bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Monocyte Chemoattractant Protein-1 and Early Development of Nephropathy in Type 1 Diabetes
Authors: Chiarelli Francesco , Cipollone Francesco , Mohn Angelika , Marini Matteo , Iezzi Annalisa , Fazia Maria , Tumini Stefano , De Cesare Domenico , Pomilio Mariapina , Pierdomenico Sante D. , Di Gioacchino Mario , Cuccurullo Franco , Mezzetti Andrea
Published: March 2007

OBJECTIVES—To investigate the possible role of hyperglycemia-dependent monocyte chemoattractant protein (MCP)-1 biosynthesis in the pathophysiology of early nephropathy in type 1 diabetes.

RESEARCH DESIGN AND METHODS—We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared with matched healthy control subjects. Plasma MCP-1 and plasma oxidant status (vitamin E, fluorescent products of lipid peroxidation [FPLPs], malondialdehyde [MDA]), HbA1c, and albumin excretion rate [AER]) were evaluated at baseline. Furthermore, MCP-1, vitamin E, AER, and HbA1c were also analyzed in the microalbuminuric diabetic patients and in the healthy volunteers after 8 weeks of high-dose (600 mg b.i.d.) vitamin E treatment.

RESULTS—FPLPs, MDA, and MCP-1 were significantly higher, whereas vitamin E was significantly lower in patients with microalbuminuria and poorer glycemic control as compared with normoalbuminuric patients and healthy control subjects. Plasma MCP-1 was positively correlated with HbA1c, FPLPs, MDA, and AER, whereas plasma MCP-1 showed an inverse correlation with vitamin E. Interestingly, both MCP-1 and AER decreased significantly after vitamin E treatment, despite no changes in HbA1c values.

CONCLUSIONS—This study suggests that prolonged hyperglycemia may lead to early renal complications in type 1 diabetes by inducing MCP-1 biosynthesis via enhanced oxidative stress. Long-term treatment of high-dose vitamin E significantly decreased MCP-1, thus providing a rationale basis for evaluating vitamin E supplementation as therapy adjuvant to conventional insulin treatment in type 1 diabetic patients in whom an acceptable glycemic control is difficult to achieve despite appropriate insulin treatment.
Irbesartan Reduces the Albumin Excretion Rate in Microalbuminuric Type 2 Diabetic Patients Independently of Hypertension
Authors: Sasso Ferdinando C. , Carbonara Ornella , Persico Marcello , Iafusco Dario , Salvatore Teresa , D’Ambrosio Rosanna , Torella Roberto , Cozzolino Domenico
Published: March 2007

OBJECTIVE—ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA1c, and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study.

RESULTS—In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER.

CONCLUSIONS—These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects.
Comparison of a Homogeneous Assay With a Precipitation Method for the Measurement of HDL Cholesterol in Diabetic Patients
Authors: Jensen Tonny , Truong Quan , Frandsen Merete , Dinesen Bo , Stender Steen
Published: March 2007

OBJECTIVE—To compare direct-measured HDL cholesterol with HDL cholesterol measured by a precipitation method.

RESEARCH DESIGN AND METHODS—We compared a homogeneous assay for direct HDL cholesterol analysis with the phosphotungstic acid magnesium chloride precipitation method in 55 type 1 diabetic patients, 70 type 2 diabetic patients, and 82 nondiabetic normal control subjects with plasma triglyceride levels <4.6 mmol/l. The cholesterol content of HDL determined by the direct assay was overall 0.1 mmol/l higher in all three groups than HDL cholesterol measured after precipitation, but the two methods were closely correlated (r2 = 0.98, P < 0.001).

RESULTS—HbA1c, blood glucose, serum albumin, serum bilirubin, or triglyceride did not influence the differences of the two HDL cholesterol measurements. Because we have previously shown HDL cholesterol isolated by phosphotungstic acid precipitation to be lower than that by ultracentrifugation, the positive bias found in this study was expected. It seems that the direct HDL cholesterol assay reacts with apolipoprotein (apo) B-containing lipoproteins in the fraction with a density of >1.063; these apo B-containing lipoproteins are suggested to be coprecipitated with the phosphotungstic acid method. We also measured LDL cholesterol directly by a LDL cholesterol plus method and found no significant differences between this method and LDL cholesterol calculated from Friedewald’s formula.

CONCLUSIONS—Direct homogeneous assay for HDL cholesterol determination in diabetic patients seems not to exhibit a negative bias, in contrast to the precipitation method, when compared with the ultracentrifugation method. In addition, the direct assay saves time and is not influenced by type of diabetes or degree of metabolic control.
The Epidemiology of Type 1 Diabetes in Children in Philadelphia 1990–1994
Authors: Lipman Terri H. , Chang Yuefang , Murphy Kathryn M.
Published: March 2007

OBJECTIVE—To determine the epidemiology of type 1 diabetes in children in Philadelphia from 1990 to 1994, and to identify whether an epidemic occurred during that time period.

RESEARCH DESIGN AND METHODS—This is a descriptive epidemiological study using a retrospective population-based registry in Philadelphia, PA, a city with large white, African-American, and Hispanic (Puerto Rican) populations. All hospitals in Philadelphia that admit children were identified. All charts meeting the following criteria were reviewed: 1) newly diagnosed type 1 diabetes, 2) children 0–14 years of age, 3) children residing in Philadelphia at the time of diagnosis, and 4) those diagnosed from 1 January 1990 to 31 December 1994. Standard type 1 diabetes registry data were abstracted from the charts. Ascertainment of the completeness of the hospital registry was validated by data from the Philadelphia School District. Communicable disease records were reviewed to identify epidemics from 1987 to 1995.

RESULTS—A total of 209 cases were identified, and the combined hospital and school registry was determined to be 96% complete. The overall age-adjusted incidence rate in Philadelphia was 13.3/100,000/year. The highest rate by race continues to be in the Hispanic population (15.5). The incidence in African-American children has increased markedly (12.8), particularly in the 10- to 14-year age-group (22.9). An epidemic of type 1 diabetes occurred from January to June 1993, ∼2 years after a measles epidemic in Philadelphia.

CONCLUSIONS—The overall incidence of type 1 diabetes in Philadelphia is similar to other U.S. registries. The incidence in the Hispanic population continues to be among the highest of any U.S. ethnic group. The marked increase in incidence in the African-American population may be due in part to misclassification of cases actually having type 2 diabetes. The 1993 epidemic may have been due to β-cell autoimmunity triggered by the measles virus.
Psychological and Behavioral Correlates of Baseline BMI in the Diabetes Prevention Program (DPP)
Authors: Delahanty Linda M. , Meigs James B. , Hayden Doug , Williamson Donald A. , Nathan David M. ,   the DPP Research Group
Published: March 2007

OBJECTIVE—To determine psychological and behavioral correlates of baseline BMI in the Diabetes Prevention Program (DPP).

RESEARCH DESIGN AND METHODS—Of 1,079 DPP lifestyle intervention participants, 274 completed validated questionnaires at baseline assessing weight loss history, stage of change, self-efficacy, dietary restraint, emotional eating, binge eating, perceived stress, depression, and anxiety.

RESULTS—The mean age of subjects was 52.5 years, 65% were women, and their mean BMI was 33.9 kg/m2. Higher BMI correlated with more frequent weight cycling (r = 0.50, P < 0.0001) and efforts at weight loss (r = 0.34, P < 0.0001); younger age when first overweight (r = −0.42, P < 0.0001); lower exercise efficacy (r = −0.15, P = 0.015); lower weight loss efficacy (r = −0.21, P < 0.001); a less advanced stage of change for weight loss (r = −0.12, P = 0.04); more perceived stress (r = 0.14, P = 0.02); emotional eating (r = 0.19, P = 0.001); poor dietary restraint (r = −0.14, P = 0.02); binge eating frequency (r = 0.18, P = 0.004) and severity (r = 0.30, P < 0.0001); feeling deprived, angry, or upset while dieting (r = 0.27, P ≤ 0.0001); and food cravings while dieting (r = 0.31, P < 0.0001). Correlations did not differ as a function of sex; however, correlations of BMI with anxiety and low-fat diet and weight loss self-efficacy differed as a function of ethnicity. In multivariate models, binge eating severity, poor dietary restraint, and food craving were independent correlates of baseline BMI.

CONCLUSIONS—Many psychological and behavioral factors are associated with higher BMI in this ethnically diverse group of men and women. Whether strategies that help patients increase levels of dietary restraint and reduce binge eating and food craving lead to long-term weight loss maintenance needs longitudinal study.
Can Motor Nerve Conduction Velocity Predict Foot Problems in Diabetic Subjects Over a 6-Year Outcome Period?
Authors: Carrington Anne L. , Shaw Jonathan E. , Van Schie Carine H.M. , Abbott Caroline A. , Vileikyte Loretta , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—This study examined motor nerve conduction velocity (MNCV) and other peripheral nerve and vascular tests as predictors for foot ulceration, amputation, and mortality in diabetes over a 6-year follow-up period.

RESEARCH DESIGN AND METHODS—We recruited 169 diabetic subjects (without significant peripheral vascular disease with an ankle brachial pressure index [ABPI] ≥0.75) for the study and separated them into groups (to ensure diversity of nerve function). The control group consisted of 22 nondiabetic people. At baseline, all subjects underwent assessment of MNCV; vibration, pressure, and temperature perception thresholds; peripheral vascular function; and other diabetes assessments.

RESULTS—Over the 6-year outcome period, 37.3% of the diabetic subjects developed at least one new ulcer, 11.2% had a lower-limb amputation (LLA) (minor or major), and 18.3% died. Using multivariate Cox’s regression analysis (RR [95% CI] and removing previous ulcers as a confounding variable, MNCV was found to be the best predictor of new ulceration (0.90 [0.84–0.96], P = 0.001) and the best predictors of amputation were pressure perception threshold (PPT) (5.18 [1.96–13.68], P = 0.001) and medial arterial calcification (2.88 [1.13–7.35], P = 0.027). Creatinine (1.01 [1.00–1.01], P < 0.001), MNCV (0.84 [0.73–0.97], P = 0.016), and skin oxygen levels (14.32 [3.04–67.52], P = 0.001) were the best predictors of mortality.

CONCLUSIONS—This study shows that MNCV, which is often assessed in clinical trials of neuropathy, can predict foot ulceration and death in diabetes. In addition, tests of PPT and medial arterial calcification can be used in the clinic to predict LLA in diabetic subjects.
Biological Variation of Homeostasis Model Assessment-Derived Insulin Resistance in Type 2 Diabetes
Authors: Jayagopal Vijay , Kilpatrick Eric S. , Jennings Paul E. , Hepburn David A. , Atkin Stephen L.
Published: March 2007

OBJECTIVE—Individuals with type 2 diabetes are particularly vulnerable to cardiovascular disease. Insulin resistance is a major determinant of this increased risk and is a potential therapeutic target. This study was undertaken to establish the natural biological variation of insulin resistance in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—The biological variation of insulin resistance was assessed by measuring insulin resistance at 4-day intervals on 10 consecutive occasions in 12 postmenopausal women with diet-controlled type 2 diabetes and in 11 weight- and age-matched postmenopausal women without type 2 diabetes. Insulin resistance was derived using the homeostasis model assessment for insulin resistance (HOMA-IR) method.

RESULTS—The distribution of HOMA-IR was log Gaussian in the type 2 diabetic study group and Gaussian in the control group. The HOMA-IR in the type 2 diabetic group was significantly greater than that of the control group (mean ± SD: 4.33 ± 2.3 vs. 2.11 ± 0.79 units, P = 0.001). After accounting for analytical variation, the mean intraindividual variation was also substantially greater in the type 2 diabetic group than in the control group (mean 1.05 vs. 0.15, P = 0.001). Consequently, at any level of HOMA-IR, a subsequent sample must increase by >90% or decrease by >47% to be considered significantly different from the first.

CONCLUSIONS—HOMA-IR is significantly greater and more variable for individuals with type 2 diabetes. Therefore, this inherent variability needs to be accounted for in studies evaluating therapeutic reduction of HOMA-IR in this group.
Cardiac Events in 735 Type 2 Diabetic Patients Who Underwent Screening for Unknown Asymptomatic Coronary Heart Disease
Authors: Faglia Ezio , Favales Fabrizio , Calia Patrizia , Paleari Felice , Segalini Giovanni , Gamba Pier Luigi , Rocca Alberto , Musacchio Nicoletta , Mastropasqua Arturo , Testori Gianpaolo , Rampini Pietro , Moratti Flavia , Braga Anna , Morabito Alberto
Published: March 2007

OBJECTIVE—To report the cardiac events in type 2 diabetic outpatients screened for unknown asymptomatic coronary heart disease (CHD) and followed for 5 years.

RESEARCH DESIGN AND METHODS—During 1993, 925 subjects aged 40–65 years underwent an exercise treadmill test (ETT). If it was abnormal, the subjects then underwent an exercise scintigraphy. Of the 925 subjects, 735 were followed for 5 years and cardiac events were recorded.

RESULTS—At the entry of the study, 638 of the 735 followed subjects had normal ETT, 45 had abnormal ETT with normal scintigraphy, and 52 had abnormal ETT and abnormal scintigraphy. The 52 subjects with abnormal scintigraphy and ETT underwent a cardiological and diabetological follow-up; the subjects with just abnormal ETT had a diabetological follow-up only. During the follow-ups, 42 cardiac events occurred: 1 fatal myocardial infarction (MI), 20 nonfatal MIs, and 10 cases of angina in the 638 subjects with normal ETT; 1 fatal MI in the 45 subjects with normal scintigraphy; and 1 fatal MI and 9 cases of angina in the 52 subjects with abnormal scintigraphy. In these 52 subjects all cardiac events were significantly more frequent (χ2 = 21.40, P < 0.0001) but the ratio of major (cardiac death and MI) to minor (angina) cardiac events was significantly lower (P = 0.002). Scintigraphy abnormality (hazard ratio 5.47; P < 0.001; 95% CI 2.43–12.29), diabetes duration (1.06; P = 0.021; 1.008–1.106), and diabetic retinopathy (2.371; P = 0.036; 1.059–5.307) were independent predictors of cardiac events on multivariate analysis.

CONCLUSIONS—The low ratio of major to minor cardiac events in the positive scintigraphy group may suggest, although it does not prove, that the screening program followed by appropriate management was effective for the reduction of risk of major cardiac events.
Combination of Insulin and Metformin in the Treatment of Type 2 Diabetes
Authors: Wulffelé Michiel G. , Kooy Adriaan , Lehert Philippe , Bets Daniel , Ogterop Jeles C. , Borger van der Burg Bob , Donker Ab J.M. , Stehouwer Coen D.A.
Published: March 2007

OBJECTIVE—To investigate the metabolic effects of metformin, as compared with placebo, in type 2 diabetic patients intensively treated with insulin.

RESEARCH DESIGN AND METHODS—Metformin improves glycemic control in poorly controlled type 2 diabetic patients. Its effect in type 2 diabetic patients who are intensively treated with insulin has not been studied. A total of 390 patients whose type 2 diabetes was controlled with insulin therapy completed a randomized controlled double-blind trial with a planned interim analysis after 16 weeks of treatment.The subjects were selected from three outpatient clinics in regional hospitals and were randomly assigned to either the placebo or metformin group, in addition to insulin therapy. Intensive glucose monitoring with immediate insulin adjustments according to strict guidelines was conducted. Indexes of glycemic control, insulin requirements, body weight, blood pressure, plasma lipids, hypoglycemic events, and other adverse events were measured.

RESULTS—Of the 390 subjects, 37 dropped out (12 in the placebo and 25 in the metformin group). Of those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with improved glycemic control (mean daily glucose at 16 weeks 7.8 vs. 8.8 mmol/l, P = 0.006; mean GHb 6.9 vs. 7.6%, P < 0.0001); reduced insulin requirements (63.8 vs. 71.3 IU, P < 0.0001); reduced weight gain (−0.4 vs. +1.2 kg, P < 0.01); and decreased plasma LDL cholesterol (−0.21 vs. −0.02 mmol/l, P < 0.01). Risk of hypoglycemia was similar in both groups.

CONCLUSIONS—In type 2 diabetic patients who are intensively treated with insulin, the combination of insulin and metformin results in superior glycemic control compared with insulin therapy alone, while insulin requirements and weight gain are less.
Insulin Resistance and Associated Compensatory Responses in African-American and Hispanic Children
Authors: Goran Michael I. , Bergman Richard N. , Cruz Martha L. , Watanabe Richard
Published: March 2007

OBJECTIVE—The objective of this study was to compare insulin resistance relative to body fat and the associated compensatory responses in 57 healthy children living in Los Angeles, California (14 Caucasians, 15 African-Americans, and 28 Hispanics).

RESEARCH DESIGN AND METHODS—Insulin sensitivity and acute insulin response were determined by intravenous glucose tolerance test. Insulin secretion, hepatic insulin extraction, and insulin clearance were estimated by C-peptide and insulin modeling.

RESULTS—Insulin sensitivity was significantly lower in Hispanics and African-Americans compared with Caucasian children, and acute insulin response was significantly higher in African-American children. No ethnic differences were noted in the first-phase secretion, but second-phase insulin secretion was significantly higher in Hispanic children than in African-American children (200 ± 53 vs. 289 ± 41 nmol/min; P = 0.03). The greater acute insulin response in African-Americans, despite lower secretion, was explained by a lower hepatic insulin extraction in African-Americans compared with Hispanics (36.6 ± 2.9 vs. 47.3 ± 2.2%; P = 0.0006).

CONCLUSIONS—In conclusion, Hispanic and African-American children are more insulin resistant than Caucasian children, but the associated compensatory responses are different across ethnic groups.
Noninvasive Blood Glucose Monitoring With Optical Coherence Tomography
Authors: Larin Kirill V. , Eledrisi Mohsen S. , Motamedi Massoud , Esenaliev Rinat O.
Published: March 2007

OBJECTIVE—To study the feasibility of noninvasive blood glucose monitoring using optical coherence tomography (OCT) technique in healthy volunteers.

RESEARCH DESIGN AND METHODS—An OCT system with the wavelength of 1,300 nm was used in 15 healthy subjects in 18 clinical experiments. Standard oral glucose tolerance tests were performed to induce changes in blood glucose concentration. Blood samples were taken from the right arm vein every 5 or 15 min. OCT images were taken every 10–20 s from the left forearm over a total period of 3 h. The slope of the signals was calculated at the depth of 200–600 μm from the skin surface.

RESULTS—A total of 426 blood samples and 8,437 OCT images and signals were collected and analyzed in these experiments. There was a good correlation between changes in the slope of noninvasively measured OCT signals and blood glucose concentrations throughout the duration of the experiments. The slope of OCT signals changed significantly (up to 2.8% per 10 mg/dl) with variation of plasma glucose values. The good correlation obtained between the OCT signal slope and blood glucose concentration is due to the coherent detection of backscattered photons, which allows measurements of OCT signal from a specific tissue layer without unwanted signal from other tissue layers.

CONCLUSIONS—This pilot study demonstrated the capability of the OCT technique to monitor blood glucose concentration noninvasively in human subjects. Further studies with a larger number of subjects including diabetic subjects are planned to validate these preliminary results.
Intrauterine Hyperglycemia Is Associated With an Earlier Diagnosis of Diabetes in HNF-1α Gene Mutation Carriers
Authors: Stride Amanda , Shepherd Maggie , Frayling Timothy M. , Bulman Mike P. , Ellard Sian , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—In animals, experimentally induced maternal hyperglycemia during pregnancy results in hyperglycemic offspring. Similarly, Pima Indian offspring with mothers who are diabetic at the time of pregnancy have increased risk of early-onset diabetes. We hypothesized that exposure to hyperglycemia in utero would decrease the age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY) due to a mutation in the hepatocyte nuclear factor 1α (HNF-1α) gene.

RESEARCH DESIGN AND METHODS—We analyzed the affect of maternal diabetes on age at diagnosis of diabetes in 150 HNF-1α gene mutation carriers from 55 families.

RESULTS—Age at diagnosis in HNF-1α mutation carriers was younger when the mother was diagnosed before pregnancy compared with when the mother was diagnosed after pregnancy (15.5 ± 5.4 vs. 27.5 ± 13.1 years, P < 0.0001). This is unlikely to represent a generalized familial decrease in age at diagnosis due to a more severe mutation, because no difference was seen in age of the offspring at diagnosis of diabetes when the father was diagnosed at a young age, and a similar trend was seen when only the single common mutation, P291fsinsC, was analyzed.

CONCLUSIONS—We conclude that maternal hyperglycemia during pregnancy probably increases the penetrance of HNF-1α mutations. The potential role of exposure to hyperglycemia in utero in a monogenic diabetic subgroup warrants prospective study.
Determinants of the Development of Diabetes (Maturity-Onset Diabetes of the Young-3) in Carriers of HNF-1α Mutations
Authors: Klupa Tomasz , Warram James H. , Antonellis Anthony , Pezzolesi Marcus , Nam Moonsuk , Malecki Maciej T. , Doria Alessandro , Rich Stephen S. , Krolewski Andrzej S.
Published: March 2007

OBJECTIVE—To determine the distribution of the age at onset of diabetes (maturity-onset diabetes of the young-3 [MODY3]) and to identify determinants of the onset of diabetes in carriers of HNF-1α mutations.

RESEARCH DESIGN AND METHODS—Extended families (n = 104) with type 2 diabetes inherited in a dominant pattern were recruited and screened for diabetes-causing mutations in HNF-1α.

RESULTS—HNF-1α mutations cosegregated with diabetes in only 13 families, all with a mean age at onset <35 years. Insulin secretion was diminished or absent in mutation carriers (n = 101), and diabetes developed in 65% by age 25 years and in 100% by age 50 years. If the mutation was inherited from the mother, diabetes onset was very young in those exposed to diabetes in utero; 57 ± 8% were affected by age 15 years as compared with 0.0% in those not exposed (P < 7 × 10−6). By age 25 years, the difference was reduced (85 ± 6 and 55 ± 12%, respectively; P = 0.02). If the mutation was inherited from the father, diabetes developed in 52 ± 8% by age 25 years. Age at diagnosis was shown to be highly heritable (h2 = 0.47, P = 0.003). When parent of origin was included in the analyses, the magnitude of genetic contribution increased markedly (h2 = 0.91).

CONCLUSIONS—Mutations in HNF-1α accounts for diabetes in a small proportion of families with a dominant pattern of inheritance. Age at onset of diabetes in MODY3 families varied widely and was influenced by familial factors (including modifying genes) and parent of origin (whether a mutation carrier was exposed to diabetes in utero).
Macular Edema Reflects Generalized Vascular Hyperpermeability in Type 2 Diabetic Patients With Retinopathy
Authors: Knudsen Søren T. , Bek Toke , Poulsen Per L. , Hove Marianne N. , Rehling Michael , Mogensen Carl E.
Published: March 2007

OBJECTIVE—Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TERalb) in type 2 diabetic patients with and without DMa.

RESEARCH DESIGN AND METHODS—In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TERalb was determined as the initial disappearance of intravenously injected 125I-labeled human serum albumin.

RESULTS—Patients with diabetic maculopathy had higher HbA1c (8.5 ± 1.5 vs. 7.4 ± 1.2%, P < 0.05) and higher total cholesterol (5.8 ± 0.7 vs. 5.2 ± 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 ×/÷ 3.1 vs. 3.9 ×/÷ 1.9 μg/min, P < 0.01). There was no difference in TERalb between the two groups (6.0 ± 1.6 vs. 6.6 ± 1.5%, NS). In the group with DMa, OCT, TERalb, and UAE correlated significantly (OCT versus TERalb: r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TERalb: r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy.

CONCLUSIONS—Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients.
Culturally Competent Diabetes Self-Management Education for Mexican Americans
Authors: Brown Sharon A. , Garcia Alexandra A. , Kouzekanani Kamiar , Hanis Craig L.
Published: March 2007

OBJECTIVE—To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A prospective, randomized, repeated measures study was conducted on the Texas-Mexico border in Starr County. A total of 256 randomly selected individuals with type 2 diabetes between 35 and 70 years of age, diagnosed with type 2 diabetes after 35 years of age, and accompanied by a family member or friend were included. The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses, dietitians, and community workers. The intervention involved 3 months of weekly instructional sessions on nutrition, self-monitoring of blood glucose, exercise, and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes. The approach was culturally competent in terms of language, diet, social emphasis, family participation, and incorporation of cultural health beliefs. Outcomes included indicators of metabolic control (HbA1c and fasting blood glucose), diabetes knowledge, and diabetes-related health beliefs.

RESULTS—Experimental groups showed significantly lower levels of HbA1c and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores. At 6 months, the mean HbA1c of the experimental subjects was 1.4% below the mean of the control group; however, the mean level of the experimental subjects was still high (>10%).

CONCLUSIONS—This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans, particularly for those individuals with HbA1c levels >10%.
Erectile Dysfunction and Quality of Life in Type 2 Diabetic Patients
Authors: De Berardis Giorgia , Franciosi Monica , Belfiglio Maurizio , Di Nardo Barbara , Greenfield Sheldon , Kaplan Sherrie H. , Pellegrini Fabio , Sacco Michele , Tognoni Gianni , Valentini Miriam , Nicolucci Antonio ,   for the Quality of Care and Outcomes in Type 2 Diabetes (QuED) Study Group
Published: March 2007

OBJECTIVE—Within the context of a large, nationwide outcomes research program in type 2 diabetes, we assess the prevalence of self-reported erectile dysfunction and evaluate its impact on quality of life.

RESEARCH DESIGN AND METHODS—The study involved 1,460 patients enrolled by 114 diabetes outpatient clinics and 112 general practitioners. Patients were asked to complete a questionnaire investigating their ability to achieve and maintain an erection. Various aspects of quality of life were also assessed depressive using the following instruments: SF-36 Health Survey, diabetes health distress, psychological adaptation to diabetes, depressive symptoms (CES-D scale), and quality of sexual life.

RESULTS—Overall, 34% of the patients reported frequent erectile problems, 24% reported occasional problems, and 42% reported no erectile problems. After adjusting for patient characteristics, erectile dysfunction was associated with higher levels of diabetes-specific health distress and worse psychological adaptation to diabetes, which were, in turn, related to worse metabolic control. Erectile problems were also associated with a dramatic increase in the prevalence of severe depressive symptoms, lower scores in the mental components of the SF-36, and a less satisfactory sexual life. A total of 63% of the patients reported that their physicians had never investigated their sexual problems.

CONCLUSIONS—Erectile dysfunction is extremely common among type 2 diabetic patients and is associated with poorer quality of life, as measured with generic and diabetes-specific instruments. Despite their relevance, sexual problems are seldom investigated by general practitioners and specialists.
Optimizing Insulin Secretagogue Therapy in Patients With Type 2 Diabetes
Authors: Schmitz Ole , Lund Sten , Andersen Per Heden , Jønler Morten , Pørksen Nils
Published: March 2007

OBJECTIVE—Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals.

RESEARCH DESIGN AND METHODS—The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA1c 7.3%, and BMI 32 kg/m2). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma C-peptide concentrations were measured at baseline and after 4 weeks of treatment.

RESULTS—Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA1c levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA1c levels) than the same total dose of repaglinide divided into morning and evening mealtime doses.

CONCLUSIONS—These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.
Early Increase of Oxidative Stress and Reduced Antioxidant Defenses in Patients With Uncomplicated Type 1 Diabetes
Authors: Marra Giampiero , Cotroneo Patrizia , Pitocco Dario , Manto Andrea , Di Leo Mauro A.S. , Ruotolo Valeria , Caputo Salvatore , Giardina Bruno , Ghirlanda Giovanni , Santini Stefano A.
Published: March 2007

OBJECTIVE—Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women.

RESEARCH DESIGN AND METHODS—We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 ± 3 years.

RESULTS—Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 ± 111.2 vs. 972.5 ± 97.7 μmol/l in men, P < 0.001; 579.8 ± 95.4 vs. 930.1 ± 84.2 in women, P < 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 ± 2.2 vs. 2.0 ± 0.7 μmol/l in men, P < 0.001; 8.1 ± 1.9 vs. 2.2 ± 0.6 in women, P < 0.001), higher total conjugated diene (CD) levels (0.037 ± 0.003 vs. 0.033 ± 0.002 A.U. in men, P < 0.001), lower 246-nm CD levels (0.0032.± 0.0010 vs. 0.0070 ± 0.0012 A.U. in men, P < 0.001; 0.0022 ± 0.0011 vs. 0.0072 ± 0.0014 A.U. in women, P < 0.001), and higher 232-nm CD levels (0.0348 ± 0.0041 vs. 0.0257 ± 0.0022 A.U. in men, P < 0.001; 0.0346 ± 0.0031 vs. 0.0246 ± 0.0074 A.U. in women, P < 0.001). Compared with diabetic men, diabetic women had lower TRAP (P < 0.01), higher ROOH levels (P < 0.01), and lower 246-nm CD levels (P < 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 ± 0.3 vs. 4.3 ± 0.2 mg/dl; P = 0.009) with a significant difference between women and men with type 1 diabetes (2.6 ± 0.3 vs. 3.9 ± 0.3, respectively; P = 0.009).

CONCLUSIONS—Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications.
Basal and Postglucagon C-Peptide Levels in Ethiopians with Diabetes
Authors: Siraj Elias S , Reddy S. Sethu K , Scherbaum Werner A , Abdulkadir Jemal , Hammel Jeffrey P , Faiman Charles
Published: March 2007

OBJECTIVE—To study basal C-peptide (BCP) and postglucagon C-peptide (PGCP) levels in Ethiopians with diabetes.

RESEARCH DESIGN AND METHODS—A total of 56 subjects with type 1 diabetes, 97 subjects with type 2 diabetes, and 50 control subjects were recruited from a hospital in Ethiopia. BCP was determined in all subjects and PGCP in 86 subjects.

RESULTS—Mean (±SEM) BCP, PGCP, and the increment after glucagon in type 1 diabetic subjects (0.14 ±0.04, 0.22 ±0.11, and 0.08 ±0.05 nmol/l, respectively) were lower (P < 0.001) than those in type 2 diabetic subjects (0.66 ±0.04, 1.25 ±0.10, and 0.56 ±0.06 nmol/l, respectively) or control subjects (0.54 ±0.04, 1.52 ±0.26, and 1.11 ±0.24 nmol/l, respectively). The mean BCP level was higher in type 2 diabetic subjects than control subjects (P=0.015), whereas the mean increment was lower (P=0.005). Insulin-treated type 2 diabetic subjects, compared with non-insulin-treated type 2 diabetic subjects, had lower mean BCP (0.55 ±0.08 nmol/l [n=37] vs. 0.73 ±0.04 [n=60], P=0.001), lower PGCP (0.97 ±0.20 nmol/l [n=18] vs. 1.40 ±0.11 [n=35], P=0.010), and a lower C-peptide increment (0.34 ±0.06 [n=18] vs. 0.67 ±0.07 nmol/l [n=35], P=0.003). In both the type 1 and type 2 diabetic groups, those with BCP levels <0.2 nmol/l had lower BMI than those with higher BCP levels (P=0.023 and P < 0.001, respectively).

CONCLUSIONS—Combined with clinical criteria, C-peptide levels are good discriminators between type 1 and type 2 diabetes in Ethiopians and may also be useful in identifying subjects with type 2 diabetes who require insulin therapy. There is a subgroup of type 2 diabetic subjects with features of type 1 diabetes.
The Impact of Cardiovascular Disease on Medical Care Costs in Subjects With and Without Type 2 Diabetes
Authors: Nichols Gregory A. , Brown Jonathan B.
Published: March 2007

OBJECTIVE—We examined whether cardiovascular disease (CVD) affects medical care costs differently in subjects with and without diabetes and explored the impact of CVD on costs across the dimensions of age and diabetes duration.

RESEARCH DESIGN AND METHODS—We compared the prevalence of CVD and medical care costs for subjects with and without CVD in all 16,180 full-year health maintenance organization members in 1999 who had been diagnosed with type 2 diabetes and in control members matched by year of birth and sex. We ascertained diagnoses from the Kaiser Permanente Northwest Region’s electronic ambulatory medical record and from hospital discharge datafiles. Utilization from these and other data systems were multiplied by unit costs.

RESULTS—CVD was 76% more prevalent in subjects with diabetes, but the risk ratios of more severe forms of CVD were even greater. Risk ratios for CVD were greatest in younger subjects. Cost profiles for subjects with both CVD and diabetes differed markedly from those with diabetes but without CVD. In the latter group, costs grew steadily with age, whereas in the former group, costs peaked in the 55- to 64-year age group before declining with age.

CONCLUSIONS—The types of CVD present in diabetic patients are more likely to be more severe and therefore more costly than in similar subjects without diabetes. CVD also disproportionately affects younger diabetic subjects. Finally, when CVD is present in diabetes, more costs occur earlier in life as well as earlier in the course of diabetes.
Plasma F2 Isoprostanes
Authors: Sampson Michael J. , Gopaul Nitin , Davies Isabel R. , Hughes David A. , Carrier Martin J.
Published: March 2007

OBJECTIVES—Acute hyperglycemia in type 2 diabetes increases the generation of plasma 8-epi-prostaglandin F2 (8-epi-PGF2α) isoprostane, a sensitive direct marker of in vivo free radical oxidative damage to membrane phospholipids.

RESEARCH DESIGN AND METHODS—A total of 21 patients with type 2 diabetes underwent an oral 75-g glucose tolerance test. Plasma 8-epi-PGF2α isoprostane concentrations (by gas chromatography [GC]/mass spectrometry [MS]), intralymphocyte reduced-to-oxidized glutathione ratios, and plasma total antioxidant capacity were measured at baseline and 90 min after glucose loading.

RESULTS—Plasma 8-epi-PGF2α isoprostane concentrations rose significantly (P=0. 010) from 0.241± 0.1 to 0.326± 0.17 ng/l after 90 min. Intracellular oxidative balance and plasma antioxidant capacity did not change in either group.

CONCLUSIONS—Plasma concentrations of 8-epi-PGF2α isoprostane increase during acute hyperglycemia in type 2 diabetes, providing direct evidence of free radical–mediated oxidative damage and demonstrating a pathway for an association between acute rather than fasting hyperglycemia and macrovascular risk in type 2 diabetes.
Risk Indicators Predictive for Severe Hypoglycemia During the First Trimester of Type 1 Diabetic Pregnancy
Authors: Evers Inge M. , ter Braak Edith W.M.T. , de Valk Harold W. , van der Schoot Bertine , Janssen Nancy , Visser Gerard H.A.
Published: March 2007

OBJECTIVES—To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma during the first trimester of type 1 diabetic pregnancy and in the 4 months before gestation and to identify risk indicators predicting first trimester SH in a nonselected nationwide cohort of pregnant women with type 1 diabetes.

RESEARCH DESIGN AND METHODS—We conducted a longitudinal cohort survey in 278 pregnant type 1 diabetic women using questionnaires at inclusion and at 17 weeks of gestation, addressing the frequencies of SH (i.e., external help required) and hypoglycemic coma, general characteristics, hypoglycemia awareness, blood glucose symptom threshold, and the Hypoglycemia Fear Survey.

RESULTS—The occurrence of SH (including hypoglycemic coma) rose from 0.9 ±2.4 episodes per 4 months before gestation to 2.6 ±6.3 episodes during the first trimester (P < 0.001), including an increase in episodes of coma from 0.3 ±1.3 to 0.7 ±3.7 (P=0.03). The proportion of women affected by SH rose from 25 to 41% (P < 0.001). First-trimester SH was independently related to a history of SH before gestation (odds ratio [95%CI]: 9.2 [3.9ndash;21.7]), a 10 years’ longer diabetes duration (1.6 [1.0ndash;2.4]), an HbA1c level ≤6.5% (2.5 [1.3ndash;5.0]), and a 0.1 unit/kg higher daily insulin dose (5.4 [1.5ndash;18.9]), adjusted for a decreased symptom threshold.

CONCLUSIONS—In type 1 diabetic pregnancy, the risk of SH is increased already before pregnancy and rises further during the first trimester. A history of SH before gestation, longer duration of diabetes, an HbA1c level ≤6.5%, and a higher total daily insulin dose were risk indicators predictive for SH during the first trimester. Further research should aim to elucidate how the benefits of strict glycemic control balance with the markedly increased risk of SH early in pregnancy.
Carpal Tunnel Syndrome in Patients With Diabetic Polyneuropathy
Authors: Perkins Bruce A. , Olaleye David , Bril Vera
Published: March 2007

OBJECTIVE—Carpal tunnel syndrome (CTS) and diabetic polyneuropathy (DPN) are common conditions in patients with diabetes and therefore frequently occur concomitantly. Diagnosis of CTS in patients with DPN is important, as therapeutic interventions directed toward relief of CTS may be effective irrespective of diffuse neuropathy. The prevalence of clinical CTS and the most efficient electrodiagnostic discriminators of CTS from diffuse neuropathy are uncertain.

RESEARCH DESIGN AND METHODS—A total of 478 subjects, including reference subjects (without diabetes and without neuropathy), nonneuropathic subjects with diabetes, and diabetic subjects with mild, moderate, and severe neuropathy, were evaluated in a cross-sectional design for clinical features of CTS. In the ascertainment of the cohort, a clinical stratification method was used to ensure a broad spectrum of neuropathy severity. All subjects underwent nerve conduction study determinations of median, ulnar, and sural nerve parameters.

RESULTS—The prevalence of clinical CTS was 2% in the reference population, 14% in diabetic subjects without DPN, and 30% in those with DPN. Multiple linear regression analysis revealed that mean electrodiagnostic parameters are not significant predictors of clinical CTS in patients with diabetes. Generally, the parameters worsened with severity of neuropathy, but none reliably distinguished diabetic patients with and without CTS.

CONCLUSIONS—Given the high prevalence of CTS in patients with DPN and that electrodiagnostic criteria cannot distinguish those with clinical CTS, it is recommended that therapeutic decisions for CTS be made independently of electrodiagnostic findings.
Behavioral Science Research in the Prevention of Diabetes
Authors: Fisher Edwin B. , Walker Elizabeth A. , Bostrom Ann , Fischhoff Baruch , Haire-Joshu Debra , Johnson Suzanne Bennett
Published: March 2007

Recent studies show diabetes can be prevented. Growing knowledge of its biological bases opens further prevention opportunities. This article focuses on behavioral science research that may advance these opportunities. An ecological model guides attention to how prevention research may be pursued at the individual, group, or community levels. Three key areas are reviewed: risk communication, screening, and preventive interventions. Research on diabetes risk communication is limited but suggests that many are relatively unaware of risks and may have misconceptions about the disease. Amid policy debates and research regarding the potential benefits and costs of screening, identification of diabetes may itself be risky in terms of psychological and social consequences. The Diabetes Prevention Program and other studies make clear that diabetes can be prevented, both by the combination of weight loss and physical activity and by medications. Research needs to address promoting these methods to individuals as well as to groups and even whole communities. Fundamental as well as applied research should address how risks of diabetes are understood and may be communicated; how to enhance benefits and minimize psychological and other risks of screening; how to promote healthy eating and weight loss, physical activity, and appropriate use of medications to prevent diabetes; and how to reduce socioeconomic and cultural disparities in all these areas.
Effects of Dietary Treatment Alone or Diet With Voglibose or Glyburide on Abdominal Adipose Tissue and Metabolic Abnormalities in Patients With Newly Diagnosed Type 2 Diabetes
Authors: Takami Kazuhisa , Takeda Noriyuki , Nakashima Kazuya , Takami Rieko , Hayashi Makoto , Ozeki Shigehiko , Yamada Akiko , Kokubo Yoshiaki , Sato Mayumi , Kawachi Shin-ichi , Sasaki Akihiko , Yasuda Keigo
Published: March 2007

OBJECTIVE—To examine the effects of diet and diet with voglibose or glyburide on abdominal adiposity and metabolic abnormalities in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 36 Japanese patients with newly diagnosed type 2 diabetes (50.8 ± 8.6 years of age, BMI 24.5 ± 3.5 kg/m2) and 273 normal control subjects were studied. The patients were treated for 3 months with diet alone (30 kcal/kg per day) (n = 15), diet with voglibose (n = 12), or diet with glyburide (n = 9). They underwent 75-g oral glucose tolerance testing, assessment of insulin sensitivity (SI), and acute insulin response (AIR) with intravenous glucose tolerance testing based on the minimal model, and measurement of abdominal visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) by computed tomography before and after treatment.

RESULTS—The diabetic patients had comparable SAT but larger VAT than the control subjects. With a mean weight loss of 2–3 kg, VAT and SAT were decreased similarly in all treatment groups. The VAT-to-SAT ratio was decreased only in the voglibose group. Glycemic control and serum lipid profiles were improved in all groups. Changes in glycemic control after diet were closely correlated with changes in VAT but not with changes in SAT. SI and AIR were unchanged in the diet group but were improved in the voglibose and glyburide groups.

CONCLUSIONS—In Japanese patients with newly diagnosed type 2 diabetes who were relatively lean but had excess VAT, diet with or without voglibose or glyburide effectively reduced VAT. Decrease in VAT was closely associated with improvement of glycemic control with diet. Additional use of voglibose or low-dose glyburide had no detrimental effects on abdominal adiposity and had beneficial effects on SI and AIR.