bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral science in diabetes. Contributions and opportunities.
Authors: Glasgow R E , Fisher E B , Anderson B J , LaGreca A , Marrero D , Johnson S B , Rubin R R , Cox D J
Published: March 2007

OBJECTIVE: To summarize the current status of behavioral research and practice in diabetes and to identify promising future directions. RESEARCH DESIGN AND METHODS: We review behavioral science contributions to diabetes in self-management and patient empowerment, interventions with children and adolescents, and special problems including blood glucose awareness training and complications such as depression. We also identify emerging areas in which behavioral science stands to make significant contributions, including quality of life, worksite and community programs, interventions using new information technologies, and translation research evaluating practical programs in representative settings. We then discuss the gap between the generally encouraging research on behavioral contributions to diabetes and the infrequent incorporation of such contributions in practice. Suggestions are made for how to close this gap, including ways to increase understanding of behavioral issues, opportunities for funding of key research and implementation questions, and how behavioral science principles can become more integrated into diabetes organizations and care. CONCLUSIONS: Changes are required on the part of behavioral scientists in how they organize and present their research and on the part of potential users of this knowledge, including other health professions, organizations, and funding agencies. Integrating behavioral science advances with other promising genetic, medical, nutritional, technology, health care, and policy opportunities promises not only to broaden our understanding of diabetes but also to improve patient care, quality of life, and public health for persons with diabetes.
Impaired endothelium-dependent vasodilation in type 2 diabetes. Relation to LDL size, oxidized LDL, and antioxidants.
Authors: Mäkimattila S , Liu M L , Vakkilainen J , Schlenzka A , Lahdenperä S , Syvänne M , Mäntysaari M , Summanen P , Bergholm R , Taskinen M R , Yki-Järvinen H
Published: March 2007

OBJECTIVE: To search for determinants of endothelial dysfunction in type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a comprehensive analysis of cardiovascular risk markers and measured blood flow responses to endothelium-dependent (acetylcholine [ACh] and NG-monomethyl-L-arginine) and -independent (sodium nitroprusside [SNP]) vasoactive agents in 30 nonsmoking men with type 2 diabetes (age 51 +/- 1 years, BMI 27.8 +/- 0.4 kg/m2, HbA1c 7.4 +/- 0.3%) and 12 matched normal control men. RESULTS: ACh-induced vasodilation was 37% lower in type 2 diabetic (6.1 +/- 0.5) than in normal subjects (9.7 +/- 1.5 ml.dl-1.min-1, P < 0.01), while flows during SNP were similar (9.1 +/- 0.6 vs. 9.9 +/- 1.3 ml.dl-1.min-1, NS). The ratio of endothelium-dependent vs. -independent flow (ACh:SNP ratio) was 31% lower in type 2 diabetic (0.70 +/- 0.05) than in normal subjects (1.10 +/- 0.18, P < 0.01). Total (2.2 +/- 0.4 vs. 1.3 +/- 0.2 mmol/l, P < 0.05), VLDL, and intermediate-density lipoprotein triglycerides were significantly higher, and the mean LDL particle diameter was significantly smaller in type 2 diabetic than in normal subjects. The lag times for LDL oxidation by Cu2+ in vitro were similar in patients with type 2 diabetes (183 +/- 7) and in normal subjects (183 +/- 9 min, NS). Measured and calculated (sum of concentration of individual antioxidants in serum) total peroxyl radical-trapping capacities (TRAPs) were comparable between the groups. In the patients with type 2 diabetes, LDL size was significantly correlated with endothelium-dependent vasodilation (r = 0.43, P < 0.05), serum triglycerides (r = -0.75, P < 0.001), and the lag time for LDL oxidation in vitro (r = 0.38, P < 0.05). HbA1c was inversely correlated with the lag time for LDL oxidation in vitro (r = -0.41, P < 0.05) and TRAP. CONCLUSIONS: In summary, patients with type 2 diabetes exhibited impaired endothelium-dependent vasodilation in vivo, elevated serum triglycerides, decreased LDL size, and normal antioxidant capacity. Of these parameters, LDL size was significantly correlated with endothelial function.
Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.
Authors: Adler A I , Boyko E J , Ahroni J H , Smith D G
Published: March 2007

OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.
Early postpartum metabolic assessment in women with prior gestational diabetes.
Authors: Pallardo F , Herranz L , Garcia-Ingelmo T , Grande C , Martin-Vaquero P , Jañez M , Gonzalez A
Published: March 2007

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.
Improved glycemic control reduces the impact of weight gain on cardiovascular risk factors in type 1 diabetes. The Epidemiology of Diabetes Complications Study.
Authors: Williams K V , Erbey J R , Becker D , Orchard T J
Published: March 2007

OBJECTIVE: To assess the prevalence and incidence of being overweight in type 1 diabetes, to identify factors associated with weight gain and improved glycemic control, and to examine relationships among weight gain, glycemic control, and cardiovascular risk factors. RESEARCH DESIGN AND METHODS: The prevalence and incidence of being overweight in the Pittsburgh Epidemiology of Diabetes Complications (EDC) cohort (n = 441) were compared with the general population (National Health and Nutrition Examination Survey [NHANES]). Factors associated with weight gain and improved glycemic control were identified, and relationships among weight gain, glycemic control, and cardiovascular risk factors were examined over a 6.9 +/- 2.2-year period. RESULTS: At baseline, the prevalence of being overweight (BMI > 27.8 kg/m2 for men and > 27.3 kg/m2 for women) was 10.4 and 11.4%, respectively, and was lower than the age- and sex-specific estimate for the general population (P < 0.05). The incidence of being overweight was comparable in men (12.6%) and women (11.8%) and did not differ from the general population (P = 0.98). Weight gain correlated with improvements in HbA1c (r = -0.21, P < 0.001). Patients with the highest baseline HbA1c levels gained the most weight and had the greatest improvement in glycemic control. A lower baseline BMI was also associated with a greater improvement in glycemic control. Weight gain favorably influenced the lipid profile in the setting of improved glycemic control, but adversely influenced the lipid profile in the absence of improved glycemic control. Weight change was directly associated with blood pressure change, but the incidence of hypertension was more strongly influenced by the development of nephropathy. CONCLUSIONS: The prevalence of being overweight in type 1 diabetes remains lower than that in the general population. Moderate weight gain did not adversely affect the cardiovascular risk profile in the setting of improved glycemic control.
Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study.
Authors: Donahue R P , Prineas R J , Donahue R D , Zimmet P , Bean J A , De Courten M , Collier G , Goldberg R B , Skyler J S , Schneiderman N
Published: March 2007

OBJECTIVE: Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity. RESULTS: The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04). CONCLUSIONS: Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.
Work disability and diabetes.
Authors: Mayfield J A , Deb P , Whitecotton L
Published: March 2007

OBJECTIVE: To determine the rates and demographic determinants of work disability, hours worked per week, work-loss days, and wages in individuals with diabetes. RESEARCH DESIGN AND METHODS: A probit regression analysis was performed on a cross-sectional population-based survey of U.S. noninstitutionalized civilian population (National Medical Expenditures Survey--2, 1987). The sample was restricted to individuals aged > or = 25 years. A total of 1,502 individuals reported having diabetes, and 20,405 did not. Information on workforce participation and income were collected quarterly. Work disability was defined as a self-report of having been unable to work because of illness or disability for > or = 2 quarters in 1987. RESULTS: Work disability was reported by 25.6% of individuals with diabetes, compared with 7.8% of those without diabetes. Work disability rates were higher for older people, females, and African-Americans, and lower for Hispanics and for individuals with greater non-wage income. Individuals with diabetes engaged in the workforce had more work-loss days than did nondiabetic individuals, but had similar hourly wages. Predicted mean earnings were significantly lower for individuals with diabetes at all ages, resulting in $4.7 million loss in earnings in 1987 due to work disability. CONCLUSIONS: Work disability is significantly higher for individuals with diabetes than for those without diabetes at all ages, and results in a significant decrease in earnings. A disproportionate burden of work disability is borne by older individuals and women with diabetes. Better information on the determinants of work disability in individuals with diabetes is needed.
Determining an episode of care using claims data. Diabetic foot ulcer.
Authors: Mehta S S , Suzuki S , Glick H A , Schulman K A
Published: March 2007

OBJECTIVE: Amid changes in the organization and financing of health care, health care decision makers are increasingly interested in episodes of care. We sought to determine an episode of care for diabetic foot ulcer using an administrative claims database. RESEARCH DESIGN AND METHODS: We used 1993-1995 claims data to assess resource utilization for privately insured patients with diabetic foot ulcers. Over a 26-week period, we determined the episode length by comparing differences in average daily charges and proportion of patients with charges before and after foot ulcer diagnosis. All 13 weeks before diagnosis were used to calculate baseline values. Significance was determined by CIs, which were calculated by a nonparametric bootstrap technique. Costs associated with the episode were also calculated. A sensitivity analysis using weeks with highest and lowest values as baseline was also conducted. RESULTS: Based on average daily charges, the episode of care for diabetic foot ulcer was 5 weeks. Using proportion of patients with charges, the episode was longer than 13 weeks. The cost for an episode of care ranged from $900 to $2,600. In the sensitivity analyses, episodes of care ranged from 1 to 13 weeks. CONCLUSIONS: Episodes of care can be defined by the period beginning with increased resource consumption and ending when resource consumption returns to baseline levels. With the growth of managed care and disease management programs, episode-of-care analysis may have an increasingly important role in health care provision and delivery.
Improved postprandial glycemic control during treatment with Humalog Mix25, a novel protamine-based insulin lispro formulation. Humalog Mix25 Study Group.
Authors: Roach P , Yue L , Arora V
Published: March 2007

OBJECTIVE: Humalog Mix25 is a manufactured premixed insulin formulation containing insulin lispro and a novel insulin lispro-protamine formulation (NPL) in a ratio of 25:75%. The objective of this study was to compare Humalog Mix25 to human insulin 30/70 (30% regular insulin/70% NPH) with respect to glycemic control. RESEARCH DESIGN AND METHODS: Humalog Mix25 was compared with human insulin 30/70 in 89 individuals with type 2 diabetes during a 6-month randomized open-label two-period crossover study. Each insulin was administered twice daily, before the morning and evening meals. Information regarding self-monitored blood glucose (BG), hypoglycemic episodes (hypoglycemic signs or symptoms or BG < or = 3.0 mmol/l), insulin dose, and HbA1c was collected. RESULTS: Treatment with Humalog Mix25 resulted in better postprandial glycemic control after the morning and evening meals compared with treatment with human insulin 30/70. Overall glycemic control and the incidence of hypoglycemia were comparable between the treatments. CONCLUSIONS: In comparison to treatment with human insulin 30/70, twice daily administration of Humalog Mix25 resulted in improved postprandial glycemic control, similar overall glycemic control, and the convenience of dosing immediately before meals.
Glucose intolerance and 23-year risk of coronary heart disease and total mortality: the Honolulu Heart Program.
Authors: Rodriguez B L , Lau N , Burchfiel C M , Abbott R D , Sharp D S , Yano K , Curb J D
Published: March 2007

OBJECTIVE: The associations between glucose intolerance measured at the study entry date and the 23-year incidence of coronary heart disease (CHD), CHD mortality, and total mortality were examined at the Honolulu Heart Program. RESEARCH DESIGN AND METHODS: This prospective study followed a cohort of 8,006 Japanese-American men who were 45-68 years old and living on the island of Oahu, HI, in 1965. Baseline glucose was measured in a nonfasting state 1 h after a 50-g glucose load. History and use of medication for diabetes was obtained during an interview. The cohort was divided into four categories of glucose tolerance: low-normal, high-normal, asymptomatic hyperglycemia, and known diabetes. RESULTS: During the 23 years of follow-up, 864 incident cases of CHD, 384 deaths from CHD, and 2,166 total deaths occurred. The relative risks (RRs) were obtained using Cox proportional hazards modeling, with the low-normal category as a reference. The RRs were adjusted for age only, as well as for age, BMI, hypertension, cholesterol, triglycerides, smoking, alcohol, and a Japanese diet index. The age-adjusted and risk factor-adjusted RRs for all outcomes were significant for the asymptomatic hyperglycemic and known diabetes groups (P<0.05). The age-adjusted RRs for CHD incidence and total mortality were marginally significant in the high-normal group, but the RRs were not significant when adjusted for risk factors. CONCLUSIONS: These results suggest a dose-response relation of glucose intolerance at baseline with CHD incidence, CHD mortality, and total mortality, independent of other risk factors, in this cohort of middle-aged and older Japanese-American men.
Effects of maternal gestational diabetes on offspring adiposity at 4-7 years of age.
Authors: Vohr B R , McGarvey S T , Tucker R
Published: March 2007

OBJECTIVE: The purpose of this study was to assess the long-term effects of maternal prenatal factors, including gestational diabetes mellitus (GDM), adiposity, and weight gain during pregnancy, on adiposity of offspring from 4 to 7 years of age. A second purpose was to investigate the relationships among childhood adiposity, blood pressure, and 2-h postprandial glucose level. RESEARCH DESIGN AND METHODS: Prospective observational study of four groups of children including large-for-gestational-age (LGA) offspring of mothers with gestational diabetes (OGDM); appropriate-for-gestational-age (AGA) OGDM; LGA control subjects; and AGA control subjects. Anthropometrics including skin-fold measurements, blood pressure measurements, and a 2-h postprandial glucose measurement were obtained at each visit. Repeated measures analysis of variance models were used to detect different patterns of longitudinal change among the groups. RESULTS: LGA OGDM were more likely to be heavier, have larger circumferences and skin-fold measurements, and have a higher BMI than AGA OGDM and control subjects, and these findings increased with increasing age. Blood pressures and postprandial glucose values were similar for OGDM and control subjects at 4-7 years. Multivariable analyses showed that infant BMI and maternal prepregnant BMI predicted 7-year BMI for OGDM, whereas for control subjects, maternal prepregnancy BMI and weight gain during pregnancy were positive predictors with a small negative contribution from birth BMI. CONCLUSIONS: We conclude that LGA OGDM have evidence of increasing body size and adiposity with increasing age and that maternal GDM and maternal prepregnant adiposity are significant predictors of their unique growth patterns.
Muscle fiber characteristics in postmenopausal women with normal or impaired glucose tolerance.
Authors: Larsson H , Daugaard J R , Kiens B , Richter E A , Ahrén B
Published: March 2007

OBJECTIVE: Muscle fiber characteristics are altered in type 2 diabetes. We studied whether these alterations also exist in impaired glucose tolerance (IGT) and whether they are determinants of insulin sensitivity and glucose tolerance in postmenopausal women. RESEARCH DESIGN AND METHODS: Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from 77 postmenopausal women aged 57-59 years: 50 women with normal glucose tolerance (NGT) and 27 with IGT. The IGT group had a reduced insulin sensitivity compared with the NGT group (euglycemic-hyperinsulinemic clamp) (P = 0.003). RESULTS: The groups did not differ in muscle fiber composition, as judged by the percentage of type I, IIa, or IIx fibers. In contrast, the IGT group had increased size of the IIa (mean +/-SD 3,776+/-987 vs. 3,078+/-862 microm2, P = 0.002) and IIx fibers (2,730+/-1,037 vs. 2,253+/-672 microm2, P = 0.017). There was a trend for the capillary diffusion areas (the muscle area supplied by each capillary) to be larger in the IGT group for the IIa (1,132+/-286 vs. 1,013+/-240 microm2, P = 0.061) and IIx fibers (1,020+/-246 vs. 906+/-240 microm2, P = 0.058). In the entire group, insulin sensitivity correlated with the size of the type IIa fibers (r = -0.28, P = 0.013), but not with the percentages of muscle fiber types. In a multiple regression, insulin sensitivity was determined by body fat content and HDL cholesterol level, while the size of the IIa fibers was not included in the model. Glucose tolerance was independently predicted by the number of capillaries/type I fiber, as well as by insulin sensitivity and triglyceride levels. CONCLUSIONS: We conclude that although muscle fiber composition is not altered, women with IGT have larger type IIa and IIx muscle fibers and a trend for increased capillary diffusion areas for these fibers, compared with women with NGT. In the entire group, insulin sensitivity was determined mainly by body fat content, while muscle fiber capillarization may be of importance for glucose tolerance.
Metabolic and immunologic effects of insulin lispro in gestational diabetes.
Authors: Jovanovic L , Ilic S , Pettitt D J , Hugo K , Gutierrez M , Bowsher R R , Bastyr E J
Published: March 2007

OBJECTIVE: To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective. RESEARCH DESIGN AND METHODS: We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer. RESULTS: Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group. CONCLUSIONS: Insulin lispro may be considered a treatment option for women with gestational diabetes.
Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.
Authors: Lee Z S , Chan J C , Yeung V T , Chow C C , Lau M S , Ko G T , Li J K , Cockram C S , Critchley J A
Published: March 2007

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.
Urinary excretion of albumin in adolescents with type 1 diabetes: persistent versus intermittent microalbuminuria and relationship to duration of diabetes, sex, and metabolic control.
Authors: Holl R W , Grabert M , Thon A , Heinze E
Published: March 2007

OBJECTIVE: Urinary excretion of albumin is a marker for incipient diabetic nephropathy in adults. The intra-individual variability, as well as the relationship to duration of diabetes, onset of the disease, and long-term metabolic control, have not been evaluated in a large sample of pediatric patients. RESEARCH DESIGN AND METHODS: A total of 5,722 nocturnal urinary albumin excretion rates were determined in 447 children, adolescents, and young adults with type 1 diabetes, comprising 1,821 years of observation. Excretion rates were related to duration of diabetes, age at onset of diabetes, sex, blood pressure, and metabolic control. RESULTS: Based on repeated measurements in individual patients, the positive predictive value of one sample was 76%, the negative 99.5%. After a duration of diabetes of 11 years, 5% of patients displayed persistent microalbuminuria (10% after 13 years). The duration of diabetes until persistent microalbuminuria was identical for patients with prepubertal or pubertal onset of diabetes. In addition to duration, female sex (P < 0.03) and insufficient long-term metabolic control (P < 0.03) contributed significantly and independently to urinary albumin excretion. CONCLUSIONS: Determination of urinary albumin excretion rate is useful in pediatric patients. Female subjects with a long duration of diabetes and insufficient metabolic control are especially at risk for microalbuminuria. Even if persistent microalbuminuria usually becomes evident in patients aged > 11 years, the prepubertal duration of diabetes contributes equally to this risk. Good metabolic control therefore should be aspired to from the onset of diabetes.
Diabetes in pregnancy and cesarean delivery.
Authors: Remsberg K E , McKeown R E , McFarland K F , Irwin L S
Published: March 2007

OBJECTIVE: To evaluate the effect of diabetes during pregnancy on cesarean delivery and to determine whether the association between diabetes during pregnancy and cesarean delivery is mediated by birth weight. RESEARCH DESIGN AND METHODS: South Carolina 1993 birth certificates were matched through a unique identifier with infant and maternal hospital discharge records for the same year, yielding a total study population of 42,071 singleton births. Adjusted odds ratios (ORs) and 95% CIs were determined for the association between diabetes in pregnancy and cesarean delivery through multiple logistic regression, controlling for maternal age, race, education, number of prenatal care visits, length of gestation, birth weight, and a number of medical indications. RESULTS: Of the study population, 0.7% were pregnancies complicated by preexisting diabetes, 2.9% were pregnancies complicated by gestational diabetes, and 23.4% were cesarean deliveries. After controlling for confounders, including birth weight, cesarean delivery was strongly associated with both preexisting diabetes (OR [95% CI] 6.20 [4.47-8.61]) and gestational diabetes (1.71 [1.41-2.07]). The estimates remained essentially unchanged without birth weight in the model, and were substantially higher in analyses restricted to deliveries without common medical indications for cesarean delivery. CONCLUSIONS: Both preexisting and gestational diabetes increase the risk for cesarean delivery, independent of the effect of birth weight. The association is markedly greater among women without other medical indications for cesarean delivery. The increased risk of cesarean delivery for women with diabetes is mediated through other factors, which may include practice patterns and physician referrals to high-risk care.
Effects of oral hypoglycemic agents and diet on protein metabolism in type 2 diabetes.
Authors: Gougeon R , Styhler K , Morais J A , Jones P J , Marliss E B
Published: March 2007

OBJECTIVE: We tested whether oral hypoglycemic agents (OHA), gliclazide with or without metformin, during an isoenergetic (ISO) and then a low-energy diet (LED) improve the altered kinetics of whole-body protein metabolism in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 13 type 2 diabetic patients (aged 51+/-2 years, weight 110+/-5 kg, BMI 41+/-1 kg/m2, fasting glucose [FSG] 11.5+/-0.9 mmol/l) (means+/-SEM) and 10 obese control subjects (48+/-3 years, 98+/-6 kg, 37+/-2 kg/m2, FSG 5.5+/-0.3 mmol/l) consumed an ISO, 1.5 g x kg(-1) x day(-1) protein for a body weight corresponding to a BMI of 25 (BMI25), a formula diet (7 days for obese control subjects, 15 days for diabetic patients), and then a 28-day LED with 50% of the energy of ISO but the same protein intake (101+/-2 g/day). OHAs were given during ISO (days 8-15) and LED. On days 6-8 (and 12-14 for diabetic subjects) of ISO and 26-28 of LED, the 60-h oral 15N-glycine method was used to obtain nitrogen flux (Q), synthesis (S), and breakdown (B). Muscle protein catabolism was estimated from N(tau)-methylhistidine (3MH) excretion. RESULTS: During ISO with hyperglycemia, Q, and B adjusted for fat-free mass, sex, and age were higher and nitrogen balance and net endogenous protein synthesis (S-B) lower than in control subjects (P<0.05). OHA decreased FSG (9+/-1 mmol/l) and 3MH and increased plasma insulin-to-glucose ratio, nitrogen retention, and S-B to levels in control subjects. The change in S-B correlated with that in FSG (r = -0.845, P = 0.001) and in fasting plasma C-peptide (r = 0.852, P = 0.0005). With LED and OHA, weight decreased 6.3 kg, glycemia reached near-normal levels, and nitrogen equilibrium was maintained; Q decreased by 7%, S and B by 11% (P<0.05) to values found in control subjects. CONCLUSIONS: OHA during ISO corrected protein turnover in relation to glycemia and plasma C-peptide. The LED maintained protein homeostasis in obese control subjects and, in diabetes patients with OHA, normalized protein metabolism. These findings have implications for diet and OHA prescription.
Depressive symptoms and metabolic control in African-Americans with type 2 diabetes.
Authors: Gary T L , Crum R M , Cooper-Patrick L , Ford D , Brancati F L
Published: March 2007

OBJECTIVE: To determine the prevalence of depressive symptoms and the relationship between depressive symptoms and metabolic control. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 183 African-American adults aged 35-75 years with type 2 diabetes who were recruited from two primary care clinics in East Baltimore, Maryland. Depressive symptoms, using the Center for Epidemiological Studies Depression Scale (CES-D), HbA1c, fasting lipid profile, BMI, and blood pressure, were measured on each participant. Diabetes-related health behaviors were assessed by questionnaire. RESULTS: The prevalence of depressive symptoms (CES-D > or =22) was 30%. After adjustment for age, sex, income, social support, and duration of diabetes in linear regression models, there were significant graded relationships between greater depressive symptoms and higher serum levels of cholesterol and triglycerides (P<0.050). Similar, albeit less statistically significant, relationships were found with higher levels of HbA1c (P = 0.104), diastolic blood pressure (P = 0.073), and LDL cholesterol (P = 0.176). Unexpectedly, individuals who reported more depressive symptoms also had higher serum levels of HDL cholesterol (P = 0.047). The associations were not explained by differences in diabetes-related health behaviors. CONCLUSIONS: Depressive symptoms are marginally associated with suboptimal levels of HbA1c, diastolic blood pressure, and LDL cholesterol, and significantly associated with suboptimal levels of total cholesterol and triglyceride levels. Prospective studies are required to determine whether improved identification and management of depressive symptoms would enhance metabolic control in this population.
Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study.
Authors: de Vegt F , Dekker J M , Stehouwer C D , Nijpels G , Bouter L M , Heine R J
Published: March 2007

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.
Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients: the Verona Diabetes Study.
Authors: Muggeo M , Zoppini G , Bonora E , Brun E , Bonadonna R C , Moghetti P , Verlato G
Published: March 2007

OBJECTIVE: In the present study, we evaluated whether the coefficient of variation (CV) of fasting plasma glucose (FPG) over a 3-year period was a significant predictor of mortality in type 2 diabetic patients aged 56-74 years. RESEARCH DESIGN AND METHODS: All type 2 diabetic patients (n = 1,409) aged 56-74 years attending the Verona Diabetes Clinic and having at least two FPG determinations in each of the years 1984-1986 were followed for 10 years (1987-1996) to assess total and cause-specific mortality Patients were grouped into tertiles of mean and CV of FPG during 1984-1986. These parameters as well as sex, age, diabetes duration, insulin treatment, smoking, hypertension, and hypercholesterolemia were included in multivariate survival analyses. RESULTS: During the follow-up, 468 patients died. The CV of FPG was an independent predictor of total, cardiovascular, and cancer mortality. Mean FPG was a predictor of total mortality only when the CV of FPG was not included in the analyses. CONCLUSIONS: Long-term variability of fasting glucose is an independent predictor of mortality in patients with type 2 diabetes. The CV of FPG might be considered a useful additional parameter in the management of these patients.
Vitreous levels of IGF-I, IGF binding protein 1, and IGF binding protein 3 in proliferative diabetic retinopathy: a case-control study.
Authors: Burgos R , Mateo C , Cantón A , Hernández C , Mesa J , Simó R
Published: March 2007

OBJECTIVE: To evaluate vitreous levels of IGF-I and its binding proteins IGFBP-1 and IGFBP-3 in patients with proliferative diabetic retinopathy (PDR). Because intravitreal proteins are elevated in patients with PDR due to the disruption of the blood-retinal barrier, we have corrected vitreal IGF-I and IGFBPs by total vitreal proteins to avoid this confounding factor. RESEARCH DESIGN AND METHODS: We compared 21 diabetic patients with proliferative retinopathy (group A) and 13 nondiabetic patients (group B) in whom a vitrectomy was performed. Both groups were matched by age, serum IGF-I, IGFBP-1, and IGFBP-3 levels. Serum and vitreous levels of IGF-I, IGFBP-1, and IGFBP-3 were measured by immunological methods. Vitreal proteins were assessed by turbidimetric method. RESULTS: Vitreal levels of IGF-I were elevated in group A (median 1.35 ng/ml [range 0.3-8.7]) in comparison with group B (median 0.25 ng/ml [range 0-1.38]), P<0.001. After adjusting by vitreal proteins [ratio IGF-I (ng/ml)/protein (mg/ml)], the differences remain significant (P<0.005). Vitreal levels of IGFBP-1 and IGFBP-3 were also elevated in diabetic patients (IGFBP-1: group A, median 1.6 ng/ml [range 0.6-20.7]; group B, median 0.4 ng/ml [range 0.3-1.9], P<0.001. IGFBP-3: group A, median 102.6 ng/ml [range 53.9-350.8]; group B, median 29.0 ng/ml [range 3.2-87.8], P<0.001). However, when the ratio IGFBP/protein was considered, the differences were not significant. CONCLUSIONS: Intraocular synthesis contributes to elevated vitreous concentrations of IGF-I found in PDR. By contrast, unspecific increase of intravitreal proteins is the main factor explaining the elevated vitreous levels of IGFBP-1 and IGFBP-3 found in diabetic patients.
Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.
Authors: Vuksan V , Sievenpiper J L , Owen R , Swilley J A , Spadafora P , Jenkins D J , Vidgen E , Brighenti F , Josse R G , Leiter L A , Xu Z , Novokmet R
Published: March 2007

OBJECTIVE: Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. RESEARCH DESIGN AND METHODS: We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. RESULTS: Decreases in serum cholesterol (total, 12.4+/-3.1%, P<0.004; LDL, 22+/-3.9%, P<0.002; total/HDL ratio, 15.2+/-3.4%, P<0.003; and LDL/HDL ratio, 22.2+/-4.1%, P< 0.002), apolipoprotein (apo) B (15.1+/-4.3%, P<0.0004), apo B/A-1 ratio (13.1+/-3.4%, P< 0.0003), and serum fructosamine (5.2+/-1.4%, P<0.002) were observed during KJM treatment compared with WB-control. Fasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. CONCLUSIONS: A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.
Diabetes is an independent risk factor for in-hospital mortality from acute spontaneous intracerebral hemorrhage.
Authors: Arboix A , Massons J , García-Eroles L , Oliveres M , Targa C
Published: March 2007

OBJECTIVE: We tested the hypothesis that diabetes is an independent determinant of outcome after intracerebral hemorrhage (ICH). RESEARCH DESIGN AND METHODS: This was a hospital-based prospective study The setting was an acute care 350-bed hospital in the city of Barcelona, Spain. Spontaneous ICH was diagnosed in 229 (11%) of 2,000 consecutive stroke patients included in a prospective stroke registry during a 10-year period. Main outcome measures were frequency of demographic variables, risk factors, clinical events, neuroimaging data, and outcome in ICH patients with and without diabetes. Variables related to vital status at discharge (alive or dead) in the univariate analysis plus age were studied in 4 logistical regression models. RESULTS: A total of 35 patients (15.3%) had diabetes. The overall in-hospital mortality rate was 54.3% in the diabetic group and 26.3% in the nondiabetic group (P < 0.001). Previous cerebral infarction, altered consciousness, sensory symptoms, cranial nerve palsy, multiple topography of the hematoma, intraventricular hemorrhage, and infectious complications were significantly more frequent in diabetic patients than in nondiabetic patients. The presence of diabetes was a significant predictive variable in the model based on demographic variables and cardiovascular risk factors (odds ratio 2.98 [95% CI 1.37-6.46]) and in the models based on these variables plus clinical variables (5.76 [2.01-16.51]), neuroimaging variables (5.59 [1.87-16.691), and outcome data (6.10 [2.04-18.291). CONCLUSIONS: Diabetes is an independent determinant of death after ICH. ICH in diabetic individuals presents some different clinical features compared with ICH in nondiabetic patients.
Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.
Authors: Hamada Y , Nakamura J , Naruse K , Komori T , Kato K , Kasuya Y , Nagai R , Horiuchi S , Hotta N
Published: March 2007

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.