Focus on severe mental illness in type 2 diabetes
The presence of severe mental illness can worsen cardiovascular morbidity and mortality suggests a study based on a nationwide type 2 diabetes cohort, reported in Diabetes Care. This high-risk group therefore merits special attention when it comes to prevention and management of heart disease. Dr Susan Aldridge reports.
People who have severe mental illness (SMI), including schizophrenia, bipolar disorder and major depression, have a 10 to 20 years shorter life expectancy than the general population. This premature mortality is largely due to a higher risk of physical disease, particularly cardiovascular disease (CVD), where diabetes is a major risk factor. Having SMI is also associated with a two to three-fold higher risk of type 2 diabetes – a risk that may even be on the increase.
While we already know that depression in people with diabetes is associated with increased risk of CVD and cardiac death, other complications and all-cause mortality, fewer studies have focused on severe depression, schizophrenia and bipolar disorder. In the few existing studies, SMI is consistently associated with an increased risk of mortality among people with diabetes, but findings on associations between SMI and macrovascular and microvascular complications have been inconsistent.
In a new study, Caroline Jackson of the University of Edinburgh and on behalf of the Scottish Diabetes Research Network Epidemiology Group, looked at a large, nationally representative diabetes cohort to determine the association between SMI and clinical outcomes. Their aim was to determine the independent effects of schizophrenia, bipolar disorder and major depression on the risk of major CVD events, CVD-specific mortality and all-cause mortality in people with type 2 diabetes.
The study drew upon data from the Scottish Diabetes Research Network National Diabetes Dataset (SDRN-NDS), which covers 99% of people with diabetes in Scotland. It includes information on type of diabetes, sociodemographics, routine diabetes care, including retinopathy screening, and linked acute and psychiatric hospital records and death records. The study population comprised 259,875 adults diagnosed with type 2 diabetes in Scotland between 2004 and 2018 whose data could be linked with hospital and death records.
The primary outcomes were major CVD events – myocardial infarction (MI) or stroke – in the whole cohort and also in the subgroup without a history of CVD, CVD-specific mortality and all-cause mortality. Secondary outcomes were related to other diabetes complications, consisting of retinopathy, renal replacement therapy and lower-limb amputation.
Characteristics of people with SMI and type 2 diabetes
The SDRN-NDS hospital record data revealed that 2,621 (1%) of this cohort had a diagnosis of schizophrenia, 1,211 (0.5%) had bipolar disorder and 7,903 (3%) had depression. The cohort was mainly of White ethnicity and there was a higher prevalence of type 2 diabetes among those from more deprived areas. This was even more striking among those with SMI. For instance, more than one-third of those with schizophrenia came from the most deprived fifth of areas in Scotland.
Diabetes was diagnosed at a younger mean age in those with a history of schizophrenia (52.1 years), bipolar disorder (57.5 years) or depression (58.9 years), compared with those without a history of SMI (60.8 years).
Furthermore, history of prior CVD, comorbidity and high cholesterol at the time of diabetes diagnosis were also more common among those with depression and bipolar disorder compared with those without SMI. This wasn’t seen for those with schizophrenia, maybe reflecting their younger age at diabetes diagnosis. Smoking, history of alcohol use disorder and overweight or obesity were also more common among those with SMI.
The impact of SMI
The researchers carried out a statistical analysis that adjusted for all the factors that could affect the findings – sociodemographics, HbA1c, hypertension, smoking and so on. This fully adjusted model helped clarify the link between the presence of SMI and health outcomes.
During a mean of 6.9 years of follow-up, there were nearly 25,000 major CVD events. All three SMIs were associated with an increased risk of having a major CVD event. The hazard ratios were 1.07, 1.37 and 1.22, for schizophrenia, bipolar disorder and depression, respectively, for the fully adjusted model. The association was similar, whether or not the individual had a history of CVD.
There were also 51,029 deaths occurring during a mean follow-up of 7.1 years. Deaths from CVD were higher among those with SMI than those without, with hazard ratios of 2.38 for schizophrenia, 1.70 for bipolar disorder and 1.84 for depression. This was for a model adjusted for sociodemographic factors – the hazard ratios were attenuated only slightly when the fully adjusted model was applied, so there is a persistent higher risk of CVD mortality in all groups with SMI and type 2 diabetes. Similar increased risk also applied to all-cause mortality.
When it came to the secondary outcomes, numbers with lower limb amputation and renal replacement therapy were low – at around 0.6% and 0.2%, respectively – in those with and without a history of SMI. Referable retinopathy occurred in around 5% of both groups. Numbers for these three complications were too low to make comparisons between those with and without SMI in this study.
Previous studies of SMI and macrovascular complications among people with diabetes report conflicting findings. For instance, a study from South Korea found a similar excess risk of heart attack and stroke among those with diabetes and schizophrenia, bipolar disorder or depression. A Taiwanese study found an association between clinical depression with diabetes and increased risk of acute coronary syndrome and stoke. And these new findings also echo those of a Danish study that found that SMI, as a composite exposure, was associated with higher CVD risk – although that was more broadly defined than in the current study. In contrast, however, there have been two studies that actually reported a lower risk of CVD events among people with schizophrenia or major depression.
Only two previous studies have reported an association between SMI and CV-specific mortality in diabetes, with similar findings. There has also been a meta-analysis of studies examining depression of any severity and the risk and the risk of CV mortality in people with diabetes – again with similar findings. And the observed excess all-cause mortality among people with diabetes and SMI compared with no mental illness is consistent with previous literature. This new study adds to scarce data on bipolar disorder, which has been less studied in this context in comparison with schizophrenia and major depression.
The mechanisms behind the increased CVD morbidity and mortality among those with diabetes and SMI shown by this new study are complicated and poorly understood. We already know that shared risk factors for poor physical and mental health include low socioeconomic status, adverse childhood experiences and lifestyle. In this study, the higher prevalence of smoking, overweight and obesity and comorbidities was made evident through statistical analysis that adjusted for these factors and showed an attenuation of the risk. Meanwhile, a study from Denmark of people with type 2 diabetes showed that excess mortality among those with depression was largely explained through smoking, physical activity and comorbidities.
There is also emerging evidence that brain insulin resistance might be part of the pathophysiology of schizophrenia and bipolar disorder. This might go some way to explaining poorer diabetes outcomes in those with SMI.
Inequalities in care for physical disease may also explain the poorer outcomes among those with SMI and diabetes. A recent study from Denmark reports lower rates of diabetes monitoring and achievement of HbA1c and cholesterol targets in those with SMI, compared with those without. However, disparities in care do not explain the findings in this new study – in Scotland, receipt of diabetes care processes is actually similar or better in those with SMI than for those without.
It may be that this does not translate into optimal treatment of those with CVD risk factors or established CVD. Previous studies of populations with and without diabetes have uncovered suboptimal CVD risk management in those with SMI. The excess risk of CV death in people with diabetes and SMI found in this new study may reflect more severe cardiovascular events and potential differences in cardiac care, both in the acute phase and subsequently. For instance, previous work from these authors has shown that patients with SMI were less likely to receive coronary revascularisation after MI, were less likely to survive for 30 days post-MI and were more likely to have a further vascular event than those without mental illness.
Cardiac and metabolic adverse effects of some antipsychotic medications may also play a role in poorer outcomes. The impact of antipsychotic and antidepressant drugs upon CV and mortality outcomes in people with diabetes is an underinvestigated topic.
This new study shines a light on an area where previous studies are scarce or contradictory and addresses a number of limitations and gaps in the literature. It draws on data from a nationally representative cohort of people with diabetes with and without SMI. This large study population and long follow-up allowed the researchers to investigate individual SMIs, analyse specific CVD outcomes and obtain reliable, precise effect estimates for outcomes. The richness of the diabetes register allowed associations to be adjusted for key lifestyle factors, which hasn’t always been done in other studies. Finally, the study also adds to scarce data on associations between SMI and CVD-specific mortality in people with diabetes and on all-cause mortality in those with bipolar disorder specifically.
In conclusion, among people with new-onset type 2 diabetes, those with a prior history of SMI have a markedly higher risk of major CVD events, CVD-specific mortality and all-cause mortality than people with no mental illness. Some of this excess risk is due to modifiable risk factors, including smoking, alcohol misuse and obesity, highlighting the need for effective lifestyle modification in people with SMI. However, there are other emerging mechanisms, including possible shared pathophysiology between SMI and diabetes, which require further investigation.
Another future avenue of research should be the role of psychotropic medication use and receipt of optimal cardiac care in primary and secondary care settings. Meanwhile, effective prevention and management of cardiovascular risk factors is needed in this high-risk group to improve clinical outcomes.
To read this paper, go to: Fleetwood KJ, Wild SH, Licence KAM, Mercer SW, Smith DJ, Jackson CA on behalf of the Scottish Diabetes Research Network Epidemiology Group. Diabetes Care 2023;46:1363–1371. https://doi.org/10.2337/dc23-0177
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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.