bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving Diabetes Processes of Care in Managed Care
Authors: Ilag Liza L. , Martin Catherine L. , Tabaei Bahman P. , Isaman Deanna J. M. , Burke Ray , Greene Douglas A. , Herman William H.
Published: March 2007

OBJECTIVE—To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices.

RESEARCH DESIGN AND METHODS—Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA1c, blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models.

RESULTS—Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes.

CONCLUSIONS—The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.
Moderate Alcohol Consumption, Estrogen Replacement Therapy, and Physical Activity Are Associated With Increased Insulin Sensitivity
Authors: Greenfield Jerry R. , Samaras Katherine , Jenkins Arthur B. , Kelly Paul J. , Spector Tim D. , Campbell Lesley V.
Published: March 2007

OBJECTIVE—To investigate 1) associations between environmental factors (alcohol consumption, hormone replacement therapy [HRT], and physical activity) and insulin resistance and secretion, independent of genetic influences; 2) the contribution of abdominal adiposity to these relationships; and 3) whether gene-environment interactions mediate these associations.

RESEARCH DESIGN AND METHODS—Reported effects of lifestyle factors on insulin resistance and secretion are inconsistent, possibly due to difficulty in dissecting environmental from genetic influences and to confounding by adiposity. We examined these relationships in 798 nondiabetic female twins. Insulin resistance and secretion were estimated by modified homeostasis model assessment (HOMA-R′ and HOMA-β′, respectively). Percent total body fat and percent central abdominal fat (CAF) were measured by dual-energy X-ray absorptiometry.

RESULTS—All categories of alcohol consumption were associated with lower insulin levels and HOMA-β′ than abstinence. Only moderate alcohol consumers (11–20 units/week) had lower HOMA-R′ than abstainers (−0.16 ± 0.09 vs. 0.14 ± 0.13 SD, P = 0.048). This difference was attenuated after controlling for percent CAF (P = 0.57), which was lower in moderate drinkers. Controlling for genetic and smoking effects in cotwin case-control analysis, monozygotic pairs discordant for alcohol consumption had greater within-pair differences in HOMA-R′ than concordant pairs (P = 0.02). Postmenopausal women using estrogen-only HRT had lower HOMA-R′ than non–HRT users (−0.33 ± 0.16 vs. 0.17 ± 0.08 SD, P = 0.003), even after controlling for percent CAF. Lower fasting glucose levels and insulin resistance and secretion indexes in physically active subjects were partly explained by lower abdominal adiposity.

CONCLUSIONS—Moderate alcohol consumption, estrogen replacement, and physical activity are associated with increased insulin sensitivity in female twins. The favorable effects of moderate alcohol consumption and physical activity on insulin sensitivity are partly mediated by lower abdominal adiposity.
Dose-Response Relationships of Inhaled Insulin Delivered via the Aerodose Insulin Inhaler and Subcutaneously Injected Insulin in Patients With Type 2 Diabetes
Authors: Kim Dennis , Mudaliar Sunder , Chinnapongse Sithipol , Chu Neelima , Boies Sarah M. , Davis Trent , Perera Ayesh D. , Fishman Robert S. , Shapiro David A. , Henry Robert
Published: March 2007

OBJECTIVE—To compare the dose-response relationship following inhalation of regular insulin delivered via the Aerodose insulin inhaler with that following subcutaneously injected regular insulin in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Twenty-four patients with type 2 diabetes (21 nonsmoking men, aged 36–80 years) each received two of three doses of 80, 160, or 240 units inhaled regular insulin, delivered via a clinical Aerodose insulin inhaler, and two of three corresponding doses of 8, 16, or 24 units by subcutaneous injection under isoglycemic clamp conditions on 4 separate study days in an incomplete block design study. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h.

RESULTS—Inhaled insulin exhibited significantly shorter time-to-peak insulin levels (Tmax 77 ± 66 vs. 193 ± 104 min, P < 0.001) and time-to-peak metabolic effects (TGIRmax 240 ± 94 vs. 353 ± 60 min, P < 0.001) compared with subcutaneously injected insulin. Comparison of total insulin absorption (insulin area under the curve [AUC]) versus total metabolic effect (GIR-AUC) from 0 to 8 h (group means) revealed overlapping dose-response relationships for both inhaled and subcutaneous injection treatments. Comparison of slopes revealed no significant differences between the inhaled and subcutaneous injection treatment groups (P = 0.6). No significant differences in either relative bioavailability or relative biopotency were found among doses, indicating a consistent subcutaneous injection-to-inhaled dosing conversion ratio among doses. No serious adverse events or clinically relevant changes in lung function were observed.

CONCLUSIONS—The overlapping dose-response curves of inhaled and subcutaneous treatments together with a consistent relative bioavailability and relative biopotency for inhaled insulin across doses suggest that the Aerodose insulin inhaler will deliver a pharmacologically predictable insulin dose to patients with diabetes similar to that observed following subcutaneous injection.
HYAFF 11-Based Autologous Dermal and Epidermal Grafts in the Treatment of Noninfected Diabetic Plantar and Dorsal Foot Ulcers
Authors: Caravaggi Carlo , De Giglio Roberto , Pritelli Chiara , Sommaria Manuela , Dalla Noce Sergio , Faglia Ezio , Mantero Manuela , Clerici Giacomo , Fratino Pietro , Dalla Paola Luca , Mariani Giulio , Mingardi Roberto , Morabito Alberto
Published: March 2007

OBJECTIVE—To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers.

RESEARCH DESIGN AND METHODS—A total of 79 patients with diabetic dorsal (n = 37) or plantar (n = 42) ulcers were randomized to either the control group with nonadherent paraffin gauze (n = 36) or the treatment group with autologous tissue-engineered grafts (n = 43). Weekly assessment, aggressive debridement, wound infection control, and adequate pressure relief (fiberglass off-loading cast for plantar ulcers) were provided in both groups. Complete wound healing was assessed within 11 weeks. Safety was monitored by adverse events.

RESULTS—Complete ulcer healing was achieved in 65.3% of the treatment group and 49.6% of the control group (P = 0.191). The Kaplan-Meier mean time to closure was 57 and 77 days, respectively, for the treatment versus control groups. Plantar foot ulcer healing was 55% and 50% in the treatment and control groups, respectively. Dorsal foot ulcer healing was significantly different, with 67% in the treatment group and 31% in the control group (P = 0.049). The mean healing time in the dorsal treatment group was 63 days, and the odds ratio for dorsal ulcer healing compared with the control group was 4.44 (P = 0.037). Adverse events were equally distributed between the two groups, and none were related to the treatments.

CONCLUSIONS—The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current standard dressing. For plantar ulcers, the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment. This treatment, however, may be useful in patients for whom the total off-loading cast is not recommended and only a less effective off-loading device can be applied.
Prospective Study of the Association Between the Proline to Alanine Codon 12 Polymorphism in the PPARγ Gene and Type 2 Diabetes
Authors: Memisoglu Asli , Hu Frank B. , Hankinson Susan E. , Liu Simin , Meigs James B. , Altshuler David M. , Hunter David J. , Manson JoAnn E.
Published: March 2007

OBJECTIVE—To determine whether the Pro12Ala polymorphism in the PPARγ gene was associated with risk of type 2 diabetes in the Nurses’ Health Study.

RESEARCH DESIGN AND METHODS—The study was a nested case-control study of 387 incident cases of type 2 diabetes and 771 matching control subjects nested within the Nurses’ Health Study, a prospective cohort study. Association between PPARγ genotype and incident type 2 diabetes was estimated using logistic regression.

RESULTS—Carriers of the PPARγ variant 12Ala allele had reduced risk of type 2 diabetes compared with noncarriers. Unadjusted and adjusted odds ratios of type 2 diabetes were 0.74 (95% CI 0.55–1.00) and 0.72 (0.52–0.99), respectively.

CONCLUSIONS—The results of this study provide further support for an inverse association between the PPARγ variant 12Ala allele and risk of type 2 diabetes.
Enhancing Incretin Action for the Treatment of Type 2 Diabetes
Authors: Drucker Daniel J.
Published: March 2007

OBJECTIVE—To examine the mechanisms of action, therapeutic potential, and challenges inherent in the use of incretin peptides and dipeptidyl peptidase-IV (DPP-IV) inhibitors for the treatment of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The scientific literature describing the biological importance of incretin peptides and DPP-IV inhibitors in the control of glucose homeostasis has been reviewed, with an emphasis on mechanisms of action, experimental diabetes, human physiological experiments, and short-term clinical studies in normal and diabetic human subjects.

RESULTS—Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert important effects on β-cells to stimulate glucose-dependent insulin secretion. Both peptides also regulate β-cell proliferation and cytoprotection. GLP-1, but not GIP, inhibits gastric emptying, glucagon secretion, and food intake. The glucose-lowering actions of GLP-1, but not GIP, are preserved in subjects with type 2 diabetes. However, native GLP-1 is rapidly degraded by DPP-IV after parenteral administration; hence, degradation-resistant, long-acting GLP-1 receptor (GLP-1R) agonists are preferable agents for the chronic treatment of human diabetes. Alternatively, inhibition of DPP-IV–mediated incretin degradation represents a complementary therapeutic approach, as orally available DPP-IV inhibitors have been shown to lower glucose in experimental diabetic models and human subjects with type 2 diabetes.

CONCLUSIONS—GLP-1R agonists and DPP-IV inhibitors have shown promising results in clinical trials for the treatment of type 2 diabetes. The need for daily injections of potentially immunogenic GLP-1–derived peptides and the potential for unanticipated side effects with chronic use of DPP-IV inhibitors will require ongoing scrutiny of the risk-benefit ratio for these new therapies as they are evaluated in the clinic.
Cigarette Smoking and the Risk of Gestational and Pregestational Diabetes in Two Consecutive Pregnancies
Authors: Terry Paul D. , Weiderpass Elisabete , Östenson Claes-Göran , Cnattingius Sven
Published: March 2007

OBJECTIVE—Cigarette smoking during pregnancy may increase the risk of gestational diabetes mellitus (GDM) or pregestational diabetes mellitus (PDM). Smoking has been associated positively with hyperinsulinemia and insulin resistance in experimental studies, although the association with diabetes remains unclear. To further explore this issue, we examined the association with smoking in the largest prospective cohort study of GDM and PDM to date.

RESEARCH DESIGN AND METHODS—The study population comprised 212,190 women in the population-based Swedish Birth Registry who had their first and second deliveries between January 1987 and December 1995. Maternal characteristics were recorded in a standardized manner at the first prenatal visit, followed by a clinical examination and a standardized in-person interview to assess lifestyle habits. Women were categorized as nonsmokers, light smokers (one to nine cigarettes per day), or moderate-to-heavy smokers (at least 10 cigarettes per day).

RESULTS—Women with GDM in their first pregnancy experienced an eight- to ninefold increased risk of GDM or PDM in their second pregnancy. Cigarette smoking was not associated with increased risk of these conditions. Neither women who smoked during their first and second pregnancies nor those who commenced smoking between pregnancies had a higher risk of GDM or PDM than nonsmokers.

CONCLUSIONS—Our findings do not support an association between cigarette smoking and risk of GDM or PDM in young women of childbearing age.
High Prevalence of Diabetes in Adana, a Southern Province of Turkey
Authors: Gokcel Adnan , Ozsahin Akatli Kursat , Sezgin Nurzen , Karakose Hatice , Ertorer Melek Eda , Akbaba Muhsin , Baklaci Nuh , Sengul Aysegul , Guvener Nilgun
Published: March 2007

OBJECTIVE—To determine the prevalence of diabetes and glucose intolerance and their relationship with risk factors in Adana, a southern province of Turkey, where risk factors are more prominent, probably because of social and economic reasons.

RESEARCH DESIGN AND METHODS—The study population included 1,637 randomly selected adults aged 20–79 years. Diagnosis of diabetes was based on plasma glucose values using the 1999 diagnostic criteria recommended by the World Health Organization.

RESULTS—The crude prevalence of diabetes was 12.9% in men and 10.9% in women (P = 0.207). Total prevalence of diabetes was 11.6%. The screening process identified previously undiagnosed diabetes in 4.2% of individuals and impaired glucose homeostasis (consisting of impaired glucose tolerance and impaired fasting glucose) in an additional 4.3% of subjects. The prevalence of hypertension was 26.4% among men and 36.6% among women (P < 0.0001). Total prevalence of hypertension was 32.9%, and prevalence of obesity was 43.4%. Age, sex, BMI, waist circumference, hypertension, family history of diabetes, and triglycerides were independently associated with diabetes.

CONCLUSIONS—The prevalence of diabetes in Adana is higher than expected in both urban and rural areas. Obesity and hypertension also seem to be common metabolic disorders in this area. Age, hypertension, obesity, high triglyceride level, and family history of diabetes are independently associated with diabetes. Therefore, primary prevention through lifestyle modifications may have a critical role in the control of diabetes.
Randomized Controlled Trial of a New Dietary Education Program to Prevent Type 2 Diabetes in a High-Risk Group of Japanese Male Workers
Authors: Watanabe Mariko , Yamaoka Kazue , Yokotsuka Masako , Tango Toshiro
Published: March 2007

OBJECTIVE—The aim of this study was to assess the effectiveness of a new dietary education (NDE) program in reducing plasma glucose (PG) levels in Japanese male workers at high risk for type 2 diabetes through a randomized controlled trial.

RESEARCH DESIGN AND METHODS—We randomly assigned 173 high-risk men (mean age, 55 years) to either the NDE or the control (conventional dietary education) group. Each subject in the NDE group received two individualized interventions especially aimed at reducing total energy intake at dinner by modifying dietary intake. The control group received conventional group counseling. An “overintake/underintake fraction” for total energy intake was used to measure the status of dietary intake. Our hypothesis was that the NDE group would have a 10% decrease in 2-h PG 1 year after the start of the education. Outcome measures were compared with ANCOVA by adjusting for baseline values.

RESULTS—The NDE group had a significantly lower total energy intake at dinner and daily than the control group. The adjusted differences in changes from baseline in the absolute value of the “overintake/underintake fraction” were −15.3% (95% CI −24.6 to −6.0%, P = 0.002) for the NDE group and −6.0% (−9.8 to −2.2%, P = 0.002) for the control group. The NDE group had a decreased 2-h PG after 1 year, whereas that value was increased in the control group. The adjusted difference in the percent change of 2-h PG was significant (−15.2%, −22.0 to −8.4%, P < 0.001).

CONCLUSIONS—The NDE was shown to reduce glucose levels in high-risk subjects for type 2 diabetes.
Clinical Efficacy of the First Metatarsophalangeal Joint Arthroplasty as a Curative Procedure for Hallux Interphalangeal Joint Wounds in Patients with Diabetes
Authors: Armstrong David G. , Lavery Lawrence A. , Vazquez Jefferey R. , Short Brian , Kimbriel Heather R. , Nixon Brent P. , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To evaluate the safety and efficacy of first metatarsophalangeal joint arthroplasty compared with standard, nonsurgical management of wounds at the plantar hallux interphalangeal joint in patients with diabetes.

RESEARCH DESIGN AND METHODS—We evaluated 41 patients with ulcers classified as University of Texas Grade 1A or 2A at the plantar aspect of the first metatarsophalangeal joint using a case-control model. Case subjects were patients treated with resectional arthroplasty and control subjects received standard nonsurgical care. Both groups received standard off-loading and wound care. Outcomes included time to healing, reulceration, infection, and amputation.

RESULTS—The surgery group healed significantly faster than patients in the standard therapy group (standard 67.1 ± 17.1 versus sugery 24.2 ± 9.9 days, P = 0.0001), and they had fewer recurrent ulcers (standard 35.0 versus surgery 4.8%, P = 0.02, odds ratio 7.6, 95% CI 1.1–261.7) Both groups had similar rates of infection (standard 38.1 versus surgery 40.0%, P = 0.9) and amputation (standard 10.0 versus surgery 4.8%, P = 0.5).

CONCLUSIONS—Results suggest that resectional arthroplasty is a safe and effective procedure to treat wounds of the plantar hallux compared with nonsurgical therapy.
Longitudinal Studies of Incidence and Progression of Diabetic Retinopathy Assessed by Retinal Photography in Pima Indians
Authors: Looker Helen C. , Krakoff Jonathan , Knowler William C. , Bennett Peter H. , Klein Ronald , Hanson Robert L.
Published: March 2007

OBJECTIVE—To examine incidence and progression of retinopathy using retinal photographs in Pima Indians and to compare the results with those obtained when retinopathy is assessed by direct ophthalmoscopy.

RESEARCH DESIGN AND METHODS—We undertook an analysis of examinations conducted between 1 April 1982 and 31 December 1990 in residents of the Gila River Community in central Arizona. Data were taken from 411 people with diabetes who had at least two examinations during this period. Incidence and progression of retinopathy were evaluated by retinal photography and fundoscopy, and hazard rate ratios were calculated for various potential risk factors measured at baseline.

RESULTS—Previously diagnosed retinopathy tended to progress, except in individuals with minimal nonproliferative retinopathy, among whom follow-up examinations were more likely to show no retinopathy. Diabetes duration (hazard rate ratio [HRR], 1.06 per year difference [P = 0.007]), hyperglycemia (HbA1 HRR, 1.27 per 1% difference [P < 0.0001]), the type of treatment for diabetes (insulin use HRR, 3.06 [P = 0.0007], and oral hypoglycemic use HRR, 2.40 [P = 0.0034], compared with individuals on no pharmacotherapy), and macroalbuminuria (HRR, 2.86, compared with individuals without macroalbuminuria [P = 0.0486]) were associated with the development of retinopathy. Although fundoscopy detected fewer cases of retinopathy, HRRs for most risk factors were similar when retinopathy was assessed by fundoscopy rather than retinal photography.

CONCLUSIONS—Although retinopathy tends to worsen over time, some eyes show improvement, especially in patients with minimal nonproliferative retinopathy. As in other populations, glycemic control is the major modifiable risk factor for the development and progression of retinopathy.
Association Between Regional Adipose Tissue Distribution and Both Type 2 Diabetes and Impaired Glucose Tolerance in Elderly Men and Women
Authors: Goodpaster Bret H. , Krishnaswami Shanthi , Resnick Helaine , Kelley David E. , Haggerty Catherine , Harris Tamara B. , Schwartz Ann V. , Kritchevsky Steven , Newman Anne B.
Published: March 2007

OBJECTIVE—We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—A total of 2,964 elderly men and women (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography.

RESULTS—Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI ≥30 kg/m2). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 ± 9.4, 10.3 ± 5.8, and 9.2 ± 5.9 cm2 for men; 12.1 ± 6.1, 10.9 ± 6.5, and 9.4 ± 5.3 cm2 for women; both P < 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 ± 79, 163 ± 72, and 145 ± 66 cm2 for men; 162 ± 66, 141 ± 60, and 116 ± 54 cm2 for women; both P < 0.0001 across groups). Higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI <25 kg/m2) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P < 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P < 0.0001). These associations were not found in obese subjects.

CONCLUSIONS—Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.
Effects of Ethnicity and Nephropathy on Lower-Extremity Amputation Risk Among Diabetic Veterans
Authors: Young Bessie A. , Maynard Charles , Reiber Gayle , Boyko Edward J.
Published: March 2007

OBJECTIVE—To describe ethnic differences in the risk of amputation in diabetic patients with diabetic nephropathy.

RESEARCH DESIGN AND METHODS—A retrospective cohort study was conducted on a national cohort of diabetic patients who received primary care within the Veterans Affairs (VA) Health Care System. Hospitalizations for lower-limb amputations were established by ICD-9-CM procedure codes. Relative risk of amputation in diabetic patients with and without diabetic nephropathy was determined using Cox proportional hazard modeling for unadjusted and adjusted models.

RESULTS—Of the 429,918 subjects identified with diabetes (mean age 64 ± 11 years, 97.4% male), 3,289 individuals were determined to have had a lower-limb amputation during the study period. Compared with diabetic patients without amputations, amputees were on average older, more likely to belong to a minority group, and were more likely to have received treatment for more comorbid conditions. Asians were more likely to have toe amputations compared with whites or other ethnicities, while Native Americans were more likely to have below-the-knee amputations. Native Americans had the highest risk of amputation (RR 1.74, 95% CI 1.39–2.18), followed by African Americans (RR 1.41, 95% CI 1.34–1.48) and Hispanics (RR 1.28, 95% CI 1.20–1.38) compared with whites. The presence of diabetic nephropathy increased the risk of amputation threefold in all groups. Asian subjects with diabetes had the lowest adjusted relative risk of amputation (RR 0.31, 95% CI 0.19–0.50).

CONCLUSIONS—Among diabetic patients, certain ethnic minority individuals have an increased risk of lower-extremity amputation compared with whites. Presence of diabetic nephropathy further increases this risk.
Quantifying the Risk of Infectious Diseases for People With Diabetes
Authors: Shah Baiju R. , Hux Janet E.
Published: March 2007

OBJECTIVE—In vitro evidence shows that immune function is compromised in people with diabetes. Although certain rare infections are more common and infection-related mortality is higher, the risk of acquiring an infectious disease for diabetic patients has never been quantified.

RESEARCH DESIGN AND METHODS—A retrospective cohort study using administrative data compared all people with diabetes in Ontario, Canada, on 1 April 1999 to matched nondiabetic people (n = 513,749 in each group). The risk ratios of having an infectious disease and of death attributable to infectious disease between those with and without diabetes were calculated. Secondary analysis individually examined common infectious diseases. The study was repeated using a second pair of cohorts defined in 1996 to confirm stability of the estimates.

RESULTS—Nearly half of all people with diabetes had at least one hospitalization or physician claim for an infectious disease in each cohort year. The risk ratio for diabetic versus nondiabetic people was 1.21 (99% CI 1.20–1.22) in both cohort years. The risk ratio for infectious disease-related hospitalization was up to 2.17 (99% CI 2.10–2.23). The risk ratio for death attributable to infection was up to 1.92 (1.79–2.05). Many individual infections were more common in people with diabetes, especially serious bacterial infections.

CONCLUSIONS—Diabetes confers an increased risk of developing and dying from an infectious disease, corroborating both in vitro evidence and commonly held clinical belief. In addition to microvascular and macrovascular sequelae, clinicians should consider infection a complication of diabetes.
Exercise Training, Without Weight Loss, Increases Insulin Sensitivity and Postheparin Plasma Lipase Activity in Previously Sedentary Adults
Authors: Duncan Glen E. , Perri Michael G. , Theriaque Douglas W. , Hutson Alan D. , Eckel Robert H. , Stacpoole Peter W.
Published: March 2007

OBJECTIVE—To determine the effects of exercise, without weight loss, on insulin sensitivity (SI), postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K2), and fasting lipids in sedentary adults.

RESEARCH DESIGN AND METHODS—At baseline and after 6 months of walk training (intensity 45–55 or 65–75% heart rate reserve, frequency 3–4 or 5–7 days/week, duration 30 min/session), anthropometric indexes, SI, PHPL, K2, and fasting lipids were measured in 18 sedentary adults (12 women, 6 men; 51.9 ± 5.8 years of age, BMI 28.9 ± 4.6 kg/m2).

RESULTS—Exercise increased SI (2.54 ± 2.74 vs. 4.41 ± 3.30 μU · ml−1 · min−1, P < 0.005) and both lipoprotein lipase (LPL) (1,890 ± 1,380 vs. 4,926 ± 1,858 nEq free fatty acid [FFA] · ml−1 · h−1) and hepatic lipase (HL) activities (3,326 ± 1,605 vs. 4,636 ± 1,636 nEq FFA · ml−1 · h−1) (both P < 0.001), without altering BMI, waist circumference, K2, or fasting lipids. Correlations between changes in LPL and the total:HDL cholesterol ratio (r = −0.54) and changes in the LPL:HL ratio and waist circumference (r = −0.50) were significant (P < 0.05).

CONCLUSIONS—Exercise, without weight loss, increases SI and PHPL activity in previously sedentary adults, without changing K2 or fasting lipid levels. Furthermore, increased LPL is associated with a decreased total:HDL ratio, and an increased LPL:HL ratio is associated with a decreased waist circumference. Therefore, even modest amounts of exercise in the absence of weight loss positively affect markers of glucose and fat metabolism in previously sedentary, middle-aged adults.
Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients With Long-Term Type 2 Diabetes
Authors: van Loon Luc J.C. , Kruijshoop Margriet , Menheere Paul P.C.A. , Wagenmakers Anton J.M. , Saris Wim H.M. , Keizer Hans A.
Published: March 2007

OBJECTIVE—Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Ten type 2 diabetic patients (aged 59.1 ± 2.0 years, BMI 26.5 ± 0.7 kg/m2) and 10 healthy control subjects (58.8 ± 2.1 years, 26.5 ± 0.7 kg/m2) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g · kg−1 · h−1 carbohydrate with or without 0.35 g · kg−1 · h−1 of the amino acid/protein mixture.

RESULTS—Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P < 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame.

CONCLUSIONS—The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal.
Losartan Reduces the Costs Associated With Diabetic End-Stage Renal Disease
Authors: Herman William H. , Shahinfar Shahnaz , Carides George W. , Dasbach Erik J. , Gerth William C. , Alexander Charles M. , Cook John R. , Keane William F. , Brenner Barry M. ,   For the RENAAL Investigators
Published: March 2007

OBJECTIVE—To evaluate the within-trial effect of losartan and conventional antihypertensive therapy (CT) compared with placebo and CT on the economic cost associated with end-stage renal disease (ESRD).

RESEARCH DESIGN AND METHODS—The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study was a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the renal protective effects of losartan on a background of CT (excluding ACE inhibitors and angiotensin II receptor agonists [AIIAs]) in patients with type 2 diabetes and nephropathy. The primary composite end point was doubling of serum creatinine, ESRD, or death. Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time. The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System. Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy.

RESULTS—We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years (P = 0.004, 95% CI 10.9–56.3). This reduction in ESRD days resulted in a decrease in cost associated with ESRD of $5,144 per patient (P = 0.003, 95% CI $1,701 to $8,587). After accounting for the cost of losartan, the reduction in ESRD days resulted in a net savings of $3,522 per patient over 3.5 years (P = 0.041, $143 to $6,900).

CONCLUSIONS—Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD, but also resulted in substantial cost savings.
Clinical Diagnosis of Diabetic Polyneuropathy With the Diabetic Neuropathy Symptom and Diabetic Neuropathy Examination Scores
Authors: Meijer Jan-Willem G. , Bosma Eelke , Lefrandt Johan D. , Links Thera P. , Smit Andries J. , Stewart Roy E. , van der Hoeven Johannes H. , Hoogenberg Klaas
Published: March 2007

OBJECTIVE—To evaluate the discriminative power of the Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores for diagnosing diabetic polyneuropathy (PNP), as well as their relation with cardiovascular autonomic function testing (cAFT) and electro-diagnostic studies (EDS).

RESEARCH DESIGN AND METHODS—Three groups (matched for age and sex) were selected: 24 diabetic patients with neuropathic foot ulcers (DU), 24 diabetic patients without clinical neuropathy or ulcers (DC), and 21 control subjects without diabetes (C). In all participants, the DNS and DNE scores were assessed and cAFT (heart rate variability [HRV], baroreflex sensitivity [BRS]), and EDS were performed (Nerve Conduction Sum [NCS] score; muscle fiber conduction velocity: fastest/slowest ratio [F/S ratio]).

RESULTS—Both the DNS and the DNE scores discriminated between the DU and DC groups significantly (P < 0.001). The DNE score even discriminated between DC and C (P < 0.05). Spearman’s correlation coefficients between both DNS and DNE scores and cAFT (HRV −0.42 and −0.44; BRS −0.30 and −0.29, respectively) and EDS (NCS 0.51 and 0.62; F/S ratio 0.44 and 0.62, respectively) were high. Odds ratios were calculated for both DNS and DNE scores with cAFT (HRV 4.4 and 5.7; BRS 20.7 and 14.2, respectively) and EDS (NCS 5.6 and 16.8; F/S ratio 7.2 and 18.8, respectively).

CONCLUSIONS—The DNS and DNE scores are able to discriminate between patients with and without PNP and are strongly related to cAFT and EDS. This further confirms the strength of the DNS and DNE scores in diagnosing diabetic PNP in daily clinical practice.
Insulin Sensitivity and the Risk of Incident Hypertension
Authors: Goff David C. , Zaccaro Daniel J. , Haffner Steven M. , Saad Mohammed F.
Published: March 2007

OBJECTIVE—The insulin resistance syndrome has been described as including hypertension. Previous studies have documented cross-sectional associations between insulin sensitivity (SI) and blood pressure or prevalent hypertension. Prospective data have been sparse.

RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study (IRAS) is a prospective study of the associations of SI with atherosclerosis and other risk factors for cardiovascular disease. We examined the association between SI, measured using the frequently sampled intravenous glucose tolerance test with minimal model analysis, and incident hypertension (defined as per the Joint National Committee), at the 5-year examination in 840 IRAS participants who were free of hypertension at the baseline examination.

RESULTS—Adjusted for age, sex, ethnicity, and smoking status, for each unit greater SI, the risk of hypertension was 10% lower (95% CI 2–19, P < 0.05).

CONCLUSIONS—These findings, from a prospective study, support the presence of a modest protective association between greater SI and lower risk of hypertension. These findings support the contention that interventions that improve SI may be beneficial with respect to the development of hypertension and cardiovascular disease. This contention should be tested in randomized clinical trials.
Insulin Secretion and Insulin Sensitivity Pattern Is Different in Isolated Impaired Glucose Tolerance and Impaired Fasting Glucose
Authors: Hanefeld Markolf , Koehler Carsta , Fuecker Katja , Henkel Elena , Schaper Frank , Temelkova-Kurktschiev Theodora
Published: March 2007

OBJECTIVE—Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance.

RESEARCH DESIGN AND METHODS—This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories.

RESULTS—All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance.

CONCLUSIONS—Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.
Value of Coronary Artery Calcium Scanning by Computed Tomography for Predicting Coronary Heart Disease in Diabetic Subjects
Authors: Qu Wenchun , Le Thuy T. , Azen Stanley P. , Xiang Min , Wong Nathan D. , Doherty Terence M. , Detrano Robert C.
Published: March 2007

OBJECTIVE—The South Bay Heart Watch is a cohort study designed to determine the significance of coronary calcium in high-risk asymptomatic patients. This is a report of the relative risk (RR) for outcomes of coronary artery calcium in diabetic and nondiabetic subjects.

RESEARCH DESIGN AND METHODS—A total of 1,312 diabetic and nondiabetic subjects underwent risk factor screening and computed tomography testing for coronary calcium at baseline and were followed clinically for 6.3 ± 1.4 years. End points were either 1) hard events of nonfatal myocardial infarction (MI) or coronary death or 2) any cardiovascular event (nonfatal MI, coronary death, coronary revascularization, or stroke).

RESULTS—The incidence rates of a hard event and any cardiovascular event for diabetic and nondiabetic subjects were 14.5 and 6.1% and 23.8 and 12.2%, respectively (P < 0.001). Cox regression analyses of the combined risk relationship of diabetes status and calcium score demonstrated that relative to nondiabetic subjects with low calcium scores (<2.8), diabetic subjects with calcium scores ≥2.8 exhibited at least a fourfold increase in the risk of either a hard or any cardiovascular event (P < 0.001). Cox regression analyses conducted separately for nondiabetic and diabetic subjects revealed that coronary calcium score risk groups were significantly associated with events in nondiabetic subjects (RR ≥ 2.6, P ≤ 0.01), but not in diabetic subjects (RR ≤ 1.7, P > 0.05).

CONCLUSIONS—The risk of coronary heart disease increases with increasing calcium scores and diabetes status. Calcium scores have less prognostic value in diabetic subjects.
Predictive Value of Foot Pressure Assessment as Part of a Population-Based Diabetes Disease Management Program
Authors: Lavery Lawrence A. , Armstrong David G. , Wunderlich Robert P. , Tredwell Jeffrey , Boulton Andrew J.M.
Published: March 2007

OBJECTIVE—To evaluate the effectiveness of dynamic plantar pressure assessment to determine patients at high risk for neuropathic ulceration. In choosing the cut point, we looked for an optimum combination of sensitivity and specificity of plantar pressure to screen for neuropathic ulceration.

RESEARCH DESIGN AND METHODS—A total of 1,666 consecutive individuals with diabetes (50.3% male) presenting to a large urban managed care-based outpatient clinic were enrolled in this longitudinal 2-year outcome study. Patients received a standardized medical and musculoskeletal assessment at the time of enrollment, including evaluation in an onsite gait laboratory.

RESULTS—Of the entire population, 263 patients (15.8%) either presented with or developed an ulcer during the 24-month follow-up period. As expected, baseline peak plantar pressure was significantly higher in the ulcerated group than in the group who did not ulcerate (95.5 ± 26.4 vs. 85.1 ± 27.3 N/cm2, P < 0.001). There was also a trend toward increased pressure with increasing numbers of foot deformities, as well as with increasing foot risk classification (P = 0.0001). Peak pressure was not a suitable diagnostic tool by itself to identify high-risk patients. After eliminating patients without loss of protective sensation, using receiver operating characteristic (ROC) analysis, the optimal cut point, as determined by a balance of sensitivity and specificity, was 87.5 N/cm2, yielding a sensitivity of 63.5% and a specificity of 46.3%.

CONCLUSIONS—The data from this evaluation continue to support the notion that elevated foot pressure is an important risk factor for foot complications. However, the ROC analysis suggests that foot pressure is a poor tool by itself to predict foot ulcers.
Evolution of Analytical Performance in Portable Glucose Meters in the Last Decade
Authors: Böhme Philip , Floriot Michele , Sirveaux Marie-Aude , Durain Danielle , Ziegler Olivier , Drouin Pierre , Guerci Bruno
Published: March 2007

OBJECTIVE—To assess and compare the technical accuracy of portable glucose meters during the last decade.

RESEARCH DESIGN AND METHODS—One-thousand preprandial (pre) and postprandial (post) capillary whole-blood glucose values measured with meters owned mainly by diabetic patients were compared with a single laboratory method yearly from 1989 to 1999. A total of 21,950 capillary measurements and their corresponding laboratory reference values were analyzed at our clinic.

RESULTS—The lowest mean absolute difference was found in 1989 (pre: 2 ± 22 mg/dl, post: 9 ± 31 mg/dl) (mean ± SD). The highest mean absolute difference was observed in 1993 (pre: 31 ± 33 mg/dl) and 1996 (post: 50 ± 35 mg/dl). The highest mean relative deviation was observed in 1990 (pre: 16.4%) and 1996 (post: 20.6%). The highest percentage of readings that were within a 5% deviation limit were observed in 1998 (pre: 44.5%) and in 1997 (post: 36.7%). Based on blood glucose levels within ±5 and ±10% of laboratory values, the technical accuracy of meters was similar for 1989 and 1999 (P = 0.27 and 0.52, respectively). The percentage of pre values in zone A of Clarke’s error grid analysis was >90% in 1989, 1997, 1998, and 1999.

CONCLUSIONS—The analytical performance of glucose meters decreased between 1990 and 1996 but was restored between 1997 and 1999. Nevertheless, our data suggest that the technical accuracy of glucose meters has not significantly improved during the last decade. Complementary studies taking into account the preanalytical improvements of the recent meters, as well as their calibration method, appear necessary.
Economic Impact of Diabetic Ketoacidosis in a Multiethnic Indigent Population
Authors: Maldonado Mario R. , Chong Erica R. , Oehl Melissa A. , Balasubramanyam Ashok
Published: March 2007

OBJECTIVE—Diabetic ketoacidosis (DKA) is a common complication of diabetes. We analyzed the inpatient costs of treating DKA in a multiethnic, indigent population in Houston, Texas.

RESEARCH DESIGN AND METHODS—We measured the cost of resources utilized for all patients admitted to our hospital with DKA from 1 January to 31 December 1998. We also analyzed their medical records to determine the factors that precipitated the episode of DKA and then grouped them into three categories: acute illnesses, noncompliance with diabetes treatment, and new-onset diabetes. The data were analyzed by one-way ANOVA. The Tukey-Kramer procedure was used for post hoc multiple comparisons.

RESULTS—There were 167 admissions for DKA. The mean age was 40 ± 13 years. The ethnic distribution was 49% African American, 32% Hispanic American, and 18% white. The total inhospital cost of treating DKA was $1,816,255. The mean cost per hospitalization was $10, 876 ± 11,024. The frequency distribution by category of DKA-precipitating factor was 18% acute illness, 59% noncompliance, and 23% new onset. There were differences in mean cost of DKA associated with the three categories: $20,864 ± 17,910 for acute illness, $11,863 ± 8,701 for new onset, and $7,470 ± 6,300 for noncompliance (P < 0.0001). The total cost for each category was $671,375 for acute illness, $694,082 for noncompliance, and $450,798 for new onset.

CONCLUSIONS—DKA is an expensive complication among indigent, multiethnic diabetic patients. Although the mean cost per admission was lowest for DKA precipitated by noncompliance, this causal category was responsible in sum for the greatest portion of the economic burden.
Use of Heart Rate Reserve and Rating of Perceived Exertion to Prescribe Exercise Intensity in Diabetic Autonomic Neuropathy
Authors: Colberg Sheri R. , Swain David P. , Vinik Aaron I.
Published: March 2007

OBJECTIVE—Individuals with diabetic autonomic neuropathy (DAN) exhibit an increased resting heart rate but depressed maximal heart rate. Thus, the purpose of this study was to examine the validity of using either percent of heart rate reserve (HRR) or a rating of perceived exertion (RPE) scale to prescribe exercise intensity in diabetic individuals both with and without DAN.

RESEARCH DESIGN AND METHODS—The subjects consisted of 23 individuals with type 2 diabetes, ages 45–75 years, with (DAN; n = 13) or without (No DAN; n = 10) clinical signs of DAN, as assessed by heart rate variability using the expiration-to-inspiration ratio of the R-R interval. Peak aerobic capacity was determined using a graded protocol on a cycle ergometer, with RPE, heart rate, and Vo2 values recorded at each stage.

RESULTS—The subjects were similar with the exception of depressed autonomic function in DAN subjects. Peak respiratory exchange ratio values were significantly higher (P < 0.05) in the DAN group (1.08 ± 0.02 vs. 1.02 ± 0.01 in No DAN subjects), although DAN subjects exhibited a significantly lower (P < 0.05) peak exercise heart rate. A similarly highly linear relationship between %HRR and percent Vo2 reserve (Vo2R) existed for both groups (r = 0.98). A similar slightly weaker relationship (r = 0.94) was found between RPE and %Vo2R.

CONCLUSIONS—In conclusion, in diabetic individuals, %HRR provides an accurate prediction of %Vo2R and can be used to prescribe and monitor exercise intensity, regardless of the presence of DAN. The RPE scale is also a valid, albeit slightly less accurate, method to monitor exercise intensity in diabetic individuals.