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Association between pre-diabetes and microvascular and macrovascular disease in newly diagnosed type 2 diabetes
  1. Raffaele Palladino1,2,3,
  2. Adam G Tabak4,5,
  3. Kamlesh Khunti6,
  4. Jonathan Valabhji7,8,
  5. Azeem Majeed3,
  6. Christopher Millett1,3,
  7. Eszter P Vamos1,3
  1. 1Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK
  2. 2Department of Public Health, University "Federico II" of Naples, Naples, Italy
  3. 3Department of Primary Care and Public Health, Imperial College London, London, UK
  4. 4Department of Epidemiology and Public Health, University College London, London, UK
  5. 51st Department of Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary
  6. 6Diabetes Research Centre, Leicester Diabetes Centre, University of Leicester, Leicester, UK
  7. 7Imperial College Healthcare NHS Trust, London, UK
  8. 8NHS England, Skipton House, London, UK
  1. Correspondence to Dr Raffaele Palladino; r.palladino{at}


Objective The associated risk of vascular disease following diagnosis of type 2 diabetes in people previously identified as having pre-diabetes in real-world settings is unknown. We examined the presence of microvascular and macrovascular disease in individuals with newly diagnosed type 2 diabetes by glycemic status within 3 years before diagnosis.

Research design and methods We identified 159 736 individuals with newly diagnosed type 2 diabetes from the UK Clinical Practice Research Datalink database in England between 2004 and 2017. We used logistic regression models to compare presence of microvascular (retinopathy and nephropathy) and macrovascular (acute coronary syndrome, cerebrovascular and peripheral arterial disease) disease at the time of type 2 diabetes diagnosis by prior glycemic status.

Results Half of the study population (49.9%) had at least one vascular disease, over one-third (37.4%) had microvascular disease, and almost a quarter (23.5%) had a diagnosed macrovascular disease at the time of type 2 diabetes diagnosis.

Compared with individuals with glycemic values within the normal range, those detected with pre-diabetes before the diagnosis had 76% and 14% increased odds of retinopathy and nephropathy (retinopathy: adjusted OR (AOR) 1.76, 95% CI 1.69 to 1.85; nephropathy: AOR 1.14, 95% CI 1.10 to 1.19), and 7% higher odds of the diagnosis of acute coronary syndrome (OR 1.07, 95% CI 1.03 to 1.12) in fully adjusted models at time of diabetes diagnosis.

Conclusions Microvascular and macrovascular diseases are detected in 37%–24% of people with newly diagnosed type 2 diabetes. Pre-diabetes before diagnosis of type 2 diabetes is associated with increased odds of microvascular disease and acute coronary syndrome. Detection of pre-diabetes might represent an opportunity for reducing the burden of microvascular and macrovascular disease through heightened attention to screening for vascular complications.

  • pre-diabetes
  • microvascular
  • macrovascular
  • retinopathy

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  • Contributors EPV, CM, and RP conceived and designed the study. RP analyzed the data. All authors discussed the data analyses and interpreted the results. EPV, CM and RP wrote the first draft of the manuscript. All authors critically revised the manuscript, approved the final manuscript for publication, and agreed to act as guarantors of the work. RP has full access to all data used in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Independent Scientific Advisory Committee (ISAC) of the CPRD (protocol no. 18_208R), before data analysis was conducted. Ethical approval is not needed for database studies and ISAC provide the necessary regulatory approvals. Each practice in CPRD has consented to be included; patients within each consented practice are automatically included.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. The data that support the findings of this study are available from CPRD, but restrictions apply to the availability of these data, which were used under license from the UK Medicines and Healthcare products Regulatory Agency for the current study, and so are not publicly available.