bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological Differences Between Interstitial Glucose and Blood Glucose Measured in Human Subjects
Authors: Kulcu Eray , Tamada Janet A. , Reach Gerard , Potts Russell O. , Lesho Matthew J.
Published: March 2007

OBJECTIVE—This study investigated whether glucose readings from a sensor sampling in interstitial fluid differ substantially from blood glucose (BG) values measured at the same time.

RESEARCH DESIGN AND METHODS—We have evaluated the relationship between BG and glucose extracted from interstitial fluid using the GlucoWatch (Cygnus, Redwood City, CA) biographer, a device that collects glucose from subcutaneous interstitial space through intact skin by application of a low electric current. We evaluated the relative change in the interstitial glucose (IG) signal (IGS) as measured by the biographer versus BG using a normalized two-point sensitivity index (NSI).

RESULTS—The results show that biographer measures of IG differ in time and magnitude from the corresponding BG values. In particular, the biographer values were shifted in time due to instrumental and physiological lag. Results show an average total lag of 17.2 ± 7.2 min for all subjects evaluated. The instrumental lag was 13.5 min, suggesting that physiological lag is ∼5 min. In addition, when glucose was increasing, the change in IGS was less than that in BG, while when BG was decreasing, the change in IGS was greater than that in BG.

CONCLUSIONS—Similar results have been reported for other measures of IG, suggesting that differences reflect physiological variation in glucose uptake, utilization, and elimination in blood and interstitial space. This further evidence of the difference between IG and BG should be considered when interpreting glucose measurements from devices that sample interstitial fluid.
Community-Based Lifestyle Interventions to Prevent Type 2 Diabetes
Authors: Satterfield Dawn W. , Volansky Michele , Caspersen Carl J. , Engelgau Michael M. , Bowman Barbara A. , Gregg Ed W. , Geiss Linda S. , Hosey Gwen M. , May Jeannette , Vinicor Frank
Published: March 2007

OBJECTIVE—To conduct a literature review of community-based interventions intended to prevent or delay type 2 diabetes.

RESEARCH DESIGN AND METHODS—Recently published findings about the potential to prevent or delay type 2 diabetes with intensive lifestyle interventions prompted a literature search for community-based diabetes prevention interventions. The literature review design was a search of databases for publications in 1990–2001 that identified reports on community-based interventions designed to prevent or modify risk factors for type 2 diabetes.

RESULTS—The search revealed 16 published interventions, 8 of which were conducted in the U.S. and involved populations disproportionately burdened by diabetes (e.g., American Indians, Native Hawaiians, Mexican Americans, and African Americans). Of the studies reporting results among youth, there were posttest improvements in intervention groups in knowledge, preventive behaviors, and self-esteem. Among studies reporting results among adults, most reported improvements in intervention groups in knowledge or adoption of regular physical activity. Several investigators offered important reflections about the process of engaging communities and sharing decision making in participatory research approaches, as well as insights about the expectations and limitations of community-based diabetes prevention research. Many of the studies reported limitations in their design, including the lack of control or comparison groups, low response rates or lack of information on nonresponders, or brief intervention periods.

CONCLUSIONS—There is a critical need to conduct and publish reports on well-designed community-based diabetes prevention research and share information on the process, results, and lessons learned. Armed with recent positive findings about diabetes prevention and literature documenting community-based efforts, advocates at local, state, and national levels can collaborate to stem the rising tide of diabetes in communities.
Diabetic Retinopathy and Diabetic Macular Edema
Authors: Ciulla Thomas A. , Amador Armando G. , Zinman Bernard
Published: March 2007

Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of blindness in the working-age population of most developed countries. The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease. Several biochemical mechanisms, including protein kinase C–β activation, increased vascular endothelial growth factor production, oxidative stress, and accumulation of intracellular sorbitol and advanced glycosylation end products, may contribute to the vascular disruptions that characterize DR/DME. The inhibition of these pathways holds the promise of intervention for DR at earlier non–sight-threatening stages. To implement new therapies effectively, more individuals will need to be screened for DR/DME at earlier stages—a process requiring both improved technology and interdisciplinary cooperation among physicians caring for patients with diabetes.
Economic Consequences of Epidemiological Changes in Diabetes in Middle-Income Countries
Authors: Arredondo Armando , Zúñiga Alexis
Published: March 2007

OBJECTIVE—To identify the costs and economic consequences of expected changes in the demand for health care services for type 2 diabetes in the three main public institutions of the Mexican health care system.

RESEARCH DESIGN AND METHODS—The cost evaluation method to estimate direct and indirect costs was based on instrumentation and consensus techniques. To estimate the costs and epidemiological changes for 2003–2005, three probabilistic models were constructed according to the Box-Jenkins technique.

RESULTS—Comparing the economic impact in 2003 versus 2005 (P < 0.05), there is a 26% increase in financial requirements. The total amount for diabetes in 2005 (in U.S. dollars) will be $317,631,206, including $140,410,816 in direct costs and $177,220,390 in indirect costs. The total direct costs, representing financial requirements to provide health care for expected cases of type 2 diabetes and its main complications in the three main public institutions in Mexico, up to 2005, will be $37,079,587 for the Ministry of Health (or Secretaría de Salud [SSA], serving the uninsured population) and $103,331,235 for the Mexican Social Security Institute, or Instituto Mexicano del Seguro Social (IMSS), and the Institute for Social Security and Services for State Workers, or Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), both of which serve the insured population.

CONCLUSIONS—Our data suggest that changes in the demand for health care services for patients with diabetes will continue with an increasing trend, mainly in the insured population. In economic terms, the results of direct and indirect costs are one of the main challenges to be solved to decrease the economic burden that diabetes represents for the population, the health care institutions, and for society as a whole.
Physician, Organizational, and Patient Factors Associated With Suboptimal Blood Pressure Management in Type 2 Diabetic Patients in Primary Care
Authors: Schaars Carel F. , Denig Petra , Kasje Willeke N. , Stewart Roy E. , Wolffenbuttel Bruce H.R. , Haaijer-Ruskamp Flora M.
Published: March 2007

OBJECTIVE—To assess the quality of hypertension care in patients with type 2 diabetes in general practice and identify physician, organizational, and patient factors associated with suboptimal care.

RESEARCH DESIGN AND METHODS—Data from 895 randomly selected diabetic patients were extracted from the electronic medical records of 95 general practitioners. Physician and organizational characteristics were collected with a questionnaire. We conducted a multilevel analysis to identify associations with blood pressure registration, hypertension treatment, and achievement of target blood pressure levels.

RESULTS—For 652 patients (73%), a blood pressure measurement was recorded in the last year. Of these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595 patients were classified as having hypertension, of whom 192 received no treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other antihypertensives. Patients visiting a diabetes facility, referred to a specialist, with a female general practitioner, or with a general practitioner with ≤10 years work experience had better recordings of their blood pressure. Suboptimal treatment was higher in older patients and smoking patients. Treatment was better in patients with coronary comorbidity, hyperlipidemia, or those referred to a specialist. Not achieving the blood pressure target was related to older age of the patients.

CONCLUSIONS—Hypertension management of type 2 diabetic patients in primary care is suboptimal. Characteristics of general practitioners as well as additional care provided by a diabetes facility or a specialist are associated with better processes of care, but blood pressure outcomes are not as clearly related to these factors.
Acute Effects of Different Intensities of Exercise in Normoalbuminuric/ Normotensive Patients With Type 1 Diabetes
Authors: Lane James T. , Ford Timothy C. , Larson LuAnn R. , Chambers Ward A. , Lane Pascale H.
Published: March 2007

OBJECTIVE—The purpose of this study was to investigate the effect of exercise occurrence and intensity on albumin excretion in normotensive, normoalbuminuric patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Eighteen patients (aged 29 ± 2 years, duration of diabetes 14 ± 2 years, blood pressure 120 ± 2/74 ± 1 mmHg, HbA1c 7.0 ± 0.2% [mean ± SE]) without microalbuminuria, hypertension, or anti–angiotensin II therapy participated in two exercise studies in a clinical research center. Exercise intensities were defined as moderate (50% heart rate reserve [HRR]) and intense (75% HRR) and were performed in random order. Subjects collected urine for albumin determination on the days before and after exercise. On the day of exercise, subjects exercised for 30 min on a treadmill at the assigned intensity. Timed urine collections were obtained over the day. Blood pressures were measured using an ambulatory blood pressure monitor.

RESULTS—Moderate exercise demonstrated no changes in albumin excretion. Intense exercise demonstrated a significant increase in albumin excretion during the first 4 h compared with the rest of the day (P = 0.03) but returned to normal thereafter. Albumin excretion did not exceed normal levels throughout the study. There was no difference in albumin excretion surrounding days of intense exercise. Ambulatory blood pressures demonstrated nocturnal dipping after moderate and intense exercise (P < 0.001).

CONCLUSIONS—We have demonstrated that normotensive, normoalbuminuric patients without anti–angiotensin II therapy do not have elevated albumin excretion following exercise intensities experienced by most patients with type 1 diabetes.
Low Synthesis and High Absorption of Cholesterol Characterize Type 1 Diabetes
Authors: Miettinen Tatu A. , Gylling Helena , Tuominen Juha , Simonen Piia , Koivisto Veikko
Published: March 2007

OBJECTIVE—Streptozotocin-induced type 1 diabetes in experimental animals inhibits cholesterol synthesis and increases cholesterol absorption. In contrast to human type 2 diabetes, virtually no information is available on cholesterol synthesis and absorption in type 1 diabetes.

RESEARCH DESIGN AND METHODS—We studied the variables of cholesterol metabolism in 27 patients with type 1 diabetes and in 10 patients with type 2 diabetes matched for body weight, using cholesterol precursor sterol ratios to cholesterol as surrogate markers of synthesis, and those of cholestanol and plant sterols of cholesterol absorption. Glucose control was good in all subjects.

RESULTS—Total and HDL cholesterol and LDL triglycerides were higher in type 2 than in type 1 diabetes. Serum sterols, measured also in VLDL, intermediate-density lipoprotein (IDL), LDL, and HDL, were transported up to >90% by LDL and HDL in type 1 diabetes. The ratios of all absorption sterols in serum and in each lipoprotein were higher, and those of the synthesis markers, especially cholestenol and lathosterol, were lower in type 1 than in type 2 diabetes.

CONCLUSIONS—In contrast to type 2 diabetes, the findings in type 1 diabetes could be related to low expression of ABC G/5 G/8 genes, resulting in high absorption of cholesterol and sterols in general and low synthesis of cholesterol.
Fasting Plasma Free Fatty Acids and Risk of Type 2 Diabetes
Authors: Pankow James S. , Duncan Bruce B. , Schmidt Maria Inês , Ballantyne Christie M. , Couper David J. , Hoogeveen Ron C. , Golden Sherita H.
Published: March 2007

OBJECTIVE—To evaluate whether plasma levels of free fatty acids (FFAs) are independently associated with incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—A case-cohort design was used to randomly select 580 incident cases of diabetes and 566 noncases from 10,275 African-American and white men and women in the Atherosclerosis Risk in Communities study, aged 45–64 years and without prevalent diabetes at the baseline exam. Incident diabetes was ascertained at three exams over 9 years of follow-up. FFA levels were measured in plasma samples collected at the baseline exam.

RESULTS—At baseline, FFA level was inversely associated with height and positively associated with female sex, BMI, waist circumference, waist-to-hip ratio, heart rate, plasma triglycerides, and an inflammation score quantifying levels of six systemic inflammation markers. Relative risks for incident diabetes (fourth vs. first quartile of FFAs) were increased in a basic model adjusted for age, sex, race, and center (hazard ratio 1.68, 95% CI 1.20–2.34) and in a model further adjusted for baseline fasting glucose, insulin, BMI, waist circumference, triglycerides, and the inflammation score (1.63, 1.04–2.57). Relative risks associated with a greater FFA level were lowest among those of normal weight and highest among the obese, but a formal test of interaction between FFAs and BMI was not statistically significant.

CONCLUSIONS—Individuals with higher fasting levels of plasma FFAs were at modestly higher risk of type 2 diabetes in this cohort of middle-aged adults.
Differences in Diabetes Prevalence, Incidence, and Mortality Among the Elderly of Four Racial/Ethnic Groups: Whites, Blacks, Hispanics, and Asians
Authors: McBean A. Marshall , Li Shuling , Gilbertson David T. , Collins Allan J.
Published: March 2007

OBJECTIVE—To examine diabetes prevalence, incidence, and mortality from 1993 to 2001 among fee-for-service Medicare beneficiaries ≥67 years of age.

RESEARCH DESIGN AND METHODS—This study was a retrospective analysis of a 5% random sample of Medicare fee-for-service beneficiaries ≥65 years of age in each year.

RESULTS—In 1993, the prevalence of diabetes among those ≥67 years of age was 145 cases per 1,000 individuals. By 2001, it was 197/1,000, an increase of 36.0%. The 2001 prevalence among Hispanics (334/1,000) was significantly higher than among blacks (296/1,000), Asians (243/1,000), and whites (184/1,000, P < 0.0001). During the 7-year period the greatest increase in diabetes prevalence was among Asians (68.0%). Between 1994 and 2001, the annual rate of newly diagnosed elderly individuals with diabetes increased by 36.9%. Hispanics had the greatest increase at 55.0%. The mortality rate among individuals with diabetes decreased by ∼5% between 1994 and 2001 from 92.1/1,000 to 87.2/1,000 (P < 0.001), due to a 6% decrease among whites. No decrease in mortality was seen among elderly individuals without diabetes, it was 55/1,000 in 1994 and 54/1,000 in 2001.

CONCLUSIONS—The dramatic increase in the incidence and prevalence of diabetes likely reflect a combination of true increases, as well as changes in the diagnostic criteria and increased interest in diagnosing and appropriately treating diabetes in the elderly. Improved treatment may have had an impact on mortality rates among individuals with diabetes, although they could have been influenced by the duration of diabetes before diagnosis, which has likely decreased. Changes in incidence, prevalence, and mortality in elderly individuals with diabetes need to continue to be monitored.
Acute Hyperglycemia Alters Mood State and Impairs Cognitive Performance in People With Type 2 Diabetes
Authors: Sommerfield Andrew J. , Deary Ian J. , Frier Brian M.
Published: March 2007

OBJECTIVE—To examine the effects of acute hyperglycemia on cognitive function and mood in people with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Twenty subjects with type 2 diabetes, median age 61.5 years (range 53.1–72.0), known duration of diabetes 5.9 years (range 2.8–11.2), BMI 29.8 kg/m2 (range 22.0–34.6), and HbA1c 7.5% (range 6.7–8.4) were studied. Treatment modalities varied from antidiabetic medications to insulin. A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose at either 4.5 (euglycemia) or 16.5 mmol/l (hyperglycemia) on two occasions in a randomized and counterbalanced fashion. Tests of information processing, immediate and delayed memory, working memory, and attention were administered, along with a mood questionnaire, during each experimental condition.

RESULTS—Speed of information processing, working memory, and some aspects of attention were impaired during acute hyperglycemia. Subjects were significantly more dysphoric during hyperglycemia, with reduced energetic arousal and increased sadness and anxiety.

CONCLUSIONS—During acute hyperglycemia, cognitive function was impaired and mood state deteriorated in a group of people with type 2 diabetes. These findings are of practical importance because intermittent or chronic hyperglycemia is common in people with type 2 diabetes and may interfere with many daily activities through adverse effects on cognitive function and mood.
Insulin Glulisine Provides Improved Glycemic Control in Patients With Type 2 Diabetes
Authors: Dailey George , Rosenstock Julio , Moses Robert G. , Ways Kirk
Published: March 2007

OBJECTIVE—Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin.

RESEARCH DESIGN AND METHODS—In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this randomized, multicenter, multinational, open-label, parallel-group study. Subjects were allowed to continue the same dose of prestudy regimens of oral antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose change).

RESULTS—A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI (−0.46 vs. −0.30% with RHI; P = 0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs. 9.02 mmol/l]; P < 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l]; P < 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall, nocturnal, and severe) and weight gain were comparable between the two treatment groups. There were no between-group differences in baseline-to-end point changes in insulin dose.

CONCLUSIONS—Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs. The clinical relevance of such a difference remains to be established.
Serum Ferritin and Risk of the Metabolic Syndrome in U.S. Adults
Authors: Jehn Megan , Clark Jeanne M. , Guallar Eliseo
Published: March 2007

OBJECTIVE—We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional study of 6,044 adults >20 years of age who participated in the Third National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least three of the following: elevated blood pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Insulin resistance was estimated using homeostasis model assessment (for insulin resistance), fasting insulin, and triglyceride–to–HDL cholesterol ratio.

RESULTS—After excluding individuals with likely hemochromatosis, mean serum ferritin values in premenopausal women, postmenopausal women, and men were 33.6, 93.4, and 139.9 μg/l, respectively. Metabolic syndrome was more common in those with the highest compared with the lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P = 0.002), postmenopausal women (47.5 vs. 28.2%, P < 0.001), and men (27.3 vs. 13.8%, P < 0.001). Insulin resistance also increased across quartiles of serum ferritin for men and postmenopausal women and persisted after adjustment for age, race/ethnicity, C-reactive protein, smoking, alcohol intake, and BMI.

CONCLUSIONS—Elevated iron stores were positively associated with the prevalence of the metabolic syndrome and with insulin resistance.
Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes
Authors: Quattrin Teresa , Bélanger André , Bohannon Nancy J.V. , Schwartz Sherwyn L. ,   for the Exubera Phase III Study Group
Published: March 2007

OBJECTIVE—The aim of this study was to determine whether premeal pulmonary delivery of rapid-acting, dry-powder insulin (Exubera) plus Ultralente could provide glycemic control comparable to a conventional insulin regimen in type 1 diabetes.

RESEARCH DESIGN AND METHODS—Three hundred thirty-five subjects were randomly assigned to receive either premeal inhaled insulin plus bedtime Ultralente or two to three injections of regular and NPH insulin for 24 weeks. The primary end point was a change in HbA1c.

RESULTS—Mean decreases in HbA1c values were comparable for inhaled (8.1–7.9%) and conventional groups (8.1–7.7%) (adjusted treatment group difference 0.16% [95% CI −0.01 to 0.32]). There were greater reductions for inhaled versus conventional regimen in fasting and postprandial plasma glucose (adjusted mean change differences −25.17 and −30.28 mg/dl, respectively [95% CI −43.39 to −6.95 and −54.58 to −5.97, respectively]). Hypoglycemia (events/subject month) was lower for the inhaled (8.6) versus the conventional (9.0) group (risk ratio, 0.96 [95% CI 0.93–0.99]). In subjects receiving inhaled insulin, increased insulin antibody levels were observed, but there were no associated clinical or laboratory changes. Adverse events were comparable between groups. Mild to moderate cough was more frequent in the inhaled insulin group (27 vs. 5%) but decreased during the treatment. Pulmonary function tests were not different between the groups except for a greater decrease in carbon monoxide diffusing capacity in the inhaled insulin group. Treatment satisfaction was greater in the inhaled than in the conventional group.

CONCLUSIONS—Inhaled insulin is effective, well tolerated, and well accepted in patients with type 1 diabetes and provides glycemic control comparable to that with a conventional insulin regimen.
Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Sulfonylurea-Treated Patients With Type 2 Diabetes
Authors: Buse John B. , Henry Robert R. , Han Jenny , Kim Dennis D. , Fineman Mark S. , Baron Alain D. ,   for the Exenatide-113 Clinical Study Group
Published: March 2007

OBJECTIVE—This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy.

RESEARCH DESIGN AND METHODS—This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 ± 11 years, BMI 33 ± 6 kg/m2, HbA1c 8.6 ± 1.2% [±SD]) and began 4 weeks at 5 μg subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo. Subsequently, subjects in arm B were escalated to 10 μg b.i.d. exenatide. All subjects continued sulfonylurea therapy.

RESULTS—At week 30, HbA1c changes from baseline were −0.86 ± 0.11, −0.46 ± 0.12, and 0.12 ± 0.09% (±SE) in the 10-μg, 5-μg, and placebo arms, respectively (adjusted P < 0.001). Of evaluable subjects with baseline HbA1c > 7% (n = 237), 41% (10 μg), 33% (5 μg), and 9% (placebo) achieved HbA1c ≤ 7% (P < 0.001). Fasting plasma glucose concentrations decreased in the 10-μg arm compared with placebo (P < 0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss, with an end-of-study loss in the 10-μg exenatide arm of −1.6 ± 0.3 kg from baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally mild or moderate and gastrointestinal in nature. No severe hypoglycemia was observed.

CONCLUSIONS—Exenatide significantly reduced HbA1c in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally well tolerated and was associated with weight loss.
Glycemic Index and Dietary Fiber and the Risk of Type 2 Diabetes
Authors: Hodge Allison M. , English Dallas R. , O’Dea Kerin , Giles Graham G.
Published: March 2007

OBJECTIVE—To examine associations between type 2 diabetes and fiber, glycemic load (GL), dietary glycemic index (GI), and fiber-rich foods.

RESEARCH DESIGN AND METHODS—This was a prospective study of 36,787 men and women aged 40–69 years without diabetes. For all self-reported cases of diabetes at 4-year follow-up, confirmation of diagnosis was sought from medical practitioners. Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes. Data were analyzed with logistic regression, adjusting for country of birth, physical activity, family history of diabetes, alcohol and energy intake, education, 5-year weight change, sex, and age.

RESULTS—Follow-up was completed by 31,641 (86%) participants, and 365 cases were identified. The odds ratio (OR) for the highest quartile of white bread intake compared with the lowest was 1.37 (95% CI 1.04–1.81; P for trend = 0.001). Intakes of carbohydrate (OR per 200 g/day 0.58, 0.36–0.95), sugars (OR per 100 g/day 0.61, 0.47–0.79), and magnesium (OR per 500 mg/day 0.62, 0.43–0.90) were inversely associated with incidence of diabetes, whereas intake of starch (OR per 100 g/day 1.47, 1.06–2.05) and dietary GI (OR per 10 units 1.32, 1.05–1.66) were positively associated with diabetes. These relationships were attenuated after adjustment for BMI and waist-to-hip ratio.

CONCLUSIONS—Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes. One way to achieve this would be to substitute white bread with low-GI breads.
Risk Factors for the Metabolic Syndrome
Authors: Carnethon Mercedes R. , Loria Catherine M. , Hill James O. , Sidney Stephen , Savage Peter J. , Liu Kiang
Published: March 2007

OBJECTIVE—The aim of this study was to describe the association of the metabolic syndrome with demographic characteristics and to identify modifiable risk factors for development of the metabolic syndrome.

RESEARCH DESIGN AND METHODS—Men and women (55%) aged 18–30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) study without the metabolic syndrome at baseline (n = 4,192, 49% black) were followed-up from 1985 to 2001. Incident metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, was ascertained 7, 10, and 15 years after baseline. Risk factors were measured via clinical examination and standardized questionnaires.

RESULTS—The age-adjusted rate of metabolic syndrome was 10 per 1,000 person-years (n = 575). Metabolic syndrome risk increased with age and was higher among black participants and those with less than a high school education. Higher baseline BMI, no alcohol intake (versus one to three drinks per day), higher intake of dietary carbohydrates, and lower intake of crude fiber were each associated with an increased risk for the metabolic syndrome (relative risk [RR] ranging from 1.3 to 1.9), and physical activity was protective (RR 0.84 [95% CI 0.76–0.92]). In models adjusting simultaneously for all factors, black participants and women were less likely to develop metabolic syndrome. Risk for metabolic syndrome increased 23% (20–27%) per 4.5 kg (10 lb) of weight gained, whereas regular physical activity over time versus low activity was protective (RR 0.49 [0.34–0.70]).

CONCLUSIONS—BMI and weight gain are important risk factors for the metabolic syndrome. Regular physical activity may counter this risk.
Trends in the Prevalence and Ratio of Diagnosed to Undiagnosed Diabetes According to Obesity Levels in the U.S.
Authors: Gregg Edward W. , Cadwell Betsy L. , Cheng Yiling J. , Cowie Catherine C. , Williams Desmond E. , Geiss Linda , Engelgau Michael M. , Vinicor Frank
Published: March 2007

OBJECTIVE—To examine trends in the prevalence of diagnosed and undiagnosed diabetes and the proportion of total cases previously diagnosed, according to obesity status in the U.S. over the past 40 years.

RESEARCH DESIGN AND METHODS—We assembled data from five consecutive cross-sectional national surveys: National Health Examination Survey I (1960–1962), National Health and Nutrition Examination Survey (NHANES) I (1971–1974), NHANES II (1976–1980), NHANES III (1988–1994), and NHANES 1999–2000. Diagnosed diabetes was ascertained, and height and weight were measured in adults aged 20–74 years in all surveys. In NHANES II, NHANES III, and NHANES 1999–2000, a fasting glucose level ≥126 mg/dl was used to identify cases among individuals not reporting diabetes. Design-based analyses and Bayesian models estimate the probability that prevalence of diabetes increased within four BMI groups (<25, 25–29, 30–34, and ≥35 kg/m2).

RESULTS—In the U.S. population aged 20–74 years between 1976–1980 and 1999–2000, significant increases in the prevalence of diagnosed diabetes (3.3–5.8%, probability >99.9%) were accompanied by nonsignificant increases in undiagnosed diabetes (2.0–2.4%, 66.6%). This resulted in an increase in total diabetes (5.3–8.2%, >99.9%) and a modest nonsignificant increase in the proportion of cases that were diagnosed (62–70%, 62.4%). However, these trends varied considerably by BMI level. In individuals with BMI ≥35 kg/m2, diagnosed diabetes increased markedly (from 4.9% in 1960, to 8.6% during 1976–1980, to 15.1% in 1999–2000; probability >99.9%), whereas undiagnosed diabetes declined considerably (12.5% during 1976–1980 to 3.2% in 1999–2000, probability of increase 4.5%) Therefore, the proportion of total diabetes cases that were diagnosed increased from 41 to 83% (probability 99.9%) among individuals with BMI ≥35 kg/m2. By comparison, changes in prevalence within BMI strata <35 kg/m2 were modest and there was no increase in the percent of total cases that were diagnosed.

CONCLUSIONS—National surveys over the last several decades have found large increases in diagnosed diabetes, particularly in overweight and obese individuals, but this has been accompanied by large decreases in undiagnosed diabetes only among individuals with BMI ≥35 kg/m2. This suggests that improvements in diabetes awareness and detection are most prominent among this subgroup.
End-Stage Renal Disease-Associated Managed Care Costs Among Patients With and Without Diabetes
Authors: Joyce Amie T. , Iacoviello John M. , Nag Soma , Sajjan Shiva , Jilinskaia Evguenia , Throop Diane , Pedan Alexander , Ollendorf Daniel A. , Alexander Charles M.
Published: March 2007

OBJECTIVE—To examine the direct costs of care before and after onset of end-stage renal disease (ESRD) for patients with and without diabetes based on analyses of retrospective healthcare claims data.

RESEARCH DESIGN AND METHODS—Patients with onset of ESRD between January 1998 though June 2002 were identified based on use of dialysis, renal transplantation, or other ESRD-related services. Continuous health plan enrollment ≥12 months before and ≥1 month after ESRD onset was required. The costs calculated include both observed and adjusted estimates; the latter were calculated using generalized linear models, controlling for demographic and clinical characteristics, “onset” period, and duration of follow-up. Analyses focus on the diabetic ESRD patient and include a comparison with ESRD patients without diabetes.

RESULTS—The study included 2,020 patients with diabetes and 2,170 without diabetes; 63% of patients were >50 years of age. Average costs were relatively stable before ESRD ($1,535 to $4,357 for diabetes, $1,082 to $2,447 for no diabetes) but more than doubled in the month preceding onset ($9,152 and $8,211, respectively). Postonset, average monthly per-patient costs escalated sharply in the 1st month ($26,507 and $26,789), declined steadily through month 6, and remained flat but elevated thereafter. Adjusted annual costs per patient pre- and postonset of ESRD were significantly higher for diabetes (P < 0.0001); annual costs were 69% ($38,041 vs. $22,538) and 79% ($96,014 vs. $53,653) higher pre- and postonset, respectively.

CONCLUSIONS—The economic burden of ESRD in the year after onset is substantial, particularly among patients with diabetes.
Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes
Authors: Ahrén Bo , Gomis Ramon , Standl Eberhard , Mills David , Schweizer Anja
Published: March 2007

OBJECTIVE—To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment.

RESEARCH DESIGN AND METHODS—We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator, to extend treatment to 1 year. Placebo (n = 51) or LAF237 (50 mg once daily, n = 56) was added to ongoing metformin treatment (1,500–3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52.

RESULTS—In patients randomized to LAF237, baseline HbA1c averaged 7.7 ± 0.1% and decreased at week 12 (Δ = −0.6 ± 0.1%), whereas HbA1c did not change from a baseline of 7.9 ± 0.1% in patients given placebo (between-group difference in ΔHbA1c = −0.7 ± 0.1%, P < 0.0001). Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 ± 0.4 mmol/l (P < 0.0001) and 1.2 ± 0.4 mmol/l (P = 0.0057), respectively, but plasma insulin levels were not affected. At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were −2.4 ± 0.6 mmol/l (P = 0.0001), 40 ± 16 pmol/l (P = 0.0153), and −1.1 ± 0.5 mmol/l (P = 0.0312), respectively. HbA1c did not change from week 12 to week 52 in LAF237-treated patients (n = 42) but increased in participants given placebo (n = 29). The between-group difference in ΔHbA1c after 1 year was −1.1 ± 0.2% (P < 0.0001).

CONCLUSIONS—Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes.
Dietary Antioxidant Intake and Risk of Type 2 Diabetes
Authors: Montonen Jukka , Knekt Paul , Järvinen Ritva , Reunanen Antti
Published: March 2007

OBJECTIVE—The intake of antioxidants was studied for its ability to predict type 2 diabetes.

RESEARCH DESIGN AND METHODS—A cohort of 2,285 men and 2,019 women 40–69 years of age and free of diabetes at baseline (1967–1972) was studied. Food consumption during the previous year was estimated using a dietary history interview. The intake of vitamin C, four tocopherols, four tocotrienols, and six carotenoids was calculated. During a 23-year follow-up, a total of 164 male and 219 female incident cases occurred.

RESULTS—Vitamin E intake was significantly associated with a reduced risk of type 2 diabetes. The relative risk (RR) of type 2 diabetes between the extreme quartiles of the intake was 0.69 (95% CI 0.51–0.94, P for trend = 0.003). Intakes of α-tocopherol, γ-tocopherol, δ-tocopherol, and β-tocotrienol were inversely related to a risk of type 2 diabetes. Among single carotenoids, β-cryptoxanthin intake was significantly associated with a reduced risk of type 2 diabetes (RR 0.58, 95% CI 0.44–0.78, P < 0.001). No association was evident between intake of vitamin C and type 2 diabetes risk.

CONCLUSIONS—This study supports the hypothesis that development of type 2 diabetes may be reduced by the intake of antioxidants in the diet.
Diabetes, Major Depression, and Functional Disability Among U.S. Adults
Authors: Egede Leonard E.
Published: March 2007

OBJECTIVE—The goal of this study was to determine prevalence and odds of functional disability in individuals with diabetes and comorbid major depression compared with individuals with either diabetes or major depression alone.

RESEARCH DESIGN AND METHODS—Data on 30,022 adults aged ≥18 years from the 1999 National Health Interview Survey (NHIS) were analyzed. Four disease categories were created: no diabetes and no major depression, major depression alone, diabetes alone, and diabetes and comorbid major depression. Prevalence of functional disability was calculated for each disease category. Multiple logistic regression was used to determine the odds and correlates of functional disability by disease category controlling for age, sex, race/ethnicity, education, income, census region, and disability-associated comorbidity. STATA was used for all analyses to account for the complex survey design of NHIS.

RESULTS—Prevalence of functional disability by disease category was as follows: no diabetes and no major depression (24.5%); major depression (51.3%); diabetes (58.1%); and diabetes and comorbid major depression (77.8%). With no diabetes and no major depression as reference and after adjusting for relevant covariates, the odds of functional disability was 3.00 (95% CI 2.62–3.42) for major depression, 2.42 (2.10–2.79) for diabetes, and 7.15 (4.53–11.28) for diabetes and comorbid major depression.

CONCLUSIONS—Individuals with diabetes and comorbid major depression have higher odds of functional disability compared with individuals with either diabetes or major depression alone. Additional studies are needed to establish a causal relationship.
Efficacy of Ipomoea batatas (Caiapo) on Diabetes Control in Type 2 Diabetic Subjects Treated With Diet
Authors: Ludvik Bernhard , Neuffer Beatrice , Pacini Giovanni
Published: March 2007

OBJECTIVE—To investigate the tolerability, efficacy, and mode of action of Caiapo, an extract of white sweet potatoes, on metabolic control in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 61 type 2 diabetic patients treated by diet were given 4 g Caiapo (n = 30; mean age 55.2 ± 2.1 years; BMI 28.0 ± 0.4 kg/m2) or placebo (n = 31; mean age 55.6 ± 1.5 years; BMI 27.6 ± 0.3 kg/m2) once daily for 12 weeks. Each subject underwent a 75-g oral glucose tolerance test (OGTT) at baseline and after 1, 2, and 3 months to assess 2-h glucose levels. Additionally, fasting blood glucose, HbA1c, total cholesterol, and triglyceride levels were measured.

RESULTS—After treatment with Caiapo, HbA1c decreased significantly (P < 0.001) from 7.21 ± 0.15 to 6.68 ± 0.14%, whereas it remained unchanged (P = 0.23) in subjects given placebo (7.04 ± 0.17 vs. 7.10 ± 0.19%). Fasting blood glucose levels decreased (P < 0.001) in the Caiapo group (143.7 ± 1.9 vs. 128.5 ± 1.7 mg/dl) and did not change in the placebo group (144.3 ± 1.9 vs. 138.2 ± 2.1 mg/dl; P = 0.052). A decrease in body weight was observed in both the placebo group (P = 0.0027) and in the Caiapo group (P < 0.0001), probably due to a better- controlled lifestyle. In the Caiapo group, body weight was related to the improvement in glucose control (r = 0.618; P < 0.0002). Two-hour glucose levels were significantly (P < 0.001) decreased in the Caiapo group (193.3 ± 10.4 vs. 162.8 ± 8.2 mg/dl) compared with the placebo group (191.7 ± 9.2 vs. 181.0 ± 7.1 mg/dl). Mean cholesterol at the end of the treatment was significantly lower in the Caiapo group (214.6 ± 11.2 mg/dl) than in the placebo group (248.7 ± 11.2 mg/dl; P < 0.05). No significant changes in triglyceride levels or blood pressure were observed, and Caiapo was well tolerated without significant adverse effects.

CONCLUSIONS—This study confirms the beneficial effects of Caiapo on plasma glucose as well as cholesterol levels in patients with type 2 diabetes. For the first time, the long-term efficacy of Caiapo on glucose control was demonstrated by the observed decrease in HbA1c. Thus, the neutraceutical Caiapo seems to be a useful agent in the treatment of type 2 diabetes.
Anti-Inflammatory and Anticoagulant Effects of Pravastatin in Patients With Type 2 Diabetes
Authors: Sommeijer Dirkje W. , MacGillavry Melvin R. , Meijers Joost C.M. , Van Zanten Anton P. , Reitsma Pieter H. , Cate Hugo Ten
Published: March 2007

OBJECTIVE—Type 2 diabetes is associated with increased plasma concentrations of coagulation and inflammation markers. Different studies have shown that treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) is associated with antithrombotic and anti-inflammatory effects in addition to a cholesterol-lowering effect. Our objective was to evaluate the effect of pravastatin (40 mg/day) on coagulation and inflammation markers in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—This was an open, randomized, crossover study designed with an 8-week intervention period. The study group was comprised of 50 patients with type 2 diabetes (median HbA1c 7.1%) and serum total cholesterol of 5–10 mmol/l. We evaluated plasma levels of fibrinogen, F1 + 2, d-dimer, soluble tissue factor (sTF), von Willebrand Factor antigen (vWFag), and C-reactive protein (CRP) in blood samples drawn after fasting on day 1 and after 8 and 16 weeks.

RESULTS—Significant reductions of total cholesterol (−22%; P < 0.001), LDL cholesterol (−32%; P < 0.001), and triglycerides (−10%; P < 0.05) were achieved after 8 weeks of treatment with pravastatin. In addition, significant reductions of plasma levels of F1 + 2 (−4.4%; P < 0.05), vWFag (−5.3%; P < 0.05), and sTF (−3.4%; P < 0.05) were observed after treatment with pravastatin. Furthermore, plasma levels of CRP were also significantly reduced (−13%; P < 0.05). Levels of fibrinogen and d-dimer did not decrease after treatment with pravastatin.

CONCLUSIONS—The results indicated that pravastatin reduces levels of coagulation and inflammation markers in type 2 diabetic patients. These antithrombotic and anti-inflammatory effects of treatment with statins could play a role in reducing cardiovascular complications in type 2 diabetic patients.
Establishment of Blood Glucose Monitoring System Using the Internet
Authors: Kwon Hyuk-Sang , Cho Jae-Hyoung , Kim Hee-Soo , Song Bok-Re , Ko Seung-Hyun , Lee Jung-Min , Kim Sung-Rae , Chang Sang-Ah , Kim Hee-Seung , Cha Bong-Yun , Lee Kwang-Woo , Son Ho-Young , Lee Jin-Hee , Lee Won-Chul , Yoon Kun-Ho
Published: March 2007

OBJECTIVE—The Internet is used worldwide as a communication tool. To improve the quality of diabetes control, we investigated the effectiveness of an Internet-based blood glucose monitoring system (IBGMS) on controlling the changes in HbA1c levels.

RESEARCH DESIGN AND METHODS—We conducted a randomized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary’s Hospital for 3 months. The study subjects were treated with IBGMS for 12 weeks, and the control group received the usual outpatient management over the same period. HbA1c and other laboratory tests were performed twice, once at the beginning of the study and again at the end of the study.

RESULTS—The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age, sex, diabetes duration, BMI, blood pressure, HbA1c, and other laboratory data. On follow-up examination 12 weeks later, HbA1c levels were significantly decreased from 7.59 to 6.94% within the intervention group (P < 0.001). At the end of the study, HbA1c levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA1c (6.94 vs. 7.62%; P < 0.001, respectively). Among patients with baseline HbA1c <7.0%, the patients in the intervention group had lower HbA1c than those in the control group (6.38 vs. 6.99%; P < 0.05). Among the patients with a baseline HbA1c ≥7.0%, the difference between the two groups appeared more obvious: HbA1c levels at the end of the study were 8.12%.

CONCLUSIONS—This new IBGMS resulted in a significant reduction of HbA1c during the study period. We propose that this IBGMS be used as a method for improving diabetes control.
Adiponectin in Youth
Authors: Bacha Fida , Saad Rola , Gungor Neslihan , Arslanian Silva A.
Published: March 2007

OBJECTIVE—Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has antiatherogenic properties. The present study investigated the relationship of adiponectin levels in adolescents to 1) obesity and body fat distribution and 2) insulin sensitivity and the components of syndrome X.

RESEARCH DESIGN AND METHODS—Twenty-three normal-weight and 26 obese adolescents had fasting adiponectin, lipid profile, and proinsulin measurements performed. Hepatic and peripheral insulin sensitivity were assessed with constant-rate [6,6-2H2]glucose infusion and a 3-h hyperinsulinemic-euglycemic clamp, respectively. Body composition was evaluated by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) and subcutaneous adipose tissue were measured by computed tomography scan at the L4-L5 level.

RESULTS—Obese adolescents had ∼50% lower adiponectin than normal-weight adolescents. Moreover, obese adolescents with high (111.8 ± 9.3 cm2) versus low (55.4 ± 2.1 cm2) VAT had lower adiponectin levels (6.2 ± 0.9 vs. 9.0 ± 1.0 μg/ml, P = 0.05). Plasma adiponectin correlated positively with peripheral and hepatic insulin sensitivity (r = 0.67, P < 0.001 and r = 0.54, P < 0.001, respectively) and HDL (r = 0.52, P < 0.001) and negatively with fasting proinsulin and the proinsulin-to-insulin ratio (r = −0.64, P < 0.001 and r = −0.43, P = 0.003, respectively). In a multiple regression analysis, adiponectin, independently and together with BMI, explained 73% (R2 = 0.73, P < 0.001) of the variance in insulin sensitivity. Adiponectin, but not adiposity, was the significant independent determinant of the proinsulin-to-insulin ratio (R2 = 0.18, P = 0.008) and of HDL (R2 = 0.45, P < 0.001).

CONCLUSIONS—In summary, hypoadiponectinemia in youth is a strong and independent correlate of insulin resistance, β-cell dysfunction, visceral adiposity, and syndrome X. The antidiabetogenic and antiatherogenic properties of adiponectin are evident early in life and compromised in youth-onset obesity.