bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Troglitazone in Young First-Degree Relatives of Patients With Type 2 Diabetes
Authors: Levin Klaus , Hother-Nielsen Ole , Henriksen Jan Erik , Beck-Nielsen Henning
Published: March 2007

OBJECTIVE—Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes. We therefore treated young, glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity, glucose metabolism, and glycogen synthase activity.

RESEARCH DESIGN AND METHODS—Relatives were randomized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo. Before and after treatment, an oral glucose tolerance test (OGTT) and a euglycemic-hyperinsulinemic clamp (40 mU · m−2 · min−1) were performed, including 3-3H glucose infusion, glycolytic flux calculations, indirect calorimetry, and muscle biopsies.

RESULTS—Twelve relatives received troglitazone and 12 placebo (aged 30.8 ± 2.0 vs. 30.3 ± 1.6 years, BMI 29.6 ± 0.8 vs. 30.5 ± 1.3 kg/m2; means ± SE). Area under the curve (AUC) for plasma glucose at the second OGTT was unchanged after troglitazone. In contrast, troglitazone reduced fasting (from 70.3 ± 6.9 to 52.2 ± 5.8 vs. 73.6 ± 11.0 to 73.3 ± 6.5 pmol/l, P < 0.02) and AUC plasma insulin (mean [CI] from 335.7 [230.9–488.1] to 277.4 [179.4–428.8] vs. 313.8 [218.2–451.2] to 353.9 [208.3–601.3] pmol/l, P < 0.05). Additionally, fasting plasma triglycerides were reduced by troglitazone (from 1.86 ± 0.33 to 1.38 ± 0.27 vs. 2.22 ± 0.44 to 2.35 ± 0.46 mmol/l, P < 0.01). Insulin-stimulated glucose disposal increased in the troglitazone group (from 208.3 ± 23.7 to 263.5 ± 30.4 vs. 197.1 ± 20.0 to 200.8 ± 20.8 mg · m−2 · min−1, P < 0.02) mainly due to increased glucose storage (from 99.9 ± 17.9 to 146.0 ± 25.3 vs. 87.1 ± 16.7 to 87.9 ± 15.7 mg · m−2 · min−1, P < 0.02), which took place without altering insulin-stimulated glycogen synthase activity.

CONCLUSIONS—In glucose-tolerant first-degree relatives, treatment with troglitazone improved insulin sensitivity almost 50%, primarily due to increased glucose storage. It is suggested that the use of insulin action enhancers can be especially valuable in this group of subjects with a known high risk for developing type 2 diabetes.
Asp299Gly and Thr399Ile Genotypes of the TLR4 Gene Are Associated With a Reduced Prevalence of Diabetic Neuropathy in Patients With Type 2 Diabetes
Authors: Rudofsky Gottfried , Reismann Peter , Witte Steffen , Humpert Per M. , Isermann Berend , Chavakis Triantafyllos , Tafel Jörg , Nosikov Valery V. , Hamann Andreas , Nawroth Peter , Bierhaus Angelika
Published: March 2007

OBJECTIVE—To establish whether single nucleotide polymorphisms (Asp299Gly and Thr399Ile) of the toll-like receptor 4 have an association with late diabetic complications.

RESEARCH DESIGN AND METHODS—The study was conducted in 246 type 1 and 530 type 2 diabetic patients. The alleles of both polymorphisms were detected using PCR and subsequent cleavage by NcoI and HinfI restriction endonucleases.

RESULTS—No difference was found between type 1 and type 2 diabetic patients in the prevalence of alleles of the Asp299Gly and Thr399Ile polymorphisms. In most cases, the alleles Gly299 and Ile399 occurred in a co-segregatory manner. The prevalence of the Gly299/Ile399 haplotype was 10.6 and 12.1% in type 1 and type 2 diabetic patients, respectively (P = 0.63). No association with diabetic nephropathy or diabetic neuropathy was found in type 1 diabetic patients. In type 2 diabetic patients, however, heterozygote carriers of the Asp299Gly and Thr399Ile genotypes had a significantly reduced prevalence of diabetic neuropathy (odds ratio 0.35 [95% CI 0.19–0.61]; P = 0.0002); no association with diabetic nephropathy was found.

CONCLUSIONS—Our data indicate that Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with reduced prevalence of diabetic neuropathy in type 2, but not in type 1, diabetes. Thus different mechanisms may be involved in the pathophysiology of diabetic neuropathy in type 1 and type 2 diabetes.
Association Between Acute-Phase Reactants and Advanced Glycation End Products in Type 2 Diabetes
Authors: Tan Kathryn C.B. , Chow Wing-Sun , Tam Sidney , Bucala Richard , Betteridge John
Published: March 2007

OBJECTIVE—Type 2 diabetes is associated with chronic low-grade inflammation, but the underlying mechanism(s) is not well understood. Because in vitro studies have shown that advanced glycation end products (AGEs) can trigger inflammatory responses, the present study has investigated whether serum concentration of AGEs is an important determinant of circulating levels of inflammatory markers, like C-reactive protein (CRP), in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—Diabetic patients (n = 210) and healthy control subjects (n = 110) of similar BMI were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit anti-sera raised against AGE-RNase. Plasma high-sensitivity CRP was measured by an immunoturbidimetric assay and interleukin (IL)-6 by enzyme-linked immunosorbent assay.

RESULTS—Serum AGEs were increased in diabetic patients compared with control subjects (4.24 ± 0.88 vs. 3.15 ± 0.81 unit/ml, respectively, P < 0.01). Both plasma CRP (1.55 [0.81–2.95] vs. 0.88 mg/dl [0.51–1.89], respectively, P < 0.01; median [interquartile range]) and IL-6 (0.80 [0.68–0.97] vs. 0.69 pg/ml [0.48–0.84], respectively, P < 0.01) were also higher in diabetic patients than in control subjects. In the diabetic patients, log(CRP) correlated with AGEs (r = 0.22, P = 0.002) and with log(IL-6) (r = 0.29, P < 0.001). Forward stepwise linear regression analysis showed that BMI, log(IL-6), and AGEs were significant independent determinants of log(CRP) in the diabetic patients, accounting for 17, 12, and 10% of the variation in log(CRP), respectively.

CONCLUSIONS—Serum concentration of AGEs is increased in patients with diabetes and is an independent determinant of plasma CRP levels. Subclinical inflammation in these patients may therefore be partly due to activation of the inflammatory response by AGEs.
Favorable Effects of Pioglitazone and Metformin Compared With Gliclazide on Lipoprotein Subfractions in Overweight Patients With Early Type 2 Diabetes
Authors: Lawrence James M. , Reid Julia , Taylor Gordon J. , Stirling Chris , Reckless John P.D.
Published: March 2007

OBJECTIVE—To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.

RESEARCH DESIGN AND METHODS—Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL1, LDL2, and LDL3) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL3.

RESULTS—HbA1c, triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL3 mass and the LDL3-to-LDL ratio fell with pioglitazone (LDL3 mass 36.2 to 28.0 mg/dl, P < 0.01; LDL3-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL3 reductions were associated with reciprocal LDL1 increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL2 increase (0.3 to 0.4 mmol/l, P < 0.05). HDL3 cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL2-to-HDL3 ratio increased compared with no change on gliclazide.

CONCLUSIONS—For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.
Type 2 Diabetes Prevalence in Asian Americans
Authors: McNeely Marguerite J. , Boyko Edward J.
Published: March 2007

OBJECTIVE—Asians are thought to be at high risk for diabetes, yet there is little population-based information about diabetes in Asian Americans. The purpose of this study was to directly compare the prevalence of type 2 diabetes in Asian Americans with other racial and ethnic groups in the U.S. using data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS).

RESEARCH DESIGN AND METHODS—The BRFSS is a population-based telephone survey of the health status and health behaviors of Americans in all 50 states, Guam, Puerto Rico, and the U.S. Virgin Islands. Subjects included 3,071 Asians, 12,561 blacks, 12,153 Hispanics, 2,299 Native Americans, 626 Pacific Islanders, and 129,116 non-Hispanic whites aged ≥30 years. Subjects who reported a physician-diagnosis of diabetes were considered to have type 2 diabetes unless they were diagnosed before age 30.

RESULTS—Compared with whites, odds ratios (95% CIs) for diabetes, adjusted for age and sex, were 1.0 (0.7–1.4) for Asians, 2.3 (2.1–2.6) for blacks, 2.0 (1.8–2.3) for Hispanics, 2.2 (1.6–2.9) for Native Americans, and 3.1 (1.4–6.8) for Pacific Islanders. Results adjusted for BMI, age, and sex were 1.6 (1.2–2.3) for Asians, 1.9 (1.7–2.2) for blacks, 1.9 (1.6–2.1) for Hispanics, 1.8 (1.3–2.5) for Native Americans, and 3.0 (1.4–6.7) for Pacific Islanders.

CONCLUSIONS—Similar proportions of Asian and non-Hispanic white Americans report having diabetes, but after accounting for the lower BMI of Asians, the adjusted prevalence of diabetes is 60% higher in Asian Americans.
Exercise Capacity and Body Composition as Predictors of Mortality Among Men With Diabetes
Authors: Church Timothy S. , Cheng Yiling J. , Earnest Conrad P. , Barlow Carolyn E. , Gibbons Larry W. , Priest Elisa L. , Blair Steven N.
Published: March 2007

OBJECTIVE—To quantify the relation of fitness to mortality among men with diabetes, adjusted for BMI and within levels of BMI.

RESEARCH DESIGN AND METHODS—In this observational cohort study, we calculated all-cause death rates in men with diabetes across quartiles of fitness and BMI categories. Study participants were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a medical examination, including a maximal exercise test, during 1970 to 1995, with mortality follow-up to 31 December 1996.

RESULTS—We identified 275 deaths during 32,161 person-years of observation. Risk of all-cause mortality was inversely related to fitness. For example, in the fully adjusted model, the risk of mortality was 4.5 (2.6–7.6), 2.8 (1.6–4.7), and 1.6 (0.93–2.76) for the first, second, and third fitness quartiles, respectively, with the fourth quartile (highest fitness level) as the referent (P for trend <0.0001). There was no significant trend across BMI categories for mortality after adjustment for fitness. Similar results were found when the fitness-mortality relation was examined within levels of body composition. In normal-weight men with diabetes, the relative risks of mortality were 6.6 (2.8–15.0), 3.2 (1.4–7.0), and 2.2 (1.1–4.6) for the first, second, and third quartiles of fitness, respectively, as compared with the fourth quartile (P for trend <0.0001). We found similar results in the overweight and obese weight categories.

CONCLUSIONS—There was a steep inverse gradient between fitness and mortality in this cohort of men with documented diabetes, and this association was independent of BMI.
The Treatment of Diabetic Gastroparesis With Botulinum Toxin Injection of the Pylorus
Authors: Lacy Brian E. , Crowell Michael D. , Schettler-Duncan Ann , Mathis Carole , Pasricha Pankaj J.
Published: March 2007

OBJECTIVE—Gastroparesis is a disorder of delayed gastric emptying that is often chronic in nature. Up to 50% of type 1 diabetic subjects have symptoms of gastroparesis, which include nausea, vomiting, and early satiety. Elevated pyloric pressures may be responsible for delayed gastric emptying in diabetic subjects. Botulinum toxin inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle. The aim of this study was to determine whether injection of the pylorus with botulinum toxin in patients with diabetic gastroparesis improves symptoms of gastroparesis, alters gastric emptying scan time, and/or changes weight and insulin use.

RESEARCH DESIGN AND METHODS—This was an open-label trial with age- and sex-matched control subjects from a tertiary care referral center for patients with gastroparesis. Eight type 1 diabetic subjects (six women and two men; mean age 41 years; mean years with diabetes 25.3) who had failed standard therapy were enrolled. Intervention consisted of injection of the pylorus with 200 units of botulinum toxin during upper endoscopy. Symptoms, antropyloric manometry, gastric emptying scan times, weight, and insulin use were all recorded before intervention and during a 12-week follow-up period.

RESULTS—Seven of the eight patients completed the full 12-week follow-up period. No complications were noted. Mean symptom scores declined from 27 to 12.1 (P < 0.01), whereas the SF-36 physical functioning domain also improved (P < 0.05). Four patients noted an increase in insulin use of >5 units/day. Six of the seven patients gained weight (P = 0.05). Gastric emptying scan time improved in four patients.

CONCLUSIONS—Botulinum toxin injection of the pylorus is safe and improves symptoms in patients with diabetic gastroparesis. These results warrant further investigation with a large, double-blind, placebo-controlled trial.
Atrophy of Foot Muscles
Authors: Andersen Henning , Gjerstad Michaela D. , Jakobsen Johannes
Published: March 2007

OBJECTIVE—Diabetic neuropathy is a length-dependent process that leads to reduced muscle strength and atrophy of leg muscles in some patients. We hypothesized that intrinsic foot muscles are atrophied in diabetic neuropathy and that the degree of atrophy is a measure of motor dysfunction closely related to the neuropathic process.

RESEARCH DESIGN AND METHODS—Consecutive cross-sectional magnetic resonance images of the nondominant foot were obtained for stereological determination of the total volume of the intrinsic foot muscles (VFM) in 23 long-term diabetic patients with (n = 15) and without (n = 8) chronic neuropathy and in 23 matched healthy nondiabetic control subjects. Based on clinical examination, nerve conduction studies, and quantitative sensory examination, a neuropathy rank-sum score was calculated for each patient.

RESULTS—Total VFM was 86 ± 52, 165 ± 34, and 168 ± 42 cm3 in neuropathic patients, nonneuropathic patients, and healthy control subjects, respectively (P < 0.001). There was a close inverse relationship between the neuropathy rank-sum score and the VFM (r = −0.75, P < 1 × 10−5).

CONCLUSIONS—Total volume of the foot muscles is halved in patients with diabetic neuropathy. Atrophy of foot muscles is closely related to the severity of neuropathy and reflects motor dysfunction.
Increased 24-h Energy Expenditure in Type 2 Diabetes
Authors: Bitz Christian , Toubro Søren , Larsen Thomas M. , Harder Helle , Rennie Kirsten L. , Jebb Susan A. , Astrup Arne
Published: March 2007

OBJECTIVE—The aim of this study was to determine whether overweight and obese individuals with type 2 diabetes have higher basal and 24-h energy expenditure compared with healthy control subjects before and after adjustment for body composition, spontaneous physical activity (SPA), sex, and age.

RESEARCH DESIGN AND METHODS—Data from 31 subjects with type 2 diabetes and 61 nondiabetic control subjects were analyzed. The 24-h energy expenditure, basal metabolic rate (BMR), and sleeping energy expenditure (EEsleep) between 1:00 a.m. and 6:00 a.m. were measured in whole-body respiratory chambers. Body composition was assessed by dual-energy X-ray absorptiometry (DXA).

RESULTS—No significant differences in unadjusted EEsleep, BMR, and 24-h energy expenditure were observed between the type 2 diabetic group and the control group. After adjustment for fat-free mass (FFM), fat mass, SPA, sex, and age, EEsleep and BMR were, respectively, 7.7 and 6.9% higher in the type 2 diabetic group compared with the control group. This was equivalent to 144 ± 40 kcal/day (P = 0.001) and 139 ± 61 kcal/day (P = 0.026), respectively. Adjusted 24-h energy expenditure was 6.5% higher in the type 2 diabetic group compared with the nondiabetic control subjects (2,679 ± 37 vs. 2,515 ± 23 kcal/day, P = 0.002). In multiple regression analyses, FFM, fat mass, SPA, and diabetes status were all significant determinants of EEsleep and 24-h energy expenditure, explaining 83 and 81% of the variation, respectively.

CONCLUSIONS—This study confirms reports in Pima Indians that basal and 24-h energy expenditure adjusted for body composition, SPA, sex, and age are higher in individuals with type 2 diabetes compared with nondiabetic control subjects and may be even more pronounced in Caucasians.
Circulating Adiponectin and Resistin Levels in Relation to Metabolic Factors, Inflammatory Markers, and Vascular Reactivity in Diabetic Patients and Subjects at Risk for Diabetes
Authors: Shetty Greeshma K. , Economides Panayiotis A. , Horton Edward S. , Mantzoros Christos S. , Veves Aristidis
Published: March 2007

OBJECTIVE—Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels.

RESEARCH DESIGN AND METHODS—Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-controlled study.

RESULTS—In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered.

CONCLUSIONS—We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin’s associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin.
Antihypertensive Therapy and Incidence of Type 2 Diabetes in an Elderly Cohort
Authors: Padwal Raj , Mamdani Muhammad , Alter David A. , Hux Jan E. , Rothwell Deanna M. , Tu Karen , Laupacis Andreas
Published: March 2007

OBJECTIVE—The aim of this study was to determine whether the incidence of type 2 diabetes differed among elderly users of four major antihypertensive drug classes.

RESEARCH DESIGN AND METHODS—This was a retrospective, observational cohort study of previously untreated elderly patients (aged ≥66 years) identified as new users of an antihypertensive drug class between April 1995 and March 2000. Using a Cox proportional hazards model, the primary analysis compared diabetes incidence in users of ACE inhibitors, β-blockers, and calcium channel blockers (CCBs), with thiazide diuretics allowed as second-line therapy. In the secondary analysis, thiazide diuretics were added as a fourth study group.

RESULTS—In the multivariable-adjusted primary analysis (n = 76,176), neither ACE inhibitor use (hazard ratio 0.96 [95% CI 0.84–1.1]) nor β-blocker use (0.86 [0.74–1.0]) was associated with a statistically significant difference in type 2 diabetes incidence compared with the CCB control group. In the secondary analysis (n = 100,653), compared with CCB users, type 2 diabetes incidence was not significantly different between users of ACE inhibitors (0.97 [0.83–1.1]), β-blockers (0.84 [0.7–1.0]), or thiazide diuretics (1.0 [0.89–1.2]).

CONCLUSIONS—Type 2 diabetes incidence did not significantly differ among users of the major antihypertensive drug classes in this elderly, population-based administrative cohort. These results do not support the theory that different antihypertensive drug classes are relatively more or less likely to cause diabetes.
Severe Hypo-α-Lipoproteinemia During Treatment With Rosiglitazone
Authors: Sarker Anita , Semple Robert K. , Dinneen Sean F. , O’Rahilly Stephen , Martin Steven C.
Published: March 2007

Thiazolidinedione drugs are in widespread use for the treatment of type 2 diabetes. In addition to improving insulin sensitivity, they generally result in a modest elevation of plasma HDL cholesterol. We report three patients, all of whom had preexisting diabetic dyslipidemia, who showed a profound reduction in plasma HDL cholesterol and apolipoprotein AI levels soon after the initiation of rosiglitazone therapy. In all three patients, HDL cholesterol levels returned to normal following drug withdrawal. The fact that this phenomenon was not seen in >1,400 patients studied in clinical trials indicates that it is likely to be rare and idiosyncratic. Until the frequency of this adverse reaction is clearer, it would seem advisable to ensure that plasma HDL cholesterol is documented before and rechecked after commencement of thiazolidinedione therapy.
Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections
Authors: Retnakaran Ravi , Hochman Jackie , DeVries J. Hans , Hanaire-Broutin Helene , Heine Robert J. , Melki Vincent , Zinman Bernard
Published: March 2007

OBJECTIVE—Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens.

RESEARCH DESIGN AND METHODS—We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes.

RESULTS—The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII − MDII) was 0.35% (95% CI −0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII − MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events.

CONCLUSIONS—When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.
Physical Activity and Television Viewing in Relation to Risk of Undiagnosed Abnormal Glucose Metabolism in Adults
Authors: Dunstan David W. , Salmon Jo , Owen Neville , Armstrong Timothy , Zimmet Paul Z. , Welborn Timothy A. , Cameron Adrian J. , Dwyer Terence , Jolley Damien , Shaw Jonathan E. ,   on behalf of the AusDiab Steering Committee
Published: March 2007

OBJECTIVE—The goal of this study was to assess the associations of physical activity time and television (TV) time with risk of “undiagnosed” abnormal glucose metabolism in Australian adults.

RESEARCH DESIGN AND METHODS—This population-based cross-sectional study using a stratified cluster design involving 42 randomly selected Census Collector Districts across Australia included 8,299 adults aged 25 years or older who were free from new type 2 diabetes and self-reported ischemic disease and did not take lipid-lowering or antihypertensive drugs. Abnormal glucose metabolism (impaired fasting glycemia [IFG], impaired glucose tolerance [IGT], or new type 2 diabetes) was based on an oral glucose tolerance test. Self-reported physical activity time and TV time (previous week) were assessed using interviewer-administered questionnaires.

RESULTS—After adjustment for known confounders and TV time, the odds ratio (OR) of having abnormal glucose metabolism was 0.62 (95% CI 0.41–0.96) in men and 0.71 (0.50–1.00) in women for those engaged in physical activity ≥2.5 h/week compared with those who were sedentary (0 h/week). The ORs of having abnormal glucose metabolism were 1.16 (0.79–1.70) in men and 1.49 (1.12–1.99) in women who watched TV >14 h/week compared with those who watched ≤7.0 h/week. Higher TV viewing (>14 h/week) was also associated with an increased risk of new type 2 diabetes in men and women and IGT in women compared with those watching <14 h/week. Total physical activity of ≥2.5 h/week was associated with a reduced risk of IFG, IGT, and new type 2 diabetes in both sexes; however, only the association with IGT in women was statistically significant.

CONCLUSIONS—These findings suggest a protective effect of physical activity and a deleterious effect of TV time on the risk of abnormal glucose metabolism in adults. Population strategies to reduce risk of abnormal glucose metabolism should focus on reducing sedentary behaviors such as TV time, as well as increasing physical activity.
Renal Impairment Associated With Diabetes in the Elderly
Authors: Wasén Elise , Isoaho Raimo , Mattila Kari , Vahlberg Tero , Kivelä Sirkka-Liisa , Irjala Kerttu
Published: March 2007

OBJECTIVE—To characterize renal impairment associated with diabetes in older adults by serum markers of glomerular filtration rate and microalbuminuria tests.

RESEARCH DESIGN AND METHODS—The study population consisted of 187 diabetic and 1,073 nondiabetic subjects (age range 64–100 years) participating in a cross-sectional, population-based survey in southwestern Finland. Renal function was estimated by serum cystatin C (Cys C), serum creatinine (Cr), and the urinary albumin-to-creatinine ratio, and determinants of elevated levels were assessed by multivariate analysis.

RESULTS—Diabetes, compared to hypertension, was a more powerful determinant of elevated Cys C and Cr levels in the very old (age ≥80 years), whereas the impact of hypertension was more pronounced in the younger group (age <80 years). The prevalence of microalbuminuria among diabetic subjects was 29.7%, and 15% had elevated Cr levels, whereas the prevalence of elevated Cys C levels varied considerably depending on whether adult or age-adjusted reference limits were used (64.7 vs. 21.4%). In 64.1% of diabetic subjects with elevated Cys C levels based on age-adjusted reference limits and in 48.2% of subjects with elevated Cr levels, microalbuminuria was absent.

CONCLUSIONS—The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research.
Preventative Effects of Rosiglitazone on Restenosis After Coronary Stent Implantation in Patients With Type 2 Diabetes
Authors: Choi Donghoon , Kim Soo-Kyung , Choi Sung-Hee , Ko Young-Guk , Ahn Chul-Woo , Jang Yangsoo , Lim Sung-Kil , Lee Hyun-Chul , Cha Bong-Soo
Published: March 2007

OBJECTIVE—Despite the popularity of coronary stenting in coronary artery disease (CAD), restenosis remains a challenging clinical problem. This study evaluated the efficacy of rosiglitazone for preventing in-stent restenosis in type 2 diabetic patients.

RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized, case-controlled trial involving 95 diabetic patients with CAD who were randomly assigned to either the control or rosiglitazone group (48 and 47 patients, respectively). Quantitative coronary angiography (QCA) was performed at study entry and again at 6-month follow-up. The primary end point was the restenosis rate, which was determined by QCA.

RESULTS—Eighty-three patients (45 patients with 55 lesions in the control group and 38 patients with 51 lesions in the rosiglitazone group) completed follow-up angiography. Rosiglitazone treatment for 6 months reduced fasting insulin concentration. The high-sensitivity C-reactive protein concentration was significantly reduced in the rosiglitazone group compared with that in the control group (from 2.92 ± 1.98 to 0.62 ± 0.44 mg/l, P < 0.001 vs. from 2.01 ± 1.33 to 1.79 ± 1.22 mg/l, P = NS). However, the baseline and follow-up glucose and lipid concentrations were not different between two groups. The rate of in-stent restenosis was significantly reduced in the rosiglitazone group compared with the control group (for stent lesions: 17.6 vs. 38.2%, P = 0.030). The rosiglitazone group had a significantly lower degree of diameter stenosis (23.0 ± 23.4% vs. 40.9 ± 31.9%, P = 0.004) compared with the control group.

CONCLUSIONS—We demonstrated that treatment with rosiglitazone significantly reduces in-stent restenosis in diabetic patients with CAD who underwent coronary stent implantation.
Depressive Symptoms, Insulin Resistance, and Risk of Diabetes in Women at Midlife
Authors: Everson-Rose Susan A. , Meyer Peter M. , Powell Lynda H. , Pandey Dilip , Torréns Javier I. , Kravitz Howard M. , Bromberger Joyce T. , Matthews Karen A.
Published: March 2007

OBJECTIVE—To examine depression and 3-year change in insulin resistance and risk of diabetes and whether associations vary by race.

RESEARCH DESIGN AND METHODS—We analyzed data from 2,662 Caucasian, African-American, Hispanic, Japanese-American, and Chinese-American women without a history of diabetes from the Study of Women’s Health Across the Nation. We estimated regression coefficients and odds ratios to determine whether depression (Center for Epidemiological Studies Depression Scale score ≥16) predicted increases in homeostasis model assessment of insulin resistance (HOMA-IR) and greater risk of incident diabetes, respectively, over 3 years.

RESULTS—Mean baseline HOMA-IR was 1.31 (SD 0.86) and increased 0.05 units per year for all women (P < 0.0001). A total of 97 incident cases of diabetes occurred. Depression was associated with absolute levels of HOMA-IR (P < 0.04) but was unrelated to changes in HOMA-IR; associations did not vary by race. The association between depression and HOMA-IR was eliminated after adjustment for central adiposity (P = 0.85). Depression predicted a 1.66-fold greater risk of diabetes (P < 0.03), which became nonsignificant after adjustment for central adiposity (P = 0.12). We also observed a depression-by-race interaction (P < 0.05) in analyses limited to Caucasians and African Americans, the only groups with enough diabetes cases to reliably test this interaction. Race-stratified models showed that depression predicted 2.56-fold greater risk of diabetes in African Americans only, after risk factor adjustment (P = 0.008).

CONCLUSIONS—Depression is associated with higher HOMA-IR values and incident diabetes in middle-aged women. These associations are mediated largely through central adiposity. However, African-American women with depression experience increased risk of diabetes independent of central adiposity and other risk factors.
Alcohol Consumption and the Prevalence of the Metabolic Syndrome in the U.S.
Authors: Freiberg Matthew S. , Cabral Howard J. , Heeren Tim C. , Vasan Ramachandran S. , Curtis Ellison R.
Published: March 2007

OBJECTIVE—The aim of this study was to examine the relations of alcohol consumption to the prevalence of the metabolic syndrome and its components in the U.S. population.

RESEARCH DESIGN AND METHODS—We performed a cross-sectional analysis on data from 8,125 participants from the Third National Health and Nutrition Examination Survey who were evaluated for each component of the metabolic syndrome, using the National Cholesterol Education Program criteria, fasting insulin, and alcohol consumption. Current alcohol consumption was defined as ≥1 alcoholic drink per month.

RESULTS—After adjustment for age, sex, race/ethnicity, education, income, tobacco use, physical activity, and diet, subjects who consumed 1–19 and ≥20 drinks of alcohol per month had odds ratios (ORs) for the prevalence of the metabolic syndrome of 0.65 and 0.34, respectively (P < 0.05 for all), compared with current nondrinkers. These findings were particularly noteworthy for beer and wine drinkers. The association of ≥20 alcoholic drinks per month with the prevalence of the metabolic syndrome was consistent across ethnicities but was most striking in white men and women (ORs 0.35 and 0.22, respectively; P < 0.05). Alcohol consumption was significantly and inversely associated with the prevalence of the following three components of the metabolic syndrome: low serum HDL cholesterol, elevated serum triglycerides, high waist circumference, as well as hyperinsulinemia (P < 0.05 for all).

CONCLUSIONS—Mild to moderate alcohol consumption is associated with a lower prevalence of the metabolic syndrome, with a favorable influence on lipids, waist circumference, and fasting insulin. This association was strongest among whites and among beer and wine drinkers.
Screening for Type 2 Diabetes and Impaired Glucose Metabolism
Authors: Colagiuri Stephen , Hussain Zafirul , Zimmet Paul , Cameron Adrian , Shaw Jonathan
Published: March 2007

OBJECTIVE—To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism.

RESEARCH DESIGN AND METHODS—The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians.

RESULTS—The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using HbA1c instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG.

CONCLUSIONS—The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including HbA1c measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.
Health-Related Quality of Life and Health-Adjusted Life Expectancy of People With Diabetes in Ontario, Canada, 1996–1997
Authors: Manuel Douglas G. , Schultz Susan E.
Published: March 2007

OBJECTIVE—To estimate the burden of illness from diabetes using a population health survey linked to a population-based diabetes registry.

RESEARCH DESIGN AND METHODS—Measures of health-related quality of life (HRQOL) from the 1996/97 Ontario Health Survey (n = 35,517) were combined with diabetes prevalence and mortality data from the Ontario Diabetes Database (n = 487,576) to estimate the impact of diabetes on life expectancy, health-adjusted life expectancy (HALE), and HRQOL.

RESULTS—Life expectancy of people with diabetes was 64.7 and 70.7 years for men and women, respectively—12.8 and 12.2 years less than that for men and women without diabetes. Diabetes had a large impact on instrumental and basic activities of daily living, more so than on functional health. HALE was 58.3 and 62.7 years, respectively, for men and women—11.9 and 10.7 years less than that of men and women without diabetes. Eliminating diabetes would increase Ontario life expectancy by 2.8 years for men and 2.6 years for women; HALE would increase by 2.7 and 3.2 years for men and women, respectively.

CONCLUSIONS—The burden of illness from diabetes in Ontario is considerable. Efforts to reduce diabetes would likely result in a “compression of morbidity.” An approach of estimating diabetes burden using linked data sources provides a robust approach for the surveillance of diabetes.
Intensification of Therapeutic Approaches Reduces Mortality in Diabetic Patients With Acute Myocardial Infarction
Authors: Schnell Oliver , Schäfer Oliver , Kleybrink Sonja , Doering Wittich , Standl Eberhard , Otter Wolfgang
Published: March 2007

OBJECTIVE—The myocardial infarction (MI) registry of the Academic Schwabing Hospital, Munich, investigates the hospital course of diabetic and nondiabetic patients with acute MI. The aim of this study was to improve quality care management and to compare hospital mortality and therapeutic approaches (i.e., PTCA, stenting, GPIIb/IIIa receptor antagonists, glucose-insulin infusion).

RESEARCH DESIGN AND METHODS—Data of diabetic patients and nondiabetic patients were analyzed. All diabetic and nondiabetic subjects who were admitted in 1999 and 2001 were included: 1999, 126 (38%) diabetic and 204 (62%) nondiabetic patients; 2001, 91 (31%) diabetic and 205 (59%) nondiabetic patients.

RESULTS—In 1999, coronary angiography (P < 0.01), percutaneous transluminal coronary angioplasty (PTCA) (P < 0.001), and stenting (P < 0.001) were performed less frequently in diabetic than in nondiabetic patients. During this period, total hospital mortality (29 vs. 16%, P < 0.01) and mortality within 24 h after admission (14 vs. 5%, P = 0.01) were higher in diabetic than in nondiabetic patients. In 2001, frequencies of coronary angiography, PTCA, and stenting were increased in diabetic patients (P < 0.001 vs. 1999), and the interventions were comparable with those performed in nondiabetic patients. Furthermore, glucose-insulin infusion was administered in 46% of diabetic subjects. In 2001, total hospital mortality decreased to 17% in diabetic subjects (P = 0.028 vs. 1999) and mortality within 24 h after admission declined to 4% (P = 0.027 vs. 1999). Logistic regression analysis revealed that an increase in the number of therapeutic approaches (also when adjusted for clinical variables) is associated with a reduction in mortality of diabetic patients with acute MI (adjusted odds ratio 0.14, P < 0.0001).

CONCLUSIONS—Intensification of multiple advanced therapeutic strategies in diabetic patients with acute MI enables a substantial reduction in hospital mortality. The enforcement leads to rates of hospital mortality that are comparable to those of nondiabetic patients.
Elevated White Blood Cell Count in Subjects With Impaired Glucose Tolerance
Authors: Ohshita Kayo , Yamane Kiminori , Hanafusa Miki , Mori Hiroshi , Mito Kazuyo , Okubo Masamichi , Hara Hitoshi , Kohno Nobuoki
Published: March 2007

OBJECTIVE—Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) differ in their risk of all-cause and cardiovascular mortality, but previous cross-sectional studies have suggested little difference in their levels of lipids or blood pressure. We compared the white blood cell (WBC) count between subjects with IFG and IGT.

RESEARCH DESIGN AND METHODS—The subjects were 4,720 nondiabetic Japanese men aged 24–84 years. Based on the 75-g oral glucose tolerance test, the subjects were classified into the following four groups: normal fasting glucose/normal glucose tolerance (n = 3,753), isolated IFG (n = 290), isolated IGT (n = 476), and IFG/IGT (n = 201). We compared the WBC count among the four groups and investigated variables that showed a significant association with the WBC count.

RESULTS—The isolated IGT group had a significantly higher WBC count than the isolated IFG group (6,530 vs. 6,210/mm3, P < 0.05). By stepwise analyses, age, triglycerides, HDL cholesterol, fasting insulin, and 2-h postchallenge plasma glucose (PG) showed an independent association with the WBC count (adjusted R2 = 0.057). In the analysis stratified by smoking status, the WBC count was independently associated with 2-h PG and triglycerides, irrespective of smoking status.

CONCLUSIONS—Individuals with isolated IGT had a significantly higher WBC count than those with isolated IFG. The WBC count was associated with 2-h PG and various components of the metabolic syndrome.
Leucine 7 to Proline 7 Polymorphism in the Preproneuropeptide Y Is Associated With Proteinuria, Coronary Heart Disease, and Glycemic Control in Type 1 Diabetic Patients
Authors: Pettersson-Fernholm Kim , Karvonen Matti K. , Kallio Jaana , Forsblom Carol M. , Koulu Markku , Pesonen Ullamari , Fagerudd Johan A. , Groop Per-Henrik ,   FinnDiane Study Group
Published: March 2007

OBJECTIVE—Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS—A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population.

RESULTS—The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA1c 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA1c (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses.

CONCLUSIONS—We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
A 5-Year Randomized Controlled Study of Learning, Problem Solving Ability, and Quality of Life Modifications in People With Type 2 Diabetes Managed by Group Care
Authors: Trento Marina , Passera Pietro , Borgo Enrica , Tomalino Marco , Bajardi Marina , Cavallo Franco , Porta Massimo
Published: March 2007

OBJECTIVE—To study time course changes in knowledge, problem solving ability, and quality of life in patients with type 2 diabetes managed by group compared with individual care and education.

RESEARCH DESIGN AND METHODS—We conducted a 5-year randomized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit. There were 120 patients with non–insulin-treated type 2 diabetes enrolled and randomly allocated to group or individual care. Eight did not start and 28 did not complete the study. The main outcome measures were knowledge of diabetes, problem solving ability, quality of life, HbA1c, BMI, and HDL cholesterol.

RESULTS—Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects (P < 0.001 for both). Quality of life improved from year 2 with group care but worsened with individual care (P < 0.001). HbA1c level progressively increased over 5 years among control subjects (+1.7%, 95% CI 1.1–2.2) but not group care patients (+0.1%, −0.5 to 0.4), in whom BMI decreased (−1.4, −2.0 to −0.7) and HDL cholesterol increased (+0.14 mmol/l, 0.07–0.22).

CONCLUSIONS—Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and settings tailored to their needs. Traditional one-to-one care, although delivered according to optimized criteria, is associated with progressive deterioration of knowledge, problem solving ability, and quality of life. Better cognitive and psychosocial results are associated with more favorable clinical outcomes.