bluuebunny/crossref_metadata_2025 huggingface dataset:
Inconsistent Use of Diabetes Medications, Diabetes Complications, and Mortality in Older Mexican Americans Over a 7-Year Period
Authors: Kuo Yong-Fang , Raji Mukaila A. , Markides Kyriakos S. , Ray Laura A. , Espino David V. , Goodwin James S.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the relationship between inconsistency in use of diabetes drugs and risk of renal, eye, and circulation problems and death over a 7-year period in community-dwelling older Mexican Americans.

RESEARCH DESIGN AND METHODS—Data are from the four waves of the Hispanic Established Population for the Epidemiologic Study of the Elderly. In-home interviewers assessed consistency in use of diabetes medications among 908 diabetic Mexican Americans, aged ≥65 years. Diabetes and complications were by self-report. Subjects with poor consistency in use of medication were those who, at any time during the 7-year follow-up, discontinued or inconsistently used their diabetes medications and those who had no diabetic medications at home despite self-report of taking medicine for diabetes.

RESULTS—Thirty-six percent of our sample were inconsistent with diabetes medication usage. Older age and lack of supplemental health insurance were significantly associated with inconsistency of use of medication. In a multivariate logistic regression model, subjects with poor consistency in use of medication were more likely to report kidney problems (odds ratio [OR] 1.59; 95% CI 1.13–2.23; P = 0.008) at follow-up compared with those with good consistency, after controlling for age, sex, medication type, duration of diabetes, education, income, marital status, language of interview, insurance status, cognitive function, presence of depressive symptoms, activities of daily living, and instrumental activities of daily living. In Cox regression models, poor consistency with diabetic medication was also associated with increased all-cause mortality (hazard ratio [HR] 1.43; 95% CI 1.13–1.82; P = 0.003) and diabetes-related deaths (1.66; 1.20–2.30; P = 0.002) over a 7-year period after adjusting for relevant confounders.

CONCLUSIONS—Inconsistent use of diabetic medication was associated with an increased risk of kidney problems and deaths over a 7-year period in older Mexican Americans.
Controlled Trial of a Multifaceted Intervention for Improving Quality of Care for Rural Patients With Type 2 Diabetes
Authors: Majumdar Sumit R. , Guirguis Lisa M. , Toth Ellen L. , Lewanczuk Richard Z. , Lee T.K. , Johnson Jeffrey A.
Published: March 2007

OBJECTIVE—Despite good evidence and clinical practice guidelines, studies document that treatment of type 2 diabetes is less than optimal. Lack of resources or limited access may put patients in rural communities at particular risk for suboptimal care.

RESEARCH DESIGN AND METHODS—We conducted a prospective, before/after study with concurrent controls to assess the effectiveness of a multidisciplinary diabetes outreach service (intervention) for improving the quality of care for rural patients with type 2 diabetes. Our intervention consisted of six monthly visits by a traveling team of specialist physicians, nurses, dieticians, and a pharmacist. The core of this service was specialist-to-rural primary care physician academic group detailing. Two comparable regions in Northern Alberta were randomly allocated to control or intervention. Data were collected before and 6 months after intervention in a representative volunteer sample. The primary outcome was a 10% improvement in any one of the following: blood pressure, total cholesterol, or HbA1c.

RESULTS—Our analysis included 200 intervention and 179 control subjects; 14 subjects were at all three primary outcome targets at baseline. The intervention was associated with a trend toward improvement in primary outcome at 6 months (44% intervention vs. 37% control; odds ratio 1.32, 95% CI 0.87–1.99). The intervention was associated with a significant improvement in blood pressure (42% intervention vs. 25% control, P = 0.004); however, there were only small, nonsignificant changes in cholesterol or HbA1c. The intervention was associated with a significant increase in satisfaction with diabetes care. Multivariate adjustment for baseline differences between intervention and control subjects did not affect any of the main results.

CONCLUSIONS—A diabetes outreach service has the potential to improve the quality of diabetes care for rural patients. Future studies need to involve longer timelines and larger sample sizes.
General Quality of Life in Youth With Type 1 Diabetes
Authors: Laffel Lori M.B. , Connell Alexa , Vangsness Laura , Goebel-Fabbri Ann , Mansfield Abigail , Anderson Barbara J.
Published: March 2007

OBJECTIVE—To evaluate self-report and parent proxy report of child/teen general quality of life in youth with type 1 diabetes, compare their responses with those of a general pediatric population, and identify relationships between diabetes management, diabetes-related family behavior, and diabetes-specific family conflict with quality of life in youth with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Study participants included 100 children, 8–17 years of age (12.1 ± 2.3), with type 1 diabetes for 0.5–6 years (2.7 ± 1.6). Each child and a parent completed the Pediatric Quality of Life Inventory (PedsQL), completed the Diabetes Family Conflict Scale, and provided data on parent involvement in diabetes management. An independent measure of adherence to treatment assessed by the patient’s clinician and a measure of glycemic control (HbA1c) were also collected.

RESULTS—PedsQL responses from youth with type 1 diabetes were stable over 1 year and similar to norms from a healthy standardization sample for all three scales of the PedsQL: total, physical, and psychosocial quality of life. After controlling for age, duration of diabetes, sex, HbA1c, and family involvement, child report of diabetes-specific family conflict (P < 0.01) was the only significant predictor of child report of quality of life (model R2 = 0.21, P < 0.02).

CONCLUSIONS—Youth with type 1 diabetes report remarkably similar quality of life to a nondiabetic youth population. Greater endorsement of diabetes-specific family conflict predicted diminished quality of life for the child. As treatment programs focus on intensifying glycemic control in youth with type 1 diabetes, interventions should include efforts to reduce diabetes-specific family conflict in order to preserve the child’s overall quality of life.
Pramlintide Reduces Postprandial Glucose Excursions When Added to Regular Insulin or Insulin Lispro in Subjects With Type 1 Diabetes
Authors: Weyer Christian , Gottlieb Alan , Kim Dennis D. , Lutz Karen , Schwartz Sherwyn , Gutierrez Maria , Wang Yan , Ruggles James A. , Kolterman Orville G. , Maggs David G.
Published: March 2007

OBJECTIVE—To assess the postprandial glucose-lowering effect of the human amylin analog pramlintide when given with either regular insulin or insulin lispro in subjects with type 1 diabetes, with an emphasis on the optimal dose timing relative to meals.

RESEARCH DESIGN AND METHODS—In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 1 diabetes using regular insulin and 21 subjects with type 1 diabetes using insulin lispro underwent five consecutive mixed meal tests. In randomized order, subjects received subcutaneous injections of placebo at −15 min or 60 μg pramlintide at −15, 0, +15, or +30 min relative to the meal after an overnight fast. Regular insulin or insulin lispro was injected at −30 and 0 min, respectively, at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period.

RESULTS—In both the regular insulin and insulin lispro groups, pramlintide injections at all four time points lowered the postprandial glucose excursion (36 to >100% reduction in incremental area under the concentration time curve from 0 to 4 h (AUC0–4 h) compared with placebo. However, only preprandial injections of pramlintide (−15 and 0 min) were able to prevent the initial postprandial surge in glucose. The optimal time for pramlintide injection was 0 min, which reduced the postprandial glucose excursion by >100% compared with regular insulin plus placebo (incremental AUC0–4 h: −0.6 ± 2.5 vs. 11.0 ± 2.9 mmol · h−1 · l−1, P < 0.0007) and by 75% compared with insulin lispro plus placebo (incremental AUC0–4 h: 2.5 ± 2.1 vs. 10.0 ± 2.5 mmol · h−1 · l−1, P < 0.0098). No serious adverse events were reported.

CONCLUSIONS—Pramlintide, given at or just before a meal, reduces the postprandial glucose excursion in subjects with type 1 diabetes, regardless of whether added to regular insulin or a rapid-acting insulin analog.
The Treat-to-Target Trial
Authors: Riddle Matthew C. , Rosenstock Julio , Gerich John ,   on behalf of the Insulin Glargine 4002 Study Investigators
Published: March 2007

OBJECTIVE—To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA1c.

RESEARCH DESIGN AND METHODS—In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA1c >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) ≤100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA1c, hypoglycemia, and percentage of patients reaching HbA1c ≤7% without documented nocturnal hypoglycemia.

RESULTS—Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA1c (6.96 vs. 6.97%). A majority of patients (∼60%) attained HbA1c ≤7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (≤72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P < 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21–48% lower with glargine.

CONCLUSIONS—Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA1c in a majority of overweight patients with type 2 diabetes with HbA1c between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.
Insulin Detemir Is Characterized by a Consistent Pharmacokinetic Profile Across Age-Groups in Children, Adolescents, and Adults With Type 1 Diabetes
Authors: Danne Thomas , Lüpke Kerstin , Walte Kerstin , von Schuetz Wolfgang , Gall Mari-Anne
Published: March 2007

OBJECTIVE—This trial aimed to characterize for the first time the pharmacokinetic profile of insulin detemir, the novel soluble basal insulin analog, in children and adolescents compared with adults. Comparisons were also made with NPH insulin to determine any between-treatment difference in the effect of age on pharmacokinetic profile.

RESEARCH DESIGN AND METHODS—This single-center, open-label, randomized, crossover trial included children (aged 6–12 years, n = 13), adolescents (aged 13–17 years, n = 10), and adults (aged 18–65 years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood sampling was performed for 24 h for analysis of serum insulin detemir, human insulin, and glucose concentrations.

RESULTS—The mean pharmacokinetic profile of insulin detemir was similar across all three age-groups. This was determined by statistical analyses of the data, which showed no overall age effect or between-group differences when pairwise comparisons were made between children (or adolescents) and adults on the parameters of the area under the curve (AUC), AUC from zero to infinity, AUC from 0 to 24 h [AUC(0–24 h)], and the maximum concentration measured during the 24 h after closing. No overall age effect for AUC(0–24 h) and Cmax was detected for NPH insulin, but data were only analyzable from seven adults and pairwise comparisons did indicate that children and adults had different pharmacokinetic profiles. Less total variability in the pharmacokinetics of insulin detemir than NPH insulin was indicated by lower coefficients of variation in AUC, Cmax, and time to maximum concentration in all three age-groups.

CONCLUSIONS—The data suggest that insulin detemir can be used in children and adolescents with type 1 diabetes using titration guidelines similar to those used in adults. Moreover, insulin detemir may offer the advantage of greater predictability of response in comparison to NPH insulin due to lower total variability and a lesser degree of kinetic disparity across age-groups.
Sex Differences in the Prognostic Importance of Diabetes in Patients With Ischemic Heart Disease Undergoing Coronary Angiography
Authors: Graham Michelle M. , Ghali William A. , Faris Peter D. , Galbraith P. Diane , Norris Colleen M. , Knudtson Merril L. ,   APPROACH Investigators
Published: March 2007

OBJECTIVE—Women with ischemic heart disease have poorer outcomes than men and are suggested to have greater risk associated with diabetes. We evaluated the prognosis associated with diabetes, in analyses stratified by sex, to determine whether similar differences are seen in a large unselected cohort of patients.

RESEARCH DESIGN AND METHODS—Using the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a clinical data collection and follow-up initiative capturing all patients undergoing cardiac catheterization in Alberta, Canada, the relative significance of diabetes on long-term survival in 13,152 men and 4,249 women was evaluated in patients presenting with or without myocardial infarction and according to first treatment received.

RESULTS—The 1-year mortality rates were 4.7% and 6.8% in men and women (P < 0.001), 4.1% and 7.4% in nondiabetic and diabetic men (P < 0.001), and 5.8% and 9.6% in nondiabetic and diabetic women, respectively (P < 0.001). The risk-adjusted Cox proportional hazard ratios associated with diabetes in myocardial infarction were 1.03 in men and 1.20 in women. The diabetes hazard ratios for percutaneous coronary intervention were 1.28 in men and 1.40 in women, 1.23 in men and 1.32 in women for bypass surgery, and 1.26 in men and 1.31 in women for medical therapy (P = NS for all diabetes hazard ratio comparisons between men and women).

CONCLUSIONS—Hazard ratios quantifying the adverse prognosis associated with diabetes in patients undergoing angiography are consistently higher among women than men, but the differences across sexes are not statistically significant. These slight sex differences noted in the APPROACH registry are similar to previously reported findings and may be clinically important.
Adiponectin in a Native Canadian Population Experiencing Rapid Epidemiological Transition
Authors: Hanley Anthony J.G. , Connelly Philip W. , Harris Stewart B. , Zinman Bernard
Published: March 2007

OBJECTIVE—Adiponectin is emerging as an important protein in the etiology of obesity and related metabolic disorders. The objectives of this study were to determine cross-sectional and prospective associations of adiponectin concentration with adiposity, type 2 diabetes, and cardiovascular disease (CVD) risk factors in a population-based study of Native Canadians, a group experiencing dramatic increases in diabetes and CVD.

RESEARCH DESIGN AND METHODS—During the 1993–1995 baseline survey, samples for glucose, insulin, adiponectin, and lipids were collected after an overnight fast. Waist circumference and percent body fat were measured, and a 75-g oral glucose tolerance test was administered: n = 505 with normal glucose tolerance (NGT), 74 with impaired glucose tolerance (IGT), and 149 with diabetes. In 1998, 95 high-risk subjects, defined as those who, at baseline, had either IGT or NGT with an elevated 2-h glucose concentration (≥7.0 mmol/l), participated in a follow-up examination using the protocol used at baseline.

RESULTS—After adjustment for covariates including percent body fat and homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin concentrations were significantly lower among men versus women (10.8 vs. 15.0 μg/ml, P < 0.0001) and among diabetic versus NGT subjects (11.1 vs. 13.1 μg/ml, P < 0.05). Adiponectin was inversely correlated with percent body fat, waist circumference, HOMA-IR, and triglyceride and positively correlated with HDL (r = |0.30|–|0.44|, all P < 0.0001). In multivariate linear regression analysis in nondiabetic subjects, HDL and percent body fat were significantly related to adiponectin variation among both men and women (R2 = 28–29%). Factor analysis returned three underlying factors among these variables, with adiponectin loading on the second factor along with insulin, waist circumference, triglyceride, and HDL. In the follow-up study, higher adiponectin at baseline was significantly associated with increases in HDL (r = 0.24, P = 0.03) and decreases in HOMA-IR (r = −0.29, P = 0.009) after adjustment for covariates, including age, adiposity, and diabetes status at baseline and follow-up.

CONCLUSIONS—These population-based findings support the hypothesis that low circulating levels of adiponectin are an important determinant of risk of CVD.
In Utero Dietary Exposures and Risk of Islet Autoimmunity in Children
Authors: Fronczak Carolyn M. , Barón Anna E. , Chase H. Peter , Ross Colleen , Brady Heather L. , Hoffman Michelle , Eisenbarth George S. , Rewers Marian , Norris Jill M.
Published: March 2007

OBJECTIVE—The goal of this study was to examine whether maternal dietary intake of vitamin D, ω-3 fatty acids, and ω-6 fatty acids during pregnancy is associated with the appearance of islet autoimmunity (IA) in offspring.

RESEARCH DESIGN AND METHODS—The Diabetes Autoimmunity Study in the Young (DAISY) is recruiting at birth and following children at increased risk for type 1 diabetes, as determined by HLA-DR genotype or by family history of type 1 diabetes. A total of 233 mothers of newly recruited DAISY subjects were asked to recall their intake of food and nutritional supplements during the third trimester of pregnancy using the Willett food frequency questionnaire. Children were followed for an average of 4 years (range 0.8–7.3 years) for the appearance of insulin, GAD65, and IA-2 autoantibodies. Sixteen children developed at least one autoantibody during this period. Unadjusted and adjusted hazard ratios (HRs) for the development of IA were estimated with survival analysis using a Weibull distribution.

RESULTS—Maternal intake of vitamin D via food was significantly associated with a decreased risk of IA appearance in offspring, independent of HLA genotype, family history of type 1 diabetes, presence of gestational diabetes mellitus, and ethnicity (adjusted HR = 0.37; 95% CI 0.17–0.78). Vitamin D intake via supplements, ω-3 fatty acids, and ω-6 fatty acids intake during pregnancy were not associated with appearance of IA in offspring.

CONCLUSIONS—Our findings suggest that maternal intake of vitamin D through food during pregnancy may have a protective effect on the appearance of IA in offspring.
Premenopausal Advantages in Postprandial Lipid Metabolism Are Lost in Women With Type 2 Diabetes
Authors: Masding Michael G. , Stears Anna J. , Burdge Graham C. , Wootton Stephen A. , Sandeman Derek D.
Published: March 2007

OBJECTIVE—Women with type 2 diabetes appear to lose the protection against cardiovascular disease afforded by estrogens. We examined the effects of menopausal status on postprandial clearance of dietary fat in healthy and diabetic women.

RESEARCH DESIGN AND METHODS—Fasting subjects (premenopausal and postmenopausal control subjects, premenopausal and postmenopausal diabetic women, all n = 8) were given a meal containing the stable isotope 1,1,1-13C-tripalmitin, with blood and breath sampled for 6 and 24 h, respectively, in the postprandial period. Lower levels of 13C-palmitic acid (13C-PA) in the triglyceride fraction implies more efficient chylomicron clearance, lower levels of 13C-PA in the nonesterified fatty acid (NEFA) fraction implies improved dietary NEFA entrapment, and higher levels of 13CO2 in the breath denote more efficient of oxidation of dietary-derived lipid.

RESULTS—In diabetic women, there were no differences between the pre- and postmenopausal groups for any of these parameters. In contrast, premenopausal control subjects, compared with postmenopausal control subjects, had lower 13C-PA in the triglyceride fraction area under the curve (AUC) (premenopausal median [range] 25.2 [12.1–49.4 mmol/l] per 6 h, postmenopausal 48.5 [15.5–77.2 mmol/l] per 6 h; P < 0.01) and higher 13CO2 levels in the breath AUC (premenopausal 22.5 [18.0–31.5%] of administered dose, postmenopausal 17.2 [11.2–31.5%] of administered dose; P < 0.01) with no difference between groups in levels of 13C-PA in the NEFA fraction AUC.

CONCLUSIONS—The premenopausal advantage in clearance of dietary lipid is not seen in premenopausal diabetic women. This is likely to promote an atherogenic lipoprotein profile and may contribute to the loss of cardiovascular disease protection seen in diabetic women.
Lowering the Criterion for Impaired Fasting Glucose Is in Order
Authors: Genuth Saul
Published: March 2007

Editor’s comment: Because of the controversial nature of the new lowered criterion for IFG, I offered the Chairman of the Expert Committee an opportunity to respond to my commentary on the subject. I would only point out that Dr. Genuth’s reference 8 shows an association between glycemia and cardiovascular disease (as have many other reports), but to date, five prospective studies, analyzed either singly or as a metanalysis, have been unable to demonstrate a beneficial effect of lowering glycemia on cardiovascular disease outcomes.
Plasma Adiponectin Plays an Important Role in Improving Insulin Resistance With Glimepiride in Elderly Type 2 Diabetic Subjects
Authors: Tsunekawa Taku , Hayashi Toshio , Suzuki Yusuke , Matsui-Hirai Hisako , Kano Hatsuyo , Fukatsu Akiko , Nomura Noriko , Miyazaki Asaka , Iguchi Akihisa
Published: March 2007

OBJECTIVE—We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2α (8-epi-PGF2α), an oxidative stress marker.

RESEARCH DESIGN AND METHODS—A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of β-cell function, HbA1c, C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2α, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp.

RESULTS—After 8 weeks of glimepiride treatment, significant reductions were observed in HbA1c (from 8.4 ± 1.9 to 6.9 ± 1.0%), HOMA-IR (from 2.54 ± 2.25 to 1.69 ± 0.95%), and plasma TNF-α concentrations (from 4.0 ± 2.0 to 2.6 ± 2.5 pg/ml). MCR-g was significantly increased from 3.92 ± 1.09 to 5.73 ± 1.47 mg · kg−1 · min−1. Plasma adiponectin increased from 6.61 ± 3.06 to 10.2 ± 7.14 μg/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers.

CONCLUSIONS—Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA1c without changing extrapancreatic β-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-α may underlie the improvement of insulin resistance with glimepiride.
Diabetes as a Predictor of Change in Functional Status Among Older Mexican Americans
Authors: Wu Jasmanda H. , Haan Mary N. , Liang Jersey , Ghosh Debashis , Gonzalez Hector M. , Herman William H.
Published: March 2007

OBJECTIVE—Epidemiological studies have demonstrated that older Mexican Americans are at high risk for type 2 diabetes and its complications. Type 2 diabetes leads to a more rapid decline in functional status among older Mexican Americans with diabetes. This study was designed to examine the impact of diabetes on change in self-reported functional status over a 2-year period among older Mexican Americans with diabetes.

RESEARCH DESIGN AND METHODS—We performed a longitudinal analysis with repeated measurements of functional limitations in a cohort of Mexican Americans aged ≥60 years in the Sacramento Area Latino Study on Aging (SALSA). Diabetes was diagnosed on the basis of self-report of physician diagnosis, medication use, and fasting plasma glucose. Functional status was measured by assessment of activities of daily living (ADL) and instrumental activities of daily living (IADL) at baseline and 1 and 2 years.

RESULTS—Of 1,789 SALSA participants, 585 (33%) had diabetes at baseline. Diabetic subjects reported 74% more limitations than nondiabetic subjects in ADL (summary score for number of limitations, 0.99 vs. 0.57; P = 0.002) and 50% more limitations in IADL (summary score for number of limitations, 7.83 vs. 5.25; P < 0.0001). The annual rate of increase in limitations of ADL and IADL was 0.046 and 0.033 (log scale) on each scale among diabetic subjects compared with 0.013 and 0.003 (log scale) among nondiabetic subjects (P < 0.0005). Complications of diabetes were found to increase ADL and IADL limitations among diabetic subjects. Longer duration of diabetes was also associated with an increase in ADL and IADL limitations.

CONCLUSIONS—There was lower baseline functional status and a more rapid decline in functional status among older Mexican Americans with diabetes versus those without diabetes.
The Effects of Diabetes on the Risks of Major Cardiovascular Diseases and Death in the Asia-Pacific Region
Authors:   Asia Pacific Cohort Studies Collaboration
Published: March 2007

OBJECTIVE—To provide reliable age- and region-specific estimates of the associations between diabetes and major cardiovascular diseases and death in populations from the Asia-Pacific region.

RESEARCH DESIGN AND METHODS—Twenty-four cohort studies from Asia, Australia, and New Zealand (median follow-up, 5.4 years) provided individual participant data from 161,214 people (58% from Asia) of whom 4,873 had a history of diabetes at baseline. The associations of diabetes with the risks of coronary heart disease, stroke, and cause-specific mortality during follow-up were estimated using time-dependent Cox models, stratified by study cohort and sex and adjusted for age at risk.

RESULTS—In all, 9,277 deaths occurred (3,635 from cardiovascular disease). The hazard ratio (95% CI) associated with diabetes was 1.97 (1.72–2.25) for fatal cardiovascular disease; there were similar hazard ratios for fatal coronary heart disease, fatal stroke, and composites of fatal and nonfatal outcomes. For all cardiovascular outcomes, hazard ratios were similar in Asian and non-Asian populations and in men and women, but were greater in younger than older individuals. For noncardiovascular death, the hazard ratio was 1.56 (1.38–1.77), with separately significant increases in the risks of death from renal disease, cancer, respiratory infections, and other infective causes. The hazard ratio for all-causes mortality was 1.68 (1.55–1.84), with similar ratios in Asian and non-Asian populations, but with significantly higher ratios in younger than older individuals.

CONCLUSIONS—The relative effect of diabetes on the risks of cardiovascular disease and death in Asian populations is much the same as that in the largely Caucasian populations of Australia and New Zealand. Hazard ratios were severalfold greater in younger people than older people. The rapidly growing prevalence of diabetes in Asia heralds a large increase in the incidence of diabetes-related death in the coming decades.
Self-Reported Diabetes and Health Behaviors in Remote Indigenous Communities in Northern Queensland, Australia
Authors: McCulloch Brad , McDermott Robyn , Miller Geoff , Leonard Dympna , Elwell Michelle , Muller Reinhold
Published: March 2007

OBJECTIVE—This study examines associations between self-reported diabetes and self-reported smoking, alcohol consumption, fruit consumption, and participation in adequate exercise in remote indigenous communities, using data from the Well Persons’ Health Check (WPHC).

RESEARCH DESIGN AND METHODS—The WPHC was a cross-sectional survey of 2,862 indigenous individuals (1,602 Aborigines, 1,074 Torres Strait Islanders, and 186 persons of joint descent) aged ≥15 years. The study was conducted in 26 remote communities in northern Queensland, Australia, between March 1998 and October 2000.

RESULTS—A total of 32% of individuals with self-reported diabetes and 25% of other individuals reported eating enough fruit, according to National Health and Medical Research Council criteria: odds ratio (OR) 1.407 (95% CI 1.108–1.786), P = 0.006. After adjustment for age, sex, and ethnicity, no significant difference could be observed: adjusted OR 1.22 (0.944–1.574), P = 0.128. A total of 58% of participants who reported diabetes and 51% of others reported adequate exercise: OR 0.761 (0.609–0.952), P = 0.018. This difference was not significant after adjustment for age, sex, and ethnicity: adjusted OR 0.896 (0.705–1.14), P = 0.370. A total of 43% of individuals who reported diabetes and 72% of others reported consuming alcohol: OR 0.295 (0.235–0.369), P < 0.001. After adjustment for age, sex, and ethnicity, this difference was still significant: adjusted OR 0.550 (0.428–0.709), P < 0.001. Diabetic drinkers consumed alcohol at harmful levels similar to those of nondiabetic drinkers (P = 0.691). A total of 40% of individuals who reported diabetes and 63% of other persons were tobacco smokers: OR 0.403 (0.322–0.505), P < 0.001. Although this crude difference was attenuated by adjustment for age, sex, and ethnicity, persons with self-reported diabetes were still significantly less likely to smoke tobacco than other participants: adjusted OR 0.666 (0.521–0.852), P = 0.001. Smoking prevalence among the diabetic indigenous participants was more than double that in nondiabetic nonindigenous Australians.

CONCLUSIONS—This study suggests that indigenous individuals with diabetes living in rural and remote communities are not adopting lifestyle changes required for optimal self-management of the disease. This contributes to the large excess of mortality and morbidity experienced by this population.
Association of NAD(P)H Oxidase p22 phox Gene Variation With Advanced Carotid Atherosclerosis in Japanese Type 2 Diabetes
Authors: Hayaishi-Okano Rieko , Yamasaki Yoshimitsu , Kajimoto Yoshitaka , Sakamoto Ken’ya , Ohtoshi Kentaro , Katakami Naoto , Kawamori Dan , Miyatsuka Takeshi , Hatazaki Masahiro , Hazama Yoji , Hori Masatsugu
Published: March 2007

OBJECTIVE—To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects.

RESEARCH DESIGN AND METHODS—C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients’ clinical characteristics and the level of 8-hydroxy-2′deoxyguanosine (8-OHdG) as an index of oxidative DNA damage.

RESULTS—The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 ± 0.31 vs. 1.31 ± 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 ± 0.14 vs. 0.94 ± 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 ± 15.6 vs. 64.2 ± 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 ± 0.66 vs. 2.60 ± 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group.

CONCLUSIONS—These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.
Insulin Sensitivity and Lipid Metabolism in Human CD36 Deficiency
Authors: Furuhashi Masato , Ura Nobuyuki , Nakata Tomoaki , Shimamoto Kazuaki
Published: March 2007

OBJECTIVE—CD36 has been proposed as a fatty acid translocase and a receptor for HDL and oxidized LDL. The association between CD36 deficiency and insulin resistance remains controversial. We investigated glucose and lipid metabolism in human CD36 deficiency.

RESEARCH DESIGN AND METHODS—A total of 61 type I CD36-deficient patients and 25 control subjects were examined. Diabetes was defined as fasting glucose level ≥7 mmol/l or use of hypoglycemic agents. A homeostasis model assessment (HOMA) index was evaluated in patients without diabetes. Insulin resistance was defined as a HOMA index ≥1.73 (sensitivity 64.3%, specificity 78.9%; J Japan Diab Soc, 2000).

RESULTS—Diabetes was identified in 12 (20%) of the 61 CD36-deficient patients. Fasting glucose, HbA1c, and total cholesterol levels in the diabetic CD36-deficient patients were significantly higher than in the control subjects and the nondiabetic CD36-deficient patients. Regardless of diabetes, HDL cholesterol concentrations in the CD36-deficient patients were significantly higher than in the control subjects. The nondiabetic CD36-deficient patients had higher triglyceride concentrations than the control subjects, and triglyceride concentrations were higher in the diabetic CD36-deficient patients than in the nondiabetic CD36-deficient patients. The prevalence of insulin resistance in the nondiabetic CD36-deficient patients was similar to that in the control subjects.

CONCLUSIONS—Human CD36 deficiency is not necessarily responsible for insulin resistance. Lipid abnormalities in CD36 deficiency may partly depend on the presence of diabetes, and increased levels of triglyceride and HDL cholesterol may be due to impaired binding of fatty acids and HDL to CD36 and subsequent clearance.
Amputation and Mortality in New-Onset Diabetic Foot Ulcers Stratified by Etiology
Authors: Moulik Probal K. , Mtonga Robert , Gill Geoffrey V.
Published: March 2007

OBJECTIVE—Foot ulcers and their complications are an important cause of morbidity and mortality in diabetes. The present study aims to examine the long-term outcome in terms of amputations and mortality in patients with new-onset diabetic foot ulcers in subgroups stratified by etiology.

RESEARCH DESIGN AND METHODS—Patients presenting with new ulcers (duration <1 month) to a dedicated diabetic foot clinic between 1994 and 1998 were studied. Outcomes were determined until March 2000 (or death) from podiatry, hospital, and district registers. Baseline clinical examination was done to classify ulcers as neuropathic, ischemic, or neuroischemic. Five-year amputation and mortality rates were derived from Kaplan-Meier survival analysis curves.

RESULTS—Of the 185 patients studied, 41% had peripheral vascular disease (PVD) and 61% had neuropathy; 45%, 16%, and 24% of patients had neuropathic, ischemic, and neuroischemic ulcers, respectively. The mean follow-up period was 34 months (range 1–65) including survivors and patients who died during the study period. Five-year amputation rates were higher for ischemic (29%) and neuroischemic (25%) than neuropathic (11%) ulcers. Five-year mortality was 45%, 18%, and 55% for neuropathic, neuroischemic, and ischemic ulcers, respectively. Mortality was higher in ischemic ulcers than neuropathic ulcers. On multivariate regression analysis, only increasing age predicted shorter survival time.

CONCLUSIONS—All types of diabetic foot ulcers are associated with high morbidity and mortality. The increased mortality appears to be independent of factors increasing ulcer risk—that is, neuropathy and PVD—in patients with established foot ulcers.
Comparative Effects of Irbesartan on Ambulatory and Office Blood Pressure
Authors: Rossing Kasper , Christensen Per K. , Andersen Steen , Hovind Peter , Hansen Henrik Post , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Irbesartan was renoprotective independently of its blood pressure-lowering effect in the Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria (IRMA2) study. However, blood pressure was evaluated by trough office blood pressure (OBP), which may underestimate reductions in 24-h ambulatory blood pressure (ABP). In the present study, we evaluated 24-h blood pressure patterns in a subpopulation of the IRMA2 trial.

RESEARCH DESIGN AND METHODS—Type 2 diabetic patients (n = 43) with persistent microalbuminuria (as determined by repeated overnight measurements of urinary albumin excretion [UAE]) and hypertension who were included in the IRMA2 study at the Steno Diabetes Center were subjected to 24-h ABP (Takeda, TM2420) measurements before and 2 years after randomization to placebo (n = 15), irbesartan 150 mg daily (Irb150; n = 13), or irbesartan 300 mg daily (Irb300; n = 15).

RESULTS—At baseline, the placebo, Irb150, and Irb300 groups were comparable: OBP: 157 ± 15/89 ± 7, 156 ±15/91 ± 11, and 159 ± 16/90 ± 9 mmHg (NS); 24-h ABP: 148 ± 13/83 ± 11, 148 ± 16/82 ± 7 and 147 ± 16/81 ± 10 mmHg (NS); and UAE (geometric mean with 95% CI): 43 (32–57), 46 (30–70), and 59 (42–85) μg/min (NS), respectively. We found that 2 years after randomization, OBP was significantly reduced in all three groups (by 11/7, 13/8, and 13/8 mmHg in the placebo, Irb150, and Irb300 groups, respectively), but that there were no significant differences among groups. Reductions in 24-h ABP were similar in the three groups (11/10, 5/7, and 7/8 mmHg, respectively; NS), as were reductions in day ABP (11/9, 7/7, and 8/9 mmHg, respectively; NS) and night ABP (4/11, 7/7, and 3/3 mmHg, respectively; NS). The reduction in UAE at the end of the study was 0% (−86 to 42), 38% (−14 to 66), and 73% (59 to 82), respectively (overall, P < 0.01).

CONCLUSION—Irbesartan is renoprotective independently of its beneficial effect in lowering 24-h blood pressure in patients with type 2 diabetes and persistent microalbuminuria.
A Comparison of the Prevalence of the Metabolic Syndrome Using Two Proposed Definitions
Authors: Ford Earl S. , Giles Wayne H.
Published: March 2007

OBJECTIVE—To compare the prevalence of the metabolic syndrome using two definitions: one proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) and one by the World Health Organization (WHO).

RESEARCH DESIGN AND METHODS—We used data from a nationally representative sample of the noninstitutionalized civilian population of the U.S. from the Third National Health and Nutrition Examination Survey, a cross-sectional health examination survey (1988–1994).

RESULTS—Among 8,608 participants aged ≥20 years, the age-adjusted prevalence was 23.9% using the ATP III definition and 25.1% using the WHO definition. Among all participants, 86.2% were classified as either having or not having the metabolic syndrome under both definitions. Estimates differed substantially for some subgroups, however. For example, in African-American men, the WHO estimate was 24.9%, compared with the ATP III estimate of 16.5%.

CONCLUSIONS—A universally accepted definition of the metabolic syndrome is needed.
The PedsQL™ in Type 1 and Type 2 Diabetes
Authors: Varni James W. , Burwinkle Tasha M. , Jacobs Jenifer R. , Gottschalk Michael , Kaufman Francine , Jones Kenneth L.
Published: March 2007

OBJECTIVE—The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents aged 2–18 years. The PedsQL 4.0 Generic Core Scales are child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease-specific modules. The PedsQL 3.0 Type 1 Diabetes Module was designed to measure diabetes-specific HRQOL.

RESEARCH DESIGN AND METHODS—The PedsQL Generic Core Scales and Diabetes Module were administered to 300 pediatric patients with type 1 or type 2 diabetes and 308 parents.

RESULTS—Internal consistency reliability for the PedsQL Generic Core Total Scale score (α = 0.88 child, 0.89 parent-report) and most Diabetes Module scales (average α = 0.71 child, 0.77 parent-report) was acceptable for group comparisons. The PedsQL 4.0 distinguished between healthy children and children with diabetes. The Diabetes Module demonstrated intercorrelations with dimensions of generic and diabetes-specific HRQOL.

CONCLUSIONS—The results demonstrate the reliability and validity of the PedsQL in diabetes. The PedsQL may be used as an outcome measure for diabetes clinical trials and research.
Visceral Adiposity and the Risk of Impaired Glucose Tolerance
Authors: Hayashi Tomoshige , Boyko Edward J. , Leonetti Donna L. , McNeely Marguerite J. , Newell-Morris Laura , Kahn Steven E. , Fujimoto Wilfred Y.
Published: March 2007

OBJECTIVE—Greater visceral adiposity, higher insulin resistance, and impaired insulin secretion increase the risk of type 2 diabetes. Whether visceral adiposity increases risk of impaired glucose tolerance (IGT) independent of other adipose depots, insulin resistance, and insulin secretion is not known.

RESEARCH DESIGN AND METHODS—Study subjects included 128 Japanese Americans with normal glucose tolerance at entry. Baseline variables included plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, fat areas by computed tomography, insulin secretion (incremental insulin response [IIR] [30 min insulin − fasting insulin]/30 min glucose), and insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]).

RESULTS—During the 10- to 11-year follow-up period, we confirmed 57 cases of IGT. Significant predictors of IGT included intra-abdominal fat area (IAFA) (odds ratio [OR] for a 1 SD increase 3.82, 95% CI 1.63–8.94 at a fasting plasma glucose [FPG] level of 4.5 mmol/l), HOMA-IR (2.41, 1.15–5.04), IIR (0.30, 0.13–0.69 at an FPG level of 4.5 mmol/l), the interactions of IAFA by FPG (P = 0.003), and IIR by FPG (P = 0.030) after adjusting for age, sex, FPG, and BMI. The multiple-adjusted OR of IAFA increased and that of IIR decreased as FPG level decreased because of these interactions. Even after adjustment for total fat area, total subcutaneous fat area, or abdominal subcutaneous fat area, all of these associations remained a significant predictor of IGT incidence.

CONCLUSIONS—Greater visceral adiposity increases the risk of IGT independent of insulin resistance, insulin secretion, and other adipose depots in Japanese Americans.
How Well Do Patients’ Assessments of Their Diabetes Self-Management Correlate With Actual Glycemic Control and Receipt of Recommended Diabetes Services?
Authors: Heisler Michele , Smith Dylan M. , Hayward Rodney A. , Krein Sarah L. , Kerr Eve A.
Published: March 2007

OBJECTIVE—Although patient diabetes self-management is a key determinant of health outcomes, there is little evidence on whether patients’ own assessments of their self-management correlates with glycemic control and key aspects of high-quality diabetes care. We explored these associations in a nationwide sample of Veterans’ Affairs (VA) patients with diabetes.

RESEARCH DESIGN AND METHODS—We abstracted information on achieved level of glycemic control (HbA1c) and diabetes processes of care (receipt of HbA1c test, eye examination, and nephropathy screen) from medical records of 1,032 diabetic patients who received care from 21 VA facilities and had answered the Diabetes Quality Improvement Program survey in 2000. The survey included sociodemographic measures and a five-item scale assessing the patients’ diabetes self-management (medication use, blood glucose monitoring, diet, exercise, and foot care [α = 0.68]). Using multivariable regression, we examined the associations of patients’ reported self-management with HbA1c level and receipt of each diabetes process of care. We adjusted for diabetes severity and comorbidities, insulin use, age, ethnicity, income, education, use of VA services, and clustering at the facility level.

RESULTS—Higher patient evaluations of their diabetes self-management were significantly associated with lower HbA1c levels (P < 0.01) and receipt of diabetes services. Those in the 95th percentile for self-management had a mean HbA1c level of 7.3 (95% CI 6.4–8.3), whereas those in the 5th percentile had mean levels of 8.3 (7.4–9.2). For every 10-point increase in patients’ ratings of their diabetes self-management, even after adjusting for number of outpatient visits, the odds of receiving an HbA1c test in the past year increased by 15% (4–27%), of receiving an eye examination increased by 16% (7–27%), and of receiving a nephropathy screen increased by 13% (2–26%).

CONCLUSIONS—In this sample, patients’ assessments of their diabetes self-care using a simple five-question instrument were significantly associated both with actual HbA1c control and with receiving recommended diabetes services. These findings reinforce the usefulness of patient evaluations of their own self-management for understanding and improving glycemic control. The mechanisms by which those patients who are more actively engaged in their diabetes self-care are also more likely to receive necessary services warrant further study.