bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Patient Readiness to Change a Predictor of Improved Glycemic Control?
Authors: O’Connor Patrick J. , Asche Stephen E. , Crain A. Lauren , Rush William A. , Whitebird Robin R. , Solberg Leif I. , Sperl-Hillen JoAnn M.
Published: March 2007

OBJECTIVE—To test the hypothesis that patient readiness to change (RTC) predicts future changes in glycemic control in adults with diabetes.

RESEARCH DESIGN AND METHODS—We linked survey data with HbA1c data for a stratified random sample of consenting adults with diabetes. Change in HbA1c from baseline to the 1-year follow-up was computed and used as a dependent variable. Linear regression models assessed RTC and other patient variables as predictors of HbA1c change.

RESULTS—Among 617 patients with baseline HbA1c ≥7% and complete data for analysis, RTC predicted subsequent improvement in HbA1c for those with higher physical functioning (interaction t = −2.45, P < 0.05). Other factors that predicted HbA1c improvement in multivariate linear regression models included higher self-reported medication adherence (t = −4.41, P < 0.01), higher baseline HbA1c (t = −15.08, P < 0.01), and older age (t = −2.61, P < 0.01).

CONCLUSIONS— Diabetes RTC independently predicts change in HbA1c for patients with high but not for patients with low functional health status. Customized use of RTC assessment may have potential to improve care.
Increased Diabetes Incidence in Greek and Italian Migrants to Australia
Authors: Hodge Allison M. , English Dallas R. , O’Dea Kerin , Giles Graham G.
Published: March 2007

OBJECTIVE—The aims of the study were to determine whether Greek or Italian migrants to Australia have an elevated incidence of type 2 diabetes compared with Australian-born individuals and to what extent any differences can be explained by known risk factors.

RESEARCH DESIGN AND METHODS—This was a prospective study of 34,097 men and women aged 40–69 years born in Greece, Italy, Australia, or New Zealand who were free from diabetes at baseline. For all self-reported cases of diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from medical practitioners. Of these, anyone for whom there was no evidence against a diagnosis of type 2 diabetes was considered a case subject.

RESULTS—Follow-up was completed by 29,331 (86%) participants, and 334 case subjects were identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and Italian (2.4%) migrants was more than three times that in Australian-born (0.7%) individuals. After adjusting for age only, the odds ratios (ORs) for being of Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9–5.0) and 3.3 (2.6–4.3), respectively. The only known risk factor for type 2 diabetes that materially affected these ORs was BMI. After adjusting for BMI and age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8–3.2) and 2.0 (1.5–2.6).

CONCLUSIONS—Greek and Italian migrants to Australia have a more than three times greater incidence of type 2 diabetes than Australian-born individuals, and this is only partly explained by BMI. Although weight control will remain important for these high-risk groups, identification of other risk factors is required.
Thermal Thresholds Predict Painfulness of Diabetic Neuropathies
Authors: Krämer Heidrun H. , Rolke Roman , Bickel Andreas , Birklein Frank
Published: March 2007

OBJECTIVE—Pathophysiology explaining pain in diabetic neuropathy (DN) is still unknown.

RESEARCH DESIGN AND METHODS—Thirty patients with peripheral DN (17 men and 13 women; mean age 52.4 ± 2.5 years) were investigated. Fifteen patients had neuropathic pain, and 15 patients were free of pain. Patients were followed over 2 years and examined at the beginning and thereafter every 6 months. Clinical severity and painfulness of the DN were assessed by the neuropathy impairment score and visual analog scales (VASs). Cold and warm perception thresholds as well as heat pain thresholds were obtained for evaluation of Aδ- and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were recorded for analysis of thickly myelinated fibers. Moreover, for assessment of cardiac vagal function, heart rate variability (HRV) was evaluated. In order to reduce day-to-day variability of pain, mean values of the five time points over 2 years were calculated and used for further analysis. Data were compared with an age- and sex-matched control group of healthy volunteers.

RESULTS—There were significant differences regarding electrophysiological studies, HRV and quantitative sensory testing (QST) between patients and healthy control subjects (P < 0.001). Generally, patients with neuropathic pain were indistinguishable from pain-free patients. In the pain group, however, VAS pain ratings were correlated to the impairment of small-fiber function (cold detection thresholds, P = 0.02; warm detection thresholds, P = 0.056).

CONCLUSIONS—Intensity of pain in painful DN seems to depend on small nerve fiber damage and deafferentation.
Different Patterns of Insulin Resistance in Relatives of Type 1 Diabetic Patients With Retinopathy or Nephropathy
Authors: Hadjadj Samy , Péan Franck , Gallois Yves , Passa Philippe , Aubert Robert , Weekers Laurent , Rigalleau Vincent , Bauduceau Bernard , Bekherraz Amine , Roussel Ronan , Dussol Bernard , Rodier Michel , Marechaud Richard , Lefebvre Pierre J. , Marre Michel ,   for the Genesis France-Belgium Study
Published: March 2007

OBJECTIVE—Insulin resistance may be a risk factor for diabetic microangiopathy, which may have a familial component. We carried out a family-based study to determine which components of the insulin resistance syndrome are associated with diabetic retinopathy and nephropathy in type 1 diabetes.

RESEARCH DESIGN AND METHODS—The Genesis France-Belgium Study is a multicenter binational study designed to investigate the genetic factors involved in the microvascular complications of type 1 diabetes using a family-based design. Probands were type 1 diabetic patients with diabetic retinopathy (classified as background, preproliferative, or proliferative) and possibly diabetic nephropathy (absent, incipient, established, or advanced). The insulin resistance score of their first-degree relatives was calculated according to their BMI and history of arterial hypertension, lipid disorders, and type 2 diabetes.

RESULTS—The insulin resistance score of relatives was positively correlated with the albumin excretion rate (P = 0.0009) and fasting plasma glucose (P = 0.0003) and HbA1c (P < 0.0001) concentrations. This score was higher in the relatives of probands with than in those without diabetic nephropathy (P = 0.0370). Similarly, it was higher in relatives of subjects with proliferative diabetic retinopathy than in those of probands without, even after controlling for subjects with versus without diabetic nephropathy (P = 0.0379). However, the components of the insulin resistance score in relatives differed according to the severity of diabetic retinopathy or nephropathy in the probands. Obesity and history of arterial hypertension were most common in relatives of probands with proliferative diabetic retinopathy, whereas obesity and history of lipid disorders were most common in the relatives of probands with diabetic nephropathy.

CONCLUSIONS—Familial insulin resistance segregates with diabetic complications: lipid disorders and obesity segregate with diabetic nephropathy, whereas arterial hypertension and obesity segregate with diabetic retinopathy.
Blood Glucose and Risk of Cardiovascular Disease in the Asia Pacific Region
Authors:   Asia Pacific Cohort Studies Collaboration
Published: March 2007

OBJECTIVE—To assess the shape and strength of the association between usual blood glucose and cardiovascular disease (CVD) in Asian and Australasian cohorts and to determine the impact of adjusting for other determinants of CVD risk and excluding people with diabetes.

RESEARCH DESIGN AND METHODS—Relative risk estimates and 95% CIs were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk on individual participant data from 17 cohort studies. Repeat measurements of blood glucose were used to adjust for regression dilution bias.

RESULTS—Fasting blood glucose data were available for 237,468 participants, and during ∼1.2 million person-years of follow-up, there were 1,661 stroke and 816 ischemic heart disease (IHD) events. Data were also available on 27,996 participants with nonfasting glucose measurements. Continuous positive associations were demonstrated between usual fasting glucose and the risks of CVD down to at least 4.9 mmol/l. Overall, each 1 mmol/l lower usual fasting glucose was associated with a 21% (95% CI 18–24%) lower risk of total stroke and a 23% (19–27%) lower risk of total IHD. The associations were similar in men and women, across age-groups, and in Asian compared with Australasian (Australia and New Zealand) populations. Adjusting for potential confounders or removing those with diabetes as baseline did not substantially affect the associations. Associations for nonfasting glucose were weaker than those with fasting glucose.

CONCLUSIONS—Fasting blood glucose is an important determinant of CVD burden, with considerable potential benefit of usual blood glucose lowering down to levels of at least 4.9 mmol/l.
Noninvasive Angiography and Assessment of Left Ventricular Function Using Multislice Computed Tomography in Patients With Type 2 Diabetes
Authors: Schuijf Joanne D. , Bax Jeroen J. , Jukema J. Wouter , Lamb Hildo J. , Vliegen Hubert W. , Salm Liesbeth P. , de Roos Albert , van der Wall Ernst E.
Published: March 2007

OBJECTIVE—Early identification of coronary artery disease (CAD) in patients with diabetes is important because these patients are at increased risk for CAD and have worse outcome than nondiabetic patients after CAD is diagnosed. Recently, noninvasive coronary angiography and assessment of left ventricular function has been demonstrated with multislice computed tomography (MSCT). The purpose of the present study was to validate this approach in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—MSCT was performed in 30 patients with confirmed type 2 diabetes. From the MSCT images, coronary artery stenoses (≥50% luminal narrowing) and left ventricular function (left ventricular ejection fraction, regional wall motion) were evaluated and compared with results of conventional angiography and two-dimensional echocardiography.

RESULTS—Two hundred twenty of 256 coronary artery segments (86%) were interpretable with MSCT. In these segments, sensitivity and specificity for detection of coronary artery stenoses were 95%. Including the uninterpretable segments, sensitivity and specificity were 81 and 82%, respectively. Bland-Altman analysis in the comparison of left ventricular ejection fractions demonstrated a mean difference of −0.48 ± 3.8% for MSCT and echocardiography, which was not significantly different from 0. Agreement between the two modalities for assessment of regional contractile function was excellent (91%, κ statistic 0.81).

CONCLUSIONS—Accurate noninvasive evaluation of both the coronary arteries and left ventricular function with MSCT is feasible in patients with type 2 diabetes. This noninvasive approach may allow optimal identification of high-risk patients.
Relation Between Development of Nephropathy and the p22phox C242T and Receptor for Advanced Glycation End Product G1704T Gene Polymorphisms in Type 2 Diabetic Patients
Authors: Matsunaga-Irie Seiko , Maruyama Taro , Yamamoto Yukihiro , Motohashi Yoshiko , Hirose Hiroshi , Shimada Akira , Murata Mitsuru , Saruta Takao
Published: March 2007

OBJECTIVE—The development of diabetic nephropathy is considered to be associated with oxidative stress. NADPH oxidase and the receptor for advanced glycation end products (RAGE) have attracted attention as mechanisms of generating oxidative stress. We studied the relation between the genotypes of the NADPH p22phox C242T and RAGE G1704T polymorphisms and the development of diabetic nephropathy in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Using a retrospective review of clinical data, we allocated 181 Japanese type 2 diabetic patients to one of two groups: patients without diabetic nephropathy (group N; n = 108) and patients developing diabetic nephropathy (group D; n = 73) for 10 years or more. The p22phox C242T and RAGE G1704T polymorphisms were examined by Taqman PCR methods.

RESULTS—The frequency of the p22phox CC genotype was significantly higher in group D than in group N (90 vs. 79%; P = 0.0427). The frequency of the RAGE GT + TT genotype was significantly higher in group D than in group N (26 vs. 13%; P = 0.0313). The frequency of the combination of p22phox CC and RAGE GT + TT genotypes was significantly higher in group D than in group N (22 vs. 8%; P = 0.0057). In multiple logistic regression analysis, systolic blood pressure, HbA1c, triglycerides, and the combination of polymorphisms were shown to be independent variables.

CONCLUSIONS—These results suggest that assessment of the combination of NADPH p22phox C242T and RAGE G1704T polymorphisms may be useful in identifying the risk for developing diabetic nephropathy in type 2 diabetic patients.
Indexes of Insulin Resistance and Secretion in Obese Children and Adolescents
Authors: Conwell Louise S. , Trost Stewart G. , Brown Wendy J. , Batch Jennifer A.
Published: March 2007

OBJECTIVE—To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2–5) adolescents using estimates from the modified minimal model frequently sampled intravenous glucose tolerance test (FSIVGTT) as a criterion measure.

RESEARCH DESIGN AND METHODS—Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 ± 2.4 years, mean BMI 35.4 ± 6.2 kg/m2, mean BMI-SDS 3.5 ± 0.5, 7 prepubertal and 11 pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). Si measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent β-cell function (HOMA-β%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples).

RESULTS—There was a significant negative correlation between HOMA-IR and Si (r = −0.89, r = −0.90, and r = −0.81, P < 0.01) and a significant positive correlation between QUICKI and Si (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and Si (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and Si (r = −90, r = −0.90, and r = −0.88, P < 0.01). HOMA-β% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05).

CONCLUSIONS—HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with Si assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β%, FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.
Obesity and the Development of Insulin Resistance and Impaired Fasting Glucose in Black and White Adolescent Girls
Authors: Klein David J. , Aronson Friedman Lisa , Harlan William R. , Barton Bruce A. , Schreiber George B. , Cohen Robert M. , Harlan Linda C. , Morrison John A.
Published: March 2007

OBJECTIVE—Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development.

RESEARCH DESIGN AND METHODS—The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) is a 10-year cohort study of the development of obesity in black and white girls. Two NGHS centers examined the associations of obesity, puberty, and race with fasting insulin, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR; a calculated index of insulin resistance) measures at 9–10 years of age (baseline) and 10 years later.

RESULTS—Black girls had greater baseline and year-10 BMI than white girls, with a greater 10-year incidence of obesity. BMI-insulin correlations were positive in both black and white girls at both visits, but insulin remained higher in black girls after controlling for BMI. In black girls, insulin and HOMA-IR were higher in the prepubertal period (before the emergence of racial differences in BMI), increased more during puberty, and decreased less with its completion. Baseline BMI predicted year-10 glucose and the development of impaired fasting glucose (IFG) in black girls. In white girls, the rate of BMI increase during follow-up predicted these outcomes. The 10-year incidence of diabetes in black girls was 1.4%.

CONCLUSIONS—Black-white differences in insulin resistance are not just a consequence of obesity, but precede the pubertal divergence in BMI. The development of IFG appears to be a function of the rate of increase of BMI in white girls and early obesity in black girls.
Risk Factors for Coronary Heart Disease in Type 1 Diabetic Patients in Europe
Authors: Soedamah-Muthu Sabita S. , Chaturvedi Nish , Toeller Monika , Ferriss Barry , Reboldi Paolo , Michel Georges , Manes Christos , Fuller John H. ,   the EURODIAB Prospective Complications Study Group
Published: March 2007

OBJECTIVE—The goal of the study was to examine risk factors in the prediction of coronary heart disease (CHD) and differences in men and women in the EURODIAB Prospective Complications Study.

RESEARCH DESIGN AND METHODS—Baseline risk factors and CHD at follow-up were assessed in 2,329 type 1 diabetic patients without prior CHD. CHD was defined as physician-diagnosed myocardial infarction, angina pectoris, coronary artery bypass graft surgery, and/or Minnesota-coded ischemic electrocardiograms or fatal CHD.

RESULTS—There were 151 patients who developed CHD, and the 7-year incidence rate was 8.0 (per 1,000 person-years) in men and 10.2 in women. After adjustment for age and/or duration of diabetes, the following risk factors were related to CHD in men: age, GHb, waist-to-hip ratio (WHR), HDL cholesterol, smoking, albumin excretion rate (AER), and autonomic neuropathy. The following risk factors were related to CHD in women: age, systolic blood pressure (BP), fasting triglycerides, AER, and retinopathy. Multivariate standardized Cox proportional hazards models showed that age (hazard ratio 1.5), AER (1.3 in men and 1.6 in women), WHR (1.3 in men), smoking (1.5 in men), fasting triglycerides (1.3 in women) or HDL cholesterol (0.74 in women), and systolic BP (1.3 in women) were predictors of CHD.

CONCLUSIONS—This study supports the evidence for a strong predictive role of baseline albuminuria in the pathogenesis of CHD in type 1 diabetes. Furthermore, sex-specific risk factors such as systolic BP, fasting triglycerides (or HDL cholesterol), and WHR were found to be important in the development of CHD.
Transdermal 17-β-Estradiol and Risk of Developing Type 2 Diabetes in a Population of Healthy, Nonobese Postmenopausal Women
Authors: Rossi Rosario , Origliani Giorgia , Modena Maria G.
Published: March 2007

OBJECTIVE—Various observational and randomized studies have demonstrated a reduction in the incidence of type 2 diabetes in postmenopausal women who received estrogen orally. No studies have been performed on the incidence of type 2 diabetes in postmenopausal women treated with transdermal 17-β-estradiol. The purpose of our study was to assess the influence of transdermal 17-β-estradiol on the incidence of type 2 diabetes in a population of healthy, nonobese postmenopausal women.

RESEARCH DESIGN AND METHODS—Between January 1998 and December 2002, 673 healthy, nonobese postmenopausal women (mean age 54 ± 5 years) were enrolled: 144 (21.4%) of these took transdermal 17-β-estradiol and 529 (78.6%) had never taken hormones during their postmenopausal period. Final elaboration of the data took place in July 2003, with a mean follow-up of 3.7 ± 0.7 years (ranging from 0.5 to 5 years).

RESULTS—Type 2 diabetes developed in 60 patients during the follow-up period, which is the equivalent of 22 cases per 1,000 women-years. In the “hormones nonusers” group, diabetes developed in 10% (54 of 529 women; equivalent of 26.5 cases/1,000 women-years), whereas in the “hormones users” group, diabetes developed in 4.16% (6 of 144 women; equivalent of 12.1 cases/1,000 women-years). Transdermal 17-β-estradiol emerged as a treatment that significantly reduced the risk of developing diabetes (RR 2.19, 95% CI 1.79–3.56; P = 0.006).

CONCLUSIONS—Our results suggest a significant reduction in the incidence of type 2 diabetes in our population of nonobese, healthy postmenopausal women who used transdermal 17-β-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis.
The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality
Authors: Fox Caroline S. , Sullivan Lisa , D’Agostino Ralph B. , Wilson Peter W.F.
Published: March 2007

OBJECTIVE—The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes.

RESEARCH DESIGN AND METHODS—The duration of diabetes (fasting glucose ≥126 mg/dl, random glucose ≥200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors.

RESULTS—Among 588 person-exams with diabetes (mean age 58 ± 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99–1.92), and the risk for CHD death was 1.86 times higher (1.17–2.93) for the same increase in duration of diabetes.

CONCLUSIONS—Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk.
Insulin Sensitivity, Insulinemia, and Coronary Artery Disease
Authors: Rewers Marian , Zaccaro Daniel , D’Agostino Ralph , Haffner Steven , Saad Mohammed F. , Selby Joe V. , Bergman Richard , Savage Peter ,   for the Insulin Resistance Atherosclerosis Study Investigators
Published: March 2007

OBJECTIVE—The aim of this study was to evaluate whether low insulin sensitivity (Si) measured using a modified frequently sampled intravenous glucose tolerance test with minimal model analysis is associated with coronary artery disease (CAD) independent of other cardiovascular risk factors.

RESEARCH DESIGN AND METHODS—We studied 1,482 women and men, age 40–69 years old, African American (28%), Hispanic (34%), or non-Hispanic white (38%), with normal (45%), impaired (23%), or diabetic (32%) glucose tolerance. CAD defined as confirmed past myocardial infarction, coronary artery bypass graft, coronary angioplasty, or presence of a major Q-wave was found in 91 participants.

RESULTS—The odds ratio (OR) for CAD was greatest among individuals in the two lowest quintiles of Si (2.4, 95% CI 1.0–5.6 and 4.7, 2.1–10.7) compared with the highest Si quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in Si was associated with a 56% increase in CAD (P = 0.028). Similar increments in fasting or 2-h insulin levels were associated with, respectively, only 15 (NS) and 3% (NS) increases in CAD. The association between Si and CAD was partially mediated by insulin, HDL cholesterol and triglyceride levels, hypertension, diabetes, and obesity, but not LDL cholesterol or cigarette smoking.

CONCLUSIONS—Low Si is associated with CAD independently of and stronger than plasma insulin levels. Part of the association is accounted for by dyslipidemia, hypertension, diabetes, and obesity.
Cardiovascular Autonomic Neuropathy Is Associated With Microalbuminuria in Older Patients With Type 2 Diabetes
Authors: Moran Andrew , Palmas Walter , Field Lesley , Bhattarai Jyoti , Schwartz Joseph E. , Weinstock Ruth S. , Shea Steven
Published: March 2007

OBJECTIVE—Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients.

RESEARCH DESIGN AND METHODS—At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 ± 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording.

RESULTS—Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest tertile of HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with urine microalbumin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA1c, and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other.

CONCLUSIONS—Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes.
A Direct Efficacy and Safety Comparison of Insulin Aspart, Human Soluble Insulin, and Human Premix Insulin (70/30) in Patients With Type 2 Diabetes
Authors: Bretzel Reinhard G. , Arnolds Sabine , Medding Jürgen , Linn Thomas
Published: March 2007

OBJECTIVE—Because there are limited data on the comparison of insulin aspart and mixed insulin in type 2 diabetes, this trial was performed to compare the efficacy and safety of preprandial insulin aspart with human soluble insulin (HI) and human premix (70% NPH/30% regular) insulin (MIX).

RESEARCH DESIGN AND METHODS—A total of 231 type 2 diabetic patients were randomized to insulin aspart (n = 75), HI (n = 80), or MIX (n = 76) for 3 months. Insulin aspart and HI were administered with or without bedtime NPH insulin. A total of 204 patients completed the trial according to protocol. HbA1c, 7-point blood glucose, insulin dosage, and hypoglycemic episodes were recorded. The primary end point was “change of HbA1c” from baseline to last visit. Analysis for equivalence was performed by t tests with three subtests.

RESULTS—HbA1c decreased 0.91 ± 1.00 for insulin aspart, 0.73 ± 0.87 for HI, and 0.65 ± 1.10 for MIX with the following confidence intervals: insulin aspart HI (−0.21 to 0.57, P = 0.025), insulin aspart MIX (−0.17 to 0.69, P = 0.092), and HI-MIX (−0.33 to 0.48, P = 0.006). Postprandial blood glucose decreased in the insulin aspart group: 0.44 mmol/l to >1.67 mmol/l compared with HI and 1.1 mmol/l to >1.67 mmol/l compared with MIX. Preprandial insulin doses were similar in the insulin aspart and HI groups (10–14.5 U). Hypoglycemic events per month were 0.56 HI, 0.40 insulin aspart, and 0.19 MIX.

CONCLUSIONS—Statistically, insulin aspart was not equivalent to another treatment in terms of HbA1c reduction. Insulin aspart treatment resulted in improved HbA1c and postprandial blood glucose. The application of insulin aspart was safe and well tolerated.
Orlistat Augments Postprandial Increases in Glucagon-like Peptide 1 in Obese Type 2 Diabetic Patients
Authors: Damci Taner , Yalin Serap , Balci Huriye , Osar Zeynep , Korugan Ustun , Ozyazar Mucahit , Ilkova Hasan
Published: March 2007

OBJECTIVE—Orlistat leads to improved glycemic control in obese type 2 diabetic patients, which is attributed to decreased insulin resistance associated with weight loss. Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are gut hormones that are secreted in response to food intake, and they both stimulate insulin secretion. Orlistat decreases fat absorption and increases intestinal fat content, which may lead to increased secretion of these peptides. In this pilot study, we tested the hypothesis that increased levels of these intestinal hormones may be involved in the improvement of postprandial hyperglycemia observed previously with orlistat in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 29 type 2 diabetic patients, who were not taking insulin or α-glucosidase inhibitors, were enrolled in the study. On a crossover and single-blind design, after an overnight fasting, the patients received 120-mg orlistat or placebo capsules, followed by a standard 600-kcal mixed meal that contained 38% fat. At baseline and 60 min after the meal, blood samples were obtained for the measurement of GLP-1, GIP, insulin, C-peptide, triglycerides, free fatty acids, and glucose.

RESULTS—All measured parameters increased significantly in response to the mixed meal compared with baseline, both with orlistat or placebo. When compared with the placebo, the orlistat administration resulted in a significantly enhanced postprandial increase in GLP-1 and C-peptide levels and attenuated the postprandial rise in glucose and triglycerides.

CONCLUSIONS—The results of this study suggest that apart from decreasing insulin resistance as a result of weight loss, orlistat may increase postprandial GLP-1 levels, thereby enhancing the insulin secretory response to the meal and blunting the postprandial rise in glucose in type 2 diabetic patients. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug.
Cost-Effectiveness Analysis of Telemedicine to Evaluate Diabetic Retinopathy in a Prison Population
Authors: Aoki Noriaki , Dunn Kim , Fukui Tsuguya , Beck J. Robert , Schull William J. , Li Helen K.
Published: March 2007

OBJECTIVE—A cost-effectiveness analysis was conducted to investigate the clinical and economic impact of teleophthalmology in evaluating diabetic retinopathy in prison inmates with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Based on a hypothetical teleophthalmology system to evaluate diabetic retinopathy patients with type 2 diabetes in a prison care setting, a Markov decision model was developed with probability and cost data derived primarily from published epidemiological and outcome studies. A 40-year-old African-American man with type 2 diabetes was used as a reference case subject. The number of quality-adjusted life-years (QALYs) gained was used as the clinical outcome, and the cost in U.S. dollars from the year 2003 was used as the economic outcome. Teleophthalmology and nonteleophthalmology strategies were compared using an expected QALYs calculation and two types of sensitivity analyses: probabilistic and traditional n-way sensitivity analyses.

RESULTS—The teleophthalmology strategy dominates in the cost-effectiveness analysis for the reference case subject: $16,514/18.73 QALYs for teleophthalmology and $17,590/18.58 QALYs for nonteleophthalmology. Ninety percent of the Monte Carlo simulations showed cost effectiveness (annual cost/QALYs ≤$50,000) in the teleophthalmology strategy based on an assumed inmate population. Teleophthalmology is the better strategy if the number of diabetic inmates in the prison community is >500.

CONCLUSIONS—Our cost-effectiveness analysis demonstrates that teleophthalmology holds great promise to reduce the cost of inmate care and reduce blindness caused by diabetic retinopathy in type 2 diabetic patients.
Repaglinide Versus Nateglinide Monotherapy
Authors: Rosenstock Julio , Hassman David R. , Madder Robert D. , Brazinsky Shari A. , Farrell James , Khutoryansky Naum , Hale Paula M. ,   for the Repaglinide Versus Nateglinide Comparison Study Group
Published: March 2007

OBJECTIVE—A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise.

RESEARCH DESIGN AND METHODS—Enrolled patients (n = 150) had received treatment with diet and exercise in the previous 3 months with HbA1c >7 and ≤12%. Patients were randomized to receive monotherapy with repaglinide (n = 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n = 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA1c and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia.

RESULTS—Mean baseline HbA1c values were similar in both groups (8.9%). Final HbA1c values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA1c were significantly greater for repaglinide monotherapy than nateglinide monotherapy (−1.57 vs. −1.04%; P = 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (−57 vs. −18 mg/dl; P < 0.001). HbA1c values <7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose <50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group.

CONCLUSIONS—In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA1c and FPG values after 16 weeks of therapy.
Relation of Lower-Extremity Amputation to All-Cause and Cardiovascular Disease Mortality in American Indians
Authors: Resnick Helaine E. , Carter Elizabeth A. , Lindsay Robert , Henly Susan J. , Ness Frederick K. , Welty Thomas K. , Lee Elisa T. , Howard Barbara V.
Published: March 2007

OBJECTIVE—To compare risk of all-cause and cardiovascular disease (CVD) mortality in people with a lower-extremity amputation (LEA) attributable to diabetes and people without an LEA.

RESEARCH DESIGN AND METHODS—The Strong Heart Study is a study of CVD and its risk factors in 13 American-Indian communities. LEA was ascertained at baseline by direct examination of the legs and feet. Mortality surveillance is complete through 2000.

RESULTS—Of 2,108 participants with diabetes at baseline, 134 participants (6.4%) had an LEA. Abnormal ankle-brachial index (53%), albuminuria (87%), and long diabetes duration (mean 19.8 years) were common among diabetic subjects with LEA. Mean diabetes duration among diabetic participants without LEA and in those with toe and below-the-knee amputations was 11.9, 18.6, and 21.1 years, respectively. During 8.7 (±2.9) years of follow-up, 102 of the participants with LEA (76%) died from all causes and 35 (26%) died from CVD. Of the 1,974 diabetic participants without LEA at baseline, 604 (31%) died from all causes and 206 (10%) died from CVD. The unadjusted hazard ratios (HRs) for all-cause and CVD mortality in diabetic participants with LEA compared with those without were 4.0 and 4.1, respectively. Adjusting for known and suspected confounders, LEA persisted as a predictor of all-cause (HR 2.2, 95% CI 1.7–2.9) and CVD mortality (HR 1.9, 95% CI 1.3–2.9). We observed a significant interaction between baseline LEA and sex on CVD mortality, with female sex conferring added risk of CVD mortality.

CONCLUSIONS—LEA is a potent predictor of all-cause and CVD mortality in diabetic American Indians. The combination of female sex and LEA is associated with greater risk of CVD mortality than either factor alone.
Use and Abuse of HOMA Modeling
Authors: Wallace Tara M. , Levy Jonathan C. , Matthews David R.
Published: March 2007

Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than β-cell function.

This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in β-cell function were modeled by changing the β-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods.

We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring β-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose.

In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.
Mortality and Causes of Death in a National Sample of Diabetic Patients in Taiwan
Authors: Tseng Chin-Hsiao
Published: March 2007

OBJECTIVE—To determine the mortality rate, causes of death, and standardized mortality ratio (SMR) in Taiwanese diabetic patients.

RESEARCH DESIGN AND METHODS—A cohort of 256,036 diabetic patients (118,855 men and 137,181 women, aged 61.2 ± 15.2 years) using the National Health Insurance were assembled during the years 1995–1998 and followed up to the end of 2001. Deaths were verified by indexing to the National Register of Deaths. Underlying causes of death were determined from death certificates coded according to the ninth revision of the International Classification of Diseases. The general population of Taiwan was used as reference for SMR calculation.

RESULTS—With a total of 1,124,348.4 person-years of follow-up, 43,888 patients died and the crude mortality rate was 39.0/1,000 person-years. Mortality rates increased with age, and diabetic men had a significantly higher risk of death than women. However, mortality rate ratio for men versus women attenuated with increasing age. The overall SMR was 1.63 (1.62–1.65), and SMRs also attenuated in the elderly. Causes of death ascribed to diabetes; cancer; cardiopulmonary disease; stroke; disease of arteries, arterioles, and capillaries; nephropathy; infection; digestive diseases; accidents; and suicide were 28.8, 18.5, 9.0, 10.5, 0.3, 4.8, 6.4, 7.9, 3.2, and 0.8%, respectively.

CONCLUSIONS—Approximately 71.2% of the diabetes-related deaths would not be ascribed to diabetes on death certificates in Taiwan. The diabetic men have higher risk of dying than women, and diabetic patients have excess mortality when compared with the general population. For underlying causes of death not listed as diabetes, total cardiovascular death, including cardiopulmonary disease, stroke, and disease of arteries, arterioles, and capillaries, is the most common cause of death, followed by cancer.
Improving Efficacy of Diabetes Management Using Treatment Algorithms in a Mainly Hispanic Population
Authors: Fanning Etta L. , Selwyn Beatrice J. , Larme Anne C. , DeFronzo Ralph A.
Published: March 2007

OBJECTIVE—To compare clinical outcomes obtained using treatment algorithms versus standard “usual care” to treat patients with type 2 diabetes in a community setting.

RESEARCH DESIGN AND METHODS—An observational group comparison was implemented in three community-based clinics in San Antonio, Texas: 1) a community clinic following treatment algorithms (CC-TA), 2) university clinic following treatment algorithms (UC-TA), and 3) a community clinic following standard “usual care” practices (CC-SC). Three hundred fifty-eight recently diagnosed type 2 diabetic patients (90% Mexican American, from low-income neighborhoods) who were consecutively identified at the three clinics were recruited. Following medical and laboratory evaluation, participants were started on treatment for hyperglycemia, hypertension, and dyslipidemia and followed for 12 months.

RESULTS—Decrements in HbA1c at 12 months in the CC-TA and UC-TA were 3.1 and 3.3%, respectively, compared to 1.3% in the CC-SC (P < 0.0001). Corresponding decrements in fasting plasma glucose at 12 months were 94 and 99 mg/dl, respectively, versus 38 mg/dl in CC-SC (P < 0.0001). Reductions in total cholesterol, LDL cholesterol, and triglycerides at 12 months were greater in both algorithm-managed clinics compared to standard care–managed clinics (P < 0.0001). In algorithm-managed clinics, there were 30% more documented eye exams and 24% more documented foot exams than in standard care–managed patients.

CONCLUSIONS—Adherence to the treatment algorithms improved metabolic outcomes in type 2 diabetic patients to a greater extent than standard care practices. These results have important clinical implications for the treatment of type 2 diabetic patients.
Pancreas Transplantation Improves Vascular Disease in Patients With Type 1 Diabetes
Authors: Larsen Jennifer L. , Colling Christopher W. , Ratanasuwan Tanaporn , Burkman Tab W. , Lynch Thomas G. , Erickson Judi M. , Lyden Elizabeth R. , Lane James T. , Mack-Shipman Lynn R.
Published: March 2007

OBJECTIVE—Pancreas transplantation (PTX) normalizes glucose and improves microvascular complications, but its impact on macrovascular disease is still debated.

RESEARCH DESIGN AND METHODS—Carotid intima-media thickness (IMT), shown to correlate with cardiovascular disease (CVD) risk and events, was determined prospectively by ultrasonography in successful pancreas transplant recipients to evaluate the effect of PTX on CVD risk. Carotid IMT and CVD risk factors of pancreas transplant recipients (n = 25) were compared with three groups: individuals with type 1 diabetes without significant nephropathy (n = 20), nondiabetic kidney transplant recipients (n = 16), and normal control subjects (n = 32). Mean age of pancreas transplant recipients at the time of transplantation was 42.4 ± 1.2 years (mean ± SE) and duration of diabetes was 25.9 ± 1.4 years.

RESULTS—After PTX, HbA1c level (P < 0.0001) decreased to normal and, whereas creatinine level (P = 0.0002) decreased, it remained elevated compared with normal control subjects (P < 0.05). Blood pressure, BMI, fasting lipid levels, smoking frequency, and use of hypolipidemic agents were unchanged. Mean carotid IMT was increased in pancreas transplant candidates but decreased by 1.8 ± 0.1 year after PTX (P = 0.0068), no longer different from that in normal control subjects or patients with type 1 diabetes.

CONCLUSIONS—Carotid IMT improves after successful PTX within 2 years of the procedure, with normalization of HbA1c and improved renal function, independent of changes in lipid levels, BMI, blood pressure, smoking, or use of hypolipidemic agents. This study suggests that CVD risk, future events, and mortality should improve after PTX in the absence of other significant, untreated CVD risk factors.
Preventing Cancer, Cardiovascular Disease, and Diabetes
Authors: Eyre Harmon , Kahn Richard , Robertson Rose Marie ,   on behalf of the ACS/ADA/AHA Collaborative Writing Committee*
Published: March 2007

Collectively, cardiovascular disease (including stroke), cancer, and diabetes account for approximately two-thirds of all deaths in the U.S. and about $700 billion in direct and indirect economic costs each year. Current approaches to health promotion and prevention of cardiovascular disease, cancer, and diabetes do not approach the potential of the existing state of knowledge. A concerted effort to increase application of public health and clinical interventions of known efficacy to reduce prevalence of tobacco use, poor diet, and insufficient physical activity—the major risk factors for these diseases—and to increase utilization of screening tests for their early detection could substantially reduce the human and economic cost of these diseases. In this article, the American Cancer Society, American Diabetes Association, and American Heart Association review strategies for the prevention and early detection of cancer, cardiovascular disease, and diabetes, as the beginning of a new collaboration among the three organizations. The goal of this joint venture is to stimulate substantial improvements in primary prevention and early detection through collaboration between key organizations, greater public awareness about healthy lifestyles, legislative action that results in more funding for and access to primary prevention programs and research, and reconsideration of the concept of the periodic medical checkup as an effective platform for prevention, early detection, and treatment.