Depression, diabetes, their comorbidity and all-cause and cause-specific mortality:a prospective cohort study

AIMS/HYPOTHESIS: The aim of this study was to investigate the risks of all-cause and cause-specific mortality among participants with neither, one or both of diabetes and depression in a large prospective cohort study in the UK. METHODS: Our study population included 499,830 UK Biobank participants without schizophrenia and bipolar disorder at baseline. Type 1 and type 2 diabetes and depression were identified using self-reported diagnoses, prescribed medication and hospital records. Mortality was identified from death records using the primary cause of death to define cause-specific mortality. We performed Cox proportional hazards models to estimate the risk of all-cause mortality and mortality from cancer, circulatory disease and causes of death other than circulatory disease or cancer among participants with either depression (n=41,791) or diabetes (n=22,677) alone and with comorbid diabetes and depression (n=3597) compared with the group with neither condition (n=431,765), adjusting for sociodemographic and lifestyle factors, comorbidities and history of CVD or cancer. We also investigated the interaction between diabetes and depression. RESULTS: During a median of 6.8 (IQR 6.1–7.5) years of follow-up, there were 13,724 deaths (cancer, n=7976; circulatory disease, n=2827; other causes, n=2921). Adjusted HRs of all-cause mortality and mortality from cancer, circulatory disease and other causes were highest among people with comorbid depression and diabetes (HRs 2.16 [95% CI 1.94, 2.42]; 1.62 [95% CI 1.35, 1.93]; 2.22 [95% CI 1.80, 2.73]; and 3.60 [95% CI 2.93, 4.42], respectively). The risks of all-cause, cancer and other mortality among those with comorbid depression and diabetes exceeded the sum of the risks due to diabetes and depression alone. CONCLUSIONS/INTERPRETATION: We confirmed that depression and diabetes individually are associated with an increased mortality risk and also identified that comorbid depression and diabetes have synergistic effects on the risk of all-cause mortality that are largely driven by deaths from cancer and causes other than circulatory disease and cancer. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-022-05723-4

Defining remission of type 2 diabetes in research studies: A systematic scoping review

BackgroundRemission has been identified as a top priority by people with type 2 diabetes. Remission is commonly used as an outcome in research studies; however, a widely accepted definition of remission of type 2 diabetes is lacking. A report on defining remission was published (but not formally endorsed) in Diabetes Care, an American Diabetes Association (ADA) journal. This Diabetes Care report remains widely used. It was the first to suggest 3 components necessary to define the presence of remission: (1) absence of glucose-lowering therapy (GLT); (2) normoglycaemia; and (3) for duration ≥1 year. Our aim is to systematically review how remission of type 2 diabetes has been defined by observational and interventional studies since publication of the 2009 report.Methods and findingsFour databases (MEDLINE, EMBASE, Cochrane Library, and CINAHL) were searched for studies published from 1 September 2009 to 18 July 2020 involving at least 100 participants with type 2 diabetes in their remission analysis, which examined an outcome of type 2 diabetes remission in adults ≥18 years and which had been published in English since 2009. Remission definitions were extracted and categorised by glucose-lowering therapy, glycaemic thresholds, and duration. A total of 8,966 titles/abstracts were screened, and 178 studies (165 observational and 13 interventional) from 33 countries were included. These contributed 266 definitions, of which 96 were unique. The 2009 report was referenced in 121 (45%) definitions. In total, 247 (93%) definitions required the absence of GLT, and 232 (87%) definitions specified numeric glycaemic thresholds. The most frequently used threshold was HbA1cConclusionsWe found that there is substantial heterogeneity in the definition of type 2 diabetes remission in research studies published since 2009, at least partly reflecting ambiguity in the 2009 report. This complicates interpretation of previous research on remission of type 2 diabetes and the implications for people with type 2 diabetes. Any new consensus definition of remission should include unambiguous glycaemic thresholds and emphasise duration. Until an international consensus is reached, studies describing remission should clearly define all 3 components of remission.Systematic review registrationPROSPERO CRD42019144619

Ethnic disparities in quality of diabetes care in Scotland:a national cohort study

Aims: The aim of this study is to compare quality of diabetes care in people with type 2 diabetes by ethnicity, in Scotland. Methods: Using a linked national diabetes registry, we included 162,122 people newly diagnosed with type 2 diabetes between 2009 and 2018. We compared receipt of nine guideline indicated processes of care in the first-year post-diabetes diagnosis using logistic regression, comparing eight ethnicity groups to the White group. We compared annual receipt of HbA1c and eye screening during the entire follow-up using generalised linear mixed effects. All analyses adjusted for confounders. Results: Receipt of diabetes care was lower in other ethnic groups compared to White people in the first-year post-diagnosis. Differences were most pronounced for people in the: African, Caribbean or Black; Indian; and other ethnicity groups for almost all processes of care. For example, compared to White people, odds of HbA1c monitoring were: 44% lower in African, Caribbean or Black people (OR 0.56 [95% CI 0.48, 0.66]); 47% lower in Indian people (OR 0.53 [95% CI 0.47, 0.61]); and 50% lower in people in the other ethnicity group (OR 0.50 [95% CI 0.46, 0.58]). Odds of receipt of eye screening were 30%–40% lower in most ethnic groups compared to the White group. During median 5 year follow-up, differences in HbA1c monitoring and eye screening largely persisted, but attenuated slightly for the former. Conclusions: There are marked ethnic disparities in routine diabetes care in Scotland in the short- and medium-term following diabetes diagnosis. Further investigation is needed to establish and effectively address the underlying reasons.</p

Severe depression and all-cause and cause-specific mortality in Scotland: a 20-year national cohort study

BackgroundUnderstanding cause of death in people with depression could inform approaches to reducing premature mortality.AimTo describe all-cause and cause-specific mortality for people with severe depression in Scotland, by sex, relative to the general population.MethodWe performed a retrospective cohort study, using psychiatric hospital admission data linked to death data, to identify adults (≥18 years old) with severe depression and ascertain cause-specific deaths, during 2000–2019. We estimated relative all-cause and cause-specific mortality for people with severe depression using standardised mortality ratios (SMRs), stratified by sex using the whole Scottish population as the standard.ResultsOf 28 808 people with severe depression, 7903 (27.4%) died during a median follow-up of 8.7 years. All-cause relative mortality was over three times higher than expected (SMR, both sexes combined: 3.26, 95% CI 3.19–3.34). Circulatory disease was the leading cause of death, and, among natural causes of death, excess relative mortality was highest for circulatory diseases (SMR 2.51, 2.40–2.66), respiratory diseases (SMR 3.79, 3.56–4.01) and ‘other’ causes (SMR 4.10, 3.89–4.30). Among circulatory disease subtypes, excess death was highest for cerebrovascular disease. Both males and females with severe depression had higher all-cause and cause-specific mortality than the general population. Suicide had the highest SMR among both males (SMR 12.44, 95% CI 11.33–13.54) and females (22.86, 95% CI 20.35–25.36).ConclusionPeople with severe depression have markedly higher all-cause mortality than the general population in Scotland, with relative mortality varying by cause of death. Effective interventions are needed to reduce premature mortality for people with severe depression.<br/

Type 1 diabetes incidence in Scotland between 2006 and 2019

Aims: To describe type 1 diabetes incidence in Scotland between 2006 and 2019. Methods: Repeated annual cross‐sectional studies of type 1 diabetes incidence were conducted. Incident cases were identified from the Scottish Care Information—Diabetes Collaboration (SCI‐DC), a population‐based register of people with diagnosed diabetes derived from primary and secondary care data. Mid‐year population estimates for Scotland were used as the denominator to calculate annual incidence with stratification by age and sex. Joinpoint regression was used to investigate whether incidence changed during the study period. Age and sex‐specific type 1 diabetes incidence over the whole time period was estimated by quintile of the Scottish Index of Multiple Deprivation (SIMD), an area‐based measure, in which Q1 and Q5 denote the most and least deprived fifths of the population, respectively, with quasi‐Poisson regression used to compare incidence for Q5 compared to Q1. Results: The median (IQR) age of the study population of 14,564 individuals with incident type 1 diabetes was 24.1 (12.3–42.4) years, 56% were men, 23% were in Q1 and 16% were in Q5. Incidence of T1DM was higher in men than women overall (at around 22 and 17 per 100,000, respectively) and in under 15 year olds (approximately 40 per 100,000 in both sexes) than other age groups and was similar across the study period in all strata. There was an inverse association between socio‐economic status and type 1 diabetes incidence for 15–29, 30–49 and 50+ year olds [incidence rate ratio (IRR) for Q5 compared to Q1; IRR (95% CI) 0.52 (0.47–0.58), 0.68 (0.61–0.76) and 0.53(0.46–0.61), respectively] but not for under 15 year olds [1.02 (0.92–1.12)]. Conclusion: Incidence of type 1 diabetes varies by age, sex and socio‐economic status and has remained approximately stable from 2006 to 2019 in Scotland

Nonalcoholic Fatty Liver Disease without overlapping Metabolic Associated Fatty Liver Disease and the risk of incident type 2 diabetes

Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex &lt;0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.<br/

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults:The Kangbuk Samsung Health Study

Aims: Whether changes in serum uric acid (SUA) are associated with resolution of nonalcoholic fatty liver disease (NAFLD) is uncertain. We aimed to determine the association between (i) baseline SUA and (ii) SUA changes over time, and NAFLD resolution. Materials and Methods: A retrospective cohort study, comprising 38,483 subjects aged &lt;40 years with pre-existing NAFLD, were undertaken. The effects of SUA changes over time were studied in 25,266 subjects. Participants underwent a health examination between 2011 and 2019, and had at least one follow-up liver ultrasound until December 2020. Exposures included baseline SUA levels, and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. Results: During a median follow-up of 4 years, low baseline SUA and decreases in SUA over time, were independently associated with NAFLD resolution (p for trend &lt;0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1 mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, the aHRs (95%CIs) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Conclusions: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.<br/