bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological Stress May Induce Diabetes-Related Autoimmunity in Infancy
Authors: Sepa Anneli , Wahlberg Jeanette , Vaarala Outi , Frodi Ann , Ludvigsson Johnny
Published: March 2007

OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.

RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.

RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.

CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.
The Efficacy and Cost of Alternative Strategies for Systematic Screening for Type 2 Diabetes in the U.S. Population 45–74 Years of Age
Authors: Johnson Susan L. , Tabaei Bahman P. , Herman William H.
Published: March 2007

OBJECTIVE—To simulate the outcomes of alternative strategies for screening the U.S. population 45–74 years of age for type 2 diabetes.

RESEARCH DESIGN AND METHODS—We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs.

RESULTS— At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion.

CONCLUSIONS— Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.
Has Control of Hypercholesterolemia and Hypertension in Type 1 Diabetes Improved Over Time?
Authors: Zgibor Janice C. , Wilson Robb R. , Orchard Trevor J.
Published: March 2007

OBJECTIVE—To determine the extent to which patients’ awareness, treatment, and control of hypertension and hypercholesterolemia have changed over time and to examine factors associated with awareness and treatment in a type 1 diabetes population.

RESEARCH DESIGN AND METHODS—Data from six examinations conducted over 10 years from the Pittsburgh Epidemiology of Diabetes Complications Study, a prospective study of subjects with childhood-onset (<17 years of age) type 1 diabetes diagnosed between 1950 and 1980 and followed since 1986, were analyzed. Hypertension and hypercholesterolemia were defined according to the concurrent Joint National Committee and National Cholesterol Education Program Adult Treatment Panel criteria, respectively.

RESULTS—Results demonstrated that awareness of both conditions has improved; however, control is not optimal (e.g., only 32.1 and 28% of those with hypertension in 1986–1988 and 1996–1998 were controlled, while for hypercholesterolemia, the rates were 0 and 5.5%, respectively). Stratified by age-group (18–29, 30–39, and >40 years), the youngest subjects with hypercholesterolemia were least likely to be treated and controlled to goal levels. Older age and physician contact were correlates of awareness and treatment of hypertension at baseline, while presence of renal or coronary complications was also associated with awareness and treatment of both hypertension and hypercholesterolemia at the 10-year follow-up.

CONCLUSIONS—There is a considerable treatment gap, particularly for hypercholesterolemia. Improved treatment of both hypertension and hypercholesterolemia are clearly needed, particularly hypercholesterolemia in younger age-groups who have not yet experienced long-term complications.
Evaluation of Removable and Irremovable Cast Walkers in the Healing of Diabetic Foot Wounds
Authors: Armstrong David G. , Lavery Lawrence A. , Wu Stephanie , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—The purpose of this study was to evaluate the effectiveness of a removable cast walker (RCW) and an “instant” total contact cast (iTCC) in healing neuropathic diabetic foot ulcerations.

RESEARCH DESIGN AND METHODS—We randomly assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations into one of two off-loading treatment groups: an RCW or the same RCW wrapped with a cohesive bandage (iTCC) so patients could not easily remove the device. Subjects were evaluated weekly for 12 weeks or until wound healing.

RESULTS—An intent-to-treat analysis showed that a higher proportion of patients had ulcers that were healed at 12 weeks in the iTCC group than in the RCW group (82.6 vs. 51.9%, P = 0.02, odds ratio 1.8 [95% CI 1.1−2.9]). Of the patients with ulcers that healed, those treated with an iTCC healed significantly sooner (41.6 ± 18.7 vs. 58.0 ± 15.2 days, P = 0.02).

CONCLUSIONS—Modification of a standard RCW to increase patient adherence to pressure off-loading may increase both the proportion of ulcers that heal and the rate of healing of diabetic neuropathic wounds.
Early Growth in Offspring of Diabetic Mothers
Authors: Touger Leslie , Looker Helen C. , Krakoff Jonathan , Lindsay Robert S. , Cook Valerie , Knowler William C.
Published: March 2007

OBJECTIVE—By age 5 years, offspring of diabetic mothers (ODMs) are heavier and have altered glucose metabolism compared with offspring of mothers without diabetes (non-DMs). This study evaluates the growth pattern of ODMs before the age of 5 years.

RESEARCH DESIGN AND METHODS—Anthropometric measures (z scores) from birth, 1.5 years, and 7.7 years in Pima Indian children were compared by maternal diabetes status.

RESULTS—After adjustment for earlier gestational age at delivery (37.8 vs. 39.3 weeks, P < 0.01), ODMs were heavier at birth (z score birth weight 0.49 vs. −0.04, P < 0.01) than non-DMs. At age 1.5 years, ODMs were shorter than the non-DMs (z score = −0.24 vs. 0.12, P < 0.01) but their weight and relative weight (RW; weight adjusted for age, sex, and length or height) were similar. From birth to 1.5 years, ODMs showed significant “catch down” of weight compared with non-DMs (change in weight z score from birth to 1.5 years of ODMs and non-DMs was −0.56 and 0.12, respectively, P < 0.01). By age 7.7 years, ODMs were heavier (weight z score 0.89 vs. −0.07, P < 0.01) but had similar height as non-DMs. Differences in glucose and insulin concentrations at age 7.7 years were dependent on RW.

CONCLUSIONS—ODMs had a dramatically different growth pattern from that of non-DMs. Gestational age–adjusted birth weight was higher. During the first 1.5 postnatal years, the change in weight z score and attained height were reduced. Subsequently, height caught up to that of non-DMs, while weight gain greatly exceeded that of non-DMs.
The Metabolic Syndrome in Older Individuals: Prevalence and Prediction of Cardiovascular Events
Authors: Scuteri Angelo , Najjar Samer S. , Morrell Christopher H. , Lakatta Edward G.
Published: March 2007

OBJECTIVE—The prevalence of the metabolic syndrome, a potent risk factor for cardiovascular diseases (CVDs), has not been adequately explored in older individuals. Moreover, two sets of criteria have been proposed for the definition of metabolic syndrome, one by the World Health Organization (WHO) and one by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). We therefore investigated the prevalence of this syndrome in a subgroup of older participants from the Cardiovascular Health Study (CHS) who were free of CVD at baseline. We also compared the prognostic significance of the two definitions of the metabolic syndrome.

RESEARCH DESIGN AND METHODS—A total of 2,175 subjects from the CHS who were free of CVD at baseline and not taking antihypertensive or lipid-lowering medications were studied. Prevalence of the metabolic syndrome was assessed with both the WHO and ATPIII criteria. The incidence of coronary or cerebrovascular disease was ascertained during a median follow-up time of 4.1 years.

RESULTS—Prevalence of the metabolic syndrome was 28.1% by ATPIII criteria and 21.0% by WHO criteria. The two sets of criteria provided concordant classification for 80.6% of participants. Multivariate Cox propotional hazard models showed that the metabolic syndrome defined with the ATPIII criteria, but not with the WHO criteria, was an independent predictor of coronary or cerebrovascular events and was associated with a 38% increased risk (hazard ratio 1.38 [95% CI 1.06–1.79], P < 0.01).

CONCLUSIONS—Prevalence of the metabolic syndrome in older individuals is ∼21–28% (depending on the definition used). The two sets of criteria have 80% concordance in classifying subjects. As defined by the ATPIII criteria, the metabolic syndrome yields independent prognostic information, even after adjusting for traditional cardiovascular risk factors and the individual domains of the metabolic syndrome.
A Randomized Controlled Trial of Insulin Pump Therapy in Young Children With Type 1 Diabetes
Authors: Fox Larry A. , Buckloh Lisa M. , Smith Shiela D. , Wysocki Tim , Mauras Nelly
Published: March 2007

OBJECTIVE—This study assesses the effects of insulin pump therapy on diabetes control and family life in children 1–6 years old with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Twenty-six children with type 1 diabetes for ≥6 months were randomly assigned to current therapy (two or three shots per day using NPH insulin and rapid-acting analog) or continuous subcutaneous insulin infusion (CSII) for 6 months. After 6 months, current therapy subjects were offered CSII. Changes in HbA1c, mean blood glucose (MBG), hypoglycemia frequency, diabetes-related quality of life (QOL), and parental adjustment were recorded.

RESULTS—Eleven subjects from each group completed the trial (age 46.3 ± 3.2 months [means ± SE]). At baseline, there were no differences between groups in HbA1c, MBG, age, sex, diabetes duration, or parental QOL. Mean HbA1c, MBG, and parental QOL were similar between groups at 6 months. Mean HbA1c and MBG did not change from baseline to 6 months in either group. The frequency of severe hypoglycemia, ketoacidosis, or hospitalization was similar between groups at any time period. Subjects on CSII had more fasting and predinner mild/moderate hypoglycemia at 1 and 6 months. Diabetes-related QOL improved in CSII fathers from baseline to 6 months. Psychological distress increased in current therapy mothers from baseline to 6 months. All subjects continued CSII after study completion.

CONCLUSIONS—CSII is safe and well tolerated in young children with diabetes and may have positive effects on QOL. CSII did not improve diabetes control when compared with injections, despite more mild/moderate hypoglycemia. The benefits and realistic expectations of CSII should be thoroughly examined before starting this therapy in very young children.
Make Your Diabetic Patients Walk
Authors: Di Loreto Chiara , Fanelli Carmine , Lucidi Paola , Murdolo Giuseppe , De Cicco Arianna , Parlanti Natascia , Ranchelli Anna , Fatone Cristina , Taglioni Chiara , Santeusanio Fausto , De Feo Pierpaolo
Published: March 2007

OBJECTIVE—To establish the impact of different amounts of increased energy expenditure on type 2 diabetes care.

RESEARCH DESIGN AND METHODS—Post hoc analysis of long-term effects of different amounts of increased energy expenditure (metabolic equivalents [METS] per hour per week) through voluntary aerobic physical activity was performed in 179 type 2 diabetic subjects (age 62 ± 1 years [mean ± SE]) randomized to a physical activity counseling intervention. Subjects were followed for 2 years and divided into six groups based on their increments in METs per hour per week: group 0 (no activity, n = 28), group 1–10 (6.8 ± 0.3, n = 27), group 11–20 (17.1 ± 0.4, n = 31), group 21–30 (27.0 ± 0.5, n = 27), group 31–40 (37.5 ± 0.5, n = 32), and group >40 (58.3 ± 1.8, n = 34).

RESULTS—At baseline, the six groups did not differ for energy expenditure, age, sex, diabetes duration, and all parameters measured. After 2 years, in group 0 and in group 1–10, no parameter changed; in groups 11–20, 21–30, 31–40, and >40, HbA1c, blood pressure, total serum cholesterol, triglycerides, and estimated percent of 10-year coronary heart disease risk improved (P < 0.05). In group 21–30, 31–40, and >40, body weight, waist circumference, heart rate, fasting plasma glucose, serum LDL and HDL cholesterol also improved (P < 0.05). METs per hour per week correlated positively with changes of HDL cholesterol and negatively with those of other parameters (P < 0.001). After 2 years, per capita yearly costs of medications increased (P = 0.008) by $393 in group 0, did not significantly change in group 1–10 ($206, P = 0.09), and decreased in group 11–20 (−$196, P = 0.01), group 21–30 (−$593, P = 0.009), group 31–40 (−$660, P = 0.003), and group >40 (−$579, P = 0.001).

CONCLUSIONS—Energy expenditure >10 METs · h−1 · week−1 obtained through aerobic leisure time physical activity is sufficient to achieve health and financial advantages, but full benefits are achieved with energy expenditure >20 METs · h−1 · week−1.
Type 1 Diabetes Is Associated With Increased Cyclooxygenase- and Cytokine-Mediated Inflammation
Authors: Basu Samar , Larsson Anders , Vessby Johan , Vessby Bengt , Berne Christian
Published: March 2007

OBJECTIVE—The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood.

RESEARCH DESIGN AND METHODS—Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F2α (a metabolite of prostaglandin F2α [PGF2α] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects.

RESULTS—The inflammatory indicators (urinary 15-keto-dihydro-PGF2α, P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF2α correlated with the degree of glycemic control, HbA1c (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements.

CONCLUSIONS—These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF2α and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
Interaction Between Dietary Lipids and Physical Inactivity on Insulin Sensitivity and on Intramyocellular Lipids in Healthy Men
Authors: Stettler Rodrigue , Ith Michael , Acheson Kevin J. , Décombaz Jacques , Boesch Chris , Tappy Luc , Binnert Christophe
Published: March 2007

OBJECTIVE—To assess the effect of a possible interaction between dietary fat and physical inactivity on whole-body insulin sensitivity and intramyocellular lipids (IMCLs).

RESEARCH DESIGN AND METHODS—Eight healthy male volunteers were studied on two occasions. After 2 days of an equilibrated diet and moderate physical activity, participants remained inactive (bed rest) for 60 h and consumed either a high–saturated fat (45% fat, of which ∼60% was saturated fat [BR-HF]) or a high-carbohydrate (70% carbohydrate [BR-HCHO]) diet. To evaluate the effect of a high-fat diet alone, six of the eight volunteers were restudied after a 2-day equilibrated diet followed by 60 h on a high–saturated fat diet and controlled physical activity (PA-HF). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and IMCL concentrations by 1H-magnetic resonance spectroscopy.

RESULTS—Insulin-mediated glucose disposal was decreased by BR-HF condition (−24 ± 6%, P < 0.05) but did not change with BR-HCHO (+19 ± 10%, NS). BR-HF and BR-HCHO increased IMCL levels (+32 ± 7%, P < 0.05 and +17 ± 8%, P < 0.0011, respectively). Although the increase in IMCL levels with PA-HF (+31 ± 19%, P = 0.12) was similar to that during BR-HF, insulin-mediated glucose disposal (−7 ± 9%, NS) was not decreased.

CONCLUSIONS—These data indicate that physical inactivity and a high–saturated fat diet may interact to reduce whole-body insulin sensitivity. IMCL content was influenced by dietary lipid and physical inactivity but was not directly associated with insulin resistance.
Magnesium Intake, C-Reactive Protein, and the Prevalence of Metabolic Syndrome in Middle-Aged and Older U.S. Women
Authors: Song Yiqing , Ridker Paul M. , Manson JoAnn E. , Cook Nancy R. , Buring Julie E. , Liu Simin
Published: March 2007

OBJECTIVE—The aim of this study was to examine whether and to what extent magnesium intake is related to systemic inflammation and the metabolic syndrome.

RESEARCH DESIGN AND METHODS—We performed a cross-sectional analysis on data from 11,686 women ≥45 years of age participating in the Women’s Health Study who were initially free of cardiovascular disease and cancer and had no use of postmenopausal hormones.

RESULTS—In age- and BMI-adjusted analyses, magnesium intake was inversely associated with plasma C-reactive protein (CRP) concentrations; CRP concentrations were 12% lower in the highest intake quintile than in the lowest (P for trend <0.0001). This association was not appreciably altered by further adjustment for other potential confounding variables including dietary factors; the mean CRP concentrations for ascending quintiles of magnesium intake were 1.50, 1.39, 1.35, 1.34, and 1.31 mg/l (P for trend = 0.0003). This inverse association was stronger for women with a BMI ≥25 kg/m2 (P < 0.0001 for interaction) and those who were current or past smokers (P = 0.0009 for interaction). After adjustment for confounding lifestyle and dietary factors, women in the highest quintile of magnesium intake had 27% lower risk of the metabolic syndrome (defined according to the National Cholesterol Education Program criteria) compared with those in the lowest quintile of intake (odds ratio 0.73 [95% CI 0.60–0.88], P for trend = 0.0008).

CONCLUSIONS—Our results suggest that magnesium intake is inversely associated with systemic inflammation and the prevalence of the metabolic syndrome in middle-aged and older women.
Metabolic Syndrome and Diabetes Are Associated With an Increased Likelihood of Inducible Myocardial Ischemia Among Patients With Subclinical Atherosclerosis
Authors: Wong Nathan D. , Rozanski Alan , Gransar Heidi , Miranda-Peats Romalisa , Kang Xingping , Hayes Sean , Shaw Leslee , Friedman John , Polk Donna , Berman Daniel S.
Published: March 2007

OBJECTIVE—Coronary artery calcification (CAC) is associated with cardiac events and the likelihood of inducible myocardial ischemia. Because metabolic syndrome contributes to atherosclerosis, we assessed whether it also influences the relationship between CAC levels and myocardial ischemia.

RESEARCH DESIGN AND METHODS—We evaluated 1,043 patients without known coronary artery disease (CAD) who underwent stress myocardial perfusion scintigraphy (MPS) and computed tomography. Metabolic syndrome was defined by modified National Cholesterol Education Program criteria. Metabolic abnormalities were present in 313 patients (30%), including 140 with diabetes (with or without metabolic syndrome) and 173 who had metabolic syndrome without diabetes.

RESULTS—Although CAC scores <100 identified a low likelihood (∼2%) of ischemia, the presence (versus absence) of metabolic abnormalities (metabolic syndrome or diabetes) was a predictor of more frequent ischemia among patients with CAC scores of 100–399 (13.0 vs. 3.6%, P < 0.02) and CAC scores ≥400 (23.4 vs. 13.6%, P = 0.03). Similar trends were observed when patients with metabolic syndrome and diabetes were considered separately. Multiple logistic regression revealed the odds of MPS ischemia to be 4.3-fold greater per SD of log CAC (P < 0.001) and 2.0-fold greater in the presence of metabolic abnormalities (P < 0.01).

CONCLUSIONS— Among patients with CAC scores ≥100, metabolic abnormalities, and even metabolic syndrome in the absence of diabetes predicted a higher likelihood of inducible ischemia. These findings suggest the need for assessment of metabolic status when interpreting the results of CAC imaging among patients undergoing such testing because of suspected CAD.
A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia
Authors: Goldberg Ronald B. , Kendall David M. , Deeg Mark A. , Buse John B. , Zagar Anthony J. , Pinaire Jane A. , Tan Meng H. , Khan Mehmood A. , Perez Alfonso T. , Jacober Scott J. ,   for the GLAI Study Investigators
Published: March 2007

OBJECTIVE—Published reports suggest that pioglitazone and rosiglitazone have different effects on lipids in patients with type 2 diabetes. However, these previous studies were either retrospective chart reviews or clinical trials not rigorously controlled for concomitant glucose- and lipid-lowering therapies. This study examines the lipid and glycemic effects of pioglitazone and rosiglitazone.

RESEARCH DESIGN AND METHODS—We enrolled subjects with a diagnosis of type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering agents). After a 4-week placebo washout period, subjects randomly assigned to the pioglitazone arm (n = 400) were treated with 30 mg once daily for 12 weeks followed by 45 mg once daily for an additional 12 weeks, whereas subjects randomly assigned to rosiglitazone (n = 402) were treated with 4 mg once daily followed by 4 mg twice daily for the same intervals.

RESULTS—Triglyceride levels were reduced by 51.9 ± 7.8 mg/dl with pioglitazone, but were increased by 13.1 ± 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments). Additionally, the increase in HDL cholesterol was greater (5.2 ± 0.5 vs. 2.4 ± 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 ± 1.6 vs. 21.3 ± 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005).

CONCLUSIONS—Pioglitazone and rosiglitazone have significantly different effects on plasma lipids independent of glycemic control or concomitant lipid-lowering or other antihyperglycemic therapy. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.
Implementation and Evaluation of a Low-Literacy Diabetes Education Computer Multimedia Application
Authors: Gerber Ben S. , Brodsky Irwin G. , Lawless Kimberly A. , Smolin Louanne I. , Arozullah Ahsan M. , Smith Everett V. , Berbaum Michael L. , Heckerling Paul S. , Eiser Arnold R.
Published: March 2007

OBJECTIVE—To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population.

RESEARCH DESIGN AND METHODS—Five public clinics in Chicago, Illinois, participated in the study with computer kiosks installed in waiting room areas. Two hundred forty-four subjects with diabetes were randomized to receive either supplemental computer multimedia use (intervention) or standard of care only (control). The intervention includes audio/video sequences to communicate information, provide psychological support, and promote diabetes self-management skills without extensive text or complex navigation. HbA1c (A1C), BMI, blood pressure, diabetes knowledge, self-efficacy, self-reported medical care, and perceived susceptibility of complications were evaluated at baseline and 1 year. Computer usage patterns and implementation barriers were also examined.

RESULTS—Complete 1-year data were available for 183 subjects (75%). Overall, there were no significant differences in change in A1C, weight, blood pressure, knowledge, self-efficacy, or self-reported medical care between intervention and control groups. However, there was an increase in perceived susceptibility to diabetes complications in the intervention group. This effect was greatest among subjects with lower health literacy. Within the intervention group, time spent on the computer was greater for subjects with higher health literacy.

CONCLUSIONS—Access to multimedia lessons resulted in an increase in perceived susceptibility to diabetes complications, particularly in subjects with lower health literacy. Despite measures to improve informational access for individuals with lower health literacy, there was relatively less use of the computer among these participants.
Should Diabetes Be Considered a Coronary Heart Disease Risk Equivalent?
Authors: Whiteley Lucinda , Padmanabhan Sandosh , Hole David , Isles Chris
Published: March 2007

OBJECTIVE—The purpose of our study was to confirm or refute the view that diabetes be regarded as a coronary heart disease (CHD) risk equivalent and to test for sex differences in mortality.

RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 7,052 men and 8,354 women aged 45–64 years from Renfrew and Paisley, Scotland, who were first screened in 1972–1976 and followed for 25 years. All-cause mortality was calculated as death per 1,000 person-years. A Cox proportional hazards model was used to adjust survival for age, smoking habit, blood pressure, serum cholesterol, BMI, and social class.

RESULTS—There were 192 deaths in 228 subjects with diabetes and 2,016 deaths in 3,076 subjects with CHD. The highest mortality was in the group with both diabetes and CHD (100.2 deaths/1,000 person-years in men, 93.6 in women) and the lowest in the group with neither (29.2 deaths/1,000 person-years in men, 19.4 in women). Men and women with diabetes only and CHD only formed an intermediate risk group. The adjusted hazard ratio (HR) for CHD mortality in men with diabetes only compared with men with CHD only was 1.17 (95% CI 0.78–1.74; P = 0.56). Corresponding HR for women was 1.97 (1.27–3.08; P = 0.003).

CONCLUSIONS—Diabetes without previous CHD carries a lifetime risk of vascular death as high as that for CHD alone. Women may be at particular risk. Our data support the view that cardiovascular risk factors in diabetes should be treated as aggressively as in people with CHD.
Relationship Between Testosterone Levels, Insulin Sensitivity, and Mitochondrial Function in Men
Authors: Pitteloud Nelly , Mootha Vamsi K. , Dwyer Andrew A. , Hardin Megan , Lee Hang , Eriksson Karl-Fredrik , Tripathy Devjit , Yialamas Maria , Groop Leif , Elahi Dariush , Hayes Frances J.
Published: March 2007

OBJECTIVE— The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men.

RESEARCH DESIGN AND METHODS—A total of 60 men (mean age 60.5 ± 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (Vo2max) and expression of oxidative phosphorylation genes in skeletal muscle.

RESULTS—A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI >25 kg/m2 and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone–binding globulin but not BMI. Testosterone levels also correlated with Vo2max (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001).

CONCLUSIONS—These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.
Noninvasive Diagnosis of Coronary Artery Disease in Patients With Diabetes by Dobutamine Stress Real-Time Myocardial Contrast Perfusion Imaging
Authors: Elhendy Abdou , Tsutsui Jeane M. , O’Leary Edward L. , Xie Feng , McGrain Anna C. , Porter Thomas R.
Published: March 2007

OBJECTIVE—The aim of this study was to assess the accuracy of real-time myocardial contrast perfusion imaging (MCPI) during dobutamine stress in the diagnosis and localization of coronary artery disease (CAD) in patients with diabetes. Myocardial contrast echocardiography is a new technique that allows evaluation of myocardial perfusion. Its utility in diabetic patients has not been defined.

RESEARCH DESIGN AND METHODS—Dobutamine-atropine stress test was performed in conjunction with MCPI using Optison or Definity at rest and at peak stress in 128 patients with diabetes and suspected CAD who underwent coronary angiography within 1 month. CAD was defined as ≥50% stenosis in one or more coronary artery. MCPI was considered diagnostic of CAD in the presence of reversible perfusion abnormalities. The normalcy rate of MCPI was additionally determined in 18 asymptomatic nondiabetic patients with low probability.

RESULTS—CAD was detected in 101 (79%) patients by angiography. Reversible perfusion abnormalities were detected in 90 patients with and 13 patients without CAD. The overall sensitivity of MCPI was 89% (95% CI 83–95), specificity 52% (33–71), and accuracy 81% (75–88). Reversible abnormalities were detected in two or more vascular distributions in 44 of 56 patients with multivessel CAD and in 8 of 63 patients without (sensitivity 68%, specificity 87%, positive predictive value 84%, and accuracy 79%). Regional sensitivity was 75% (65–85) for left anterior descending CAD, 71% (60–83) for left circumflex, and 67% (55–78) for right CAD. MCPI was normal in 16 of the 18 patients with low clinical probability of CAD (normalcy rate 89%).

CONCLUSIONS—MCPI is a useful noninvasive technique for the diagnosis and localization of CAD in diabetic patients. The extent of perfusion abnormalities can identify patients with multivessel CAD with a moderate sensitivity and high specificity.
Clinical, Socioeconomic, and Lifestyle Parameters Associated With Erectile Dysfunction Among Diabetic Men
Authors: Kalter-Leibovici Ofra , Wainstein Julio , Ziv Arnona , Harman-Bohem Ilana , Murad Havi , Raz Itamar ,   for the Israel Diabetes Research Group (IDRG) Investigators
Published: March 2007

OBJECTIVE—Erectile dysfunction is frequently observed in diabetes. The current study aims to assess the association of a comprehensive set of clinical, socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic men.

RESEARCH DESIGN AND METHODS—Participants were randomly selected from male patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants completed a self-reported questionnaire on demographic, socioeconomic, and lifestyle characteristics and on erectile function, using the IIEF-15 (International Index of Erectile Function). Information on diabetes type, duration, treatment, and control; microvascular complications and cardiovascular disease; drug therapy; blood pressure; and lipid levels was also obtained.

RESULTS—Information on erectile function was obtained in 1,040 patients. Their mean age was 57 years, and their median diabetes duration was 8 years (range <1–50). Normal erectile function was found in 13.5% of the patients and severe erectile dysfunction in 30.1%. The characteristics found to be significantly associated with erectile dysfunction [associations presented as adjusted odds ratio (95% CI)] were: patient’s age (5-year increments): 1.38 (1.29–1.48); diabetes duration (5-year increments): 1.16 (1.07–1.26); current HbA1c level (1% increment): 1.10 (1.01–1.19); any microvascular disease: 1.43 (1.09–1.88); cardiovascular disease: 1.78 (1.27–2.48); and diuretic treatment: 1.78 (1.09–2.91). Leisure time and work-related physical activity and consumption of small amounts of alcohol were found to be protective: 0.51 (0.36–0.72) and 0.70 (0.51–0.97), respectively.

CONCLUSIONS—In diabetic men, erectile dysfunction severity increases with age and diabetes duration, poor glycemic control, presence of microvascular complications, diuretic treatment, and cardiovascular disease. Physical activity and alcohol intake may be protective. These findings can guide clinicians in taking preventive measures and undertaking early screening and treatment in high-risk patients.
Osteoprotegerin Is Associated With Silent Coronary Artery Disease in High-Risk but Asymptomatic Type 2 Diabetic Patients
Authors: Avignon Antoine , Sultan Ariane , Piot Christophe , Elaerts Stéphane , Cristol Jean Paul , Dupuy Anne Marie
Published: March 2007

OBJECTIVE—Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured.

RESULTS—The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18–58.68], P = 0.034) and nephropathy (21.98 [1.24–388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients.

CONCLUSIONS—Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.
Alcohol Intake Among Women and Its Relationship to Diabetes Incidence and All-Cause Mortality
Authors: Lapidus Leif , Bengtsson Calle , Bergfors Elisabet , Björkelund Cecilia , Spak Fredrik , Lissner Lauren
Published: March 2007

OBJECTIVE— The purpose of the study was to explore the predictive value of women’s alcohol habits in relation to incidence of diabetes and all-cause mortality. Special attention was paid to potential confounding factors such as age, heredity, education, socioeconomic group, physical inactivity, smoking, blood pressure, serum lipids, and, in particular, obesity.

RESEARCH DESIGN AND METHODS— A longitudinal population study consisting of a representative sample of 1,462 women aged 38–60 started in Göteborg, Sweden, in 1968–1969 monitoring for diabetes and mortality over 32 years.

RESULTS— Alcohol intake, expressed as intake of wine, hard liquor, or total grams of alcohol, was significantly negatively associated to 32-year diabetes incidence independent of age. However, the apparently protective effect of the alcohol variables was attenuated when BMI was included as a covariate. The inverse relationship between wine intake and diabetes did not remain after adjustment for physical activity or socioeconomic group. Beer and wine intake were significantly negatively associated to mortality. Increase of alcohol intake between the examination in 1968–1969 and 1980–1981 was significantly inversely related to the mortality between 1980–1981 and 2000–2001 and independent of all covariates. No relationship was observed between an increase in alcohol intake and diabetes incidence. However, after adjustment for age, family history, and basal alcohol consumption altogether, a significant inverse relationship was observed between increase of alcohol and diabetes incidence.

CONCLUSIONS— The initially significant inverse associations observed between alcohol and diabetes as well as mortality were dependent on a number of confounding factors, of which BMI seems to be the most important.
Infection and Diabetes Mellitus
Authors: Wheat L Joseph
Published: March 2007

Most physicians believe that diabetic individuals are predisposed to infections and that infection complicates the control of the diabetes. However, only bacteriuria can be documented to occur with increased frequency in diabetic compared with nondiabetic patients. Although most bacteriuric diabetic patients are asymptomatic, severe infections such as emphysematous pyelonephritis, papillary necrosis, perinephric abscess, and candida pyelonephritis may occur. Tuberculosis, once a proven threat to diabetic individuals, is a less serious problem now that effective screening and chemoprophylaxis programs have been initiated. Several unusual infections such as malignant external otitis, rhinocerebral mucormycosis, emphysematous pyelonephritis, and emphysematous cholecystitis occur also exclusively in diabetics. Foot infections are very important in diabetic patients; successful treatment requires accurate assessment of the extent and etiology of the infections and often involves surgery as well as broad antibiotic coverage. The important problem of infection in diabetic patients deserves careful evaluation. Questions such as do diabetic individuals have a higher incidence of infection, why are diabetic patients predisposed to infection, why is necrosis common in several of the infections, what is the course of asymptomatic bacteriuria, who do diabetic patients develop foot infections, and how should foot infections be prevented and treated should be topics of clinical investigation.
Biologic Activity and Pharmacokinetics of Biosynthetic Human Insulin in the Rat
Authors: Halban Philippe A , Berger Michael , Gjinovci Asllan , Renold Albert E
Published: March 2007

The biologic potency (plasma glucose depression) of pancreatic human insulin was compared with that of biosynthetic human insulin (BHI), manufactured by recombinant DNA techniques in bacteria, following intravenous injection in rats. The specific activity of the pancreatic human insulin was 32 U/mg, while that for BHI was 27 U/mg. These values were not significantly difference, but were higher than the value for pancreatic pork insulin (25 U/mg). The pharmacokinetics of i.v. injected A14-mono-125I-insulin (pork) were found to be similar to those observed for semisynthetic [3H]insulin (pork), the respective metabolic clearance rates (MCR) being 20.8 ± 0.8 ml/min/kg (N = 4) and 23.6 ± 1 ml/min/kg (N = 5) (P > 0.1). The MCR for A14-mono-125I-BHI was 24.6 ± 2.2 ml/min/kg (N = 4), which was significantly higher (P > 0.025) than the value for A14-mono-125I-pork insulin. BHI is thus no less active than pork insulin in rats and possibly somewhat more active. The small difference in activity may be due to increased affinity for rat insulin receptors, resulting in a more rapid MCR for BHI. In addition, the A14-monoiodinated insulin tracer used in these studies is indistinguishable from semisynthetic [3H]insulin in terms of its rate of clearance, indicating that the insulin molecule has not suffered any iodination damage and is thus a valid tracer for metabolic and receptor studies.
Hemoglobin A1c Compared with Three Conventional Measures of Diabetes Control
Authors: Blanc Marc H , Barnett Donald M , Gleason Ray E , Dunn Peter J , Soeldner J Stuart
Published: March 2007

Control of diabetes was studied during an 8-wk camp program in 18 insulin-dependent counselors with a mean age of 19.3 yr and a mean duration of diabetes of 11.4 yr. A composite score was obtained for each subject derived from three factors: percent sugar-free urine tests, 24-h glucose excretion as percent of carbohydrate intake, and mean preprandial blood glucose (MPBG). The mean hemoglobin A1c (HbA1c) at the end of the period was 8.3 ± 1.6% (± SD) (normal range, 4–6%). Scores ranging from 24 (fair control) to 45 (excellent control) showed a significant inverse correlation with HbA1c (r = – 0.807, P < 0.001) and MPBG (r = – −0.674, P < 0.01). HbA1c showed a significant correlation with the MPBG (r = 0.693, P < 0.01). The HbA1c level was predicted better by percent sugar-free urine tests than by the 24-h glucose excretion. Thus it appears that accurate quantification of control may be obtained by using a scoring system. Critical comparison of HbA1c levels to various glycemic indices may provide useful alternatives for estimating diabetes control.
successful Treatment of Extremely Brittle, Insulin-dependent Diabetes with a Novel Subcutaneous Insulin Pump Regimen
Authors: Nathan David M
Published: March 2007

Brittle, insulin-dependent diabetic patients with extremely labile glucose control requiring frequent hospitalizations were treated with a continuous subcutaneous insulin infusion delivered with a programme ble pump. As reported by others, the patients did not improve with a regimen of preprandial boluses superimposed on a continuous single-rate infusion. However, they demonstrated dramatic clinical and metabolic improvement with a modified pump regimen that delivered a variable square-wave insulin infusion and avoided any boluses. These very difficult patients can benefit by insulin pump therapy.
Use of a Physiologic Pharmacokinetic Model of Glucose Homeostasis for Assessment of Performance Requirements for Improved Insulin Therapies
Authors: Sorensen John T , Colton Clark K , Hillman Robert S , Soeldner J Stuart
Published: March 2007

Methods are presented for assessing insulin therapies using a physiologic pharmacokinetic model of glucose homeostasis in man. The model is composed of simultaneous differential equations that represent physiologic compartments and spaces in which glucose and insulin are distributed and undergo metabolic reactions. The model is used to simulate clinical experiments in which blood glucose concentration is controlled by artificial device therapies. Predictions of the theoretical model for responses of normal and diabetic individuals to standard intravenous and oral glucose tolerance tests are compared to clinical data. Reasonable agreement is obtained between predictions of the computer simulations and clinical data for normal individuals. The responses of a diabetic person to oral glucose tolerance tests are simulated by removal of the pancreas from the glucose homeostasis model and introduction of insulin into the model by a prescribed therapy. Model simulations reaffirm expectations concerning the poor blood glucose control attainable by intramuscular insulin injection. Simulations of blood glucose regulation by an artificial pancreas using closed-loop feedback control for controlling insulin delivery rate reveal hyperinsulinemia that results in a net shift in the deposition of a glucose load from liver to peripheral tissues. Simulations of this system in which the time delay for glucose measurement is varied from 1.5 to 30 min show that increases in sensor delay result in progressive loss in glucose regulation, exacerbation of hyperinsulinemia, and increased insulin requirements.
Potentiometric Measurement of Glucose Concentration with an Immobilized Glucose Oxidase/Catalase Electrode
Authors: Wingard Lemuel B , Liu Chung C , Wolfson Sidney K , Yao Shang J , Drash Allan L
Published: March 2007

A series of enzyme electrodes for measurement of glucose have been constructed. The electrodes contain glucose oxidase immobilized on platinum, either with or without co-immobilization of catalase. When placed in buffered glucose, the enzyme electrodes show a potentiometric response to glucose with respect to a Ag/AgCl reference electrode. This response is reproducible in the physiologic range of glucose concentrations. The immobilization technique, some of the environmental variables such as oxygen concentration and pH, and several compounds that might interfere with the selectivity of the enzyme electrodes for glucose have received preliminary study. This direct potentiometric approach is undergoing further evaluation to determine the basic electrochemical mechanism responsible for the potentiometric signal and whether it can be adapted for continuous in vivo monitoring of the glucose concentration in body fluids.
Impaired Glucose Tolerance and Diabetes Mellitus in Elderly Subjects
Authors: Agner Erik , Thorsteinsson Birger , Erikson Marie
Published: March 2007

In a 10-yr prospective population study 406 subjects who were 70 yr old received an oral glucose tolerance test. Of these subjects 169 were retested at 80. Three sets of diagnostic criteria were evaluated, of which the WHO criteria are recommended for screening studies in this age group. The prevalences of diabetes mellitus (DM) and impaired glucose tolerance (IGT) according to the latter criteria were 10% vand 26% at 70 and 12% and 35% at 80 in men and women. Excess 10-yr mortality was seen in both sexes when DM existed at 70, and in men also when IGT existed at this age. The excess mortality in men could solely—and in women partly—be explained by cardiovascular diseases. The 10-yr incidence of DM was 20% if IGT existed at 70, but only 4% when normal glucose tolerance was present at 70.