significantly elevated in NIDDM (7.9 ± 1.0 ng/ml), as compared with control subjects (3.1 ± 0.4 ng/ml, P &lt; 0.001) and correlated with glycosylated hemoglobin (r2 = 0.42; P &lt; 0.001). Thrombocyte levels of TGF-β1 were similar in control subjects (54 ± 7 pg/ml, n = 16) and diabetic patients (61.6 ± 18 pg/ml, n = 13; P = 0.357). Elevated TGF-β1 levels were associated with retinopathy and neuropathy.

CONCLUSIONS
We conclude that plasma levels of TGF-β1 are elevated in NIDDM patients and may be related to average blood glucose. Preliminary data suggest that they may contribute to the occurrence of diabetic complications.
Persistent Activation of CD8+ T-cells Characterizes Prediabetic Twins
Authors: Peakman Mark , Leslie R David G , Alviggi Lorenzo , Hawa Mohammed , Vergani Diego 
Published: March 2007

OBJECTIVE
Elevated circulating levels of activated CD3+ T-cells are characteristic of type I diabetes at diagnosis, and activated CD8+ (cytotoxic/suppressor) T-cells predominate in the islet infiltrate. The aim of this study was to examine the peripheral blood of prediabetic and nondiabetic identical twins of patients with type I diabetes for the presence of activated CD8+ T-cells and by comparing these groups, analyze the relationship of such cells to the development of the disease.

RESEARCH DESIGN AND METHODS
In a 10-year prospective study, blood T-cell subsets (CD3+ total T-cells, CD4+ helper/inducer, and CD8+ cytotoxic/suppressor) were analyzed for evidence of activation (cell surface expression of HLA-DR, CD25) in 18 identical twins of patients with type I diabetes, 8 of whom became diabetic (prediabetic twins), while 10 remained nondiabetic after at least 8 years of follow-up and are now at low risk for type I diabetes. Fifteen healthy individuals were studied as control subjects.

RESULTS
At the beginning and during the study, percentage levels of activated CD3+ HLA-DR+ T-cells were significantly elevated in prediabetic and low-risk twins compared with control subjects (P &lt; 0.005) but remained high only in prediabetic twins (P &lt; 0.005). Both prediabetic and low-risk twins had elevated levels of HLA-DR+ CD4+ T helper cells compared with control subjects throughout the study (P &lt; 0.001), and these remained high in both (P &lt; 0.001 and P &lt; 0.05, respectively). Only prediabetic twins had elevated levels of HLA-DR+ CD8+ T-cells during the study. These were significantly higher than in control subjects (P &lt; 0.005) and low-risk twins (P &lt; 0.05) and remained persistently elevated to diagnosis (P &lt; 0.001). Abnormally elevated levels of HLA-DR+ CD8+ T-cells in twins indicate a 50% risk of progression to type I diabetes by life-table analysis (P = 0.01), with a positive predictive value of 100%, sensitivity of 50%, and specificity of 100%. Elevated CD25+ T-cell levels in prediabetic and low-risk twins were less marked and less able to discriminate between the twin groups.

CONCLUSIONS
These results demonstrate that prediabetes is characterized by persistent elevation of HLA-DR+ CD8+ T-cells with the same cytotoxic phenotype as cells predominating in the islet at diagnosis, suggesting that the circulating cells may have a role in the pathogenesis of islet damage.
Acute Effects of Intraperitoneal Versus Subcutaneous Insulin Delivery on Glucose Homeostasis in Patients With NIDDM
Authors: Kelley David E , Henry Robert R , Edelman Steven V ,   The Veterans Affairs Implantable Insulin Pump Study Group
Published: March 2007

OBJECTIVE
The objective of this study is to compare the effect of intraperitoneal versus subcutaneous insulin injection on hepatic glucose production (HGP) and systemic glucose utilization (Rd) in patients with NIDDM.

RESEARCH DESIGN AND METHODS
Eight male volunteers with NIDDM, each of whom had a programmable-rate, implantable insulin pump, were given an injection of insulin (0.15 units/kg body wt) by intraperitoneal or subcutaneous injection on separate days in randomized order. Plasma glucose was kept constant for 5 h using the glucose clamp technique, and HGP and Rd were measured using isotope dilution.

RESULTS
Intraperitoneal insulin injection resulted in higher and earlier peak systemic insulin concentrations (1,469 ± 245 vs. 454 ± 48 pmol/l, P &lt; 0.01). Glucose Rd doubled within 1 h after intraperitoneal injection and was greater than that attained with subcutaneous injection (3.91 ± 0.27 vs. 2.60 ± 0.19 mg · kg−1 · min−1, P &lt; 0.01). Intraperitoneal and subcutaneous injections suppressed HGP and plasma free fatty acid to a similar extent during the first 3 h, effects that persisted through 5 h after subcutaneous insulin injection but waned 3–4 h after intraperitoneal injection.

CONCLUSIONS
In patients with NIDDM, intraperitoneal insulin injection achieves more rapid and greater peak values for stimulation of glucose Rd than subcutaneous insulin injection. With regard to HGP and lipolysis, intraperitoneal and subcutaneous injections achieve similar initial suppression but this is maintained for a more limited duration with intraperitoneal as compared with subcutaneous injection. These differences in insulin action seem directly related to the rapidity of insulin absorption with intraperitoneal injection.
Feasibility and Effectiveness of Peripheral Percutaneous Transluminal Balloon Angioplasty in Diabetic Subjects With Foot Ulcers
Authors: Faglia Ezio , Favales Fabrizio , Quarantiello Anthonella , Calia Patrizia , Brambilla Giorgio , Rampoldi Antonio , Morabito Alberto 
Published: March 2007

OBJECTIVE
The aim of this study was to evaluate the feasibility and effectiveness of this vascular procedure in diabetic inpatients with foot ulcers.

RESEARCH DESIGN AND METHODS
In 80 consecutive inpatient diabetic subjects with a foot ulcer, an angiographic study of the lower limbs was carried out to evaluate the necessity and possibility of performing vascular procedures. In 22 subjects, vascular procedure was not necessary; in 26 subjects, peripheral transluminal angioplasty was carried out; in 10 subjects, angioplasty was considered impossible and a peripheral bypass graft was performed; and in 22 subjects, no vascular procedure was considered possible.

RESULTS
Of the 26 angioplasties, 8 were performed in iliac or femoral arteries and 18 were performed in the popliteal artery and its branches. The angioplasty was considered unsuccessful in 4 subjects and successful in 22. After angioplasty, on discharge, parameters of limb perfusion improved significantly: transcutaneous oxygen tension was 27.0 ± 14 mm/Hg on admission and 44.6 ± 14 mm/Hg on discharge (P &lt; 0.001); ankle-brachial index was 0.61 ± 0.23 on admission and 0.77 ± 0.20 on discharge (P = 0.018). Of 22 subjects who underwent successful angioplasty, 21 ended the follow-up of 12 months: during this period, they showed no relapses in the salvaged limb, and their parameters of limb perfusion did not significantly vary.

CONCLUSIONS
Angioplasty is feasible in a large percentage of diabetic subjects with peripheral occlusive arterial disease and foot ulcer and is often also practicable in the popliteal artery and its branches. In these subjects, angioplasty significantly improves the parameters of limb perfusion. Angioplasty is therefore an important therapeutic tool in ulcerated diabetic foot care.
Meta-Analysis of Nicotinamide Treatment in Patients With Recent-Onset IDDM
Authors: Pozzilli Paolo , Browne Peter D , Kolb Hubert ,   The Nicotinamide Trialists
Published: March 2007

OBJECTIVE
Nicotinamide, a vitamin of the B group, has in vitro actions capable of interfering with the pathogenetic process leading to IDDM. Since 1987, several studies have evaluated nicotinamide as a means of protecting β-cells from end-stage destruction in insulin-treated patients with newly diagnosed IDDM. The aim of the study was to determine whether nicotinamide protects residual β-cell function when given at IDDM diagnosis.

RESEARCH DESIGN AND METHODS
We performed a meta-analysis of the integrated parameters of metabolic control (C-peptide, glycosylated hemoglobin, insulin dose) in 10 randomized (5 of which were placebo) controlled trials conducted in recent-onset IDDM patients for a total of 211 nicotinamide-treated patients. Data on the adverse effects of nicotinamide were also collected from an additional four trials to yield a grand total of 291 nicotinamide-receiving patients.

RESULTS
One year after diagnosis, baseline C-peptide was significantly higher in nicotinamide-treated patients, compared with control patients (0.73 ± 0.65 vs. 0.32 ± 0.56 ng/ml, P &lt; 0.005). This statistical difference remained also when the five placebo-controlled trials only were considered (P &lt; 0.05). No differences were observed in the insulin dose required or glycosylated hemoglobin values between nicotinamide and control patients. Adverse effects were reported in few patients (transient elevation of transaminase, n = 2; skin rash, n = 2; recurrent hypoglycemia, n = 2).

CONCLUSIONS
This combined analysis demonstrates a therapeutic effect of nicotinamide in preserving residual β-cell function when given at IDDM diagnosis in addition to insulin. Since adverse effects were negligible, we suggest that prolonged use of nicotinamide after IDDM diagnosis should be tested to see whether residual β-cell function can be preserved for longer periods.
Separate Associations Between Visceral and Subcutaneous Adipose Tissue Distribution, Insulin and Glucose Levels in Obese Women
Authors: Ross R , Fortier L , Hudson R 
Published: March 2007

OBJECTIVE
The primary purpose of this study was to determine the separate associations between visceral (VAT) and subcutaneous adipose tissue (SAT) distribution, skeletal muscle (SM), and plasma insulin and glucose levels, and. A second objective was to determine whether anthropometric methods could be used to identify those women who are at increased metabolic risk.

RESEARCH DESIGN AND METHODS
Whole-body SAT, SM, and VAT volume were measured (in liters), using a multislice magnetic resonance imaging (MRI) protocol in 40 premenopausal obese women. Plasma insulin and glucose levels were measured after an overnight fast and in response to a 75-g oral glucose tolerance test (OGTT).

RESULTS
With the exception of fasting glucose, VAT was positively correlated with all insulin and glucose variables (P &lt; 0.01). This observation remained true whether VAT was derived from multiple MR images (i.e., VAT volume [in liters]) or from a single MR image (i.e., VAT area [in squared centimeters]). Furthermore, the segmentation of intraperitoneal adipose tissue (portally drained adipose tissue) from VAT did not improve the observed relationships. VAT remained a significant (P &lt; 0.05) correlate of insulin and glucose area after adjusting for either SAT or abdominal SAT (ASAT). SAT, ASAT, and SM volume were not related to any metabolic variable. Waist circumference (WC) was the single strongest anthropometric correlate for fasting insulin and insulin area (P &lt; 0.05). Because it has been reported that disturbances in insulin-glucose homeostasis are more likely associated with a WC value &gt; 1 m, in subjects matched for total adiposity, we compared the glucose and insulin area values for those with a WC above (n = 17) and below (n = 15) this value. The group with a WC &gt; 1 m had significantly higher values for both insulin and glucose areas (P &lt; 0.05).

CONCLUSIONS
The primary observation is that VAT is associated with plasma insulin and glucose variables independent of whole-body SAT, ASAT, and SM in obese women. In addition, the findings provide support for the utility of WC as an anthropometric tool that may be used to identify a subgroup of obese patients at increased metabolic risk.
The Development of Foot Deformities and Ulcers After Great Toe Amputation in Diabetes
Authors: Quebedeaux Terri L , Lavery Lawrence A , Lavery David C 
Published: March 2007

OBJECTIVE
Our aim was to compare the prevalence and severity of foot deformities and the development of ulcerations in patients after a great toe amputations.

RESEARCH DESIGN AND METHODS
We evaluated the presence of deformities of the toes and metatarsophalangeal joints (MTPJs) in patients with a great toe amputation who had an intact unamputated contralateral foot. The contralateral foot served as the patient's own control. We used a binomial test for paired data to compare the presence of deformity and ulcer formation and Fisher's exact test to compare joint flexibility in toes and MTPJs with foot deformities.

RESULTS
There were more deformities of the second (P = 0.012) and third (P = 0.002) toes and lesser MTPJs (P &lt; 0.05) and more rigid deformities of the second (P = 0.002) and third (P = 0.016) toes and second MTPJs (P = 0.035) in feet with great toe amputations. New ulcers were more common in feet that had an amputation (P = 0.002).

CONCLUSIONS
We concluded that amputation of the great toe contributes to the development of deformities of the second and third toes and lesser MTPJs and new ulcer formation in patients with diabetes. When deformities were present, the second and third toes and second MTPJ were more severe in feet with a great toe amputation.
Diminished Thyroxine-Binding Globulin in Pubertal Diabetic Children
Authors: Connors Matthew H , Dunger David B , Chapel Helen , Jefferson Ian , Jowett Terence P , Edwards Philip R 
Published: March 2007

OBJECTIVE
To determine the effect of diabetes on thyroid hormone and thyroxine-binding globulin (TBG) concentrations during puberty.

RESEARCH DESIGN AND METHODS
Total thyroxine (TT4), free thyroxine (FT4), and TBG levels of 171 thyroid microsomal antibody-negative subjects with normal thyroid-stimulating hormone (TSH) levels were measured and compared with those of nondiabetic adolescents. A random subset of 68 diabetic patients (40 boys and 28 girls) and 51 control subjects (24 boys and 27 girls) were analyzed for puberty-related changes.

RESULTS
Most TT4 levels of diabetic subjects (80% of girls and 63% of boys) were below the 50th percentile for the normal range. TT4 increased with age in girls (r = 0.25, P &lt; 0.04) but not in boys. FT4 was within normal limits in both sexes. TBG measurements were below the 50th percentile and 20% were below the 95% CI for both sexes; TT4 correlated with TBG in boys (r = 0.54, P &lt; 0.001) and in girls (r = 0.58, P &lt; 0.001). Duration of diabetes had no effect, whereas TT4 and FT4 levels were higher in girls with the lowest HbA1 levels (r = −0.29, P &lt; 0.01 and r = −0.45, P &lt; 0.01). Levels of TBG were reduced for all male pubertal stages (P &lt; 0.01) and for early and late female pubertal stages (P &lt; 0.01). There was no direct relationship between glucose control or the duration of diabetes and levels of TBG.

CONCLUSIONS
Because TT4 levels are low and correlate with the low levels of TBG, it is important to measure free thyroid hormone and TSH levels in diabetic adolescents to establish euthyroidism.
A Case-Control Study of Diet in Newly Diagnosed NIDDM in the Wanigela People of Papua New Guinea
Authors: Hodge Allison M , Montgomery Janice , Dowse Gary K , Mavo Barnabas , Watt Tahlia , Zimmet Paul Z 
Published: March 2007

OBJECTIVE
To study the association between diet and newly diagnosed NIDDM in the Wanigela people of Papua New Guinea, a population with an extraordinary susceptibility for NIDDM.

RESEARCH DESIGN AND METHODS
We performed a case-control study of Wanigela people from an urban settlement (Koki). Case patients (n = 145) were asymptomatic subjects in whom NIDDM was newly diagnosed using a 2-h 75-g oral glucose tolerance test. Control subjects with glucose tolerance (n = 140) were group-matched on the basis of age and sex. A detailed food frequency questionnaire was used to determine energy and nutrient intakes. Nutrient intakes were compared directly and after calculation of residuals to correct for energy intake. Odds ratios for NIDDM were computed in relation to total energy and specific nutrient intakes, adjusting for age, sex, BMI, waist-to-hip ratio, and physical activity.

RESULTS
There were no differences between case patients and control subjects in mean values of total energy-adjusted nutrient intakes. In logistic regression models, neither total energy nor any specific nutrients were associated with increased risk of NIDDM. When models were repeated with nutrients categorized by textiles, there were marginally significant associations with intakes of fiber (positive) and cholesterol, protein, and sugar (negative).

CONCLUSIONS
This study does not support the hypothesis that saturated fat is an independent risk factor for NIDDM. The weak associations of intakes of fiber and cholesterol with newly diagnosed NIDDM were in the opposite directions to those expected and are probably due to chance. Relative homogeneity of diet within a community, such as that found in Koki, makes it difficult to demonstrate risk factor-disease associations. However, changes in diet and reduced levels of physical activity accompanying urbanization undoubtedly contribute to the high prevalence of obesity observed in this community, and hence diet is likely to contribute to NIDDM risk at least by indirect means.