bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin Detemir Is Associated With More Predictable Glycemic Control and Reduced Risk of Hypoglycemia Than NPH Insulin in Patients With Type 1 Diabetes on a Basal-Bolus Regimen With Premeal Insulin Aspart
Authors: Vague Philippe , Selam Jean-Louis , Skeie Svein , De Leeuw Ivo , Elte Jan W.F. , Haahr Hanne , Kristensen Allan , Draeger Eberhard
Published: March 2007

OBJECTIVE—Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals.

RESEARCH DESIGN AND METHODS—This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively.

RESULTS—After 6 months, comparable HbA1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (−0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300–0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001).

CONCLUSIONS—Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.
Incidence of Type 1 Diabetes in Lithuanians Aged 0–39 Years Varies by the Urban-Rural Setting, and the Time Change Differs for Men and Women During 1991–2000
Authors: Pundziute-Lyckå Auste , Urbonaite Brone , Ostrauskas Rytas , Zalinkevicius Rimas , Dahlquist Gisela G.
Published: March 2007

OBJECTIVE—Type 1 diabetes has been associated with factors related to welfare and social class. During the past decade, Lithuania has experienced a transition period, leading to dramatic changes in the socioeconomic structure of the society.

RESEARCH DESIGN AND METHODS—Incidence in the group aged 0–39 years by urban-rural setting (cities >100,000 inhabitants, towns, and rural areas), period (1991–1995 and 1996–2000), age, and sex were studied using Poisson regression.

RESULTS—The age- and sex-standardized incidence per 100,000 inhabitants per year was higher in men aged 0–39 years than in women (9.5 and 6.9, respectively, incidence rate ratio [IRR] = 1.39, P < 0.001). Incidence was lower in rural areas than in towns and cities (7.1, 9.0, and 8.8, respectively, P < 0.001). The urban-rural differences in incidence were most marked among children aged 0–9 years. From 1991–1995 to 1996–2000, the overall incidence increased from 8.7 to 10.5 (IRR = 1.22, P = 0.001) in men and from 6.2 to 7.8 (IRR = 1.25, P = 0.002) in women. For men, the increase over time occurred predominantly in the cities, from 8.4 to 11.8 (IRR = 1.40, P < 0.001), and in the older age-groups. In contrast, for women, the incidence increased more in small towns and rural areas, from 5.8 to 7.7 (IRR = 1.33, P = 0.003), and in the younger age-groups.

CONCLUSIONS—The incidence of type 1 diabetes in Lithuania differs depending on the urban-rural setting, and the pattern of change over time differs between the sexes, both by urban-rural setting and age-group. The findings support the theory that lifestyle-related factors connected to socioeconomic status are important for the occurrence of type 1 diabetes.
The Confidence in Diabetes Self-Care Scale
Authors: van der Ven Nicole C.W. , Weinger Katie , Yi Joyce , Pouwer Frans , Adèr Herman , van der Ploeg Henk M. , Snoek Frank J.
Published: March 2007

OBJECTIVE—To examine psychometric properties of the Confidence in Diabetes Self-Care (CIDS) scale, a newly developed instrument assessing diabetes-specific self-efficacy in Dutch and U.S. patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Reliability and validity of the CIDS scale were evaluated in Dutch (n = 151) and U.S. (n = 190) outpatients with type 1 diabetes. In addition to the CIDS scale, assessment included HbA1c, emotional distress, fear of hypoglycemia, self-esteem, anxiety, depression, and self-care behavior. The Dutch sample completed additional measures on perceived burden and importance of self-care. Test-retest reliability was established in a second Dutch sample (n = 62).

RESULTS—Internal consistency (Cronbach’s α = 0.86 for Dutch patients and 0.90 U.S. patients) and test-retest reliability (Spearman’s r = 0.85, P < 0.0001) of the CIDS scale were high. Exploratory factor analysis showed one strong general factor. Spearman’s correlations between the CIDS scale and other measures were moderate and in the expected directions, and high HbA1c levels were associated with low CIDS scores in the U.S. sample only. Low CIDS scores were positively associated with self-care but not with glycemic control in the original samples. CIDS scores in the U.S. and Dutch samples did not show any statistically significant differences. U.S. men had higher CIDS scores than U.S. women.

CONCLUSIONS—The CIDS scale is a reliable and valid measure of diabetes-specific self-efficacy for use in patients with type 1 diabetes. High psychometric similarity allows for cross-cultural comparisons.
Changes in Diabetes Self-Care Behaviors Make a Difference in Glycemic Control
Authors: Jones Helen , Edwards Lynn , Vallis T. Michael , Ruggiero Laurie , Rossi Susan R. , Rossi Joseph S. , Greene Geoffrey , Prochaska James O. , Zinman Bernard
Published: March 2007

OBJECTIVE—This study compared diabetes Treatment As Usual (TAU) with Pathways To Change (PTC), an intervention developed from the Transtheoretical Model of Change (TTM), to determine whether the PTC intervention would result in greater readiness to change, greater increases in self-care, and improved diabetes control.

RESEARCH DESIGN AND METHODS—Participants were stratified by diabetes treatment and randomized to treatment with PTC or TAU as well as being randomized regarding receipt of free blood testing strips. The PTC consisted of stage-matched personalized assessment reports, self-help manuals, newsletters, and individual phone counseling designed to improve readiness for self-monitoring of blood glucose (SMBG), healthy eating, and/or smoking cessation. A total of 1,029 individuals with type 1 and type 2 diabetes who were in one of three pre-action stages for either SMBG, healthy eating, or smoking were recruited.

RESULTS—For the SMBG intervention, 43.4% of those receiving PTC plus strips moved to an action stage, as well as 30.5% of those receiving PTC alone, 27.0% of those receiving TAU plus strips, and 18.4% of those receiving TAU alone (P < 0.001). For the healthy eating intervention, more participants who received PTC than TAU (32.5 vs. 25.8%) moved to action or maintenance (P < 0.001). For the smoking intervention, more participants receiving PTC (24.3%) than TAU (13.4%) moved to an action stage (P < 0.03). In intention-to-treat (ITT) analysis of those receiving the SMBG intervention, PTC resulted in a greater reduction of HbA1c than TAU, but this did not reach statistical significance. However, in those who moved to an action stage for the SMBG and healthy eating interventions, HbA1c was significantly reduced (P < 0 0.001). Individuals who received the healthy eating intervention decreased their percentage of calories from fat to a greater extent (35.2 vs. 36.1%, P = 0.004), increased servings of fruit per day (1.89 vs. 1.68, P = 0.016), and increased vegetable servings (2.24 vs. 2.06, P = 0.011) but did not decrease weight. However, weight loss for individuals who received the healthy eating intervention and who increased SMBG frequency as recommended was significantly greater, with a 0.26-kg loss in those who remained in a pre-action SMBG stage but a 1.78-kg loss in those performed SMBG as recommended (P ≤ 0. 01).

CONCLUSIONS—This study demonstrates that this intervention has the potential of positively impacting the health of broad populations of individuals with diabetes, not just the minority who are ready for change.
Soluble Tumor Necrosis Factor-α Receptors in Young Obese Subjects With Normal and Impaired Glucose Tolerance
Authors: Dzienis-Straczkowska Stella , Straczkowski Marek , Szelachowska Malgorzata , Stepien Agnieszka , Kowalska Irina , Kinalska Ida
Published: March 2007

OBJECTIVE— Tumor necrosis factor-α (TNF-α) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes. Data about TNF-α and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study was to assess plasma TNF-α, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects with IGT.

RESEARCH DESIGN AND METHODS— A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical parameters were measured and euglycemic-hyperinsulinemic clamp was performed.

RESULTS— Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat, plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity was present only in the obese-NGT group.

CONCLUSIONS— Our data suggest that TNF-α receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings indicate that the TNF-α system might contribute to the development of insulin resistance in glucose-intolerant subjects.
Assessing the Shape of the Glucose Curve During an Oral Glucose Tolerance Test
Authors: Tschritter Otto , Fritsche Andreas , Shirkavand Fatemeh , Machicao Fausto , Häring Hans , Stumvoll Michael
Published: March 2007

OBJECTIVE—The oral glucose tolerance test (OGTT) is used to define the status of glucose tolerance based on the plasma glucose level at 120 min. The purpose of the present study was to identify parameters that determine the shape of the plasma glucose course measured at 0, 30, 60, 90, and 120 min during an OGTT.

RESEARCH DESIGN AND METHODS—OGTT data from 551 subjects (485 with normal glucose tolerance [NGT] and 66 with impaired glucose tolerance [IGT]) were analyzed. We distinguished between “monophasic,” “biphasic,” and unclassified glucose shapes. A “shape” index based on the extent and the direction of the plasma glucose change in the second hour allowed us to treat shape as a continuous variable.

RESULTS—In the biphasic group, the NGT-to-IGT ratio was slightly higher (173/20 vs. 209/40, P = 0.08) and the male-to-female ratio was lower (60/133 vs. 120/129, P = 0.0003). Subjects with a biphasic shape had significantly lower age, BMI, waist-to-hip ratio (WHR), HbA1c, plasma glucose, and area under the insulin curve (insulinAUC) and a better estimated insulin sensitivity and secretion (using validated indexes) than monophasic subjects (all P < 0.05). By adjusting this shape index for glucoseAUC (as continuous measure of glucose tolerance), correlations with age, BMI, WHR, HbA1c, and insulinAUC were completely abolished. The adjusted shape index was still higher in female than in male subjects but lower in IGT than in NGT subjects (both P = 0.0003). Finally, we tested common polymorphisms in insulin receptor substrate (IRS)-1, IRS-2, calpain-10, hepatic lipase, and peroxisome proliferator-activated receptor-γ for association with the shape index.

CONCLUSIONS—We conclude that the plasma glucose shape during an OGTT depends on glucose tolerance and sex. In addition, genetic factors seem to play a role. The shape index may be a useful metabolic screening parameter in epidemiological and genetic association studies.
Effect of Family History of Type 2 Diabetes on the Intima-Media Thickness of the Common Carotid Artery in Normal-Weight, Overweight, and Obese Glucose-Tolerant Young Adults
Authors: Pannacciulli Nicola , De Pergola Giovanni , Ciccone Marco , Rizzon Paolo , Giorgino Francesco , Giorgino Riccardo
Published: March 2007

OBJECTIVE—To evaluate the effect of a first-degree family history of type 2 diabetes on the intima-media thickness of the common carotid artery (IMT-CCA), a surrogate marker of coronary atherosclerosis, in glucose-tolerant young adults.

RESEARCH DESIGN AND METHODS—IMT-CCA was measured by high-resolution B-mode ultrasound imaging in 401 individuals aged 18–45 years with normal glucose tolerance (NGT). A total of 213 subjects had no family history of type 2 diabetes until the third generation (FH−), and 188 subjects had a family history of type 2 diabetes (FH+), defined as having one or both parents with type 2 diabetes. Other measurements included: central fat accumulation, evaluated by waist circumference; insulin resistance, estimated by homeostasis model assessment for insulin resistance (HOMAIR); systolic and diastolic blood pressure; fasting and postload concentrations of glucose; fasting insulin levels; and lipid profile.

RESULTS—IMT-CCA and both 1- and 2-h postchallenge glucose concentrations were significantly higher in FH+ than in FH− subjects. IMT-CCA was positively correlated with age, BMI, waist circumference, triglycerides, systolic and diastolic blood pressure levels, basal glucose concentrations, 1- and 2-h postchallenge glucose concentrations, and HOMAIR. IMT-CCA was inversely associated with HDL cholesterol. After multivariate analysis, IMT-CCA maintained a significant association with family history of type 2 diabetes, BMI, waist circumference, HDL cholesterol, diastolic blood pressure, and fasting glucose.

CONCLUSIONS—This study indicates that a genetic predisposition to type 2 diabetes, probably in association with slightly elevated glucose levels, may accelerate the development of atherosclerosis and increase the risk for coronary heart disease in glucose-tolerant individuals.
Carotid Atherosclerosis and Coronary Heart Disease in the Metabolic Syndrome
Authors: Bonora Enzo , Kiechl Stefan , Willeit Johann , Oberhollenzer Friedrich , Egger Georg , Bonadonna Riccardo C. , Muggeo Michele
Published: March 2007

OBJECTIVE— The present study aimed at prospectively evaluating carotid atherosclerosis and coronary heart disease (CHD) in subjects with the metabolic syndrome.

RESEARCH DESIGN AND METHODS— Within a prospective population-based survey examining 888 subjects aged 40–79 years, 303 subjects were identified as fulfilling World Health Organization (WHO) criteria and 158 as fulfilling the National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria for diagnosing the metabolic syndrome. The 5-year change in carotid status, as assessed by echo-duplex scanning, and incident fatal and nonfatal CHD, as assessed by medical history and death certificates, were compared in subjects with the metabolic syndrome and in the rest of the sample (control subjects).

RESULTS— Compared with the control subjects, subjects with the metabolic syndrome by WHO criteria had an increased 5-year incidence and progression of carotid atherosclerosis: 51 vs. 35% developed new plaques (P = 0.021) and 34 vs. 19% developed carotid stenosis >40% (P = 0.002) after adjusting for several confounders. Subjects with the metabolic syndrome by these criteria also had an increased incidence of CHD during follow-up: 8 vs. 3% in control subjects (P = 0.012). Similar results were found when the NCEP-ATPIII criteria were used.

CONCLUSIONS— Subjects with the metabolic syndrome are at increased risk for both progressive carotid atherosclerosis and CHD.
New Insights on Oxidative Stress and Diabetic Complications May Lead to a “Causal” Antioxidant Therapy
Authors: Ceriello Antonio
Published: March 2007

Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. However, intervention studies with classic antioxidants, such as vitamin E, failed to demonstrate any beneficial effect. Recent studies demonstrate that a single hyperglycemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain seems to be the first and key event in the activation of all other pathways involved in the pathogenesis of diabetic complications. These include increased polyol pathway flux, increased advanced glycosylation end product formation, activation of protein kinase C, and increased hexosamine pathway flux. Superoxide overproduction is accompanied by increased nitric oxide generation, due to an endothelial NOS and inducible NOS uncoupled state, a phenomenon favoring the formation of the strong oxidant peroxynitrite, which in turn damages DNA. DNA damage is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase activation in turn depletes the intracellular concentration of its substrate NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, and produces an ADP-ribosylation of the GAPDH. These processes result in acute endothelial dysfunction in diabetic blood vessels that, convincingly, also contributes to the development of diabetic complications. These new findings may explain why classic antioxidants, such as vitamin E, which work by scavenging already-formed toxic oxidation products, have failed to show beneficial effects on diabetic complications and may suggest new and attractive “causal” antioxidant therapy. New low–molecular mass compounds that act as SOD or catalase mimetics or l-propionyl-carnitine and lipoic acid, which work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such a strategy, and preliminary studies support this hypothesis. This “causal” therapy would also be associated with other promising tools such as LY 333531, PJ34, and FP15, which block the protein kinase β isoform, poly(ADP-ribose) polymerase, and peroxynitrite, respectively. While waiting for these focused tools, we may have other options: thiazolinediones, statins, ACE inhibitors, and angiotensin 1 inhibitors can reduce intracellular oxidative stress generation, and it has been suggested that many of their beneficial effects, even in diabetic patients, are due to this property.
Motivational Brochures Increase the Number of Medicare-Eligible Persons With Diabetes Making Therapeutic Footwear Claims
Authors: LeMaster Joseph W. , Sugarman Jonathan R. , Baumgardner Greg , Reiber Gayle E.
Published: March 2007

OBJECTIVE—This study tests the hypothesis that Medicare beneficiaries at high risk of foot complications who are mailed a motivational brochure describing the Medicare diabetes-related therapeutic footwear benefit will increase their therapeutic footwear–related Medicare claims.

RESEARCH DESIGN AND METHODS—In this quasi-experimental study, a motivational brochure was mailed in the summer of 1997 to 5,872 Medicare beneficiaries in Washington, Alaska, and Idaho who were identified as being at high risk for foot-related claims on the basis of their prior Medicare claims history. Beneficiaries were identified through footwear claims made in these states—and also in three comparison states (Oregon, Montana, and Wyoming)—during the 18 months before and after the mailing. Linear regression was used to compare the number of persons making claims in the intervention states with the comparison states before, at the time of, and after the mailing.

RESULTS—Before the intervention, the number of persons making claims was increasing in the nonintervention states and decreasing in the intervention states. During the first month after the intervention mailing, the number of persons making claims remained nearly the same in nonintervention states, but increased 13 persons per month in intervention states (95% CI 3.5–11 persons/month). After the intervention, the number of persons making claims continued to increase similarly in both intervention and nonintervention states.

CONCLUSIONS—Mailed motivational brochures were associated with an increase in the number of persons making therapeutic footwear claims. Randomized trials should confirm these findings.
Surrogate End Points for the Treatment of Diabetic Neuropathic Foot Ulcers
Authors: Margolis David J. , Gelfand Joel M. , Hoffstad Ole , Berlin Jesse A.
Published: March 2007

OBJECTIVE—The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care.

RESEARCH DESIGN AND METHODS—This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated.

RESULTS—Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care.

CONCLUSIONS—The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful.
Effect of Nurse-Directed Diabetes Care in a Minority Population
Authors: Davidson Mayer B.
Published: March 2007

OBJECTIVE—To determine whether diabetes care directed by nurses following detailed protocols and algorithms and supervised by a diabetologist results in meeting the evidence-based American Diabetes Association (ADA) process and outcome measures more often than care directed under usual care in a minority population.

RESEARCH DESIGN AND METHODS—Studies were mainly conducted in two Los Angeles County clinics. In clinic A, nurse-directed diabetes care was provided to 252 patients (92% Hispanic and 2% African-American) referred by their primary care providers. These patients were hierarchically matched with 252 diabetic patients in clinic B (79% Hispanic and 19% African American). When nurse-directed care was abruptly discontinued in clinic A for administrative reasons, it was reestablished in clinic B. Those patients were randomly selected from a teaching clinic, and the outcomes in 114 patients who completed 1 year were compared with outcomes derived the year before receiving nurses’ care. The following process and outcome measures were assessed in the study: 1) number of visits, 2) diabetes education, 3) nutritional counseling, 4) HbA1c, 5) lipid profiles, 6) eye exams, 7) foot exams, 8) renal evaluations, and 9) ACE inhibitor therapy in appropriate patients.

RESULTS—For patients under nurse-directed diabetes care in both clinics A and B, almost all process measures were carried out significantly more frequently than for the appropriate control patients. Under the care of nurses in clinic A, HbA1c levels fell 3.5% from 13.3 to 9.8% in the 120 patients who were followed for at least 6 months, as compared with a 1.5% fall from 12.3 to 10.8% under usual (physician-directed) care in clinic B. During the year before enrolling in nurse-directed care in clinic B, mean HbA1c levels decreased from 10.0 to 8.5%. At the end of a year under the nurses’ care, the values fell further to 7.1%. The median value fell from 8.3 to 6.6%.

CONCLUSIONS—Specially trained nurses who follow detailed protocols and algorithms under the supervision of a diabetologist can markedly improve diabetes outcomes in a minority population. This approach could help blunt the increased morbidity and mortality noted in minority populations.
Within-Trial Cost-Effectiveness of Lifestyle Intervention or Metformin for the Primary Prevention of Type 2 Diabetes
Authors:   Diabetes Prevention Program Research Group
Published: March 2007

OBJECTIVE—The Diabetes Prevention Program (DPP) demonstrated that intensive lifestyle and metformin interventions reduced the incidence of type 2 diabetes compared with a placebo intervention. The aim of this study was to assess the cost-effectiveness of the lifestyle and metformin interventions relative to the placebo intervention.

RESEARCH DESIGN AND METHODS—Analyses were performed from a health system perspective that considered direct medical costs only and a societal perspective that considered direct medical costs, direct nonmedical costs, and indirect costs. Analyses were performed with the interventions as implemented in the DPP and as they might be implemented in clinical practice.

RESULTS—The lifestyle and metformin interventions required more resources than the placebo intervention from a health system perspective, and over 3 years they cost approximately $2,250 more per participant. As implemented in the DPP and from a societal perspective, the lifestyle and metformin interventions cost $24,400 and $34,500, respectively, per case of diabetes delayed or prevented and $51,600 and $99,200 per quality-adjusted life-year (QALY) gained. As the interventions might be implemented in routine clinical practice and from a societal perspective, the lifestyle and metformin interventions cost $13,200 and $14,300, respectively, per case of diabetes delayed or prevented and $27,100 and $35,000 per QALY gained. From a health system perspective, costs per case of diabetes delayed or prevented and costs per QALY gained tended to be lower.

CONCLUSIONS—Over 3 years, the lifestyle and metformin interventions were effective and were cost-effective from the perspective of a health system and society. Both interventions are likely to be affordable in routine clinical practice, especially if implemented in a group format and with generic medication pricing.
Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity
Authors: Sierksma Aafje , Patel Hamina , Ouchi Noriyuki , Kihara Shinji , Funahashi Tohru , Heine Robert J. , Grobbee Diederick E. , Kluft Cornelis , Hendriks Henk F.J.
Published: March 2007

OBJECTIVE—Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin sensitivity. Moderate alcohol consumption may increase adiponectin, which in turn causes a decrease of tumor necrosis factor (TNF)-α. A decreased TNF-α level may consequently increase insulin sensitivity.

RESEARCH DESIGN AND METHODS—To test this hypothesis, we performed a randomized crossover partially diet-controlled study. A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky (40 g ethanol) or tap water with dinner during two successive periods of 17 days.

RESULTS—Moderate alcohol consumption increased plasma adiponectin level (11%; P = 0.0002) but did not affect plasma TNF-α level. An increase in insulin sensitivity index was observed in an insulin-resistant subgroup (21%; P = 0.11), which positively correlated with the relative alcohol-induced increase in plasma adiponectin level (r = 0.73, P = 0.02).

CONCLUSIONS—The experimental results are in agreement with observational data. Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men, an effect that may be mediated through alcohol-induced increases in adiponectin.
A Standardized Triglyceride and Carbohydrate Challenge
Authors: Mohanlal Nina , Holman Rury R.
Published: March 2007

OBJECTIVE—A standardized method of assessing postprandial triglyceride changes is not available. We evaluated an oral triglyceride tolerance test (OTTT) designed for routine clinical and research use.

RESEARCH DESIGN AND METHODS—A 200-ml strawberry-flavored test drink (50 g fat, 50 g carbohydrate) was administered twice to 30 diabetic and 20 nondiabetic subjects. Venous plasma triglyceride and glucose levels were measured when fasting and every 2 h for 8 h after the drink. Fingerprick plasma triglyceride levels were measured when fasting and at 6 and 8 h after the drink.

RESULTS—The drink was consumed within 3 min and well tolerated by all subjects. The median triglyceride rise at 6 h was similar in diabetic and nondiabetic subjects (0.23 vs. 0.42 mmol/l, NS) and correlated with glucose increase at 2 h (r = 0.429, P = 0.018 and r = 0.509, P = 0.026; respectively). Diabetic subjects had higher 6-h geometric mean (1 SD range) triglyceride levels (1.82 [1.87 to 3.23] vs. 1.11 [0.66 to 1.11 mmol/l], P < 0.003) but a similar coefficient of variation (17.5 vs. 17.0%, NS) and a similar median (interquartile range) time to achieve maximal concentration (Tmax) (6.0 [4.0 to 6.0] vs. 5.0 [4.0 to 6.0] h, NS). Capillary triglyceride values were equivalent to simultaneous venous samples but consistently 10% greater.

CONCLUSIONS—The OTTT permits simple evaluation of postchallenge triglyceride levels, is acceptable to subjects, and can be performed with capillary sampling. It could be used to monitor triglyceride-lowering therapies and to provide additional information concerning cardiovascular disease risk, particularly in diabetic subjects.
The Effect of Diabetes on B-Type Natriuretic Peptide Concentrations in Patients With Acute Dyspnea
Authors: Wu Alan H.B. , Omland Torbjørn , Duc Philippe , McCord James , Nowak Richard M. , Hollander Judd E. , Herrmann Howard C. , Steg Philippe G. , Wold Knudsen Cathrine , Storrow Alan B. , Abraham William T. , Perez Alberto , Kamin Richard , Clopton Paul , Maisel Alan S. , McCullough Peter A. ,   for the Breathing Not Properly Multinational Study Investigators
Published: March 2007

OBJECTIVE—Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea.

RESEARCH DESIGN AND METHODS—The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure).

RESULTS—There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03–2.02; P < 0.05).

CONCLUSIONS—History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure.
Incidence of Diabetes in Middle-Aged Men Is Related to Sleep Disturbances
Authors: Nilsson Peter M. , Rööst Mattias , Engström Gunnar , Hedblad Bo , Berglund Göran
Published: March 2007

OBJECTIVE—Sleep deprivation in healthy men has been experimentally found to result in disturbances in glucose metabolism and in sympathovagal imbalance. The aim of the present study was to investigate whether sleep disturbances and elevated resting heart rate are associated with increased risk of developing diabetes.

RESEARCH DESIGN AND METHODS—A group of 6,599 initially healthy, nondiabetic men aged 44.5 ± 4.0 years took part in a prospective, population-based study in Malmö, Sweden. The incidence of diabetes during a mean follow-up of 14.8 ± 2.4 years was examined in relation to self-reported difficulties in falling asleep and resting heart rate at baseline. Diabetes was assessed at follow-up in all subjects by questionnaire and in a subgroup of 1,551 men by blood glucose measurement.

RESULTS—A total of 615 (9.3%) subjects reported either difficulties in falling asleep or regular use of hypnotics (seen as markers of sleep disturbances), and 158 (2.4%) subjects reported both of these. Altogether, 281 (4.3%) of the men developed diabetes during the follow-up period. Logistic regression models showed difficulties in falling asleep or regular use of hypnotics (odds ratio [OR] 1.52 [95% CI 1.05–2.20]) and resting heart rate (OR per 10 bpm 1.13 [0.99–1.30]) to be associated with development of diabetes when full adjustments were made for baseline age, biological risk factors, lifestyle, family history of diabetes, and social class.

CONCLUSIONS—The results suggest that sleep disturbances and, possibly, elevated resting heart rate, in middle-aged men, are associated with an increased risk of diabetes.
The Blood Glucose Monitoring Communication Questionnaire
Authors: Hood Korey K. , Butler Deborah A. , Volkening Lisa K. , Anderson Barbara J. , Laffel Lori M.B.
Published: March 2007

OBJECTIVE—The aim of this study was to present the psychometric properties of a new tool for evaluating affective response to blood glucose monitoring (BGM) in youths with type 1 diabetes and their parents.

RESEARCH DESIGN AND METHODS—Study participants included 153 youths with type 1 diabetes and their parents. Each youth and parent completed the Blood Glucose Monitoring Communication (BGMC) questionnaire, Diabetes Family Conflict Scale, and Pediatric Quality of Life Inventory. Statistical analyses evaluated the psychometric properties of the BGMC questionnaires and their association with glycemic outcomes.

RESULTS—Youth and parent BGMC questionnaires had acceptable internal consistency (youth, α = 0.77; parent, α = 0.82) and 1-year test-retest reliability (youth, r = 0.60; parent, r = 0.80). Higher BGMC questionnaire scores (indicating more negative affect) showed a strong association with higher levels of diabetes-specific family conflict (youth, r = 0.33; parent, r = 0.44) and poorer health-related psychosocial quality of life (youth, r = −0.50; parent, r = −0.42). Higher BGMC questionnaire scores were also associated with poorer glycemic control (youth, r = 0.28; parent, r = 0.20), even when the effects of diabetes-specific family conflict and psychosocial quality of life were controlled. Youths with BGMC questionnaire scores in the upper quartile had A1c values 1 percentage point higher (9.1%) than youths with scores in the lowest quartile (8.0%).

CONCLUSIONS—The BGMC questionnaires have strong psychometric properties and are convenient measures of affect specific to BGM. Further, BGM affect is associated with glycemic outcomes and may provide a unique contribution to factors associated with glycemic control in youths.
Diet, Growth, and the Risk for Type 1 Diabetes in Childhood
Authors: Pundziūtė-Lyckå Austė , Persson Lars-Åke , Cedermark Gunilla , Jansson-Roth Agneta , Nilsson Ulla , Westin Vera , Dahlquist Gisela
Published: March 2007

OBJECTIVE— To study the association between type 1 diabetes risk and previous intake of energy, accounting for body size and previous intake of nutrients and foods, accounting for the energy intake.

RESEARCH DESIGN AND METHODS—We conducted an incident population-based case-referent study in Stockholm, Sweden, including 99 of 100 eligible 7- to 14-year-old diabetic children and 180 of 200 age-, sex-, and area-matched referent children identified through the Swedish population register. Average daily energy and nutrient intake 1 year before diabetes diagnosis/interview was estimated using the food frequency questionnaire with assessment of consumed food amounts. Mean SD scores of growth measurements taken during the last 4 years before the diagnosis were used. Odds ratios (ORs) were calculated by conditional logistic regression.

RESULTS—Average intake of energy, carbohydrate, fat, and protein was significantly higher among the case subjects as well as mean weight-for-age SD score. Higher energy intake and weight-for-age were both associated with increased diabetes risk after adjustment for each other: OR (95% CI) for medium and high levels of energy intake were 1.33 (0.52–3.42) and 5.23 (1.67–16.38), respectively, and for weight-for-age were 3.20 (1.30–7.88) and 3.09 (1.16–8.22), respectively. High intake of carbohydrates, especially disaccharides and sucrose, increased diabetes risk.

CONCLUSIONS— Higher energy intake and larger body size were independently associated with increased diabetes risk. Of the different nutrients, higher intake of carbohydrates, particularly disaccharides and sucrose, increased the risk. Lifestyle habits leading to higher energy intake and more rapid growth in childhood may contribute to the increase of childhood-onset type 1 diabetes by different mechanisms.
Serum 25-Hydroxyvitamin D, Diabetes, and Ethnicity in the Third National Health and Nutrition Examination Survey
Authors: Scragg Robert , Sowers MaryFran , Bell Colin
Published: March 2007

OBJECTIVE—To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.

RESEARCH DESIGN AND METHODS—We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.

RESULTS—Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicity-specific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11–0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≤43.9 nmol/l). This inverse association was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P = 0.0024) and non-Hispanic whites (P = 0.058) but not non-Hispanic blacks (P = 0.93), adjusting for confounders.

CONCLUSIONS—These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.
Gender Difference in the Impact of Type 2 Diabetes on Coronary Heart Disease Risk
Authors: Juutilainen Auni , Kortelainen Saara , Lehto Seppo , Rönnemaa Tapani , Pyörälä Kalevi , Laakso Markku
Published: March 2007

OBJECTIVE—To explain the stronger effect of type 2 diabetes on the risk of coronary heart disease (CHD) in women compared with men.

RESEARCH DESIGN AND METHODS—The study population consisted of 1,296 nondiabetic subjects and 835 type 2 diabetic subjects aged 45–64 years without cardiovascular disease. The end points were CHD death and a major CHD event (CHD death or nonfatal myocardial infarction). The follow-up time was 13 years.

RESULTS—Major CHD event rate per 1,000 person-years was 11.6 in nondiabetic men, 1.8 in nondiabetic women, 36.3 in diabetic men, and 31.6 in diabetic women. The diabetes-related hazard ratio for a major CHD event from the Cox model, adjusted for age and area of residence, was 2.9 (95% CI 2.2–3.9) in men and 14.4 (8.4–24.5) in women, and after further adjustment for cardiovascular risk factors, 2.8 (2.0–3.7) and 9.5 (5.5–16.9), respectively. The burden of conventional risk factors in the presence of diabetes was greater in women than in men at baseline. Prospectively, elevated blood pressure, low HDL cholesterol, and high triglycerides contributed to diabetes-related CHD risk more in women than in men. However, after adjusting for conventional risk factors, a substantial proportion of diabetes-related CHD risk remained unexplained in both genders.

CONCLUSIONS—The stronger effect of type 2 diabetes on the risk of CHD in women compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in diabetic women.
A Randomized Trial Evaluating a Predominately Fetal Growth–Based Strategy to Guide Management of Gestational Diabetes in Caucasian Women
Authors: Schaefer-Graf Ute M. , Kjos Siri L. , Fauzan Ostary H. , Bühling Kai J. , Siebert Gerda , Bührer Christoph , Ladendorf Barbara , Dudenhausen Joachim W. , Vetter Klaus
Published: March 2007

OBJECTIVE—To compare the management of Caucasian women with gestational diabetes (GDM) based predominantly on monthly fetal growth ultrasound examinations with an approach based solely on maternal glycemia.

RESEARCH DESIGN AND METHODS—Women with GDM who attained fasting capillary glucose (FCG) <120 mg/dl and 2-h postprandial capillary glucose (2h-CG) <200 mg/dl after 1 week of diet were randomized to management based on maternal glycemia alone (standard) or glycemia plus ultrasound. In the standard group, insulin was initiated if FCG was repeatedly >90 mg/dl or 2h-CG was >120 mg/dl. In the ultrasound group, thresholds were 120 and 200 mg/dl, respectively, or a fetal abdominal circumference >75th percentile (AC>p75). Outcome criteria were rates of C-section, small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants, neonatal hypoglycemia (<40 mg/dl), and neonatal care admission.

RESULTS—Maternal characteristics and fetal AC>p75 (36.0 vs. 38.4%) at entry did not differ between the standard (n = 100) and ultrasound groups (n = 99). Assignment to (30.0 vs. 40.4%) and mean duration of insulin treatment (8.3 vs. 8.1 weeks) did not differ between groups. In the ultrasound group, AC>p75 was the sole indication for insulin. The ultrasound-based strategy, as compared with the maternal glycemia-only strategy, resulted in a different treatment assignment in 34% of women. Rates of C-section (19.0 vs. 18.2%), LGA (10.0 vs. 12.1%), SGA (13.0 vs. 12.1%), hypoglycemia (16.0 vs. 17.0%), and admission (15.0 vs. 14.1%) did not differ significantly.

CONCLUSIONS—GDM management based on fetal growth combined with high glycemic criteria provides outcomes equivalent to management based on strict glycemic criteria alone. Inclusion of fetal growth might provide the opportunity to reduce glucose testing in low-risk pregnancies.
Trunk Fat and Leg Fat Have Independent and Opposite Associations With Fasting and Postload Glucose Levels
Authors: Snijder Marieke B. , Dekker Jacqueline M. , Visser Marjolein , Bouter Lex M. , Stehouwer Coen D.A. , Yudkin John S. , Heine Robert J. , Nijpels Giel , Seidell Jacob C.
Published: March 2007

OBJECTIVE—Waist and hip circumferences have been shown to have independent and opposite associations with glucose levels. Waist circumference is positively associated with glucose levels, whereas hip circumference is negatively associated. It is unclear which tissues are involved in the pathophysiological mechanism causing these associations. The main goal was to determine which tissue in the trunk and legs, fat or lean tissue, is associated with measures of glucose metabolism.

RESEARCH DESIGN AND METHODS—In 623 participants of the third examination of the Hoorn Study, whole-body dual-energy X-ray absorptiometry was performed to determine fat and lean soft-tissue mass in the trunk and legs. Fasting and 2-h postload glucose levels after 75-g oral glucose tolerance test (OGTT) were determined. After exclusion of known diabetic patients, cross-sectional analyses were performed in 275 men aged 60–87 years (140 with normal glucose metabolism, 92 with impaired glucose metabolism; and 43 with diabetes) and in 281 women (148 with normal glucose metabolism, 90 with impaired glucose metabolism, and 43 with diabetes).

RESULTS—Greater trunk fat mass was associated with higher glucose levels after adjustment for age, trunk lean mass, leg lean mass, and leg fat mass. Standardized β (95% CI) in men were 0.44 (0.25–0.64) for fasting and 0.41 (0.22–0.60) for postload glucose. For women, these values were 0.49 (0.35–0.63) and 0.47 (0.33–0.61), respectively. In contrast, in the same regression models, a larger leg fat mass was associated with lower glucose levels. Standardized β in men were −0.24 (−0.43 to −0.05) and −0.12 (−0.31 to 0.07) and in women −0.24 (−0.37 to −0.10) and −0.27 (−0.40 to −0.13) for fasting and postload glucose, respectively. In these models, larger leg lean mass was also associated with lower glucose levels but was only statistically significant in men.

CONCLUSIONS—If trunk fat is taken into account, accumulation of fat in the legs seems to be protective against a disturbed glucose metabolism, particularly in women. Further research is needed to unravel underlying pathophysiological mechanisms.