General Practice - Research Publications

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    Comparison of body mass index at diagnosis of diabetes in a multi-ethnic population: A case-control study with matched non-diabetic controls
    Paul, SK ; Adjah, ESO ; Samanta, M ; Patel, K ; Bellary, S ; Hanif, W ; Khunti, K (WILEY, 2017-07-01)
    AIMS: To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non-diabetic controls in a multi-ethnic population. MATERIALS AND METHODS: This was a case-control study of 90 367 patients with incident diabetes and 362 548 age-sex-ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated. RESULTS: Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m2 at diagnosis (32.2 kg/m2 ) compared to the matched controls (27.4 kg/m2 ). White Europeans (n = 79 270), African-Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m2 , respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m2 (38%) than White Europeans (26%) and African-Caribbeans (29%) (all P  < .01). Within the 18 to 70-year age range, South Asian males and females had a significantly higher probability of developing diabetes in the continuously measured BMI range of 18 to 30 kg/m2 , compared to White Europeans and African-Caribbeans. Across all age groups <70 years, South Asians and African-Caribbeans had a significantly higher probability of developing T2DM in the normal weight and overweight categories, compared to White Europeans. However, this risk pattern of developing diabetes was reversed amongst the obese in all age groups. CONCLUSION: Risk patterns of developing diabetes at different levels of obesity varies among ethnic groups across all ages, while South Asians and African-Caribbeans carry the highest risk at a younger age and at lower adiposity burden.
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    Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes
    Paul, SK ; Klein, K ; Thorsted, BL ; Wolden, ML ; Khunti, K (BMC, 2015-08-07)
    BACKGROUND: The aim of the study was to evaluate the effect of delay in treatment intensification (IT; clinical inertia) in conjunction with glycaemic burden on the risk of macrovascular events (CVE) in type 2 diabetes (T2DM) patients. METHODS: A retrospective cohort study was carried out using United Kingdom Clinical Practice Research Datalink, including T2DM patients diagnosed from 1990 with follow-up data available until 2012. RESULTS: In the cohort of 105,477 patients mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one CVE during 5.3 years of median follow-up. In patients with HbA1c consistently above 7/7.5% (53/58 mmol/mol, n = 23,101/11,281) during 2 years post diagnosis, 26/22% never received any IT. Compared to patients with HbA1c <7% (<53 mmol/mol), in patients with HbA1c ≥7% (≥53 mmol/mol), a 1 year delay in receiving IT was associated with significantly increased risk of MI, stroke, HF and composite CVE by 67% (HR CI: 1.39, 2.01), 51% (HR CI: 1.25, 1.83), 64% (HR CI: 1.40, 1.91) and 62% (HR CI: 1.46, 1.80) respectively. One year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE. CONCLUSIONS: Among patients with newly diagnosed T2DM, 22% remained under poor glycaemic control over 2 years, and 26% never received IT. Delay in IT by 1 year in conjunction with poor glycaemic control significantly increased the risk of MI, HF, stroke and composite CVE.
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    Prevalence and incidence of complications at diagnosis of T2DM and during follow-up by BMI and ethnicity: a matched case-control analysis
    Adjah, ESO ; Bellary, S ; Hanif, W ; Patel, K ; Khunti, K ; Paul, SK (BMC, 2018-05-15)
    AIMS: To estimate the risk of developing long-term major cardiovascular and renal complications in relation to levels of body mass index (BMI) in a population of White European (WE), African-Caribbean (AC), and South Asian (SA) patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Patients with new diagnosis of T2DM, aged ≥ 18 years from January 2000 (n = 69,436) and their age-sex-ethnicity matched non-diabetic controls (n = 272,190) were identified from UK primary care database. Incidence rates ratios (IRRs) for non-fatal major cardiovascular events (MACE) and chronic kidney disease (CKD) in patients with T2DM compared to controls were estimated using multivariate Mantel-Cox model. RESULTS: Among normal weight patients with T2DM, WEs had significantly higher prevalence of cardiovascular multi-morbidity (95% CI 9.5, 11.3), compared to SAs (95% CI 4.8, 9.5). AC and SA overweight and obese patients had similar prevalence, while obese WEs had significantly higher prevalence. During a median 7 years of follow-up, risk of MACE was significantly higher for overweight (95% CI of IRR 1.50, 2.46) and obese (95% CI of IRR 1.49, 2.43) SAs compared to their WE counterparts. However, similar risk levels were observed for normal weight WEs and SAs, respectively. Risk of CKD was higher and uniform for BMI ≥ 25 kg/m2 amongst WEs and ACs, whereas only overweight patients had significantly higher risk of CKD amongst SA [IRR 2.08 (95% CI 1.49, 2.93)]. CONCLUSION: Risk of MACE/CKD varies over levels of BMI within each ethnic group, with overweight SAs having a disproportionate risk of CKD.
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    Weight loss and mortality risk in patients with different adiposity at diagnosis of type 2 diabetes: a longitudinal cohort study
    Owusu, ESA ; Samanta, M ; Shaw, JE ; Majeed, A ; Khunti, K ; Paul, SK (NATURE PUBLISHING GROUP, 2018-06-01)
    BACKGROUND: Undiagnosed comorbid diseases that independently lead to weight loss before type 2 diabetes mellitus (T2DM) diagnosis could explain the observed increased mortality risk in T2DM patients with normal weight. OBJECTIVES: To evaluate the impact of weight change patterns before the diagnosis of T2DM on the association between body mass index (BMI) at diagnosis and mortality risk. METHODS: This was a longitudinal cohort study using 145,058 patients from UK primary care, with newly diagnosed T2DM from January 2000. Patients aged 18-70, without established disease history at diagnosis (defined as the presence of cardiovascular diseases, cancer, and renal diseases on or before diagnosis) were followed up to 2014. Longitudinal 6-monthly measures of bodyweight three years before (used to define groups of patients who lost bodyweight or not before diagnosis) and 2 years after diagnosis were obtained. The main outcome was all-cause mortality. RESULTS: At diagnosis, mean (SD) age was 52 (12) years, 56% were male, 52% were current or ex-smokers, mean BMI was 33 kg/m2, and 66% were obese. Normal weight and overweight patients experienced a small but significant reduction in body weight 6 months before diagnosis. Among all categories of obese patients, consistently increasing body weight was observed within the same time window. Among patients who did not lose body weight pre-diagnosis (n = 117,469), compared with the grade 1 obese, normal weight patients had 35% (95% CI of HR: 1.17, 1.55) significantly higher adjusted mortality risk. However, among patients experiencing weight loss before diagnosis (n = 27,589), BMI at diagnosis was not associated with mortality risk (all p > 0.05). CONCLUSIONS: Weight loss before the diagnosis of T2DM was not associated with the observed increased mortality risk in normal weight patients with T2DM. This emphasises the importance of addressing risk factors post diagnosis for excess mortality in this group.
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    Therapeutic inertia in the management of dyslipidaemia and hypertension in incident type 2 diabetes and the resulting risk factor burden: Real-world evidence from primary care
    Ling, JZJ ; Montvida, O ; Khunti, K ; Zhang, AL ; Xue, CC ; Paul, SK (WILEY, 2021-03-25)
    OBJECTIVE: To investigate trends in the prevalence of hypertension and dyslipidaemia in incident type 2 diabetes (T2DM), time to antihypertensive (AHT) and lipid-lowering therapy (LLT), and the association with systolic blood pressure (SBP) and lipid control. RESEARCH DESIGN AND METHODS: Using The Health Improvement Network UK primary care database, 254 925 people with incident T2DM and existing dyslipidaemia or hypertension were identified. Among those without atherosclerotic cardiovascular disease (ASCVD) history and not on AHT or LLT at diagnosis, the adjusted median months to initiating an AHT or an LLT, and the probabilities of high SBP or lipid levels over 2 years in people initiating therapy within or after 1 year were evaluated according to high and low ASCVD risk status. RESULTS: At diabetes diagnosis, 66% and 66% had dyslipidaemia and hypertension, respectively. During 2005 to 2016, dyslipidaemia prevalence increased by 10% in people aged <60 years, while hypertension prevalence remained stable in all age groups. Among those with high ASCVD risk status in the age groups 18 to 39, 40 to 49, and 50 to 59 years, the median number of months to initiation of therapy were 20.4 (95% confidence interval [CI] 20.3-20.5), 10.9 (95% CI 10.8-11.0), and 9.5 (95% CI 9.4-9.6) in the dyslipidaemia subcohort, and 28.1 (95% CI 28.0-28.2), 19.2 (95% CI 19.1-19.3), and 19.9 (95% CI 19.8-20.0) in the hypertension subcohort. Among people with high and low ASCVD risk status, respectively, compared to early LLT initiators, those who initiated LLT after 1 year had a 65.3% to 85.3% and a 65.0% to 85.3% significantly higher probability of failing lipid control at 2 years of follow-up, while late AHT initiators had a 46.5% to 57.9% and a 40.0% to 58.7% significantly higher probability of failing SBP control. CONCLUSIONS: Significant delay in initiating cardioprotective therapies was observed, and time to first prescription was similar in the primary prevention setting, irrespective of ASCVD risk status across all T2DM diagnosis age groups, resulting in poor risk factor control at 2 years of follow-up.
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    Temporal trends in co-morbidities and cardiometabolic risk factors at the time of type 2 diabetes diagnosis in the UK
    Ling, J ; Koye, D ; Buizen, L ; Khunti, K ; Montvida, O ; Paul, SK (WILEY, 2021-03-12)
    AIM: To evaluate temporal patterns in co-morbidities, cardiometabolic risk factors and a high atherosclerotic cardiovascular disease (ASCVD) risk population at type 2 diabetes (T2D) diagnosis by age groups and sex. MATERIALS AND METHODS: From the UK primary care database, 248,619 people with a new diagnosis of T2D during 2005-2016 were identified. Among people without ASCVD, high ASCVD risk was defined as two or more of current smoker, grade 2+ obesity, hypertension, dyslipidaemia or microvascular disease. Cardiometabolic multimorbidity (CMM) was defined as two or more of cardiovascular disease, microvascular disease, hypertension, dyslipidaemia, grade 2+ obesity or cancer. Temporal patterns in the distribution of cardiometabolic risk factors were evaluated. RESULTS: While the prevalence of ASCVD was stable over time (approximately 18%), 50% were identified to have a high ASCVD risk (26% and 38% in the 18-39 and 40-49 years age groups, respectively), with an increasing trend across all age groups. Overall, 51% had CMM at diagnosis, increasing during 2005-2016 for the 18-39 years age group by 14%-17%, for the 40-49 years age group by 27%-33%, for the 50-59 years age group by 41%-50%, for the 60-69 years age group by 56%-65%, and for the 70-79 years age group by 65%-80%. People with young-onset T2D had significantly higher HbA1c, body mass index and lipids at diagnosis (all p < .01). The proportions with an HbA1c of 7.5% or higher in the 18-39 and 40-49 years age groups were 58% and 54%, respectively, significantly and consistently higher over the last decade compared with those aged 50 years or older, with males having higher proportions of 15-26 and 10-18 percentage points, respectively, compared with females. CONCLUSIONS: CMM and high ASCVD risk have been increasing consistently across all age groups and in both sex, in particular CMM in those aged younger than 50 years. Our findings indicate that the European Society of Cardiology-European Association for the Study of Diabetes recommendations need to change to consider people with young-onset T2D as a high-risk group, as recommended in the Primary Care Diabetes Europe position statement.