People with depression have increased premature mortality and elevated prevalence of diabetes-mellitus compared to general population. However, risk of mortality and diabetes-related complications among patients with depression and co-occurring diabetes is under-studied. This population-based propensity score-matched (1:10) cohort study identified 12,175 patients with pre-existing depression and incident-diabetes (depression-diabetes group) and 117,958 patients with incident-diabetes only (diabetes-only group) between 2002 and 2021 in Hong-Kong, using territory-wide medical-record database of public-healthcare services, to investigate whether depression increased the risk of overall mortality, complications and post-complication mortality in people with diabetes. Associations of depression with all-cause mortality, complication and post-complication all-cause mortality rates were examined by Cox proportional-hazards model. Complications were assessed by Diabetes-Complications-Severity-Index (DCSI). Associations of complications, in terms of DCSI scores (complication burden), specific types and two-way combinations of complications (complication patterns) with all-cause mortality rate in depression were also examined. Our results showed that depression-diabetes group exhibited increased all-cause mortality risk (adjusted hazards-ratio: 1.06 [95 %CI: 1.02-1.10]) relative to diabetes-only group, particularly among men and older age group, with significantly higher rate of experiencing neuropathy (1.44 [1.27-1.62]) and metabolic complications (1.30 [1.09-1.56]) and lower likelihood of peripheral-vascular complications, retinopathy and nephropathy, albeit comparable macrovascular and microvascular complication rates. The mortality-rate-ratio for patients with depression and diabetes was significantly higher than patients with diabetes-only at a low level of complication burden. In conclusion, depression patients with co-occurring diabetes are at increased risk of excess mortality. Further research is warranted to improve diabetes-related outcomes and reduce mortality gap in this vulnerable population.

Extensive observational evidence has suggested an association between depression and type 2 diabetes (T2D). However, the causal relationships between these two diseases require further investigation. This study aimed to evaluate the bidirectional causal effect between two types of depression and T2D using two-sample Mendelian randomization (MR).

We applied two-step MR techniques, using single-nucleotide polymorphisms (SNPs) as the genetic instruments for analysis. We utilized summary data from genome-wide association studies (GWASs) for major depression (MD), depressive status (frequency of depressed mood in the last two weeks), T2D, and other known T2D risk factors such as obesity, sedentary behavior (time spent watching television), and blood pressure. The analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, MR pleiotropy residual sum, and outlier methods to determine potential causal relationships.

The study found that MD was positively associated with T2D, with an odds ratio (OR) of 1.26 (95% CI: 1.10-1.43, p = 5.6×10-4) using the IVW method and an OR of 1.21 (95% CI: 1.04-1.41, p = 0.01) using the weighted median method. Depressive status was also positively associated with T2D, with an OR of 2.26 (95% CI: 1.03-4.94, p = 0.04) and an OR of 3.62 (95% CI: 1.33-9.90, p = 0.01) using the IVW and weighted median methods, respectively. No causal effects of MD and depressive status on T2D risk factors were observed, and T2D did not influence these factors.

Our study demonstrates a causal relationship between depression and an increased risk of developing T2D, with both major depression and depressive status being positively associated with T2D.

We still do not have comprehensive knowledge of which framework of patient-centered care (PCC) is appropriate for diabetes care, which elements of PCC are evidence-based, and the mechanism by which PCC elements are associated with outcomes through mediators. In this review, we elaborate on these issues. We found that for diabetes care, PCC elements such as autonomy support (patient individuality), cooperation and collaboration (system-level approach), com-munication and education (behavior change techniques), emotional support (biopsychosocial approach), and family/other involvement and support are critically important. All of these factors are directly associated with different patient outcomes and indirectly associated with outcomes through patient activation. We present the practical implications of these PCC elements.

Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders.

In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20-29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30-33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis.

From 2001 to 2015, 66,914 individuals were identified as having T2D. In 2015, 1.5% of the study population had schizophrenia spectrum disorder and 1.4% had an affective disorder. The number of people who used biochemical tests or had poor biochemical risk factor control was essentially unrelated to SMI status. One exception was that fewer LDL cholesterol tests were done on people with affective disorders and schizophrenia spectrum disorders at the beginning of the study period compared to people in the non-SMI group. This difference gradually diminished and was almost nonexistent by 2011. There was also a slightly slower rise in UACR test rates in the SMI groups compared to other people with T2D during the period. Throughout the study period, all groups changed their use of medications in similar ways: more metformin, less sulfonylurea, more lipid-lowering drugs, and more ACEi/ARBs. However, people with schizophrenia disorder consistently used fewer cardiovascular medications. Cardiovascular events were more common in the affective disorder group compared to the non-SMI group from 2009 to 2015 (rate ratio 2015 : 1.36 [95% CI 1.18-1.57]). After adjustment for age and sex, all-cause mortality was significantly higher among people with a schizophrenia spectrum disorder each year from 2003 to 2015 compared to the non-SMI group (rate ratio 2015 : 1.99 [95% CI 1.26-3.12]).

Persons with schizophrenia or affective disorders demonstrated the same treatment changes for T2D as those without SMI in general practice. The lower use of most types of cardiovascular medications among people with schizophrenia disorders indicates potential undertreatment of hypertension and dyslipidemia and remains throughout the study period. Cardiovascular events were most common among people with affective disorders, but this was not reflected in a higher proportion using cardiovascular preventive medications. This knowledge should be considered in the management of this vulnerable patient group.

Serum insulin-like growth factor binding protein-2 (IGFBP-2) is low in persons with type 2 diabetes mellitus (T2D) and possibly regulated by metformin. Counter-intuitively, high IGFBP-2 associates with mortality. We investigated the association between IGFBP-2, metformin-treatment, and indices of insulin sensitivity, and assessed IGFBP-2 in relation to prior comorbidity and mortality during five-year follow-up.

The study included 859 treatment-naive and 558 metformin-treated persons enrolled in the Danish Centre for Strategic Research in T2D and followed for 4.9 (3.9-5.9) years through national health registries. All proteins were determined in serum collected at enrollment.

Following adjustment for age, metformin-treated and treatment-naive persons has similar IGFBP-2 levels. Low IGFBP-2 level was associated with increased BMI, fasting glucose, and C-peptide. IGFBP-2 was higher in the 437 persons who had comorbidities at enrollment than in those with T2D only (343 (213;528) vs. 242 (169;378) ng/mL). During follow-up, 87 persons died, and IGFBP-2 predicted mortality with an unadjusted HR (95% CI) per doubling in IGFBP-2 concentration of 2.62 (2.04;3.37) and a HR of 2.21 (1.61;3.01) following full adjustment.

In T2D, high IGFBP-2 associates with low glucose and insulin secretion, is unaffected by metformin treatment, and associates with risk of prior comorbidity and mortality.