Risk of mortality and complications in patients with severe mental illness and co-occurring diabetes mellitus: A systematic review and meta-analysis.

People with severe-mental-illness (SMI), often defined as "schizophrenia-spectrum disorders and bipolar disorder", have increased premature mortality and elevated prevalence of diabetes compared with general population. Evidence indicated that one-third of their premature death was from cardiovascular diseases (CVD), with risk conferred by diabetes. Although earlier studies have examined SMI-associated diabetes-related outcomes, findings were inconsistent and not systematically evaluated. We systematically reviewed and quantitatively synthesized diabetes-related outcomes in patients with SMI (schizophrenia-spectrum disorders and bipolar disorder) by searching Embase, MEDLINE, PsycInfo, and Web-of-Science from inception to 31-March-2024, and included studies examining mortality and complication outcomes in SMI patients with co-occurring diabetes relative to patients with diabetes-only. Results were synthesized by random-effects models, with stratified-analyses by study-level characteristics. The study was registered with PROSPERO (CRD42023448490). Twenty-one studies involving 161,156 SMI patients with co-occurring diabetes were identified from ten regions. Regarding mortality risk, SMI-diabetes group exhibited increased risks of all-cause mortality (RR=1.77[95 % CI: 1.46-2.14]) and CVD-specific mortality (1.88[1.73-2.04]) relative to diabetes-only group. All-cause mortality risk was present in distinct regions and has persisted over time. Regarding complication risk, SMI-diabetes group showed higher risk of any complications (1.23[1.06-1.43]) than comparison, with stratified-analyses showing higher risk of metabolic-complications (1.84[1.58-2.15]), and lower likelihood of peripheral-vascular complications (0.91[0.84-0.99]), neuropathy (0.85[0.78-0.93]), and retinopathy (0.70[0.60-0.82]), albeit comparable cardiovascular-complications (1.04[0.89-1.22]), cerebrovascular-complications (1.07[0.86-1.33]), and nephropathy (0.92[0.72-1.17]). High heterogeneity was noted and could not be fully-explained by subgroup-analyses. Implementation of targeted interventions is needed to rectify their diabetes-related outcomes and mortality gap.