Type 2 diabetes mellitus (T2DM) disproportionately affects individuals of nonwhite ethnic origin. Timely and appropriate initiation and intensification of glucose-lowering therapy is key to reducing ...the risk of major vascular outcomes. Given that ethnic inequalities in outcomes may stem from differences in therapeutic management, the aim of this study was to identify ethnic differences in the timeliness of initiation and intensification of glucose-lowering therapy in individuals newly diagnosed with T2DM in the United Kingdom.
An observational cohort study using the Clinical Practice Research Datalink was conducted using 162,238 adults aged 18 and over diagnosed with T2DM between 1990 and 2017 (mean age 62.7 years, 55.2% male); 93% were of white ethnicity (n = 150,754), 5% were South Asian (n = 8,139), and 2.1% were black (n = 3,345). Ethnic differences in time to initiation and intensification of diabetes treatment were estimated at three time points (initiation of noninsulin monotherapy, intensification to noninsulin combination therapy, and intensification to insulin therapy) using multivariable Cox proportional hazards regression adjusted for factors a priori hypothesised to be associated with initiation and intensification: age, sex, deprivation, glycated haemoglobin (HbA1c), body mass index (BMI), smoking status, comorbidities, consultations, medications, calendar year, and clustering by practice. Odds of experiencing therapeutic inertia (failure to intensify treatment within 12 months of HbA1c >7.5% 58 mmol/mol), were estimated using multivariable logistic regression adjusted for the same hypothesised confounders. Noninsulin monotherapy was initiated earlier in South Asian and black groups (South Asian HR 1.21, 95% CI 1.08-1.36, p < 0.001; black HR 1.29, 95% CI 1.05-1.59, p = 0.017). Correspondingly, no ethnic differences in therapeutic inertia were evident at initiation. Intensification with noninsulin combination therapy was slower in both nonwhite ethnic groups relative to white (South Asian HR 0.80, 95% CI 0.74-0.87, p < 0.001; black HR 0.79, 95% CI 0.70-0.90, p < 0.001); treatment inertia at this stage was greater in nonwhite groups relative to white (South Asian odds ratio OR 1.45, 95% CI 1.23-1.70, p < 0.001; black OR 1.43, 95% CI 1.09-1.87, p = 0.010). Intensification to insulin therapy was slower again for black groups relative to white groups (South Asian HR 0.49, 95% CI 0.41-0.58, p < 0.001; black HR 0.69, 95% CI 0.53-0.89, p = 0.012); correspondingly, treatment inertia was significantly higher in nonwhite groups at this stage relative to white groups (South Asian OR 2.68, 95% CI 1.89-3.80 p < 0.001; black OR 1.82, 95% CI 1.13-2.79, p = 0.013). At both stages of treatment intensification, nonwhite groups had fewer HbA1c measurements than white groups. Limitations included variable quality and completeness of routinely recorded data and a lack of information on medication adherence.
In this large UK cohort, we found persuasive evidence that South Asian and black groups intensified to noninsulin combination therapy and insulin therapy more slowly than white groups and experienced greater therapeutic inertia following identification of uncontrolled HbA1c. Reasons for delays are multifactorial and may, in part, be related to poorer long-term monitoring of risk factors in nonwhite groups. Initiatives to improve timely and appropriate intensification of diabetes treatment are key to reducing disparities in downstream vascular outcomes in these populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is unknown whether associations between blood pressure (BP) and stroke vary between Europeans and South Asians, despite higher stroke rates in the latter. We report findings from a UK cohort study ...of 1375 European and 1074 South Asian men, not receiving antihypertensive medication, aged 40 to 69 years at baseline (1988–1991). Assessment included BP, blood tests, anthropometry, and questionnaires. Incident stroke was established at 20 years from death certification, hospital and primary care records, and participant report. South Asians had higher systolic BP, diastolic BP, and mean arterial pressure than Europeans, and similar pulse pressure. Associations between systolic BP or diastolic BP and stroke were stronger in South Asians than Europeans, after adjustment for age, smoking status, waist/hip ratio, total/high-density lipoprotein-cholesterol ratio, diabetes mellitus, fasting glucose, physical activity, and heart rate (systolic BPEuropeans odds ratio, 1.22; 95% confidence interval, 0.98–1.51, South Asians 1.56; 1.24–1.95; ethnic difference P=0.04; diastolic BPEuropeans 0.90; 0.71–1.13, South Asians 1.68; 1.32–2.15; P<0.001). Hemodynamic correlates of stroke risk differed by ethnicityin combined models, mean arterial pressure but not pulse pressure was detrimentally associated with stroke in South Asians, whereas the converse was true for Europeans. The combination of hyperglycemia and hypertension appeared particularly detrimental for South Asians. There are marked ethnic differences in associations between BP parameters and stroke. Undue focus on systolic BP for risk prediction, and current age and treatment thresholds may be inappropriate for individuals of South Asian ancestry.
3D-speckle tracking echocardiography(3D-STE) allows simultaneous assessment of ejection fraction(EF) and multidirectional strains, but its prognostic utility in the general population is unknown. We ...investigated if 3D-STE strains predicted a composite of major cardiac endpoints(MACE) beyond cardiovascular risk factors(CVDRF), and whether they were superior to 3D-EF. 529 participants in SABRE, a UK-based tri-ethnic general population cohort (69±6y; 76.6% male) with acceptable 3D-STE imaging were studied. Associations between 3D-EF or multidirectional myocardial strains and MACE(coronary heart disease(fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia and cardiovascular mortality) were determined using Cox regression including adjustment for CVDRF and 2D-EF. Whether 3D-EF, global longitudinal strain(3D-GLS) and principle tangential strain(3D-PTS/3D-strain) improved cardiovascular risk stratification over CVDRF was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models and Harrell's C statistics. During follow-up(median, 12y), there were 92 events. 3D-EF, 3D-GLS and 3D-PTS and 3D-RS were associated with MACE in unadjusted and models adjusted for CVDRF but not CVDRF+2D-EF. Compared to 3D-EF, both 3D-GLS and 3D-PTS slightly improved the predictive value over CVDRF for MACE, but the improvement was modest(C statistic increased from 0.698(0.647, 0.749) to 0.715(0.663, 0.766) comparing CVDRF with CVDRF +3D-GLS). 3D-STE-derived LV myocardial strains predicted MACE in a multi-ethnic general population sample of elderly individuals from the UK; however the added prognostic value of 3D-STE myocardial strains was small.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Adverse effects of air pollution on cardiovascular mortality are well established.
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There are comparatively fewer studies in the UK compared to North America.
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In two British cohort studies, we ...investigated associations between gases, particulates and cardiovascular mortality.
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Detrimental associations, non-statistically significant, between cardiovascular mortality and particulates were found.
To evaluate QRISK2 and Framingham cardiovascular disease (CVD) risk scores in a tri-ethnic U.K. population.
Cohort study.
West London.
Randomly selected from primary care lists. Follow-up data were ...available for 87% of traced participants, comprising 1866 white Europeans, 1377 South Asians, and 578 African Caribbeans, aged 40-69 years at baseline (1998-1991).
First CVD events: myocardial infarction, coronary revascularisation, angina, transient ischaemic attack or stroke reported by participant, primary care or hospital records or death certificate.
During follow-up, 387 CVD events occurred in men (14%) and 78 in women (8%). Both scores underestimated risk in European and South Asian women (ratio of predicted to observed risk: European women: QRISK2: 0.73, Framingham: 0.73; South Asian women: QRISK2: 0.52, Framingham: 0.43). In African Caribbeans, Framingham over-predicted in men and women and QRISK2 over-predicted in women. Framingham classified 28% of participants as high risk, predicting 54% of all such events. QRISK2 classified 19% as high risk, predicting 42% of all such events. Both scores performed poorly in identifying high risk African Caribbeans; QRISK2 and Framingham identified as high risk only 10% and 24% of those who experienced events.
Neither score performed consistently well in all ethnic groups. Further validation of QRISK2 in other multi-ethnic datasets, and better methods for identifying high risk African Caribbeans and South Asian women, are required.
Summary Background Diabetic retinopathy remains a leading cause of visual loss in people of working age. We examined whether candesartan treatment could slow the progression and, secondly, induce ...regression of retinopathy in people with type 2 diabetes. Methods We did a randomised, double-blind, parallel-group, placebo-controlled trial in 309 centres worldwide. We recruited normoalbuminuric, normotensive, or treated hypertensive people with type 2 diabetes with mild to moderately severe retinopathy and assigned them to candesartan 16 mg once a day or placebo. After a month, the dose was doubled to 32 mg once per day. Investigators and patients were unaware of the treatment allocation status. Progression of retinopathy was the primary endpoint, and regression was a secondary endpoint. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00252694. Findings 1905 participants (aged 37–75 years) were randomised to candesartan (n=951) or placebo (n=954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio HR 0·87, 95% CI 0·70–1·08, p=0·20). Regression on active treatment was increased by 34% (1·34, 1·08–1·68, p=0·009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1·17, 95% CI 1·05–1·30, p=0·003). Adverse events did not differ between the treatment groups. Interpretation Treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy might induce improvement of retinopathy. Funding AstraZeneca and Takeda.
Summary Background Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy ...Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. Methods Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent 1 trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After 1 month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression of retinopathy and were defined as at least a two-step and at least a three-step increase on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, respectively. These trials are registered with ClinicalTrials.gov , numbers NCT00252733 for DIRECT-Prevent 1 and NCT00252720 for DIRECT-Protect 1. Findings 1421 participants (aged 18–50 years) were randomly assigned to candesartan (n=711) or to placebo (n=710) in DIRECT-Prevent 1, and 1905 (aged 18–55 years) to candesartan (n=951) or to placebo (n=954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%) participants in the candesartan group versus 217 (31%) in the placebo group. Progression of retinopathy occurred in 127 (13%) participants in the candesartan group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs placebo) was 0·82 (95% CI 0·67–1·00, p=0·0508) for incidence of retinopathy and 1·02 (0·80–1·31, p=0·85) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0·65 (0·48–0·87, p=0·0034), which was attenuated but still significant after adjustment for baseline characteristics (0·71, 0·53–0·95, p=0·046). Final ETDRS level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1·16, 95% CI 1·05–1·30, p=0·0048) and DIRECT-Protect 1 (1·12, 95% CI 1·01–1·25, p=0·0264). Adverse events did not differ between the treatment groups. Interpretation Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression. Funding AstraZeneca and Takeda.
Background The "healthy obese" hypothesis suggests the risks associated with excess adiposity are reduced in those with higher muscle quality (mass/strength). Alternative possibilities include loss ...of muscle quality as people become unwell (reverse causality) or unmeasured confounding. Methods and Results We conducted a cohort study using the UK Biobank (n=452 931). Baseline body mass index ( BMI) was used to quantify adiposity and handgrip strength ( HGS ) used for muscle quality. Outcomes were fatal and non-fatal cardiovascular disease, and mortality. As a secondary analysis we used waist-hip-ratio or fat mass percentage instead of BMI , and skeletal muscle mass index instead of HGS . In a subsample, we used gene scores for BMI , waist-hip-ratio and HGS in a Mendelian randomization ( MR ). BMI defined obesity was associated with an increased risk of all outcomes (hazard ratio HR range 1.10-1.82). Low HGS was associated with increased risks of cardiovascular and all-cause mortality ( HR range 1.39-1.72). HR s for the association between low HGS and cardiovascular disease events were smaller ( HR range 1.05-1.09). There was no suggestion of an interaction between HGS and BMI to support the healthy obese hypothesis. Results using other adiposity metrics were similar. There was no evidence of an association between skeletal muscle mass index and any outcome. Factorial Mendelian randomization confirmed no evidence for an interaction. Low genetically predicted HGS was associated with an increased risk of mortality ( HR range 1.08-1.19). Conclusions Our analyses do not support the healthy obese concept, with no evidence that the adverse effect of obesity on outcomes was reduced by improved muscle quality. Lower HGS was associated with increased risks of mortality in both observational and MR analyses, suggesting reverse causality may not be the sole explanation.
Both long and short sleep duration increase risk of mortality. Most previous studies have been performed in Europeans and have focused on sleep duration. Thus, we aimed to investigate the association ...between sleep quality and mortality across three different ethnic groups.
We used data from the Southall and Brent REvisited Study (SABRE) cohort, which comprises first generation migrant South Asian and African Caribbean men and women, aged 40–69 years, recruited between 1988 and 1991. In sum, 4399 participants provided complete data at baseline and follow-up. Of those, 1656 died by December 2017. Our exposures (eg, difficulty falling asleep, early morning waking and waking up tired in the morning) were self-reported and our primary outcome was mortality. We used Cox proportional hazards models to analyse our data, adjusting for baseline-measured confounders.
None of the sleep measures were strongly associated with all-cause mortality in Europeans or African Caribbeans, whilst in South Asians difficulty falling asleep was related to an increased risk of all-cause mortality (HR = 1.28, 95%CI = 1.01; 1.61). In Europeans, early morning waking was associated with a moderately increased risk of cardiovascular death (HR = 1.31, 95%CI = 1.05; 1.63); alternately, this association was not as strong in the other groups.
Our findings suggest that the relationship between sleep quality and mortality may differ by ethnic group, but formal heterogeneity tests indicated that the strongest difference in HRs was observed for early morning waking and cardiovascular disease (CVD) mortality across the three groups (Cochran's Q test p = 0.036). As such, these results are novel and provide support for ethnic differences in sleep quality and mortality, and may have implications for precision medicine.
•We explored the association between sleep quality and cancer, CVD and all-cause mortality.•We used data from a white Europeans, African Caribbeans and South Asians.•Early morning waking was associated with greater CVD mortality risk in Europeans.•Findings suggest ethnic differences in these effects, warranting further investigation.
Background South Asians are at high risk for chronic kidney disease. However, unlike those in the United States and United Kingdom, laboratories in South Asian countries do not routinely report ...estimated glomerular filtration rate (eGFR) when serum creatinine is measured. The objectives of the study were to: (1) evaluate the performance of existing GFR estimating equations in South Asians, and (2) modify the existing equations or develop a new equation for use in this population. Study Design Cross-sectional population-based study. Setting & Participants 581 participants 40 years or older were enrolled from 10 randomly selected communities and renal clinics in Karachi. Predictors eGFR, age, sex, serum creatinine level. Outcomes Bias (the median difference between measured GFR mGFR and eGFR), precision (the IQR of the difference), accuracy (P30 ; percentage of participants with eGFR within 30% of mGFR), and the root mean squared error reported as cross-validated estimates along with bootstrapped 95% CIs based on 1,000 replications. Results The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation performed better than the MDRD (Modification of Diet in Renal Disease) Study equation in terms of greater accuracy at P30 (76.1% 95% CI, 72.7%-79.5% vs 68.0% 95% CI, 64.3%-71.7%; P < 0.001) and improved precision (IQR, 22.6 95% CI, 19.9-25.3 vs 28.6 95% CI, 25.8-31.5 mL/min/1.73 m2 ; P < 0.001). However, both equations overestimated mGFR. Applying modification factors for slope and intercept to the CKD-EPI equation to create a CKD-EPI Pakistan equation (such that eGFRCKD-EPI(PK) = 0.686 × eGFRCKD-EPI1.059 ) in order to eliminate bias improved accuracy (P30 , 81.6% 95% CI, 78.4%-84.8%; P < 0.001) comparably to new estimating equations developed using creatinine level and additional variables. Limitations Lack of external validation data set and few participants with low GFR. Conclusions The CKD-EPI creatinine equation is more accurate and precise than the MDRD Study equation in estimating GFR in a South Asian population in Karachi. The CKD-EPI Pakistan equation further improves the performance of the CKD-EPI equation in South Asians and could be used for eGFR reporting.
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