Depression After T2D Diagnosis Links With A1c Variability

Researchers published the study covered in this summary on medRxiv as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Among more than 9000 patients diagnosed with type 2 diabetes, those who were diagnosed with major depressive disorder (clinical depression) following onset of their type 2 diabetes had significantly greater variability in their A1c levels compared with patients diagnosed with MDD before they developed type 2 diabetes and with those who never had MDD.

  • The findings suggest that people who develop type 2 diabetes and later also receive a diagnosis of MDD have an increased risk for developing impaired glycemic control.

Why This Matters

  • In patients with type 2 diabetes, elevated A1c levels and greater variability in A1c over time are each associated with increased risk for long-term diabetic complications such as stroke and cardiovascular disease.

  • Having MDD in addition to type 2 diabetes is associated with worse prognosis, an elevated risk of diabetic complications, and a higher suicide risk.

  • The current findings suggest that a diagnosis of MDD following a diagnosis of type 2 diabetes contributes to worse glycemic control and hence worse outcomes. No prior reported study examined the timing of onset of type 2 diabetes and MDD and trends in A1c level over time.

  • The findings suggest that clinicians need to monitor mean A1c levels over time in patients with type 2 diabetes and also closely monitor within-patient variability in A1c levels, especially when the patient receives a diagnosis of MDD following a diagnosis of type 2 diabetes.

Study Design

  • The researchers analyzed data from the UK Biobank, which prospectively enrolled UK residents who were aged 40-69 years during the period 2006 to 2020.

  • They identified individuals who had type 2 diabetes, based on fulfilling at least two of these criteria: (1) a recorded diagnostic code for type 2 diabetes, (2) a record of an A1c level >6.5%, (3) a prescription for a glucose-lowering medication, or (4) a self-reported diagnosis for type 2 diabetes at 35 years old or later. People who did not fulfil these criteria were considered free of type 2 diabetes and were eligible to be included as controls.

  • They also identified subjects with MDD based on a history of an MDD diagnosis at least twice in their medical records. They divided the subjects into three groups: diabetes without MDD, a diagnosis of MDD before the diabetes diagnosis, or MDD diagnosed after diabetes diagnosis.

Key Results

  • The longitudinal analysis sample consisted of 9264 eligible patients with type 2 diabetes, followed for a median of 7.6 years: 82% without MDD, 13% with MDD diagnosed before their diabetes diagnosis, and 5% with their MDD diagnosed after their diabetes diagnosis.

  • Within-patient variability in A1c was 14% higher in those who were diagnosed with MDD after they had been diagnosed with type 2 diabetes compared with those with type 2 diabetes without clinical depression, a difference that was significant.

  • The analysis showed no significant increase in A1c variability over time in patients diagnosed with clinical depression before their initial diagnosis of type 2 diabetes.

  • Changes in mean A1c over time were similar in all three patient groups based on their MDD status.


  • The study relied in part on A1c measurements made during regular, routine visits to primary care clinicians, but development of MDD may have altered this schedule in some subjects resulting in fewer recorded A1c values.

  • This was a retrospective, observational study, so confounders may have affected the results.

  • Many measures of A1c and many diagnoses of type 2 diabetes appeared to be missing.

  • The validity of the age when subjects first received their diagnosis of MDD is uncertain.


  • The study did not receive commercial funding.

  • None of the authors had relevant financial disclosures.

This is a summary of a preprint research study “The impact of major depressive disorder on glycaemic control in type 2 diabetes: a cohort study using UK Biobank primary care records” written by researchers from King’s College London and the University of Exeter, UK, on medRxiv and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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