bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.
Authors: Heinemann L , Klappoth W , Rave K , Hompesch B , Linkeschowa R , Heise T
Published: March 2007

OBJECTIVE: To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously RESEARCH DESIGN AND METHODS: In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration. RESULTS: After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+/-47 vs. 182+/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+/-2.6 vs. 8.8+/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+/-0.25 vs. 0.59+/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+/-0.76 vs. 2.56+/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+/-3.5% (absolute bioefficacy 10.1+/-3.1%) but was highest in the first 2 h after application (18.5+/-3.7%; absolute bioefficacy 8.2+/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+/-9% for the maximal glucose infusion rate, 15+/-10% for the time-to-maximal effect, and 16+/-12% for the total amount of glucose infused. CONCLUSIONS: This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.
Diabetes in Hong Kong Chinese: evidence for familial clustering and parental effects.
Authors: Lee S C , Pu Y B , Chow C C , Yeung V T , Ko G T , So W Y , Li J K , Chan W B , Ma R C , Critchley J A , Cockram C S , Chan J C
Published: March 2007

OBJECTIVE: To investigate transmission patterns of diabetes and their relationships with clinical characteristics in Hong Kong Chinese patients with late-onset (age > or =35 years) type 2 diabetes. RESEARCH DESIGN AND METHODS: This study involved 2,310 patients consecutively selected from a hospital clinic-based diabetes registry. These patients all reported the diabetes status of their parents as well as siblings. RESULTS: Approximately 36% of the 2,310 patients reported at least 1 affected parent or sibling (25 and 21% reported at least 1 diabetic parent and sibling, respectively). These patients, irrespective of their sex, were more likely to have a diabetic mother than a diabetic father (17 vs. 13% of the male patients and 18 vs. 9% of the female patients, P<0.01). The male patients were more likely than the female patients to have a diabetic father (13 vs. 9%, P<0.01). The female patients with a diabetic mother were found to have higher levels of plasma total cholesterol compared with the female patients with a diabetic father in multiple comparisons with adjustment for significance (5.56+/-1.30 vs. 5.09+/-0.95 mmol/l, P<0.05). In 2-group comparisons, there was also evidence that the male patients with a diabetic father had higher BMI values than the male patients with a diabetic mother (25.9+/-3.5 vs. 25.0+/-3.5 kg/m2, P<0.05). CONCLUSIONS: We found familial clustering of diabetes in the Hong Kong Chinese population as well as a significant maternal influence and a male sex-specific paternal effect. We suggest that both maternal and paternal factors may be implicated in the development of type 2 diabetes in the Chinese population.
Limited Joint Mobility in Type 1 Diabetic Patients
Authors: Frost Dietmar , Beischer Wolfgang
Published: March 2007

OBJECTIVE— To study the relationship of limited joint mobility(LJM) in type 1 diabetic patients with microvascular complications,hypertension, and early atherosclerosis and to determine whether sex has an influence on possible associations.

RESEARCH DESIGN AND METHODS— A total of 335 consecutive unselected patients (191 women and 144 men), aged 14-40 years, were studied for LJM, retinopathy, nephropathy (stages III and IV), and hypertension. Standard laboratory tests were performed; the intima-media thickness (IMT) of the carotid arteries, which reflects the extent of early atherosclerosis, was measured by high-resolution ultrasound, and plaques were identified.

RESULTS— The frequency of LJM was 33.7% (29.8% in women and 38.9% in men). Subjects with LJM had a longer diabetes duration (P< 0.001) than those without (women 16.7 ± 9.1 vs. 10.3 ± 6.0 years; men 15.0 ± 9.0 vs. 9.4 ± 6.3 years). Age,HbA1c, lipids, and systolic/diastolic blood pressure were not different between men and women with or without LJM. Men with LJM had a higher albumin excretion rate (37.1 vs. 13.1 μg/min, P < 0.05) than those without LJM and showed a higher risk of proteinuria (odds ratio 1.8, 95%CI 1.2-2.7; P < 0.05), retinopathy (2.4, 1.7-3.5; P <0.001), and hypertension (1.7, 1.2-2.6; P < 0.05). The occurrence of these complications was not different between women with and without LJM,but only women with LJM had a greater IMT (0.59 ± 0.13 vs. 0.55± 0.10 mm, P < 0.05) and a higher risk of plaques (odds ratio 2.1, 95% CI 1.3-3.4; P < 0.05) than women without LJM. In a multiple logistic regression analysis, adjusted for age and diabetes duration,male sex independently predicted the presence of LJM. Moreover, LJM proved to be an independent predictor of retinopathy in men only.

CONCLUSIONS— LJM is an indicator of microvascular disease in men, and LJM is associated with early macrovascular disease in women.
Influence of Intensive Diabetes Treatment on Body Weight and Composition of Adults With Type 1 Diabetes in the Diabetes Control and Complications Trial
Authors: Group The Diabetes Control and Complications Trial Research
Published: March 2007

OBJECTIVE—To examine the differential effects of intensive and conventional diabetes therapy on weight gain and body composition in adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Between 1982 and 1989, 1,246 adults (aged 18–39 years) in the Diabetes Control and Complications Trial were randomly assigned to either conventional therapy (1–2 injections of insulin per day) or intensive therapy (multiple daily injections or continuous subcutaneous infusion with frequent blood-glucose testing). Height and weight were measured at baseline and at annual visits for an average of 6 years (range 3–9). Body composition was assessed cross-sectionally with bioelectrical impedance analysis during 1992, at which time waist and hip circumferences were measured.

RESULTS—Intensively treated patients gained an average of 4.75 kg more than their conventionally treated counterparts (P < 0.0001). This represented excess increases in BMI of 1.5 kg/m2 among men and 1.8 kg/m2 among women. Growth-curve analysis showed that weight gain was most rapid during the first year of therapy. Intensive therapy patients were also more likely to become overweight (BMI ≥27.8 kg/m2 for men, ≥27.3 kg/m2 for women) or experience major weight gain (BMI increased ≥5 kg/m2). Waist-to-hip ratios, however, did not differ between treatment groups. Major weight gain was associated with higher percentages of body fat and greater fat-free mass, but among patients without major weight gain, those receiving intensive therapy had greater fat-free mass with no difference in adiposity.

CONCLUSIONS—Intensive therapy for type 1 diabetes produces substantial excess weight gain compared with conventional therapy. However, the additional weight appears to include lean tissue as well as fat.
Contributors to Depression in Latino and European-American Patients With Type 2 Diabetes
Authors: Fisher Lawrence , Chesla Catherine A. , Mullan Joseph T. , Skaff Marilyn M. , Kanter Richard A.
Published: March 2007

OBJECTIVE—To determine the independent and cumulative contributions of diabetes and other life stresses on depression and anxiety in Latino and European-American (EA) patients with diabetes.

RESEARCH DESIGN AND METHODS—A total of 75 Latino and 113 EA patients with type 2 diabetes, recruited from managed care settings, were assessed regarding three groups of potential stresses: demographics (age, sex, and education), disease status (functional impact, time since diagnosis, comorbidities, HbA1c, and BMI), and family stress (financial stress, spouse conflict resolution, and family closeness). Dependent variables were depression (Center for Epidemiological Studies–Depression scale [CES-D]) and anxiety (Symptom Checklist [SCL-90]). Multiple regression equations assessed the independent contribution of each predictor on depression and anxiety.

RESULTS—For both ethnic groups, education, functional impact, and financial stress significantly and independently predicted depression; poor spouse conflict resolution was a fourth significant predictor for EA patients only. The equations accounted for a high percentage of variance (43– 55%). Excluding education, the same variables predicted anxiety for both ethnic groups. The disease status and family stress variable groups significantly predicted outcomes independently. The relationships among these variables and depression and anxiety generally occurred for all patients, not only for those classified as likely depressed.

CONCLUSIONS—The findings suggest the utility of considering many life stresses, not just diabetes alone, that combine to affect depression and anxiety. We suggest that these effects are experienced cumulatively as general psychological distress for all patients with diabetes, not just those classified as likely depressed. Taken together, the findings emphasize a life-centered, patient-focused approach to the treatment of depression, rather than an exclusive disease-related perspective.
Limitations of Conventional Methods of Self-Monitoring of Blood Glucose
Authors: Boland Elizabeth , Monsod Teresa , Delucia Maria , Brandt Cynthia A. , Fernando Sanjay , Tamborlane William V.
Published: March 2007

OBJECTIVE—Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA1c measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring.

RESEARCH DESIGN AND METHODS—A total of 56 children with type 1 diabetes (age 2–18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified.

RESULTS—Despite satisfactory HbA1c levels (7.7 ± 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose <60 mg/dl) in almost 70% of the children.

CONCLUSIONS—Despite excellent HbA1c levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.
Acute Fructose Administration Improves Oral Glucose Tolerance in Adults With Type 2 Diabetes
Authors: Moore Mary Courtney , Davis Stephen N. , Mann Stephnie L. , Cherrington Alan D.
Published: March 2007

OBJECTIVE—In normal adults, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to a glucose load, especially in those with the poorest glucose tolerance. We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Five adults with type 2 diabetes underwent an oral glucose tolerance test (OGTT) on two separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose (OGTT + F or OGTT – F), in random order. Arterialized blood samples were collected from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward.

RESULTS—The area under the curve (AUC) of the plasma glucose response was reduced by fructose administration in all subjects; the mean AUC during the OGTT + F was 14% less than that during the OGTT – F (P < 0.05). The insulin AUC was decreased 21% with fructose administration (P = 0.2). Plasma glucagon concentrations declined similarly during OGTT – F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT – F was ∼50% of that observed during the OGTT + F (P < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs.

CONCLUSIONS—Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes, and this effect is not a result of stimulation of insulin secretion.
A Randomized Controlled Trial Using Glycemic Plus Fetal Ultrasound Parameters Versus Glycemic Parameters to Determine Insulin Therapy in Gestational Diabetes With Fasting Hyperglycemia
Authors: Kjos Siri L. , Schaefer-Graf Ute , Sardesi Smeeta , Peters Ruth K. , Buley Ann , Xiang Anny H. , Bryne James D. , Sutherland Cher , Montoro Martin N. , Buchanan Thomas A.
Published: March 2007

OBJECTIVE—To compare management based on maternal glycemic criteria with management based on relaxed glycemic criteria and fetal abdominal circumference (AC) measurements in order to select patients for insulin treatment of gestational diabetes mellitus (GDM) with fasting hyperglycemia.

RESEARCH DESIGN AND METHODS—In a pilot study, 98 women with fasting plasma glucose (FPG) concentrations of 105–120 mg/dl were randomized. The standard group received insulin treatment. The experimental group received insulin if the AC, measured monthly, was ≥70th percentile and/or if any venous FPG measurement was >120 mg/dl. Power was projected to detect a 250-g difference in birth weights.

RESULTS—Gestational ages, maternal glycemia, and AC percentiles were similar at randomization. After initiation of protocol, venous FPG (P = 0.003) and capillary blood glucose levels (P = 0.049) were significantly lower in the standard group. Birth weights (3,271 ± 458 vs. 3,369 ± 461 g), frequencies of birth weights >90th percentile (6.3 vs 8.3%), and neonatal morbidity (25 vs. 25%) did not differ significantly between the standard and experimental groups, respectively. The cesarean delivery rate was significantly lower (14.6 vs. 33.3%, P = 0.03) in the standard group; this difference was not explained by birth weights. In the experimental group, infants of women who did not receive insulin had lower birth weights than infants of mothers treated with insulin (3,180 ± 425 vs. 3,482 ± 451 g, P = 0.03).

CONCLUSIONS—In women with GDM and fasting hyperglycemia, glucose plus fetal AC measurements identified pregnancies at low risk for macrosomia and resulted in the avoidance of insulin therapy in 38% of patients without increasing rates of neonatal morbidity.
A Pilot Study of the Continuous Glucose Monitoring System
Authors: Kaufman Francine R. , Gibson Leena C. , Halvorson Mary , Carpenter Sue , Fisher Lynda K. , Pitukcheewanont Pisit
Published: March 2007

OBJECTIVE—To determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) could be used to make clinical decisions and whether it has an impact on glycemia in pediatric type 1 diabetic subjects.

RESEARCH DESIGN AND METHODS—Pediatric subjects were recruited if they had HbA1c >8.0% with management problems (n = 35) or episodes of severe or nocturnal hypoglycemia or hypoglycemia unawareness associated with HbA1c ≤8.0% (n = 12). A total of 47 patients with a mean HbA1c value of 8.6 ± 1.6% (mean age 11.8 ± 4.6 years, youngest 2.7 years, and diabetes duration 5.5 ± 3.5 years) on three to four insulin injections/day (n = 24) or insulin pump therapy (n = 23) were followed with the CGMS for a mean of 69.5 ± 28 h. Comparisons were made between the number of high (>150 mg/dl) and low (<70 mg/dl) glucose patterns discerned with the sensor or the logbook, and HbA1c levels were evaluated.

RESULTS—In patients on injection therapy, 30 high or low glucose patterns were discerned with the logbook records and 120 patterns with the CGMS. Specific alterations of the diabetes regimen were made. An overall significant change in HbA1c, from 3 months before wearing the sensor to 6 months after (analysis of variance 0.04), was found in the subjects. Post hoc analysis showed a significant change in HbA1c from 8.6 ± 1.5% at baseline to 8.4 ± 1.3% at 3 months (paired Student’s t test 0.03).

CONCLUSIONS—The CGMS can be used by pediatric patients to detect abnormal patterns of glycemia. The information that was obtained could be used to alter the diabetes regimen and impact glycemic outcome.
Prevalence and Determinants of Type 2 Diabetes Among Filipino-Americans in the Houston, Texas Metropolitan Statistical Area
Authors: Cuasay Luceli C. , Lee Eun Sul , Orlander Philip P. , Steffen-Batey Lyn , Hanis Craig L.
Published: March 2007

OBJECTIVE—The few available studies suggest that Filipino-Americans have an increased risk for developing type 2 diabetes. The purpose of this study was to determine the prevalence of previously diagnosed type 2 diabetes and its major risk factors among Filipino-Americans.

RESEARCH DESIGN AND METHODS—A cross-sectional survey was conducted in the Houston, Texas, metropolitan statistical area between September 1998 and March 2000. The convenience sample included 831 Filipino-American participants aged 20–74 years. The major risk factors assessed were age, sex, family history of diabetes, socioeconomic status, obesity (BMI >30), physical inactivity, acculturation, region of birth and, in women, history of gestational diabetes and delivery of a baby weighing >9 lb.

RESULTS—Overall prevalence was estimated to be 16.1% (95% CI 13.5–18.7). Multivariate logistic regression analyses identified independent risk factors: increasing age from ages 35–44 years (odds ratio [OR] 5.6, 95% CI 1.5–20.5) to 65–74 years (34.2, 7.2–163.0); male sex (1.8, 1.1–32.1); family history of diabetes (4.7, 2.6–8.5); obesity (3.6, 1.4–9.0); region of birth, Mindanao (3.2, 1.3–7.7); and, among women, gestational diabetes (21.7, 6.7–69.7) and low income (5.3, 1.4–20.2).

CONCLUSIONS—The study observed a high prevalence of type 2 diabetes and supports earlier studies suggesting that Filipinos are at higher risk for type 2 diabetes than the U.S. non-Hispanic white population.
Type 2 Diabetes in Older Well-Functioning People: Who Is Undiagnosed?
Authors: Franse Lonneke V. , Di Bari Mauro , Shorr Ron I. , Resnick Helaine E. , van Eijk Jacques T. M. , Bauer Doug C. , Newman Anne B. , Pahor Marco ,   for the Health, Aging, and Body Composition Study Group
Published: March 2007

OBJECTIVE—To assess, in an older population, the prevalence of diagnosed and undiagnosed diabetes, the number needed to screen (NNTS) to identify one individual with undiagnosed diabetes, and factors associated with undiagnosed diabetes.

RESEARCH DESIGN AND METHODS—Socioeconomic and health-related factors were assessed at the baseline examination of the Health, Aging, and Body Composition (Health ABC) Study, a cohort of 3,075 well-functioning people aged 70–79 years living in Memphis, Tennessee and Pittsburgh, Pennsylvania (42% blacks and 48% men). Diabetes was defined according to the 1985 World Health Organization criteria (fasting glucose ≥7.8 mmol/l or 2-h glucose ≥11.1 mmol/l) and the 1997 American Diabetes Association criteria (fasting glucose ≥7.0 mmol/l).

RESULTS—The prevalence of diagnosed and undiagnosed diabetes was 15.6 and 8.0%, respectively, among all participants (NNTS 10.6), 13.9 and 9.1% among white men (NNTS 9.5), 7.8 and 7.4% among white women (NNTS 12.4), 22.7 and 9.1% among black men (NNTS 8.5), and 21.6 and 6.2% among black women (NNTS 12.6). In multivariate analyses, compared with individuals without diabetes, individuals with undiagnosed diabetes were more likely to be men and were more likely to have a history of hypertension, higher BMI, and larger waist circumference. NNTS was lowest in men (9.1), individuals with hypertension (8.7), individuals in the highest BMI quartile (6.9), and individuals in the largest waist circumference quartile (6.8).

CONCLUSIONS—In approximately one-third of all older people with diabetes, the condition remains undiagnosed. Screening for diabetes may be more efficient among men and individuals with hypertension, high BMI, and large waist circumference.
Teaching Subjects With Type 2 Diabetes How to Incorporate Sugar Choices Into Their Daily Meal Plan Promotes Dietary Compliance and Does Not Deteriorate Metabolic Profile
Authors: Nadeau Julie , Koski Kristine G. , Strychar Irene , Yale Jean-François
Published: March 2007

OBJECTIVE— To determine whether teaching free-living subjects with type 2 diabetes how to incorporate added sugars or sweets into their daily meal plan results in a greater consumption of calories (fat or sugar)and deteriorates their glycemic or lipid profiles but improves their perceived quality of life.

RESEARCH DESIGN AND METHODS— In an 8-month randomized controlled trial, 48 free-living subjects with type 2 diabetes were taught either a conventional (C) meal plan (no concentrated sweets) or one permitting as much as 10% of total energy as added sugars or sweets (S). Mean individual nutrient intake was determined using the average of six 24-h telephone recalls per 4 months. Metabolic control and quality of life were evaluated every 2 months. Quality of life was assessed using the Medical Outcome Survey and the Diabetes Quality of Life questionnaire.

RESULTS— The S group did not consume more calories (fat or sugar) and in fact ate significantly less carbohydrate (- 15 vs. 10 g) and less starch (- 7 vs. 8 g) and had a tendency to eat fewer calories (- 77 vs. 81 kcal) than the C group. Weight remained stable, and there was no evidence that consuming more sugar worsened metabolic profile or improved their perceived quality of life.

CONCLUSIONS— Giving individuals with type 2 diabetes the freedom to include sugar in their daily meal plan had no negative impact on dietary habits or metabolic control. Health professionals can be reassured and encouraged to teach the new “sugar guidelines,” because doing so may result in a more conscientious carbohydrate consumption.
Renin-Angiotensin System Gene Polymorphisms, Blood Pressure,Dyslipidemia, and Diabetes in Hong Kong Chinese
Authors: Thomas G. Neil , Tomlinson Brian , Chan Juliana C.N. , Sanderson John E. , Cockram Clive S. , Critchley Julian A.J.H.
Published: March 2007

OBJECTIVE— In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease,particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms—the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms—for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome.

RESEARCH DESIGN AND METHODS— The three gene polymorphisms of this crosssectional study were detected using polymerase chain reaction—based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia usingχ2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance.

RESULTS— No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels.

CONCLUSIONS— These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele—containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.
Changes in Cognitive Abilities Over a 4-Year Period Are Unfavorably Affected in Elderly Diabetic Subjects
Authors: Fontbonne Annick , Berr Claudine , Ducimetière Pierre , Alpérovitch Annick
Published: March 2007

OBJECTIVE— To compare 4-year changes in cognitive performance among elderly subjects according to category of fasting blood glucose (FBG)using American Diabetes Association criteria.

RESEARCH DESIGN AND METHODS— Subjects without any detectable cognitive dysfunction were selected from the Epidemiology of Vascular Aging(EVA) Study, a cohort of community-dwelling people aged 59-71 years at baseline. They were classified into glucose categories (normal, impaired fasting glucose [IFG], or diabetic) based on FBG values or known diabetes. Their cognitive abilities were assessed by a global test (Mini Mental Status Examination [MMSE]) and eight domain-specific tests, and they were reassessed 4 years later. Serious cognitive worsening was defined as a score evolution into the worst 15% of the sample's distribution of score differences (4-year score minus baseline score) for each test.

RESULTS— At baseline, age-, sex-, and education-adjusted scores for all cognitive tests except one were similar across glucose categories. After 4 years, diabetic subjects had a lower performance on all tests except the MMSE, with differences reaching statistical significance on four tests. Adjusted odds ratios for serious worsening over 4 years in diabetic subjects, with reference to normal subjects, were >2 for four tests (P < 0.05) and bordering this value for two others(P < 0.09). Further adjustment for blood pressure or potential cognition-affecting substances (alcohol, tobacco, and medications) did not modify these results.

CONCLUSIONS— Despite similar high initial cognitive function,diabetic subjects tended to have an unfavorable evolution of cognitive performance over 4 years compared with subjects who had normal glucose or IFG.
Behavior Therapy for Families of Adolescents With Diabetes
Authors: Wysocki Tim , Greco Peggy , Harris Michael A. , Bubb Jeannie , White Neil H.
Published: March 2007

OBJECTIVE—This study reports 6- and 12-month follow-up for the families of adolescents with diabetes who participated in a trial of Behavioral–Family Systems Therapy (BFST).

RESEARCH DESIGN AND METHODS—A total of 119 families of adolescents with type 1 diabetes were randomized to 3 months of treatment with either BFST, an education and support (ES) group, or current therapy (CT). Family relationships, adjustment to diabetes, treatment adherence, and diabetic control were assessed at baseline, after 3 months of treatment, and 6 and 12 months later. This report focuses on the latter two evaluations.

RESULTS—Compared with CT and ES, BFST yielded lasting improvements in parent-adolescent relationships and diabetes-specific conflict. Delayed effects on treatment adherence emerged at 6- and 12-month follow-ups. There were no immediate or delayed effects on adolescents’ adjustment to diabetes or diabetic control.

CONCLUSIONS—BFST yielded lasting improvement in parent-adolescent relationships and delayed improvement in treatment adherence, but it had no effect on adjustment to diabetes or diabetic control. A variety of adaptations to BFST could enhance its impact on diabetes outcomes.
HbA1c Measurement Improves the Detection of Type 2 Diabetes in High-Risk Individuals With Nondiagnostic Levels of Fasting Plasma Glucose
Authors: Perry R. Clark , Shankar R. Ravi , Fineberg Naomi , McGill Janet , Baron Alain D.
Published: March 2007

OBJECTIVE—Whereas new diagnostic criteria based on a fasting plasma glucose (FPG) of >126 mg/dl (7.8 mmol/l) have improved the detection of diabetes, multiple reports indicate that many people with diabetes diagnosed by 2-h oral glucose tolerance test (OGTT) glucose measurements of ≥11.1 mmol/l (200 mg/dl) would remain undiagnosed based on this FPG criteria. Thus, improved methods to detect diabetes are particularly needed for high-risk individuals. We evaluated whether the combination of FPG and HbA1c measurements enhanced detection of diabetes in those individuals at risk for diabetes with nondiagnostic or minimally elevated FPG.

RESEARCH DESIGN AND METHODS—We analyzed FPG, OGTT, and HbA1c data from 244 subjects screened for participation in the Early Diabetes Intervention Program (EDIP).

RESULTS—Of 244 high-risk subjects studied by FPG measurements and OGTT, 24% of the individuals with FPG levels of 5.5–6.0 mmol/l (100–109 mg/dl) had OGTT-diagnosed diabetes, and nearly 50% of the individuals with FPG levels of 6.1–6.9 mmol/l (110–125 mg/dl) had OGTT-diagnosed diabetes. In the subjects with OGTT-diagnosed diabetes and FPG levels between 5.5 and 8.0 mmol/l, detection of an elevated HbA1c (>6.1% or mean + 2 SDs) led to a substantial improvement in diagnostic sensitivity over the FPG threshold of 7.0 mmol/l (61 vs. 45%, respectively, P = 0.002). Concordant FPG levels ≥7.0 mmol/l (currently recommended for diagnosis) occurred in only 19% of our cohort with type 2 diabetes.

CONCLUSIONS—Diagnostic criteria based on FPG criteria are relatively insensitive in the detection of early type 2 diabetes in at-risk subjects. HbA1c measurement improves the sensitivity of screening in high-risk individuals.
Improvement of Glycemic Control by 1 Year of Insulin Therapy Leads to a Sustained Decrease in sE-Selectin Concentrations in Type 2 Diabetes
Authors: Ryysy Leena , Yki-Järvinen Hannele
Published: March 2007

OBJECTIVE—To examine whether and how improvement of glycemic control by long-term insulin therapy decreases endothelial activation as measured by serum levels of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule (VCAM-1) and whether the drug used to lower blood glucose in addition to insulin influences such a response.

RESEARCH DESIGN AND METHODS—Circulating adhesion molecules were measured before and after 3 and 12 months of therapy in 81 patients with type 2 diabetes and 41 subjects without diabetes. The patients were treated with bedtime administration of NPH insulin combined with either glibenclamide (n = 19), metformin (n = 17), glibenclamide and metformin (n = 17), or morning administration of NPH insulin (n = 23).

RESULTS—Before insulin therapy, serum sE-selectin level was 71% higher in the patients with type 2 diabetes (77 ± 4 ng/ml) than in the normal subjects (45 ± 3 ng/ml, P < 0.001), whereas levels of sVCAM-1 were comparable (420 ± 25 vs. 400 ± 11 ng/ml, respectively). Glycemic control in all patients improved as judged from a decrease in HbA1c from 9.7 ± 0.2 to 7.6 ± 0.1% (P < 0.001). sE-selectin decreased to 67 ± 4 ng/ml by 3 months (P < 0.001 vs. 0 months) and then remained unchanged until 12 months (70 ± 4 ng/ml, P < 0.001 vs. 0 months). sVCAM-1 levels at 12 months was similar to those at 0 months (416 ± 25 ng/ml). The change in glycemic control, measured by HbA1c, but not in other parameters, was correlated with the change of sE-selectin (r = 0.41, P < 0.001) within the patients with type 2 diabetes. The decreases in sE-selectin were not different between the various treatment groups.

CONCLUSIONS—We conclude that improvement in glycemic control by administration of insulin alone or insulin combined with either glibenclamide, metformin, or both agents induces a sustained decrease in sE-selectin, the magnitude of which seems to be dependent on the degree of improvement in glycemia. These data suggest that sE-selectin might provide a marker of effects of treatment of chronic hyperglycemia on endothelial activation.
Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects
Authors: Lee Shao C. , Ko Gary T.C. , Li June K.Y. , Chow Chun C. , Yeung Vincent T.F. , Critchley Julian A.J.H. , Cockram Clive S. , Chan Juliana C.N.
Published: March 2007

OBJECTIVE—To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese.

RESEARCH DESIGN AND METHODS—The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes. Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios.

RESULTS—Approximately 29% of the index patients were diagnosed with type 2 diabetes at ≤35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at >35 years of age (hereby defined as late-onset), the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c, waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal as well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted older age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes. Predictors for younger age at diagnosis in the female patients were higher HbA1c, WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child-parent pairs and child-parent-grandparent trios, there was a decrease in age at diagnosis in successive generations.

CONCLUSIONS—Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.
Rates and Risk Factors for Recurrence of Gestational Diabetes
Authors: MacNeill Stephanie , Dodds Linda , Hamilton David C. , Armson B. Anthony , VandenHof M.
Published: March 2007

OBJECTIVE—To determine the recurrence rate of gestational diabetes (GDM) during a subsequent pregnancy among women who had GDM during an index pregnancy and to identify factors associated with the probability of recurrence.

RESEARCH DESIGN AND METHODS—A retrospective longitudinal study was performed in Nova Scotia, Canada, of women who were diagnosed as having GDM during a pregnancy between the years of 1980 and 1996 and who had at least one subsequent pregnancy during this time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 651 women. The recurrence rate of GDM in the pregnancy after the pregnancy with the initial diagnosis of GDM was determined. Multivariate regression models were constructed to model the recurrence of GDM in a subsequent pregnancy as functions of potential predictors to estimate RRs and CIs.

RESULTS—The rate of recurrence of GDM in the pregnancy subsequent to the index pregnancy was found to be 35.6% (95% CI = 31.9–39.3%). Multivariate regression models showed that infant birth weight in the index pregnancy and maternal prepregnancy weight before the subsequent pregnancy were predictive of recurrent GDM.

CONCLUSIONS—In this large cohort of women, slightly more than one-third of the subjects had diabetes in a subsequent pregnancy, which is consistent with recurrence rates in other predominately white populations. Strategies to reduce the occurrence of neonatal macrosomia and maternal prepregnancy obesity may help lower the rate of recurrence of GDM.
Comprehensive Evaluation of Community-Based Diabetic Patients
Authors: Hiss Roland G. , Gillard Mary Lou , Armbruster Betty A. , McClure Leslie A.
Published: March 2007

OBJECTIVE—To demonstrate improvements in diabetes care stimulated by comprehensive evaluation of community-based diabetic patients with feedback to the patients and their physicians.

RESEARCH DESIGN AND METHODS—A comprehensive evaluation of community-based diabetic patients with annotated reporting of results to both patients and their physicians (universal intervention) was followed by random assignment of 50% of patients to individual counseling (randomized intervention). In four communities, two large and two small, 55 type 1 and 376 type 2 diabetic patients were recruited, evaluated, and reassessed at 1 year. Outcome measures were HbA1c, serum cholesterol, and systolic and diastolic blood pressure.

RESULTS—There were significant improvements in all outcome measures for type 2 diabetic patients randomized to individual counseling (P = 0.03; follow-up rate 84%) and significant improvements in all outcome measures for all high-risk type 2 patients (highest P value = 0.004; follow-up rate 85%).

CONCLUSIONS—Comprehensive evaluation of diabetic patients at the community level with annotated reporting of results to the patients and their physicians was associated with improvement of mean HbA1c, cholesterol, and systolic and diastolic blood pressure, particularly in patients in high-risk status for these outcome variables. Individual counseling of 50% of patients, randomly selected, enhanced these results.
Serum 8-Hydroxy-Guanine Levels Are Increased in Diabetic Patients
Authors: Shin Chan Soo , Moon Byung Sool , Park Kyong Soo , Kim Seong Yeon , Park Su Jin , Chung Myung Hee , Lee Hong Kyu
Published: March 2007

OBJECTIVE—The production of reactive oxygen species is increased in diabetic patients, especially in those with poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker.

RESEARCH DESIGN AND METHODS—We studied 41 type 2 diabetic patients and compared them with 33 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography.

RESULTS—The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 ± 0.69 vs. 0.96 ± 0.15 pmol/ml; P < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also could not find any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin excretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria.

CONCLUSIONS—Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes.
TNFRSF1Bin Genetic Predisposition to Clinical Neuropathy and Effect on HDL Cholesterol and Glycosylated Hemoglobin in Type 2 Diabetes
Authors: Benjafield Adam V. , Glenn Cheryl L. , Wang Xing Li , Colagiuri Stephen , Morris Brian J.
Published: March 2007

OBJECTIVE—Genetic variation in the tumor necrosis factor (TNF) receptor 2 gene (TNFRSF1B) has shown association with insulin resistance in type 2 diabetes, hypercholesterolemia, coronary artery disease, and essential hypertension. Here we tested the TNFRSF1B marker used in the latter studies in type 2 diabetes patients.

RESEARCH DESIGN AND METHODS—A case-control study of a microsatellite marker with five alleles (CA13– CA17) in intron 4 of TNFRSF1B was performed in 357 well-characterized white patients and 183 healthy control subjects.

RESULTS—The CA16 allele was associated with clinical neuropathy (frequency = 27% in 69 patients with the condition versus 16% in 230 subjects without the condition; χ2 = 9.0, P = 0.011; odds ratio = 2.1 [95% CI 1.2–3.8]). No association was seen with other complications or diabetes itself. The CA16 allele tracked with elevation plasma HDL cholesterol (1.3 ± 0.2, 1.2 ± 0.4, and 1.1 ± 0.2 for CA16/CA16, CA16/–, and –/–, respectively; n = 9, 110, and 218, respectively; P = 0.009) and reduction in plasma glycosylated hemoglobin (6.6 ± 0.3, 8.3 ± 0.2, and 8.1 ± 0.1 for CA16/CA16, CA16/–, and –/–, respectively; n = 9, 102, 205, respectively; P = 0.007). Significance remained after Bonferroni correction for multiple testing.

CONCLUSIONS—Genetic variation in or near TNFRSF1B may predispose clinical neuropathy, reduced glycosylated hemoglobin, and increased HDL cholesterol in type 2 diabetes patients. The latter could be part of a protective response.
Abnormal Glucose Tolerance in Transfusion-Dependent β-Thalassemic Patients
Authors: Chern Jimmy P.S. , Lin Kai-Hsin , Lu Meng-Yao , Lin Dong-Tsam , Lin Kuo-Sin , Chen Jong-Dar , Fu Cheng-Chung
Published: March 2007

OBJECTIVE—To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent β-thalassemic patients.

RESEARCH DESIGN AND METHODS—A total of 89 transfusion-dependent β-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, χ2 test, and Fisher’s exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance. A two-tailed P value of <0.05 was considered to be statistically significant.

RESULTS—The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent β-thalassemic patients were serum ferritin concentration and hepatitis C infection.

CONCLUSIONS—The interaction of iron overload and hepatitis C infection worsened the prognosis of thalassemic patients. Aggressive iron-chelation therapy as well as prevention and treatment of hepatitis C infection should be mandatory in managing glucose homeostasis in transfusion-dependent β-thalassemic patients in Taiwan.
Elevation of N-(Carboxymethyl)valine Residue in Hemoglobin of Diabetic Patients
Authors: Uchimura Tomonori , Nakano Kazushi , Hashiguchi Teruto , Iwamoto Hisahiko , Miura Keisuke , Yoshimura Yoshimichi , Hanyu Naohiro , Hirata Koichiro , Imakuma Misturu , Motomiya Yoshihiro , Maruyama Ikuro
Published: March 2007

OBJECTIVE—Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein, we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathy.

RESEARCH DESIGN AND METHODS—BALB/c mice were immunized with carboxymethylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 ± 12.0 vs. 61.1 ± 13.2 years, NS; HbA1c 6.9 ± 1.5 vs. 5.2 ± 0.4%, P < 0.0001).

RESULTS—A monoclonal antibody against CMV-Hb β-chain NH2-terminal and an assay method for measurement for CMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 ± 6.9 vs. 12.7 ± 6.9 pmol CMV/mg Hb, P < 0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed.

CONCLUSIONS—We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.
Disturbances of Glucose Metabolism in Men Referred for Coronary Arteriography
Authors: Kowalska Irina , Prokop Jolanta , Bachórzewska-Gajewska Hanna , Telejko Beata , Kinalskal Ida , Kochman Waclaw , Musial Wlodzimierz
Published: March 2007

OBJECTIVE—In some studies, fasting and postload glycemia are a strong predictor of coronary events and cardiac death. Therefore, we investigated the relationship between fasting and postload glucose concentrations and coronary status in 363 men referred for coronary arteriography without a previous history of diabetes.

RESEARCH DESIGN AND METHODS—A total of 363 men (mean age 53.0 ± 9.1 years, mean BMI 27.9 ± 3.7 kg/m2) with positive results of exercise testing were included in the study. A standard oral glucose tolerance test (OGTT) with glucose and insulin estimations was performed on all subjects. The concentrations of total cholesterol, HDL cholesterol, triglycerides, and HbA1c were also measured. All patients were divided into four groups, according to coronary status: no changes in coronary arteries (group 0, n = 61), one-vessel disease (group I, n = 113), two-vessel disease (group II, n = 116), and three-vessel disease (group III, n = 73).

RESULTS—The highest postload glucose concentrations were observed in group III. Also, insulin concentrations and HbA1c increased with the progression of atherosclerotic lesions in the coronary arteries. Based on results of the OGTT, 16% of the patients (n = 59) fulfilled the World Health Organization criteria for type 2 diabetes and 36% of the patients (n = 131) met criteria for impaired glucose tolerance. Significant correlations were observed between the number of involved vessels and postload glycemia, HbA1c, fasting insulin, and postload insulin. The multiple stepwise regression analysis showed that age, total cholesterol, and HDL cholesterol independently correlated with the number of involved vessels.

CONCLUSIONS—We conclude that patients with advanced changes in the coronary arteries experience more pronounced metabolic disturbances. Postload glycemia could be an important predictor of nondiagnosed disturbances of glucose metabolism.