bluuebunny/crossref_metadata_2025 huggingface dataset:
The Network of Psychological Variables  in Patients With Diabetes and Their Importance for Quality of Life and Metabolic Control
Authors: Rose Matthias , Fliege Herbert , Hildebrandt Martin , Schirop Thea , Klapp Burghard F.
Published: March 2007

OBJECTIVE—The primary goals in treating patients with diabetes are maintaining blood glucose levels as close to normal as possible and making a relatively normal quality of life achievable. Both of these goals are influenced by a multitude of somatic and psychological factors that should be seen as building a complex network. We examined whether a mathematical model can be construed that can depict the relative significance of each factor for achieving these treatment goals.

RESEARCH DESIGN AND METHODS—A total of 625 patients from 32 different treatment facilities were examined (224 type 1 and 401 type 2 diabetic patients) using HbA1c values (high-performance liquid chromatography), number of secondary illnesses, and standardized questionnaires with respect to health-related quality of life (World Health Organization Quality of Life questionnaire), coping behavior (Freiburger Illness-Coping Strategies questionnaire), diabetes-specific knowledge (Test of Diabetes-Specific Knowledge), doctor-patient relationship (Medical Interview Satisfaction Scale), and personality characteristics (Giessen Test and Assessment of Beliefs in Self-Efficacy and Optimism). The analyses were carried out by means of a structural equation model.

RESULTS—The model proved to be valid (χ2 = 88.5, df = 76, P = 0.16), showing a sound fit (adjusted goodness of fit [AGFI] = 0.94). It explained 62% of the variance of the quality of life and 5% of the HbA1c values. Subjects characterized by strong beliefs in their self-efficacy and an optimistic outlook on life were more likely to be satisfied with their doctor-patient relationships. They demonstrated more active coping behavior and proved to have a higher quality of life. Active coping behavior was the only psychological variable significant for the HbA1c values.

CONCLUSIONS—It was possible to illustrate the various factors involved and their mutual dependency and significance for the treatment goals. Belief in self-efficacy and active coping behavior appear to have the greatest relevance for achieving the primary treatment goals.
Cause-Specific Mortality in a Population With Diabetes
Authors: Roper Nick A. , Bilous Rudy W. , Kelly William F. , Unwin Nigel C. , Connolly Vincent M.
Published: March 2007

OBJECTIVE—To describe the mortality of a population with diabetes compared with the local nondiabetic population, using age-, sex-, and cause-specific death rates and relative and absolute differences in death rates.

RESEARCH DESIGN AND METHODS—A population-based cohort of 4,842 people with diabetes living within South Tees, U.K., was identified and followed from 1 January 1994 to 31 December 1999. Causes of death were obtained from death certificates, and mortality rates were compared with the nondiabetic population of the same area for the same time period.

RESULTS—There were 1,205 deaths (24.9%) in the study population during the 6 years of study. For type 2 diabetes, mortality from cardiovascular causes was significantly increased in both sexes and at all ages. Relative death rates for the age band 40–59 years were 5.47 (95% CI 4.18–7.15) for men and 5.60 (3.44–9.14) for women. The relative death rates declined with age for both sexes, but absolute excess mortality increased with age. There were no consistent differences in noncardiovascular death rates, other than for renal disease. Similar outcomes were found for type 1 diabetes, although these results were limited by a much smaller population size. People with diabetes and renal impairment had significantly higher mortality than people with diabetes alone, with a rate ratio of 7.27 for people with type 2 diabetes aged 40–59 years.

CONCLUSIONS—In an area of the U.K. with high cardiovascular death rates, people with diabetes had significantly higher cardiovascular death rates than people without diabetes. Interventions targeted at cardiovascular risk factors should be used to try and reduce this excess premature mortality, which is especially high in those with renal impairment.
Comparison of Antigenicity of Hoechst 21PH Insulin Using Either Implantable Intraperitoneal Pump or Subcutaneous External Pump Infusion in Type 1 Diabetic Patients
Authors: Jeandidier Nathalie , Boullu Sylvie , Busch-Brafin Marie-Sophie , Chabrier Gerard , Sapin Rémy , Gasser Françoise , Pinget Michel
Published: March 2007

OBJECTIVE—To assess the antigenicity of the insulin Hoechst 21PH (Hoe21PH) using continuous subcutaneous insulin infusion (CSII) and to compare the antigenicity of this insulin when administered intraperitoneally or subcutaneously.

RESEARCH DESIGN AND METHODS—Peritoneal administration of Hoe21PH (Hoechst-Roussel, Somerville, NJ) insulin using implantable devices (continuous peritoneal insulin infusion [CPII]) increases anti-insulin antibody (AIA) levels in type 1 diabetic patients. Intraperitoneal administration, addition of a stabilizer (polyethylene polypropylene glycol), or insulin modifications due to storage in the pump may be involved in this antigenicity. In this nonrandomized study, 24 type 1 diabetic patients were treated with either CSII (n = 11, group 1) or CPII (n = 13, group 2). AIA levels were measured by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) before starting patients on Hoe21PH and again after 3 and 6 months.

RESULTS—Patients were comparable in the two groups. AIA levels (RIA) remained stable (24.3 ± 8.5% [month 0] to 24.9 ± 8.5.5% [month 6]) in group 1 and increased (21.8 ± 6.7% [month 0] to 41.8 ± 6.9% [month 6]) in group 2 (P = 0.005, Wilcoxon’s rank-sum test). Using ELISA, AIA remained stable in the patients in group 1 (n = 9; 3.8 ± 0.8 units/ml [month 0] and 4.1 ± 1.0 units/ml [month 6]) and tended to increase in the patients in group 2 (n = 12; 4.1 ± 0.7 units/ml [month 0] to 17.5 ± 4.6 units/ml [month 6]) (P = 0.07). Comparison of the evolution of AIA formation between the two groups, using RIA at months 0, 3, and 6 showed a significant difference (analysis of variance, P = 0.009).

CONCLUSIONS—No increase in AIA levels was demonstrated when Hoe21PH insulin was administered subcutaneously as assessed by two different assays. CPII is proven to be more antigenic than CSII, and this is not related to a specific antigenicity of Hoe21PH insulin. The intraperitoneal route of administration or insulin modifications due to insulin storage in implantable devices might explain this antigenicity.
Dual Blockade of the Renin-Angiotensin System in Diabetic Nephropathy
Authors: Rossing Kasper , Christensen Per K. , Jensen Berit R. , Parving Hans-Henrik
Published: March 2007

OBJECTIVE—Many patients with diabetic nephropathy (DN) have levels of albuminuria >1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS).

RESEARCH DESIGN AND METHODS—We performed a randomized double-blind crossover study of 2 months treatment with candesartan cilexetil 8 mg once daily and placebo in addition to previous antihypertensive treatment. We included 18 type 2 diabetic patients with DN fulfilling the above-mentioned criteria. All received recommended doses of ACE inhibitor and, in addition, 15 patients received diuretics, 11 received a calcium channel antagonist, and 3 received a β-blocker. At the end of each treatment period, we measured the glomerular filtration rate (GFR), 24-h blood pressure, albuminuria, and IgGuria .

RESULTS—The addition of candesartan to usual antihypertensive therapy induced a mean (95% CI) reduction in albuminuria of 25% (2–58), P = 0.036 (geometric mean [95% CI] from 1,764 mg/24 h [1,225–2,540] to 1,334 mg/24 h [890–1,998]). It also produced a mean reduction of 35% (9–53) in the fractional clearance of albumin (P = 0.016), a reduction of 32% (1–54) in fractional clearance of IgG (P = 0.046), a reduction in 24-h systolic blood pressure of 10 mmHg (2–18) (P = 0.019) (mean ± ± SE) from 148 ± 3 to 138 ± 5 mmHg, and a mean reduction in GFR of 5 ml · min−1 · 1.73 m−2 (0.1–9) (P = 0.045).

CONCLUSIONS—Dual blockade of the RAS reduces albuminuria and blood pressure in type 2 diabetic patients with DN responding insufficiently to previous antihypertensive therapy, including ACE inhibitors in recommended doses.
Effect of Fish Oil Versus Corn Oil Supplementation on LDL and HDL Subclasses in Type 2 Diabetic Patients
Authors: Petersen Martin , Pedersen Helle , Major-Pedersen Atheline , Jensen Tonny , Marckmann Peter
Published: March 2007

OBJECTIVE—The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol (TAG), low HDL cholesterol, and a predominance of atherogenic small dense LDLs. Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might, therefore, be a good nonpharmacological treatment for type 2 diabetic patients. In the present study, we investigate the effect of fish oil supplementation on the fasting lipid profile, including LDL and HDL subclasses.

RESEARCH DESIGN AND METHODS—A total of 42 type 2 diabetic patients were randomized to supplementation (capsules) with 4 g daily of either fish oil (n = 20) or corn oil (n = 22) for 8 weeks preceded by a 4-week run-in period of corn oil supplementation. Blood was drawn before and after the 8-week intervention period. Plasma lipoproteins, including LDL and HDL subclasses, were separated by ultracentrifugation.

RESULTS—Fish oil lowered TAG (group difference: P = 0.025) and raised HDL-2b cholesterol (P = 0.012) and HDL-2a cholesterol (P = 0.007) concentrations as compared with corn oil. We observed no significant effects of fish oil on LDL cholesterol, HDL cholesterol, or the concentration of small dense LDL particles.

CONCLUSIONS—Fish oil supplementation may partially correct the dyslipidemia of type 2 diabetic patients. However, the putative very important aspect of diabetic dyslipidemia—the predominance of small dense LDL particles—was unaffected by fish oil.
Dietary Fiber Intake and Glycemic Index and Incidence of Diabetes in African-American and White Adults
Authors: Stevens June , Ahn Kyungmi , Juhaeri  , Houston Denise , Steffan Lyn , Couper David
Published: March 2007

OBJECTIVE—To determine the association of dietary fiber and glycemic index with incident type 2 diabetes in African-Americans and whites.

RESEARCH DESIGN AND METHODS—We studied 12,251 adults aged 45–64 years and free of diabetes at baseline (1987–1989). A total of 1,447 cases of diabetes were reported between baseline and 9 years of follow-up. Diabetes status was determined by fasting glucose level ≥126 mg/dl (7.0 mmol/l), nonfasting glucose level ≥200 mg/dl (11.1 mmol/l), self-report of physician diagnosis, or use of diabetes medication. Usual dietary intake over the previous year was obtained at baseline using a 66-item food-frequency questionnaire. Nutrients were energy-adjusted using the residuals method. Proportional hazard regression analysis was used to examine dietary fiber intake and glycemic index as predictors of type 2 diabetes in both ethnic groups.

RESULTS—After adjustment for age, BMI, education, smoking status, physical activity, sex, and field center, there were no statistically significant associations of intake of total dietary fiber, fruit fiber, legume fiber, glycemic index, or glycemic load with incident diabetes. The hazard ratio for the fifth compared with the first quintile of cereal fiber was 0.75 (95% CI 0.60–0.92) in whites and 0.86 (0.65–1.15) in African-Americans.

CONCLUSIONS—This finding supports a protective role for cereal fiber in the development of diabetes in whites. More studies are needed to determine the role of dietary fiber and glycemic index in diabetes in African-Americans.
Diabetic Patients Detected by Population-Based Stepwise Screening Already Have a Diabetic Cardiovascular Risk Profile
Authors: Spijkerman Annemieke M.W. , Adriaanse Marcel C. , Dekker Jacqueline M. , Nijpels Giel , Stehouwer Coen D.A. , Bouter Lex M. , Heine Robert J.
Published: March 2007

OBJECTIVE—To describe a population-based two-step screening procedure for type 2 diabetes and to study the cardiovascular risk profile of the patients identified by the screening.

RESEARCH DESIGN AND METHODS—The first step of the screening procedure consisted of the Symptom Risk Questionnaire (SRQ), and the second step was a fasting capillary glucose measurement. In subjects with an SRQ score of >6 and a capillary glucose level of >5.5 mmol/l, an oral glucose tolerance test was performed.

RESULTS—A total of 11,679 inhabitants of the West-Friesland region of the Netherlands, aged 50–75 years, were invited. Of the inhabitants, 9,169 (78%) responded, and, of those, 417 had previously diagnosed diabetes. The SRQ score was calculated for 7,736 participants, and 3,301 of those had a score of >6. A total of 2,885 subjects (87.3%) attended for capillary glucose measurement. Diagnostic testing was carried out in 509 participants, and we identified 217 diabetic patients. In these patients detected by screening, mean HbA1c was 6.7% (±1.4). Hypertension and high total cholesterol levels (>5.0 mmol/l) were present in 70%, 33% had high triglyceride (>3.0 mmol/l) or low HDL cholesterol levels (<1.0 mmol/l in men and <1.1 mmol/l in women), and 40% were obese (BMI ≥30 kg/m2).

CONCLUSIONS—The high response rate was the main feature of the screening by means of the Symptom Risk Questionnaire and fasting capillary glucose measurement followed by diagnostic testing. The 217 diabetic patients detected by the screening were characterized by relatively low HbA1c levels and by a cardiovascular risk profile typical of diabetic patients.
High Frequency of Vα24+ Vβ11+ T-Cells Observed in Type 1 Diabetes
Authors: Oikawa Yoichi , Shimada Akira , Yamada Satoru , Motohashi Yoshiko , Nakagawa Yoshinori , Irie Jun-ichiro , Maruyama Taro , Saruta Takao
Published: March 2007

OBJECTIVE—Natural killer T-cells (NKT cells) are believed to play an important role in the regulation of immune response, and a numerical and functional deficit of NKT cells has been reported to be associated with the pathogenesis of autoimmune diseases. Thus far, it has been shown that subjects with type 1 diabetes have a lower frequency of NKT cells than nondiabetic subjects. In this study, we measured the frequency of peripheral Vα24+ Vβ11+ T-cells, which include human NKT cells, in Japanese diabetic patients.

RESEARCH DESIGN AND METHODS—Peripheral blood samples were obtained from 164 Japanese diabetic patients and 67 healthy subjects. The diabetic patients were classified into four categories as follows: islet-associated autoantibody–positive (Ab+) and –negative (Ab–) classic type 1 diabetes, latent autoimmune diabetes in adults (LADA), and type 2 diabetes. We measured the frequency of peripheral Vα24+ Vβ11+ CD3+ triple-positive cells.

RESULTS—Unexpectedly, a higher frequency of Vα24+ Vβ11+ T-cells was observed in Ab+ and Ab− patients compared with LADA patients (P = 0.0294 and P = 0.0021), type 2 diabetic patients (P < 0.0001 and P < 0.0001), and healthy subjects (P = 0.0046 and P = 0.0001). Moreover, an inverse correlation between Vα24+ Vβ11+ T-cell frequency and disease duration was observed in Ab+ (ρ = −0.455; P = 0.0023) and Ab− (ρ = −0.432; P = 0.0162) patients.

CONCLUSIONS—Our findings indicate that a high frequency of Vα24+ Vβ11+ T-cells is a unique finding in recent-onset classic type 1 diabetes, and measurement of Vα24+ Vβ11+ T-cell frequency may be useful to assess the disease activity of classic type 1 diabetes.
Fasting and Postchallenge Glycemia and Cardiovascular Disease Risk
Authors: Meigs James B. , Nathan David M. , D’Agostino Ralph B. , Wilson Peter W.F.
Published: March 2007

OBJECTIVE—To test the hypothesis that fasting hyperglycemia (FHG) and 2-h postchallenge glycemia (2hPG) independently increase the risk for cardiovascular disease (CVD).

RESEARCH DESIGN AND METHODS—During 1991–1995, we examined 3,370 subjects from the Framingham Offspring Study who were free from clinical CVD (coronary heart disease, stroke, or intermittent claudication) or medication-treated diabetes, and we followed them for 4 years for incident CVD events. We used proportional-hazards regression to assess the risk associated with FHG (fasting plasma glucose ≥7.0 mmol/l) and 2hPG, independent of the risk predicted by standard CVD risk factors.

RESULTS—Mean subject age was 54 years, 54% were women, and previously undiagnosed diabetes was present in 3.2% by FHG and 4.9% (164) by FHG or a 2hPG ≥11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPG ≥11.1 without FHG, but these 55 subjects represented only 1.7% of the 3,261 subjects without FHG. During 12,242 person-years of follow-up, there were 118 CVD events. In separate sex- and CVD risk-adjusted models, relative risk (RR) for CVD with fasting plasma glucose ≥7.0 mmol/l was 2.8 (95% CI 1.6–5.0); RR for CVD per 2.1 mmol/l increase in 2hPG was 1.2 (1.1–1.3). When modeled together, the RR for FHG decreased to 1.5 (0.7–3.6), whereas the RR for 2hPG remained significant (1.1, 1.02–1.3). The c-statistic for a model including CVD risk factors alone was 0.744; with addition of FHG, it was 0.746, and with FHG and 2hPG, it was 0.752.

CONCLUSIONS—Postchallenge hyperglycemia is an independent risk factor for CVD, but the marginal predictive value of 2hPG beyond knowledge of standard CVD risk factors is small.
Meal-Related Structured Self-Monitoring of Blood Glucose
Authors: Schwedes Ulrich , Siebolds Markus , Mertes Gabriele ,   For the SMBG Study Group
Published: March 2007

OBJECTIVE—To investigate the effect of meal-related self-monitoring of blood glucose on glycemic control and well-being in non-insulin-treated type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—This 6-month study, which included 6 months of follow-up, adopted a prospective, multicenter, randomized controlled design. Subjects were randomized to two groups: one group used a blood glucose-monitoring device, kept a blood glucose/eating diary, and received standardized counseling; the control group received nonstandardized counseling on diet and lifestyle. The primary efficacy parameter was the change in HbA1c. Secondary efficacy variables included changes in body weight, lipids, and microalbumin and changes in treatment satisfaction and well-being.

RESULTS—In the per-protocol analysis, the use of a self-monitoring blood glucose device significantly reduced HbA1c levels by 1.0 ± 1.08% compared with 0.54 ± 1.41% for the control group (P = 0.0086); subgroup analysis showed three types of responders. Body weight, total cholesterol, and microalbumin improved when using a glucometer, but there was no statistically significant difference between the two groups. Treatment satisfaction increased in both groups to a similar extent (P = 0.9). Self-monitoring resulted in a marked improvement of general well-being with significant improvements in the subitems depression (P = 0.032) and lack of well-being (P = 0.02).

CONCLUSIONS—Meal-related self-monitoring of blood glucose within a structured counseling program improved glycemic control in the majority of non-insulin-treated type 2 diabetic patients in this study. The finding of three types of responders will be important for future planning of counseling and educational interventions.
Impact of a Program to Improve Adherence to Diabetes Guidelines by Primary Care Physicians
Authors: Kirkman M. Sue , Williams Susanna R. , Caffrey Helena H. , Marrero David G.
Published: March 2007

OBJECTIVES—Previous studies have shown that primary care physician (PCP) adherence to diabetes guidelines is suboptimal. We sought to determine the state of diabetes care given by independently practicing PCPs in a rural county in Indiana and whether a multifaceted intervention targeting PCPs, patients, and the health care system would improve adherence to diabetes guidelines.

RESEARCH DESIGN AND METHODS—Baseline audits to assess adherence to diabetes guidelines were done on charts of the seven PCPs in the county. Audits were repeated after development of local consensus guidelines and feedback of baseline performance and after implementation of various interventions (practice aids, physician detailing, patient education sessions, and implementation of computerized individual meal planning).

RESULTS—Before any intervention, rates of adherence to guidelines were low (15% for foot exams, 20% for HbA1c measurement, 23% for eye exam referrals, 33% for urine protein screening, 44% for lipid profiles, 73% for home glucose monitoring, and 78% for blood pressure measurements). One year after development of local consensus guidelines and feedback of baseline performance, significant improvements were seen in blood pressure measurements (71 vs. 83%; P = 0.002), foot exams (19 vs. 42%; P < 0.001), HbA1c measurements (26 vs. 37%; P = 0.012), and PCP eye exams (38 vs. 46%; P = 0.043); a trend toward improvement was seen in referral to eye specialists (25 vs. 33%; P = 0.059). After a second year of multiple interventions, only blood pressure measurements (70 vs. 92%; P < 0.001) and foot exams (22 vs. 47%; P < 0.001) remained significantly improved; all other areas returned to rates indistinguishable from baseline.

CONCLUSIONS—In busy primary care practices lacking organizational support and computerized tracking systems, sustained improvements in diabetes care are difficult to attain using traditional physician-targeted approaches.
The Impact of Planned Care and a Diabetes Electronic Management System on Community-Based Diabetes Care
Authors: Montori Victor M. , Dinneen Sean F. , Gorman Colum A. , Zimmerman Bruce R. , Rizza Robert A. , Bjornsen Susan S. , Green Erin M. , Bryant Sandra C. , Smith Steven A. ,   for The Translation Project Investigator Group
Published: March 2007

OBJECTIVE—The Mayo Health System Diabetes Translation Project sought to assess models of community-based diabetes care and use of a diabetes electronic management system (DEMS). Planned care is a redesigned model of chronic disease care that involves guideline implementation, support of self-management, and use of clinical information systems.

RESEARCH DESIGN AND METHODS—We studied adult diabetic patients attending three primary care practice sites in Wisconsin and Minnesota. We implemented planned care at all sites and DEMS in the practice of 16 primary care providers. We assessed quality of diabetes care using standard indicators for 200 patients randomly selected from each site at baseline and at 24 months of implementation. We used multivariable analyses to estimate the association between planned care and DEMS and each quality indicator.

RESULTS—Planned care was associated with improvements in measurement of HbA1c (odds ratio 7.0 [95% CI 4.2–11.6]), HDL cholesterol (5.6 [4.1–7.5]), and microalbuminuria (5.3 [3.5–8.0]), as well as the provision of tobacco advice (6.9 [4.7–10.1]), among other performance measures. DEMS use was associated with improvements in all indicators, including microalbuminuria (3.2 [1.9–5.2]), retinal examination (2.4 [1.5–3.9]), foot examinations (2.3 [1.2–4.4]), and self-management support (2.6 [1.7–3.8]). Although planned care was associated with improvements in metabolic control, we observed no additional metabolic benefit when providers used DEMS.

CONCLUSIONS—Planned care was associated with improved performance and metabolic outcomes in primary care. DEMS use augmented the impact of planned care on performance outcomes but not on metabolic outcomes. Optimal identification of the best translation of evidence to diabetes practice will require longer follow-up or new care-delivery models.
Clinical Usefulness of Cystatin C for the Estimation of Glomerular Filtration Rate in Type 1 Diabetes
Authors: Tan G.D. , Lewis A.V. , James T.J. , Altmann P. , Taylor R.P. , Levy J.C.
Published: March 2007

OBJECTIVE—Assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Plasma creatinine is insensitive for a glomerular filtration rate (GFR) >50 ml/min and creatinine clearance is unwieldy and subject to collection inaccuracies. We aimed to assess the reproducibility, reliability, and accuracy of plasma cystatin C as a measure of GFR ranging from normal to moderate impairment due to type 1 diabetes in the presence of a normal plasma creatinine concentration.

RESEARCH DESIGN AND METHODS—A sensitive immunoturbidimetric cystatin C assay was examined in 29 subjects with type 1 diabetes and 11 nondiabetic subjects. Duplicate measurements of the following were collected from each subject, 2 weeks apart: cystatin C, enzymatic plasma creatinine, 24-h creatinine clearance, GFR estimated from plasma creatinine by the Cockcroft-Gault equation, and iohexol clearance as a gold standard.

RESULTS—Iohexol clearance ranged from 35 to 132 ml · min−1 · 1.73 m−2. Plasma cystatin C compared well with the other clinically used tests. The reliability of cystatin C, as assessed by the discriminant ratio, was superior to creatinine clearance (3.4 vs. 1.5, P < 0.001) and the correlation of cystatin C with iohexol clearance (Rs −0.80) was similar to that of creatinine clearance (Rs −0.74) and superior to that of plasma creatinine and the Cockcroft-Gault estimate (Rs −0.54 and 0.66, respectively). Duplicate estimations were used to provide an unbiased equation to convert plasma cystatin C to GFR.

CONCLUSIONS—Based on this study, cystatin C is a more reliable measure of GFR than creatinine clearance, is more highly correlated with iohexol clearance than plasma creatinine, and is worthy of further investigation as a clinical measure of GFR in type 1 diabetes.
A Direct Comparison of Insulin Aspart and Insulin Lispro in Patients With Type 1 Diabetes
Authors: Plank Johannes , Wutte Andrea , Brunner Gernot , Siebenhofer Andrea , Semlitsch Barbara , Sommer Romana , Hirschberger Sabine , Pieber Thomas R.
Published: March 2007

OBJECTIVE—Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control.

RESEARCH DESIGN AND METHODS—A total of 24 type 1 diabetic patients (age 36 ± 8 years, 16 men and 8 women, BMI 24.3 ± 2.6 kg/m2, diabetes duration 17 ± 11 years, HbA1c 7.9 ± 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal.

RESULTS—With respect to blood glucose excursions from time 0 to 6 h (Excglu(0–6 h)) and from time 0 to 4 h (Excglu(0–4 h)), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (Cmax(glu)) (estimated ratio aspart/lispro ANOVA [90% CI]: 0.95 [0.80–1.13], 0.97 [0.82–1.17], and 1.01 [0.95–1.07] for Excglu(0–6 h), Excglu(0–4 h), and Cmax(glu), respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed.

CONCLUSIONS—These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions.
Nateglinide Improves Early Insulin Secretion and Controls Postprandial Glucose Excursions in a Prediabetic Population
Authors: Saloranta Carola , Guitard Christiane , Pecher Eckhard , de Pablos-Velasco Pedro , Lahti Kaj , Brunel Patrick , Groop Leif
Published: March 2007

OBJECTIVE—The purpose of this study was to evaluate the metabolic effectiveness, safety, and tolerability of nateglinide in subjects with impaired glucose tolerance (IGT) and to identify a dose appropriate for use in a diabetes prevention study.

RESEARCH DESIGN AND METHODS—This multicenter, double-blind, randomized, parallel-group, fixed-dose study of 8 weeks’ duration was performed in a total of 288 subjects with IGT using a 2:2:2:1 randomization. Subjects received nateglinide (30, 60, and 120 mg) or placebo before each main meal. Metabolic effectiveness was assessed during a standardized meal challenge performed before and after the 8-week treatment. All adverse events (AEs) were recorded, and confirmed hypoglycemia was defined as symptoms accompanied by a self-monitoring of blood glucose measurement ≤3.3 mmol/l (plasma glucose ≤3.7 mmol/l).

RESULTS—Nateglinide elicited a dose-related increase of insulin and a decrease of glucose during standardized meal challenges, with the predominant effect on early insulin release, leading to a substantial reduction in peak plasma glucose levels. Nateglinide was well tolerated, and symptoms of hypoglycemia were the only treatment-emergent AEs. Confirmed hypoglycemia occurred in 28 subjects receiving nateglinide (30 mg, 0 [0%]; 60 mg, 5 [6.6%]; 120 mg, 23 [26.7%]) and in 1 (2.3%) subject receiving placebo.

CONCLUSIONS—Nateglinide was safe and effective in reducing postprandial hyperglycemia in subjects with IGT. Preprandial doses of 30 or 60 mg nateglinide would be appropriate to use for longer-term studies to determine whether a rapid-onset, rapidly reversible, insulinotropic agent can delay or prevent the development of type 2 diabetes.
The Benefits of Metformin Therapy During Continuous Subcutaneous Insulin Infusion Treatment of Type 1 Diabetic Patients
Authors: Meyer Laurent , Bohme Philip , Delbachian Irene , Lehert Philippe , Cugnardey Nathalie , Drouin Pierre , Guerci Bruno
Published: March 2007

OBJECTIVE—This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period.

RESULTS—Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of −4.3 ± 9.9 units (−7.8 ± 18%) compared with an increase with placebo treatment of 1.7 ± 8.3 units (2.8 ± 12.7%) (P = 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of −2.6 ± 3.2 units (−7.9 ± 23.8%) compared with an increase with placebo treatment of 1.9 ± 5.7 units (8.8 ± 27.1%) (P = 0.023). HbA1c remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (<60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P = 0.04) and LDL cholesterol (P = 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P = 0.069).

CONCLUSIONS—Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.
Plasma and Dietary Vitamin E in Relation to Incidence of Type 2 Diabetes
Authors: Mayer-Davis Elizabeth J. , Costacou Tina , King Irena , Zaccaro Daniel J. , Bell Ronny A.
Published: March 2007

OBJECTIVE—To evaluate the association of vitamin E with incidence of type 2 diabetes and to do so separately among individuals who did and those who did not report regular use of vitamin supplementation.

RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study (IRAS) included 895 nondiabetic adults at baseline (including 303 with impaired glucose tolerance [IGT]), 148 of whom developed type 2 diabetes according to World Health Organization (WHO) criteria during the 5-year follow-up. At baseline, dietary vitamin E was estimated by a validated food frequency interview, usual supplement use was confirmed by supplement label, and plasma α-tocopherol was measured. Analyses were conducted separately for individuals who did (n = 318) and did not (n = 577) use vitamin E supplements.

RESULTS—Among supplement nonusers, reported mean intake of vitamin E (mg α-tocopherol equivalents [α-TE]) did not differ between those who remained nondiabetic (n = 490) and those who developed diabetes (n = 87) (10.5 ± 5.5 vs. 9.5 ± 4.8 [means ± SD], respectively, NS). After adjustment for demographic variables, obesity, physical activity, and other nutrients, the association remained nonsignificant (odds ratio [OR] 0.80, 95% CI 0.13–5.06) for the highest level of intake (≥20 mg α-TE) compared with the lowest level (1–4 α-TE). However, results for plasma concentration of α-tocopherol showed a significant protective effect both before and after adjustment for potential confounders (adjusted OR 0.12, 95% CI 0.02–0.68, for the highest quintile vs. the lowest quintile; overall test for trend, P < 0.01). Among individuals who reported habitual use of vitamin E supplements (at least once per month in the year before baseline; 259 remained nondiabetic and 59 developed diabetes), no protective effect was observed for either reported intake of vitamin E or plasma concentration of α-tocopherol

CONCLUSIONS—A protective effect of vitamin E may exist within the range of intake available from food. This effect may go undetected within studies of high-dose supplement use, which appears to hold no additional protective benefit.
Usefulness of Home Blood Pressure Measurement in the Morning in Type 2 Diabetic Patients
Authors: Kamoi Kyuzi , Miyakoshi Masashi , Soda Satoshi , Kaneko Susumu , Nakagawa Osamu
Published: March 2007

OBJECTIVE—Recently, repeated home blood pressure (HBP) measurements in the morning for a long period have been shown to have a stronger predictive power for mortality in patients with hypertension than occasional casual/clinic blood pressure (CBP) measurements. We studied whether HBP in the morning in type 2 diabetic patients is useful for prediction of diabetic complications.

RESEARCH DESIGN AND METHODS—The occurrence of diabetic complications (nephropathy, retinopathy, coronary heart disease [CHD], and cerebrovascular disease [CVD]) were examined in relation to morning HBP as well as to CBP in 170 type 2 diabetic patients treated with antidiabetic and antihypertensive drugs. Blood pressure was measured at the clinic during the day and at home after awakening in the morning. Clinic hypertension (CH) and morning hypertension (MH) were defined as systolic blood pressure (SBP) ≥130 mmHg and/or diastolic blood pressure (DBP) ≥85 mmHg. The relation of CH and MH to the prevalence of these events was examined.

RESULTS—There were no significant differences in the prevalence of nephropathy, retinopathy, CHD, and CVD between the two groups with (n = 131) and without CH (n = 39), whereas the prevalences of these events in the patients with MH (n = 97) were significantly higher (P < 0.05) than in those without MH (n = 73). The prevalence of nephropathy was highly associated with systolic MH.

CONCLUSIONS—Elevations of HBP in the morning in diabetic patients are strongly related to microvascular and macrovascular complications, especially nephropathy. It is concluded that the control of MH may prevent vascular complications in type 2 diabetic patients.
Valuing Health-Related Quality of Life in Diabetes
Authors: Coffey J. Todd , Brandle Michael , Zhou Honghong , Marriott Deanna , Burke Ray , Tabaei Bahman P. , Engelgau Michael M. , Kaplan Robert M. , Herman William H.
Published: March 2007

OBJECTIVE—Cost-utility analyses use information on health utilities to compare medical treatments that have different clinical outcomes and impacts on survival. The purpose of this study was to describe the health utilities associated with diabetes and its treatments, complications, and comorbidities.

RESEARCH DESIGN AND METHODS—We studied 2,048 subjects with type 1 and type 2 diabetes recruited from specialty clinics at a university medical center. We administered a questionnaire to each individual to assess demographic characteristics, type and duration of diabetes, treatments, complications, and comorbidities, and we used the Self-Administered Quality of Well Being index (QWB-SA) to calculate a health utility score. We then created regression models to fit the QWB-SA-derived health utility scores to indicator variables for type 1 and type 2 diabetes and each demographic variable, treatment, and complication. The coefficients were arranged in clinically meaningful ways to develop models to describe penalties from the health utility scores for nonobese diabetic men without additional treatments, complications, or comorbidities.

RESULTS—The utility scores for nonobese diet-controlled men and women with type 2 diabetes and no microvascular, neuropathic, or cardiovascular complications were 0.69 and 0.65, respectively. The utility scores for men and women with type 1 diabetes and no complications were slightly lower (0.67 and 0.64, respectively). Blindness, dialysis, symptomatic neuropathy, foot ulcers, amputation, debilitating stroke, and congestive heart failure were associated with lower utility scores.

CONCLUSIONS—Major diabetes complications are associated with worse health-related quality of life. The health utility scores provided should facilitate studies of the health burden of diabetes and the cost-utility of alternative strategies for the prevention and treatment of diabetes.
Decreased Mortality Associated With the Use of Metformin Compared With Sulfonylurea Monotherapy in Type 2 Diabetes
Authors: Johnson Jeffrey A. , Majumdar Sumit R. , Simpson Scot H. , Toth Ellen L.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents.

RESEARCH DESIGN AND METHODS—Saskatchewan Health databases were used to examine population-based mortality rates for new users of oral antidiabetic agents. Individuals with prescriptions for sulfonylurea or metformin in 1991–1996 and no use in the year prior were identified as new users. Prescription records were prospectively followed for 1–9 years; subjects with any insulin use were excluded. Causes of death were identified based on ICD-9 codes in an electronic vital statistics database. Multivariate logistic regression and survival analyses were used to assess the differences in mortality between drug cohorts, after adjusting for potential confounding variables.

RESULTS—The total study sample comprised 12,272 new users of oral antidiabetic agents; the average length of follow-up was 5.1 (SD 2.2) years. In subjects with at least 1 year of drug exposure and no insulin use, mortality rates were 750/3,033 (24.7%) for those receiving sulfonylurea monotherapy, 159/1,150 (13.8%) for those receiving metformin monotherapy, and 635/4,683 (13.6%) for those receiving combination therapy over an average 5.1 (SD 2.2) years of follow-up. The adjusted odds ratio (OR) for all-cause mortality for metformin monotherapy was 0.60 (95% CI 0.49–0.74) compared with sulfonylurea monotherapy. Sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR 0.66, 95% CI 0.58–0.75). Reduced cardiovascular-related mortality rates were also observed in metformin users compared with sulfonylurea monotherapy users.

CONCLUSIONS—Metformin therapy, alone or in combination with sulfonylurea, was associated with reduced all-cause and cardiovascular mortality compared with sulfonylurea monotherapy among new users of these agents.
A Novel Noninvasive Blood Glucose Monitor
Authors: Malchoff Carl D. , Shoukri Kamal , Landau Julian I. , Buchert Janusz M.
Published: March 2007

OBJECTIVE—To evaluate the precision and accuracy of a new advanced prototype of a noninvasive blood glucose monitor across a wide range of serum glucose concentrations.

RESEARCH DESIGN AND METHODS—An advanced handheld noninvasive glucose monitor prototype was calibrated and tested using patients recruited by the General Research Center of the University of Connecticut Health Center. The monitor, developed by Infratec, uses principles of thermal emission spectroscopy. The noninvasive measurement of tympanic membrane glucose concentration was calibrated to the serum glucose concentration using 432 paired measurements from 20 subjects with insulin-requiring diabetes. This calibration was subsequently tested (results of power analyses) in a blind fashion with 126 paired measurements from six diabetic subjects who require insulin.

RESULTS—In vivo measurements demonstrated the reproducibility of the methodology of the noninvasive glucose monitor. Based on the calibration model, predicted glucose concentrations for six subjects were as follows (for 126 data points): SD = 32 mg/dl, mean absolute relative error (%MARE) = 11.6, with a correlation coefficient of r = 0.87. Noninvasive glucose results were also compared with laboratory reference measurements using an error-in-variables method. Clark error grid analysis showed that 100% of the measurements fell within zones A and B (90% in zone A and 10% in zone B). The SD for all noninvasive measured concentrations was 27 mg/dl, %MARE was 8.6, and the correlation coefficient was r = 0.94.

CONCLUSIONS—This first independent clinical study of an advanced noninvasive blood glucose prototype based on thermal emission in the mid-infrared spectral region has demonstrated glucose measurements with clinically acceptable accuracy but without the necessity of individual daily calibration.
Association of HLA-DQ Genotype in Autoantibody-Negative and Rapid-Onset Type 1 Diabetes
Authors: Tanaka Shoichiro , Kobayashi Tetsuro , Nakanishi Koji , Koyama Rikako , Okubo Minoru , Murase Toshio , Odawara Masato , Inoko Hidetoshi
Published: March 2007

OBJECTIVE—Some type 1 diabetic patients have a distinct phenotype characterized by the absence of pancreatic autoantibodies and fulminant clinical symptoms at onset, including marked hyperglycemia, severe diabetic ketoacidosis, and normal to near-normal HbA1c levels with complete destruction of β-cells. However, little is known about genetic factors of this distinct subtype of diabetes (fulminant autoantibody-negative type 1 diabetes).

RESEARCH DESIGN AND METHODS—We analyzed HLA-DQ genotypes in fulminant autoantibody-negative type 1 diabetes (n = 22) and autoantibody-positive type 1 diabetes (immune-mediated type 1 diabetes, n = 78) recruited from a cohort between 1980 and 2000.

RESULTS—Fulminant autoantibody-negative type 1 diabetes had a significantly high prevalence of the HLA-DQA1*0303-DQB1*0401 haplotype in a homozygous manner (RR 39) or in a heterozygous manner with the HLA-DQA1*0302-DQB1*0303 haplotype (RR 13). In contrast, autoantibody-positive type 1 diabetic patients had a high prevalence of the HLA-DQA1*0302-DQB1*0303 haplotype in a homozygous manner (RR 10) or in a heterozygous manner with the HLA-DQA1*0303-DQB1*0401 haplotype (RR 12).

CONCLUSIONS—Pathogenic roles of genotypic combinations of specific HLA-DQ haplotypes in a homozygous manner are suggested as causative mechanisms of aggressive β-cell damage in a subtype of autoantibody-negative type 1 diabetes with fulminant clinical features.
A Randomized Controlled Trial of Resistance Exercise Training to Improve Glycemic Control in Older Adults With Type 2 Diabetes
Authors: Castaneda Carmen , Layne Jennifer E. , Munoz-Orians Leda , Gordon Patricia L. , Walsmith Joseph , Foldvari Mona , Roubenoff Ronenn , Tucker Katherine L. , Nelson Miriam E.
Published: March 2007

OBJECTIVE—To determine the efficacy of high-intensity progressive resistance training (PRT) on glycemic control in older adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS—We performed a 16-week randomized controlled trial in 62 Latino older adults (40 women and 22 men; mean ± SE age 66 ± 8 years) with type 2 diabetes randomly assigned to supervised PRT or a control group. Glycemic control, metabolic syndrome abnormalities, body composition, and muscle glycogen stores were determined before and after the intervention.

RESULTS—Sixteen weeks of PRT (three times per week) resulted in reduced plasma glycosylated hemoglobin levels (from 8.7 ± 0.3 to 7.6 ± 0.2%), increased muscle glycogen stores (from 60.3 ± 3.9 to 79.1 ± 5.0 mmol glucose/kg muscle), and reduced the dose of prescribed diabetes medication in 72% of exercisers compared with the control group, P = 0.004–0.05. Control subjects showed no change in glycosylated hemoglobin, a reduction in muscle glycogen (from 61.4 ± 7.7 to 47.2 ± 6.7 mmol glucose/kg muscle), and a 42% increase in diabetes medications. PRT subjects versus control subjects also increased lean mass (+1.2 ± 0.2 vs. −0.1 ± 0.1 kg), reduced systolic blood pressure (–9.7 ± 1.6 vs. +7.7 ± 1.9 mmHg), and decreased trunk fat mass (−0.7 ± 0.1 vs. +0.8 ± 0.1 kg; P = 0.01–0.05).

CONCLUSIONS—PRT as an adjunct to standard of care is feasible and effective in improving glycemic control and some of the abnormalities associated with the metabolic syndrome among high-risk older adults with type 2 diabetes.
Obesity and Treatment of Diabetes With Glyburide May Both Be Risk Factors for Acute Pancreatitis
Authors: Blomgren Kerstin B. , Sundström Anders , Steineck Gunnar , Wiholm Bengt E.
Published: March 2007

OBJECTIVE—To evaluate risk factors, notably drugs, for acute pancreatitis.

RESEARCH DESIGN AND METHODS—A population-based case-control study was conducted of 1.4 million inhabitants, aged 20–85 years, of four regions in Sweden between 1 January 1995 and 31 May 1998. A total of 462 case subjects were hospitalized in surgery departments for their first episode of acute pancreatitis without previous gallbladder disease. A total of 1,781 control subjects were randomly selected from a population register. Information was obtained from case records and through telephone interviews.

RESULTS—A total of 27 case subjects (6%) and 55 control subjects (3%) had prevalent diabetes. A total of 53 case subjects (11%) and 130 control subjects (7%) had a BMI >30 kg/m2. Use of glyburide had a crude odds ratio (OR) of 3.2 (95% CI 1.5–5.9), and in a multivariate logistic regression adjusted for covariates, the OR for use of glyburide was 2.5 (1.1–5.9). BMI had a continuous OR of 1.2 (1.1–1.4) per 5 units of BMI. The relative risk for hospitalization longer than 14 days or treatment in an intensive care unit was 2.4 (1.1–5.4) among patients with a BMI >30 kg/m2 when compared with patients with a BMI between 20 and 25 kg/m2.

CONCLUSIONS—Use of glyburide and obesity may both be risk factors for acute pancreatitis. Obesity is associated with an extended hospitalization time in subjects with acute pancreatitis.