bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Developing Retinopathy in Diabetes Control and Complications Trial Type 1 Diabetic Patients With Good or Poor Metabolic Control
Authors: Zhang LiYing , Krzentowski Georges , Albert Adelin , Lefebvre Pierre J.
Published: March 2007

OBJECTIVE—The study goal was to assess and predict the risk of developing retinopathy in type 1 diabetic patients with extreme metabolic control.

RESEARCH DESIGN AND METHODS—Based on material from the Diabetes Control and Complications Trial (DCCT) study (n = 1,441 patients), patients without retinopathy at baseline (DCCT primary cohort) were considered under good or poor metabolic control if the mean HbA1c level (until the last visit) fell in the lower or upper 20% of the overall HbA1c distribution, respectively. Retinopathy was recorded as either absent or present. Logistic regression was used to predict retinopathy from covariates used in the DCCT retinopathy study.

RESULTS—Among the 153 DCCT patients with “good metabolic control” (mean HbA1c ≤6.87%), three-step change retinopathy developed in 15 (9.8%), and 138 (90%) remained free of retinopathy. Conversely, among the 166 patients with “poor metabolic control” (mean HbA1c ≥9.49%), the complication did not develop in 71 (43%) and did develop in 95 (57%). Whereas occurrence of diabetic retinopathy was primarily due to metabolic control (P < 0.0001) and duration of participation in the study (P < 0.0001), two other covariates were found to be significant prognostic factors of the complication: HbA1c at baseline (OR 1.37, P < 0.001) and BMI (OR 1.11, P < 0.05).

CONCLUSIONS—This study confirms that retinopathy develops in ∼10% of patients with type 1 diabetes under good metabolic control, whereas >40% of patients with type 1 diabetes remain free of retinopathy despite poor metabolic control. After adjusting for metabolic control and duration of participation in the study, it was found that previous glycemic exposure (HbA1c) and BMI may provide a possible explanation to such paradoxical clinical situations.
Psychosocial Therapies in Diabetes
Authors: Delamater Alan M. , Jacobson Alan M. , Anderson Barbara , Cox Daniel , Fisher Lawrence , Lustman Patrick , Rubin Richard , Wysocki Timothy
Published: March 2007

OBJECTIVE—To review key advances in the behavioral science literature related to psychosocial issues and therapies for persons with diabetes, to discuss barriers to research progress, and to make recommendations for future research.

RESEARCH DESIGN AND METHODS—Key findings from the literature on psychosocial research in diabetes are reviewed separately for children and adults. Specific issues covered include psychosocial adjustment and psychiatric disorders, neurocognitive functioning, quality of life, and psychosocial therapies. Barriers that must be addressed to allow research in this area to progress are discussed. Recommendations are then made concerning high-priority areas for advancing research in the field.

CONCLUSIONS—A substantial amount of behavioral science research has demonstrated that psychosocial factors play an integral role in the management of diabetes in both children and adults. Research has also shown the efficacy of a number of psychosocial therapies that can improve regimen adherence, glycemic control, psychosocial functioning, and quality of life. More research in this area is needed to develop psychosocial intervention programs for specific patient populations and to demonstrate the cost-effectiveness of these approaches.
Glucagon-Like Peptide-1 Infusion Must Be Maintained for 24 h/day to Obtain Acceptable Glycemia in Type 2 Diabetic Patients Who Are Poorly Controlled on Sulphonylurea Treatment
Authors: Larsen Jens , Hylleberg Birgitte , Ng Kevin , Damsbo Peter
Published: March 2007

OBJECTIVE—To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment.

RESEARCH DESIGN AND METHODS—This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng · kg–1 · min–1 for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded.

RESULTS—For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P ≤ 0.001). The GLP-1 8 ng · kg–1 · min–1 dose given for 24 h was more efficacious than any of the other doses (P ≤ 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P ≤ 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3–4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated.

CONCLUSIONS—This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.
NeuroD/BETA2 Gene G→A Polymorphism May Affect Onset Pattern of Type 1 Diabetes in Japanese
Authors: Yamada Satoru , Motohashi Yoshiko , Yanagawa Tatsuo , Maruyama Taro , Kasuga Akira , Hirose Hiroshi , Matsubara Koichi , Shimada Akira , Saruta Takao
Published: March 2007

OBJECTIVE—The majority of type 1 diabetes is considered to be autoimmune with, for the most part, abrupt development. However, type 1 diabetes with slow onset, or the so-called slowly progressive type 1 diabetes or latent autoimmune diabetes in adults, has been recently recognized and is considered to be autoimmune-related. Although some investigators tried to explain the difference in onset pattern by the genetic background, including HLA type, it has not been established thus far. We hypothesized that the difference in onset pattern may relate to regeneration or differentiation of pancreatic β-cells, and we therefore focused on the NeuroD/BETA2 gene, which encodes a transcription factor for the insulin gene and β-cell differentiation.

RESEARCH DESIGN AND METHODS—We examined the NeuroD/BETA2 gene polymorphism in 105 Japanese type 1 diabetic patients and in 122 nondiabetic Japanese subjects in a case-control study, and we stratified the patients according to their onset pattern and islet-associated autoantibody positivity.

RESULTS—Regardless of the existence of islet-associated autoantibody, we found a significant difference in A allele frequency between type 1 diabetic patients with acute-onset type and control subjects. However, no difference was found between type 1 slow-onset diabetic patients and control subjects.

CONCLUSIONS—These results support our hypothesis that NeuroD/BETA2 may affect the ability of regeneration of β-cells, leading to a difference in the onset pattern and clinical course of type 1 diabetes.
Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)
Authors: Pozzilli Paolo , Di Mario Umberto
Published: March 2007

Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting β-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.
Clinical and Psychological Course of Diabetes From Adolescence to Young Adulthood
Authors: Bryden Kathryn S. , Peveler Robert C. , Stein Alan , Neil Andrew , Mayou Richard A. , Dunger David B.
Published: March 2007

OBJECTIVE—To determine the clinical and psychological course of diabetes through adolescence and the relationship with glycemic control in young adulthood.

RESEARCH DESIGN AND METHODS—A longitudinal cohort study of adolescents recruited from the register of the outpatient pediatric diabetes clinic. A total of 76 individuals (43 male patients, 33 female patients) aged 11–18 years completed baseline assessments, and 65 individuals (86%) were reinterviewed as young adults (20–28 years of age). Longitudinal assessments were made of glycemic control (HbA1c), weight gain (BMI), and development of complications. Adolescents completed self-report questionnaires to assess emotional and behavioral problems as well as self-esteem. As young adults, psychological state was assessed by the Revised Clinical Interview Schedule and the self-report Brief Symptom Inventory.

RESULTS—Mean HbA1c levels peaked in late adolescence and were worse in female participants (average 11.1% at 18–19 years of age). The proportion of individuals who were overweight (BMI >25.0 kg/m2) increased during the 8-year period from 21 to 54% in female patients and from 2 to 28% in male patients. Serious diabetes-related events included death in one patient and cognitive impairment in two patients. Individuals in whom diabetic complications developed (25% of male patients and 38% of female patients) had significantly higher mean HbA1c levels than those without complications (difference 1.9%, 95% CI 1.1–2.7, P < 0.0001). Behavioral problems at baseline were related to higher mean HbA1c during the subsequent 8 years (β = 0.15, SEM (β) 0.04, P < 0.001, 95% CI 0.07–0.24).

CONCLUSIONS—The outcome for this cohort was generally poor. Behavioral problems in adolescence seem to be important in influencing later glycemic control.
Developing a Prediction Rule From Automated Clinical Databases to Identify High-Risk Patients in a Large Population With Diabetes
Authors: Selby Joe V. , Karter Andrew J. , Ackerson Lynn M. , Ferrara Assiamira , Liu Jennifer
Published: March 2007

OBJECTIVE—To develop and validate a prediction rule for identifying diabetic patients at high short-term risk of complications using automated data in a large managed care organization.

RESEARCH DESIGN AND METHODS—Retrospective cohort analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern California, aged ≥19 years. Data from 1994 to 1995 were used to model risk for macro- and microvascular complications (n = 3,977), infectious complications (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory records, pharmacy records, utilization records, and survey data. Using split-sample validation, the risk scores derived from logistic regression models in half of the population were evaluated in the second half. Sensitivity, positive predictive value, and receiver operating characteristics curves were used to compare scores obtained from full models to those derived using simpler approaches.

RESULTS—History of prior complications or related outpatient diagnoses were the strongest predictors in each complications set. For patients without previous events, treatment with insulin alone, serum creatinine ≥1.3 mg/dl, use of two or more antihypertensive medications, HbA1c >10%, and albuminuria/microalbuminuria were independent predictors of two or all three complications. Several risk scores derived from multivariate models were more efficient than simply targeting patients with elevated HbA1c levels for identifying high-risk patients.

CONCLUSIONS—Simple prediction rules based on automated clinical data are useful in planning care management for populations with diabetes.
Treatment Satisfaction With Inhaled Insulin in Patients With Type 1 Diabetes
Authors: Gerber Robert A. , Cappelleri Joseph C. , Kourides Ione A. , Gelfand Robert A.
Published: March 2007

OBJECTIVE—In patients with type 1 diabetes, glycemic control can be achieved as effectively with an inhaled insulin regimen, comprising preprandial inhaled intrapulmonary insulin plus a bedtime ultralente injection, as with a conventional subcutaneous insulin regimen involving two to three injections per day. Our objective was to compare patient satisfaction between inhaled insulin and subcutaneous insulin.

RESEARCH DESIGN AND METHODS—Subjects with type 1 diabetes participated in a 12-week open-label trial and were randomized to either an inhaled insulin regimen or a subcutaneous insulin regimen. Subjects (n = 69) were asked to complete a 15-item self-administered satisfaction questionnaire, the Patient Satisfaction with Insulin Therapy (PSIT) Questionnaire, at baseline and week 12. Outcomes included mean percentage changes in global (overall) satisfaction and two subscales: convenience/ease of use and social comfort.

RESULTS—The mean percentage improvement in overall satisfaction with inhaled insulin (35.1%, 95% CI 18.0–52.2) was greater than with subcutaneous insulin (10.6%, 4.7–16.5) (P < 0.01), as was the improvement in convenience/ease of use: inhaled insulin 41.3% (22.9–59.6) versus subcutaneous insulin 11.2% (4.1–18.3; P < 0.01). Improvement in social comfort was greater with inhaled insulin but was not statistically significant. The 12-week change in HbA1c was associated with improved overall satisfaction (r = −0.27, P = 0.04).

CONCLUSIONS—Inhaled insulin may offer the first practical, noninvasive alternative to insulin injections. For patients with type 1 diabetes, inhaled insulin maintains glycemic control and provides greater overall satisfaction and convenience/ease of use than subcutaneous insulin.
Elevated Incidence of Type 2 Diabetes in San Antonio, Texas, Compared With That of Mexico City, Mexico
Authors: Burke James P. , Williams Ken , Haffner Steven M. , Villalpando Clicerio Gonzalez , Stern Michael P.
Published: March 2007

OBJECTIVE—To compare the incidence of type 2 diabetes between low-income Mexican-Americans residing in San Antonio, Texas, and low-income residents in Mexico City, Mexico.

RESEARCH DESIGN AND METHODS—Using data from the San Antonio Heart Study and the Mexico City Diabetes Study, we compared the incidence of type 2 diabetes in 35- to 64-year-old low-income Mexican-American residents of San Antonio with similarly aged low-income residents of Mexico City. Because of the different follow-up times in the two studies, Poisson regression was used to compare the rates of diabetes. Potential risk factors for diabetes were also analyzed to determine whether they explained or contributed to a difference in incidence.

RESULTS—The age- and sex-adjusted incidence of type 2 diabetes was significantly higher in San Antonio (RR 2.01) compared with Mexico City. This difference was seen primarily in the oldest age group (55–64 years of age) and remained statistically significant after adjusting for a number of diabetes risk factors, including demographic, anthropometric, and metabolic variables. Follow-up rates were similar in both cities.

CONCLUSIONS—We conclude that there was a higher incidence of type 2 diabetes in San Antonio than in Mexico City, and that difference occurred primarily in individuals in the oldest age group. The potential mediating factors we examined did not account for this difference. Other factors, such as exercise and diet, which were not available for analysis in this study, in addition to a cohort effect, may have contributed to the difference in incidence of type 2 diabetes in the two cities. In addition, there was no evidence of a higher case fatality among diabetic individuals from Mexico City compared with San Antonio.
Temporal Trends in BMI Among Adults With Diabetes
Authors: Leibson Cynthia L. , Williamson David F. , Melton L. Joseph , Palumbo Pasquale J. , Smith Steven A. , Ransom Jeanine E. , Schilling Peter L. , Narayan K. M. Venkat
Published: March 2007

OBJECTIVE—Increasing obesity within the general population has been accompanied by rising rates of diabetes. The extent to which obesity has increased among people with diabetes is unknown, as are the potential consequences for diabetes outcomes.

RESEARCH DESIGN AND METHODS—Community medical records (hospital and ambulatory) of all Rochester, Minnesota, residents aged ≥30 years who first met standardized research criteria for diabetes from 1970 to 1989 (n = 1,306) were reviewed to obtain data on BMI and related characteristics as of the diabetes identification date (±3 months). Vital status as of 31 December 1999 and date of death for those who died were obtained from medical records, State of Minnesota death tapes, and active follow-up.

RESULTS—As of the identification date, data on BMI were available for 1,290 cases. Of the 272 who first met diabetes criteria in 1970–1974, 33% were obese (BMI ≥30), including 5% who were extremely obese (BMI ≥40). These proportions increased to 49% (P < 0.001) and 9% (P = 0.012), respectively, for the 426 residents who first met diabetes criteria in 1985–1989. BMI increased significantly with increasing calendar year of diabetes identification in multivariable regression analysis. Analysis of survival revealed an increased hazard of mortality for BMI ≥41, relative to BMI of 23–25 (hazard ratio 1.60, 95% CI 1.09–2.34, P = 0.016).

CONCLUSIONS—The prevalence of obesity and extreme obesity among individuals at the time they first met criteria for diabetes has increased over time. This is disturbing in light of the finding that diabetic individuals who are extremely obese are at increased risk of mortality compared with their nonobese diabetic counterparts.
Smoking as a Modifiable Risk Factor for Type 2 Diabetes in Middle-Aged Men
Authors: Wannamethee S. Goya , Shaper A. Gerald , Perry Ivan J.
Published: March 2007

OBJECTIVE—To examine the effects of cigarette smoking, giving up smoking, and primary or secondary pipe or cigar smoking on the risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS—A prospective study followed 7,735 men aged 40–59 years from general practices in 24 British towns for an average of 16.8 years. Incident cases of physician-diagnosed diabetes were ascertained by repeated postal questionnaires and systematic reviews of primary care records.

RESULTS—A total of 290 incident cases of diabetes were found in 7,124 men with no history of diabetes, coronary heart disease, or stroke. Cigarette smoking was associated with a significant increase in risk of diabetes, even after adjustment for age, BMI, and other potential confounders. The benefit of giving up smoking was only apparent after 5 years of smoking cessation, and risk reverted to that of never-smokers only after 20 years. The risk of diabetes in those who switched from smoking cigarettes to pipe or cigars remained equal to the risk in continuing cigarette smokers. Men who gave up smoking during the first 5 years of follow-up showed significant weight gain and subsequently higher risk of diabetes than continuing smokers.

CONCLUSIONS—Cigarette smoking is an independent and modifiable risk factor for type 2 diabetes. Smoking cessation is associated with weight gain and a subsequent increase in risk of diabetes, but in the long term, the benefits of giving up smoking outweigh the adverse effects of early weight gain.
Congestive Heart Failure in Type 2 Diabetes
Authors: Nichols Gregory A. , Hillier Teresa A. , Erbey John R. , Brown Jonathan B.
Published: March 2007

OBJECTIVE—To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF.

RESEARCH DESIGN AND METHODS—We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF.

RESULTS—CHF was prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF.

CONCLUSIONS—Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.
The Insertion/Deletion Polymorphism of the ACE Gene Is Related to Insulin Sensitivity in Overweight Women
Authors: Ryan Alice S. , Nicklas Barbara J. , Berman Dora M. , Ferrell Robert E.
Published: March 2007

OBJECTIVE—The ACE insertion/deletion (I/D) polymorphism has been identified as a genetic risk factor for coronary heart disease (CHD). The deletion (D) allele of the ACE gene may be associated with higher insulin sensitivity. Individuals who are homozygous for the DD allele have higher ACE levels and possibly more angiotensin II, which, when infused exogenously, causes an increase in insulin sensitivity. The purpose of this study was to investigate the association of the I/D polymorphism of the ACE gene with insulin sensitivity and CHD risk factors.

RESEARCH DESIGN AND METHODS—The study included 66 women (ages 57 ± 1 years) who were overweight or obese (means ± SEM, BMI = 33 ± 1 kg/m2) and sedentary (Vo2max = 19.6 ± 0.4 ml · kg–1 · min1). Total body fat mass and percent fat were determined by dual-energy X-ray absorptiometry, and abdominal fat was by computed tomography. Insulin sensitivity was measured during the last 30 min of 3-h hyperinsulinemic-euglycemic clamps (40 mU · m−2 · min−1). Comparisons were made among women with the II (n = 9), ID (n = 36), and DD (n = 21) genotypes.

RESULTS—Age, percent body fat, waist-to-hip ratio, visceral and subcutaneous abdominal fat areas, plasma lipid levels, and systolic and diastolic blood pressures did not differ by ACE genotype. Fasting glucose and 2-h glucose levels were similar among genotypes, but fasting plasma insulin levels were lower in DD women than in ID women (P < 0.05). Glucose utilization was higher in women with the DD genotype than in women with the II genotype (53.1 ± 3.9 vs. 36.0 ± 3.8 μmol · kg−1 FFM · min−1, P = 0.01) and was higher in ID women than in II women (48.5 ± 2.5 μmol · kg−1 FFM · min−1, P = 0.04).

CONCLUSIONS—These data suggest that the I/D polymorphism is not associated with risk factors for CHD in overweight sedentary women; however, women who are homozygous for the D allele of the ACE gene are more insulin sensitive, whereas women who are homozygous for the I allele of the ACE gene have greater insulin resistance and potential risk for type 2 diabetes.
Peripheral Artery Disease, Diabetes, and Reduced Lower Extremity Functioning
Authors: Dolan Nancy C. , Liu Kiang , Criqui Michael H. , Greenland Philip , Guralnik Jack M. , Chan Cheeling , Schneider Joseph R. , Mandapat Aimee Luna , Martin Gary , McDermott Mary M.
Published: March 2007

OBJECTIVE—To characterize lower extremity function and dysfunction in peripheral artery disease (PAD) patients with and without diabetes.

RESEARCH DESIGN AND METHODS—In this cross-sectional study, 460 men and women with PAD (147 with diabetes) were recruited from three academic medical centers. Assessments included ankle brachial index (ABI), neuropathy score, 6-min walk distance, 4-m walking velocity, Walking Impairment Questionnaire (0–100 scale, 100 = best), and summary performance score (SPS) (0–12 scale, 12 = best).

RESULTS—The mean ABI was similar in PAD patients with and without diabetes. PAD patients with diabetes were younger, had a higher BMI, had a worse neuropathy score, and had a greater number of cardiovascular comorbidities compared with those without diabetes. Participants with diabetes were less likely to report classical symptoms of intermittent claudication and more likely to report exertional leg pain, which sometimes started at rest. After adjusting for age, those with diabetes had a shorter mean 6-min walk distance (1,040 vs. 1,168 feet, P < 0.001), slower fast-pace 4-m walk velocity (0.83 vs. 0.90 m/sec, P < 0.001), and a lower SPS (7.3 vs. 8.6, P < 0.001) than those without diabetes. Patients with diet-controlled diabetes performed better than those on diabetes medications. Differences in lower extremity functioning between patients with and without diabetes were largely attenuated but not abolished for SPS and fast-pace 4-m walk velocity after adjustment for type of exertional leg pain, neuropathy score, and number of cardiovascular comorbidities.

CONCLUSIONS—Subjects with PAD and diabetes have poorer lower extremity function than those with PAD alone. This difference in functioning appears to be largely explained by diabetes-associated neuropathy, differences in exertional leg symptoms, and greater cardiovascular disease in patients with diabetes.
“Diabetic Mastopathy,” or Sclerosing Lymphocytic Lobulitis, Is Strongly Associated With Type 1 Diabetes
Authors: Kudva Yogish C. , Reynolds Carol , O’Brien Timothy , Powell Claudia , Oberg Ann L. , Crotty Thomas B.
Published: March 2007

OBJECTIVE—To demonstrate the strong association of diabetic mastopathy or sclerosing lymphocytic lobulitis with type 1 diabetes mellitus by studying appropriate control groups and to describe risk factors and natural history of the disorder.

RESEARCH DESIGN AND METHODS—This was a retrospective cross-sectional study of four groups of patients conducted at a setting tertiary care medical center. We examined benign breast biopsies (investigator masked to identity) from age-matched patients with types 1 and 2 diabetes, autoimmune thyroid disease, or none of the above disorders for sclerosing lymphocytic lobulitis. Several risk factors proposed for the disorder (age at diagnosis of benign breast disease, duration of diabetes, age at onset of diabetes, prevalence of retinopathy, neuropathy, nephropathy and cheiroarthropathy, glycemic control, parity, oral contraceptive use, menopausal status, or number of breast biopsies) were evaluated, and patients were contacted to describe the natural history of the disorder.

RESULTS—Sclerosing lymphocytic lobulitis was identified in 69.7% of the subjects with type 1 diabetes and 1.8% of those with autoimmune thyroid disease diagnosed with benign breast disease at surgery. It did not occur in patients with type 2 diabetes with or without insulin treatment or in control subjects. Only retinopathy and peripheral neuropathy were associated with sclerosing lymphocytic lobulitis. Breast carcinoma or lymphoma did not occur subsequently in any type 1 diabetes patient with or without sclerosing lymphocytic lobulitis.

CONCLUSIONS—Sclerosing lymphocytic lobulitis is strongly associated with type 1 diabetes. Retinopathy and neuropathy are associated with the disorder. The risk of malignancy is not increased.
Stress Management Improves Long-Term Glycemic Control in Type 2 Diabetes
Authors: Surwit Richard S. , van Tilburg Miranda A.L. , Zucker Nancy , McCaskill Cynthia C. , Parekh Priti , Feinglos Mark N. , Edwards Christopher L. , Williams Paula , Lane James D.
Published: March 2007

OBJECTIVE—There is conflicting evidence regarding the utility of stress management training in the treatment of diabetes. The few studies that have shown a therapeutic effect of stress management have used time-intensive individual therapy. Unfortunately, widespread use of such interventions is not practical. The aim of the present investigation is to determine whether a cost-effective, group-based stress management training program can improve glucose metabolism in patients with type 2 diabetes and to determine whether a particular subset of patients is more likely to get positive results.

RESEARCH DESIGN AND METHODS—Patients with type 2 diabetes were randomized to undergo a five-session group diabetes education program with or without stress management training. Participants (n = 108) were followed for 1 year, during which HbA1c tests and questionnaires assessing perceived stress, anxiety, and psychological health were administered at regular intervals to evaluate treatment effects.

RESULTS—Stress management training was associated with a small (0.5%) but significant reduction in HbA1c. Compliance with the treatment regimen decreased over time but was similar to that seen in patients receiving stress management for other reasons in the clinic. Trait anxiety (a measure of stable individual differences in anxiety proneness) did not predict response to treatment, showing that highly anxious patients did not derive more benefit from training.

CONCLUSIONS—The current results indicate that a cost-effective, group stress management program in a “real-world” setting can result in clinically significant benefits for patients with type 2 diabetes.
Incidence of Diabetes in American Indians of Three Geographic Areas
Authors: Lee Elisa T. , Welty Thomas K. , Cowan Linda D. , Wang Wenyu , Rhoades Dorothy A. , Devereux Richard , Go Oscar , Fabsitz Richard , Howard Barbara V.
Published: March 2007

OBJECTIVE—To estimate incidence rates of diabetes and associated risk factors among participants of the Strong Heart Study.

RESEARCH DESIGN AND METHODS—Of the 4,549 Strong Heart Study participants examined at baseline, 3,638 returned for a similar examination after an average of 4 years. The 1985 World Health Organization criteria for diabetes were used to identify new diabetes cases. Rates of diabetes among participants who did not have diabetes at baseline examination were determined. The relationships between the incidence rates of diabetes and a number of risk factors measured at baseline examination were studied.

RESULTS—Significant variables associated with the development of diabetes included triglycerides, obesity, fasting plasma glucose, insulin, and degree of American Indian blood among participants with NGT at baseline. For those with IGT at baseline, significant predictors included fasting plasma glucose, 2-h glucose, BMI, degree of American Indian blood, and albuminuria.

CONCLUSIONS—The high incidence rates found in this study were alarming. To slow down the rapid increase of this disease in the American Indian population, preventive programs must be designed and implemented. Patients with IGT should be treated with diabetes medication or put on a rigid weight-reduction program to reduce the risk of progression to diabetes.
Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes– Associated HLA Genotypes in Women With Gestational Diabetes Mellitus
Authors: Weng Jianping , Ekelund Magnus , Lehto Markku , Li Haiyan , Ekberg Göran , Frid Anders , Åberg Anders , Groop Leif C. , Berntorp Kerstin
Published: March 2007

OBJECTIVE—To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—We studied mutations in MODY1–4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum.

RESULTS—There was no increase in type 1 diabetes–associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1α gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum.

CONCLUSIONS—MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.
Strong in Body and Spirit
Authors: Gilliland Susan S. , Azen Stanley P. , Perez Georgia E. , Carter Janette S.
Published: March 2007

OBJECTIVE—To determine the effects of a culturally appropriate diabetes lifestyle intervention for Native Americans on risk factors for complications of diabetes.

RESEARCH DESIGN AND METHODS—A nonrandomized, community-based diabetes intervention trial was conducted in three Native American sites in New Mexico from 1993–1997. Participants were assigned to intervention or control based on community of residence. Intervention sessions were held ∼6 weeks apart over ∼10 months. The intervention was delivered in site A in family and friends (FF) groups (n = 32); site B received the same intervention in one-on-one (OO) appointments (n = 39); and site C received usual medical care (UC) (n = 33) (total participants, n = 104). Primary change in HbA1c level was assessed at 1 year.

RESULTS—Adjusted mean change in HbA1c value varied significantly across the three arms at 1 year (P = 0.05). The UC arm showed a statistically significant increase in adjusted mean HbA1c change (1.2%, P = 0.001), whereas both intervention arms showed a small nonsignificant (P > 0.05) increase in the adjusted mean change (0.5% and 0.2% for FF and OO arms, respectively). The increase was statistically significantly smaller in the combined intervention arms (0.4%) compared with the UC arm (1.2%, P = 0.02).

CONCLUSIONS—Lifestyle intervention has the potential to substantially reduce microvascular complications, mortality, and health care utilization and costs if the change is sustained over time.
Beneficial Effects of Soy Phytoestrogen Intake in Postmenopausal Women With Type 2 Diabetes
Authors: Jayagopal Vijay , Albertazzi Paula , Kilpatrick Eric S. , Howarth Elaine M. , Jennings Paul E. , Hepburn David A. , Atkin Stephen L.
Published: March 2007

OBJECTIVE—Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.

RESULTS—Compliance with the dietary supplementation was >90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean ± SD 8.09 ± 21.9%, P = 0.006), insulin resistance (6.47 ± 27.7%, P = 0.003), HbA1c (0.64 ± 3.19%, P = 0.048), total cholesterol (4.07 ± 8.13%, P = 0.004), LDL cholesterol (7.09 ± 12.7%, P = 0.001), cholesterol/HDL cholesterol ratio (3.89 ± 11.7%, P = 0.015), and free thyroxine (2.50 ± 8.47%, P = 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.

CONCLUSIONS—These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile.
A Diabetes Outcome Progression Trial (ADOPT)
Authors: Viberti Giancarlo , Kahn Steven E. , Greene Douglas A. , Herman William H. , Zinman Bernard , Holman Rury R. , Haffner Steven M. , Levy Daniel , Lachin John M. , Berry Rhona A. , Heise Mark A. , Jones Nigel P. , Freed Martin I.
Published: March 2007

OBJECTIVE—Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet β-cell failure or long-term deterioration in glycemia. Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy.

RESEARCH DESIGN AND METHODS—A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind, parallel-group study consisting of a screening visit, a 4-week placebo run-in, a 4-year treatment period, and an observational follow-up of ∼3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years. After run-in, patients will be randomized to rosiglitazone, glyburide, or metformin titrated to the maximum effective daily doses (8 mg rosiglitazone, 15 mg glyburide, or 2 g metformin). The primary outcome is time to monotherapy failure, defined as the time following titration to the maximal effective or tolerated dose when fasting plasma glucose exceeds 180 mg/dl (10 mmol/l). Secondary outcomes include measures of islet β-cell function, insulin sensitivity, dyslipidemia, changes in urinary albumin excretion, plasminogen activator inhibitor-1 antigen, fibrinogen, and C-reactive protein. Safety and tolerability will also be evaluated. Patient-reported outcomes and resource utilization data will be collected and analyzed.

CONCLUSIONS—ADOPT will provide data on the effect of mechanistically differing treatment options on metabolic control, β-cell function, and markers of macrovascular disease risk in type 2 diabetes.
Rapid Early Growth Is Associated With Increased Risk of Childhood Type 1 Diabetes in Various European Populations
Authors:   the EURODIAB Substudy 2 Study Group
Published: March 2007

OBJECTIVE—To confirm that early growth is associated with type 1 diabetes risk in European children and elucidate any role of infant feeding.

RESEARCH DESIGN AND METHODS—Five centers participated, each with a population-based register of type 1 diabetes diagnosed at <15 years of age. Control subjects were randomly chosen from population registers, schools, or polyclinics. Growth data were obtained from routine records and infant feeding information from parental questionnaire or interview. Patient/control subject differences in mean standard deviation score (SDS) were obtained for each center and pooled. Odds ratios (ORs) were pooled by the Mantel-Haenszel method, and logistic regression was used to adjust for confounders.

RESULTS—Growth data were available for 499 patients and 1,337 control subjects. Height and weight SDS were significantly increased among patients from 1 month after birth, the maximum differences of 0.32 (95% CI 0.14–0.50) and 0.41 (0.26–0.55), respectively, occurring between 1 and 2 years of age. Significant excesses in BMI SDS were observed from 6 months of age, with the largest difference of 0.27 (0.10, 0.44) evident between 1 and 2 years. Breast-feeding was associated with reduced disease risk, OR 0.75 (0.58–0.96). Introduction of cow’s milk, formula, or solid foods before 3 months was not associated with significant risk elevation.

CONCLUSION—Increased early growth is associated with disease risk in various European populations. Any role of infant feeding in this association remains unclear.
Relationship Between Gestational Diabetes Mellitus and Low Maternal Birth Weight
Authors: Seghieri Giuseppe , Anichini Roberto , De Bellis Alessandra , Alviggi Lorenzo , Franconi Flavia , Breschi Maria Cristina
Published: March 2007

OBJECTIVE—To study the relationship between low birth weight and the presence of gestational diabetes mellitus (GDM) or peripheral insulin resistance during pregnancy.

RESEARCH DESIGN AND METHODS—We studied the relationship between peripheral insulin sensitivity (calculated by Matsuda and DeFronzo’s oral glucose tolerance test (OGTT)-derived insulin sensitivity index [ISIOGTT]) or GDM prevalence and birth weight in 604 pregnant women, classified as normally glucose tolerant (n = 462) or affected with GDM (n = 142) after a 100-g 3-h oral glucose tolerance test. We then categorized these subjects into two groups: individuals with birth weight in the <10th percentile (<2,600 g; n = 68) and individuals with birth weight in the >10th percentile (n = 536).

RESULTS—GDM prevalence was higher in the group in the lowest birth weight decile (<2,600 g; 24/68; 35%) than in the group with normal/high birth weight (118/536; 22%; χ2 = 5.917; P = 0.01). Relative risk for GDM adjusted for age, parity, family history of diabetes, and prepregnancy body weight was about twofold in the group with low birth weight (odds ratio = 1.89 [95% CI 1.088–3.285; P = 0.023]), and the prevalence of low birth weight was about threefold higher in the first ISIOGTT decile. In 450 women whose newborn’s weight was known, the delivery of macrosomic babies was associated with a twofold higher relative risk for GDM in women who themselves had low birth weight. In the latter, the relationships between their newborn’s weight and either maternal glucose tolerance (positive) or ISIOGTT (negative) were amplified.

CONCLUSIONS—Low maternal birth weight was associated with a twofold higher risk for GDM, independent of major confounders. Such a risk was highest in women with low birth weight who delivered macrosomic babies, and in the group with low birth weight, the relationship between maternal glucose tolerance or insulin resistance and offspring’s neonatal weight was much more evident.
Components of the Metabolic Syndrome and Risk of Cardiovascular Disease and Diabetes in Beaver Dam
Authors: Klein Barbara E.K. , Klein Ronald , Lee Kristine E.
Published: March 2007

OBJECTIVE—To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes.

RESEARCH DESIGN AND METHODS—A population of individuals aged 43–84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up.

RESULTS—Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (≥30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components.

CONCLUSIONS—Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.
Increased Plasma-Soluble Tumor Necrosis Factor-α Receptor 2 Level in Lean Nondiabetic Offspring of Type 2 Diabetic Subjects
Authors: Straczkowski Marek , Kowalska Irina , Stepien Agnieszka , Dzienis-Straczkowska Stella , Szelachowska Malgorzata , Kinalska Ida
Published: March 2007

OBJECTIVE—Tumor necrosis factor-α (TNF-α) is one of the proposed mediators of insulin resistance, upregulated in human obesity. Insulin resistance, however, might precede the development of obesity, especially in subjects with a family history of type 2 diabetes. Therefore, the aim of the present study was to assess plasma levels of TNF-α and soluble forms of its receptors (soluble TNF-α receptors 1 [sTNFR1] and 2 [sTNFR2]) and to evaluate the relationship of the TNF-α system with insulin resistance in lean, nondiabetic offspring of type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—We compared 20 lean offspring (BMI <25 kg/m2, 8 men and 12 women) of type 2 diabetic patients with 20 lean subjects with no family history of diabetes, matched for age, sex, and BMI (control group). Anthropometry and blood biochemical parameters were measured, and insulin sensitivity was evaluated with the euglycemic-hyperinsulinemic clamp technique.

RESULTS—Both men and women in the offspring group were markedly more insulin-resistant and had higher plasma levels of sTNFR2 (all P < 0.05). TNF-α, sTNFR1, and other examined parameters did not differ between the studied groups. Both TNF-α receptors were related to waist-to-hip ratio (WHR), fat-free mass (FFM), plasma total cholesterol, HDL cholesterol, LDL cholesterol, and nonesterified fatty acids (NEFAs). sTNFR2, but not sTNFR1, was also associated with insulin sensitivity (r = −0.49, P = 0.001). This relationship remained significant after adjustment for WHR, FFM, plasma insulin, and NEFA.

CONCLUSIONS—TNF-α system might be involved in modulating insulin action before the onset of obesity in subjects at high risk for type 2 diabetes.