bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Letting in High-Ferritin Type 2 Diabetes
Authors: Fernández-Real José Manuel , Peñarroja Georgina , Castro Antoni , García-Bragado Fernando , López-Bermejo Abel , Ricart Wifredo
Published: March 2007

OBJECTIVE—In a recent study, iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease. We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration.

RESEARCH DESIGN AND METHODS—A total of 28 type 2 diabetic male patients with serum ferritin levels >200 ng/ml (∼18% of consecutive type 2 diabetic men attending our outpatient clinic) were randomized to iron depletion (three extractions of 500 ml blood at 2-week intervals; group 1A) or to observation (group 1B). C282Y mutation was absent in all patients. Vascular reactivity (high-resolution external ultrasound) was evaluated at baseline and at 4 and 12 months thereafter. The two groups of patients were matched for age, BMI, pharmacological treatment, and chronic diabetic complications.

RESULTS—Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients. In contrast, the vasodilation induced by glyceryl trinitrate (GTN) improved significantly after iron depletion (P = 0.006). These changes occurred in parallel to decreases in transferrin saturation index and HbA1c levels (−0.6%, P < 0.05) only in group 1A patients. The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA1c levels. Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin (r = −0.45, P = 0.04). At 12 months, transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects.

CONCLUSIONS—Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations. The mechanisms by which these changes occur should be further investigated.
Cardiac Autonomic Nervous Dysfunction in Diabetic Patients With a Mitochondrial DNA Mutation
Authors: Momiyama Yukihiko , Suzuki Yoshihiko , Ohtomo Masako , Atsumi Yoshihito , Matsuoka Kempei , Ohsuzu Fumitaka , Kimura Mitsuru
Published: March 2007

OBJECTIVE—To elucidate the degree and characteristics of cardiac autonomic nervous dysfunction in diabetic patients associated with a mitochondrial DNA mutation at base pair 3243.

RESEARCH DESIGN AND METHODS—We investigated heart rate variability using 24-h Holter monitoring in 10 diabetic patients with the mutation compared with 55 ordinary diabetic patients and 45 nondiabetic control subjects.

RESULTS—Age and sex were similar in the three groups. Between patients with the mutation and ordinary diabetic patients, the duration of diabetes and blood glycemic levels were not different. In the time domain analysis of heart rate variability, patients with the mutation and ordinary diabetic patients had significantly smaller SDNN index and pNN50 than control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller SDNN index (P < 0.02), but rMSSD and pNN50 were not different. In the frequency domain analysis, total, low frequency (LF), and high frequency (HF) spectra were significantly smaller in patients with the mutation and ordinary diabetic patients than in control subjects. Compared with ordinary diabetic patients, patients with the mutation had smaller total and LF spectra (P < 0.02). However, HF spectra were not significantly different. Notably, the LF/HF spectra ratio was lower in patients with the mutation than in ordinary diabetic patients and control subjects (P < 0.05), but this ratio was similar in ordinary diabetic patients and control subjects.

CONCLUSIONS—Our results suggest that diabetic patients with the mitochondrial DNA mutation have more severely impaired cardiac autonomic nervous function with sympathovagal imbalance, as compared with ordinary diabetic patients.
Mortality in Concurrent Type 1 Diabetes and Anorexia Nervosa
Authors: Nielsen Søren , Emborg Charlotte , Mølbak Anne-Grethe
Published: March 2007

OBJECTIVE—Previous studies in this field report early occurrence of diabetic complications, but excess mortality, though expectable, has not been reported. We combined information from earlier studies to estimate the mortality for this group of patients.

RESEARCH DESIGN AND METHODS—The observed mortality is analyzed using crude mortality rate (a percentage), standardized mortality ratio (SMR), incidence rate ratio, risk difference, and survival analysis.

RESULTS—After ∼10 years of follow-up, 13 of 510 females with type 1 diabetes, 43 of 658 females with anorexia nervosa (AN), and 8 of 23 concurrent case subjects had died. Mortality rate was 2.2 (per 1,000 person-years) for type 1 diabetes, 7.3 for AN cases, and 34.6 for concurrent cases. Crude mortality rates were 2.5, 6.5, and 34.8%, respectively. SMR was 4.06 in type 1 diabetes, 8.86 in AN, and 14.5 in concurrent cases. Survival analysis indicated between-group differences in mortality.

CONCLUSIONS—Concurrent type 1 diabetes and AN is a rare but serious condition in females. All indexes of mortality evidence excess mortality in this preliminary study. Vigorous and well-directed treatment efforts seem vital for this subpopulation. Collaboration between diabetologists and eating disorder specialists is warranted. The implications of other eating disorders and subclinical eating disorders in diabetic populations need to be analyzed, especially because these conditions are more frequent than clinical eating disorders.
Parent Report of Mealtime Behavior and Parenting Stress in Young Children With Type 1 Diabetes and in Healthy Control Subjects
Authors: Powers Scott W. , Byars Kelly C. , Mitchell Monica J. , Patton Susana R. , Standiford Debbie A. , Dolan Lawrence M.
Published: March 2007

OBJECTIVE—This study assessed parent report of mealtime behavior and parenting stress in preschoolers with type 1 diabetes. It was hypothesized that children with type 1 diabetes would be seen as exhibiting more mealtime behavior problems and that their parents would evidence greater parenting stress when compared with healthy subjects. It was also hypothesized that report of mealtime behavior problems would be positively correlated with parenting stress.

RESEARCH DESIGN AND METHODS—A total of 40 children (aged 1–6 years) with type 1 diabetes were recruited from a pediatric hospital. Another 40 children matched for age, sex, marital status, and socioeconomic status were used as control subjects. Reliable and valid parent report measures, such as the Behavioral Pediatrics Feeding Assessment Scale and the Parenting Stress Index, were used for data collection.

RESULTS—Parents of children with type 1 diabetes reported more behavioral feeding problems than parents of healthy control subjects. Additionally, parents of children with type 1 diabetes reported higher frequencies of parenting behaviors associated with poor nutritional intake and a greater number of parenting problems concerning mealtimes when compared with parents of healthy control subjects. Parents of children with type 1 diabetes also reported higher stress levels than parents of control subjects. A moderate relationship between mealtime behavior problems and general parenting stress was observed for families coping with type 1 diabetes.

CONCLUSIONS—Mealtime problems reported in preschool children with type 1 diabetes are appropriate targets for behavioral intervention. Behavioral observation techniques and training in child behavior management skills should be used in future research aimed at assessing and treating barriers to effective nutrition management in young children with type 1 diabetes.
Effect of a High-Protein, High–Monounsaturated Fat Weight Loss Diet on Glycemic Control and Lipid Levels in Type 2 Diabetes
Authors: Parker Barbara , Noakes Manny , Luscombe Natalie , Clifton Peter
Published: March 2007

OBJECTIVE—To determine the effect of a high-protein (HP) weight loss diet compared with a lower-protein (LP) diet on fat and lean tissue and fasting and postprandial glucose and insulin concentrations.

RESEARCH DESIGN AND METHODS—Replacing dietary protein for carbohydrate (CHO) during energy restriction and weight loss has been effective in sparing lean mass and improving insulin sensitivity in obese subjects but has not been tested in subjects with type 2 diabetes. We compared an HP diet (28% protein, 42% CHO, 28% fat [8% saturated fatty acids, 12% monounsaturated fatty acids, 5% polyunsaturated fatty acids]) with an LP diet (16% protein, 55% CHO, 26% fat [8% saturated fatty acids, 11% monounsaturated fatty acids, 5% polyunsaturated fatty acids]) in 54 obese men and women with type 2 diabetes during 8 weeks of energy restriction (1,600 kcal) and 4 weeks of energy balance. Body composition was determined by dual-energy X-ray absorptiometry at weeks 0 and 12.

RESULTS—Overall, weight loss of 5.2 ±1.8 kg was achieved independently of diet composition. However, women on the HP diet lost significantly more total (5.3 vs. 2.8 kg, P=0.009) and abdominal (1.3 vs. 0.7 kg, P=0.006) fat compared with the women on the LP diet, whereas, in men, there was no difference in fat loss between diets (3.9 vs. 5.1 kg). Total lean mass decreased in all subjects independently of diet composition. LDL cholesterol reduction was significantly greater on the HP diet (5.7%) than on the LP diet (2.7%) (P < 0.01).

CONCLUSIONS—Both dietary patterns resulted in improvements in the cardiovascular disease (CVD) risk profile as a consequence of weight loss. However, the greater reductions in total and abdominal fat mass in women and greater LDL cholesterol reduction observed in both sexes on the HP diet suggest that it is a valid diet choice for reducing CVD risk in type 2 diabetes.
Comorbid Depression is Associated With Increased Health Care Use and Expenditures in Individuals With Diabetes
Authors: Egede Leonard E. , Zheng Deyi , Simpson Kit
Published: March 2007

OBJECTIVE—This study ascertained the odds of diagnosed depression in individuals with diabetes and the relation between depression and health care use and expenditures.

RESEARCH DESIGN AND METHODS—First, we compared data from 825 adults with diabetes with that from 20,688 adults without diabetes using the 1996 Medical Expenditure Panel Survey (MEPS). Second, in patients with diabetes, we compared depressed and nondepressed individuals to identify differences in health care use and expenditures. Third, we adjusted use and expenditure estimates for differences in age, sex, race/ethnicity, health insurance, and comorbidity with analysis of covariance. Finally, we used the Consumer Price Index to adjust expenditures for inflation and used SAS and SUDAAN software for statistical analyses.

RESULTS—Individuals with diabetes were twice as likely as a comparable sample from the general U.S. population to have diagnosed depression (odds ratio 1.9, 95% CI 1.5–2.5). Younger adults (<65 years), women, and unmarried individuals with diabetes were more likely to have depression. Patients with diabetes and depression had higher ambulatory care use (12 vs. 7, P < 0.0001) and filled more prescriptions (43 vs. 21, P < 0.0001) than their counterparts without depression. Finally, among individuals with diabetes, total health care expenditures for individuals with depression was 4.5 times higher than that for individuals without depression ($247,000,000 vs. $55,000,000, P < 0.0001).

CONCLUSIONS—The odds of depression are higher in individuals with diabetes than in those without diabetes. Depression in individuals with diabetes is associated with increased health care use and expenditures, even after adjusting for differences in age, sex, race/ethnicity, health insurance, and comorbidity.
Type 2 Diabetes and Metabolic Syndrome in Filipina-American Women
Authors: Araneta Maria Rosario G. , Wingard Deborah L. , Barrett-Connor Elizabeth
Published: March 2007

OBJECTIVE—To compare the prevalence of type 2 diabetes and features of the metabolic syndrome among Filipina and Caucasian women in San Diego County, California.

RESEARCH DESIGN AND METHODS—Data on several chronic diseases were collected between 1992 and 1999 from community-dwelling Filipina (n=294) and Caucasian (n=379) women aged 50–69 years.

RESULTS—Filipina and Caucasian women did not differ in mean age (59.7 vs. 60 years, respectively), BMI (25.6 vs. 25.4 kg/m2), percentage of body fat (33.5 vs. 34.2%), or waist-to-hip ratio (0.84 vs. 0.83), although Filipinas had larger waist circumferences and higher percentages of truncal fat. Compared with Caucasians, Filipinas were less likely to be obese (BMI ≥ 30 kg/m2, 8.8 vs. 14%, P=0.04) and less likely to smoke, consume alcohol, or take postmenopausal estrogen; Filipinas also had lower levels of HDL cholesterol. Compared with Caucasians, Filipinas had higher prevalence of type 2 diabetes by oral glucose tolerance test criteria (36 vs. 9%) and the metabolic syndrome (34 vs. 13%). These differences persisted after adjusting for age, body size, fat distribution, percentage of body fat, smoking, alcohol consumption, exercise, and estrogen therapy.

CONCLUSIONS—A total of 10% of Filipinas with diabetes were obese, compared with one third of Caucasians with diabetes. The finding of a high prevalence of diabetes in an unstudied nonobese ethnic group reinforces the importance of expanding the study of diabetes to diverse populations. The high prevalence of diabetes in populations who are not of Northern European ancestry may be missed when they are not obese by Western standards.
Posttransplantation Diabetes
Authors: Montori Victor M. , Basu Ananda , Erwin Patricia J. , Velosa Jorge A. , Gabriel Sherine E. , Kudva Yogish C.
Published: March 2007

OBJECTIVES— To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management.

RESEARCH DESIGN AND METHODS— We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence.

RESULTS— Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (<10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P = 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted.

CONCLUSIONS— Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs.
Prevalence of Q-T Interval Dispersion in Type 1 Diabetes and Its Relation With Cardiac Ischemia
Authors: Veglio Massimo , Giunti Sara , Stevens Linda K. , Fuller John H. , Perin Paolo Cavallo ,   The EURODIAB IDDM Complications Study Group
Published: March 2007

OBJECTIVE—The interlead variation in duration of the Q-T interval on the surface electrocardiogram (Q-T interval dispersion [QTd]) has been shown to predict mortality in type 2 diabetic patients. We evaluated the prevalence of QTd prolongation in the EURODIAB population and its relation to corrected Q-T interval (QTc), sex, age, duration of diabetes, blood glucose control, and complications.

RESEARCH DESIGN AND METHODS—A total of 3,042 type 1 diabetic patients were studied. QTc was calculated according to the Bazett’s formula; QTc > 0.44 s was considered abnormally prolonged. QTd was calculated using the difference between the maximum and the minimum QTc in any thoracic lead. QTd >0.080 s was considered abnormally prolonged.

RESULTS—The prevalence of an increased QTd was 7%. A significant relation was observed between QTd prolongation and diastolic blood pressure (P < 0.05). A higher prevalence of QTd prolongation was observed in patients with ischemic heart disease (P = 0.004), whereas no relationship was observed with retinopathy, albumin excretion rate, or measures of somatic and autonomic neuropathy. QTc and QTd were significantly related (P = 0.001); however, a proportion of patients with normal QTd showed a prolonged QTc (>0.44 s).

CONCLUSIONS—In patients with type 1 diabetes, QTd is associated with ischemic heart disease and diastolic blood pressure but not neuropathy. Although QTd is statistically related to duration of QTc, increased QTd and increased QTc identify different patients, and their predictive value deserves prospective evaluation.
The Incidence of Type 1 Diabetes in the Age Group 0–39 Years Has Not Increased in Antwerp (Belgium) Between 1989 and 2000
Authors: Weets Ilse , De Leeuw Ivo H. , Du Caju Marc V.L. , Rooman Raoul , Keymeulen Bart , Mathieu Chantal , Rottiers Raoul , Daubresse Jean-Claude , Rocour-Brumioul Danielle , Pipeleers Daniel G. , Gorus Frans K. ,   The Belgian Diabetes Registry
Published: March 2007

OBJECTIVE—A worldwide increase in the incidence of childhood type 1 diabetes has been observed. Because in various countries the majority of new type 1 diabetic patients are diagnosed in adulthood, we investigated whether the rising incidence of this disorder in children reflects a global increase in the incidence of diabetes or a shift toward earlier clinical presentation.

RESEARCH DESIGN AND METHODS—The incidence of type 1 diabetes presenting before age 40 years was prospectively measured in the Antwerp district over a 12-year period (1989–2000). The completeness of ascertainment was evaluated by the capture-recapture method. Trends in incidence during the study period were analyzed by Poisson regression.

RESULTS—The incidence of type 1 diabetes diagnosed before age 40 years remained constant over the 12-year period, averaging 9.9 cases per 100,000 individuals per year. The incidence was similar in both sexes under age 15 years, but a marked male excess was noted for adult-onset disease, in particular after age 20 years, resulting in a male-to-female ratio of 0.9 under age 15 years vs. 1.6 thereafter (P = 0.001). During the 12-year observation period, there was a significant tendency toward increasing incidence under age 15 years at the expense of a decreasing incidence between ages 15 and 40 years (P = 0.025). The annual increase in incidence averaged 1.8% under age 15 years and 5.0% under age 5 years (P = 0.06).

CONCLUSIONS—Our results indicate that in Belgium, the increasing incidence of childhood type 1 diabetes—especially for children under age 5 years—is not attributable to a global increase in disease incidence, but rather to earlier clinical manifestation. The results suggest that an environmental factor may preferentially accelerate the subclinical disease process in young diabetes-prone subjects.
Advanced Glycation End Products and Endothelial Dysfunction in Type 2 Diabetes
Authors: Tan Kathryn C.B. , Chow Wing-Sun , Ai Victor H.G. , Metz Christine , Bucala Richard , Lam Karen S.L.
Published: March 2007

OBJECTIVE—Data from experimental studies have suggested that the increased formation of advanced glycation end products (AGEs) is one of the causes of endothelial dysfunction in diabetes. This study was performed to investigate whether changes in endothelium-dependent vasodilation, a marker of endothelial function, were related to serum AGEs concentrations in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—For this study, 170 patients with type 2 diabetes and 83 healthy nondiabetic control subjects of similar age were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay. Endothelium-dependent and -independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound.

RESULTS—Serum AGEs were increased in diabetic patients compared with control subjects (4.6 ± 0.7 vs. 3.1 ± 0.8 unit/ml; P < 0.01), and both endothelium-dependent (5.1 ± 2.5 vs. 9.1 ± 4.1%; P < 0.01) and endothelium-independent vasodilation (13.2 ± 4.6 vs. 16.4 ± 5.5%; P < 0.01) were impaired. On univariate analysis of all subjects, serum AGEs correlated with endothelium-dependent vasodilation (r = −0.51, P < 0.01); a weaker association was found with endothelium-independent vasodilation (r = −0.24, P < 0.01). On multiple regression analyses including age, sex, smoking status, and plasma lipids, only serum AGEs remained a significant independent determinant of endothelium-dependent vasodilation (r2 = 0.34, P < 0.01).

CONCLUSIONS—Increased serum concentrations of AGEs in patients with type 2 diabetes is associated with endothelial dysfunction, independent of other cardiovascular risk factors. Further studies to determine whether treatment targeting AGEs will lead to an amelioration of endothelial dysfunction are warranted.
HOMA-Estimated Insulin Resistance Is an Independent Predictor of Cardiovascular Disease in Type 2 Diabetic Subjects
Authors: Bonora Enzo , Formentini Gianni , Calcaterra Francesco , Lombardi Simonetta , Marini Franco , Zenari Luciano , Saggiani Francesca , Poli Maurizio , Perbellini Sandro , Raffaelli Andrea , Cacciatori Vittorio , Santi Lorenza , Targher Giovanni , Bonadonna Riccardo , Muggeo Michele
Published: March 2007

OBJECTIVE—To evaluate whether homeostasis model assessment-estimated insulin resistance (HOMA-IR) is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes.

RESEARCH DESIGN AND METHODS—Conventional CVD risk factors (sex, age, smoking, plasma lipids, blood pressure, and metabolic control) and insulin resistance (estimated by HOMA) were evaluated at baseline in 1,326 patients with type 2 diabetes examined within the Verona Diabetes Complications Study. At baseline and after a mean follow-up of 4.5 years, CVD was assessed by medical history, physical examination, electrocardiography, and echo-Doppler of carotid and lower limb arteries. Death certificates and medical records of subjects who died during the follow-up were carefully scrutinized to identify cardiovascular deaths. In statistical analyses, CVD was an aggregate end point including both fatal and nonfatal coronary, cerebrovascular, and peripheral vascular disease as well as ischemic electrocardiographic abnormalities and vascular lesions identified by echo-Doppler.

RESULTS—At baseline, 441 subjects were coded positive for CVD (prevalent cases). Incident cases numbered 126. Multiple logistic regression analyses showed that, along with sex, age, smoking, HDL/total cholesterol ratio, and hypertension, HOMA-IR was an independent predictor of both prevalent and incident CVD. A 1-unit increase in (log)HOMA-IR value was associated with an odds ratio for prevalent CVD at baseline of 1.31 (95% CI 1.10–1.56, P = 0.002) and for incident CVD during follow-up of 1.56 (95% CI 1.14–2.12, P < 0.001).

CONCLUSIONS—HOMA-IR is an independent predictor of CVD in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes.
Homeostasis Model Assessment of Insulin Resistance in Relation to the Incidence of Cardiovascular Disease
Authors: Hanley Anthony J.G. , Williams Ken , Stern Michael P. , Haffner Steven M.
Published: March 2007

OBJECTIVE—The prospective association between insulin levels and risk of cardiovascular disease (CVD) is controversial. The objective of the present study was to investigate the relationship of the homeostasis model assessment of insulin resistance (HOMA-IR), as well as insulin levels, with risk of nonfatal and fatal CVD over the 8-year follow-up of the San Antonio Heart Study.

RESEARCH DESIGN AND METHODS—Between 1984 and 1988, randomly selected Mexican-American and non-Hispanic white residents of San Antonio participated in baseline examinations that included fasting blood samples for glucose, insulin, and lipids, a glucose tolerance test, anthropometric measurements, and a lifestyle questionnaire. Between 1991 and 1996, 2,569 subjects who were free of diabetes at baseline were reexamined using the same protocol.

RESULTS—Over the follow-up period, 187 subjects experienced an incident cardiovascular event (heart attack, stroke, heart surgery, angina, or CVD death). Logistic regression analysis indicated that risk of a CVD event increased across quintiles of HOMA-IR after adjustment for age, sex, and ethnicity (P for trend <0.0001; quintile 5 vs. quintile 1, odds ratio [OR] 2.52, 95% CI 1.46–4.36). Additional adjustment for LDL, triglyceride, HDL, systolic blood pressure, smoking, alcohol consumption, exercise, and waist circumference only modestly reduced the magnitude of these associations (P for trend 0.02; quintile 5 vs. quintile 1, OR 1.94, 95% CI 1.05–3.59). Furthermore, there were no significant interactions between HOMA-IR and ethnicity, sex, hypertension, dyslipidemia, glucose tolerance (impaired glucose tolerance versus normal glucose tolerance), or obesity. The magnitude and direction of the relationship between insulin concentration and incident CVD were similar.

CONCLUSIONS—We found a significant association between HOMA-IR and risk of CVD after adjustment for multiple covariates. The topic remains controversial, however, and additional studies are required, particularly among women and minority populations.
Weight Control Practices and Disordered Eating Behaviors Among Adolescent Females and Males With Type 1 Diabetes
Authors: Neumark-Sztainer Dianne , Patterson Joan , Mellin Alison , Ackard Diann M. , Utter Jennifer , Story Mary , Sockalosky Joseph
Published: March 2007

OBJECTIVE—This study examines the prevalence of specific weight control practices/disordered eating behaviors and associations with sociodemographic characteristics, BMI and weight perceptions, family functioning, and metabolic control among adolescent females and males with type 1 diabetes.

RESEARCH DESIGN AND METHODS—The study population included 70 adolescent females and 73 adolescent males with type 1 diabetes who completed the AHEAD (Assessing Health and Eating among Adolescents with Diabetes) survey. Data on BMI and glycosylated hemoglobin (HbA1c) were drawn from medical records.

RESULTS—Unhealthy weight control practices were reported by 37.9% of the females and by 15.9% of the males. Among the females, 10.3% reported skipping insulin and 7.4% reported taking less insulin to control their weight. Only one male reported doing either of these behaviors. Weight control/disordered eating behaviors were not associated with age, parental level of education, family structure, or race/ethnicity. Higher levels of weight dissatisfaction tended to be associated with unhealthy weight control/disordered eating; associations with BMI were inconsistent. Family cohesion was negatively associated with disordered eating among females (r = −0.52; P < 0.001) and males (r = −0.41; P < 0.001), but correlations with other measures of family environment (control, independence, and responsibility for diabetes management) were not significant. Correlations between disordered eating and HbA1c levels were significant among females (r = 0.33; P < 0.01) and males (r = 0.26; P < 0.05).

CONCLUSIONS—Special attention is needed for youth with weight concerns and those from less cohesive families to assist in the development of healthy diabetes management behaviors.
Blood Pressure, Lipids, and Obesity Are Associated With Retinopathy
Authors: van Leiden Hendrik A. , Dekker Jacqueline M. , Moll Annette C. , Nijpels Giel , Heine Robert J. , Bouter Lex M. , Stehouwer Coen D.A. , Polak Bettine C.P.
Published: March 2007

OBJECTIVE—To study potential risk factors for retinopathy in diabetic and nondiabetic individuals.

RESEARCH DESIGN AND METHODS—The Hoorn Study is a population-based study including 2,484 50- to 74-year-old Caucasians. A subsample of 626 individuals stratified by age, sex, and glucose tolerance underwent extensive measurements during 1989–1992, including ophthalmologic examination and two-field 45-degree fundus photography. The prevalence of (diabetic) retinopathy was assessed among individuals with normal glucose metabolism (NGM) and impaired glucose metabolism (IGM) and individuals with newly diagnosed diabetes mellitus (NDM) and known diabetes mellitus (KDM) (new World Health Organization 1999 criteria).

RESULTS—The prevalence of retinopathy was 9% in NGM, 11% in IGM, 13% in NDM, and 34% in KDM. Retinopathy worse than minimal nonproliferative diabetic retinopathy was present in 8% in KDM and 0–2% in other glucose categories. The prevalence of retinopathy was positively associated with elevated blood pressure, BMI, cholesterol, and triglyceride serum levels in all glucose categories. The age-, sex-, and glucose metabolism category–adjusted odds ratios were 1.5 (95% CI 1.2–1.9), 1.3 (1.0–1.7), and 1.3 (1.0–1.6) per SD increase of systolic blood pressure, BMI, and total cholesterol concentration, respectively, and 1.2 (1.0–1.5) per 50% increase of triglyceride level. Elevated blood pressure and plasma total and LDL cholesterol levels showed associations with retinal hard exudates.

CONCLUSIONS—Retinopathy is a multifactorial microvascular complication, which, apart from hyperglycemia, is associated with blood pressure, lipid concentrations, and BMI.
Elevated C-Reactive Protein Associates With Early-Stage Carotid Atherosclerosis in Young Subjects With Type 1 Diabetes
Authors: Hayaishi-Okano Rieko , Yamasaki Yoshimitsu , Katakami Naoto , Ohtoshi Kentaro , Gorogawa Shin-Ichi , Kuroda Akio , Matsuhisa Munehide , Kosugi Keisuke , Nishikawa Norikiyo , Kajimoto Yoshitaka , Hori Masatsugu
Published: March 2007

OBJECTIVE—To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes.

RESEARCH DESIGN AND METHODS—The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 ± 3.6 years (± SD), duration of diabetes 14.2 ± 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer.

RESULTS—The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05–1.47 mg/l vs. median 0.14, range 0.05–1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 ± 0.09 vs. 0.72 ± 0.04 mm, P = 0.003; max IMT 0.84 ± 0.11 vs. 0.77 ± 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes.

CONCLUSIONS—Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis.
Intrarenal Hemodynamic Changes After Captopril Test in Patients With Type 2 Diabetes
Authors: Taniwaki Hiromichi , Ishimura Eiji , Kawagishi Takahiko , Matsumoto Naoki , Hosoi Masayuki , Emoto Masanori , Shoji Tetsuo , Shoji Shigeichi , Nakatani Tatsuya , Inaba Masaaki , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—ACE inhibitors are known to be effective in preventing the progression of diabetic nephropathy. Activation of the renin-angiotensin system (RAS) is reported to contribute to intrarenal hemodynamic abnormality in diabetic patients. We examined whether RAS blockade by captopril induces intrarenal hemodynamic changes in normotensive patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—The patients ranged in age from 40 to 65 years (20 men and 20 women). A total of 15 age- and sex-matched healthy individuals served as control subjects. Resistive index (RI) of interlobar arteries was examined by duplex Doppler sonography before and after the oral captopril (25 mg) test.

RESULTS—At baseline, no significant differences in RI values or plasma renin activity (PRA) were seen between the patients and healthy subjects. In healthy subjects, the RI values after the captopril test were significantly higher than baseline values (P < 0.01). However, in patients with type 2 diabetes, both with normoalbuminuria and microalbuminuria, RI values after the test were significantly lower than baseline values (P < 0.001). There were significant negative correlations between ΔRI value and HbA1c (r = −0.458, P < 0.005) and between ΔRI value and baseline PRA in diabetic patients (r = −0.339, P < 0.05). Multiple regression analysis showed that HbA1c and baseline PRA significantly and independently affected the magnitude of decrease in RI values after captopril administration in diabetic patients (R2 = 0.391, P < 0.0001).

CONCLUSIONS—These results indicate that the intrarenal RAS may be activated in diabetic patients, that such activation may be affected by poor glycemic control, and that blockade of RAS activation by ACE inhibitor reduces intrarenal vascular resistance in diabetic patients. The results emphasize the beneficial effects of ACE inhibition in improving intrarenal hemodynamics in diabetic patients.
Non-HDL Cholesterol as a Predictor of Cardiovascular Disease in Type 2 Diabetes
Authors: Lu Weiquan , Resnick Helaine E. , Jablonski Kathleen A. , Jones Kristina L. , Jain Arvind K. , Howard Wm. James , Robbins David C. , Howard Barbara V.
Published: March 2007

OBJECTIVE—To determine whether non-HDL cholesterol, a measure of total cholesterol minus HDL cholesterol, is a predictor of CVD in patients with diabetes.

RESEARCH DESIGN AND METHODS—The Strong Heart Study, a population-based study of CVD and its risk factors in 13 American Indian communities in three geographic areas in the U.S. The baseline examination, conducted between July 1989 and January 1992, consisted of a personal interview, a physical examination, and laboratory tests. Of the 4,549 women and men aged 45−74 years participating in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and nonfatal CVD were collected during the follow-up period through 31 December 1998 (average 9 years).

RESULTS—Multivariable analyses indicated that non-HDL cholesterol is a strong predictor of CVD in men and women with diabetes and is particularly indicative of coronary events. Hazard ratios for the highest tertile of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80, respectively) were higher than those for either LDL cholesterol or triglycerides alone in both men and women and were higher than the ratio of total/HDL cholesterol in women. The utility of non-HDL cholesterol in predicting CVD extended over a wide range of triglyceride concentrations.

CONCLUSIONS—This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes.
Comparison of an Insulin Analog, Insulin Aspart, and Regular Human Insulin With No Insulin in Gestational Diabetes Mellitus
Authors: Pettitt David J. , Ospina Paulina , Kolaczynski Jerzey W. , Jovanovic Lois
Published: March 2007

OBJECTIVE—To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests.

RESEARCH DESIGN AND METHODS—The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed—the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart.

RESULTS—The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg · h · dl−1; P = 0.018), but not with regular insulin (30.2 mg · h · dl−1; P = 0.997), than with no insulin (29.4 mg · h · dl−1).

CONCLUSIONS—This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.
A Cross-Sectional Study of the Effects of Type 2 Diabetes and Other Cardiovascular Risk Factors on Structure and Function of Nonstenotic Arteries of the Lower Limb
Authors: O’Neal David N. , Dragicevic George , Rowley Kevin G. , Ansari Mohamed Z. , Balazs Nicholas , Jenkins Alicia , Best James D.
Published: March 2007

OBJECTIVE—To compare intimal-medial thickness (IMT) and pulse wave conduction velocity (PWCV) in unstenosed arteries of the lower limb in subjects with and without type 2 diabetes and to determine the contribution of a range of cardiovascular risk factors.

RESEARCH DESIGN AND METHODS—IMT and PWCV were determined in lower-limb arteries of 79 subjects with diabetes and 77 euglycemic subjects. Plasma lipids were determined by enzymatic assays, and LDL particle size was measured by gradient gel electrophoresis. Lag time for copper-induced oxidation of LDL was determined. α-Tocopherol, retinol, and ascorbate levels were determined by high-performance liquid chromatography, soluble E-selectin by enzyme-linked immunosorbent assay, and fibrinogen and factor VII by automated assays.

RESULTS—Subjects with diabetes had greater superficial femoral artery (SFA) IMT, popliteal artery (PA) IMT, and SFA PWCV (all P < 0.0001). In univariate analysis, IMT and PWCV correlated with increased waist-to-hip ratio, triglycerides, and fibrinogen and inversely with HDL cholesterol and LDL size. Ascorbate was inversely associated with IMT, and LDL lag time was inversely correlated with PWCV. Subjects with the greatest number of features of the metabolic syndrome had the highest IMT and PWCV.

CONCLUSIONS—Adverse changes in the structure and function of unstenosed lower-limb arteries are present in type 2 diabetes and are associated with features of the metabolic syndrome.
Effect of Leptin Replacement on Intrahepatic and Intramyocellular Lipid Content in Patients With Generalized Lipodystrophy
Authors: Simha Vinaya , Szczepaniak Lidia S. , Wagner Anthony J. , DePaoli Alex M. , Garg Abhimanyu
Published: March 2007

OBJECTIVE—To investigate whether leptin-induced improvements in glycemic control, hyperlipidemia, and insulin sensitivity in hypoleptinemic patients with generalized lipodystrophies are accompanied by reduction in intrahepatic and intramyocellular lipid (IMCL) accumulation.

RESEARCH DESIGN AND METHODS—We examined the effects 8–10 months of subcutaneous leptin replacement therapy on insulin sensitivity, IMCL, and intrahepatic lipid content in two patients with acquired generalized lipodystrophy and one patient with congenital generalized lipodystrophy. All patients had extreme lack of body fat, low plasma leptin levels, and elevated serum triglycerides, but only two had diabetes. Insulin sensitivity was measured by a high-dose (0.2 IU/kg) insulin tolerance test, as well as by hyperinsulinemic-euglycemic glucose clamp studies in two patients. IMCL and intrahepatic lipid content were measured by 1H magnetic resonance spectroscopy. All measurements were obtained before and during 2–10 months of leptin therapy.

RESULTS—Glycemic control and lipoprotein levels markedly improved with leptin therapy in the two diabetic patients, and a slight improvement in lipoprotein levels was seen in the nondiabetic patients. Insulin stimulated glucose uptake during 60–120 min of the euglycemic clamp studies, and the rate of glucose disappearance during the insulin tolerance test nearly doubled with leptin therapy. As compared with the baseline period, after 8–10 months of leptin therapy, the mean intrahepatic lipid content was reduced by ∼80% and the IMCL content was reduced by ∼42%.

CONCLUSIONS—Reduction in IMCL and intrahepatic lipid content may partly explain leptin-induced improvement in insulin sensitivity in patients with generalized lipodystrophy.
Life Course Influences on Insulin Resistance
Authors: Lawlor Debbie A. , Davey Smith George , Ebrahim Shah
Published: March 2007

OBJECTIVE—To assess the independent associations of a broad range of early life risk factors and adult obesity with adult insulin resistance.

RESEARCH DESIGN AND METHODS—This was a cross-sectional study of 1,394 women, aged 60–79 years, from 23 British towns.

RESULTS—There was a strong (independent of confounding factors, other early life factors, and adult waist-to-hip ratio) inverse association between birth weight and insulin resistance in women in the highest third of BMI (>28.77 kg/m2): −0.12 (95% CI −0.19 to −0.04) log homeostasis model assessment (HOMA) score per 1 SD birth weight, but no association between birth weight and insulin resistance in women in the two lowest thirds of BMI (P for interaction = 0.04). Offspring birth weight, own leg length, and childhood manual social class did not interact with adult obesity and were all independently inversely associated with insulin resistance: −0.05 (−0.09 to −0.01) log HOMA score per 1 SD offspring birth weight, −0.09 (−0.12 to −0.06) log HOMA score per 1 SD leg length, and a −0.07 (−0.14 to 0.00) difference in log HOMA score between manual and nonmanual childhood social class. Childhood manual social class and shorter leg length were both independently associated with adverse lipid profiles. BMI and waist-to-hip ratio were independently positively associated with insulin resistance and with all other components of the insulin resistance syndrome.

CONCLUSIONS—Insulin resistance is an important risk factor for type 2 diabetes and coronary heart disease. Our results suggest that genetic factors, intrauterine environment, early childhood, and adult environmental factors are all relevant in determining adult insulin resistance.
Diabetes, Insulin Resistance, and the Metabolic Syndrome in Patients With Acute Myocardial Infarction Without Previously Known Diabetes
Authors: Tenerz Åke , Norhammar Anna , Silveira Angela , Hamsten Anders , Nilsson Göran , Rydén Lars , Malmberg Klas
Published: March 2007

OBJECTIVE—Individuals with diabetes have an increased morbidity from acute myocardial infarction (AMI). Based on an oral glucose tolerance test (OGTT), 40–45% of patients with AMI have diabetes. The objective of this study was to characterize the glucometabolic profile of patients with AMI without known diabetes and to see if sustained glucometabolic perturbations are predictable during the hospital phase of the disease.

RESEARCH DESIGN AND METHODS—A total of 145 patients with AMI and no previous diagnosis of diabetes were subjected to an OGTT at hospital discharge and 3 months thereafter. Based on the OGTT after 3 months, they were defined as having normal glucose tolerance (NGT; n = 50), impaired glucose tolerance (IGT; n = 59), or diabetes (n = 36). Components of the metabolic syndrome, including insulin resistance assessed by homeostasis model assessment (HOMA-IR), were recorded.

RESULTS—Patients with AMI had no changes in insulin resistance from hospital discharge to follow-up. An OGTT and/or a single blood glucose taken 60 min (BG-60) after ingestion of 75 g glucose at hospital discharge were predictors of the outcome of the OGTT at follow-up. With a cutoff value for BG-60 of 8.6 mmol/l, 70% of the patients were correctly predicted as either belonging to the NGT group or the IGT/diabetes group after 3 months. Age, BMI, antihypertensive treatment, HbA1c, fasting blood glucose, blood lipids, insulin, proinsulin, HOMA-IR, and plasminogen activator inhibitor 1 did not add predictive power.

CONCLUSIONS—Patients with AMI and no previous diagnosis of diabetes have no changes in insulin resistance from hospital discharge to a 3-month follow-up. An OGTT or a single BG-60 performed at hospital discharge predicts the diagnosis of IGT or diabetes 3 months thereafter.
Testing the Accelerator Hypothesis
Authors: Kibirige M. , Metcalf B. , Renuka R. , Wilkin T. J.
Published: March 2007

OBJECTIVE—Previous reports have predicted greater risk of type 1 diabetes among people who were heavier as young children. The Accelerator Hypothesis predicts earlier onset in heavier people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. Insulin resistance is a function of fat mass, and increasing body weight in the industrialized world has been accompanied by earlier presentation (i.e., acceleration) of type 2 diabetes. We wanted to establish whether increasing body weight was also asociated with the earlier presentation of type 1 diabetes, as the Accelerator Hypothesis would predict.

RESEARCH DESIGN AND METHODS— The relationships between fatness and age at diagnosis were examined in context of birth weight, weight change since birth, weight at diagnosis, BMI at diagnosis, and BMI 12 months later in 94 children aged 1–16 years (49 boys and 45 girls) presenting for management of acute-onset type 1 diabetes.

RESULTS—BMI standard deviation score (SDS) at diagnosis, weight SDS change since birth, and BMI SDS 12 months later were all inversely related to age at presentation (r = −0.39 to −0.40, P < 0.001). The boys were significantly fatter than the girls (BMI SDS 0.56 vs. −0.08, respectively; P = 0.006) and presented with diabetes at a significantly younger age (6.74 vs. 8.32 years, respectively; P < 0.05). The sex difference in age at diagnosis, however, disappeared when corrected for BMI (P = 0.31), suggesting that fatness or something related to it was the responsible factor.

CONCLUSIONS—The data are consistent with the hypothesis that the age at presentation of type 1 diabetes is associated with fatness. The implications for prevention of type 1 diabetes may be important.