bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Metformin on Glycemic Control and Serum Lipids in Insulin-Treated NIDDM Patients With Suboptimal Metabolic Control
Authors: Robinson Adam C , Burke John , Robinson Stephen , Johnston Desmond G , Elkeles Robert S 
Published: March 2007

OBJECTIVE
To test the hypothesis that metformin therapy, given as an adjunct to insulin therapy, improves metabolic control in insulin-treated NIDDM patients with suboptimal glycemic control.

RESEARCH DESIGN AND METHODS
A total of 33 subjects with insulin-treated NIDDM were investigated; all had commenced insulin after secondary failure of antihyperglycemic agents. Two randomized double-blind placebo-controlled crossover studies were run. In study 1 (n = 19), insulin-treated subjects with suboptimal glycemic control received 12 weeks of metformin 1 g b.i.d. and 12 weeks of placebo. In study 2 (n = 14), subjects already established on adjunctive metformin/insulin therapy stopped the metformin component and received 12 weeks of metformin at their baseline dosage (range 1–2.5 g) and 12 weeks of equivalent placebo. Fasting plasma glucose, HbA1c, and serum lipids were measured at baseline and midway through and at the end of each treatment phase. The effect of 12 weeks of metformin treatment was compared with the effect of 12 weeks of placebo in each study and in both studies combined.

RESULTS
In study 1, metformin treatment was associated with significant improvements in fasting plasma glucose (mean 12-week difference fromplacebo [95% CI]: 5.8 mmol/1 [3.5–8.1], P &lt; 0.001) and HbA1c (1.6% [0.9–2.4], P &lt; 0.001). In study 2, metformin treatment was associated with significantly lower fasting plasma glucose (5.3 mmol/1 [0.6–9.9], P = 0.029) and lower HbA1c(2.4% [1.0–3.8], P = 0.003) compared with those for placebo. Study 2 also showed metformin treatment to be associated with significantly lower total cholesterol than that for placebo (1.0 mmol/1 [0.1–1.9], P = 0.032) and lower LDL cholesterol (1.0 mmol/1 [0.1–1.9], P = 0.028). This significant difference in serum lipids seen in study 2 was not seen in study 1, but was present when both sets of data were combined (n = 33, mean total cholesterol difference at 12 weeks [95% CI]: 0.6 mmol/1 [0.1–1.1], P = 0.015). Metformin had no significant effect on triglyceride, HDL cholesterol, weight, or blood pressure. Twosubjects on metformin withdrew because of side effects.

CONCLUSIONS
Metformin, when given as adjunctive therapy, was well tolerated and improved glycemic control and lipid concentrations in patients with insulin-treated NIDDM whose diabetes was poorly controlled. These improvements could be maintained over the long term.
Development and Application of a Model to Estimate the Impact of Type 1 Diabetes on Health-Related Quality of Life
Authors: Wu Shin-Yi , Sainfort François , Tomar Russell H , Tollios James L , Fryback Dennis G , Klein Ronald , Klein Barbara EK 
Published: March 2007

OBJECTIVE
To develop a simulation model to assess the impact of type 1 diabetes and its associated complications on health-related quality of life of a population.

RESEARCH DESIGN AND METHODS
The methodology builds upon 1) an existing population model of type 1 diabetes progression, 2) an empirical study designed to measure state- and age-specific health statuses of type 1 diabetes, and 3) existing literature to quantify quality of life of the corresponding health status. Health statuses were measured in a group of type 1 diabetic patients using the Medical Outcomes Study short form 36 (SF-36). A published empirical regression equation was then used to predict corresponding Quality of Well-Being Index (QWB) scores from these assessments. The QWB scores were incorporated into a previously developed type 1 diabetes progressionand cost simulation model. Sensitivity analyses on key parameters were performed, and the model was found to be robust.

RESULTS
The augmented model can estimate quality-adjusted life years (QALYs) as well as costs associated with type 1 diabetes on any population of interest over any period of time. The model is used to compare intensive versus conventional treatment strategies using a simplified set of assumptions regarding the relative effects of these alternative treatments. With these assumptions, intensive strategy produces more QALYs than does conventional strategy and is cost-beneficial after 5 years.

CONCLUSIONS
The model enables health planners to perform cost-effectiveness analyses to compare alternative treatment strategies for type 1 diabetes and support subsequent decision making.
Patterns of Expenditures and Use of Services Among Older Adults With Diabetes: Implications for the transition to capitated managed care
Authors: Krop Julie S , Powe Neil R , Weller Wendy E , Shaffer Thomas J , Saudek Christopher D , Anderson Gerard F 
Published: March 2007

OBJECTIVE
To examine health care use and expenditures among older adults with diabetes, investigate factors that are associated with higher expenditures, and describe the policy implications of caring for this population under managed care.

RESEARCH DESIGN AND METHODS
A cross-sectional analysis of expenditures for individuals with diabetes over age 65 years from a nationwide 5% random sample of Medicare beneficiaries was conducted during 1992. All components of medical care covered under Medicare were examined. Multivariate analysis was used to assess the contribution of age, race, sex, number of diabetic complications, and comorbidity (Charlson Index) on total expenditures.

RESULTS
On average, individuals with diabetes (n = 188,470) were 1.5 times (P &lt; 0.0001) as expensive as all Medicare beneficiaries (n = 1,371,960). However, there were wide variations, with the most expensive 10% of beneficiaries with diabetes accounting for 56% of expenditures for individuals with diabetes and the least expensive 50% accounting for 4% Acute carehospitalizations accounted for the majority (60%) of total expenditures, whereas outpatient and physician services accounted for 7 and 33%, respectively. There were no differences in the number of complications for all older adults with diabetes compared with those with the highest expenditures. However, the average number of hospitalizations was 1.6 times (0.53 vs. 0.34; P &lt; 0.0001) higher, and the average length of stay was 2 days longer, among older adults with diabetes (P &lt; 0.0001). In the regression model, age and male sex (factors currently used to set payment rates for Medicare managed care enrollees), and number of diabetic complications, but not race, were positively related to expenditures, yet had minimal predictive power (R2 = 0.0006). The addition of the Charlson Index, also positively related to expenditures, was able to explain up to 20% of the variation in total expenditures (R2 = 0.196).

CONCLUSIONS
There are large variations in expenditures among older adults with diabetes. Because elderly beneficiaries with diabetes are more expensive than the average older adult, current Medicare capitation rates may be inadequate. To avoid selection bias and undertreatment of this vulnerable population under managed care, methods to construct fair payment rates and safeguard quality of care are desirable.
Use of the Therapeutic Footwear Benefit Among Diabetic Medicare Beneficiaries in Three States, 1995
Authors: Sugarman Jonathan R , Reiber Gayle E , Baumgardner Greg , Prela Cecilia M , Lowery Joseph 
Published: March 2007

OBJECTIVE
To determine the extent to which Medicare provided reimbursement for therapeutic footwear to diabetic Medicare beneficiaries in Washington, Alaska, and Idaho in 1995.

RESEARCH DESIGN AND METHODS
Using inpatient, outpatient, and durable medical equipment claims data, we selected a cohort of diabetic Medicare beneficiaries. Therapeutic footwear claims were identified using a set of billing codes intended only for the diabetes footwear benefit. People at “high risk” or “possibly increased risk” for foot problems who might benefit from therapeutic footwear were identified using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (1CD-9-CM) diagnostic codes in any of the databases.

RESULTS
Among 608,804 beneficiaries, 10.2% (62,170) met the inclusion criteria for diabetes. Of the diabetic beneficiaries, 13.0% (8,079) had at least one “high risk” diagnosis, and 14.0% (8,686) had at least one “possibly increased risk” diagnosis. The percentage of diabetic beneficiaries with therapeutic footwear claims was 2.9% among those with diagnoses high risk, 0.7% among those with diagnoses indicating possibly increased risk, and 0.1% among those with no diagnosis from the list. Altogether, only 0.6% of beneficiaries meeting the diabetes case ascertainment criteria had a therapeutic footwear claim in 1995.

CONCLUSIONS
Few diabetic Medicare beneficiaries in Washington, Alaska, and Idaho had claims for reimbursement for therapeutic footwear in 1995. The low utilization of the footwear benefit may represent an important opportunity to improve care for Medicare beneficiaries with diabetes. Further work should be done to characterize the use of the benefit in other regions and to assess whether the low level of usage reflects underutilization.
Objective Assessment of Smoking Habits by Urinary Cotinine Measurement in Adolescents and Young Adults With Type 1 Diabetes: Reliability of reported cigarette consumption and relationship to urinary albumin excretion
Authors: Holl Reinhard W , Grabert Mathias , Heinze Eberhard , Debatin Klaus-Michael 
Published: March 2007

OBJECTIVE
To examine the relationship of objective smoking status to age, sex, longterm metabolic control, and urinary albumin excretion. Patients with type 1 diabetes who smoke are at increased risk to develop diabetic microvascular and macrovascular complications. While this has repeatedly been demonstrated in adults, smoking habits have rarely been investigated in adolescents.

RESEARCH DESIGN AND METHODS
Urinary cotinine excretion has been determined by radioimmunoassay in 238 adolescents and young adults with type 1 diabetes. This biochemical parameter of nicotine use was related to age, to the number of cigarettes allegedly consumed per day, and to urinary albumin excretion.

RESULTS
A total of 46 patients (19.3%) with urinary cotinine values &gt;500 ng/ml were classified as smokers. In 26 patients (10.9%), cotinine values between 100 and 500 ng/ml were found (infrequent smokers or environmental nicotine exposure), while the remaining 166 patients excreted &lt;100 ng/ml of cotinine in the urine (nonsmokers). Smokers were significantly older (20.2 ± 0.6 years [mean ± SE]) compared with the intermediate group (18.3 ± 0.7 years) or with nonsmokers (15.9 ± 0.4 years; P &lt; 0.0001, Wilcoxon's signed-rank test). Of 46 smokers, 12 denied smoking cigarettes entirely, and among biochemically defined smokers, no correlation was present between urinary cotinine excretion and the reported number of cigarettes consumed per day. Urinary albumin excretion was significantly higher in smokers compared with nonsmokers (P &lt; 0.003).

CONCLUSIONS
These data demonstrate that cigarette smoking is common among German adolescents and young adults with type 1 diabetes in this study. Many patients deny nicotine use or refuse to disclose their smoking habits. Increased urinary albumin excretion is consistent with an increased risk of nephropathy in subjects with diabetes who smoke. Pediatricians in charge of adolescents with type 1 diabetes should actively discuss the risk of nicotine consumption with their patients.
Troglitazone Decreases the Proportion of Small, Dense LDL and Increases the Resistance of LDL to Oxidation in Obese Subjects
Authors: Tack Cees JJ , Smits Paul , Demacker Pierre NM , Stalenhoef Anton FH 
Published: March 2007

OBJECTIVE
Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation.

RESEARCH DESIGN AND METHODS
In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined.

RESULTS
Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 ± 0.18 to 2.77 ± 0.20 mmol/1 (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 ± 0.04 to 0.62 ± 0.09 mmol/1, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase.

CONCLUSIONS
In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.
Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM
Authors: Hofmann Marion A , Kohl Brigitte , Zumbach Martina S , Borcea Valentin , Bierhaus Angelika , Henkels Mechthild , Amiral Jean , Schmidt Ann Marie , Fiehn Walter , Ziegler Reinhard , Wahl Peter , Nawroth Peter P 
Published: March 2007

OBJECTIVE
Considering that elevated blood levels of homocyst(e)ine represent a known independent risk factor for macrovascular disease, we assessed the link between hyperhomocyst(e)inemia and diabetic microvascular complications.

RESEARCH DESIGN AND METHODS
Homocyst(e)ine and thrombomodulin plasma levels, a marker of endothelial cell damage, were measured before and 3 h after oral methionine loading in 75 patients with stable, well-controlled IDDM and 40 healthy control subjects matched for sex and age. Exclusion criteria were hyperlipidemia, hypertension, smoking, or positive family history for cardiovascular disease.

RESULTS
IDDM patients had higher pre- and postload homocyst(e)ine plasma levels than did healthy control subjects (12.0 vs. 7.7 umol/1 and 27.6 vs. 16.0 umol/1; P &lt; 0.001). Of 75 IDDM patients, 26 had homocyst(e)ine plasma levels above the normal range (defined as mean ± 2 SD of values obtained in the control group). The IDDM patients with hyperhomocyst(e)inemia had higher thrombomodulin plasma levels (62.2 vs. 38.2 ng/ml; P &lt; 0.001), higher albumin excretion rates (485 vs. 115 mg/1; P &lt; 0.005), and a higher prevalence of late diabetic complications (nephropathy 76 vs. 33%; retinopathy 69 vs. 51%; neuropathy, 57 vs. 41%; macroangiopathy 57 vs. 33%) compared with IDDM patients with normal plasma homocyst(e)ine. In vitro experiments with human umbilical vein cells show an increased release of thrombomodulin into the culture supernatant only when endothelial cells were pretreated with advanced glycation end product (AGE)-albumin before L-homocystine was added. A synergistic action of homocyst(e)ine and AGEs might contribute to vascular complications of patients with diabetes.

CONCLUSIONS
Hyperhomocyst(e)inemia is common in nephropathic diabetic patients and may contribute to the enhanced morbidity and mortality from cardiovascular diseases characteristically observed in IDDM patients with diabetic nephropathy.
Validation of a Diabetic Wound Classification System: The contribution of depth, infection, and ischemia to risk of amputation
Authors: Armstrong David G , Lavery Lawrence A , Harkless Lawrence B 
Published: March 2007

OBJECTIVE
To validate a wound classification instrument that includes assessment of depth, infection, and ischemia based on the eventual outcome of the wound.

RESEARCH DESIGN AND METHODS
We evaluated the medical records of 360 diabetic patients presenting for care of foot wounds at a multidisciplinary tertiary care foot clinic. As per protocol, all patients had a standardized evaluation to assess wound depth, sensory neuropathy, vascular insufficiency, and infection. Patients were assessed at 6 months after their initial evaluation to see whether an amputation had been performed.

RESULTS
There was a significant overall trend toward increased prevalence of amputations as wounds increased in both depth (χ2trend = 143.1, P &lt; 0.001) and stage (χ2trend = 91.0, P &lt; 0.001). This was true for every subcategory as well with the exception of noninfected, nonischemic ulcers. There were no amputations performed within this stage during the follow-up period. Patients were more than 11 times more likely to receive a midfoot or higher level amputation if their wound probed to bone (18.3 vs. 2.0%, P &lt; 0.001, χ2 = 31.5, odds ratio (OR) = 11.1, CI = 4.0–30.3). Patients with infection and ischemia were nearly 90 times more likely to receive a midfoot or higher amputation compared with patients in less advanced wound stages (76.5 vs. 3.5%, P &lt; 0.001, χ2 = 133.5, OR = 89.6, CI = 25–316).

CONCLUSIONS
Outcomes deteriorated with increasing grade and stage of wounds when measured using the University of Texas Wound Classification System.
Carotid Atherosclerosis in Adolescents and Young Adults With IDDM: Relation to urinary endothelin, albumin, free cortisol, and other factors
Authors: Peppa-Patrikiou Melpomeni , Scordili Maria , Antoniou Aristidis , Giannaki Maria , Dracopoulou Maria , Dacou-Voutetakis Catherine 
Published: March 2007

OBJECTIVE
To investigate 1) alterations of carotid intimal-plus-medial thickness (IMT) in subjects with IDDM and 2) the relation of IMT to indexes of diabetic angiopathy and to risk factors of atherosclerosis.

RESEARCH DESIGN AND METHODS
IMT was assessed by ultrasound B-mode imaging in 39 subjects with IDDM (23 male, 16 female young adults aged 17.5 ± 5.2 years, diabetes duration 8.8 ± 5.9) and in 22 control subjects (healthy siblings of the IDDM subjects) of comparable age. Urinary endothelin (UET1) and urinary free cortisol (UFC) were determined by radioammunoassay (RIA), urinary albumin by nephelometry, HbA1c by high-performance liquid chromatography (HPLC), and plasma renin by immunoradiometric assay (IRMA).

RESULTS
The IMT values were greater in IDDM subjects than in control subjects (0.49 ± 0.1 mm, 0.44 ± 0.09 mm, respectively; P = 0.048) and greater in IDDM male subjects than in control male subjects (0.52 ± 0.09 and 0.44 ± 0.06 mm, respectively; P = 0.015), with no difference between IDDM and control female subjects. The IMT values were greater in diabetic male subjects than in female subjects (0.52 ± 0.09 and 0.45 ± 0.1 mm, respectively; P = 0.017). In IDDM subjects, but not in control subjects, there was a positive correlation of IMT to urinary albumin (P = 0.008), systolic blood pressure (P = 0.023), UET1 (P = 0.016), UFC (P = 0.002), and BMI (P = 0.021). Multiple regression analysis demonstrated that in IDDM subjects the variable that interacts independently with IMT was the BMI (P = 0.001).

CONCLUSIONS
IMT, an index of atherosclerosis (macroangiopathy), is increased in IDDM subjects quite early (already in adolescence), and it is positively related to urinary albumin, UET1, blood pressure, and UFC.
Elevated Concentrations of Soluble E-Selectin and Vascular Cell Adhesion Molecule-1 in NIDDM: Effect of intensive insulin treatment
Authors: Albertini Jean-Paul , Valensi Paul , Lormeau Boris , Aurousseau Marie-Hélène , Ferrière Francoise , Attali Jean-Raymond , Gattegno Liliane 
Published: March 2007

OBJECTIVE
To evaluate the effects of a 14-day intensive insulin therapy and short-term improvement of glycemic control on serum levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in NIDDM patients with poor glycemic control.

RESEARCH DESIGN AND METHODS
A total of 16 NIDDM patients were compared with 23 healthy subjects (control group) and investigated before and after intensive insulin treatment.

RESULTS
On day 0, sE-selectin and sVCAM-1 levels were significantly higher in NIDDM patients than in nondiabetic control subjects (median 87, range 63–115; median 544, range 408–797 vs. 58, 43–80; 443, 395–573 ng/ml, respectively) (P &lt; 0.008 in both cases). On day 15, the fall in sE-selectin levels was significant (P &lt; 0.0001) and at a lesser extent in sVCAM-1 levels (64, 48–85; 506, 417–678 ng/ml, respectively); these levels reached values that no longer differed from those of control subjects (P = 0.23 and 0.15, respectively). Moreover, the fall in sE-selectin was positively associated with the change in LDL cholesterol and the improvement of glycemia.

CONCLUSIONS
In poorly controlled NIDDM patients, sE-selectin levels are increased and significantly fall to normal after short-term improvement of glycemic control. This suggests that assaying sE-selectin makes it possible to detect endothelium activation and to follow its reversal with euglycemia.
Influence of Interindividual Variability of Aldose Reductase Protein Content on Polyol-Pathway Metabolites and Redox State in Erythrocytes in Diabetic Patients
Authors: Hamada Yoji , Nishimura Chihiro , Koh Naoki , Sakakibara Fumihiko , Nakamura Jiro , Tanimoto Tsuyoshi , Hotta Nigishi 
Published: March 2007

OBJECTIVE
To clarify the influence of interindividual difference in the level of aldose reductase on the polyol pathway-related metabolism in diabetic patients.

RESEARCH DESIGN AND METHODS
The enzyme protein content was determined by a two-site enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies to recombinant human aldose reductase in erythrocytes from 35 diabetic patients and 11 healthy volunteers. Patients were stratified into two groups by the median of aldose reductase content, and the erythrocyte sorbitol level, the fructose level, and the lactate-to-pyruvate ratio were compared between the two groups. We also examined the correlation of the enzyme content with these metabolic parameters.

RESULTS
The group of patients whose enzyme content was above the median showed a significant increase in the levels of sorbitol (34.7 ± 4.9 vs. 20.4 ± 2.0 nmol/g Hb, P &lt; 0.05) and fructose (99.8 ± 17.2 vs. 45.9 ± 4.6 nmol/g Hb, P &lt; 0.05), along with an elevated lactate-to-pyruvate ratio (28.6 ± 6.1 vs. 11.7 ± 1.2, P &lt; 0.05), compared with patients with low enzyme levels. The aldose reductase content in erythrocytes was well correlated with its activity, and there was a significant correlation between the enzyme content and the erythrocyte sorbitol (r = 0.58, P &lt; 0.001) or fructose (r = 0.57, P &lt; 0.001) levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r = 0.38, P &lt; 0.05).

CONCLUSIONS
These results suggest that the interindividual variability of aldose reductase content may contribute tangibly to the polyol-pathway flux and cytoplasmic redox alteration in diabetic patients.