bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival in Patients With Type 2 Diabetes in a Swedish Community
Authors: Östgren Carl Johan , Lindblad Ulf , Melander Arne , Råstam Lennart
Published: March 2007

OBJECTIVE—To explore risk factors for all-cause mortality in patients with type 2 diabetes treated in primary care.

RESEARCH DESIGN AND METHODS—A prospective population-based study of 400 patients with type 2 diabetes who consecutively completed an annual checkup in primary care in Skara, Sweden, during 1992–1993. Vital status was ascertained to year 2000. Baseline characteristics as predictors for mortality were analyzed by Cox regression and expressed as relative risks (RRs), with 95% CIs.

RESULTS—During a mean follow-up time of 5.9 years, 131 patients died (56 deaths per 1,000 patients per year). In both sexes, all-cause mortality was predicted by HbA1c (by 1%; RR 1.14, 95% CI 1.01–1.27), and by LDL-to-HDL cholesterol ratios (1.15, 1.00–1.32). Increased mortality was also seen with prevalent hypertension (1.72, 1.21–2.44), microalbuminuria (1.87, 1.27–2.76), and previous cardiovascular disease (1.70, 1.15–2.50). Subanalyses revealed that increased mortality related to HbA1c was restricted to hypertensive patients with type 2 diabetes (1.23, 1.04–1.47). Serum triglycerides (by 1 mmol/l) predicted all-cause mortality in women (1.25, 1.06–1.47).

CONCLUSIONS—Poor glucose and lipid control and hypertension predicted all-cause mortality. Survival was also predicted by prevalent microalbuminuria and by previous cardiovascular disease. Confirming results from clinical trials, this population-based study has implications for primary and secondary prevention.
Thyroid Autoimmunity in Children and Adolescents With Type 1 Diabetes
Authors: Kordonouri Olga , Klinghammer Albrecht , Lang Egbert B. , Grüters-Kieslich Annette , Grabert Matthias , Holl Reinhard W. ,   On behalf of the DPV-Initiative of the German Working Group for Pediatric Diabetology
Published: March 2007

OBJECTIVE—To investigate thyroid autoimmunity in a very large nationwide cohort of children and adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Data were analyzed from 17,749 patients with type 1 diabetes aged 0.1–20 years who were treated in 118 pediatric diabetes centers in Germany and Austria. Antibodies to thyroglobulin (anti-TG) and thyroperoxidase (anti-TPO) were measured and documented at least once in 7,097 patients. A total of 49.5% of these patients were boys, the mean age was 12.4 years (range 0.3–20.0 years), and the mean duration of diabetes was 4.5 years (range 0.0–19.5 years). A titer exceeding 100 units/ml or 1:100 was considered significantly elevated.

RESULTS—In 1,530 patients, thyroid antibody levels were elevated on at least one occasion, whereas 5,567 were antibody-negative during the observation period. Patients with thyroid antibodies were significantly older (P < 0.001), had a longer duration of diabetes (P < 0.001), and developed diabetes later in life (P < 0.001) than those without antibodies. A total of 63% of patients with positive antibodies were girls, compared with 45% of patients without antibodies (P < 0.001). The prevalence of significant thyroid antibody titers increased with increasing age; the highest prevalence was in the 15- to 20-year age group (anti-TPO: 16.9%, P < 0.001; anti-TG: 12.8%, P < 0.001). Thyroid-stimulating hormone (TSH) levels were higher in patients with thyroid autoimmunity (3.34 μU/ml, range 0.0–615.0 μU/ml) than in control subjects (1.84 μU/ml, range 0.0–149.0 μU/ml) (P < 0.001). Even higher TSH levels were observed in patients with both anti-TPO and anti-TG (4.55 μU/ml, range 0.0–197.0 μU/ml).

CONCLUSIONS—Thyroid autoimmunity seems to be particularly common in girls with diabetes during the second decade of life and may be associated with elevated TSH levels, indicating subclinical hypothyroidism.
Is Insulin Sensitivity a Causal Intermediate in the Relationship Between Alcohol Consumption and Carotid Atherosclerosis?
Authors: Cooper Daniel E. , Goff David C. , Bell Ronny A. , Zaccaro Dan , Mayer-Davis Elizabeth J. , Karter Andrew J.
Published: March 2007

OBJECTIVE—A J-shaped association has been demonstrated between alcohol consumption and atherosclerosis. Insulin resistance, also a risk factor for atherosclerosis, has been shown to have a similar J-shaped association with alcohol intake. This raises the question of whether insulin sensitivity (SI) is a causal intermediate in the alcohol-atherosclerosis relationship.

RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study was a multicenter cohort study designed to investigate relationships among SI, risk factors for cardiovascular disease, and carotid artery atherosclerosis. Using regression analysis, we tested whether adjustment for SI attenuated the alcohol-atherosclerosis relationship observed at baseline.

RESULTS—A J-shaped association was observed between alcohol consumption and common carotid artery intimal medial thickness. The protective aspect of the alcohol-atherosclerosis relationship was attenuated by 25% after the adjustment for SI. However, an interaction was observed between alcohol consumption and glucose tolerance (GT) status. In comparison with never drinkers, all levels of alcohol consumption were associated with less atherosclerosis in participants with normal GT status. Participants with impaired GT status (but not diabetes) demonstrated a J-shaped alcohol-atherosclerosis association. All levels of alcohol consumption were associated with more atherosclerosis in participants with diabetes.

CONCLUSIONS—SI may be a causal intermediate at protective levels of alcohol intake, but an alcohol-GT interaction precluded a definitive conclusion. Moderate alcohol consumption may increase the risk of atherosclerosis in people with diabetes. These findings contrast with previous reports and do not support current recommendations regarding moderate alcohol consumption in people with diabetes. More research is needed to clarify this issue.
Intrinsic Muscle Atrophy and Toe Deformity in the Diabetic Neuropathic Foot
Authors: Bus Sicco A. , Yang Qing X. , Wang Jinghua H. , Smith Michael B. , Wunderlich Roshna , Cavanagh Peter R.
Published: March 2007

OBJECTIVE—The objectives of this study were to compare intrinsic foot muscle cross-sectional area (CSA) in patients with diabetic polyneuropathy and nondiabetic control subjects and to examine the association between intrinsic muscle CSA and clawing/hammering of the toes in neuropathic feet.

RESEARCH DESIGN AND METHODS—High-resolution T2-weighted fast spin-echo images and parametric T2 multiple spin-echo images were acquired using multiple spin-echo magnetic resonance imaging (MRI) of frontal plane sections of the metatarsal region of the foot in a sample of eight individuals with diabetic polyneuropathy and eight age- and sex-matched nonneuropathic nondiabetic control subjects. The configuration of joints of the second toe was obtained using a three-dimensional contact digitizer.

RESULTS—Remarkable atrophy was found in all the intrinsic muscles of neuropathic subjects as compared with nondiabetic control subjects. Quantitative T2 analysis showed a 73% decrease in muscle tissue CSA distally in the neuropathic subjects. Muscle comprised only 8.3 ± 2.9% (means ± SD) of total foot CSA compared with 30.8 ± 3.9% in control subjects. No significant differences were found between the groups in the metatarso-phalangeal and proximal and distal interphalangeal joint angles of the second ray. Moreover, clawing/hammering of the toes was found in only two of eight neuropathic subjects.

CONCLUSIONS—Although sensory neuropathy is often emphasized in considerations of diabetic foot pathology, our results show that the consequences of motor neuropathy in the feet are profound in people with diabetes. This has implications for foot function and may play a significant role in postural instability. However, intrinsic muscle atrophy does not necessarily appear to imply toe deformity.
Association of Type and Duration of Diabetes With Erectile Dysfunction in a Large Cohort of Men
Authors: Bacon Constance G. , Hu Frank B. , Giovannucci Edward , Glasser Dale B. , Mittleman Murray A. , Rimm Eric B.
Published: March 2007

OBJECTIVE—Differences in risk of erectile dysfunction (ED) by characteristics of diabetes among older men are not well understood. We examined the association of type and duration of diabetes with erectile function in men >50 years of age in a large prospective cohort study.

RESEARCH DESIGN AND METHODS—Subjects included 31,027 men aged 53–90 years in the Health Professionals Follow-Up Study cohort. On a questionnaire mailed in 2000, participants rated their ability (without treatment) in the past 5 years to have and maintain an erection sufficient for intercourse. Men who reported poor or very poor function were considered to have ED. Diabetes information was ascertained via self-report and documented with supplementary medical data.

RESULTS—Men with diabetes had an age-adjusted relative risk (RR) of 1.32 (95% CI 1.3–1.4) for having ED compared with men without diabetes. In multivariable regression analyses, men with type 1 and type 2 diabetes were at a significantly higher risk for ED (type 1 diabetes RR = 3.0, 95% CI 1.5–5.9; type 2 diabetes RR = 1.3, 1.1–1.5) than nondiabetic men. Men with type 2 diabetes had an increasingly greater risk of ED with increased duration since diagnosis (trend test P value <0.0001) (RR = 1.7, 95% CI 1.1–2.7, for men diagnosed >20 years previously).

CONCLUSIONS—For men over age 50 years, increasing duration of diabetes was positively associated with increased risk of ED relative to nondiabetic subjects. This association persisted despite the higher prevalence of other comorbid conditions. ED prevention and diabetes management efforts are likely to go hand-in-hand.
Improvement of BMI, Body Composition, and Body Fat Distribution With Lifestyle Modification in Japanese Americans With Impaired Glucose Tolerance
Authors: Liao David , Asberry Pamela J. , Shofer Jane B. , Callahan Holly , Matthys Colleen , Boyko Edward J. , Leonetti Donna , Kahn Steven E. , Austin Melissa , Newell Laura , Schwartz Robert S. , Fujimoto Wilfred Y.
Published: March 2007

OBJECTIVE—To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—This study compared the effects of an American Heart Association (AHA) step 2 diet (<30% of total calories as fat, <7% saturated fat, 55% carbohydrate, and < 200 mg cholesterol daily) plus endurance exercise for 1 h three times a week (treatment group) with an AHA step 1 diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and <300 mg cholesterol) plus stretching exercise three times a week (control group) on BMI, body composition (% fat), and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT, 58 of whom completed the study.

RESULTS—At 6 months, the treatment group showed significantly greater reduction in percent, body fat (−1.4 ± 0.4 vs. −0.3 ± 0.3%); BMI (−1.1 ± 0.2 vs. −0.4 ± 0.1 kg/m2); subcutaneous fat by computed tomography at the abdomen (−29.3 ± 4.2 vs. −5.7 ± 5.9 cm2), thigh (−13.2 ± 3.6 vs. −3.6 ± 3.0 cm2), and thorax (−19.6 ± 3.6 vs. −8.9 ± 2.6 cm2); and skinfold thickness at the bicep (−2.0 ± 0.6 vs. 1.1 ± 0.6 mm) and tricep (−3.7 ± 0.8 vs. −0.9 ± 0.6 mm), which continued despite moving to home-based exercise for the last 18 months.

CONCLUSIONS—Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT.
Fetal Overnutrition in Polynesian Pregnancies and in Gestational Diabetes May Lead to Dysregulation of the Adipoinsular Axis in Offspring
Authors: Simmons David , Breier Bernhard H.
Published: March 2007

OBJECTIVE—To compare umbilical cord leptin concentrations in different ethnic groups and between pregnancies with and without gestational diabetes mellitus (GDM) in Auckland, New Zealand.

RESEARCH DESIGN AND METHODS—A cross-sectional study of 116 European, Polynesian, and South Asian women and their infants with and without GDM. Maternal metabolic measures were recorded at 36 weeks’ gestation, umbilical cord samples were collected at birth, and neonatal anthropometric measures were recorded 24 h after delivery.

RESULTS—Compared with Europeans and South Asians, samples of Polynesian umbilical cords had higher leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026). Umbilical cord samples from pregnancies complicated by GDM had higher leptin concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml, respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar across ethnic groups and with and without GDM. Cord leptin correlated with birth weight, measures of fetal size, and cord insulin in normal pregnancies and those complicated by GDM. In multivariate analyses, cord leptin was related to birth weight (P < 0.001), gestation at delivery (P = 0.038), and ethnic group (P = 0.017) in normal pregnancies and to birth weight (P < 0.001), gestation at delivery (P < 0.001), and sex (P = 0.003) but not maternal diabetes status (P = 0.909) in pregnancies complicated by GDM.

CONCLUSIONS—Offspring of Polynesian women are relatively hyperleptinemic, independent of birth size. Offspring of women with GDM are also relatively hyperleptinemic at birth, but this was associated with their increased birth weight. We speculate that this GDM-associated relative hyperleptinemia may be due to fuel-mediated teratogenesis affecting the adipoinsular axis, which in turn could also lead to leptin resistance and obesity in adult life. The reason for the ethnic difference in hyperleptinemia is unclear.
Low Levels of Leisure-Time Physical Activity and Cardiorespiratory Fitness Predict Development of the Metabolic Syndrome
Authors: Laaksonen David E. , Lakka Hanna-Maaria , Salonen Jukka T. , Niskanen Leo K. , Rauramaa Rainer , Lakka Timo A.
Published: March 2007

OBJECTIVE—Little is known about the association of leisure-time physical activity (LTPA) and cardiorespiratory fitness with development of the metabolic syndrome, which predisposes diseases such as diabetes and atherosclerosis. We studied the associations of LTPA and cardiorespiratory fitness with development of the metabolic syndrome (World Health Organization [WHO] and the National Cholesterol Education Program [NCEP] definitions).

RESEARCH DESIGN AND METHODS—LTPA over the previous 12 months, Vo2max (ml · kg−1 · min−1), and cardiovascular and metabolic risk factors were assessed in a population-based cohort of 612 middle-aged men without the metabolic syndrome.

RESULTS—At the 4-year follow-up, 107 men had metabolic syndrome (WHO definition). Men engaging in >3 h/week of moderate or vigorous LTPA were half as likely as sedentary men to have the metabolic syndrome after adjustment for major confounders (age, BMI, smoking, alcohol, and socioeconomic status) or potentially mediating factors (insulin, glucose, lipids, and blood pressure), especially in high-risk men. Vigorous LTPA had an even stronger inverse association, particularly in unfit men. Men in the upper third of Vo2max were 75% less likely than unfit men to develop the metabolic syndrome, even after adjustment for major confounders. Adjustment for possible mediating factors attenuated the association. Associations of LTPA and Vo2max with development of the metabolic syndrome, as defined by the NCEP, were qualitatively similar.

CONCLUSIONS—In particular, high-risk men engaging in currently recommended levels of physical activity were less likely to develop the metabolic syndrome than sedentary men. Cardiorespiratory fitness was also strongly protective, although possibly not independent of mediating factors.
A Randomized Trial of Sibutramine in the Management of Obese Type 2 Diabetic Patients Treated With Metformin
Authors: McNulty Steven J. , Ur Ehud , Williams Gareth ,   For the Multicenter Sibutramine Study Group
Published: March 2007

OBJECTIVE—To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m2 were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA1c, fasting glucose, and lipids.

RESULTS—Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 ± 0.6 kg at 12 months) and 20 mg/day (8.0 ± 0.9 kg), whereas placebo did not (0.2 ± 0.5 kg). Weight loss ≥10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost ≥10% weight showed significant decreases in both HbA1c (1.2 ± 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of ≥10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by ≥5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of ≥10% weight. Pulse rate increased significantly more with sibutramine, being ≥10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).

CONCLUSIONS—Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight.
Rosiglitazone Improves Insulin Sensitivity and Lowers Blood Pressure in Hypertensive Patients
Authors: Raji Annaswamy , Seely Ellen W. , Bekins Shannon A. , Williams Gordon H. , Simonson Donald C.
Published: March 2007

OBJECTIVE—To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension, classified based on abnormalities of their renin-angiotensin system.

RESEARCH DESIGN AND METHODS—A total of 24 hypertensive nondiabetic patients (age 58 ± 6 years, BMI 30 ± 5 kg/m2) were studied before and after rosiglitazone treatment. After 2 weeks off antihypertensive medication, subjects received a euglycemic-hyperinsulinemic clamp (40 mU · m−2 · min−1) with 6,6-[2H2]glucose infusion, ambulatory blood pressure monitoring, and blood tests for cardiovascular risk factors. Subjects were then placed on rosiglitazone (4 mg orally b.i.d.) and their usual antihypertensive medications (but not ACE inhibitors) for 16 weeks, and baseline tests were repeated.

RESULTS—There was no change in fasting plasma glucose (83 ± 2 vs. 82 ± 2 mg/dl, P = 0.60), but fasting insulin decreased (16.1 ± 1.4 vs. 12.5 ± 0.9 μU/ml, P < 0.01). Total glucose disposal during the clamp increased (5.0 ± 0.4 vs. 5.9 ± 0.5 mg · kg−1 · min−1, P < 0.001), with no change in suppression of hepatic glucose output. There were significant decreases in mean 24-h systolic (138 ± 2 vs. 134 ± 2 mmHg, P < 0.02) and diastolic (85 ± 2 vs. 80 ± 2 mmHg, P < 0.0001) blood pressure, and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity (r = 0.59, P < 0.005). Triglycerides (135 ± 16 vs. 89 ± 8 mg/dl, P < 0.01), LDL cholesterol (129 ± 6 vs. 122 ± 8 mg/dl, P = 0.18), and HDL cholesterol (51 ± 3 vs. 46 ± 3 mg/dl, P < 0.02) all decreased, with no change in the LDL-to-HDL ratio. Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly.

CONCLUSIONS—Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity, reduces systolic and diastolic blood pressure, and induces favorable changes in markers of cardiovascular risk. Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension.
Determinants of Fetal Growth at Different Periods of Pregnancies Complicated by Gestational Diabetes Mellitus or Impaired Glucose Tolerance
Authors: Schaefer-Graf Ute M. , Kjos Siri L. , Kilavuz Ömer , Plagemann Andreas , Brauer Martin , Dudenhausen Joachim W. , Vetter Klaus
Published: March 2007

OBJECTIVE—To determine maternal parameters with the strongest influence on fetal growth in different periods of pregnancies complicated by an abnormal glucose tolerance test (GTT).

RESEARCH DESIGN AND METHODS—Retrospective study of 368 women with gestational diabetes mellitus (GDM; ≥2 abnormal GTT values, n = 280) and impaired glucose tolerance (IGT; one abnormal value, n = 88) with 869 ultrasound examinations at entry to and during diabetic care. Both groups were managed comparably. Abdominal circumference (AC) ≥90th percentile defined fetal macrosomia. Maternal historical and clinical parameters, and diagnostic and glycemic values of glucose profiles divided into five categories of 4 weeks of gestational age (GA; <24 weeks, 24 weeks/0 days to 27 weeks/6 days, 28/0–31/6, 32/0–35/6, and 36/0–40/0 [referred to as <24 GA, 24 GA, 28 GA, 32 GA, and 36 GA categories, respectively]) were tested by univariate and multiple logistic regression analysis for their ability to predict an AC ≥90th percentile at each GA group and large-for-gestational-age (LGA) newborn. Data obtained at entry were also analyzed separately irrespective of the GA.

RESULTS—Maternal weight, glycemia after therapy, rates of fetal macrosomia, and LGA were not significantly different between GDM and IGT; thus, both groups were analyzed together. LGA in a previous pregnancy, (odds ratio [OR] 3.6; 95% CI 1.8–7.3) and prepregnancy obesity (BMI ≥30 kg/m2; 2.1; 1.2–3.7) independently predicted AC ≥90th percentile at entry. When data for each GA category were analyzed, no predictors were found for <24 GA. Independent predictors for each subsequent GA category were as follows: at 24 GA, LGA history (OR 9.8); at 28 GA, LGA history (OR 4.2), and obesity (OR 3.3); at 32 GA, fasting glucose of 32 GA (OR 1.6 per 5-mg/dl increase); at 36 GA, fasting glucose of 32 GA (OR 1.6); and for LGA at birth, LGA history (OR 2.7), and obesity (OR 2.4).

CONCLUSIONS—In the late second and early third trimester, maternal BMI and LGA in a previous pregnancy appear to have the strongest influence on fetal growth, while later in the third trimester coincident with the period of maximum growth described in diabetic pregnancies, maternal glycemia predominates.
Costs Associated With the Primary Prevention of Type 2 Diabetes Mellitus in the Diabetes Prevention Program
Authors:   The Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—To describe the costs of the Diabetes Prevention Program (DPP) interventions to prevent or delay type 2 diabetes.

RESEARCH DESIGN AND METHODS—We describe the direct medical costs, direct nonmedical costs, and indirect costs of the placebo, metformin, and intensive lifestyle interventions over the 3-year study period of the DPP. Resource use and cost are summarized from the perspective of a large health system and society. Research costs are excluded.

RESULTS—The direct medical cost of laboratory tests to identify one subject with impaired glucose tolerance (IGT) was $139. Over 3 years, the direct medical costs of the interventions were $79 per participant in the placebo group, $2,542 in the metformin group, and $2,780 in the lifestyle group. The direct medical costs of care outside the DPP were $272 less per participant in the metformin group and $432 less in the lifestyle group compared with the placebo group. Direct nonmedical costs were $9 less per participant in the metformin group and $1,445 greater in the lifestyle group compared with the placebo group. Indirect costs were $230 greater per participant in the metformin group and $174 less in the lifestyle group compared with the placebo group. From the perspective of a health system, the cost of the metformin intervention relative to the placebo intervention was $2,191 per participant and the cost of the lifestyle intervention was $2,269 per participant over 3 years. From the perspective of society, the cost of the metformin intervention relative to the placebo intervention was $2,412 per participant and the cost of the lifestyle intervention was $3,540 per participant over 3 years.

CONCLUSIONS—The metformin and lifestyle interventions are associated with modest incremental costs compared with the placebo intervention. The evaluation of costs relative to health benefits will determine the value of these interventions to health systems and society.
Alcohol Consumption and Risk for Development of Impaired Fasting Glucose or Type 2 Diabetes in Middle-Aged Japanese Men
Authors: Nakanishi Noriyuki , Suzuki Kenji , Tatara Kozo
Published: March 2007

OBJECTIVE—To investigate the association between alcohol consumption and risk for development of diabetes.

RESEARCH DESIGN AND METHODS—We examined 2,953 Japanese male office workers aged 35–59 years who did not have impaired fasting glucose (IFG) (a fasting plasma glucose concentration of 6.1–6.9 mmol/l), type 2 diabetes (a fasting plasma glucose concentration of ≥7.0 mmol/l or receipt of hypoglycemic medication), medication for hypertension, or a history of cardiovascular disease. Fasting plasma glucose concentrations were measured at periodic annual health examinations from May 1994 through May 2001.

RESULTS—There was a U-shaped association between alcohol consumption and the incidence of IFG or type 2 diabetes during 7 years of follow-up, with the lowest incidence at alcohol intake of 23.0–45.9 g ethanol/day. After controlling for age, family history of diabetes, BMI, cigarette smoking, and physical activity, the relative risk for development of IFG or type 2 diabetes compared with alcohol consumption of 23.0–45.9 g ethanol/day was 1.51 (95% CI, 1.07–2.13), 1.31 (95% CI, 0.93–1.84), 1.18 (95% CI, 0.87–1.61), and 1.43 (95% CI, 1.01–2.02) with alcohol consumption of 0, 0.1–22.9, 46.0–68.9, and ≥69.0 g ethanol/day, respectively (P for quadratic trend = 0.016). Analyses by presence or absence of a risk factor revealed that a U-shaped association was more evident in older men, men without a family history of diabetes, and nonsmokers.

CONCLUSIONS—These results indicate that moderate alcohol consumption among apparently healthy Japanese men is associated with reduced risk for development of IFG or type 2 diabetes.
Age- and Sex-Specific Prevalences of Diabetes and Impaired Glucose Regulation in 13 European Cohorts
Authors:   The DECODE Study Group
Published: March 2007

OBJECTIVE—To report the age- and sex-specific prevalences of diabetes and impaired glucose regulation (IGR) according to the revised 1999 World Health Organization criteria for diabetes in Europe.

RESEARCH DESIGN AND METHODS—A total of 13 studies from nine European countries with 7,680 men and 9,251 women aged 30–89 years were included in the data analysis.

RESULTS—In most of the study populations, the age-specific prevalences of diabetes were <10% in subjects younger than 60 years and between 10 and 20% at 60–79 years of age. Mean 2-h plasma glucose (2hPG) concentration increased linearly with age, but fasting plasma glucose (FPG) concentration did not. The increase in the prevalence of undiagnosed diabetes and IGR in the elderly was mainly a result of the large increase in 2hPG rather than FPG. Diabetes and impaired fasting glycemia defined by isolated fasting hyperglycemia was more common in men than in women 30–69 years of age, whereas the prevalence of isolated postload hyperglycemia, particularly impaired glucose tolerance, was higher in women than in men, especially in the elderly (individuals >70 years of age). More than half of the diabetes was undiagnosed in subjects younger than 50 years of age.

CONCLUSIONS—Most European populations have a moderate to low prevalence of diabetes and IGR. Diabetes and IGR will be underestimated in Europe, particularly in women and in elderly men, if diagnoses are based on fasting glucose determination alone.
Incidence of Retinopathy and Nephropathy in Youth-Onset Compared With Adult-Onset Type 2 Diabetes
Authors: Krakoff Jonathan , Lindsay Robert S. , Looker Helen C. , Nelson Robert G. , Hanson Robert L. , Knowler William C.
Published: March 2007

OBJECTIVE—To examine the risk of retinopathy and nephropathy in participants in whom type 2 diabetes was diagnosed in youth (before 20 years of age) compared with those in whom type 2 diabetes was diagnosed at older ages.

RESEARCH DESIGN AND METHODS—Subjects in whom youth-onset or adult-onset diabetes was diagnosed in the longitudinal study of health in the Pima Indians of Arizona were followed for microvascular complications. Diabetes was diagnosed in 178 subjects before 20 years of age (youth), in 1,359 subjects at 20–39 years of age (younger adults), and in 971 subjects at 40–59 years of age (older adults). Incidence rates of diabetic retinopathy diagnosed by direct ophthalmoscopy through dilated pupils and nephropathy (protein-to-creatinine ratio ≥0.5 g/g) were calculated by age at diagnosis.

RESULTS—Over 25 years, nephropathy developed in 35 of the participants with youth-onset type 2 diabetes; this incidence rate was not significantly different from that in patients with adult-onset diabetes (P = 0.77). Incidence rates of retinopathy, however, were significantly lower for the youth-onset group (P = 0.007). Adjusted for sex, glycemia, and blood pressure, risk of retinopathy was lower in patients with youth-onset diabetes than in those with adult-onset diabetes (hazard rate ratio [HRR] 0.42, 95% CI 0.24–0.74, P = 0.003), but risk of nephropathy was not different (HRR 1.2, 95% CI 0.77–1.3, P = 0.38).

CONCLUSIONS—In Pima Indians, the risk of nephropathy as a function of duration of diabetes is similar in all age groups. By contrast, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes.
Autoimmune Gastropathy in Type 1 Diabetic Patients With Parietal Cell Antibodies
Authors: De Block Christophe E.M. , De Leeuw Ivo H. , Bogers Johannes J.P.M. , Pelckmans Paul A. , Ieven Margareta M. , Van Marck Eric A.E. , Van Acker Kristien L. , Van Gaal Luc F.
Published: March 2007

OBJECTIVE—Approximately 15–20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) targeting gastric H+/K+ATPase. We examined whether iron deficiency anemia, pernicious anemia, and autoimmune gastritis, which may predispose to gastric tumors, were more frequent in PCA+ than in PCA- patients.

RESEARCH DESIGN AND METHODS—Gastric biopsies from 88 consecutively recruited type 1 diabetic patients (51 men and 37 women, 47 PCA+ and 41 PCA-, aged 42 ± 13 years) were evaluated using the updated Sydney system. Immunostaining was done for parietal cells, B- and T-cells, enterochromaffin-like (ECL) cells, and Helicobacter pylori (HP). PCAs were assayed by indirect immunofluorescence, H+/K+ATPase antibodies by enzyme immunoassay, and HP by serology, urea breath test, and histology. Pentagastrin tests were performed in 42 subjects.

RESULTS—Autoimmune gastritis (AG) was present in 57% of PCA+ and 10% of PCA- cases (OR 12.5, P < 0.0001). PCA positivity (β = 1.44; P = 0.04) and hypergastrinemia (β = 0.01; P = 0.026), but not HP, age, diabetes duration, sex, and HLA-DQ type were risk factors for AG. Iron deficiency anemia (OR 3.9, P = 0.015), pernicious anemia (OR = 4.6, P = 0.022), and hypochlorhydria (OR = 20.0, P = 0.0002) were more frequent in AG+ individuals. HP infection was present in 47 patients but did not influence corpus histology or gastrinemia. (Pre)malignant lesions were found in 26% of PCA+ subjects: ECL cell hyperplasia in 7 AG+ patients, comprising 1 with a gastric carcinoid tumor, and corpus intestinal metaplasia in 11 AG+ patients, including 1 with linitis plastica.

CONCLUSIONS—PCA+ type 1 diabetic patients should be screened for autoimmune gastritis, iron deficiency, and pernicious anemia. Particularly hypergastrinemic PCA+ patients with autoimmune gastritis are at increased risk for (pre)malignant gastric lesions.
Secondary Prevention of Cardiovascular Events With Long-Term Pravastatin in Patients With Diabetes or Impaired Fasting Glucose
Authors: Keech Anthony , Colquhoun David , Best James , Kirby Adrienne , Simes R. John , Hunt David , Hague Wendy , Beller Elaine , Arulchelvam Manjula , Baker Jennifer , Tonkin Andrew ,   for the LIPID Study Group
Published: March 2007

OBJECTIVE—Diabetes, a major health problem worldwide, increases the risk of cardiovascular disease and its associated mortality. Evidence of the overall benefits of lipid modification in this area is needed.

RESEARCH DESIGN AND METHODS—The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that cholesterol-lowering treatment with pravastatin reduced mortality and coronary heart disease (CHD) events in 9,014 patients aged 31–75 years with CHD and total cholesterol 4.0–7.0 mmol/l. We measured the effects of pravastatin therapy, 40 mg/day over 6.0 years, on the risk of CHD death or nonfatal myocardial infarction and other cardiovascular outcomes in 1,077 LIPID patients with diabetes and 940 patients with impaired fasting glucose (IFG).

RESULTS—In patients allocated to placebo, the risk of a major CHD event was 61% higher in patients with diabetes and 23% higher in the IFG group than in patients with normal fasting glucose, and the risk of any cardiovascular event was 37% higher in the diabetic group and 19% higher in the IFG group. Pravastatin therapy reduced the risk of a major CHD event overall from 15.9 to 12.3% (relative risk reduction [RRR] 24%, P < 0.001) and from 23.4 to 19.6% in the diabetic group (19%, P = 0.11); in the diabetic group, the reduction was not significantly different from the reductions in the other groups. Pravastatin reduced the risk of any cardiovascular event from 52.7 to 45.2% (21%, P < 0.008) in patients with diabetes and from 45.7 to 37.1% (26%, P = 0.003) in the IFG group. Pravastatin reduced the risk of stroke from 9.9 to 6.3% in the diabetic group (RRR 39%, CI 7–61%, P = 0.02) and from 5.4 to 3.4% in the IFG group (RRR 42%, CI −9 to 69%, P = 0.09). Pravastatin did not reduce the incidence of diabetes. Over 6 years, pravastatin therapy prevented one major CHD event (CHD death or nonfatal myocardial infarction) in 23 patients with IFG and 18 patients with diabetes. A meta-analysis of other major trials confirmed the high absolute risks of diabetes and IFG and the absolute benefits of statin therapy in these patients.

CONCLUSIONS—Cholesterol-lowering treatment with pravastatin therapy prevents cardiovascular events, including stroke, in patients with diabetes or IFG and established CHD.
Relation of Left Ventricular Hypertrophy to Inflammation and Albuminuria in Adults With Type 2 Diabetes
Authors: Palmieri Vittorio , Tracy Russell P. , Roman Mary J. , Liu Jennifer E. , Best Lyle G. , Bella Jonathan N. , Robbins David C. , Howard Barbara V. , Devereux Richard B.
Published: March 2007

OBJECTIVE—To evaluate in adults with type 2 diabetes the extent to which the relation of left ventricular hypertrophy (LVH) to markers of systemic inflammation (fibrinogen and high-sensitivity C-reactive protein [hsCRP]) are affected by microangiopathy.

RESEARCH DESIGN AND METHODS—We selected adults with type 2 diabetes using American Diabetes Association criteria from a population-based cohort, excluding those with medical history or electrocardiographic evidence of coronary heart disease or dialysis-dependent renal failure. LVH was assessed by echocardiogram.

RESULTS—Of the 1,299 eligible participants, 384 (29.6%) had LVH, which was associated with higher BMI, hsCRP, fibrinogen, and albuminuria in univariate analyses. After controlling for significant confounders, fibrinogen and albuminuria were higher in the presence of LVH (both P < 0.01), whereas hsCRP was not (P = 0.2), mostly because of the confounding effect of BMI. Adjustment for albuminuria abolished the relation of LVH to higher fibrinogen (P = 0.2). However, fibrinogen was significantly higher in participants with LVH among those without pathologic levels of albuminuria (<30 mg/g creatinuria), but not independent of BMI. Although hsCRP and fibrinogen were moderately correlated, fibrinogen, but not CRP, showed a significant relation with albuminuria.

CONCLUSIONS—In adults with type 2 diabetes, echocardiographic LVH is associated with susceptibility to atherothrombosis and increased albuminuria, which is a marker of microangiopathy and endothelial dysfunction that appears in turn to be a relevant pathogenetic link between LVH and inflammation. However, in the absence of significant microalbuminuria, elevated BMI is a relevant pathogenetic factor in the relation of LVH to increased levels of markers of inflammation, potentially preceding development of significant albuminuria. In the presence of microangiopathy, we found that the atherothrombotic risk profile associated with LVH was independent of BMI and possibly reflected the association of LVH with a higher degree of endothelial dysfunction.
Prediction of Coronary Heart Disease in Middle-Aged Adults With Diabetes
Authors: Folsom Aaron R. , Chambless Lloyd E , Duncan Bruce B. , Gilbert Adam C. , Pankow James S. ,   the Atherosclerosis Risk in Communities Study Investigators
Published: March 2007

OBJECTIVE—To determine the 10-year probability of coronary heart disease (CHD) in diabetic adults and how well basic and novel risk factors predict CHD risk.

RESEARCH DESIGN AND METHODS—We measured risk factors in 14,054 participants (1,500 with diabetes) initially free of CHD in the Atherosclerosis Risk in Communities study from 1987 to 1989 and followed them prospectively for CHD incidence through 1998. We used proportional hazards regression models and receiver operating characteristic (ROC) curves for CHD risk prediction.

RESULTS—Based on our model using basic risk factors (age, race, total and HDL cholesterol, systolic blood pressure, antihypertensives, and smoking status), ∼61% of diabetic women and 86% of diabetic men had a predicted 10-year CHD probability ≥10%. This CHD risk-prediction model had an area under the ROC curve of 0.72 in diabetic women and 0.67 in diabetic men. Novel risk factors or subclinical disease markers individually added only modest predictivity, but the addition of multiple markers (BMI, waist-to-hip ratio, Keys dietary score, serum albumin and creatinine, factor VIII, white blood cell count, left ventricular hypertrophy determined by electrocardiogram, and carotid intima-media thickness) increased the area under the curve by ∼10%.

CONCLUSIONS—Although all diabetic adults are at high risk for CHD, their variation in CHD risk can be predicted moderately well by basic risk factors. No single novel risk marker greatly enhanced absolute CHD risk assessment, but a battery of novel markers did. Our model can provide estimates of CHD risk for the primary prevention of this disease in people with type 2 diabetes.
Tele-Screening for Diabetic Retinopathy With the Retinal Thickness Analyzer
Authors: Neubauer Aljoscha S. , Welge-Lüßen Ulrich C. , Thiel Martin J. , Alge Claudia , Priglinger Siegfried G. , Hirneiß Christoph , Ulbig Michael W. , Kampik Anselm
Published: March 2007

OBJECTIVE—To compare the effectiveness of tele-screening using a novel enhanced retinal thickness analyzer (RTA) with onsite routine ophthalmologic examination for diabetic retinopathy.

RESEARCH DESIGN AND METHODS—A consecutive series of 31 eyes from diabetic patients were included. All underwent ophthalmologic examination, including stereoscopic dilated funduscopy and scanning with the RTA. The RTA reports consisted of a wide-angle, red-free fundus photograph and a macular-region retinal thickness map. Reports were graded by three independent graders in a masked manner. The diagnoses of proliferative retinopathy, macular edema, and treatment decisions made by the RTA graders and the clinical examiner were compared.

RESULTS—On clinical examination 5 of 31 eyes were diagnosed with proliferative diabetic retinopathy (PDR). All five were referred for treatment by two graders and four eyes by one grader. All eyes with PDR and 12 of the 26 eyes with nonproliferative diabetic retinopathy showed severe macular edema. Seven of the 12 eyes with macular edema were clinically eligible for focal laser treatment, and all of them were detected by all RTA graders. Macular thickening was detected in eight eyes by RTA where no treatment was necessary, as judged by clinical examination. Thus, sensitivity was 93% (mean) for detecting PDR and 100% for detecting macular edema, with a specificity of 58–96% depending on the grader. The RTA did not allow valid assessment due to poor image quality in only one case.

CONCLUSIONS—Screening for diabetic retinopathy with a combination of wide-angle fundus photography and macular thickness mapping by an objective method, such as optical coherence tomography or the RTA, offers the prerequisites for establishing a successful tele-screening program.
Effective Exercise Modality to Reduce Insulin Resistance in Women With Type 2 Diabetes
Authors: Cuff Darcye J. , Meneilly Graydon S. , Martin Alan , Ignaszewski Andrew , Tildesley Hugh D. , Frohlich Jiri J.
Published: March 2007

OBJECTIVE—The purpose of this study was to evaluate whether a combined resistance and aerobic training program would improve insulin sensitivity compared with aerobic training alone in postmenopausal women with type 2 diabetes. A second objective was to relate the improved insulin sensitivity to changes in abdominal adipose tissue (AT) and thigh muscle density.

RESEARCH DESIGN AND METHODS—A total of 28 obese postmenopausal women with type 2 diabetes were randomly assigned to one of three 16-week treatments: control, aerobic only training (Ae only), or aerobic plus resistance training (Ae+RT). Pre- and posttreatment outcome measures included glucose disposal by hyperinsulinemic-euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh skeletal muscle.

RESULTS—Glucose infusion rates increased significantly (P < 0.05) in the Ae+RT group. Both exercise groups had reduced abdominal subcutaneous and visceral AT and increased muscle density. The Ae+RT training group exhibited a significantly greater increase in muscle density than the Ae only group. Improved glucose disposal was independently associated with changes in subcutaneous AT, visceral AT, and muscle density. Muscle density retained a relationship with glucose disposal after controlling for abdominal AT.

CONCLUSIONS—Adding resistance training to aerobic training enhanced glucose disposal in postmenopausal women with type 2 diabetes. The improved insulin sensitivity is related to loss of abdominal subcutaneous and visceral AT and to increased muscle density.
Complications in Young Adults With Early-Onset Type 2 Diabetes
Authors: Hillier Teresa A. , Pedula Kathryn L.
Published: March 2007

OBJECTIVE—To determine whether adults diagnosed with type 2 diabetes from age 18 to 44 years more aggressively develop clinical complications after diagnosis than adults diagnosed at ≥45 years of age.

RESEARCH DESIGN AND METHODS—We compared outcomes among 7,844 adults in a health maintenance organization who were newly diagnosed with type 2 diabetes between 1996 and 1998. We abstracted clinical data from electronic medical, laboratory, and pharmacy records. To adjust for length of follow-up and sex, we used proportional hazards models to compare incident complication rates through 2001 between onset groups (mean follow-up 3.9 years). To adjust for the increasing prevalence of macrovascular disease with advancing age, onset groups were matched by age and sex to control subjects without diabetes for macrovascular outcomes.

RESULTS—Adults with early-onset type 2 diabetes were 80% more likely to begin insulin therapy than those with usual-onset type 2 diabetes (hazards ratio [HR] 1.8, 95% CI 1.5–2.0), despite a similar average time to requiring insulin (∼2.2 years). Although the combined risk of microvascular complications did not differ overall, microalbuminuria was more likely in early-onset type 2 diabetes than usual-onset type 2 diabetes (HR 1.2, 95% CI 1.1–1.4). The hazard of any macrovascular complication in early-onset type 2 diabetic patients compared with control subjects was twice as high in usual-onset type 2 diabetic patients compared with control subjects (HR 7.9 vs. 3.8, respectively). Myocardial infarction (MI) was the most common macrovascular complication, and the hazard of developing an MI in early-onset type 2 diabetic patients was 14-fold higher than in control subjects (HR 14.0, 95% CI 6.2–31.4). In contrast, adults with usual-onset type 2 diabetes had less than four times the risk of developing an MI compared with control subjects (HR 3.7, P < 0.001).

CONCLUSIONS—Early-onset type 2 diabetes appears to be a more aggressive disease from a cardiovascular standpoint. Although the absolute rate of cardiovascular disease (CVD) is higher in older adults, young adults with early-onset type 2 diabetes have a much higher risk of CVD relative to age-matched control subjects.
The Relationship Between Provider Coordination and Diabetes-Related Foot Outcomes
Authors: Wrobel James S. , Charns Martin P. , Diehr Paula , Robbins Jeffrey M. , Reiber Gayle E. , Bonacker Kristin M. , Haas Linda B. , Pogach Leonard
Published: March 2007

OBJECTIVE—To investigate the relationship between provider coordination and amputations in patients with diabetes.

RESEARCH DESIGN AND METHODS—The study design was a cross-sectional, descriptive study of process and outcomes for diabetes-related foot care at 10 Department of Veterans Affairs (VA) medical centers representing different geographic regions, population densities, patient populations, and amputation rates. The subjects included all providers of diabetes foot care and a random sample of primary care providers at each medical center. The main outcome measures were the Foot Systems Assessment Tool (FootSAT), nontraumatic lower extremity amputation rates, and investigators’ ordinal ranking of site effectiveness based on site visits.

RESULTS—The survey response rate was 48%. Scale reliability, as measured by Cronbach’s α, ranged from 0.73 to 0.93. The scale scores for programming coordination (i.e., electronic medical record, policies, reminders, protocols, and educational seminars) and feedback coordination (i.e., discharge planning, quality of care meetings, and curbside consultations) were negatively associated with amputation rates, suggesting centers with higher levels of coordination had lower amputation rates. Statistically significant associations were found for programming coordination with minor amputations (P = 0.02) and total amputations (P = 0.04).

CONCLUSIONS—The FootSAT demonstrated a stronger association with amputation rates than site visit rankings. Among these 10 VA facilities, those with higher levels of programming and feedback coordination had significantly lower amputation rates.