bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Patient Preferences on the Cost-Effectiveness of Intensive Glucose Control in Older Patients With New-Onset Diabetes
Authors: Huang Elbert S. , Shook Morgan , Jin Lei , Chin Marshall H. , Meltzer David O. 
Published: May 2006

OBJECTIVE—Cost-effectiveness analyses have reported that intensive glucose control is not cost-effective in older patients with new-onset diabetes. However, these analyses have had limited data on patient preferences concerning diabetic health states. We examined how the cost- effectiveness of intensive glucose control changes with the incorporation of patient preferences.RESEARCH DESIGN AND METHODS—We collected health state preferences/utilities from 519 older diabetic patients. We incorporated these utilities into an established cost-effectiveness model of intensive glucose control and compared incremental cost-effectiveness analyses ratios (ICERs) (cost divided by quality-adjusted life-year [QALY]) when using the original and patient-derived utilities for complications and treatments.RESULTS—The mean utilities were ∼0.40 for major complications, 0.76 (95% CI 0.74–0.78) for conventional glucose control, 0.77 (0.75–0.80) for intensive therapy with oral medications, and 0.64 (0.61–0.67) for intensive therapy with insulin. Incorporating our patient-derived complication utilities alone improved ICERs for intensive glucose control (e.g., patients aged 60–65 years at diagnosis, $136,000/QALY→$78,000/QALY), but intensive therapy was still not cost-effective at older ages. When patient-derived treatment utilities were also incorporated, the cost-effectiveness of intensive treatment depended on the method of glucose control. Intensive control with insulin generated fewer QALYs than conventional control. However, intensive control with oral medications was beneficial on average at all ages and had an ICER ≤$100,000 to age 70.CONCLUSIONS—The cost-effectiveness of intensive glucose control in older patients with new-onset diabetes is highly sensitive to assumptions regarding quality of life with treatments. Cost-effectiveness analyses of diabetes care should consider the sensitivity of results to alternative utility assumptions.
Increased Cancer-Related Mortality for Patients With Type 2 Diabetes Who Use Sulfonylureas or Insulin
Authors: Bowker Samantha L. , Majumdar Sumit R. , Veugelers Paul , Johnson Jeffrey A. 
Published: May 2006

OBJECTIVE—Numerous studies have identified an increased risk of cancer in type 2 diabetes. We explored the association between antidiabetic therapies and cancer-related mortality in patients with type 2 diabetes, postulating that agents that increase insulin levels might promote cancer.
RESEARCH DESIGN AND METHODS—This was a population-based cohort study using administrative databases from Saskatchewan Health. Cancer-related mortality was compared among inception cohorts of metformin users and sulfonylurea monotherapy users. Multivariate Cox regression was used to estimate the hazard ratio (HR) of cancer-related mortality, after adjusting for age, sex, insulin use, and chronic disease score. All statistical tests were two-sided.
RESULTS—We identified 10,309 new users of metformin or sulfonylureas with an average follow-up of 5.4 ± 1.9 years (means ± SD). The mean age for the cohort was 63.4 ± 13.3 years, and 55% were men. Cancer mortality over follow-up was 4.9% (162 of 3,340) for sulfonylurea monotherapy users, 3.5% (245 of 6,969) for metformin users, and 5.8% (84 of 1,443) for subjects who used insulin. After multivariate adjustment, the sulfonylurea cohort had greater cancer-related mortality compared with the metformin cohort (adjusted HR 1.3 [95% CI 1.1–1.6]; P = 0.012). Insulin use was associated with an adjusted HR of cancer-related mortality of 1.9 (95% CI 1.5–2.4; P &lt; 0.0001).
CONCLUSIONS—Patients with type 2 diabetes exposed to sulfonylureas and exogenous insulin had a significantly increased risk of cancer-related mortality compared with patients exposed to metformin. It is uncertain whether this increased risk is related to a deleterious effect of sulfonylurea and insulin or a protective effect of metformin or due to some unmeasured effect related to both choice of therapy and cancer risk.
Mean Blood Glucose and Biological Variation Have Greater Influence on HbA1c Levels Than Glucose Instability
Authors: McCarter Robert J. , Hempe James M. , Chalew Stuart A. 
Published: May 2006

OBJECTIVE—Mean blood glucose (MBG) over 2–3 months is a strong predictor of HbA1c (A1C) levels. Glucose instability, the variability of blood glucose levels comprising the MBG, and biological variation in A1C (BV) have also been suggested as predictors of A1C independent of MBG. To assess the relative importance of MBG, BV, and glucose instability on A1C, we analyzed patient data from the Diabetes Control and Complications Trial (DCCT).
RESEARCH DESIGN AND METHODS—A glucose profile set and sample for A1C were collected quarterly over the course of the DCCT from each participant (n = 1,441). The glucose profile set consisted of seven samples, one each drawn before and 90 min after breakfast, lunch, and dinner and one before bedtime. MBG and glucose instability (SD of blood glucose [SDBG]) were calculated as the arithmetic mean and SD of glucose profile set samples for each visit, respectively. A statistical model was developed to predict A1C from MBG, SDBG, and BV, adjusted for diabetes duration, sex, treatment group, stratum, and race.
RESULTS—Data from 32,977 visits were available. The overall model was highly statistically significant (log likelihood = −41,818.75, likelihood ratio χ2[7] = 7,218.71, P &gt; χ2 = 0.0000). MBG and BV had large influences on A1C based on their standardized coefficients. SDBG had only 1/14 of the impact of MBG and 1/10 of the impact of BV.
CONCLUSIONS—MBG and BV have a large influence on A1C, whereas SDBG is relatively unimportant. Consideration of BV as well as MBG in the interpretation of A1C may enhance our ability to monitor diabetes management and predict complications.
Improving Metabolic Control Leads to Better Working Memory in Adults With Type 2 Diabetes
Authors: Ryan Christopher M. , Freed Martin I. , Rood Julie A. , Cobitz Alexander R. , Waterhouse Brian R. , Strachan Mark W.J. 
Published: May 2006

OBJECTIVE—The goals of this study were to determine whether improvements in metabolic control can ameliorate the cognitive dysfunction associated with type 2 diabetes and evaluate the possibility that such improvements are mediated by changes in circulating insulin or insulin resistance.
RESEARCH DESIGN AND METHODS—This randomized double-blind trial enrolled 145 subjects at 18 centers in the U.S. Older adults with type 2 diabetes receiving metformin monotherapy received add-on therapy with either rosiglitazone, a thiazolidinedione insulin sensitizer, or glyburide. Cognitive function was assessed at baseline and week 24 using the Digit Symbol Substitution Test, the Rey Auditory Verbal Learning Test, and the Cambridge Neuropsychological Test Automated Battery.
RESULTS—Pretreatment fasting plasma glucose (FPG) in both groups was similar, and after 24 weeks both treatment groups showed similar significant reductions in FPG (2.1–2.3 mmol/l). Working memory improved with both rosiglitazone (P &lt; 0.001) and glyburide (P = 0.017). Improvement (25–31% reduction in errors) was most evident on the Paired Associates Learning Test and was significantly correlated (r = 0.30) with improved glycemic control as measured by FPG.
CONCLUSIONS—Similar and statistically significant cognitive improvement was observed with both rosiglitazone and glyburide therapy, and the magnitude of this effect was correlated with the degree to which FPG improved. These results suggest that a cognitive benefit is achievable with pharmacological interventions targeting glycemic control.
Monocyte Telomere Shortening and Oxidative DNA Damage in Type 2 Diabetes
Authors: Sampson Mike J. , Winterbone Mark S. , Hughes Jackie C. , Dozio Nicoletta , Hughes David A. 
Published: May 2006

OBJECTIVE—Telomeres are DNA sequences necessary for DNA replication, which shorten at cell division at a rate related to levels of oxidative stress. Once shortened to a critical length, cells are triggered into replicative senescence. Type 2 diabetes is associated with oxidative DNA damage, and we hypothesized that telomere shortening would characterize type 2 diabetes.
RESEARCH DESIGN AND METHODS—We studied 21 male type 2 diabetic subjects (mean age 61.2 years, mean HbA1c 7.9%) selected to limit confounding effects on telomere length and 29 matched control subjects. Telomere length was measured in peripheral venous monocyte and T-cells (naïve and memory) by fluorescent in situ hybridization and oxidative DNA damage by flow cytometry of oxidized DNA bases. Peripheral insulin resistance (homeostasis model assessment) and high-sensitivity C-reactive protein (hsCRP) were measured.
RESULTS—Mean monocyte telomere length in the diabetic group was highly significantly lower than in control subjects (4.0 [1.1] vs. 5.5 [1.1]; P &lt; 0.0001), without significant differences in lymphocyte telomere length. There was a trend toward increased oxidative DNA damage in all diabetes cell types examined and a significant inverse relationship between oxidative DNA damage and telomere length (r = −0.55; P = 0.018) in the diabetic group. Telomere length was unrelated to plasma CRP concentration or insulin resistance.
CONCLUSIONS—Monocyte telomere shortening in type 2 diabetes could be due to increased oxidative DNA damage to monocyte precursors during cell division. This data suggests that monocytes adhering to vascular endothelium and entering the vessel wall in type 2 diabetes are from a population with shorter telomeres and at increased risk of replicative senescence within vascular plaque.
The Effect of Smoking Cessation and Subsequent Resumption on Absorption of Inhaled Insulin
Authors: Becker Reinhard H.A. , Sha Sue , Frick Annke D. , Fountaine Robert J. 
Published: May 2006

OBJECTIVE—To assess the absorption profile of inhaled insulin in healthy, actively smoking subjects at baseline, after smoking cessation, and after smoking resumption and compare it with nonsmoking subjects.
RESEARCH DESIGN AND METHODS—Insulin pharmacokinetics and glucodynamics were measured in 20 male smoking subjects (10–20 cigarettes/day) and 10 matched nonsmoking subjects after receiving inhaled insulin (1 mg) or the approximate subcutaneous insulin equivalent (3 units) in a randomized cross-over fashion. All smokers then received inhaled insulin 12 h, 3 days, and 7 days into a smoking cessation period. They then resumed smoking for 2–3 days before again receiving inhaled insulin 1 h after the last cigarette.
RESULTS—Before smoking cessation, maximum insulin concentration (Cmax) and area under the curve (AUC) for insulin concentration time (AUC-Insulin0–360) with inhaled insulin were higher, and time to Cmax (tmax) shorter, in smokers than nonsmokers (Cmax 26.8 vs. 9.7 μU/ml; AUC-Insulin0–360 2,583 vs. 1,645 μU · ml−1 · min−1; tmax 20 vs. 53 min, respectively; all P &lt; 0.05), whereas with subcutaneous insulin, systemic exposure was unchanged (AUC-Insulin0–360 2,324 vs. 2,269 μU · ml−1 · min−1; P = NS). After smoking cessation, AUC-Insulin0–360 decreased with inhaled insulin by up to 50% within 1 week and approached nonsmoker levels. Cmax decreased and tmax increased relative to baseline but were still not comparable with nonsmoker values. Smoking resumption completely reversed the effect of smoking cessation. Glucodynamics corroborated the observed findings in insulin pharmacokinetics.
CONCLUSIONS—Cessation and resumption of smoking greatly altered the pharmacokinetics of inhaled insulin. As rapid changes in systemic insulin exposure increase hypoglycemia risk, inhaled insulin should not be used in people with diabetes who choose to continue smoking. This is consistent with recommendations that people with diabetes refrain from smoking altogether.
Models for Predicting Type 1 Diabetes in Siblings of Affected Children
Authors: Mrena Samy , Virtanen Suvi M. , Laippala Pekka , Kulmala Petri , Hannila Marja-Leena , Åkerblom Hans K. , Knip Mikael ,   the Childhood Diabetes in Finland Study Group
Published: May 2006

OBJECTIVE—To generate predictive models for the assessment of risk of type 1 diabetes and age at diagnosis in siblings of children with newly diagnosed type 1 diabetes.
RESEARCH DESIGN AND METHODS—Cox regression analysis was used to assess the risk of progression to type 1 diabetes, and multiple regression analysis was used to estimate the age at disease presentation in 701 siblings of affected children. Sociodemographic, genetic, and immunological variables were included in the analyses. Subanalyses were performed in a group of 77 autoantibody-positive siblings with additional metabolic data.
RESULTS—A total of 47 siblings (6.7%) presented with type 1 diabetes during the 15-year observation period. Young age, an increasing number of detectable diabetes-associated autoantibodies at initial sampling and of affected first-degree relatives, and HLA DR–conferred disease susceptibility predicted progression to type 1 diabetes. In the subgroup of 77 autoantibody-positive siblings, young age, HLA DR–conferred susceptibility, an increasing number of autoantibodies, a reduced first-phase insulin response, and decreased insulin sensitivity in relation to first-phase insulin response were associated with increased risk of progression to type 1 diabetes. Age at diagnosis was predicted by age, insulinoma-associated protein 2 antibody levels, and number of autoantibodies at initial sampling (R2 = 0.76; P &lt; 0.001). In the smaller cohort of autoantibody-positive subjects, first-phase insulin response and HLA DR–conferred susceptibility were additional predictors of age at diagnosis.
CONCLUSIONS—Information on autoantibody status and levels, HLA-conferred disease susceptibility, and insulin secretion and sensitivity seems to be useful in addition to age and family history of type 1 diabetes when assessing risk of progression to type 1 diabetes and time to diagnosis in siblings of children with newly diagnosed type 1 diabetes.
Correspondence Between the Adult Treatment Panel III Criteria for Metabolic Syndrome and Insulin Resistance
Authors: Sierra-Johnson Justo , Johnson Bruce D. , Allison Thomas G. , Bailey Kent R. , Schwartz Gary L. , Turner Stephen T. 
Published: May 2006

OBJECTIVE—The aim of the present study was to assess the diagnostic accuracy of the Adult Treatment Panel III (ATP-III) definition of the metabolic syndrome in identifying insulin-resistant individuals and to explore alternative approaches to improve identification of insulin-resistant individuals among asymptomatic adults from the general population.
RESEARCH DESIGN AND METHODS—The sample consisted of 256 non-Hispanic white subjects without treated hypertension or diabetes, from the Rochester (Minnesota) Heart Family Study (123 men and 133 women; aged 20–60 years). Frequently sampled intravenous glucose tolerance tests were performed in all subjects. The reference standard for insulin resistance was determined by Bergman’s minimal model; insulin resistance was defined as an insulin sensitivity index &lt;2 × 10 min−1 · μU−1 · ml−1. Component metabolic syndrome measures included blood pressure determined by sphygmomanometer; fasting serum triglycerides, HDL cholesterol, and glucose concentrations determined enzymatically; and waist circumference determined by tape measure.
RESULTS—By ATP-III criteria, the prevalence of metabolic syndrome was 15.6% (16.3% in men and 15.1% in women; P = 0.465). The presence of metabolic syndrome had low sensitivity to identify insulin resistance (45% in men and 39% in women; sex difference, P = 0.137) but high specificity (93% in men and 95% in women; sex difference, P = 0.345). Based on the area under the receiver operating characteristic curve (AUC) constructed by counting metabolic syndrome components as recommended by ATP-III, diagnostic accuracy was fair (AUC = 0.797 in men and 0.747 in women). When component metabolic syndrome measures were considered as quantitative traits rather than dichotomized, use of waist circumference alone, rather than counting metabolic syndrome components, improved diagnostic accuracy for insulin resistance (in men, AUC = 0.906, P = 0.001; in women, AUC = 0.822, P = 0.10).
CONCLUSIONS—Application of the ATP-III metabolic syndrome criteria provides good specificity but low sensitivity to screen asymptomatic white adults for insulin resistance. Measuring just waist circumference is simpler and may provide greater accuracy for identifying insulin resistance.
Cardiovascular Risk Factors and Disease Management in Type 2 Diabetic Patients With Diabetic Nephropathy
Authors: Sasso Ferdinando C. , De Nicola Luca , Carbonara Ornella , Nasti Rodolfo , Minutolo Roberto , Salvatore Teresa , Conte Giuseppe , Torella Roberto ,   for the NID-2 (Nephropathy in Diabetes-Type 2) Study Group
Published: May 2006

OBJECTIVE—The purpose of this study was to assess the prevalence of cardiorenal risk factors, their management in a routine clinical setting, and the actual achievement of international guideline targets in a large cohort of type 2 diabetic patients with diabetic nephropathy.
RESEARCH DESIGN AND METHODS—A multicentric cross-sectional study was performed in the Campania region in Italy to evaluate cardiorenal risk factors and their management in light of international guidelines. Overall, 28,550 diabetic patients were screened in the 21 participating centers; 847 (348 male and 449 female) patients with type 2 diabetes and a clinical diagnosis of diabetic nephropathy were recruited.
RESULTS—Of these subjects, 749 had microalbuminuria and 98 had macroalbuminuria. Targets for blood pressure, HbA1c, LDL cholesterol, HDL cholesterol, and triglycerides were reached in, respectively, 17.5, 32.3, 30.7, 47, and 55.2% of the patients. Chronic renal failure (glomerular filtration rate &lt;60 ml/min) was revealed in 41% and anemia in 23.8% of the patients.
CONCLUSIONS—This is the first study to investigate a large cohort of type 2 diabetic patients with early and moderate diabetic nephropathy strictu sensu. Notably, impaired renal function can be often diagnosed in these patients even in the presence of microalbuminuria. Thus, clinical diagnosis of diabetic nephopathy allows us to identify a group of patients at very high cardiorenal risk, for whom care is really difficult. We suggest that a correct diagnosis of diabetic nephropathy should always be made and that sodium intake and anemia should be routinely evaluated in these patients.
Diabetes and Function in Different Cognitive Systems in Older Individuals Without Dementia
Authors: Arvanitakis Zoe , Wilson Robert Smith , Li Yan , Aggarwal Neelum Thanik , Bennett David Alan 
Published: May 2006

OBJECTIVE—To examine the relation of type 2 diabetes to the level of function in five different cognitive systems in older individuals without dementia.
RESEARCH DESIGN AND METHODS—Participants were 882 older men and women without dementia participating in the Rush Memory and Aging Project, a longitudinal clinical-pathological study of aging and dementia. They underwent uniform evaluations, which included clinical classification of dementia, and detailed cognitive function testing from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability, and global cognition were derived. Diabetes was identified by history and direct medication inspection.
RESULTS—Diabetes was present in 116 (13%) participants. In separate linear regression models controlling for age, sex, and education, diabetes was associated with lower levels of semantic memory (P &lt; 0.001) and perceptual speed (P = 0.005), but not with episodic memory, working memory, or visuospatial ability or with a measure of global cognition. The associations of diabetes with cognition were reduced when controlling for several vascular variables, and the associations were substantially stronger in current smokers than in individuals who never smoked or formerly smoked.
CONCLUSIONS—These results suggest that type 2 diabetes is associated with cognitive impairment, especially in semantic memory and perceptual speed and that these effects may be modified by smoking status.
Long-Acting Injectable Progestin Contraception and Risk of Type 2 Diabetes in Latino Women With Prior Gestational Diabetes Mellitus
Authors: Xiang Anny H. , Kawakubo Miwa , Kjos Siri L. , Buchanan Thomas A. 
Published: May 2006

OBJECTIVE—To investigate the impact of a long-acting injectable progestin, depo-medroxyprogesterone acetate (DMPA), compared with combination oral contraceptives (COCs) on the risk of diabetes in Latino women with prior gestational diabetes mellitus (GDM).
RESEARCH DESIGN AND METHODS—An observational cohort study of 526 Hispanic women with prior GDM who were not diabetic in their postpartum visit during January 1987 to October 1997 and who elected DMPA (n = 96) or COCs (n = 430) as initial contraception were followed for a maximum of 9.2 years with a median follow-up of ∼12 months. Oral glucose tolerance tests were performed and choice of contraception method was recorded at each visit as part of routine clinical care.
RESULTS—Annual diabetes incidence rates were 19% in the DMPA group and 12% in the COC group, with an unadjusted hazard ratio (HR) of 1.58 (95% CI 1.00–2.50; P = 0.05) for DMPA compared with COCs. Adjustment for baseline imbalances reduced the HR to 1.18 (0.67–2.28; P = 0.57). Additional adjustment for weight gain during follow-up, which was on average 1.8 kg higher in the DMPA group (P &lt; 0.0001), reduced the HR to 1.07. DMPA interacted with baseline serum triglyceride levels and, separately, with breast-feeding to increase the diabetes risk.
CONCLUSIONS—DMPA use was associated with an increased risk of diabetes that appeared to be explained by three factors: 1) use in women with increased baseline diabetes risk, 2) weight gain during use, and 3) use with high baseline triglycerides and/or during breast-feeding.
Association of Serum Proinsulin With Hormone Replacement Therapy in Nondiabetic Older Women
Authors: Kim Dong-Jun , Barrett-Connor Elizabeth 
Published: May 2006

OBJECTIVE—One putative benefit of hormone replacement therapy (HRT) is a reduced risk of diabetes or reduced fasting glucose level. We report here the association of HRT with proinsulin, insulin, and fasting and postchallenge glucose levels in older adults.
RESEARCH DESIGN AND METHODS—Current HRT use was validated and cross-sectionally compared with diabetes-related variables in 785 women without diabetes by history or glucose tolerance test.
RESULTS—Median age was 72 years (range 50–97); median value of fasting plasma glucose, postchallenge plasma glucose, and proinsulin was 5.08 mmol/l, 6.93 mmol/l, and 9.3 pmol/l, respectively. In age-adjusted comparisons, current HRT use was associated with significantly lower fasting plasma glucose and higher postchallenge plasma glucose compared with never/previous HRT use, as well as with lower LDL and higher HDL cholesterol and higher triglycerides. Fasting and postchallenge intact insulin did not differ by HRT group, but proinsulin was significantly lower in current HRT users than in previous and never HRT users. The significant association between proinsulin and HRT status persisted after adjustment for age, waist-to-hip ratio, pulse pressure, LDL-to-HDL cholesterol ratio, triglycerides, fasting and postchallenge glucose, and intact insulin.
CONCLUSIONS—Reduced fasting and increased 2-h glucose replicate findings in a randomized clinical trial. The proinsulin effect has not been previously reported. Decreased fasting glucose and proinsulin levels in current HRT use suggest a potential antidiabetes effect of HRT. Increased postchallenge glucose in HRT, however, suggests insulin resistance and would be expected to increase the risk of heart disease.