bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular Compliance Is Reduced in the Early Stages of Type 1 Diabetes
Authors: Romney Jacques S. , Lewanczuk Richard Z.
Published: March 2007

OBJECTIVE—To determine whether arterial compliance of patients with type 1 diabetes is reduced before the development of clinically apparent diabetes complications.

RESEARCH DESIGN AND METHODS—Pulse-wave analysis was used to compare vascular compliance between patients with type 1 diabetes and nondiabetic control subjects. Analysis of covariance was used to determine differences between the two groups with adjustment for age if needed.

RESULTS—A total of 59 patients with type 1 diabetes were studied; age ranged from 17–61 years. Of the 59 patients, 32 had no evidence of diabetes complications and 27 had microvascular complications. The control group consisted of 57 healthy subjects ranging in age from 23–79 years. In the control group, large artery compliance (C1) and small artery compliance (C2) were inversely proportional to age (r = −0.55 for C1 and −0.50 for C2; P < 0.01). When the control subjects were compared with type 1 diabetic patients without microvascular complications, C1 was 1.51 ± 0.04 (SEM) for the control group and 1.33 ± 0.06 (SE) ml/mmHg for the diabetic group, whereas C2 was 0.080 ± 0.005 (SE) and 0.065 ± 0.005 (SE) ml/mmHg for the control and diabetic subjects, respectively, when adjusted for age (P = 0.03 for both C1 and C2).

CONCLUSIONS—Vascular compliance of both the large and small arteries is reduced in type 1 diabetic patients before any clinical complications from the diabetes are evident. This study serves to emphasize that vascular changes occur at an early point in the disease and may increase risk of cardiovascular events in patients with diabetes. Larger prospective studies are required to confirm this finding and to investigate the efficacy of medical intervention.
Productivity Losses Associated With Diabetes in the U.S.
Authors: Ng Ying Chu , Jacobs Philip , Johnson J.A.
Published: March 2007

OBJECTIVE— The objective of this study was to estimate the cost of productivity losses in the U.S. attributable to diabetes, with regard to specific demographic and disease-related characteristics in the U.S.

RESEARCH DESIGN AND METHODS— We used the 1989 National Health Interview Survey, a random survey of individuals in the U.S. that included a diabetes supplement. Data on individuals were obtained for labor force participation, hours of work, demographic and occupational characteristics,self-reported health status, and several variables that indicated the presence, duration, and severity (complications) of diabetes. Using multivariate regression analyses, we estimated the association of independent variables (e.g., demographics, health, and diabetes status) with labor force participation, hours of work lost, and the economic value of lost work attributable to diabetes and its complications and duration.

RESULTS— In general, the presence of diabetes and complications were found to be related to workforce participation variables. The magnitude of the lost-productivity costs depended on personal characteristics and on the presence and status of diabetes. In general, the loss of yearly earnings amounted to about a one-third reduction in earnings and ranged from $3,700 to $8,700 per annum.

CONCLUSIONS— Diabetes has a considerable net effect on earnings, and the complications and duration of diabetes have compound effects. Our findings have implications for the cost-effectiveness of diabetes control; the presence of complicating factors is the single most important predictive factor in lost productivity costs attributable to diabetes, and thus the avoidance or retardation of complications will have an impact on indirect health-related costs.
Graftskin, a Human Skin Equivalent, Is Effective in the Management of Noninfected Neuropathic Diabetic Foot Ulcers
Authors: Veves Aristidis , Falanga Vincent , Armstrong David G. , Sabolinski Michael L. ,   the Apligraf Diabetic Foot Ulcer Study
Published: March 2007

OBJECTIVE— We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers.

RESEARCH DESIGN AND METHODS— In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit.

RESULTS— At the 12-week follow-up visit, 63 (56%)Graftskin-treated patients achieved complete wound healing compared with 36(38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group.

CONCLUSIONS— Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.
Homeostasis Model Assessment Is a Reliable Indicator of Insulin Resistance During Follow-up of Patients With Type 2 Diabetes
Authors: Katsuki Akira , Sumida Yasuhiro , Gabazza Esteban C. , Murashima Shuichi , Furuta Masahiko , Araki-Sasaki Rika , Hori Yasuko , Yano Yutaka , Adachi Yukihiko
Published: March 2007

OBJECTIVE— To investigate the usefulness of the homeostasis model assessment as an index of insulin resistance (HOMA-IR) for evaluating the clinical course of patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS— The usefulness of HOMA-IR and its relationship with insulin resistance assessed by the hyperinsulinemic-euglycemic clamp study (clamp IR) were evaluated in 55 Japanese patients with type 2 diabetes before and after treatment. The patients were subjected to diet (∼1,440-1,720 kcal/day) and exercise therapy (walking 10,000 steps daily) for 6 weeks during their hospitalization.

RESULTS— Univariate regression analysis disclosed a significant correlation between log-transformed HOMA-IR and log-transformed clamp IR before (r = -0.613, P < 0.0001) and after(r = -0.734, P < 0.0001) treatment. Neither the slopes(-0.71 ± 0.12 vs. -0.79 ± 0.09, F = 0.25, P =0.61) nor the intercepts (y-intercept = 1.67 vs. 1.70, x-intercept = 2.36 vs. 2.15, F = 0.02, P = 0.88) of the regression lines between HOMA-IR and clamp IR were significantly different before and after treatment. There was a significant correlation between the decrease in log-transformed HOMA-IR and the increase in clamp IR during treatment (r = -0.617, P < 0.0001).

CONCLUSIONS— HOMA-IR may constitute a useful method not only for diagnosing insulin resistance, but also for follow-up during the treatment of patients with type 2 diabetes.
Corneal Advanced Glycation End Products Increase in Patients With Proliferative Diabetic Retinopathy
Authors: Sato Eiichi , Mori Fumihiko , Igarashi Sho , Abiko Tohru , Takeda Masumi , Ishiko Satoshi , Yoshida Akitoshi
Published: March 2007

OBJECTIVE—To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects.

RESEARCH DESIGN AND METHODS—Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360–370 nm and 430–450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups.

RESULTS—In the PDR group (11.9 ± 3.9 arbitrary units [mean ± SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 ± 1.3 arbitrary units), the patients without DR (7.4 ± 2.1 arbitrary units), and the patients without PDR (6.9 ± 2.2 arbitrary units) (P < 0.05).

CONCLUSIONS—We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.
Elevated Serum IP-10 Levels Observed in Type 1 Diabetes
Authors: Shimada Akira , Morimoto Jiro , Kodama Keiichi , Suzuki Ryuji , Oikawa Yoichi , Funae Osamu , Kasuga Akira , Saruta Takao , Narumi Shosaku
Published: March 2007

OBJECTIVE—Although most patients with type 1 diabetes are considered to have T-cell–mediated autoimmune disease, a method of measuring of pancreatic β-cell–specific T-cell function in cases of type 1 diabetes has yet to be established. Here, we focused on interferon-inducible protein-10 (IP-10), a chemokine that promotes the migration of activated T-helper 1 (Th1) cells and measured serum IP-10 levels in patients with human type 1 diabetes, which is regarded as a Th1-mediated disease.

RESEARCH DESIGN AND METHODS—Serum samples were obtained from diabetic patients, and the levels of autoantibodies (GAD and insulinoma-associated protein-2 [IA-2]) and IP-10 were measured. Diabetic patients positive for either or both of the autoantibodies were classified as Ab+ type 1, and those negative for both were classified as Ab− type 1. To evaluate islet antigen–specific responses, peripheral blood from patients stimulated with or without GAD was used, and intracellular cytokine staining for flowcytometry was performed.

RESULTS—The Ab+ and Ab− type 1 groups both showed a significantly higher serum IP-10 level than the healthy subjects (P < 0.001 and P < 0.05, respectively), and the IP-10 level in the recent-onset Ab+ subgroup was significantly higher than that in the established (longstanding) Ab+ subgroup (P < 0.002). Furthermore, there was a significant positive correlation between the serum IP-10 level and the number of GAD-reactive γ-interferon–producing CD4+ cells in the Ab+ type 1 group (P < 0.007).

CONCLUSIONS—Our findings demonstrate that measurement of serum IP-10 concentrations is useful in patients with type 1 diabetes.
Impact of Insulin Resistance and Nephropathy on Homocysteine in Type 2 Diabetes
Authors: Emoto Masanori , Kanda Hiroyuki , Shoji Tetsuo , Kawagishi Takahiko , Komatsu Miyoko , Mori Katsuhito , Tahara Hideki , Ishimura Eiji , Inaba Masaaki , Okuno Yasuhisa , Nishizawa Yoshiki
Published: March 2007

OBJECTIVE—To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy.

RESEARCH DESIGN AND METHODS—Plasma tHcy levels were measured using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas.

RESULTS—Plasma tHcy levels and their log-transformed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 ± 0.7 [SE] vs. 8.7 ± 0.3 μmol/l, P < 0.0001; log tHcy, 1.040 ± 0.021 vs. 0.920 ± 0.016 μmol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy correlated with insulin sensitivity indexes (r = –0.319, P = 0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (β = –0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHcy (β = –0.438, R2 = 0.561, P < 0.001).

CONCLUSION—Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.
A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test
Authors: Mari Andrea , Pacini Giovanni , Murphy Elaine , Ludvik Bernhard , Nolan John J.
Published: March 2007

OBJECTIVE—Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data.

RESEARCH DESIGN AND METHODS—OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU · min−1 · m−2 insulin infusion euglycemic clamp. Glucose clearance (ClCLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT).

RESULTS—OGIS and ClCLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and ClCLAMP were similar (coefficients of variation: OGIS 7.1%, ClCLAMP 6.4%). OGIS was as effective as ClCLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 ± 16 vs. 362 ± 11 ml · min−1 · m−2, P < 0.001; lean vs. type 2 diabetes: 440 ± 16 vs. 239 ± 7, P < 0.0001; obese vs. type 2 diabetes: 362 ± 11 vs. 239 ± 7, P < 0.0001; results were similar for ClCLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to ClCLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar.

CONCLUSIONS—OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.
Baseline Characteristics of the Diabetic Participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Authors: Barzilay Joshua I. , Jones Cheryl L. , Davis Barry R. , Basile Jan N. , Goff David C. , Ciocon Jerry O. , Sweeney Mary Ellen , Randall Otelio S. ,   for the ALLHAT Collaborative Research Group
Published: March 2007

OBJECTIVE—Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes.

RESEARCH DESIGN AND METHODS—The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a double-blind randomized trial of 42,448 high-risk hypertensive participants, ages ≥55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002.

RESULTS—There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, respectively, for detecting a 16% difference between the diuretic and each of the nondiuretic treatments for the two study outcomes.

CONCLUSIONS—The diabetic cohort in ALLHAT will be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.
Chronic Care Clinics for Diabetes in Primary Care
Authors: Wagner Edward H. , Grothaus Louis C. , Sandhu Nirmala , Galvin Mary Sue , McGregor Mary , Artz Karen , Coleman Eric A.
Published: March 2007

OBJECTIVE—To evaluate the impact of primary care group visits (chronic care clinics) on the process and outcome of care for diabetic patients.

RESEARCH DESIGN AND METHODS—We evaluated the intervention in primary care practices randomized to intervention and control groups in a large-staff model health maintenance organization (HMO). Patients included diabetic patients ≥30 years of age in each participating primary care practice, selected at random from an automated diabetes registry. Primary care practices were randomized within clinics to either a chronic care clinic (intervention) group or a usual care (control) group. The intervention group conducted periodic one-half day chronic care clinics for groups of ∼8 diabetic patients in their respective doctor’s practice. Chronic care clinics consisted of standardized assessments; visits with the primary care physician, nurse, and clinical pharmacist; and a group education/peer support meeting. We collected self-report questionnaires from patients and data from administrative systems. The questionnaires were mailed, and telephoned interviews were conducted for nonrespondents, at baseline and at 12 and 24 months; we queried the process of care received, the satisfaction with care, and the health status of each patient. Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems.

RESULTS—In an intention-to-treat analysis at 24 months, the intervention group had received significantly more recommended preventive procedures and helpful patient education. Of five primary health status indicators examined, two (SF-36 general health and bed disability days) were significantly better in the intervention group. Compared with control patients, intervention patients had slightly more primary care visits, but significantly fewer specialty and emergency room visits. Among intervention participants, we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes, including patient satisfaction and HbA1c levels.

CONCLUSIONS—Periodic primary care sessions organized to meet the complex needs of diabetic patients improved the process of diabetes care and were associated with better outcomes.
Additive Glucose-Lowering Effects of Glucagon-Like Peptide-1 and Metformin in Type 2 Diabetes
Authors: Zander Mette , Taskiran Mustafa , Toft-Nielsen Mai-Britt , Madsbad Sten , Holst Jens Juul
Published: March 2007

OBJECTIVE—The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol · kg–1 · min–1) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite.

RESULTS—Fasting plasma glucose (day 2) decreased from 13.9 ± 1 (no treatment) to 11.2 ± 0.4 (metformin) and 11.5 ± 0.5 (GLP-1) and further decreased to 9.4 ± 0.7 (combination therapy) (P = 0.0005, no difference between monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2) decreased from 11.8 ± 0.5 (metformin) and 11.7 ± 0.8 (GLP-1) to 9.8 ± 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect on appetite scores.

CONCLUSIONS—Monotherapy with GLP-1 and metformin have equal effects on plasma glucose and additive effects upon combination.
Higher Intakes of Fish Protein Are Related to a Lower Risk of Microalbuminuria in Young Swedish Type 1 Diabetic Patients
Authors: Möllsten Anna V. , Dahlquist Gisela G. , Stattin Eva-Lena , Rudberg Susanne
Published: March 2007

OBJECTIVE—To examine the influence of dietary intake from various protein and fat sources on the occurrence of microalbuminuria in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS—In this nested case control study, 1,150 patients with diabetes duration >5 years reported dietary habits for the previous 12 months and submitted urinary samples for the analysis of albumin excretion rate (AER). A total of 75 cases of albuminuria (overnight AER ≥15 μg/min) were identified and compared with 225 duration-matched control subjects.

RESULTS—Neither mean protein, fat intake, average fish protein intake (control subjects 4.56 ± 3.83 g/day and cases 3.82 ± 2.87 g/day; P = 0.12), nor intake of meat and vegetable protein differed between the cases of albuminuria and the control subjects. High consumers of fish protein (greater than the 75th percentile) (12 cases and 63 control subjects, mean intake 9.35 g fish protein/day, i.e., ∼53 g fish/day) had lower odds ratios (ORs) for microalbuminuria than individuals consuming less fish protein (mean 2.72 g/day) (crude OR 0.49 and 95% CI 0.25–0.97). When adjusted for known confounding factors, such as HbA1c, mean arterial pressure, diabetes duration, age, sex, smoking, BMI, country region, and total energy, individuals with a high intake of fish protein and fish fat showed a reduction in the risk for microalbuminuria (OR 0.22 and 0.31, respectively; 95% CI 0.09–0.56 and 0.13–0.76, respectively). When fish protein and fat were adjusted for each other, a high intake of fish protein but not of fish fat was still significantly associated with a decrease in the risk for microalbuminuria.

CONCLUSIONS—Total protein and fat intake were not associated with the presence of microalbuminuria, but a diet including a high amount of fish protein seemed to lessen the risk.
Personal Models of Diabetes in Relation to Self-Care, Well-Being, and Glycemic Control
Authors: Skinner T. Chas , Hampson Sarah E.
Published: March 2007

OBJECTIVE—Personal models of diabetes have been shown to be proximal determinants of self-care behavior in adults with diabetes, both cross-sectionally and prospectively. This study set out to test the predictive utility of this approach in adolescents with diabetes.

RESEARCH DESIGN AND METHODS—Participants were recruited from four regional hospitals in southern England (n = 54). They completed questionnaires assessing diabetes self-care, well-being, and personal models of diabetes (perceived impact, perceived seriousness, and short- and long-term treatment effectiveness) at baseline and 1-year follow-up. GHb assays performed as part of the patients’ usual diabetes care were used to assess glycemic control.

RESULTS—After controlling for baseline anxiety, change in perceived impact of diabetes prospectively predicted adolescents’ anxiety (β = −0.21; t = −2.65; P < 0.01). After controlling for baseline dietary self-care, change in perceived effectiveness of the diabetes treatment regimen to control diabetes predicted dietary self-care (β = −0.39; t = −3.28; P < 0.0005). Poorer dietary self-care and being female were predictive of poorer glycemic control (r2 = 0.29; F = 2.74; P < 0.005).

CONCLUSIONS—This study provides further support for the role of personal models of illness in determining responses to illness. As adolescents take responsibility for the management of their diabetes, parents, clinicians, educators, and interventionists should consider these adolescents’ beliefs about their diabetes and its treatment as key factors influencing self-care, emotional well-being, and glycemic control.
Impact of Diabetic Nephropathy on Pharmacodynamic and Pharmacokinetic Properties of Insulin in Type 1 Diabetic Patients
Authors: Rave Klaus , Heise Tim , Pfützner Andreas , Heinemann Lutz , Sawicki Peter T.
Published: March 2007

OBJECTIVE—To quantify pharmacokinetic and pharmacodynamic properties of regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy.

RESEARCH DESIGN AND METHODS—In this double-blind, two-way cross-over, euglycemic (5 mmol/l) glucose clamp study, we investigated the metabolic response to subcutaneous injections of regular insulin and insulin lispro (0.2 U/kg) in 12 type 1 diabetic patients with overt diabetic nephropathy (proteinuria >500 mg/24 h and/or serum creatinine >1.5 mg/dl; NP group) and in a control group of 12 type 1 diabetic patients with normal renal function (DC group).

RESULTS—Peak plasma free insulin levels with insulin lispro (359 [NP] vs. 254 pmol/l [DC]) were higher and time to maximal insulin concentrations (85 [NP] vs. 99 min [DC]) shorter than with regular insulin (213 [NP] vs. 144 pmol/l [DC]; 118 [NP] vs. 153 min [DC]) in both patient groups. Overall insulin levels for regular insulin and for insulin lispro were higher in patients with overt diabetic nephropathy compared with control patients. Time to maximal metabolic effect was shorter with insulin lispro than with regular insulin in both patient groups (102 vs. 191 min [NP]; 105 vs. 172 min [DC]). The overall metabolic effect of regular insulin but not of insulin lispro was lower in patients with diabetic nephropathy than in diabetic control patients (967 vs. 1,510 mg/kg, respectively).

CONCLUSIONS—Although insulin levels are higher in patients with overt diabetic nephropathy, the metabolic response to regular insulin is reduced. Insulin lispro maintains its characteristic pharmacokinetic and pharmacodynamic properties in patients with overt diabetic nephropathy.
Reduction of ACE Activity Is Insufficient to Decrease Microalbuminuria in Normotensive Patients With Type 1 Diabetes
Authors: Bojestig Mats , Karlberg Bengt E. , Lindström Torbjörn , Nystrom Fredrik H.
Published: March 2007

OBJECTIVE—To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1–4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA).

RESULTS—Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups.

CONCLUSIONS—Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.
Contribution of Abdominal Adiposity to Age-Related Differences in Insulin Sensitivity and Plasma Lipids in Healthy Nonobese Women
Authors: DeNino Walter F. , Tchernof Andre , Dionne Isabelle J. , Toth Michael J. , Ades Philip A. , Sites Cynthia K. , Poehlman Eric T.
Published: March 2007

OBJECTIVE—We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women.

RESEARCH DESIGN AND METHODS—We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (Vo2max) in 178 nonobese women categorized into four age groups: group 1, 28 ± 4 years, n = 88; group 2, 46 ± 2 years, n = 38; group 3, 53 ± 2 years, n = 31; and group 4, 67 ± 6 years, n = 21.

RESULTS—Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, age-related changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on age-related changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of Vo2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood–lipid profile were noted.

CONCLUSIONS—We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue.
Establishing Surveillance for Diabetes in American Indian Youth
Authors: Harwell Todd S. , McDowall Janet M. , Moore Kelly , Fagot-Campagna Anne , Helgerson Steven D. , Gohdes Dorothy
Published: March 2007

OBJECTIVE—To determine prevalence estimates in order to monitor diabetes, particularly type 2 diabetes, in American Indian youth.

RESEARCH DESIGN AND METHODS—To explore the feasibility of developing a case definition using information from primary care records, all youth aged <20 years with an outpatient visit or hospitalization for diabetes were identified from the Billings Area Indian Health Service database in Montana and Wyoming from 1997 to 1999, and the medical records were reviewed. Classification for probable type 1 diabetes was based on age ≤5 years, weight per age ≤15th percentile at diagnosis, or positive results of islet cell antibody test. Classification for probable type 2 diabetes was based on weight per age ≥85th percentile or presence of acanthosis nigricans at diagnosis, elevated C-peptide or insulin, family history for type 2 diabetes, or use of oral hypoglycemic agents with or without insulin or absence of current treatment 1 year after diagnosis.

RESULTS—A total of 52 case subjects with diabetes were identified, 3 of whom had diabetes secondary to other conditions. Of the remaining 49 case subjects, 25 (51%) were categorized as having probable type 2 diabetes, 14 (29%) as having probable type 1 diabetes, and 10 (20%) could not be categorized because of missing or negative information. Prevalence estimates for diabetes of all types, type 1 diabetes, and type 2 diabetes were 2.3, 0.6, and 1.1, respectively, per 1,000 youth aged <20 years.

CONCLUSIONS—Our definitions may be useful for surveillance in primary care settings until further studies develop feasible case definitions for monitoring trends in diabetes among youth.
Diabetes Screening in Canada (DIASCAN) Study
Authors: Leiter Lawrence A. , Barr Aiala , Bélanger André , Lubin Stanley , Ross Stuart A. , Tildesley Hugh D. , Fontaine Nathalie
Published: March 2007

OBJECTIVE—To assess the prevalence of undiagnosed diabetes and glucose intolerance in individuals ≥40 years of age who contacted their family physician for routine care.

RESEARCH DESIGN AND METHODS—The study used a stratified randomized selection of family physicians across Canada that was proportional to provincial and urban/rural populations based on Statistics Canada Census data (1996). Consecutive patients ≥40 years of age were screened for diabetes. If a casual fingerprick blood glucose was >5.5 mmol/l, the patient returned for a fasting venous blood glucose test. If the fasting blood glucose was 6.1–6.9 mmol/l, a 2-h 75-g post–glucose load venous blood glucose was obtained. Results of these tests were used to classify patients in diagnostic categories.

RESULTS—Data were available for 9,042 patients. Previously undiagnosed diabetes was discovered in 2.2% of the patients, and new glucose intolerance was found in an additional 3.5% of patients. Overall, 16.4% of patients had previously known diabetes. The decrease in fasting plasma glucose criterion from 7.8 to 7.0 mmol/l resulted in a 2.2% versus a 1.6% prevalence of new diabetes. Several risk factors were reported in a significantly greater proportion of patients with new glucose intolerance and either new and known diabetes compared with the normal glucose tolerance group of patients.

CONCLUSIONS—Routine screening for diabetes by family physicians is justified in patients ≥40 years of age, given the finding of previously undiagnosed diabetes in 2.2% of these patients and newly diagnosed glucose intolerance in an additional 3.5% of these patients. Another 16.4% of primary care patients ≥40 years of age have known diabetes. This has important implications regarding health resources and physician education.
The Association of Heart-Rate Variability With Cardiovascular Risk Factors and Coronary Artery Calcification
Authors: Colhoun Helen M. , Francis Darrel P. , Rubens Michael B. , Underwood S. Richard , Fuller John H.
Published: March 2007

OBJECTIVE—To examine the association of heart-rate variability with cardiovascular risk factors and coronary calcification in type 1 diabetic and nondiabetic subjects without a history of cardiovascular disease. Reduced heart-rate variability is associated with increased risk of coronary events. Whether it is associated with coronary atherosclerosis is unknown.

RESEARCH DESIGN AND METHODS—Power spectral analysis was used to define heart-rate variability in a cross-sectional study of 160 type 1 diabetic patients and 163 randomly selected nondiabetic adults from the general population aged 30–55 years. Coronary artery calcification was measured using electron beam–computed tomography.

RESULTS—Reduced heart-rate variability was associated with similar risk factors in the diabetic and nondiabetic subjects, namely higher HbA1c, triglycerides, systolic blood pressure, BMI, and albumin excretion rate. Reduced heart-rate variability was significantly associated with coronary artery calcification in all subjects (odds ratio per tertile lower total power = 1.5, P = 0.01). This association was not independent of blood pressure or BMI (odds ratio on adjustment = 1.3, P = 0.1).

CONCLUSIONS—Reduced heart-rate variability clusters with other cardiovascular disease risk factors, especially those that are more common in the insulin resistance syndrome, and is associated with increased coronary calcification in asymptomatic young adults. Whether reduced heart-rate variability leads to other risk factor disturbances or mediates the effects of other risk factors on atherosclerosis deserves further study.
Group Visits Improve Metabolic Control in Type 2 Diabetes
Authors: Trento Marina , Passera Pietro , Tomalino Marco , Bajardi Marina , Pomero Fulvio , Allione Attilio , Vaccari Piero , Molinatti Gian Michele , Porta Massimo
Published: March 2007

OBJECTIVE—To evaluate whether group visits, delivered as routine diabetes care and structured according to a systemic education approach, are more effective than individual consultations in improving metabolic control in non–insulin-treated type 2 diabetes.

RESEARCH DESIGN AND METHODS—In a randomized controlled clinical trial of 112 patients, 56 patients were allocated to groups of 9 or 10 individuals who participated in group consultations, and 56 patients (considered control subjects) underwent individual visits plus support education. All visits were scheduled every 3 months.

RESULTS—After 2 years, HbA1c levels were lower in patients seen in groups than in control subjects (P < 0.002). Levels of HDL cholesterol had increased in patients seen in groups but had not increased in control subjects (P = 0.045). BMI (P = 0.06) and fasting triglyceride level (P = 0.053) were lower. Patients participating in group visits had improved knowledge of diabetes (P < 0.001) and quality of life (P < 0.001) and experienced more appropriate health behaviors (P < 0.001). Physicians spent less time seeing 9–10 patients as a group rather than individually, but patients had longer interaction with health care providers.

CONCLUSIONS—Group consultations may improve metabolic control in the medium term by inducing more appropriate health behaviors. They are feasible in everyday clinical practice without increasing working hours.
The Effect of Flexible Low Glycemic Index Dietary Advice Versus Measured Carbohydrate Exchange Diets on Glycemic Control in Children With Type 1 Diabetes
Authors: Gilbertson Heather R. , Brand-Miller Jennie C. , Thorburn Anne W. , Evans Sharon , Chondros Patty , Werther George A.
Published: March 2007

OBJECTIVE—To determine the long-term effect of low glycemic index dietary advice on metabolic control and quality of life in children with type 1 diabetes.

RESEARCH DESIGN AND METHODS—Children with type 1 diabetes (n = 104) were recruited to a prospective, stratified, randomized, parallel study to examine the effects of a measured carbohydrate exchange (CHOx) diet versus a more flexible low–glycemic index (GI) dietary regimen on HbA1c levels, incidence of hypo- and hyperglycemia, insulin dose, dietary intake, and measures of quality of life over 12 months.

RESULTS—At 12 months, children in the low-GI group had significantly better HbA1c levels than those in the CHOx group (8.05 ± 0.95 vs. 8.61 ± 1.37%, P = 0.05). Rates of excessive hyperglycemia (>15 episodes per month) were significantly lower in the low-GI group (35 vs. 66%, P = 0.006). There were no differences in insulin dose, hypoglycemic episodes, or dietary composition. The low-GI dietary regimen was associated with better quality of life for both children and parents.

CONCLUSIONS—Flexible dietary instruction based on the food pyramid with an emphasis of low-GI foods improves HbA1c levels without increasing the risk of hypoglycemia and enhances the quality of life in children with diabetes.
Type 1 and Type 2 Diabetes and Incident Hip Fractures in Postmenopausal Women
Authors: Nicodemus Kristin K. , Folsom Aaron R.
Published: March 2007

OBJECTIVE—To examine whether postmenopausal women with diabetes experienced a higher incidence of hip fracture than women without diabetes.

RESEARCH DESIGN AND METHODS—A prospective cohort of 32,089 postmenopausal women residing in Iowa were surveyed by mail in 1986 and followed for 11 years. Diabetes status and other potential risk factors were assessed by questionnaires at baseline; incidence of hip fracture was ascertained by follow-up questionnaires.

RESULTS—A total of 490 hip fractures were reported over 306,900 person-years of follow-up. After adjustment for age, smoking status, estrogen use, BMI, and waist-to-hip ratio, women with type 1 diabetes (n = 47) were 12.25 times (95% CI 5.05–29.73) more likely to report an incident hip fracture than women without diabetes. Women with type 2 diabetes had a 1.70-fold higher risk (1.21–2.38) of incident hip fracture than women without diabetes. Longer duration of type 2 diabetes was associated with higher incidence, as was use of insulin or oral diabetes medications in women with type 2 diabetes. Furthermore, women who were initially free of diabetes but in whom diabetes developed had a relative risk of hip fracture of 1.60 (1.14–2.25) compared with women who never had diabetes.

CONCLUSIONS—Postmenopausal women who have diabetes or in whom diabetes develops are at higher risk for hip fracture than nondiabetic postmenopausal women. Strategies to prevent osteoporosis and/or falling may be especially warranted in women with diabetes.
Diabetes and Diabetic Retinopathy in a Mexican-American Population
Authors: West Sheila K. , Klein Ronald , Rodriguez Jorge , Muñoz Beatriz , Broman Aimee T. , Sanchez Rosario , Snyder Robert
Published: March 2007

OBJECTIVES The prevalence rate of diabetes is probably higher in Hispanics than in Caucasians, although there is controversy about differences in the risk of diabetic retinopathy. The purpose of the study is to determine the prevalence rates of diabetes and diabetic retinopathy in a population-based study of Hispanics aged ≥40 years.

RESEARCH DESIGN AND METHODS—Proyecto VER is a random sample of Hispanic populations aged ≥40 years in Arizona. A total of 4,774 individuals (71.6% of the eligible sample) completed the examinations. Diabetes was defined as self-report of a physician diagnosis or HbA1c value of ≥7.0%. Diabetic retinopathy was assessed on stereo fundus photographs of fields 1, 2, and 4.

RESULTS—The prevalence rate of diabetes in the Hispanic community (individuals ≥40 years of age) was 22%. The prevalence rate of diabetic retinopathy (DR) was 48%; 32% had moderate to severe nonproliferative and proliferative retinopathy. DR increased with increasing duration of diabetes and increasing level of HbA1c. The prevalence rate of DR-like changes in the sample of individuals without diabetic retinopathy was 15% and was not associated with hypertension, systolic blood pressure, or diastolic blood pressure.

CONCLUSIONS—The prevalence rate of diabetes in this population of Hispanics is high, almost twice that of Caucasians. The prevalence rate of DR is high but similar to reports in a Caucasian population. The prevalence rate of 9% moderate to severe retinopathy in the newly diagnosed group suggests that efforts to improve detection and treatment of diabetes in Hispanics may be warranted.
A Randomized Trial of Rosiglitazone Therapy in Patients With Inadequately Controlled Insulin-Treated Type 2 Diabetes
Authors: Raskin Philip , Rendell Marc , Riddle Matthew C. , Dole Jo F. , Freed Martin I. , Rosenstock Julio ,   For the Rosiglitazone Clinical Trials Study Group
Published: March 2007

OBJECTIVE—To determine the efficacy and safety of rosiglitazone (RSG) when added to insulin in the treatment of type 2 diabetic patients who are inadequately controlled on insulin monotherapy.

RESEARCH DESIGN AND METHODS—After 8 weeks of insulin standardization and placebo (PBO) run-in, 319 type 2 diabetic patients with mean baseline HbA1c ≥7.5% (8.9 ± 1.1 to 9.1 ± 1.3) on twice-daily insulin therapy (total daily dose ≥30 U) were randomized to 26 weeks of additional treatment with RSG (4 or 8 mg daily) or PBO. Insulin dose could be down- titrated only for safety reasons. The primary end point was reduction of HbA1c from baseline.

RESULTS—RSG 4 and 8 mg daily significantly improved glycemic control, which was unchanged on PBO. By intent-to-treat analysis, treatment with RSG 8 mg plus insulin resulted in a mean reduction from baseline in HbA1c of 1.2% (P < 0.0001), despite a 12% mean reduction of insulin dosage. Over 50% of subjects treated daily with RSG 8 mg plus insulin had a reduction of HbA1c ≥1.0%. Neither total:HDL cholesterol nor LDL:HDL cholesterol ratios significantly changed with RSG treatment. Serious adverse events did not differ among groups.

CONCLUSIONS—The addition of RSG to insulin treatment results in significant improvement in glycemic control and is generally well tolerated.
Prevalence of Clinical and Isolated Subclinical Cardiovascular Disease in Older Adults With Glucose Disorders
Authors: Barzilay Joshua I. , Spiekerman Charles F. , Kuller Lewis H. , Burke Gregory L. , Bittner Vera , Gottdiener John S. , Brancati Fred L. , Orchard Trevor J. , O’Leary Daniel H. , Savage Peter J.
Published: March 2007

OBJECTIVE—Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes.

RESEARCH DESIGN AND METHODS—Participants in the Cardiovascular Health Study, aged ≥65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease.

RESULTS—Approximately 30% of the cohort had clinical disease, and ∼60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was ∼88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes.

CONCLUSIONS—Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.