bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Diabetes in Chinese With the Metabolic Syndrome
Authors: Cheung Bernard M.Y. , Wat Nelson M.S. , Man Yu Bun , Tam Sidney , Thomas G. Neil , Leung Gabriel M. , Cheng Chun Ho , Woo Jean , Janus Edward D. , Lau Chu Pak , Lam Tai Hing , Lam Karen S.L. 
Published: May 2007

OBJECTIVE—We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort.
RESEARCH DESIGN AND METHODS—We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose ≥7.0 mmol/l with fasting and/or ≥11.1 mmol/l at 2 h.
RESULTS—The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8–6.0] and 3.5 [2.3–5.2], respectively. HRs for fasting plasma glucose (FPG) ≥6.1 or 5.6 mmol/l were 6.9 [4.1–11.5] and 4.1 [2.8–6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ∼20%, but their negative predictive values were ∼95%.
CONCLUSIONS—The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes.
The Relationship Between Adrenomedullin, Metabolic Factors, and Vascular Function in Individuals With Type 2 Diabetes
Authors: Lim Su Chi , Morgenthaler Nils G. , Subramaniam Tavintharan , Wu Yew Seng , Goh Siew Kheng , Sum Chee Fang 
Published: May 2007

OBJECTIVE—Subjects with type 2 diabetes are at risk for vascular injury. Several vasoactive factors (e.g., angiotensin) have been implicated. We hypothesize that adrenomedullin, a novel vascoactive factor, is deranged in subjects with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Using a new immunoluminometric method, plasma midregional proadrenomedullin (MR-proADM) was measured in four groups of Chinese subjects: healthy (n = 100, fasting plasma glucose [FPG] &lt;5.6 mmol/l), impaired fasting glucose (IFG) (n = 60, FPG 5.6–6.9 mmol/l), and diabetic subjects with (n = 100) and without (n = 100) nephropathy. Resting forearm cutaneous microcirculatory perfusion (RCMP) was quantified in vivo using 2-dimensional laser Doppler flowmetry. We investigated the relationship between plasma MR-proADM concentrations, multiple metabolic factors, and vascular function.
RESULTS—We observed a stepwise increase in MR-proADM among the groups: healthy group mean ± SD 0.27 ± 0.09, IFG group 0.29 ± 0.13, diabetic group 0.42 ± 0.13, and diabetic nephropathy group 0.81 ± 0.54 nmol/l (diabetic vs. healthy and IFG groups, P = 0.04; and diabetic nephropathy group vs. all, P &lt; 0.01). Statistical adjustment for sex, age, BMI, and blood pressure did not affect the conclusions. Multiple linear regression analysis revealed that highly sensitive C-reactive protein (β = 0.11; P = 0.01), insulin resistance index (β = 0.20; P = 0.001), LDL cholesterol (β = 0.31; P &lt; 0.001), and adiponectin (β = 0.33; P &lt; 0.001) were significant predictors of plasma MR-proADM concentrations among nondiabetic individuals. Among subjects with diabetes, plasma MR-proADM concentrations correlated significantly with RCMP (r = 0.43, P = 0.002).
CONCLUSIONS—Plasma MR-proADM concentration was elevated in subjects with type 2 diabetes. This was further accentuated when nephropathy set in. MR-proADM was related to multiple metabolic factors and basal microcirculatory perfusion. Adrenomedullin might play a role in the pathogenesis of diabetic vasculopathy.
Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication
Authors: Poa Nicola R. , Edgar Paul F. 
Published: May 2007

OBJECTIVE—Type 2 diabetes is more prevalent in the indigenous Polynesian population of New Zealand (Maori) than in Europeans. The aim of this study was to determine whether insulin resistance in Maori psychiatric patients was associated with antipsychotic treatment and to investigate the mechanism of an association.
RESEARCH DESIGN AND METHODS—Thirty adult Maori psychiatric patients receiving antipsychotic medication for &gt;6 months and 30 healthy, age-, sex-, and BMI-matched control subjects were enrolled. Early morning fasting blood samples were analyzed for plasma levels of glucose, insulin, A1C, triglycerides, total cholesterol, IGF-1, cortisol, cortisol-binding globulin (CBG), and adiponectin.
RESULTS—The patient group had significantly higher median fasting insulin plasma levels than the control group (P = 0.002), which were independent of BMI, age, and sex. In addition, the patient group had significantly higher total cortisol (P = 0.03) and lower CBG levels (P = 0.004) than the control group, resulting in significantly higher levels of free cortisol (P = 0.004). The patient group was also significantly more hypoglycemic (P = 0.026) and hypertriglyceridemic (P = 0.028) than the control group. There was no significant difference in BMI, waist circumference, A1C, total cholesterol, IGF-1, or adiponectin levels between the two groups.
CONCLUSIONS—An increase in insulin resistance is seen in Maori psychiatric patients treated with antipsychotic medication. Therefore, Polynesian ethnicity should be considered in prescribing practice and general care of this group. In addition, the hypothalamic-pituitary-adrenal axis may have an important role in the mechanism by which this insulin resistance develops.
Relationship Between Metabolic Risk Factor Clustering and Cardiovascular Mortality Stratified by High Blood Glucose and Obesity
Authors: Kadota Aya , Hozawa Atsushi , Okamura Tomonori , Kadowak Takashi , Nakmaura Koshi , Murakami Yoshitaka , Hayakawa Takehito , Kita Yoshikuni , Okayama Akira , Nakamura Yasuyuki , Kashiwagi Atsunori , Ueshima Hirotsugu ,   for the NIPPON DATA Research Group
Published: May 2007

OBJECTIVE—Metabolic syndrome is diagnosed according to several criteria. Of these, some require glucose intolerance and others require obesity for the diagnosis. We investigated the relationship between metabolic risk factor clustering and cardiovascular disease (CVD) mortality stratified by high blood glucose or obesity.
RESEARCH DESIGN AND METHODS—We followed 7,219 Japanese men and women without a history of CVD for 9.6 years. We defined high blood pressure, high blood glucose, high triglycerides, low HDL cholesterol, and obesity as metabolic factors. The multivariate adjusted hazard ratio (HR) for CVD mortality according to the number of clustering metabolic factors was calculated using the Cox proportional hazards model.
RESULTS—During follow-up, 173 participants died of CVD. The numbers of metabolic risk factors and CVD mortality were positively correlated (Ptrend = 0.07). The HR was obviously higher among participants with than among those without high blood glucose and clustering of ≥2 other metabolic risk factors (HR 3.67 [95% CI 1.49–9.03]). However, the risk increase was only modest in participants without high blood glucose even if they had ≥2 other metabolic risk factors (1.99 [0.93–4.28]). Conversely, metabolic risk factor clustering was related to CVD mortality irrespective of obesity.
CONCLUSIONS—Our findings suggest that glucose tolerance plays an important role in CVD mortality. Because the prevalence of nonobese participants with several metabolic risk factors was quite high and their CVD risk was high, excluding them from the diagnosis of metabolic syndrome because of the absence of obesity might overlook their risk.
Severe Hypoglycemia and Smoking in a Long-Term Type 1 Diabetic Population
Authors: Hirai Flavio E. , Moss Scot E. , Klein Barbara E.K. , Klein Ronald 
Published: May 2007

OBJECTIVE—The purpose of this study was to evaluate the relationship of severe hypoglycemia and smoking in a population-based cohort of individuals with long-term type 1 diabetes.
RESEARCH DESIGN AND METHODS—This was a cross-sectional analysis of the population-based cohort of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. The analyses in this report were limited to 537 type 1 diabetic individuals with complete data who participated in the last examination phase (2000–2001). Severe hypoglycemia was defined as having one or more episodes of loss of consciousness or overnight hospitalization attributable to hypoglycemia in a 1-year period before the examination.
RESULTS—The prevalence of severe hypoglycemia in this population was 14.3%. In univariate analysis, current smokers had a greater chance of having severe hypoglycemia compared with never smokers (odds ratio 2.40 [95% CI 1.30–4.40]). When we controlled for relevant confounders such as age, sex, A1C, waist-to-hip ratio, orthostatic hypotension, alcohol consumption, intensive insulin treatment, past history of severe hypoglycemia, and late complications of diabetes (nephropathy, neuropathy, and retinopathy), the association remained statistically significant, with current smoking presenting ∼2.6 times greater odds of developing severe hypoglycemia.
CONCLUSIONS—Current smokers with type 1 diabetes have higher odds of severe hypoglycemia episodes.
Racial and Ethnic Variation in Access to Health Care, Provision of Health Care Services, and Ratings of Health Among Women With Histories of Gestational Diabetes Mellitus
Authors: Kim Catherine , Sinco Brandy , Kieffer Edith A. 
Published: May 2007

OBJECTIVE—The purpose of this study was to assess racial/ethnic variation in access to health care, use of particular health care services, presence of cardiovascular risk factors, and perceptions of health and impairment among women at risk for type 2 diabetes because of their histories of gestational diabetes mellitus (hGDM).
RESEARCH DESIGN AND METHODS—We performed a cross-sectional study using the 2001–2003 Behavioral Risk Factor Surveillance System, a national population-based, random sample telephone survey. We assessed access to health care, use of family planning, measurement and elevation of cholesterol, elevation of blood pressure, and respondents’ perceptions of health and impairment among women aged 18–44 years with hGDM (n = 4,718). Multivariate models adjusted for sociodemographic characteristics, BMI, presence of children in the household, and current smoking.
RESULTS—Outcome measures were suboptimal across racial/ethnic groups. Approximately one-fifth of the overall population reported no health insurance, cost barriers to physician visits, and no primary care provider. One-quarter had no examination within the past year, and almost one-fifth reported no family planning and elevated cholesterol levels. Latinas were the most disadvantaged, with 40% reporting no health insurance and no primary care provider and one-fourth reporting suboptimal perceptions of health. Asian/Pacific Islanders were the most advantaged in terms of health care access, cholesterol and blood pressure elevation, and impaired physical health. Racial/ethnic differences in health care use and presence of risk factors were not entirely explained by health care access or other covariates.
CONCLUSIONS—Significant racial/ethnic variation exists among women with hGDM for access to and use of health care, presence of risk factors, and perceptions of health.
Valsartan and the renin-angiotensin-aldosterone system: Blood pressure control and beyond
Authors: Dahlöf Björn 
Published: May 2007

Summary Patients treated for hypertension are still at significantly elevated risk for cardiovascular complications when compared with normotensive patients, even when on antihypertensive therapy. In all fairness though, a majority of these patients have uncontrolled blood pressure. Blocking the renin-angiotensin-aldosterone system (RAAS) prevents or reverses cardiac remodelling and improves prognosis in cardiovascular disease beyond the effects on blood pressure (BP). Valsartan acts by selectively blocking the AT1-receptor and shows similar efficacy and improved tolerability compared with ACE inhibitors. This drug may provide additional benefits in controlling the cardiovascular complications of hypertension. Results of large clinical trials with valsartan, such as VALUE, Val-HEFT, VALIANT and ABCD-2V, are eagerly awaited.
Rationale for angiotensin II receptor blocker therapy in chronic heart failure
Authors: Cohn Jay N 
Published: May 2007

Summary Inhibiting the synthesis of angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) inhibitor treatment has long been established as the recommended therapy for heart failure (HF). As ACE inhibitors are only partially effective in blocking the formation of Ang II, additional treatment with selective Ang II receptor blockers (ARBs) promise additional benefits in patients with H F. This hypothesis is currently being evaluated in Val-HeFT, a large-scale, randomised, double-blind, placebo-controlled study on the effects of adding the highly selective ARB valsartan to usual therapy (diuretics, digoxin, beta-blockers, ACE inhibitors) for HF treatment.
Angiotensin receptor blocker selectivity at the AT1- and AT2-receptors: conceptual and clinical effects
Authors: Unger Thomas , Sandmann Steffen 
Published: May 2007

Summary The advent of specific angiotensin II (Ang II) receptor blockers (ARBs) some ten years ago has provided substantial information on the specific actions of the AT1- and AT2-receptors. Most of the early research concentrated on the AT1-receptor, and the actions and biological roles of the AT2-receptor are much less well characterised. The AT2-receptor is involved in the inhibition of cell proliferation, and in cell differentiation and development, regeneration and apoptosis. By raising local Ang II concentrations at the AT2-receptor, selective blocking of the AT1-receptor may therefore have beneficial effects. This concept may be important for antihypertensive therapy and in cardiovascular disease in general.
The pharmacological potency of various AT1 antagonists assessed by Schild regression technique in man
Authors: Belz Gustav G , Breithaupt-Grögler Kerstin , Butzer Raunhild , Fuchs Winfried , Hausdorf Christian , Mang Christian 
Published: May 2007

Rationale A quantitative technique was used to compare the pharmacological potency in healthy volunteers of angiotensin II receptor antagonists (AIIA): candesartan cilexetil, losartan, irbesartan, valsartan, and telmisartan. Methods In a randomised, double-blind, parallel-group (4x12 subjects) study, single oral doses of candesartan cilexetil 4, 8 and 16 mg, losartan potassium 25, 50 and 100 mg, valsartan 40, 80 and 160 mg, and irbesartan 75, 150 and 300 mg were administered on three consecutive days. Telmisartan 20, 40 and 80 mg was similarly evaluated in 12 volunteers in an open amendment. Angiotensin II (Ang II) antagonistic effects were determined in vivo from rightward shifts in Ang II dose-response curves for diastolic blood pressure (BP) and dose ratios were calculated. Apparent Ki-doses, i.e. doses (in mg) required to induce a two-fold shift in Ang II dose-response curves (equivalent to approx. 50% blockade of receptors) were determined, using Schild regression analysis. Results All treatments dose-dependently attenuated increases in diastolic BP induced by infusion of exogenous Ang II. Candesartan cilexetil appeared to have a more pronounced increase in effect following cumulative dosing. At 24 hours, apparent K i-doses were: candesartan cilexetil 6 mg, irbesartan 123 mg, valsartan 93.5 mg, and telmisartan 54 mg. It was not possible to determine an apparent Ki-dose for losartan at 24 hours. Conclusion Consistent with results from experimental pharmacology, candesartan cilexetil displayed the highest pharmacological potency (i.e. antagonistic activity per mg substance) of the AIIAs tested. Apparent Ki-doses at 24 hours were within the dose range recommended for clinical use in patients with hypertension.
Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat
Authors: van Dijk David Jonathan , Boner Geoffrey , Giler Shaul , Erman Arie 
Published: May 2007

Objective The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, electrolyte balance and renal function in normal human pregnancy. The present study was designed to assess various components of the RAS and renal function during pregnancy and immediately after pregnancy in the streptozotocin (STZ)-diabetic rat. Methods Pregnant Wistar rats were allocated to three groups: I- control, non-diabetic rats (n=24), II- STZ-diabetic rats (STZ 55 mg/kg body weight, i.v. on day 10 of pregnancy, n=24), III- diabetic rats, as above, treated with insulin (4 units/day, s.c. n=21). On days 17—18 of pregnancy, or within 24 hours after delivery, the rats were sacrificed and the various components of the RAS were determined. Results Urinary protein excretion (UP) and creatinine clearance (CCr) were greater in group II, four days after STZ, than in group I (UP: I-7.6±2.8, II-18.6±6.3 mg/24-hour, p<0.001, CCr: I-1.04±0.33, II-2.38±0.7 ml/minute, p<0.001). Mean (±SD) serum angiotensin-converting enzyme (ACE) activity and plasma angiotensin II (Ang II) levels at days 17—18 of pregnancy were greater in the untreated diabetic rats than in control pregnant rats (ACE: 163±18 vs . 111±21 nmol/ml/minute, p<0.001, Ang II: 115±45 vs. 43±10 pg/ml, p<0.005). Postpartum serum ACE activity and plasma Ang II levels were greater in group II (ACE: I-123±14, II-142±24, III-108±21 nmol/ml/minute, p<0.01, Ang II: I-56±38, II-148±62, III-38±17 pg/ml, p<0.001). ACE activity in the lung was greater, whereas the activity in the renal cortex was less, in group II than in group I. Kidney weight in untreated diabetic rats was greater than in the other two groups. Conclusion Increased serum ACE activity during pregnancy and postpartum in the untreated diabetic rat is associated with enhanced serum Ang II levels, which may contribute to increased protein excretion and renal hypertrophy.
Renin-angiotensin blockade improves renal cGMP production via non-AT2-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat
Authors: Uhlenius Nina , Vuolteenaho Olli , Tikkanen Ilkka 
Published: May 2007

Background To investigate the changes in the angiotensin II (Ang II) receptors and nitric oxide (NO)-cGMP pathway in the rat kidney after nitric oxide synthase (NOS) blockade. Methods Captopril, an angiotensin-converting enzyme (ACE) inhibitor, 20 mg/100 ml; and/or L-158,809 (an Ang II AT 1-receptor antagonist, 5 mg/100 ml) and L-NAME (NOS inhibitor, 50 mg/100 ml) were administered orally for 12 weeks. Blood pressure (BP), urinary albumin, urinary cGMP excretion, plasma ANP, and plasma renin activity were measured. In vitro autoradiography was used to locate the Ang II receptors in the kidney. Results Captopril and L-158,809 treatments normalised BP and prevented the appearance of albuminuria in rats receiving L-NAME. Urinary cGMP excretion was significantly increased in L-158,809-treated rats compared with the non-treated group, suggesting that the dysfunctional NO system may be activated by the treatment. AT1 -receptor binding in the kidney was inhibited to about 40% of the control value after administration of L-158,809. The AT2-receptor binding was inhibited to less than 15% of the control value. NOS inhibition had no effect on receptor binding. Conclusion Blockade of NOS causes hypertension and renal damage. Treatment with an ACE inhibitor and/or Ang II receptor antagonist prevented these changes equally effectively. The stimulatory effect of AT1-receptor antagonism on cGMP production was not mediated by AT2-receptor-dependent mechanisms, since renal AT2-receptor binding density was suppressed following treatment with L-158,809. AT1-receptor blockade per se favours activation of humoral pathways that stimulate cGMP production potentially contributing to renal and vascular protection in hypertension and chronic renal disease.
Comparison of the effects of antihypertensive treatment with angiotensin II blockade and beta-blockade on carotid wall structure and haemodynamics: protocol and baseline demographics
Authors: Ariff Ben , Stanton Alice , Barratt Dean , Augst Alex , Glor Fadi , Poulter Neil , Sever Peter , Yun Xu  , Hughes Alun , Thom Simon AMcG 
Published: May 2007

Several systemic factors have been shown to contribute to the acceleration of large vessel atheroma. Correction of these factors leads to a reduction in the progression of plaque formation and associated arterial wall thickness. Atheroma remains, however, a focal disease, developing at characteristic sites within the arterial tree. These sites are typically at areas of vessel branching or marked curvature, and correspond to regions of high tensile stress and low sheer stress, leading to the hypothesis that local haemodynamic factors and vessel wall mechanics potentiate the focal development of atheroma. Current assessment of vascular haemodynamics suffers from an inability to handle complex flow, and does not allow accurate determination of locally varying flow, and shear stress patterns. The application of computational fluid dynamic (CFD) flow simulation techniques to ultrasound and local pressure data, however, allows a comprehensive, non-invasive appraisal of haemodynamic flow parameters to be performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint Trial (CACHET) study compares the effects of two antihypertensive regimens, one β-blocker-based, the other angiotensin receptor blocker based, on carotid intima-media thickness. The collection of ultrasound and pressure data on each subject provides a unique opportunity to apply these data to the CFD model to study the effects of these antihypertensive regimens on local fluid dynamics. This will lead to a greater understanding of the relationship of these factors to atheroma formation and regression.