bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing practice guidelines for diabetes care using problem-based learning. A prospective controlled trial using firm systems.
Authors: Benjamin E M , Schneider M S , Hinchey K T
Published: March 2007

OBJECTIVE: A controlled trial with 15-month follow-up was conducted in two outpatient clinics to study the effects of using the problem-based learning technique to implement a diabetes clinical practice guideline. RESEARCH DESIGN AND METHODS: A total of 144 patients with type 2 diabetes aged 25-65 years in two internal medicine outpatient clinics were enrolled in the study. African-Americans and Hispanics made up > 75% of the patients. Doctors and staff in one of the clinics were trained in the use of a clinical practice guideline based on Staged Diabetes Management. A problem-based learning educational program was instituted to reach consensus on a stepped intensification scheme for glycemic control and to determine the standards of care used in the clinic. HbA1c was obtained at baseline and at 9 and 15 months after enrollment. RESULTS: At 9 months, there was a mean -0.90% within-subject change in HbA1c in the intervention group, with no significant changes in the control group. The 15-month mean within-subject change in HbA1c of -0.62% in the intervention group was also significant. Among intervention patients, those with the poorest glycemic control at baseline realized the greatest benefit in improvement of HbA1c. The intervention group also exhibited significant changes in physician adherence with American Diabetes Association standards of care. CONCLUSIONS: Clinical practice guidelines are an effective way of improving the processes and outcomes of care for patients with diabetes. Problem-based learning is a useful strategy to gain physician support for clinical practice guidelines. More intensive interventions are needed to maintain treatment gains.
Relationship between urinary albumin excretion, body composition, and hyperinsulinemia in normotensive glucose-tolerant adults.
Authors: Nielsen S , Jensen M D
Published: March 2007

OBJECTIVE: Elevated urinary albumin excretion (UAE) has been associated with insulin resistance and is suggested to be elevated in prediabetic individuals. Upper body obesity, especially visceral obesity, predicts insulin resistance and development of type 2 diabetes. We examined whether UAE clusters with obesity-associated insulin resistance traits in healthy glucose-tolerant normotensive subjects. RESEARCH DESIGN AND METHODS: There were 49 volunteers with a wide range of body fat and body fat distribution studied. All had normal blood pressure and glucose tolerance and were maintained on a controlled diet for 2 weeks. UAE was assessed from three overnight urine collections, and body composition was assessed by whole-body dual-energy X-ray absorptiometry scanning and abdominal computed tomography scanning. RESULTS: Fasting insulin and insulin responses to oral glucose were significantly increased in obese subjects, who also tended to have more dyslipidemia, greater blood pressure, and more visceral fat than lean subjects. These differences were more apparent in upper body obese subjects. UAE was normal in obese and upper body obese subjects and not different from that of lean subjects. UAE ranged from 0.3 to 8.3 micrograms/min in lean subjects and from 0.2 to 7.2 micrograms/min in obese subjects. UAE was not significantly correlated with body composition, plasma insulin, glucose, or lipids. CONCLUSIONS: Obese subjects (even upper body obese subjects) with increased visceral and total body fat, high plasma insulin and triglycerides, and low HDL cholesterol concentrations do not have elevated UAE. This suggests that UAE is not closely associated with these characteristics and implies a later onset of abnormal albuminuria in the course of the insulin resistance syndrome.
Continuous subcutaneous insulin infusion. A new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes.
Authors: Boland E A , Grey M , Oesterle A , Fredrickson L , Tamborlane W V
Published: March 2007

OBJECTIVE: Recommendations from the Diabetes Control and Complications Trial (DCCT) indicate that adolescents with type 1 diabetes should be treated with intensive therapy involving multiple daily injections (MDI) of insulin or insulin pump therapy (continuous subcutaneous insulin infusion [CSII] to help obtain better metabolic control and prevent later complications. Interest has thus focused on insulin pump therapy to help adolescents meet this challenge. The purpose of this study was to examine responses to CSII and MDI in a large group of adolescents with established type 1 diabetes during a 12-month period and to determine whether either treatment regimen more favorably affected clinical and psychosocial outcomes. RESEARCH DESIGN AND METHODS: One-third of 75 youths aged 12-20 years who were candidates for intensive therapy chose CSII as their mode of treatment. Patients received intensive treatment and education as described by the DCCT investigators. Psychosocial data (e.g., quality of life, depression, self-efficacy, and coping) were collected at baseline and at 6-month intervals, and clinical data (e.g., HbA1c levels, adverse events) were collected every 4-6 weeks. RESULTS: Although both MDI- and CSII-treated adolescents initially exhibited improved metabolic control, this level of control was more difficult to sustain for 12 months in the MDI group (at 6 months HbA1c = 8.1, at 12 months HbA1c = 8.3), whereas average HbA1c levels in the CSII group continued to decrease during the 12 months of treatment (at 6 months HbA1c = 7.7, at 12 months HbA1c = 7.5). Despite lower HbA1c levels in CSII-versus MDI-treated patients, the rate of severe hypoglycemic events was reduced by almost 50% in the CSII group (P = 0.01). Self-reported questionnaires demonstrated that there was improvement in self-efficacy, depression, and quality of life in both MDI- and CSII-treated patients. Finally, adolescents using CSII found coping with diabetes to be less difficult than adolescents using MDI did. CONCLUSIONS: CSII is an alternative means to lower HbA1c levels and reduce the risk of hypoglycemia without adversely affecting psychosocial outcomes in adolescents with type 1 diabetes.
Rapid changes in the prevalence of obesity and known diabetes in an adult Norwegian population. The Nord-Trøndelag Health Surveys: 1984-1986 and 1995-1997.
Authors: Midthjell K , Krüger O , Holmen J , Tverdal A , Claudi T , Bjørndal A , Magnus P
Published: March 2007

OBJECTIVE: To determine whether changes in mean BMI and the prevalence of obesity in a total adult population during a short (11-year) period were associated with changes in the prevalence of diabetes. RESEARCH DESIGN AND METHODS: This study involved cross-sectional surveys of all inhabitants aged > or = 20 years of the county of Nord-Trøndelag from 1984 to 1986 (n = 85,100) and from 1995 to 1997 (n = 92,434). Attendance rates were 88.1 and 71.3%, respectively, and 90.0% in an additional survey of people aged 13-19 years from 1995 to 1997 (n = 9,593). Main outcome measures were age-specific mean BMI for the diabetic and nondiabetic subgroups and the prevalence of obesity and diabetes. For comparison, mean BMIs from 18 of 19 Norwegian counties for the group aged 40-42 years were examined. RESULTS: Mean BMI increased from 27.2 to 29.0 kg/m2 in the diabetic population and from 25.1 to 26.3 kg/m2 in the nondiabetic population. The BMI distribution curve shifted to the right, but homogeneity was also reduced. A comparison with other Norwegian counties indicated that this increase occurred during the last 6 years between the surveys. The prevalence of obesity (BMI > or = 30 kg/m2) increased from 7.5 to 14% in nondiabetic men and from 13 to 18% in nondiabetic women. The increase was particularly great in men aged < 60 years and in women aged < 50 years. The overall prevalence of known diabetes increased between the two surveys (from 2.9 to 3.2%) but only in men. The largest increase was observed in the corresponding younger sex and age-groups. CONCLUSIONS: A substantial increase in mean BMI and the prevalence of obesity occurred in the younger age-groups at the same time as an increase in the prevalence of diabetes. A greater increase in diabetes prevalence in this ethnically stable Western European population may follow if effective primary preventive strategies are not undertaken.
Type 2 diabetes and acute myocardial infarction. Angiographic findings and results of an invasive therapeutic approach in type 2 diabetic versus nondiabetic patients.
Authors: Waldecker B , Waas W , Haberbosch W , Voss R , Steen-Müller M K , Hiddessen A , Bretzel R , Tillmanns H
Published: March 2007

OBJECTIVE: Mortality in diabetic patients with acute myocardial infarction (MI) is high. The significance of the pretreatment coronary status in type 2 diabetic patients with acute MI, as well as the effect of mechanical revascularization using percutaneous transluminal coronary angioplasty (PTCA), has not been established. RESEARCH DESIGN AND METHODS: All patients with type 2 diabetes and acute MI (n = 54) were prospectively enrolled into a study of immediate coronary angiography to guide PTCA of the occluded infarct vessel. Hospital and long-term course were assessed and compared with an unselected control group of nondiabetic patients (n = 358) who were enrolled in the same study. RESULTS: Angiography showed that sites of occlusion and acute coronary flow were similar in both groups. Multivessel disease and shock were more common in type 2 diabetic versus nondiabetic patients: 69 vs. 51% and 21 vs. 10% (P < 0.02), respectively. Direct PTCA was successful in > 90% in both groups. Mortality after 30 days was 13% in type 2 diabetic patients versus 5% in patients without diabetes (P < 0.04). Left ventricular (LV) ejection fraction before discharge was lower in diabetic patients (48 +/- 17 vs. 55 +/- 15%, P < 0.05). Mortality 1 year after discharge was 11 vs. 4% in diabetic versus nondiabetic patients (P < 0.02). Multivariate analysis identified type 2 diabetes as an independent risk factor for acute, but not for late, mortality. CONCLUSIONS: Direct PTCA is safe and effective in type 2 diabetic patients with acute MI. Mortality after 30 days in unselected diabetic patients is < 15% with this approach. Advanced disease and shock contribute to an increased mortality in type 2 diabetic patients with acute MI versus nondiabetic patients.
Correlation between the intima-media thickness of the carotid artery and aortic pulse-wave velocity in patients with type 2 diabetes. Vessel wall properties in type 2 diabetes.
Authors: Taniwaki H , Kawagishi T , Emoto M , Shoji T , Kanda H , Maekawa K , Nishizawa Y , Morii H
Published: March 2007

OBJECTIVE: The aim of this study was to assess the relationship between atherotic (structural) and sclerotic (functional) changes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Aortic distensibility and carotid intimal-media thickness (IMT) were evaluated using carotid-femoral aortic pulse-wave velocity (a-PWV) and high-resolution B-mode ultrasonography in 271 patients with type 2 diabetes and 285 age-matched control subjects. RESULTS: a-PWV and carotid IMT were significantly higher in the patients than in the control subjects in all age-groups (P < 0.0001, respectively). The carotid IMT and a-PWV were significantly correlated with age in both the patients with type 2 diabetes and control subjects. There was a significant positive relationship between the carotid IMT and a-PWV in both the patients (r = 0.482, P < 0.0001) and control subjects (r = 0.424, P < 0.0001). The slope of the regression line for the carotid IMT to the a-PWV was significantly steeper in the diabetic patients than in the control subjects (P < 0.05). Multiple regression analysis in all subjects showed that age, diabetic state, and cigarette smoking were independently common risk factors for the increase in carotid IMT and a-PWV. In the diabetic patients, the independent risk factors associated with the carotid IMT were age, hyperlipidemia, and duration of diabetes (R2 = 0.232, P < 0.0001), while those associated with a-PWV were age and duration of diabetes (R2 = 0.334, P < 0.0001). CONCLUSIONS: The results indicated that diabetic patients showed more advanced changes in atherosis than that in sclerosis as compared with age- and sex-matched control subjects. Such atherotic changes in diabetic patients may be associated with hyperlipidemia.
Chronic cigarette smoking is associated with increased plasma circulating intercellular adhesion molecule 1 levels in young type 1 diabetic patients.
Authors: Zoppini G , Targher G , Cacciatori V , Guerriero A , Muggeo M
Published: March 2007

OBJECTIVE: The purposes of this study were to compare plasma concentrations of circulating intercellular adhesion molecule 1 (cICAM-1), a marker of endothelial dysfunction, in nondiabetic subjects and type 1 diabetic patients and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma cICAM-1 levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma cICAM-1 concentrations were measured in 54 young type 1 diabetic patients without clinical macroangiopathy and in 20 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Type 1 diabetic patients had significantly higher plasma levels of cICAM-1 than control subjects (280.4 +/- 59 vs. 224 +/- 53.6 ng/ml, respectively) (P < 0.001). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, blood pressure, glycemic control, diabetes duration, and chronic complications of diabetes that were super-imposable on their nonsmoking counterparts. Nevertheless, plasma cICAM-1 levels were markedly elevated in type 1 diabetic smokers (321.4 +/- 64.2 vs. 257.3 +/- 41.5 ng/ml, respectively) (P < 0.001) in a dose-dependent fashion (P < 0.001 by analysis of variance when subjects were categorized by number of cigarettes smoked per day). CONCLUSIONS: Chronic cigarette smoking has a deleterious effect on plasma cICAM-1 levels in young type 1 diabetic patients, which further supports the clinical importance of discouraging the initiation of smoking and promoting its cessation in people with type 1 diabetes.
Sex hormone-binding globulin levels in middle-aged premenopausal women. Associations with visceral obesity and metabolic profile.
Authors: Tchernof A , Toth M J , Poehlman E T
Published: March 2007

OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.
Smoking and diabetes.
Authors: Haire-Joshu D , Glasgow R E , Tibbs T L
Published: March 2007

The objective of this review is to summarize the literature on diabetes and smoking related to epidemiological risks, efficacy and cost-effectiveness of different cessation approaches, and implications for clinical practice. Over 200 studies were reviewed, with special emphasis placed on publications within the past 10 years. Intervention studies that included patients with diabetes but did not report results separately by disease are included. Diabetes-specific studies are highlighted. There are consistent results from both cross-sectional and prospective studies showing enhanced risk for micro- and macrovascular disease, as well as premature mortality from the combination of smoking and diabetes. The general cessation literature is extensive, generally well-designed, and encouraging regarding the impact of cost-effective practical office-based interventions. In particular, system-based approaches that make smoking a routine part of office contacts and provide multiple prompts, advice, assistance, and follow-up support are effective. Although there is minimal information on the effectiveness of cessation interventions specifically for people with diabetes, there is no reason to assume that cessation intervention would be more or less effective in this population. There is a clear need to increase the frequency of smoking cessation advice and counseling for patients with diabetes given the strong and consistent data on smoking prevalence; combined risks of smoking and diabetes for morbidity, mortality, and several complications; and the proven efficacy and cost-effectiveness of cessation strategies.
Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.
Authors: Komulainen J , Kulmala P , Savola K , Lounamaa R , Ilonen J , Reijonen H , Knip M , Akerblom H K
Published: March 2007

OBJECTIVE: To study the characteristics of type 1 diabetes in very young children. RESEARCH DESIGN AND METHODS: Clinical outcome, islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies against GAD (GADA), IA-2 antibodies (IA-2A), and HLA-DQB1-defined genetic risk were analyzed in 35 children diagnosed with type 1 diabetes before 2 years of age and compared with those in 146 children who were diagnosed between 2.0 and 4.9 years of age and with those in 620 children diagnosed between 5.0 and 14.9 years of age. RESULTS: The youngest age-group had severer metabolic decompensation at clinical onset, and their serum C-peptide levels, compared with those of older children, were lower at the time of diagnosis and during the first 2 years after the diagnosis. The levels of ICA and IAA were highest in children < 2 years of age, but there were no differences in GADA levels among the three age-groups. The youngest age-group had the lowest IA-2A levels. The HLA DQB1*02/*0302 genotype associated with strong genetic susceptibility was more frequent in children diagnosed < 5 years of age, whereas the proportion of children carrying a genotype, which includes protective alleles, was higher among those diagnosed at > or = 5 years of age. CONCLUSIONS: The clinical presentation of type 1 diabetes at a very young age is associated with severe metabolic decompensation, poorly preserved residual beta-cell function, strong humoral autoimmunity against islet cells and insulin, and strong HLA-defined disease susceptibility.
Body mass index, diabetes, and C-reactive protein among U.S. adults.
Authors: Ford E S
Published: March 2007

OBJECTIVE: The author examined the relationship between C-reactive protein and BMI and diabetes status among 16,573 participants aged > or = 20 years of the Third National Health and Nutrition Examination Survey (1988-1994). RESEARCH DESIGN AND METHODS: The study had a cross-sectional design. RESULTS: Geometric mean concentrations of C-reactive protein were lowest among individuals with a BMI < 18.5 kg/m2 and increased with increasing BMI categories. Restricting the analysis to participants without various medical conditions did not change the relation. After adjusting for age, sex, race or ethnicity, and education, using logistic regression analysis, odds ratios for an elevated C-reactive protein concentration (> or = 85th percentile of the sex-specific C-reactive protein concentration distribution) among participants with a BMI of 25 to < 30, 30 to < 35, 35 to < 40, and > or = 40 kg/m2 were 1.51 (95% CI 1.23-1.86), 3.19 (2.60-3.91), 6.11 (4.67-7.98), and 9.30 (6.43-13.46), respectively, compared with participants with a BMI < 25 kg/m2. C-reactive protein concentrations were lowest among those individuals without diabetes or with impaired fasting glucose and highest among those with newly or previously diagnosed diabetes. Compared with participants with a normal fasting glucose, participants with impaired fasting glucose, newly diagnosed diabetes, and previously diagnosed diabetes had 0.99 (0.72-1.37), 1.84 (1.25-2.71), and 1.59 (1.25-2.01) odds of having an elevated C-reactive protein concentration after adjustment for age, sex, race or ethnicity, education, and BMI. CONCLUSIONS: These results confirm cross-sectional findings from previous studies that show elevated C-reactive protein concentrations among individuals who are obese or have diabetes. The implications of these findings, however, remain unclear.
Exogenous estrogen exposures and changes in diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.
Authors: Klein B E , Klein R , Moss S E
Published: March 2007

OBJECTIVE: To investigate whether the use of exogenous estrogen is associated with changes in the severity of diabetic retinopathy and the incidence of macular edema. RESEARCH DESIGN AND METHODS: The study design involved observation of two well-defined cohorts of women with diabetes. One group was diagnosed with diabetes at < 30 years of age and used insulin (younger-onset group), and the other group was diagnosed at > or = 30 years of age with no criteria regarding therapy (older-onset group). Subjects received standard examinations, medical interviews, and retinal photography in 1980-1982. Specific questions about exogenous hormone exposure were added to the study questionnaire at the first follow-up examination 4 years after the baseline examination. Change in the severity of retinopathy 6 and 10 years after the 4-year follow-up examination were examined regarding the use of oral contraceptives at the first follow-up examination in the younger-onset group and at 6 years after the first follow-up examination regarding hormone replacement therapy in the older-onset group. RESULTS: Changes in the severity of retinopathy and incidence of macular edema were unrelated to either type of estrogen exposure in univariable and multivariable analyses. CONCLUSIONS: These data are compatible with the hypothesis that the medications used by our population do not affect the severity of diabetic retinopathy or macular edema.
Diabetes management in a health maintenance organization. Efficacy of care management using cluster visits.
Authors: Sadur C N , Moline N , Costa M , Michalik D , Mendlowitz D , Roller S , Watson R , Swain B E , Selby J V , Javorski W C
Published: March 2007

OBJECTIVE: To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS: This study involved a randomized controlled trial among patients of Kaiser Permanente's Pleasanton, CA, center who were aged 16-75 years and had either poor glycemic control (HbA1c > 8.5%) or no HbA1c test performed during the previous year. Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator, a psychologist, a nutritionist, and a pharmacist in cluster visit settings of 10-18 patients/month for 6 months. Outcomes included change (from baseline) in HbA1c levels; self-reported changes in self-care practices, self-efficacy, and satisfaction; and utilization of inpatient and outpatient health care. RESULTS: After the intervention, HbA1c levels declined by 1.3% in the intervention subjects versus 0.2% in the control subjects (P < 0.0001). Several self-care practices and several measures of self-efficacy improved significantly in the intervention group. Satisfaction with the program was high. Both hospital (P = 0.04) and outpatient (P < 0.01) utilization were significantly lower for intervention subjects after the program. CONCLUSIONS: A 6-month cluster visit group model of care for adults with diabetes improved glycemic control, self-efficacy, and patient satisfaction and resulted in a reduction in health care utilization after the program.
Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia.
Authors: Gabriely I , Wozniak R , Mevorach M , Kaplan J , Aharon Y , Shamoon H
Published: March 2007

OBJECTIVE: To analyze a transcutaneous near-infrared spectroscopy system as a technique for in vivo noninvasive blood glucose monitoring during euglycemia and hypoglycemia. RESEARCH DESIGN AND METHODS: Ten nondiabetic subjects and two patients with type 1 diabetes were examined in a total of 27 studies. In each study, the subject's plasma glucose was lowered to a hypoglycemia level (approximately 55 mg/dl) followed by recovery to a glycemic level of approximately 115 mg/dl using an intravenous infusion of insulin and 20% dextrose. Plasma glucose levels were determined at 5-min intervals by standard glucose oxidase method and simultaneously by a near-infrared spectroscopic system. The plasma glucose measured by the standard method was used to create a calibration model that could predict glucose levels from the near-infrared spectral data. The two data sets were correlated during the decline and recovery in plasma glucose, within 10 mg/dl plasma glucose ranges, and were examined using the Clarke Error Grid Analysis. RESULTS: Two sets of 1,704 plasma glucose determinations were examined. The near-infrared predictions during the fall and recovery in plasma glucose were highly correlated (r = 0.96 and 0.95, respectively). When analyzed during 10 mg/dl plasma glucose segments, the mean absolute difference between the near-infrared spectroscopy method and the chemometric reference ranged from 3.3 to 4.4 mg/dl in the nondiabetic subjects and from 2.6 to 3.8 mg/dl in the patients with type 1 diabetes. Using the Error Grid Analysis, 97.7% of all the near-infrared predictions were assigned to the A-zone. CONCLUSIONS: Our findings suggest that the near-infrared spectroscopy method can accurately predict plasma glucose levels during euglycemia and hypoglycemia in humans.
Performance of a predictive model to identify undiagnosed diabetes in a health care setting.
Authors: Baan C A , Ruige J B , Stolk R P , Witteman J C , Dekker J M , Heine R J , Feskens E J
Published: March 2007

OBJECTIVE: To develop a predictive model to identify individuals with an increased risk for undiagnosed diabetes, allowing for the availability of information within the health care system. RESEARCH DESIGN AND METHODS: A sample of participants from the Rotterdam Study (n = 1,016), aged 55-75 years, not known to have diabetes completed a questionnaire on diabetes-related symptoms and risk factors and underwent a glucose tolerance test. Predictive models were developed using stepwise logistic regression analyses with the absence or presence of newly diagnosed diabetes as the dependent variable and various items with a plausible connection to diabetes as the independent variables. The models were evaluated in another Dutch population-based study, the Hoorn Study (n = 2,364), in which the participants were aged 50-74 years. Performances of the predictive models were compared by using receiver-operator characteristics (ROC) curves. RESULTS: We developed three predictive models (PMs), PM1 contained information routinely collected by the general practitioner, while PM2 also contained variables obtainable by additional questions. The third predictive model, PM3, included variables that had to be obtained from a physical examination. These latter variables did not have additive predictive value, resulting in a PM3 similar to PM2. The area under the ROC curve was higher for PM2 than for PM1, but the 95% Cls overlapped (0.74 [0.70-0.78] and 0.68 [0.64-0.72], respectively). CONCLUSIONS: Using only information normally present in the files of a general practitioner, a predictive model was developed that performed similarly to one supplemented by information obtained from additional questions. The simplicity of PM1 makes it easy to implement in the current health care setting.
Mortality and hormone-related exposures in women with diabetes.
Authors: Klein B E , Klein R , Moss S E
Published: March 2007

OBJECTIVE: Hormone-related events and exposures are related to mortality and especially to cardiovascular disease in women. We evaluated whether such exposures influenced risk in a well-defined group of women with diabetes. RESEARCH DESIGN AND METHODS: Women with younger- and older-onset diabetes who were identified during a population-based study were queried about number of pregnancies, age at menarche, use of oral contraceptives, use of estrogen replacement therapy, and menopausal status at examinations in 1984-1986. Analyses are limited to women aged > or = 18 years (n = 398 and 542 in those with younger- and older-onset diabetes, respectively). Cohort mortality was monitored carefully, and causes of death were abstracted from death certificates. RESULTS: There were 58 deaths in the first group and 338 deaths in the second group since the 1984-1986 examination. The number of pregnancies was significantly associated with all-cause mortality (hazard ratio, 0.96 [95% CI 0.92-1.00]) in older-onset women only. CONCLUSIONS: These data suggest and are compatible with the notion that the hormone exposures examined are unrelated to cardiovascular mortality in women with diabetes, with the exception of a minimal effect of the number of pregnancies in older-onset women. Whether there is a difference in these exposure-outcome relationships between women with diabetes and those without diabetes is uncertain and requires further investigation.
Capillary whole blood measurement of islet autoantibodies.
Authors: Bazzigaluppi E , Bonfanti R , Bingley P J , Bosi E , Bonifacio E
Published: March 2007

OBJECTIVE: Islet cell antibody (ICA) measurements in serum are used for large-scale screening to identify subjects who are at high risk of developing type 1 diabetes. The aim of this study was to adapt measurements to capillary whole blood samples to facilitate and reduce screening costs. RESEARCH DESIGN AND METHODS: GAD65, IA-2, and combined GAD65/IA-2 antibody tests were performed on patients with type 1 diabetes, first-degree relatives of patients, and control subjects, and results from serum, plasma, whole venous blood, and capillary whole blood lysates were compared. Measurements obtained in serum and eluates from dried capillary blood spots from 36 ICA+ first-degree relatives were also compared. RESULTS: GAD65, IA-2, and combined GAD65/IA-2 antibody levels were completely concordant with measurements obtained from serum, plasma, whole venous blood, and capillary whole blood lysates. Antibody levels obtained in eluates from dried capillary blood spots were lower than corresponding serum samples, and weak antibodies were not detected. CONCLUSIONS: Initial screening for diabetes risk can be performed using one drop of capillary whole blood without further processing to separate serum. This method should be considered as a way to simplify and reduce costs of screening programs.
Effect of oxidized lipids in the diet on oxidized lipid levels in postprandial serum chylomicrons of diabetic patients.
Authors: Staprans I , Hardman D A , Pan X M , Feingold K R
Published: March 2007

OBJECTIVE: To determine whether humans with type 2 diabetes have increased levels of oxidized fatty acids in their serum chylomicron fraction after the ingestion of dietary oxidized fatty acids. RESEARCH DESIGN AND METHODS: The study was performed on 31 male type 2 diabetic patients and 24 age-matched control subjects. Among the diabetic patients, 22 had poor glycemic control, defined as HbA1 > 10% (normal value < 7.7%). Nine patients had good glycemic control (HbA1 < or = 10). Heated corn oil containing low or high levels of oxidized fatty acids was used as a test meal. At 2.5 h after the test meal, 50-ml blood samples were obtained from all subjects, and the chylomicron fraction (Sf > 1,000) was isolated. The degree of oxidation in chylomicrons was determined by measuring conjugated dienes. For determining the postprandial levels of triglycerides and of oxidized lipids in serum chylomicrons over an extended time period, blood samples were obtained at 0, 2.5, 5.0, and 7.5 h for isolation of chylomicrons and determination of fatty acid oxidation. RESULTS: We found that at 2.5 h after the consumption of the test meal containing either a low or high oxidized fatty acid content, conjugated dienes in serum chylomicrons in diabetic subjects in poor glycemic control were increased compared with those in control subjects. Diabetic patients in good glycemic control had similar levels of oxidized lipid in their chylomicrons when compared with control subjects. Additionally, in diabetic patients in poor glycemic control, the levels of oxidized lipids in chylomicrons remained elevated for an extended post-prandial period. CONCLUSIONS: In diabetic subjects with poor glycemic control, dietary oxidized lipids induce an exaggerated and sustained increase in the levels of oxidized lipids in chylomicrons when compared with either control subjects or diabetic patients with good glycemic control. These increased postprandial levels of potentially atherogenic oxidized lipids may contribute to the accelerated atherosclerosis associated with diabetes.
Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes.
Authors: Littorin B , Sundkvist G , Hagopian W , Landin-Olsson M , Lernmark A , Ostman J , Arnqvist H J , Blohmé G , Bolinder J , Eriksson J W , Lithner F , Scherstén B , Wibell L
Published: March 2007

OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes. RESEARCH DESIGN AND METHODS: The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay. RESULTS: Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone. CONCLUSIONS: Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.
Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes.
Authors: Okada E , Oida K , Tada H , Asazuma K , Eguchi K , Tohda G , Kosaka S , Takahashi S , Miyamori I
Published: March 2007

OBJECTIVE: An increased plasma homocysteine level is an important risk factor for vascular disease, including coronary atherosclerosis, in the general population. However, the role of hyperhomocysteinemia in the development of coronary artery disease (CAD) in patients with type 2 diabetes is unknown. Therefore, we have endeavored to determine the relationship between plasma homocysteine levels and the presence of coronary arteriosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study group consisted of 145 Japanese patients (95 men and 50 women) who underwent routine coronary angiography to assess chest pain or suspected CAD. Plasma total homocysteine level, lipid level, and parameters of fibrinolytic activity were measured. All patients were identified as diabetic or nondiabetic by the new American Diabetes Association (ADA) criteria. The diagnoses of all patients studied were confirmed by coronary angiography. The severity of coronary artery stenosis was quantified using CAD scoring on the basis of prior reports, and subjects were graded as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel based on the number of stenotic coronary arteries. Patients were classified into two groups: those with stenotic vessels and those without stenotic vessels. RESULTS: The plasma homocysteine level was significantly higher in patients with than in patients without stenotic vessels (13.8 +/- 3.9 vs. 11.7 +/- 3.9 mumol/l, respectively; P = 0.0009). The number of stenotic coronary arteries, which was used to grade each case as nonstenotic, stenotic single-vessel, stenotic two-vessel, or stenotic three-vessel, was related only to the total homocysteine level in the diabetic (diabetes mellitus [DM]) group, but it was associated with lipoprotein(a) in the nondiabetic (non-diabetes mellitus [non-DM]) group. Spearman's rank correlation test demonstrated that the plasma homocysteine level was strongly correlated with CAD score, both in the entire study group and in the DM group (P = 0.003 for the entire group and P = 0.011 for the DM group). Hyperhomocysteinemia, which was defined as total homocysteine level > 14.0 mumol/l, was seen in 57 (39.3%) of the patients. The CAD score was highest in diabetic patients with hyperhomocysteinemia (P < 0.05). CONCLUSIONS: There seems to be a clear relationship between hyperhomocysteinemia and an increased risk of coronary arteriosclerosis in Japanese patients with type 2 diabetes.
T-cell insulitis found in anti-GAD65+ diabetes with residual beta-cell function. A case report.
Authors: Shimada A , Imazu Y , Morinaga S , Funae O , Kasuga A , Atsumi Y , Matsuoka K
Published: March 2007

CASE HISTORY: We recently encountered a 65-year-old anti-GAD+ diabetic woman with residual beta-cell function who was proved to have T-cell insulitis. The proportion of CD4+ and CD8+ cells varied among individual islets, although CD4+ cells tended to be the predominant T-cell type in the islets examined. All of the islets examined still contained insulin, suggesting that beta-cell mass may have been preserved. DISCUSSION: It is well known that lymphocytic infiltration of pancreatic islets, a condition referred to as "insulitis," is seen in acute-onset type 1 diabetes at autopsy and in biopsy specimens. However, there have been no proven cases of insulitis in type 1 diabetes with residual beta-cell function. We believe that this is the first type 1 diabetic patient with residual beta-cell function who was proven to have T-cell insulitis. This novel evidence will contribute to the proper classification and treatment of diabetes and to a better understanding of the pathophysiology of type 1 diabetes.
Amputation prevention by vascular surgery and podiatry collaboration in high-risk diabetic and nondiabetic patients. The Operation Desert Foot experience.
Authors: Van Gils C C , Wheeler L A , Mellstrom M , Brinton E A , Mason S , Wheeler C G
Published: March 2007

OBJECTIVE: To describe a unique multidisciplinary outpatient intervention for patients at high risk for lower-extremity amputation. RESEARCH DESIGN AND METHODS: Patients with foot ulcers and considered to be high risk for lower-extremity amputation were referred to the High Risk Foot Clinic of Operation Desert Foot at the Carl T. Hayden Veterans Affairs' Medical Center in Phoenix, Arizona, where patients received simultaneous vascular surgery and podiatric triage and treatment. Some 124 patients, consisting of 90 diabetic patients and 34 nondiabetic patients, were initially seen between 1 October 1991 and 30 September 1992 and followed for subsequent rate of lower-extremity amputation. RESULTS: In a mean follow-up period of 55 months (range 3-77), only 18 of 124 patients (15%) required amputation at the level of the thigh or leg. Of the 18 amputees, 17 (94%) had type 2 diabetes. The rate of avoiding limb loss was 86.5% after 3 years and 83% after 5 years or more. Furthermore, of the 15 amputees surviving longer than 2 months, only one (7%) had to undergo amputation of the contralateral limb over the following 12-65 months (mean 35 months). Compared with nondiabetic patients, patients with diabetes had a 7.68 odds ratio for amputation (95% CI 5.63-9.74) (P < 0.01). CONCLUSIONS: A specialized clinic for prevention of lower-extremity amputation is described. Initial and contralateral amputation rates appear to be far lower in this population than in previously published reports for similar populations. Relative to patients without diabetes, patients with diabetes were more than seven times as likely to have a lower-extremity amputation. These data suggest that aggressive collaboration of vascular surgery and podiatry can be effective in preventing lower-extremity amputation in the high-risk population.
Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis.
Authors: Margolis D J , Kantor J , Berlin J A
Published: March 2007

OBJECTIVE: The aim of the study was to determine the percentage of individuals with neuropathic diabetic foot ulcers receiving good wound care who heal within a defined period of time. RESEARCH DESIGN AND METHODS: We conducted a systematic review of the control groups of clinical trials that evaluated a treatment for diabetic neuropathic foot ulcers. The meta-analytic techniques used include an estimation of the weighted mean percentage healed by end point, an evaluation of the homogeneity of trials, and an estimate of the 95% CI of the grouped data. Grouped-data univariate and multivariate logistic regression was conducted to assess the impact of mean age, ulcer size, and duration on the percentage of ulcers healed at end point. RESULTS: We found a total of 10 control groups meeting our criteria. Six control groups used 20 weeks as the end point for healing or nonhealing. For the six control arms with a 20-week end point, we found a weighted mean healing rate of 30.9% (95% CI 26.6-35.1). A similar analysis for the four 12-week arms found a mean healing rate of 24.2% (19.5-28.8). We failed to detect any statistically significant heterogeneity for either the 20-week or the 12-week trials. CONCLUSIONS: After 20 weeks of good wound care, approximately 31% of diabetic neuropathic ulcers heal. Similarly, after 12 weeks of good care, approximately 24% of neuropathic ulcers attain complete healing. Further patient-level analyses are necessary to definitively determine the associations of age, wound size, and wound duration with likelihood of healing.
Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study.
Authors: Duncan B B , Schmidt M I , Offenbacher S , Wu K K , Savage P J , Heiss G
Published: March 2007

OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.
Abnormality in urinary protein excretion in Japanese men with impaired glucose tolerance.
Authors: Fujita H , Narita T , Ito S
Published: March 2007

OBJECTIVE: To examine whether subjects with impaired glucose tolerance (IGT) for more than 2 years have any abnormality in the kidney. RESEARCH DESIGN AND METHODS: We measured urinary excretion rate and clearance of various plasma proteins with different molecular radii and different isoelectric points in 22 Japanese men with IGT (IGT group) and 37 age-matched healthy control subjects (control group). RESULTS: Clearance of ceruloplasmin (molecular radius approximately 45 A; isoelectric point 4.4), IgG4 (molecular radius 55 A; isoelectric point 5.4), and IgG (molecular radius 55 A; isoelectric point 7.4) was significantly higher in the IGT group than in the control group, whereas there were no significant differences in urinary excretion rate of albumin (molecular radius 36 A; isoelectric points 4.8-5.2) and clearance of alpha 2-macroglobulin (molecular radius 88 A; isoelectric point 5.4) between the two groups. CONCLUSIONS: In the present study, we found that clearance of neutral-charged IgG, negatively charged IgG4, and ceruloplasmin with molecular radii of approximately 45-55 A was selectively increased in IGT subjects. This finding does not seem to be explained by impairment of charge and pore-size selectivity in the glomerulus. Therefore, considering the present result together with our recent finding that enhanced glomerular filtration rate (GFR) after acute protein loading in healthy subjects induced a selective increase in clearance of IgG, IgG4, and ceruloplasmin, we suggest that increased intraglomerular hydraulic pressure, although enhanced GFR was not demonstrated, may be at work in these mildly hyperglycemic subjects.