bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical Variation in Risk HLA-DQB1 Genotypes for Type 1 Diabetes and Signs of β-Cell Autoimmunity in a High-Incidence Country
Authors: Kukko Marika , Virtanen Suvi M. , Toivonen Anna , Simell Satu , Korhonen Sari , Ilonen Jorma , Simel Olli , Knip Mikael
Published: March 2007

OBJECTIVE—To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of β-cell autoimmunity among three geographical regions in Finland.

RESEARCH DESIGN AND METHODS—The series comprised 4,642 children with increased HLA-DQB1–defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of β-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A).

RESULTS—The high- and moderate-risk genotypes were unevenly distributed among the three areas (P < 0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P < 0.001) or Tampere regions (27.2%; P < 0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36–2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28–0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0.51–1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16–0.82).

CONCLUSIONS—These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1–defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.
Adequacy of Glycemic, Lipid, and Blood Pressure Management for Patients With Diabetes in a Managed Care Setting
Authors: Beaton Sarah J. , Nag Soma S. , Gunter Margaret J. , Gleeson Jeremy M. , Sajjan Shiva S. , Alexander Charles M.
Published: March 2007

OBJECTIVE—We conducted a retrospective study to evaluate the adequacy of glycemic, lipid, and blood pressure (BP) management for diabetic patients in a managed care organization (MCO).

RESEARCH DESIGN AND METHODS—Patients aged ≥18 years with diabetes (n = 7,114) were retrospectively identified over a 2-year period from the MCO’s administrative database based on the Health Plan Employer Data and Information Set 2000 selection criteria using pharmacy, laboratory, and encounter data. Analyses examined demographics and percentages of patients tested and meeting American Diabetes Association goals for HbA1c, lipids, and BP, both overall and for those receiving medication treatment versus no treatment.

RESULTS—Testing rates for A1C, LDL cholesterol, and BP were 77, 54, and 95%, respectively. The percentage of patients tested who were at goal were 37% for A1C, 23% for LDL cholesterol, and 41% for systolic BP. Of the patients in our sample, 72% were treated for glycemic control, 64% were treated for BP control, and only 28% were treated for lipid control. Of the patients who received medication treatment, less than one-third were at goal for A1C (29%) and LDL cholesterol (32%), whereas 40% were at goal for systolic BP.

CONCLUSIONS—We found that although a large percentage of diabetic patients were tested for A1C, LDL cholesterol, and systolic BP, a much smaller percentage had reached their respective goals. More aggressive glycemic, lipid, and BP management appears to be needed to improve care for these patients.
Heart Failure Prevalence, Incidence, and Mortality in the Elderly With Diabetes
Authors: Bertoni Alain G. , Hundley W. Gregory , Massing Mark W. , Bonds Denise E. , Burke Gregory L. , Goff David C.
Published: March 2007

OBJECTIVE—The goal of this study was to determine heart failure prevalence and incidence rates, subsequent mortality, and risk factors for heart failure among older populations in Medicare with diabetes.

RESEARCH DESIGN AND METHODS—We used a national 5% sample of Medicare claims from 1994 to 1999 to perform a population-based, nonconcurrent cohort study in 151,738 beneficiaries with diabetes who were age ≥65 years, not in managed care, and were alive on 1 January 1995. Prevalent heart failure was defined as a diagnosis of heart failure in 1994; incident heart failure was defined as a new diagnosis in 1995–1999 among those without prevalent heart failure. Mortality was assessed through 31 December 1999.

RESULTS—Heart failure was prevalent in 22.3% in 1994. Among individuals without heart failure in 1994, the heart failure incidence rate was 12.6 per 100 person-years (95% CI 12.5–12.7 per 100 person-years). Incidence was similar by sex and race and increased significantly with age and diabetes-related comorbidities. The adjusted hazard of incident heart failure increased for individuals with the following: metabolic complications of diabetes (a proxy for poor control and/or severity) (hazards ratio 1.23, 95% CI 1.18–1.29), ischemic heart disease (1.74, 1.70–1.79), nephropathy (1.55, 1.45–1.67), and peripheral vascular disease (1.35, 1.31–1.39). Over 60 months, incident heart failure among older adults with diabetes was associated with high mortality—32.7 per 100 person-years compared with 3.7 per 100 person-years among those with diabetes who remained heart failure free.

CONCLUSIONS—These data demonstrate alarmingly high prevalence, incidence, and mortality for heart failure in individuals with diabetes. Prevention of heart failure should be a research and clinical priority.
Elevated Plasma Asymmetric Dimethylarginine as a Marker of Cardiovascular Morbidity in Early Diabetic Nephropathy in Type 1 Diabetes
Authors: Tarnow Lise , Hovind Peter , Teerlink Tom , Stehouwer Coen D.A. , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Increased plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been associated with endothelial dysfunction, insulin resistance, and atherosclerosis in nondiabetic populations. In end-stage renal failure, circulating ADMA is elevated and a strong predictor of cardiovascular outcome. This study investigated the relation between ADMA and diabetic micro- and macrovascular complications in a large cohort of type 1 diabetic patients with and without early diabetic nephropathy.

RESEARCH DESIGN AND METHODS—ADMA concentrations in plasma were determined by a high-performance liquid chromatography method in 408 type 1 diabetic patients with overt diabetic nephropathy (252 men; mean age 42.7 years [SD 11.0], mean duration of diabetes 28 years [SD 9], median serum creatinine level 102 μmol/l [range 52–684]). A group of 192 patients with longstanding type 1 diabetes and persistent normoalbuminuria served as control subjects (118 men; mean age 42.6 years [SD 10.2], mean duration of diabetes 27 years [SD 9]).

RESULTS—In patients with diabetic nephropathy, mean ± SD plasma ADMA concentration was elevated 0.46 ± 0.08 vs. 0.40 ± 0.08 μmol/l in normoalbuminuric patients (P < 0.001). An increase in plasma ADMA of 0.1 μmol/l increased the odds ratio of nephropathy to 2.77 (95% CI 1.89–4.05) (P < 0.001). Circulating ADMA increased in nephropathy patients with declining kidney function, as indicated by elevated values in the lower quartiles of glomerular filtration rate (<76 ml · min–1 · 1.73 m–2) (P < 0.001 ANOVA). Mean ADMA levels were similar in patients with or without diabetic retinopathy (P > 0.2). However, in 44 patients with nephropathy and history of myocardial infarction and/or stroke, ADMA was significantly elevated at 0.48 ± 0.08 μmol/l compared with 0.46 ± 0.08 μmol/l in patients without major cardiovascular events (P = 0.05).

CONCLUSIONS—Elevated circulating ADMA may contribute to the excess cardiovascular morbidity and mortality in early diabetic nephropathy.
Insulin Resistance and Cardiovascular Disease Risk Factors in Children of Parents With the Insulin Resistance (Metabolic) Syndrome
Authors: Pankow James S. , Jacobs David R. , Steinberger Julia , Moran Antoinette , Sinaiko Alan R.
Published: March 2007

OBJECTIVE—To evaluate whether children of parents with the insulin resistance syndrome (IRS) themselves have greater insulin resistance and unfavorable patterns of cardiovascular disease (CVD) risk factors.

RESEARCH DESIGN AND METHODS—This cross-sectional study included 220 white and 36 black children aged 11–15 years identified through a school-based blood pressure screening program, along with 378 of their parents. Measures of insulin resistance (glucose disposal per minute per kilogram of lean body mass in a euglycemic-hyperinsulinemic clamp [Mlbm] and fasting insulin), adiposity, and other CVD risk factors were compared in children with and without a parental history of IRS, defined according to the National Cholesterol Education Program Adult Treatment Panel III consensus definition.

RESULTS—Compared with children in whom neither parent had IRS, children who had at least one parent with the syndrome had statistically significantly lower mean Mlbm (12.1 vs. 13.6 mg · kg–1 · min–1; P = 0.04) and higher fasting insulin (geometric means 99 vs. 76 pmol/l; P = 0.01) after adjustment for sex, race, age, and Tanner stage. Mean BMI, waist circumference, waist-to-hip ratio, triceps and subscapular skinfolds, and percentage of body fat were also significantly higher in children of an affected parent, but there were no significant differences in lipid or blood pressure levels between the two groups.

CONCLUSIONS—Insulin resistance and obesity may be the earliest manifestations of IRS in children with a parental history of the syndrome.
High Incidence of Childhood Type 1 Diabetes in the Avalon Peninsula, Newfoundland, Canada
Authors: Newhook Leigh A. , Curtis Joseph , Hagerty Donna , Grant Marie , Paterson Andrew D. , Crummel Cheryl , Bridger Tracey , Parfrey Patrick
Published: March 2007

OBJECTIVE—The aim of this study was to determine the incidence of type 1 diabetes among children aged 0–14 years in the Avalon Peninsula in the Canadian Province of Newfoundland.

RESEARCH DESIGN AND METHODS—This was a prospective cohort study of the incidence of childhood type 1 diabetes in children aged 0–14 years who were diagnosed with type 1 diabetes from 1987 to 2002 on the Avalon Peninsula. Identified case subjects during this time period were ascertained from several sources and verified using the capture-recapture technique. Data were obtained from the only pediatric diabetes treatment center for children living on the Avalon Peninsula.

RESULTS—Over the study period, 294 children aged 0–14 years from the Avalon Peninsula were diagnosed with type 1 diabetes. The incidence of type 1 diabetes in this population over the period 1987–2002 inclusive was 35.93 with a 95% CI of 31.82–40.03. The incidence over this period increased linearly at the rate of 1.25 per 100,000 individuals per year.

CONCLUSIONS—The Avalon Peninsula of Newfoundland has one of the highest incidences of type 1 diabetes reported worldwide. The incidence increased over the 16-year study period.
Behavioral and Clinical Factors Associated With Depression Among Individuals With Diabetes
Authors: Katon Wayne , Von Korff Michael , Ciechanowski Paul , Russo Joan , Lin Elizabeth , Simon Gregory , Ludman Evette , Walker Edward , Bush Terry , Young Bessie
Published: March 2007

OBJECTIVE—The goal of this study was to determine the behavioral and clinical characteristics of diabetes that are associated with depression after controlling for potentially confounding variables.

RESEARCH DESIGN AND METHODS—A population-based mail survey was sent to patients with diabetes from nine primary care clinics of a health maintenance organization. The Patient Health Questionnaire was used to diagnose depression, and automated diagnostic, pharmacy, and laboratory data were used to measure diabetes treatment intensity, HbA1c levels, and diabetes complications.

RESULTS—Independent factors that were associated with a significantly higher likelihood of meeting criteria for major depression included younger age, female sex, less education, being unmarried, BMI ≥30 kg/m2, smoking, higher nondiabetic medical comorbidity, higher numbers of diabetes complications in men, treatment with insulin, and higher HbA1c levels in patients <65 years of age. Independent factors associated with a significantly higher likelihood of meeting criteria for minor depression included younger age, less education, non-Caucasian status, BMI ≥30 kg/m2, smoking, longer duration of diabetes, and a higher number of complications in older (≥65 years) patients.

CONCLUSIONS—Smoking and obesity were associated with a higher likelihood of meeting criteria for major and minor depression. Diabetes complications and elevated HbA1c were associated with major depression among demographic subgroups: complications among men and HbA1c among individuals <65 years of age. Older patients with a higher number of complications had an increased likelihood of minor depression.
Low-Intensity Laser Therapy for Painful Symptoms of Diabetic Sensorimotor Polyneuropathy
Authors: Zinman Lorne H. , Ngo Mylan , Ng Eduardo T. , Nwe Khin T. , Gogov Sven , Bril Vera
Published: March 2007

OBJECTIVE—Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP.

RESEARCH DESIGN AND METHODS—We conducted a randomized, double-masked, sham therapy-controlled clinical trial in 50 patients with painful DSP diagnosed with the Toronto Clinical Neuropathy Score. All patients received sham therapy over a 2-week baseline period and were then randomized to receive biweekly sessions of either sham or LILT for 4 weeks. The primary efficacy parameter was the difference in the weekly mean pain scores on a visual analog scale (VAS).

RESULTS—The patients had similar baseline characteristics for pain intensity, HbA1c, and duration of DSP. Both groups noted a decrease in weekly mean pain scores during sham treatment. After the 4-week intervention, the LILT group had an additional reduction in weekly mean pain scores of −1.0 ± 0.4 compared with −0.0 ± 0.4 for the sham group (P = 0.07). LILT had no effect on the Toronto Clinical Neuropathy Score, nerve conduction studies, sympathetic skin response, or quantitative sensory testing.

CONCLUSIONS—Although an encouraging trend was observed with LILT, the study results do not provide sufficient evidence to recommend this treatment for painful symptoms of DSP.
Type 2 Diabetes and Intravenous Thrombolysis Outcome in the Setting of ST Elevation Myocardial Infarction
Authors: Zairis Michael N. , Lyras Anastassios G. , Makrygiannis Stamatis S. , Psarogianni Paraskevi K. , Adamopoulou Evdokia N. , Handanis Stelios M. , Papantonakos Apostolos , Argyrakis Spyros K. , Prekates Athanasios A. , Foussas Stefanos G.
Published: March 2007

OBJECTIVE—There are conflicting results regarding the impact of type 2 diabetes on intravenous thrombolysis effectiveness during ST elevation myocardial infarction (STEMI). The present study, using a continuous 12-lead electrocardiogram, examined the possible association of type 2 diabetes with both acute intravenous thrombolysis effectiveness and long-term prognosis in this setting.

RESEARCH DESIGN AND METHODS—The study included 726 consecutive subjects (214 type 2 diabetic subjects) with STEMI who received intravenous thrombolysis in the first 6 h from index pain and were followed up for 3.5 years.

RESULTS—Type 2 diabetic subjects had significantly lower incidence of sustained ≥50% ST recovery than nondiabetic subjects (P = 0.03). Additionally, the former required a significantly greater time interval through the achievement of this criterion than the latter (P < 0.001). In both type 2 diabetic (P < 0.001) and nondiabetic subjects (P < 0.001), those who had not attained ≥50% ST recovery were at significantly higher risk of cardiac death than subjects who had reached this criterion. The subjects who attained the above electrocardiographic criterion in ≥60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in <60 min (P = 0.02). However, this association was true only for type 2 diabetic subjects (P = 0.01) and not for nondiabetic subjects (P = 0.9).

CONCLUSIONS—The present study suggests that type 2 diabetes is a strong predictor of acute intravenous thrombolysis failure during STEMI. This finding may significantly contribute to the worse prognosis for type 2 diabetic subjects compared with nondiabetic ones in this setting.
Critical Evaluation of Adult Treatment Panel III Criteria in Identifying Insulin Resistance With Dyslipidemia
Authors: Liao Youlian , Kwon Soonho , Shaughnessy Sara , Wallace Penny , Hutto Amy , Jenkins Alicia J. , Klein Richard L. , Garvey W. Timothy
Published: March 2007

OBJECTIVE—The goal of this study was to evaluate the efficacy of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) in identifying insulin resistance.

RESEARCH DESIGN AND METHODS—This study included 74 nondiabetic Caucasians who were evaluated for insulin resistance and risk factors associated with the metabolic syndrome. Glucose disposal rate (GDR) was measured by hyperinsulinemic-euglycemic clamp and was used to quantify insulin resistance. Sensitivity and specificity of ATP III criteria in detecting insulin resistance were calculated for various cutoffs of GDR.

RESULTS—Insulin resistance was associated with increased waist circumference, fasting glucose, blood pressure, triglycerides, and decreased levels of HDL cholesterol. Only 12.2% of study subjects met ATP III criteria for metabolic syndrome, and ATP III criteria exhibited low sensitivity for detecting insulin resistance. Although high in specificities (>90%), the sensitivities of ATP III criteria ranged only between 20 and 50% when insulin resistance was defined as various GDR cutoff values below 10 to 12 mg · kg−1 · min−1. The larger number of subjects who were insulin resistant but did not meet ATP III criteria were found to have an adverse cardiovascular disease risk profile, including higher BMI, waist circumference, fasting glucose, triglycerides, and an unfavorable lipoprotein subclass profile determined by nuclear magnetic resonance compared with insulin-sensitive individuals (i.e., increased large VLDL, increased small LDL, and decreased large HDL particle concentrations).

CONCLUSIONS—ATP III criteria have low sensitivity for identifying insulin resistance with dyslipidemia in nondiabetic individuals who are at increased risk for cardiovascular disease and diabetes. More sensitive criteria should be developed for clinical assessment of metabolic and cardiovascular disease risk relevant to the metabolic syndrome.
Testosterone and Sex Hormone–Binding Globulin Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men
Authors: Laaksonen David E. , Niskanen Leo , Punnonen Kari , Nyyssönen Kristiina , Tuomainen Tomi-Pekka , Valkonen Veli-Pekka , Salonen Riitta , Salonen Jukka T.
Published: March 2007

OBJECTIVE—In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone–binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men.

RESEARCH DESIGN AND METHODS—Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome.

RESULTS—After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5–3.4; 1.7, 1.2–2.5; and 2.8, 1.9–4.1, respectively) and diabetes (2.3, 1.3–4.1; 1.7, 0.9–3.0; and 4.3, 2.4–7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone.

CONCLUSIONS—Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.
Reduction in Diabetes-Related Lower-Extremity Amputations in the Netherlands: 1991–2000
Authors: van Houtum William H. , Rauwerda Jan A. , Ruwaard Dirk , Schaper Nicolaas C. , Bakker Karel
Published: March 2007

OBJECTIVE—Lower-extremity amputation is a common complication among patients with diabetes throughout the world. However, few data exist on the actual impact of the recent moves to improve the management of diabetic foot ulcers to reduce the incidence of lower-extremity amputations. The aim was to determine the incidence of lower-extremity amputations among diabetic patients from 1991 to 2000 in the Netherlands.

RESEARCH DESIGN AND METHODS—A secondary database containing information regarding all hospital admissions in which a lower-extremity amputation occurred for the years 1991–2000 was obtained from the Dutch National Medical Register. Because a patient-unique identifier was included, multiple amputations and hospitalizations for a single individual could be identified. Furthermore, age- and sex-specific diabetes prevalence rates were calculated using a 3-year average for every year, calculating the total diabetic population in the Netherlands at risk for every year.

RESULTS—In 1991, a total of 1,687 patients with diabetes had been admitted 1,865 times for 2,409 amputations. In 2000, a total of 1,673 patients with diabetes were admitted 1,932 times for 2,448 amputations. The overall incidence rates of the number of patients who underwent lower-extremity amputation decreased over the years from 55.0 to 36.3 per 10,000 patients with diabetes (P < 0.05). Both in men (71.8 vs. 46.1, P < 0.05) and women (45.0 vs. 28.0, P < 0.05) with diabetes, a significant decrease could be observed. Mean duration of hospitalization decreased from 45.0 days (SD 44.4) in 1991 to 36.2 days (SD 38.4) in 2000; decreases were observed for both men and women.

CONCLUSIONS—Over the years observed in this study, the incidence rates of diabetes-related lower-extremity amputation in the Netherlands was found to decrease in both men (36%) and women (38%) with diabetes. Furthermore, the duration of hospitalization decreased over time.
Treatment of Diabetic Gastroparesis by High-Frequency Gastric Electrical Stimulation
Authors: Lin Zhiyue , Forster Jameson , Sarosiek Irene , McCallum Richard W.
Published: March 2007

OBJECTIVE—To investigate the long-term efficacy of high-frequency gastric electrical stimulation (GES) for treating diabetic gastroparesis.

RESEARCH DESIGN AND METHODS—This is a retrospective review of 48 adult diabetic patients with refractory gastroparesis who had a GES system implanted surgically and had follow-up evaluations at 6 and 12 months. The outcome measures were total symptom score (TSS), derived from six upper gastrointestinal (GI) symptom subscores; health-related quality of life (HQOL), including physical composite score (PCS) and mental composite score (MCS) assessed by SF-36 questionnaire, radionuclide gastric emptying test, nutritional status, HbA1c, and adverse events.

RESULTS—In comparison with baseline, TSS, all six upper GI symptom subscores, PCS, and MCS were significantly improved at 6 months, with the improvement sustained at 12 months. Of 13 patients receiving nutritional support at baseline by tube feeding, only 5 required supplemental enteral feeding at 12 months, and none of the 9 on total parenteral nutrition continued this support. The mean number of hospitalization days during the year after GES was significantly reduced by 52 days compared with the prior year. HbA1c levels were significantly reduced at 12 months. Gastric emptying was only minimally and not significantly faster. Because of infections at the pulse generator pocket site, four patients had their GES systems removed 3–17 months postsurgery.

CONCLUSIONS—In diabetic patients with refractory gastroparesis, high-frequency GES by a permanently implanted system significantly improved upper GI symptoms, HQOL, nutritional status, glucose control, and hospitalizations with an acceptably low complication rate.
Sural Nerve Sorbitol in Patients With Diabetic Sensorimotor Polyneuropathy
Authors: Bril Vera , Ono Yoshiyuki , Buchanan Robert A.
Published: March 2007

OBJECTIVE—Nerve sorbitol levels have been measured in sural nerve biopsy samples from patients with diabetic sensorimotor polyneuropathy in several studies using different methods and measurement units. In this study, we compared the results of sorbitol assays to determine the required sensitivity of analytical methods for nerve sorbitol measurements.

RESEARCH DESIGN AND METHODS—We performed a literature search using PaperChase for reports of nerve sorbitol in diabetic patients and selected those with nerve conduction studies to delineate the severity of nerve damage.

RESULTS—In patients who had undergone a nerve conduction study, the standardized nerve sorbitol levels were 0.034–0.300 nmol/mg wet nerve.

CONCLUSIONS—Our results showed the level of sensitivity required in laboratory methodology to perform this assay in the target population and aid in the planning of clinical research trials of aldose reductase inhibitor agents.
Increasing Incidence of Diabetes After Gestational Diabetes
Authors: Lauenborg Jeannet , Hansen Torben , Jensen Dorte Møller , Vestergaard Henrik , Mølsted-Pedersen Lars , Hornnes Peter , Locht Henning , Pedersen Oluf , Damm Peter
Published: March 2007

OBJECTIVE—To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes.

RESEARCH DESIGN AND METHODS—Women with diet-treated GDM during 1978–1985 (old cohort, n = 241, also followed up around 1990) or 1987–1996 (new cohort, n = 512) were examined in 2000–2002. Women were classified by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies. Historical data from index-pregnancy and anthropometrical measurements were collected.

RESULTS—A total of 481 (63.9%) women were examined (median 9.8 years [interquartile range 6.4–17.2]) after index pregnancy. Diabetes and impaired glucose tolerance (IGT)/impaired fasting glucose were present in 40.0 and 27.0% of women, respectively. In the new cohort, 40.9% had diabetes compared with 18.3% in the old cohort at the 1990 follow-up (P < 0.0005). Prepregnancy BMI was significantly higher in the new compared with the old cohort (26.0 [22.5–30.8] vs. 22.9 kg/m2 [20.2–28.0], P < 0.0005). Among others, new-cohort membership, prepregnancy overweight (BMI ≥25 kg/m2), and IGT postpartum were identified as independent predictors of diabetes by multiple logistic regression analyses.

CONCLUSIONS—The incidence of diabetes among Danish women with previous diet-treated GDM was very high and had more than doubled over a 10-year period. This seems to be due to a substantial increase in BMI in women with GDM.
High-Fiber Cereal Reduces Postprandial Insulin Responses in Hyperinsulinemic but not Normoinsulinemic Subjects
Authors: Wolever Thomas M.S. , Campbell Janice E. , Geleva Daniela , Anderson G. Harvey
Published: March 2007

OBJECTIVE—The objective of this study was to compare the plasma glucose and insulin responses elicited by two ready-to-eat breakfast cereals (one being high and the other being low in cereal fiber) and to see if the differences in response depended on subjects’ fasting plasma insulin.

RESEARCH DESIGN AND METHODS—Nondiabetic men (n = 77) were studied on two occasions after 10- to 14-h overnight fasts. They consumed 25 g of available carbohydrate from high- or low-fiber breakfast cereals in random order with blood taken at intervals for 2 h. Data from the 42 men with high fasting plasma insulin (FPI) on screening (>40 pmol/l) were compared with those from the 35 men with normal FPI (≤40 pmol/l).

RESULTS—Hyperinsulinemic men had significantly higher waist circumference and BMI, lower HDL cholesterol, and a trend toward higher triglycerides (P = 0.07) than control subjects. In all 77 subjects, the incremental area under the glucose response curve (AUC) after high-fiber cereal was 11.8 ± 5.5% (P = 0.036) less than after low-fiber cereal with the reductions being equivalent in the hyperinsulinemic (12.6 ± 8.3%) and control (10.9 ± 9.1%) groups. However, insulin peak rise was reduced by the high-fiber cereal only in hyperinsulinemic men (351 ± 29 vs. 485 ± 55 pmol/l) but not in control subjects (211 ± 20 vs. 220 ± 20 pmol/l; cereal × group interaction P = 0.044). Insulin AUC after the high-fiber cereal, expressed as a percentage of that after low-fiber cereal, was negatively related to FPI (P = 0.009) but not to age, BMI, or waist circumference.

CONCLUSIONS—The high-fiber cereal reduced glucose responses to the same extent in normal and hyperinsulinemic men, but reduced insulin responses only in hyperinsulinemic subjects.
Ragaglitazar Improves Glycemic Control and Lipid Profile in Type 2 Diabetic Subjects
Authors: Saad Mohammed F. , Greco Susan , Osei Kwame , Lewin Andrew J. , Edwards Christopher , Nunez Margarita , Reinhardt Rickey R. ,   for the Ragaglitazar Dose-Ranging Study Group
Published: March 2007

OBJECTIVE—Ragaglitazar is a novel insulin sensitizer with dual peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-α stimulating activities that improve plasma glucose and lipid profiles. The aim of the present dose-ranging study was to assess the efficacy and safety of ragaglitazar in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—This study included 177 hypertriglyceridemic type 2 diabetic subjects who participated in a 12-week, double-blind, parallel, randomized, placebo-controlled dose-ranging study (open pioglitazone arm). Subjects received ragaglitazar (0.1, 1, 4, or 10 mg), placebo, or pioglitazone (45 mg). Efficacy parameters included fasting plasma levels of triglycerides and glucose (FPG) along with other lipid levels, A1C, and insulin.

RESULTS—Ragaglitazar in doses of 1, 4, and 10 mg resulted in a significant decrease from baseline as compared with placebo in FPG (−48, −74, −77 mg/dl) and triglycerides (−40, −62, −51%), free fatty acids (−36, −54, −62%), apolipoprotein B (−13, −29, −25%), LDL cholesterol (−14 and −19% for 4- and 10-mg groups), and total cholesterol (−16 and −15% for 4 and 10 mg) and a significant increase in HDL cholesterol (20 and 31% for 1- and 4-mg groups, respectively). Changes in triglycerides and FPG for pioglitazone treatment were similar to 1 mg ragaglitazar. Mean A1C values of the 1-, 4-, and 10-mg ragaglitazar and pioglitazone groups were significantly reduced compared with placebo (−0.5, −1.3, −1.1, and −0.3%, respectively). Common adverse events were edema, weight increase, leukopenia, and anemia.

CONCLUSIONS—Ragaglitazar provided glycemic control that was comparable with that of pioglitazone and, compared with placebo, provided significant improvement in the lipid profile.
Vascular Effects of Improving Metabolic Control With Metformin or Rosiglitazone in Type 2 Diabetes
Authors: Natali Andrea , Baldeweg Stephanie , Toschi Elena , Capaldo Brunella , Barbaro Daniele , Gastaldelli Amalia , Yudkin John S. , Ferrannini Ele
Published: March 2007

OBJECTIVE—The aim of this study was to test whether vascular reactivity is modified by improving metabolic control and peripheral insulin resistance in type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a randomized, double-blind design, we assigned 74 type 2 diabetic patients to rosiglitazone (8 mg/day), metformin (1,500 mg/day), or placebo treatment for 16 weeks and measured insulin sensitivity (euglycemic insulin clamp), ambulatory blood pressure, and forearm blood flow response to 1) intra-arterial acetylcholine (ACh), 2) intra-arterial nitroprusside, 3) the clamp, and 4) blockade of nitric oxide (NO) synthase.

RESULTS—Compared with 25 nondiabetic subjects, patients had reduced insulin sensitivity (30 ± 1 vs. 41 ± 3 μmol · min−1 · kg fat-free mass−1; P < 0.001) and reduced maximal response to ACh (586 ± 42 vs. 883 ± 81%; P < 0.001). Relative to placebo, 16 weeks of rosiglitazone and metformin similarly reduced fasting glucose (−2.3 ± 0.5 and −2.3 ± 0.5 mmol/l) and HbA1c (−1.2 ± 0.3 and −1.6 ± 0.3%). Insulin sensitivity increased with rosiglitazone (+6 ± 3 μmol · min−1 · kg fat-free mass−1; P < 0.01) but not with metformin or placebo. Ambulatory diastolic blood pressure fell consistently (−2 ± 1 mmHg; P < 0.05) only in the rosiglitazone group. Nitroprusside dose response, clamp-induced vasodilatation, and NO blockade were not affected by either treatment. In contrast, the slope of the ACh dose response improved with rosiglitazone (+40% versus baseline, P < 0.05, +70% versus placebo, P < 0.005) but did not change with either metformin or placebo. This improvement in endothelium-dependent vasodilatation was accompanied by decrements in circulating levels of free fatty acids and tumor necrosis factor-α.

CONCLUSIONS—At equivalent glycemic control, rosiglitazone, but not metformin, improves endothelium dependent vasodilatation and insulin sensitivity in type 2 diabetes.
The Arg972 Variant in Insulin Receptor Substrate-1 Is Associated With an Increased Risk of Secondary Failure to Sulfonylurea in Patients With Type 2 Diabetes
Authors: Sesti Giorgio , Marini Maria Alelaide , Cardellini Marina , Sciacqua Angela , Frontoni Simona , Andreozzi Francesco , Irace Concetta , Lauro Davide , Gnasso Agostino , Federici Massimo , Perticone Francesco , Lauro Renato
Published: March 2007

OBJECTIVE—The aim of this study was to investigate whether diabetic patients carrying the Arg972 insulin receptor substrate-1 (IRS-1) variant are at increased risk for secondary failure to sulfonylurea.

RESEARCH DESIGN AND METHODS—A total of 477 unrelated Caucasian type 2 diabetic patients were recruited according to the following criteria: onset of diabetes after age 35 years, absence of ketonuria at diagnosis, and anti-GAD− antibody. Type 2 diabetes was diagnosed according to the American Diabetes Association criteria. Patients with secondary sulfonylurea failure were defined as those requiring insulin due to uncontrolled hyperglycemia (fasting plasma glucose >300 mg/dl) despite sulfonylurea-metformin combined therapy, appropriate diet, and absence of any conditions causing hyperglycemia.

RESULTS—Of the total patients, 53 (11.1%) were heterozygous for the Arg972 IRS-1 variant, 1 (0.2%) was homozygous, and the remainder (88.7%) were homozygous for the wild-type allele. The genotype frequency of the Arg972 IRS-1 variant was 8.7% among diabetic patients well controlled with oral therapy and 16.7% among patients with secondary failure to sulfonylurea (odds ratio 2.1 [95% CI 1.18–3.70], P = 0.01). Adjustment for age, sex, BMI, metabolic control, age at diagnosis, duration of diabetes, and Pro12Ala polymorphism of peroxisome proliferator–activated receptor-γ2 gene in a logistic regression analysis with secondary failure to sulfonylurea as a dependent variable did not change this association (2.0 [1.38–3.86], P = 0.038).

CONCLUSIONS—These data demonstrate that the Arg972 IRS-1 variant is associated with increased risk for secondary failure to sulfonylurea, thus representing a potential example of pharmacogenetics in type 2 diabetes.
Estimation of Resting Energy Expenditure Considering Effects of Race and Diabetes Status
Authors: Martin Kelley , Wallace Penny , Rust Philip F. , Garvey W. Timothy
Published: March 2007

OBJECTIVE—To evaluate the impact of diabetes status and race, in addition to other covariables, on the estimation of resting energy expenditure (REE).

RESEARCH DESIGN AND METHODS—Demographic, anthropometric, and clinical parameters were assessed in 166 adults of varying weights. Subjects were categorized by race (white versus black) and into three subgroups based on glucose tolerance (normoglycemia, impaired glucose tolerance, and type 2 diabetes), termed the diabetes status index (DSI). REE was measured by indirect calorimetry. A multiple regression model was established for optimal prediction of REE based on covariables.

RESULTS—An average decrease in REE of 135 kcal/day independent of all other variables was observed in blacks (P < 0.001). DSI was found to be a significant covariable (P = 0.002) in predicting REE, which was observed to be higher in diabetic women. Therefore, race and DSI entered the multiple regression equation to predict REE as significant independent variables, together with lean body mass (LBM) and age × BMI interaction (P < 0.001). Overall, REE prediction resulted in an R2 of 0.79 and a root mean square error of 136 kcal/day. These values indicate that the resultant equations could offer advantages over other key published prediction equations. The equations are: 1) REEfemale = 803.8 + 0.3505 × age × (BMI − 34.524) − 135.0 × race + 15.866 × LBM + 50.90 × DSI; and 2) REEmale = 909.4 + 0.3505 × age × (BMI –34.524) –135.0 × race + 15.866 × LBM –9.10 × DSI. The predictive value of the equations did not diminish substantially when fat-free mass estimated by skinfold calipers was substituted for dual-energy X-ray absorptiometry scan measurements of LBM.

CONCLUSIONS—Race and diabetes status are important when predicting REE, coupled with LBM, age, BMI, and sex. Race and DSI have not been considered in equations commonly used to predict REE. Their inclusion could improve individualization of dietary prescriptions for type 2 diabetic subjects and heterogeneous populations.
Effect of Alendronate on Bone Mineral Density and Biochemical Markers of Bone Turnover in Type 2 Diabetic Women
Authors: Keegan Theresa H.M. , Schwartz Ann V. , Bauer Douglas C. , Sellmeyer Deborah E. , Kelsey Jennifer L.
Published: March 2007

OBJECTIVE—Alendronate sodium (ALN) increases bone mineral density (BMD) in heterogeneous populations of postmenopausal women, but its effect is unknown in women with type 2 diabetes. The objective of this project was to compare changes in BMD during 3 years of ALN treatment versus placebo in diabetic women.

RESEARCH DESIGN AND METHODS—We used data from the Fracture Intervention Trial, a randomized blinded placebo-controlled trial conducted at 11 centers in which 6,458 women aged 54–81 years with a femoral neck BMD of ≤0.68 g/cm2 were randomly assigned to either placebo or 5 mg/day ALN for 2 years, followed by 10 mg/day for the remainder of the trial. BMD was measured by dual-energy X-ray absorptiometry. Type 2 diabetes (n = 297) was defined by self-report, use of insulin or other hypoglycemic agents, or a random nonfasting glucose value ≥200 mg/dl.

RESULTS—In diabetic women, 3 years of ALN treatment was associated with increased BMD at all sites studied, including 6.6% at the lumbar spine and 2.4% at the hip, whereas women in the placebo group experienced a decrease in BMD at all sites except the lumbar spine. The safety/tolerability of ALN was similar to placebo, except for abdominal pain, which was more likely in the ALN group.

CONCLUSIONS—ALN increased BMD relative to placebo in older women with type 2 diabetes and was generally well tolerated as a treatment for osteoporosis. Increases in BMD with ALN therapy compared with placebo were similar between women with and without diabetes.
Tuberculosis and Diabetes in Southern Mexico
Authors: Ponce-de-Leon Alfredo , Garcia-Garcia Ma. de Lourdes , Garcia-Sancho Ma. Cecilia , Gomez-Perez Francisco J. , Valdespino-Gomez Jose Luis , Olaiz-Fernandez Gustavo , Rojas Rosalba , Ferreyra-Reyes Leticia , Cano-Arellano Bulmaro , Bobadilla Miriam , Small Peter M. , Sifuentes-Osornio Jose
Published: March 2007

OBJECTIVE—To determine the impact of diabetes on the rates of tuberculosis in a region where both diseases are prevalent.

RESEARCH DESIGN AND METHODS—Data from a population-based cohort of patients with pulmonary tuberculosis undergoing clinical and mycobacteriologic evaluation (isolation, identification, drug-susceptibility testing, and IS6110-based genotyping and spoligotyping) were linked to the 2000 National Health Survey (ENSA2000), a national probabilistic, polystage, stratified, cluster household survey of the civilian, noninstitutionalized population of Mexico.

RESULTS—From March 1995 to March 2003, 581 patients with Mycobacterium tuberculosis culture and fingerprint were diagnosed, 29.6% of whom had been diagnosed previously with diabetes by a physician. According to the ENSA2000, the estimated prevalence of diabetes in the study area was 5.3% (95% CI 4.1–6.5). The estimated rates of tuberculosis for the study area were greater for patients with diabetes than for nondiabetic individuals (209.5 vs. 30.7 per 100,000 person-years, P < 0.0001).

CONCLUSIONS—In this setting, the rate of tuberculosis was increased 6.8-fold (95% CI 5.7–8.2, P < 0.0001) in patients with diabetes due to increases in both reactivated and recently transmitted infection. Comorbidity with diabetes may increase tuberculosis rates as much as coinfection with human immunodeficiency virus (HIV), with important implications for the allocation of health care resources.
Health-Related Social Disengagement in Elderly Diabetic Patients
Authors: Kuo Yong-Fang , Raji Mukaila A. , Peek M. Kristen , Goodwin James S.
Published: March 2007

OBJECTIVE—We examined the relationship between health-related social disengagements, as opposed to disengagements related to financial and other non–health-related factors, and subsequent risk of disability and death among initially nondisabled elderly diabetic patients enrolled in Medicare Managed Care plans.

RESEARCH DESIGN AND METHODS—We used data from the Medicare Health Outcomes Survey (HOS) Cohort 1 Baseline (1998) and Cohort 1 Follow-Up (2000). Through mail and telephone surveys, trained interviewers collected information on sociodemographic variables, physical and mental health functioning (using Medical Outcomes Study Short Form-36 [SF-36]), activities of daily living (ADL), and medical conditions. This study reported on diabetic subjects aged ≥65 years with no ADL disability at baseline (n = 8,949). Health-related social disengagement (degree to which physical health or emotional problems interfere with social activities) was derived from the social functioning subscale of SF-36 (range 0–100; higher scores depicting better social functioning).

RESULTS—For each 10-point increase in social functioning score at baseline, older diabetic subjects in our study experienced an 18% less chance of any ADL disability (odds ratio [OR] 0.82, 95% CI 0.75–0.89; P < 0.001) and a 12% less chance of death (0.88, 0.78–1.00; P = 0.043) over a 2-year period, adjusting for demographic factors, comorbidities, depression, and general health (assessed by the SF-36).

CONCLUSIONS—Among initially nondisabled older diabetic subjects, health-related interferences with social activities at baseline may be early warning signs of subsequent ADL disability and premature death, independent of other measures of health status.
Sensory Function and Albumin Excretion According to Diagnostic Criteria for Diabetes
Authors: Sosenko Jay M. , Kato Martha , Goldberg Ronald B.
Published: March 2007

OBJECTIVE—The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes.

RESEARCH DESIGN AND METHODS—Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples.

RESULTS—Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values ≥126 mg/dl, whereas 25 had 2-h glucose values ≥200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels ≥126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values ≥200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels ≥126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl.

CONCLUSIONS—Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels ≥126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels ≥126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.
Lowering the Criterion for Impaired Fasting Glucose
Authors: Tai E. Shyong , Goh Su Yen , Lee Jeannette J.M. , Wong Moh-Sim , Heng Derrick , Hughes Kenneth , Chew Suok Kai , Cutter Jeffery , Chew William , Gu Ken , Chia Kee Seng , Tan Chee Eng
Published: March 2007

OBJECTIVE—To determine the effect of lowering the fasting plasma glucose (FPG) criterion for impaired fasting glucose (IFG) on the prevalence of IFG, the risks of diabetes, and cardiovascular disease (CVD) associated with IFG.

RESEARCH DESIGN AND METHODS—Three studies were used: 1) the 1998 National Health Survey (NHS98), a randomly selected cross-sectional sample of 4,723 subjects; 2) the Singapore Impaired Glucose Tolerance (IGT) Follow-up Study, a cohort study comprising 295 IGT and 292 normal glucose tolerance subjects (frequency matched for age, sex, and ethnic group) followed up from 1992 to 2000; and 3) the Singapore CVD Cohort Study, comprising 5,920 subjects from three cross-sectional studies in whom the first ischemic heart disease (IHD) event was identified through linkage to registry databases. Risk of diabetes (Singapore IGT Follow-up study) was estimated using logistic regression adjusted for age, sex, and ethnicity. Risk of IHD (Singapore CVD cohort) was estimated using stratified (by study, from which data were derived) Cox’s proportional hazards models adjusted for age, sex, and ethnicity.

RESULTS—Lowering the criterion for diagnosing IFG to 5.6 mmol/l increased the prevalence of IFG from 9.5 to 32.3% in the NHS98. The lower cutoff identified more subjects at risk of diabetes and IHD, but the relative risk was lower than that for IGT.

CONCLUSIONS—Greater efforts to identify those with IGT, or a group at similar risk of diabetes and CVD, may be a more efficient public health measure than lowering the FPG criterion for diagnosing IFG.