People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this ...population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France.
We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs.
Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 95% confidence interval (CI) 6.47-7.15 versus 1.38 1.24-1.54). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 107.7-159.0 versus 126.4 117.2-136.4; stroke recurrence: 86.7 66.4-113.4 versus 66.5 59.2-74.6; mortality 291.5 259.1-327.9 versus 144.1 134.3-154.6). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 95% CI 1.66-2.92). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378).
The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.
Lanreotide depot/autogel antitumor activity in intestinal/pancreatic neuroendocrine tumors (NETs) was demonstrated in the phase-3 CLARINET study (NCT00353496), based on significantly prolonged ...progression-free survival (PFS) versus placebo.
During CLARINET, patients with metastatic intestinal/pancreatic NETs received lanreotide depot/autogel 120 mg or placebo every 4 weeks for 96 weeks. Imaging data (response evaluation criteria in solid tumors RECIST v1.0, centrally reviewed) were re-evaluated in this post hoc analysis of tumor growth rate (TGR) in NETs. TGR (%/month) was calculated from two imaging scans during relevant periods: pre-treatment (TGR
); 12-24 weeks before randomization versus baseline; each treatment visit versus baseline (TGR
); between consecutive treatment visits (TGR
). To assess TGR as a measure of prognosis, PFS was compared for TGR
subgroups stratified by optimum TGR
cut-off; a multivariate analysis was conducted to identify prognostic factors for PFS.
TGR
revealed tumors growing during pre-treatment (median interquartile range TGR
: lanreotide 2.1%/month 0.2; 6.1; placebo 2.7%/month 0.15; 6.8), contrary to RECIST status. TGR was significantly reduced by 12 weeks with lanreotide versus placebo (difference in least-square mean TGR
of - 2.9 - 5.1, - 0.8, p = 0.008), a difference that was maintained at most subsequent visits. TGR
> 4%/month had greater risk of progression/death than ≤4%/month (hazard ratio 4.1; 95% CI 2.5-6.5; p < 0.001); multivariate analysis revealed lanreotide treatment, progression at baseline, TGR
, hepatic tumor load, and primary tumor type were independently associated with PFS.
TGR provides valuable information on tumor activity and prognosis in patients with metastatic intestinal/pancreatic NETs, and identifies early lanreotide depot/autogel antitumor activity.
Retrospective registration, 18 July 2006; EudraCT: 2005-004904-35; ClinicalTrials.gov: NCT00353496 .
Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution.
We aimed to identify differences across ethnic groups in interrelations between ...BMI, abdominal adiposity, liver fat, and CMR profile.
In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured.
Higher ranges of BMI were associated with higher levels of visceral visceral adipose tissue (VAT) and deep subcutaneous deep subcutaneous adipose tissue (DSAT) adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration.
Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.
Abdominal adiposity is a growing clinical and public health problem. It is not known whether it is similarly associated with cardiovascular disease (CVD) and diabetes mellitus in different regions ...around the world, and thus whether measurement of waist circumference (WC) in addition to body mass index (BMI) is useful in primary care practice.
Randomly chosen primary care physicians in 63 countries recruited consecutive patients aged 18 to 80 years on 2 prespecified half days. WC and BMI were measured and the presence of CVD and diabetes mellitus recorded. Of the patients who consulted the primary care physicians, 97% agreed to participate in the present study. Overall, 24% of 69,409 men and 27% of 98,750 women were obese (BMI > or = 30 kg/m2). A further 40% and 30% of men and women, respectively, were overweight (BMI 25 to 30 kg/m2). Increased WC (> 102 for men and > 88 cm for women) was recorded in 29% and 48%, CVD in 16% and 13%, and diabetes mellitus in 13% and 11% of men and women, respectively. A statistically significant graded increase existed in the frequency of CVD and diabetes mellitus with both BMI and WC, with a stronger relationship for WC than for BMI across regions for both genders. This relationship between WC, CVD, and particularly diabetes mellitus was seen even in lean patients (BMI < 25 kg/m2).
Among men and women who consulted primary care physicians, BMI and particularly WC were both strongly linked to CVD and especially to diabetes mellitus. Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality.
Background:
Visceral adiposity is an important correlate of cardiometabolic risk, yet its association after the diagnosis of type 2 diabetes remains unclear.
Methods:
Our objective was to assess the ...independent and combined associations of visceral adiposity and type 2 diabetes to cardiometabolic risk. The INternational Study of Prediction of Intra-abdominal adiposity and its RElationships with cardioMEtabolic risk/Intra-Abdominal Adiposity (INSPIRE ME IAA) is a cross-sectional computed tomography imaging study with data collected from June 2006 to May 2008. General physicians, cardiologists, and diabetologists (n = 297) in 29 countries recruited 4144 (51.8% men) men (39–71 yr) and women (44–71 yr). Patients were categorized according to visceral adiposity tertiles, type 2 diabetes status, and sex. All results were adjusted for age, body mass index, region, and physician's specialty.
Results:
Markers of insulin resistance, lipid/lipoproteins, inflammatory markers, and liver fat increased with visceral adiposity in men and women with and without type 2 diabetes. Prevalent cardiovascular disease increased with visceral adiposity tertiles, regardless of type 2 diabetes status. Visceral adiposity odds ratio = 1.25 (1.09–1.44) for men and 1.78 (1.50–2.12) for women was positively associated with type 2 diabetes, whereas liver attenuation (inversely related to liver fat) was negatively associated with type 2 diabetes odds ratio = 0.66 (0.59–0.75) for men and 0.63 (0.55–0.72) for women. Subcutaneous adipose tissue was inversely related to type 2 diabetes in women 0.76 (0.0.66–0.88) and not associated with type 2 diabetes in men 0.97 (0.85–1.11).
Conclusions:
Visceral, but not sc, abdominal adiposity is strongly related to cardiometabolic risk factors and to the prevalence of cardiovascular disease and may be an important driver of cardiometabolic risk in patients regardless of type 2 diabetes status.
Summary
Objectives To evaluate the relevance of obesity and abdominal obesity in the prevalence of cardiovascular disease (CVD), diabetes mellitus, hyperlipidaemia and hypertension in primary care ...patients and to ascertain whether waist circumference (WC) measurement should be included in routine clinical practice in addition to body mass index (BMI).
Methods As part of the IDEA study, primary care physicians from Spain recruited patients aged 18–80 years. WC and BMI and the presence of CVD, diabetes mellitus, hyperlipidaemia and hypertension were recorded. Finally, 17 980 were analysed.
An age‐related increase in adiposity was observed. Overall 33% were obese by BMI, and 51% of subjects presented abdominal obesity by the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATPIII) (WC > 102 cm for men and > 88 cm for women). Although there was a correlation between BMI and WC, they presented different distribution patterns. Women, but not men, with a high level of education, professional activity and smoking were associated with a lower WC. Abdominal obesity was significantly associated with CVD. Some subjects with abdominal obesity but lean by BMI, showed an increased prevalence of CVD and diabetes. Furthermore, abdominal obesity was strongly associated with dyslipidaemia and hypertension.
Conclusions Half of the primary care patients studied showed abdominal obesity as measured by WC, whereas one‐third was obese by BMI. Abdominal obesity was strongly associated with CVD and diabetes, even in patients lean by BMI. WC should be included in the routine clinical practice in addition to BMI.
Exercise increases fatty acid oxidation (FAO), improves serum high density lipoprotein cholesterol (HDLc) and triglycerides (TG), and upregulates skeletal muscle peroxisome proliferator activated ...receptor (PPAR)delta expression. In parallel, PPARdelta agonist-upregulated FAO would induce fatty-acid uptake (via peripheral lipolysis), and influence HDLc and TG-rich lipoprotein particle metabolism, as suggested in preclinical models.
Healthy volunteers were allocated placebo (n=6) or PPARdelta agonist (GW501516) at 2.5 mg (n=9) or 10 mg (n=9), orally, once-daily for 2 weeks while hospitalized and sedentary. Standard lipid/lipoproteins were measured and in vivo fat feeding studies were conducted. Human skeletal muscle cells were treated with GW501516 in vitro and evaluated for lipid-related gene expression and FAO. Serum TG trended downwards (P=0.08, 10 mg), whereas TG clearance post fat-feeding improved with drug (P=0.02). HDLc was enhanced in both treatment groups (2.5 mg P=0.004, 10 mg P<0.001) when compared with the decrease in the placebo group (-11.5+/-1.6%, P=0.002). These findings complimented in vitro cell culture results whereby GW501516 induced FAO and upregulated CPT1 and CD36 expression, in addition to a 2-fold increase in ABCA1 (P=0.002). However, LpL expression remained unchanged.
This is the first report of a PPARdelta agonist administered to man. In this small study, GW501516 significantly influenced HDLc and TGs in healthy volunteers. Enhanced in vivo serum fat clearance, and the first demonstrated in vitro upregulation in human skeletal muscle fat utilization and ABCA1 expression, suggests peripheral fat utilization and lipidation as potential mechanisms toward these HDL:TG effects.
The authors explored whether the waist circumference (WC) cutoffs currently proposed to define abdominal obesity (AO) are associated with diabetes and cardiovascular disease (CVD) in Latin America. ...Primary care physicians in 12 countries were randomly chosen to measure WC and body mass index and record the presence of diabetes and CVD in all consecutive adult patients, consulting them on 2 prespecified half‐days. Overall, 70% of 9719 men, and 76% of 18,526 women had AO. Diabetes was reported in 10% of men and 9% of women and CVD in 9% of men and 7% of women. AO was significantly related with diabetes (age‐adjusted odds ratio, 1.63 for men and 2.86 for women) and with CVD (odds ratio, 1.41 for men and 1.62 for women). Obesity was also significantly related with diabetes and CVD. Strikingly, abdominal adiposity was very frequent in women with normal body mass index, suggesting that an evidence‐based definition of abdominal adiposity in Latin America is needed.
Background: Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution.
Objective: We aimed to identify differences across ethnic groups in ...interrelations between BMI, abdominal adiposity, liver fat, and CMR profile.
Design: In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured.
Results: Higher ranges of BMI were associated with higher levels of visceral visceral adipose tissue (VAT) and deep subcutaneous deep subcutaneous adipose tissue (DSAT) adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration.
Conclusions: Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.
Dehydroepiandrosterone (DHEA; 50 and 25 mg) and placebo tablets were orally administered daily to 24 healthy aging men and women (67.8 +/- 4.3 yr) for 8 days according to a balanced incomplete block ...design. Nine blood tests on both the first and eighth days allowed the measurement of DHEA, its sulfate DHEAS, and metabolites: testosterone, 5alpha-androstan-3alpha,17beta-diol glucuronide, estradiol, and estrone. Relatively low background levels of DHEA(S) were observed, and with the reestablishment of "young" levels, four important results were obtained. 1) Blood DHEA had an apparent terminal half-life of more than 20 h, the same order of magnitude as that of blood DHEAS, a result explainable by back-hydrolysis of the large amount of DHEAS formed after oral administration of DHEA, a mechanism providing long-lived unconjugated DHEA and metabolites. 2) The metabolic conversion of DHEAS to DHEA was significantly greater in women than in men. 3) No accumulation of steroids was observed. 4) No worrying transformation to androgen and estrogen was recorded; indeed, the limited increased estradiol in aged women could be predicted to be beneficial. These results suggested that daily oral administration of DHEA (25/50 mg) is safe in elderly subjects. The 50-mg dose was chosen for a 1 yr, double blind, placebo-controlled trial of daily oral administration of DHEA in 60- to 80-yr-old individuals (DHEAge).
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