bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetic Nephropathy in Hypertransfused Patients With β-Thalassemia: The role of oxidative stress
Authors: Loebstein Ronen , Lehotay Denis C , Luo Xiaoping , Bartfay Wally , Tyler Bev , Sher Graham D 
Published: March 2007

OBJECTIVE
Pathogenesis of diabetes-related microvascular complications involving oxidative damage by free radicals has been demonstrated. Free radical generation has been shown to derive largely from iron. Our objectives, therefore, were to determine if there is an increased incidence and/or an accelerated course of nephropathy in patients with diabetes, secondary to transfusional hemochromatosis, and to examine whether free radical activity contributes to the development of this complication.

RESEARCH DESIGN AND METHODS
We evaluated nine patients with homozygous β-thalassemia, complicated by clinically overt diabetes, for diabetic nephropathy over a 7-year period. Lipid peroxidation was quantified by measuring the presence of 20 saturated and unsaturated aldehydes, and results were compared with five normotensive type 1 diabetic patients without iron overload.

RESULTS
Nephropathy developed in five of nine patients (55%) after a mean duration of overt diabetes of 3.6 ± 2.0 years. Three patients showed evidence of progressive microalbuminuria over a 7-year period (24.7–46.2, 52.2–430.1, and 17.7–54.3 μg/min, respectively). Two patients with borderline microalbuminuria (19.9 and 14.5 μg/min, respectively) demonstrated stable albumin excretion rates over the follow-up period. Total aldehyde concentration was significantly higher in β-thalassemia diabetic patients, compared with nonthalassemic diabetic control subjects (8,106 ± 1,280 vs. 4,594 ± 247 nmol/l; P &lt; 0.0001). The three patients with progressive microalbuminuria demonstrated significantly higher total aldehyde concentration, compared with the other β-thalassemia diabetic patients with stable albumin excretion (9,428 ± 337 vs. 7,445 ± 1,003 nmol/l; P &lt; 0.01). Serum vitamin E concentrations were significantly lower in β-thalassemia patients with diabetes, compared with diabetic patients without iron overload (12.1 ± 6.0 vs. 25.9 ± 11.4 μ/l; P = 0.02). Serum vitamin C concentrations did not differ between the two groups. Multiple regression analysis demonstrated total aldehyde concentration to be the most significant predictor for the development of microalbuminuria (P = 0.01), followed by the duration of diabetes (P = 0.02) and glycemic control (P = 0.02).

CONCLUSIONS
Early development and an accelerated course of diabetic nephropathy in iron-loaded patients with β-thalassemia are observed. These findings may be attributed to high oxidative stress in these patients, which is secondary to iron-derived free radicals and to the patients' diminished antioxidant reserves.
Physiological Importance of First-Phase Insulin Release in Elderly Patients With Diabetes
Authors: Meneilly Graydon S , Elahi Dariush 
Published: March 2007

OBJECTIVE
To assess the physiological role of first-phase insulin release in obese elderly patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
Moderately obese elderly patients (n = 14, mean age 77 ± 2 years, BMI 28.4 ± 0.7 kg/m2) with type 2 diabetes underwent three 180-min hyperglycemic clamp studies. In the control study, glucose alone was infused. In the first-phase study, human insulin was infused for the first 4 min at 12 mU/m2 to mimic first-phase insulin release. In the first-phase enhanced study, insulin was infused for the first 4 min at 24 mU · m−2 · min−1. Tritiated glucose methodology was used in all studies to measure glucose production and disposal rates.

RESULTS
Glucose values were similar in all studies. In the control study, first-phase insulin response was absent. The peak insulin response occurred at 4 min in the first-phase and first-phase enhanced studies, but insulin values were substantially higher in the latter study (528 ± 40 vs. 340 ± 24 pmol/l, P &lt; 0.0001). Second-phase insulin responses were not different among the studies. Glucose production and disposal rates were not significantly different among the studies.

CONCLUSIONS
While absent first-phase insulin secretion is a marker of abnormal pancreatic function in obese elderly patients with type 2 diabetes, it is not important in the regulation of hepatic glucose output or peripheral glucose disposal.
Differences in Foot and Forearm Skin Microcirculation in Diabetic Patients With and Without Neuropathy
Authors: Arora Subodh , Smakowski Paula , Frykberg Robert G , Simeone Louis R , Freeman Roy , LoGerfo Frank W , Veves Aristidis 
Published: March 2007

OBJECTIVE
We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects.

RESEARCH DESIGN AND METHODS
We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44°C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response).

RESULTS
The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 ± 4 vs. 55 ± 10 [mean ± SEM] P &lt; 0.01)], the non-neuropathic group (33 ± 6 vs. 88 ± 14; P &lt; 0.01), and the control subjects (43 ± 6 vs. 93 ± 13; P &lt; 0.001). Similar results were observed during the iontophoresis of NaNP (P &lt; 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 ± 0.24; non-neuropathic group, 2.55 ± 0.35; and control subjects, 2.11 ± 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 ± 0.27; non-neuropathic group, 2.08 ± 0.33; and control subjects, 2.77 ± 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups.

CONCLUSIONS
In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.
Attitudes of Primary Care Providers Toward Diabetes: Barriers to guideline implementation
Authors: Larme Anne C , Pugh Jacqueline A 
Published: March 2007

OBJECTIVE
Primary care providers have been slow to adopt standards of care for diabetes, and continuing medical education (CME) programs have been minimally effective in changing provider behavior. The objective of this study was to explore the previously reported finding that attitudes, rather than knowledge, may impede primary care provider adherence to standards of care.

RESEARCH DESIGN AND METHODS
Study participants included 31 primary care providers attending an eight-session CME program on diabetes. Providers rated on a 10-point scale how the treatment of diabetes compared with that of five other chronic conditions (hypertension, hyperlipidemia, angina, arthritis, and heart failure; 1 = easier to 10 = harder; midpoint 5.5). In a subsequent open-ended qualitative interview, providers explained their scale ratings.

RESULTS
Diabetes was rated as significantly harder to treat than hypertension (24 of 30 &gt;5.5; P &lt; 0.001) and angina (20 of 30 &gt;5.5; P = 0.03). A majority also rated hyperlipidemia (18 of 30) and arthritis (18 of 30) as easier to treat than diabetes. Explanatory themes underlying provider frustrations with diabetes include characteristics of the disease itself and the complexity of its management, and a perceived lack of support from society and the health care system for their efforts to control diabetes.

CONCLUSIONS
CME that addresses provider attitudes toward diabetes in addition to updating knowledge may be more effective than traditional CME in promoting adherence to standards of care. Additional changes are needed in our health care system to shift from an acute to a chronic disease model to effectively support diabetes care efforts.
Accuracy of Calculated Serum Low-Density Lipoprotein Cholesterol for the Assessment of Coronary Heart Disease Risk in NIDDM Patients
Authors: Branchi Adriana , Rovellini Angelo , Torri Adriana , Sommariva Domenico 
Published: March 2007

OBJECTIVE
To evaluate the accuracy of LDL cholesterol calculated with Friedewald's equation in the assessment of cardiovascular risk in NIDDM patients.

RESEARCH DESIGN AND METHODS
The calculation of LDL cholesterol according to Friedewald's formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c ≤10%) and in 405 nondiabetic subjects.

RESULTS
Measured and calculated LDL cholesterol was found to be well correlated in both diabetic (r = 0.95) and nondiabetic (r = 0.97) subjects. Compared with measured LDL cholesterol, the calculated LDL cholesterol differed by ≥10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (χ2 = 3.885, P &lt; 0.05). The percentage of error increased when the serum triglyceride (TG) level was ≥200 mg/dl (2.26 mmol/l) and when the ratio of VLDL cholesterol to TG was &lt;0.20 or &gt;0.29 in both groups of subjects. Although the percentage of error from calculated LDL cholesterol was greater in diabetic than in nondiabetic subjects because of the greater prevalence of hypertriglyceridemia in the former group, the misclassification of coronary heart disease risk, according to the cutoff points of the National Cholesterol Education Program (NCEP), was similar in the two groups (25% in diabetic and 22% in nondiabetic subjects). In both groups of patients, the misclassification of coronary heart disease risk was higher when calculation of LDL cholesterol produced values near the cutoff points.

CONCLUSIONS
Although accuracy in the estimation of LDL cholesterol is less than ideal, Friedewald's equation seems to be of value in the correct assignment of coronary heart disease risk classes in the great majority of diabetic as well as nondiabetic subjects. Caution must be exercised for subjects in whom calculated LDL cholesterol is close to the cutoff points of the NCEP guidelines.
Troglitazone in Combination With Sulfonylurea Restores Glycemic Control in Patients With Type 2 Diabetes
Authors: Horton Edward S , Whitehouse Fred , Ghazzi Mahmoud N , Venable Tom C ,   The Troglitazone Study Group, Whitcomb Randall W 
Published: March 2007

OBJECTIVE
To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-γ activator) and sulfonylurea will provide efficacy not attainable by either medication alone.

RESEARCH DESIGN AND METHODS
There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA1c, fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed.

RESULTS
Patients on T600/G12 had significantly lower mean (± SEM) FSG (9.3 ± 0.4 mmol/l; 167.4 ± 6.6 mg/dl) compared with control subjects (13.7 ± 0.4 mmol/l; 246.5 ± 6.8 mg/dl; P &lt; 0.0001) and significantly lower mean HbA1c (7.79 ± 0.2 vs. 10.58 ± 0.18%, P &lt; 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA1c ≤8%, 42% achieved HbA1c ≤7%, and 40% achieved FSG ≤7.8 mmol/l (140 mg/dl). Fasting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G 12 patients compared with &lt;1% on G12 or troglitazone monotherapy

CONCLUSIONS
Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association.
Biologic Material in Needles and Cartridges After Insulin Injection With a Pen in Diabetic Patients
Authors: Le Floch Jean-Pierre , Herbreteau Catherine , Lange Françoise , Perlemuter Léon 
Published: March 2007

OBJECTIVE
To evaluate the frequency of non-inert material, including cells, in needles and cartridges after insulin injection with pen-like devices in diabetic patients.

RESEARCH DESIGN AND METHODS
A prospective study was conducted in 120 insulin-treated diabetic patients who used pen-like devices. The patients, 46 women and 74 men, were 20–77 years old; 60% had type 1 diabetes, and 38% were overweight. Duration of diabetes ranged from 1 month to 40 years, and insulin therapy ranged from 1 month to 30 years. Insulin injection was performed by a trained nurse, using the patient's usual pen and cartridge. A cytopathological examination was performed on the material obtained from the needle and found in the cartridge after centrifugation. All slides were read by a single investigator.

RESULTS
In 62% of the patients, non-inert material was found, including squamous (32%) and epithelial (58%) cells. Biologic material was found in 30% of the needles and 58% of the cartridges, and in both needle and cartridge in 25% of the population. Biologic material was found more frequently in patients who had a longer duration of diabetes, who were treated with insulin for a longer time, and who performed injection in the thighs or upper arms (P &lt; 0.05). In multivariate analysis, the presence of biologic material was associated with the duration of diabetes (R2 = 0.09; P &lt; 0.01).

CONCLUSIONS
Our data suggest that biologic material can be trapped in the delivery system, including the cartridge, after an insulin injection with a pen-like device. Our results emphasize the strict need for individual use of insulin delivery systems, including cartridges and nonrefillable pens, especially in clinics and hospitals.
Abnormal Glucose Tolerance and Increased Risk for Cardiovascular Disease in Japanese-Americans With Normal Fasting Glucose
Authors: Liao David , Shofer Jane B. , Boyko Edward J. , McNeely Marguerite J. , Leonetti Donna L. , Kahn Steven E. , Fujimoto Wilfred Y. 
Published: March 2007

OBJECTIVE— To compare the American Diabetes Association (ADA)fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD).
RESEARCH DESIGN AND METHODS— Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance(NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance(DGT).
RESULTS— Of 503 patients with NFG, 176 had IGT and 20 had DGT. These patients had worse CVD risk factors than those with NGT. The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance Pvalues, adjusted for age and sex, are as follows: intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P &lt; 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P &lt; 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80,0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P= 0.01).
CONCLUSIONS— NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.
Diastolic Dysfunction in Normotensive Men with Well-Controlled Type 2 Diabetes
Authors: Poirier Paul , Bogaty Peter , Garneau Caroline , Marois Louise , Dumesnil Jean-G. 
Published: March 2007

OBJECTIVE— Because a pseudonormal pattern of ventricular filling has never been considered in studies that reported a prevalence of left ventricular diastolic dysfunction (LVDD) between 20 and 40%, our aim was to more completely evaluate the prevalence of LVDD in subjects with diabetes.
RESEARCH DESIGN AND METHODS— We studied 46 men with type 2 diabetes who were aged 38-67 years; without evidence of diabetic complications, hypertension, coronary artery disease, congestive heart failure, or thyroid or overt renal disease; and with a maximal treadmill exercise test showing no ischemia. LVDD was evaluated by Doppler echocardiography, which included the use of the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of left ventricular filling.
RESULTS— LVDD was found in 28 subjects (60%), of whom 13 (28%)had a pseudonormal pattern of ventricular filling and 15 (32%) had impaired relaxation. Systolic function was normal in all subjects, and there was no correlation between LVDD and indexes of metabolic control.
CONCLUSIONS— LVDD is much more common than previously reported in subjects with well-controlled type 2 diabetes who are free of clinically detectable heart disease. The high prevalence of this phenomenon in this high-risk population suggests that screening for LVDD in type 2 diabetes should include procedures such as the Valsalva maneuver and pulmonary venous recordings to unmask a pseudonormal pattern of ventricular filling.
All-Cause Mortality in the Canterbury (New Zealand) Insulin-Treated Diabetic Registry Population
Authors: Brown Laurie J. , Scott Russell S. , Moir Cameron L. 
Published: March 2007

OBJECTIVE— To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand.
RESEARCH DESIGN AND METHODS— Insulin-treated diabetic subjects(n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time.
RESULTS— At study entry, age ranged from 2.9 to 92.7 years,with mean 48.7 ± 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 ± 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 ± 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2[4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality. The SMR for subjects with type 1 diabetes and age at onset &lt;30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8-2.6) for those with onset ≥30 years, and 3.1 (2.5-3.7)for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages.
CONCLUSIONS— Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes.
Pregnancy Outcome in Type 1 Diabetic Women With Microalbuminuria
Authors: Ekbom Pia , Damm Peter , Feldt-Rasmussen Bo , Feldt-Rasmussen Ulla , Mølvig Jens , Mathiesen Elisabeth R. 
Published: March 2007

OBJECTIVE—To determine the influence of microalbuminuria on pregnancy outcome in women with type 1 diabetes.
RESEARCH DESIGN AND METHODS—This prospective cohort study took place at the Obstetric Clinic at National University Hospital, Copenhagen, from January 1996 to February 2000. All Caucasian women with type 1 diabetes, unselected from the eastern part of Denmark, with a living fetus before 17 weeks of gestation on admission were asked to participate. For women with more than one delivery in the study period, only the first pregnancy was included. Of the remaining 246 women, 240 (98%) entered the study. They were categorized according to their urinary albumin excretion (normal urinary albumin excretion, &lt;30 mg/24 h; microalbuminuria, 30–300 mg/24 h; or diabetic nephropathy, &gt;300 mg/24 h) before pregnancy or in the first trimester.
RESULTS—A total of 203 women (85%) had normal urinary albumin excretion, 26 (11%) had microalbuminuria, and 11 (5%) had diabetic nephropathy. Mean HbA1c at 2–6 weeks was 7.5% (SD 1.1), 8.1 (0.9), and 8.8 (1.3) (P &lt; 0.001), respectively. Of all deliveries in women with normal urinary albumin excretion, microalbuminuria, and diabetic nephropathy, 35, 62, and 91% (P &lt; 0.001), respectively, were preterm, and 2, 4, and 45% (P &lt; 0.001), respectively, were small-for-gestational-age infants. Preeclampsia developed in 6, 42, and 64% of the women (P &lt; 0.001), respectively. Category of urinary albumin excretion (P &lt; 0.01) and HbA1c at 2–6 weeks (P &lt; 0.05) were independently associated with preterm delivery.
CONCLUSIONS—The prevalence of preterm delivery is considerably increased in women with microalbuminuria, mainly caused by preeclampsia. Classification according to urinary albumin excretion and metabolic control around the time of conception are superior to the White classification in predicting preterm delivery in women with type 1 diabetes.