Association and relative importance of multiple risk factor control on cardiovascular disease, end-stage renal disease and mortality in people with type 2 diabetes: A population-based retrospective cohort study

Published:August 27, 2020DOI:


      • Evidence on the relative importance of risk factor control targets is lacking.
      • A retrospective cohort of 53,942 newly diagnosed type 2 diabetes was analysed.
      • Only 11.5% of patients have achieved risk factor control targets in primary care.
      • Lower risks of study outcome events were observed as added number of risk factor targets attained.



      To evaluate the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality, when implementing a multifactorial optimal control approach in primary care in the United Kingdom (UK), in individuals with newly diagnosed type 2 diabetes.

      Materials and methods

      A retrospective cohort of 53 942 patients were stratified into 1 of the 8 groups according to whether glycated haemoglobin (HbA1c), blood pressure (BP) and total cholesterol (TC) target values were achieved or not from baseline to the date of last follow-up. Those with single or combinations of risk factor control targets achieved, were compared to those who achieved no targets in any of the risk factor. Hazard ratios from the Cox proportional hazards models were estimated against patients who achieved no targets.


      Of 53 942 patients with newly diagnosed type 2 diabetes, 28%, 55%, and 68% were at target levels for HbA1c <48 mmol/mol (<6.5%), BP < 140/85 mm Hg, and TC < 5 mmol/L respectively, 36%, 40%, and 12% were at target levels for any one, two, or all three risk factors respectively. Being at HbA1c, BP, and TC targets was associated with an overall 47%, 25%, 42%, 55% and 42% reduction in the risk of ischemic heart disease, cerebrovascular disease, ESRD, cardiovascular-mortality, and all-cause-mortality respectively. Among all subgroups, the risk reduction of study outcome events was greater in the subgroups of patients with microalbuminuria, males, smokers, and patients with BMI ≥ 30 kg/m2.


      Optimal levels of HbA1c, BP, and TC occurring together in patients with newly diagnosed type 2 diabetes are uncommon. Achieving multiple risk factor control targets could substantially reduce the risk of CVD, ESRD and mortality.


      To read this article in full you will need to make a payment


      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Diagnosis and classification of diabetes mellitus.
        Diabetes Care. 2010; 33 (S62-S9)
        • The Emerging Risk Factors Collaboration
        Association of cardiometabolic multimorbidity with mortality.
        Jama. 2015; 314: 52-60
        • Campbell I.
        Epidemiology and clinical presentation of type 2 diabetes.
        Value Health. 2000; 3: 3-6
        • International Diabetes Federation Guideline Development Group
        Global guideline for type 2 diabetes.
        Diabetes Res. Clin. Pract. 2014; 104: 1
        • National Institute for Health and Care Excellence
        Type 2 Diabetes in Adults: Management: NICE Clinical Guideline [NG28].
        2019 (accessed 20/03/2019)
        • American Diabetes Association
        Standards of medical care in diabetes—2015 abridged for primary care providers.
        Clinical diabetes: a publication of the American Diabetes Association. 2015; 33: 97
        • Stone M.A.
        • Charpentier G.
        • Doggen K.
        • et al.
        Quality of care of people with type 2 diabetes in eight European countries: findings from the Guideline Adherence to Enhance Care (GUIDANCE) study.
        Diabetes Care. 2013; DC_121759
        • Wong N.D.
        • Patao C.
        • Wong K.
        • Malik S.
        • Franklin S.S.
        • Iloeje U.
        Trends in control of cardiovascular risk factors among US adults with type 2 diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease status.
        Diab. Vasc. Dis. Res. 2013; 10: 505-513
        • Fan W.
        • Song Y.
        • Inzucchi S.E.
        • et al.
        Composite cardiovascular risk factor target achievement and its predictors in US adults with diabetes: the Diabetes Collaborative Registry.
        Diabetes Obes. Metab. 2019; 21: 1121-1127
        • Ali M.K.
        • Bullard K.M.
        • Saaddine J.B.
        • Cowie C.C.
        • Imperatore G.
        • Gregg E.W.
        Achievement of goals in US diabetes care, 1999–2010.
        N. Engl. J. Med. 2013; 368: 1613-1624
        • Khunti K.
        • Kosiborod M.
        • Ray K.K.
        Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia?.
        Diabetes Obes. Metab. 2018; 20: 1337-1341
        • Usman M.
        • Gillies C.L.
        • Khunti K.
        • Davies M.J.
        Effects of intensive interventions compared to standard care in people with type 2 diabetes and microalbuminuria on risk factors control and cardiovascular outcomes: a systematic review and meta-analysis of randomised controlled trials.
        Diabetes Res. Clin. Pract. 2018; 146: 76-84
        • Herrett E.
        • Gallagher A.M.
        • Bhaskaran K.
        • et al.
        Data resource profile: clinical practice research datalink (CPRD).
        Int. J. Epidemiol. 2015; 44: 827-836
        • Von Elm E.
        • Altman D.G.
        • Egger M.
        • et al.
        The strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
        PLoS Med. 2007; 4: e296
        • Wan E.Y.F.
        • Fung C.S.C.
        • Yu E.Y.T.
        • et al.
        Effect of multifactorial treatment targets and relative importance of hemoglobin A1c, blood pressure, and low‐density lipoprotein‐cholesterol on cardiovascular diseases in chinese primary care patients with type 2 diabetes mellitus: a population‐based retrospective cohort study.
        J. Am. Heart Assoc. 2017; 6e006400
        • Gulliford Mc
        • Charlton J.
        • Ashworth M.
        • Rudd A.G.
        • Toschke A.M.
        • eR Team
        Selection of medical diagnostic codes for analysis of electronic patient records. Application to stroke in a primary care database.
        PLoS One. 2009; 4: e7168
        • Bhattarai N.
        • Charlton J.
        • Rudisill C.
        • Gulliford M.C.
        Coding, recording and incidence of different forms of coronary heart disease in primary care.
        PLoS One. 2012; 7e29776
        • Crellin E.
        • Mansfield K.E.
        • Leyrat C.
        • et al.
        Clinical Code List - ICD-10 - End-stage Renal Disease.
        London School of Hygiene & Tropical Medicine, London, United Kingdom2017
        • Molenberghs G.
        • Kenward M.
        Missing Data in Clinical Studies.
        John Wiley & Sons, 2007
        • Fielding S.
        • Fayers P.
        • Ramsay C.
        Predicting missing quality of life data that were later recovered: an empirical comparison of approaches.
        Clin. Trials. 2010; 7: 333-342
        • Ulm K.
        Simple method to calculate the confidence interval of a standardized mortality ratio (SMR).
        Am. J. Epidemiol. 1990; 131: 373-375
        • Gaede P.
        • Vedel P.
        • Parving H.H.
        • Pedersen O.
        Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.
        Lancet. 1999; 353: 617-622
        • Gaede P.
        • Lund-Andersen H.
        • Parving H.H.
        • Pedersen O.
        Effect of a multifactorial intervention on mortality in type 2 diabetes.
        N. Engl. J. Med. 2008; 358: 580-591
        • Gæde P.
        • Oellgaard J.
        • Carstensen B.
        • et al.
        Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial.
        Diabetologia. 2016; 59: 2298-2307
        • Rawshani A.
        • Rawshani A.
        • Franzén S.
        • et al.
        Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes.
        N. Engl. J. Med. 2018; 379: 633-644
        • Wong N.D.
        • Zhao Y.
        • Patel R.
        • et al.
        Cardiovascular risk factor targets and cardiovascular disease event risk in diabetes, a pooling project of the atherosclerosis risk in communities study, multi-ethnic study of atherosclerosis, and jackson heart study.
        Diabetes Care. 2016; : dc152439
        • Vazquez-Benitez G.
        • Desai J.R.
        • Xu S.
        • et al.
        Preventable major cardiovascular events associated with uncontrolled glucose, blood pressure, and lipids and active smoking in adults with diabetes with and without cardiovascular disease: a contemporary analysis.
        Diabetes Care. 2015; : dc141877
        • Wong N.D.
        • Patao C.
        • Malik S.
        • Iloeje U.
        Preventable coronary heart disease events from control of cardiovascular risk factors in US adults with diabetes (projections from utilizing the UKPDS risk engine).
        Am. J. Cardiol. 2014; 113: 1356-1361
        • Grenier J.
        • Leiter L.A.
        • Langer A.
        • et al.
        Glycaemic control and cardiovascular risk factor management in patients with diabetes with and without coronary artery disease: insights from the diabetes mellitus status in Canada survey.
        European Heart Journal–Quality of Care and Clinical Outcomes. 2016; 2: 277-284
        • Khunti K.
        • Millar-Jones D.
        Clinical inertia to insulin initiation and intensification in the UK: a focused literature review.
        Prim. Care Diabetes. 2017; 11: 3-12
        • Hayward R.A.
        • Reaven P.D.
        • Wiitala W.L.
        • et al.
        Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes.
        N. Engl. J. Med. 2015; 372: 2197-2206