bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Amadori-Modified Plasma Proteins in Type 2 Diabetes and the Effect of Short-Term Intensive Insulin Treatment
Authors: Jaleel Abdul , Halvatsiotis Panagiotis , Williamson Brian , Juhasz Peter , Martin Stephen , Nair K. Sreekumaran
Published: March 2007

OBJECTIVE—Growing evidence supports that nonenzymatic glycation products may cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are the intermediate products of nonenzymatic glycation and constitute the forms of glycated proteins in diabetes. The objective of the current study was to utilize two-dimensional gel electrophoresis, Western blot, and mass spectrometry to identify Amadori-modified plasma proteins in type 2 diabetic patients with poor glycemic control and assess the impact of short-term insulin treatment on the glycation of these proteins.

RESEARCH DESIGN AND METHODS—We compared eight type 2 diabetic subjects (aged 56 ± 3 years and BMI 29.7 ± 0.9 kg/m2) with an average diabetes duration of 8.5 years (range 3–19) with equal numbers of weight-matched (aged 56 ± 2 years and BMI 30.1 ± 10.0 kg/m2) and lean (aged 58 ± 2 years and BMI 25 ± 00.5 kg/m2) nondiabetic subjects who have no first-degree relatives with diabetes. Two separate blood samples were collected from the type 2 diabetic subjects, one following 2 weeks of withdrawal of all antidiabetic medications (T2D−; plasma glucose 12.6 ± 1.0 mmol/l) and another following 10 days of intensive insulin treatment (T2D+; plasma glucose 5.5 ± 0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel electrophoresis. Western blot analysis was performed, and several proteins, which reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by tandem mass spectrometry.

RESULTS—No significant differences in the glycation of proteins between the obese and lean groups were noted, but type 2 diabetic patients had several proteins with higher glycation than the control groups. We identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody upon intensive insulin treatment. A significant (P < 0.03) difference in Amadori modification was observed between the T2D− and control subjects for all these proteins except the Ig light chain. Insulin treatment reduced Amadori modification of albumin (23.2%, P < 0.02), fibrin (34.6%, P < 0.001), Ig heavy chain constant region (20.7%, P < 0.05), transferrin (25.4%, P < 0.04), and Ig light chain (13%, P < 0.02). In addition, Western blot analysis of two-dimensional gel electrophoresis identified α-fibrinogen precursor, β-fibrinogen precursor, fibrinogen γ-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment.

CONCLUSIONS—The current approach offers the opportunity to identify Amadori modification of many proteins that may cause functional alterations and offers the potential for monitoring short-term glycemic control in diabetic patients.
Moderate Alcohol Consumption Lowers the Risk of Type 2 Diabetes
Authors: Koppes Lando L.J. , Dekker Jacqueline M. , Hendriks Henk F.J. , Bouter Lex M. , Heine Robert J.
Published: March 2007

OBJECTIVE—This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI.

RESEARCH DESIGN AND METHODS—The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years.

RESULTS—After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed ≤6 g/day alcohol was 0.87 (95% CI 0.79–0.95). For the moderate consumption ranges of 6–12, 12–24, and 24–48 g/day, RRs of 0.70 (0.61–0.79), 0.69 (0.58–0.81), and 0.72 (0.62–0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (≥48 g/day) was equal to that in nonconsumers (1.04 [0.84–1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI.

CONCLUSIONS—The present evidence from observational studies suggests an ∼30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of ≥48 g/day.
The Effects of Type 1 Diabetes on Cognitive Performance
Authors: Brands Augustina M.A. , Biessels Geert Jan , de Haan Edward H.F. , Kappelle L. Jaap , Kessels Roy P.C.
Published: March 2007

OBJECTIVE—To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control.

RESEARCH DESIGN AND METHODS—MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen’s d), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies.

RESULTS—A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence (d = −0.7), speed of information processing (d = −0.3), psychomotor efficiency (d = −0.6), visual (d = −0.4) and sustained attention (d = −0.3), cognitive flexibility (d = −0.5), and visual perception (d = −0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control.

CONCLUSIONS—In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.
Impact of Fasting Plasma Glucose Levels on Gastric Cancer Incidence in a General Japanese Population
Authors: Yamagata Hajime , Kiyohara Yutaka , Nakamura Shotaro , Kubo Michiaki , Tanizaki Yumihiro , Matsumoto Takayuki , Tanaka Keiichi , Kato Isao , Shirota Tomoko , Iida Mitsuo
Published: March 2007

OBJECTIVE—Several studies have shown associations between diabetes and various types of cancer other than gastric cancer. The aim of this cohort study was to evaluate the impact of fasting plasma glucose (FPG) levels on gastric cancer occurrence.

RESEARCH DESIGN AND METHODS—A total of 2,466 Japanese subjects aged ≥40 years were stratified into three groups according to FPG tertiles (<5.3 mmol/l, low FPG; 5.3–5.8 mmol/l, modest FPG; >5.8 mmol/l, high FPG) and followed up prospectively for 9 years.

RESULTS—During the follow-up, 66 subjects experienced gastric cancer. In men, the age-adjusted incidences were significantly higher in the modest-FPG (7.0 per 1,000 person-years, P < 0.05) and high-FPG (7.2, P < 0.05) groups than in the low-FPG group (2.2). In women, the high-FPG group also had a significantly higher age-adjusted incidence of gastric cancer compared with the low-FPG group (2.5 vs. 0.8, P < 0.05). The multivariate analysis with Cox’s proportional hazards model revealed that the risks of gastric cancer in the modest-FPG (relative risk [RR] 2.3 [95% CI 1.1–5.0]) and high-FPG (3.1 [1.5–6.4]) groups were significantly higher than that in the low-FPG group, even after adjusting for other comprehensive risk factors, including Helicobacter pylori status, smoking, and dietary factors. However, this FPG-cancer association was observed only among H. pylori–seropositive subjects.

CONCLUSIONS—Our findings suggest that a modest increase in FPG is a risk factor for gastric cancer and that hyperglycemia is a possible cofactor increasing the risk posed by Helicobacter pylori infection.
The Prevalence of Diabetes and Impaired Glucose Tolerance in Sivas, Central Anatolia, Turkey
Authors: Özdemir Levent , Topçu Saniye , Nadir Işılay , Nur Naim , Arslan Seher , Sümer Haldun
Published: March 2007

OBJECTIVE—The aim of this study was to determine type 2 diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) prevalence in Sivas, Turkey.

RESEARCH DESIGN AND METHODS—This cross-sectional study was conducted in the city center of Sivas. The study population of 771 subjects was selected by the cluster sampling method from 115,998 individuals aged ≥30 years. Participants with fasting venous plasma glucose concentrations <100 mg/dl were classified as “normal.” Diabetes was diagnosed in participants if they had fasting blood glucose levels ≥126 mg/dl. An oral glucose tolerance test (OGTT) was performed in subjects with fasting blood glucose levels ≥100 mg/dl and <126 mg/dl.

RESULTS—According to the fasting blood glucose levels of the 771 subjects, 44 (5.7%) had diabetes. OGTTs were performed in 80 (10.4%) subjects. According to OGTT results, there were 5 subjects with diabetes, 20 subjects with IGT (2.6%), and 55 subjects with IFG (7.1%). The combined prevalence of IFG and IGT was 9.7%. After OGTT, the total number of diabetic subjects was determined to be 49 (6.4%). Twenty-four (3.1%) of the subjects had a previous diagnosis of diabetes. Multivariate analyses showed that age, sex, hypertension, cigarette smoking, obesity, and family history of diabetes were risk factors for type 2 diabetes (P < 0.05).

CONCLUSIONS—Diabetes incidence increases with changes in dietary habits and lifestyle. Education is particularly important for public health, as the community may then have required knowledge about the disease and its risk factors.
The Relation Between Hyperglycemia and Outcomes in 2,471 Patients Admitted to the Hospital With Community-Acquired Pneumonia
Authors: McAlister Finlay A. , Majumdar Sumit R. , Blitz Sandra , Rowe Brian H. , Romney Jacques , Marrie Thomas J.
Published: March 2007

OBJECTIVE— To examine whether hyperglycemia at the time of presentation was associated with outcomes in patients admitted to non–intensive care settings with community-acquired pneumonia (CAP).

RESEARCH DESIGN AND METHODS— Prospective cohort study of consecutive patients admitted to six hospitals between 15 November 2000 and 14 November 2002.

RESULTS— Of the 2,471 patients in this study (median age 75 years), 279 (11%) had serum glucose at presentation >11 mmol/l: 178 of the 401 patients (44%) with a prior diagnosis of diabetes and 101 of the 2,070 patients (5%) without a history of diabetes. Of patients hospitalized with CAP, 9% died and 23% suffered an in-hospital complication. Compared with those with values ≤11 mmol/l, patients with an admission glucose >11 mmol/l had an increased risk of death (13 vs. 9%, P = 0.03) and in-hospital complications (29 vs. 22%, P = 0.01). Compared with those patients with admission glucose ≤6.1 mmol/l, the mortality risk was 73% higher (95% CI 12–168%) and the in-hospital complication risk was 52% higher (12–108%) in patients with admission glucose >11 mmol/l. Even after adjustment for factors in the Pneumonia Severity Index, hyperglycemia on admission remained significantly associated with subsequent adverse outcomes: for each 1-mmol/l increase, risk of in-hospital complications increased 3% (0.2–6%).

CONCLUSIONS— Hyperglycemia on admission is independently associated with adverse outcomes in patients with CAP, with the increased risks evident at lower glucose levels than previously reported.
The Metabolic Syndrome and Concentrations of C-Reactive Protein Among U.S. Youth
Authors: Ford Earl S. , Ajani Umed A. , Mokdad Ali H.
Published: March 2007

OBJECTIVE—Adults with the metabolic syndrome show biochemical evidence of low-grade inflammation. We sought to examine whether this is true among U.S. youth with the metabolic syndrome.

RESEARCH DESIGN AND METHODS—We used data from 1,366 participants aged 12–17 years from the National Health and Nutrition Examination Survey 1999–2000. A modification of the definition of the metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. C-reactive protein (CRP) was measured by latex-enhanced nephelometry.

RESULTS—Mean and median concentrations of CRP were higher among participants who had the metabolic syndrome (mean 3.8 mg/l, geometric mean 1.8 mg/l) than among those who did not (mean 1.4 mg/l, geometric mean 0.4 mg/l). The percentage of participants with a concentration of CRP >3.0 mg/l was 38.4% among those with the metabolic syndrome and 10.3% among those without the syndrome (P = 0.007). Of the five components of the syndrome, only abdominal obesity was significantly and independently associated with log-transformed concentrations of CRP in multiple linear regression analysis.

CONCLUSIONS—Our results show that a large percentage of children and adolescents with the metabolic syndrome have elevated concentrations of CRP. Whether the elevated concentrations of CRP among children and adolescents who have the metabolic syndrome predict future adverse health events remains to be determined.
Cardiorespiratory Fitness Attenuates Metabolic Risk Independent of Abdominal Subcutaneous and Visceral Fat in Men
Authors: Lee SoJung , Kuk Jennifer L. , Katzmarzyk Peter T. , Blair Steven N. , Church Timothy S. , Ross Robert
Published: March 2007

OBJECTIVE—Moderate to high levels of cardiorespiratory fitness (CRF) are associated with a lower risk of the metabolic syndrome and all-cause mortality. Unknown is whether CRF attenuates health risk for a given level of abdominal visceral fat, subcutaneous fat, and/or waist circumference.

RESEARCH DESIGN AND METHODS—The sample studied comprised 297 apparently healthy men with available computed tomography or magnetic resonance imaging scans of the abdomen, metabolic data, and maximal treadmill exercise test results. Men were categorized into low-CRF (20%, n = 56), moderate-CRF (40%, n = 94), and high-CRF (40%, n = 147) groups based on age and exercise test results. All analyses were adjusted for age.

RESULTS—For a given level of waist circumference, visceral fat, or subcutaneous fat, the high-CRF group had lower triglyceride levels (P < 0.05) and higher HDL cholesterol levels than the low- or moderate-CRF groups. There was a significant group interaction (P < 0.01) for blood pressure, indicating that the increase in blood pressure per unit increase in visceral fat or waist circumference was greater in men in the low-CRF group compared with the high-CRF group. The relative risks of having the metabolic syndrome were 1.8 (95% CI 1.0–3.1) and 1.6 (0.9–2.7) times higher in the low- and moderate-CRF groups, respectively, compared with the high-CRF group after adjusting for age, visceral fat, and subcutaneous fat (P for trend = 0.06).

CONCLUSIONS—High levels of CRF are associated with a substantial reduction in health risk for a given level of visceral and subcutaneous fat.
Pregnancy Experience Among Women With and Without Gestational Diabetes in the U.S., 1995 National Survey of Family Growth
Authors: Saydah Sharon H. , Chandra Anjani , Eberhardt Mark S.
Published: March 2007

OBJECTIVE—To compare the pregnancy experience among women with and without gestational diabetes mellitus (GDM) using a nationally representative survey.

RESEARCH DESIGN AND METHODS—We analyzed data from the 1995 National Survey of Family Growth conducted by National Center for Health Statistics on 3,088 women age 15–44 years with at least one pregnancy between 1991 and 1995 to compare demographics, fecundity, and pregnancy experience by GDM (n = 116) or nondiabetes (n = 2,969) status.

RESULTS—Among women with a pregnancy during 1991–1995, 3.6% reported GDM history. Women with GDM were older at age of delivery (31.8 years) than women without diabetes (29.0 years, P < 0.001). There was no significant difference between the groups by race/ethnicity. Compared with women without diabetes, women with gestational diabetes were more likely to report being currently surgically sterile (20.4 vs. 32.6%) or having impaired fecundity (12.6 vs. 19.7%, P < 0.001). GDM patients were more likely to have had a caesarean section than those without diabetes (31.7 vs. 20.9%, P = 0.02) and were more likely to report at least one of six additional nonroutine medical complications during pregnancy than nondiabetic patients (48.8 vs. 17.1%, P < 0.001). The odds ratio of a maternal medical complication during pregnancy for women with GDM compared with nondiabetic women, after adjusting for age at pregnancy and nongestational hypertension, was 4.3 (95% CI 2.7–6.8).

CONCLUSIONS—These findings suggest that pregnancies in women with GDM are more likely to be associated with maternal medical complications compared with pregnancies in women without diabetes.
The Influence of Adiponectin Gene Polymorphism on the Rosiglitazone Response in Patients With Type 2 Diabetes
Authors: Kang Eun Seok , Park So Young , Kim Hyeong Jin , Ahn Chul Woo , Nam Moonsuk , Cha Bong Soo , Lim Sung Kil , Kim Kyung Rae , Lee Hyun Chul
Published: March 2007

OBJECTIVE —The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms.

RESEARCH DESIGN AND METHODS —A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined.

RESULTS —Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA1c value in the carriers of the GG genotype than in the carriers of the other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P = 0.001). In the haplotype analysis, the reductions in the FPG and HbA1c levels were smaller for the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P = 0.003).

CONCLUSIONS —These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients.
Reduction in Cardiovascular Events With Atorvastatin in 2,532 Patients With Type 2 Diabetes
Authors: Sever Peter S. , Poulter Neil R. , Dahlöf Björn , Wedel Hans , Collins Rory , Beevers Gareth , Caulfield Mark , Kjeldsen Sverre E. , Kristinsson Arni , McInnes Gordon T. , Mehlsen Jesper , Nieminen Markku , O’Brien Eoin , Ostergren Jan ,   for the ASCOT Investigators
Published: March 2007

OBJECTIVE—This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease.

RESEARCH DESIGN AND METHODS—In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors were randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at randomization were compared.

RESULTS—During a median follow-up of 3.3 years, concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were ∼1 mmol/l lower in those allocated atorvastatin compared with placebo. There were 116 (9.2%) major cardiovascular events or procedures in the atorvastatin group and 151 (11.9%) events in the placebo group (hazard ratio 0.77, 95% CI 0.61–0.98; P = 0.036). For the individual components of this composite end point, the number of events occurring in the diabetes subgroup was small. Therefore, although fewer coronary events (0.84, 0.55–1.29; P = 0.14) and strokes (0.67, 0.41–1.09; P = 0.66) were observed among the patients allocated atorvastatin, these reductions were not statistically significant.

CONCLUSIONS—Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations. The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes. Allocation to atorvastatin prevented ∼9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year.
Use of the Diabetes Risk Score for Opportunistic Screening of Undiagnosed Diabetes and Impaired Glucose Tolerance
Authors: Franciosi Monica , De Berardis Giorgia , Rossi Maria C.E. , Sacco Michele , Belfiglio Maurizio , Pellegrini Fabio , Tognoni Gianni , Valentini Miriam , Nicolucci Antonio ,   for the IGLOO Study Group
Published: March 2007

OBJECTIVE—To evaluate an opportunistic screening strategy addressed to individuals with one or more cardiovascular risk factor, based on the Diabetes Risk Score (DRS) as the initial instrument, for the identification of individuals with type 2 diabetes or impaired glucose tolerance (IGT).

RESEARCH DESIGN AND METHODS—The DRS, a simple self-administered questionnaire, was completed by individuals identified by general practitioners and presenting with one or more cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance test (OGTT). The optimal DRS cutoff was calculated by applying the receiver-operating characteristic curve.

RESULTS—Overall, 1,377 individuals aged between 55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a marked variation according to glucose metabolism categories, as follows: 8.7 ± 3.0 in normoglycemic individuals, 9.5 ± 3.1 in individuals with impaired fasting glucose, 9.9 ± 3.3 in individuals with IGT, and 12.0 ± 3.5 in individuals with type 2 diabetes. The receiver-operating characteristic curve showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity 45%. The use of the DRS as an initial screening instrument, followed by the measurement of fasting blood glucose in individuals with a score ≥9 and by the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l, would lead to the identification of 83% of the case subjects with type 2 diabetes and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample and a fasting blood glucose in 64%.

CONCLUSIONS—The DRS can represent a valid inexpensive instrument for opportunistic screening and a useful alternative to indiscriminate fasting blood glucose measurement, not readily available in general practice.
Natural History of Kidney Graft Survival, Hypertrophy, and Vascular Function in End-Stage Renal Disease Type 1 Diabetic Kidney-Transplanted Patients
Authors: Fiorina Paolo , Venturini Massimo , Folli Franco , Losio Claudio , Maffi Paola , Placidi Claudia , La Rosa Stefano , Orsenigo Elena , Socci Carlo , Capella Carlo , Del Maschio Alessandro , Secchi Antonio
Published: March 2007

OBJECTIVE—Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant.

RESEARCH DESIGN AND METHODS—The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 ± 0.3 years from kidney transplant).

RESULTS—The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P < 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 ± 0.08 to 2.78 ± 0.44 mg/dl, P < 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 ± 0.01 to 0.68 ± 0.01%, P < 0.01; KI-s at baseline: 0.72 ± 0.02 to 0.69 ± 0.02%, P < 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 ± 9.0 to 82.9 ± 33.6 mg/l, P < 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown).

CONCLUSIONS—In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function.
Influence of Caffeine on Frequency of Hypoglycemia Detected by Continuous Interstitial Glucose Monitoring System in Patients With Long-Standing Type 1 Diabetes
Authors: Richardson Tristan , Thomas Peter , Ryder Jacqueline , Kerr David
Published: March 2007

OBJECTIVE—The aim of this study was to investigate the effect of caffeine (in doses equivalent to normal daily ingestion) on rates and severity of hypoglycemia in patients with long-standing type 1 diabetes to determine the relationship between caffeine, autonomic function, and hypoglycemia.

RESEARCH DESIGN AND METHODS—Using a double-blinded randomized study, we investigated the effect of caffeine versus placebo in 19 patients with long-standing type 1 diabetes using continuous glucose sensing technology and simultaneous assessment of autonomic function using Holter monitoring.

RESULTS—Caffeine reduced the duration of nocturnal hypoglycemia with a mean duration of 49 minutes (range 0–235) versus 132 (0–468) minutes (P = 0.035). The reduction in duration of nighttime hypoglycemia was due to a decline in the number of episodes of moderate hypoglycemia at the expense of mild hypoglycemic episodes (P = 0.04). There was no overall correlation between reduced heart rate variability (a marker of autonomic dysfunction) and hypoglycemic events (rs = 0.12, P = 0.62).

CONCLUSIONS—Our results suggest that caffeine is associated with a significant reduction in nocturnal hypoglycemia. The reduction in nocturnal hypoglycemia was not linked to the concomitant rise in parasympathetic activity associated with caffeine.
Measuring Diabetes Self-Care
Authors: Weinger Katie , Butler Heather A. , Welch Garry W. , La Greca Annette M.
Published: March 2007

OBJECTIVE—To examine psychometric properties of the Self-Care Inventory-revised (SCI-R), a self-report measure of perceived adherence to diabetes self-care recommendations, among adults with diabetes.

RESEARCH DESIGN AND METHODS—We used three data sets of adult type 1 and type 2 diabetic patients to examine psychometric properties of the SCI-R. Principal component and factor analyses examined whether a general factor or common factors were present. Associations with measures of theoretically related concepts were examined to assess SCI-R concurrent and convergent validity. Internal reliability coefficients were calculated. Responsiveness was assessed using paired t tests, effect size, and Guyatt’s statistic for type 1 patients who completed psychoeducation.

RESULTS—Principal component and factor analyses identified a general factor but no consistent common factors. Internal consistency of the SCI-R was α = 0.87. Correlation with a measure of frequency of diabetes self-care behaviors was r = 0.63, providing evidence for SCI-R concurrent validity. The SCI-R correlated with diabetes-related distress (r = −0.36), self-esteem (r = 0.25), self-efficacy (r = 0.47), depression (r = −0.22), anxiety (r = −0.24), and HbA1c (r = −0.37), supporting construct validity. Responsiveness analyses showed SCI-R scores improved with diabetes psychoeducation with a medium effect size of 0.62 and a Guyatt’s statistic of 0.85.

CONCLUSIONS—The SCI-R is a brief, psychometrically sound measure of perceptions of adherence to recommended diabetes self-care behaviors of adults with type 1 or type 2 diabetes.
Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects
Authors: Cernea Simona , Kidron Miriam , Wohlgelernter Jay , Modi Pankaj , Raz Itamar
Published: March 2007

OBJECTIVE—To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin.

RESEARCH DESIGN AND METHODS—In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin.

RESULTS—The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 ± 9 vs. 145.7 ± 49.5 min, P < 0.05). Maximum serum insulin levels (Cmax) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 ± 19.6 vs. 34.0 ± 7.4 μU/ml, NS). The Ins-AUC0–120 (area under the curve from 0 to 120 min for serum insulin) (339.8 ± 218, 681.3 ± 407, and 1,586.7 ± 8 μU/ml, P < 0.05) and Cmax (7.6 ± 2.8, 16.4 ± 9.3, and 39.1 ± 19.6 μU/ml, P < 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 ± 12 vs. 77.8 ± 3 min, P < 0.05), earlier peak (44.2 ± 10 vs. 159.2 ± 68 min, P < 0.05), and a shorter duration of action (85.1 ± 25 vs. 319.2 ± 45 min, P < 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 ± 1.0, 3.09 ± 1.7, and 4.6 ± 1.5 mg · kg−1 · min−1, P < 0.05) and the GIR-AUC0–120 (amount of glucose infused from 0 to 120 min) (106.7 ± 74.3, 162.9 ± 116.1, and 254 ± 123 mg/kg) increased in a dose-dependent relationship for the three doses.

CONCLUSIONS—Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted.
Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia
Authors: Koh Kwang Kon , Han Seung Hwan , Quon Michael J. , Yeal Ahn Jeong , Shin Eak Kyun
Published: March 2007

OBJECTIVE—Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity.

RESEARCH DESIGN AND METHODS—We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design.

RESULTS—Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 ± 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 ± 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 ± 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 ± 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = −0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome.

CONCLUSIONS—Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.
Influence of an Early-Onset Age of Type 1 Diabetes on Cerebral Structure and Cognitive Function
Authors: Ferguson Stewart C. , Blane Annette , Wardlaw Joanna , Frier Brian M. , Perros Petros , McCrimmon Rory J. , Deary Ian J.
Published: March 2007

OBJECTIVE—Children who develop type 1 diabetes before age 7 years (early-onset diabetes; EOD) have comparatively poorer cognitive abilities. Whether this relates to psychosocial consequences of chronic illness or organic factors related to diabetes and its complications remains unresolved. We hypothesized that if differences in neuroradiological structure and cognitive ability coexisted in those who had EOD, then an organic component to their etiology was likely.

RESEARCH DESIGN AND METHODS—A cohort of 71 young adults with long-duration type 1 diabetes diagnosed during childhood or adolescence participated in a cross-sectional evaluation of cognitive ability (neuropsychological test battery) and brain structure (magnetic resonance imaging). Diabetes onset age, preceding severe hypoglycemia exposure, retinopathy status, and diabetes duration were examined as potential correlates of cognitive and neuroradiological differences. No participants had previous neuropsychological pathology.

RESULTS—In EOD participants (n = 26), current intellectual ability (Wechsler Adult Intelligence Scale−Revised performance IQ; P = 0.03) and information processing ability (Choice Reaction Time; P = 0.006) were comparatively poorer than was observed in those with later- onset diabetes (n = 45). Furthermore, lateral ventricular volumes were 37% greater (P = 0.002) and ventricular atrophy was more prevalent (61 vs. 20%; P = 0.01) in the EOD group than in those who had later-onset type 1 diabetes.

CONCLUSIONS—An early childhood onset of type 1 diabetes was associated with mild central brain atrophy and significant differences in intellectual performance in adulthood, implying that neurodevelopment may be adversely affected by EOD. The differences observed in brain structure support an organic contribution to their etiology but do not exclude a coexistent contribution of psychosocial factors.
Long-Term Impact of Breast-Feeding on Body Weight and Glucose Tolerance in Children of Diabetic Mothers
Authors: Rodekamp Elke , Harder Thomas , Kohlhoff Rainer , Franke Kerstin , Dudenhausen Joachim W. , Plagemann Andreas
Published: March 2007

OBJECTIVE—Offspring of diabetic mothers (ODM) are at increased risk of developing overweight and impaired glucose tolerance (IGT). Recently, we observed that early neonatal ingestion of breast milk from diabetic mothers (DBM) may dose-dependently increase the risk of overweight in childhood. Here, we investigate whether DBM intake during the late neonatal period and early infancy also influences later adipogenic and diabetogenic risk in ODM.

RESEARCH DESIGN AND METHODS—A total of 112 ODM were evaluated for influence of DBM ingestion during the late neonatal period (2nd–4th neonatal week) and early infancy on relative body weight (RBW) and glucose tolerance in early childhood.

RESULTS—Exclusive breast-feeding was associated with increased childhood RBW (P = 0.011). Breast-fed ODM had an increased risk of overweight (odds ratio 1.98 [95% CI 1.12–3.50]). Breast-feeding duration was also positively related to childhood RBW (P = 0.004) and 120-min blood glucose during an oral glucose tolerance test (P = 0.022). However, adjustment for the DBM volume ingested during the early neonatal period, i.e., 1st week of life, eliminated all these relations with late neonatal breast-feeding and its duration. Interestingly, no relationship was observed between maternal blood glucose in the middle of the third trimester and the outcome.

CONCLUSIONS—Neither late neonatal DBM intake nor the duration of breast-feeding has an independent influence on childhood risk of overweight or IGT in ODM. Therefore, the 1st week of life appears to be the critical window for nutritional programming in ODM by ingestion of maternal “diabetic” breast milk.
Determinants of Exercise Capacity in Patients With Type 2 Diabetes
Authors: Fang Zhi You , Sharman James , Prins Johannes B. , Marwick Thomas H.
Published: March 2007

OBJECTIVE—Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes.

RESEARCH DESIGN AND METHODS—Subclinical left ventricular (LV) dysfunction was sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 ± 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 ± 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model.

RESULTS—Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r = −0.37, P < 0.001), male sex (r = 0.26, P = 0.001), BMI (r = −0.19, P = 0.012), HbA1c (A1C; r = −0.22, P = 0.009), Em (r = 0.43, P < 0.001), HRR (r = 0.42, P < 0.001), diabetes duration (r = −0.18, P = 0.021), and hypertension history (r = −0.28, P < 0.001). Age (P < 0.001), male sex (P = 0.007), BMI (P = 0.001), Em (P = 0.032), HRR (P = 0.013), and A1C (P = 0.0007) were independent predictors of exercise capacity.

CONCLUSIONS—Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR.
Increased Heat Generation From Atherosclerotic Plaques in Patients With Type 2 Diabetes
Authors: Toutouzas Konstantinos , Markou Virginia , Drakopoulou Maria , Mitropoulos Ioannis , Tsiamis Eleftherios , Vavuranakis Manolis , Vaina Sophia , Stefanadis Christodoulos
Published: March 2007

OBJECTIVE— Patients with coronary artery disease (CAD) and diabetes show increased inflammatory activation. Thermography detects local inflammatory involvement as heat generation. The aim of this study was to investigate whether patients with CAD and diabetes have increased local heat generation compared with nondiabetic patients.

RESEARCH DESIGN AND METHODS—We enrolled patients undergoing percutaneous coronary interventions: 45 diabetic patients and 63 nondiabetic patients, serving as the control group, matched for age, type of clinical syndrome, statin and aspirin intake, and angiographic stenosis (%). Coronary thermography was performed, and temperature difference (ΔT) between the atherosclerotic plaque and the proximal vessel wall was measured.

RESULTS—Patients with diabetes had increased temperature difference compared with nondiabetic patients (ΔT: 0.17 ± 0.18°C vs. 0.09 ± 0.02°C, P = 0.01). Twenty-one diabetic and 22 nondiabetic patients suffered from acute coronary syndromes (ACSs) (P = 0.22). Patients with diabetes and ACSs had increased temperature difference compared with nondiabetic patients with ACSs (ΔT: 0.29 ± 0.31°C vs. 0.15 ± 0.21°C, P = 0.02), which is the same as patients with diabetes and chronic stable angina (ΔT: 0.09 ± 0.08°C vs. 0.05 ± 0.04°C, P = 0.006). Twenty-three diabetic and 30 nondiabetic patients were under therapy with statins (P = 0.72). Patients with diabetes under statins had lower temperature difference compared with untreated patients (ΔT: 0.11 ± 0.12°C vs. 0.22 ± 0.21°C, P = 0.02), which is the same as nondiabetic patients under statins (ΔT: 0.05 ± 0.04°C vs. 0.13 ± 0.18°C, P = 0.01).

CONCLUSIONS—Patients with diabetes have increased temperature difference compared with nondiabetic patients. Patients with diabetes under statins showed decreased temperature difference compared with untreated patients, suggesting that statins have a favorable effect in patients with diabetes and CAD.
The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease
Authors: Beishuizen Edith D. , Tamsma Jouke T. , Jukema J. Wouter , van de Ree Marcel A. , van der Vijver J. Carel M. , Meinders A. Edo , Huisman Menno V.
Published: March 2007

OBJECTIVE—Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD.

RESEARCH DESIGN AND METHODS—A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years.

RESULTS—Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years.

CONCLUSIONS—The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.
Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria
Authors: Song Ki-Ho , Ko Seung Hyun , Kim Hyung-Wook , Ahn Yu-Bae , Lee Jong-Min , Son Hyun-Shik , Yoon Kun-Ho , Cha Bong-Yun , Lee Kwang-Woo , Son Ho-Young
Published: March 2007

OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy.

RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value.

RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 108.1 ± 34.9 μmol/l, P = 0.004) and after 2 years (216.9 ± 144.5 vs. 131.3 ± 47.3 μmol/l, P = 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 ± 26.7 vs. 33.5 ± 27.5 mg/dl, P < 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy.

CONCLUSIONS—Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria.
β-Cell Dysfunction, Insulin Sensitivity, and Glycosuria Precede Diabetes in Hepatocyte Nuclear Factor-1α Mutation Carriers
Authors: Stride Amanda , Ellard Sian , Clark Penny , Shakespeare Lynette , Salzmann Maurice , Shepherd Maggie , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—Patients with diabetes due to hepatocyte nuclear factor (HNF)-1α mutations have β-cell deficiency, insulin sensitivity, altered proinsulin levels, and a low renal threshold for glucose. It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1α mutation carriers.

RESEARCH DESIGN AND METHODS—A total of 47 offspring from 19 extended families underwent genetic testing, a standard oral glucose tolerance test, and urine testing.

RESULTS—HNF-1α mutations were found in 20 offspring, 7 with diabetes and 13 without diabetes. The 13 nondiabetic mutation carriers were compared with 27 family control subjects, who were matched for age, sex, and BMI. There was marked β-cell deficiency with reduced insulinogenic index (53.5 [31.5–90.9] vs. 226.0 [126.0–407.1], SD [range], P < 0.001) and area under the curve for insulin (P < 0.001). Insulin sensitivity was increased in mutation carriers (homeostatic model assessment of insulin sensitivity 144.6 [82.7–252.7] vs. 100 [66.9–149.4], P = 0.025). A total of 38% of mutation carriers had glycosuria at 2 h compared with 0% of control subjects (P = 0.0034). Those with glycosuria had peak glucose values that were higher than the mutations carriers without glycosuria (range 8.1–11.8 vs. 6.2–8.4 mmol/l, P = 0.002). The seven subjects with diabetes all showed glycosuria.

CONCLUSIONS—We conclude that marked β-cell deficiency, increased insulin sensitivity, and a low renal threshold are present in young nondiabetic HNF-1α mutation carriers. The presence of glycosuria post–glucose load could be used to screen children of mutation carriers as it occurs in all mutation carriers with a peak glucose in the oral glucose tolerance test >8.4 mmol/l.