Low-Grade Inflammation Associated with Major Depression Subtypes: A Cross-Sectional Study.

Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context.

Major Depressive Disorder, Inflammation, and Nutrition: A Tricky Pattern?

Major depressive disorder (MDD) is a psychiatric disease associated with inflammation. The Western diet (WD) is a high-fat, high-sugar diet also associated with inflammation. We aimed to show whether the diet of MDD patients was a WD and could act as a risk factor in this context. We conducted a transversal study of MDD patients and controls (CTRLs) without comorbidities. We performed blood analyses including C-reactive protein (CRP), a diet anamnesis, and an advanced glycation end-product assessment. We found that 34.37% of MDD patients had a CRP level above 3 to 10 mg/L, which remained higher than CTRLs after adjustments (sex, BMI, age, smoking status). The MDD patients had an excess of sugar and saturated and trans fatty acids; a deficiency in n-3 polyunsaturated fatty acid, monounsaturated acid, dietary fibers, and antioxidants; a high glycemic load; and aggravating nutritional factors when compared to the CTRLs. We found correlations between nutritional factors and CRP in univariate/multivariate analysis models. Thus, MDD patients showed an elevated CRP level and a WD pattern that could contribute to sustaining an inflammatory state. Further studies are required to confirm this, but the results highlighted the importance of nutrition in the context of MDD.

Suicidal Ideations in Major Depressed Subjects: Role of the Temporal Dynamics of Anhedonia.

Given the limited data available in the literature, the aim of this study was to investigate the potential role played by the temporal dynamics of anhedonia (lifelong anhedonia and recent changes in anhedonia) in the occurrence of suicidal ideations in major depressed subjects. The clinical data of 285 major depressed subjects recruited from the database of the Erasme Hospital Sleep Laboratory were analyzed. A score on item nine of the Beck Depression Inventory (BDI-II) ≥1 and/or an identification during the systematic psychiatric assessment were used to determine the presence of suicidal ideations. The association between anhedonia complaints (lifelong anhedonia and recent change in anhedonia) and suicidal ideations in major depressed subjects was assessed by logistic regression analyzes. The prevalence of suicidal ideations was 39.3% in our sample of major depressed subjects. After adjusting for the main confounding factors, multivariate logistic regression analysis demonstrated that unlike lifelong anhedonia, only recent changes in anhedonia were a risk factor for suicidal ideations in major depressed subjects. Given this potential involvement of the recent change in anhedonia in the occurrence of suicidal ideations in major depressed subjects, it seems essential to better identify and adequately manage this specific form of anhedonia in order to open new perspectives for the prevention of suicide in this particular sub-population.

10-Year Risk for Cardiovascular Disease Associated with COMISA (Co-Morbid Insomnia and Sleep Apnea) in Hypertensive Subjects.

Due to the few studies available, this study aimed to investigate the 10-year risk for cardiovascular disease (CVD) associated with COMISA (co-morbid insomnia and sleep apnea) in hypertensive subjects. Clinical data of 1009 hypertensive subjects extracted from the Sleep Laboratory database were analyzed. Framingham Risk Score ≥ 10% was used as a cut-off to identify hypertensive subjects with high 10-year risk for CVD. The association between 10-year risk for CVD and COMISA was investigated using logistic regression analyses. 65.3% of hypertensive subjects from our sample presented a high 10-year risk for CVD. After controlling for major confounding factors, multivariate logistic regression analyses demonstrated that unlike its components present separately, COMISA was significantly associated with high 10-year risk for CVD in hypertensive subjects (OR 1.88, 95% CI 1.01-3.51). In this study, we have demonstrated that the negative synergy between obstructive sleep apnea syndrome and insomnia disorder seems to play a central role in the 10-year risk for CVD in hypertensive subjects, which seems to indicate that the establishment of a systematic research and an adapted treatment of COMISA could open new perspectives to promote a better cardiovascular outcome in this specific subgroup of patients.

Anhedonia and suicidal ideation in young people with early psychosis: Further findings from the 2-year follow-up of the ReARMS program.

Hedonic deficits have been extensively studied in schizophrenia, but little is known about their association with suicidal ideation in early psychosis. The aim of this research was to examine the relationship between anhedonia and suicidal thoughts across a 2-year follow-up period in people with First Episode Psychosis (FEP) and at Ultra High Risk (UHR) of psychosis. Ninty-six UHR and 146 FEP, aged 13-35 years, completed the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Beck Depression Inventory-II (BDI-II). The BDI-II "Anhedonia" subscale score to assess anhedonia and the CAARMS "Depression" item 7.2 subscore to measure depression were used across the 2 years of follow-up. Hierarchical regression analyses were performed. No difference in anhedonia scores between FEP and UHR individuals was found. In the FEP group, a significant enduring association between anhedonia and suicidal ideation was found at baseline and across the follow-up, independent of clinical depression. In the UHR subgroup, the enduring relationship between anhedonia and suicidal thoughts were not completely independent from depression severity. Anhedonia is relevant in predicting suicidal ideation in early psychosis. Specific pharmacological and/or psychosocial interventions on anhedonia within specialized EIP program could reduce suicide risk overtime.

Relationship Between Recent Change of Anhedonia and Suicidal Ideation Taking Into Account the Severity and the Acuteness of Suicidal Ideation As Well As the Specific Roles of Loss of Pleasure and Loss of Interest in People: A Study on Medical Students.

The aim of the study was to explore the relationships between recent changes of anhedonia or particular symptoms of recent changes of anhedonia and suicidal ideation taking into account the severity of suicidal ideations. In a group of 173 medical students, scores of the anhedonia subscale (ANH-BDI) of the BDI-II (i.e. 4 anhedonia items: loss of pleasure, loss of interest, loss of energy and loss of interest in sex) were compared between 95 subjects without suicidality, 24 subjects with life-time suicidal ideation, 28 subjects with recent suicidal ideation and 26 planners. Analyses of covariance (ANCOVA) were performed referring to groups as independent variables, the cognitive-affective subscale (CA-BDI) of the BDI-II as a covariate, the ANH-BDI and each of the four anhedonia items as dependent variables. High levels of loss of interest characterized planners when compared to the other three groups. Loss of interest could be associated with recent and severe suicidal ideation.

Relationships between Recent Suicidal Ideation and Recent, State, Trait and Musical Anhedonias in Depression.

The aim of the study was to explore in depression the relationship between recent suicidal ideation and the different anhedonias taking into account the severity of depression. Recent studies have suggested that recent change of anhedonia and not state or trait anhedonia is associated with recent suicidal ideations even when the level of depression is controlled. Three samples were used (74 severe major depressives, 43 outpatients with somatic disorders presenting mild or moderate depression and 36 mild or moderate depressives hospitalized in the intensive coronary unit). Recent change of anhedonia was rated by the anhedonia subscale of the Beck Depression Inventory (BDI-II), state anhedonia by the Snaith-Hamilton Pleasure Scale (SHAPS), trait anhedonia by the TEPS (Temporal Experience of Pleasure Scale), musical anhedonia by the BMRQ (Barcelona Music Reward Questionnaire), social recent change of anhedonia by the SLIPS (Specific Loss of Interest and Pleasure Scale), the severity of depression by the BDI-II and the distinction between melancholic and non-melancholic was found using a subscale of the BDI-II. Bivariate and multivariate regression analyses were performed in each sample. In severe major depressives and, notably, in melancholia, recent suicidal ideation was associated with trait anhedonia; however, in mild or moderate depression, recent suicidal ideation was associated with recent change of anhedonia. Musical anhedonia and social recent change of anhedonia were not associated with recent suicidal ideation. Trait anhedonia could be, in severe depression, a strong predictor of recent suicidal ideation.

Prevalence and Relationships between Alexithymia, Anhedonia, Depression and Anxiety during the Belgian COVID-19 Pandemic Lockdown.

Alexithymia and anhedonia are associated with psychiatric disorders, such as depression and anxiety. The COVID-19 pandemic lead to a significant deterioration in the mental health of the population. It is therefore important to examine the effects of lockdown on alexithymia and anhedonia and their relationships with anxiety and depression. We compared the scores and characteristics of 286 patients divided into two groups: one before lockdown (group 1, N = 127), the other during the progressive lockdown release (group 2, N = 159). The groups were homogeneous in terms of age, sex ratio, socio-professional categories, and somatic and psychiatric comorbidities. The groups were compared on the Toronto Alexithymia Scale (TAS-20) measuring alexithymia, the Beck Depression Inventory (BDI-II) measuring depression, the anhedonia subscale of the BDI-II measuring state-anhedonia and the State Trait Anxiety Inventory (STAI) measuring state and trait anxiety. The ratio of alexithymic subjects in group 1 is 22.83% to 33.33% in group 2 (p-value = 0.034). This suggests a significant increase in the number of alexithymic patients after lockdown. We did not observe any difference in the proportion of depressed and anxious subjects before or after lockdown. Among the different scales, higher scores were only found on the cognitive factor of alexithymia on group 2 comparatively to group 1. This study indicates an increase in the proportion of alexithymic subjects following lockdown. Unexpectedly, this was unrelated to depression, anxiety or anhedonia levels, which remained stable. Further studies are needed to confirm this result and to evaluate precisely which factors related to the lockdown context are responsible for such an increase.

Suicidal Ideation in Major Depressed Individuals: Role of Type D Personality.

Major depressed individuals are a subpopulation at high-risk of suicide. However, despite the evidence for a particular relationship between suicidal ideation (SI) and type D personality, few studies have investigated the role played by this personality structure in the occurrence of SI in major depressed individuals. Data from 318 major depressed individuals recruited from the clinical database of the Sleep Laboratory were analysed. Suicidal ideation was considered present if the score in item 9 of the Beck Depression Inventory (BDI-II) was ≥1 and/or if they were highlighted during the systematic psychiatric assessment conducted on admission to the Sleep Laboratory. Logistic regression analyses were used to determine the risk of SI associated with type D personality in major depressed individuals. The prevalence of suicidal ideation was 38.4% in our sample of major depressed individuals. After adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that type D personality was a risk factor for SI in major depressed individuals. Thus, given the potential role played by type D personality in the occurrence of SI in major depressed individuals, it seems necessary to more systematically research and adequately manage this personality structure to allow for a better prevention of suicidal behaviours in this subpopulation.

Risk of Cardiovascular Disease in Apnoeic Individuals: Role of Comorbid Insomnia Disorder.

Given the limited data available, the aim of this study was to examine the 10-year cardiovascular disease (CVD) risk associated with comorbid insomnia disorder and its specific subtypes in apnoeic individuals. Data from 1104 apnoeic individuals recruited from the database of the Erasme Hospital Sleep Laboratory were analysed. Only apnoeic individuals with a Framingham Risk Score ≥10% were included in the group at moderate-to-high 10-year CVD risk. Logistic regression analyses were conducted to examine the risk of 10-year CVD risk associated with comorbid insomnia disorder and its specific subtypes in apnoeic individuals. Moderate-to-high 10-year CVD risk was present in 59.6% of the apnoeic individuals in our sample. After adjustment for the main confounding factors, multivariate logistic regression analyses revealed that comorbid insomnia disorder and, more particularly, its subtype with short sleep duration were significantly associated with moderate-to-high 10-year CVD risk in apnoeic individuals. In this study, we demonstrate that comorbid insomnia disorder and, more specifically, its subtype with short sleep duration appear to have a negative cumulative effect on 10-year CVD risk in apnoeic individuals, which justifies more systematic research and adequate therapeutic management of this disorder to allow for better cardiovascular disease prevention in this particular subpopulation.

Risk of relapse within 6 months associated with borderline personality disorder in major depressed individuals treated with electroconvulsive therapy.

Given the limited data in the literature, the aim of this study was to investigate the risk of relapse within 6 months associated with borderline personality disorder (BPD) in major depressed individuals treated with electroconvulsive therapy. Demographic and clinical data from 109 major depressed individuals with partial or complete response to electroconvulsive therapy recruited from the database of the Psychiatry Department of Erasme Hospital were analysed. Cox regression analyses were used to determine the risk of relapse within 6 months associated with BPD in major depressed individuals treated with electroconvulsive therapy. Relapses within 6 months were frequent (37.6%) in our sample of major depressed individuals treated with electroconvulsive therapy. After adjusting for major confounding factors, multivariate Cox regression analyses demonstrated that BPD was a risk factor for relapse within 6 months in major depressed individuals treated with electroconvulsive therapy. In our study, we demonstrated that BPD is associated with higher risk of relapse within 6 months in major depressed individuals treated with electroconvulsive therapy, which seems to justify a more systematic screening for BPD in order to allow the implementation of more effective prevention strategies for relapse within 6 months in this particular subpopulation.

Impact of Alexithymia on the Lipid Profile in Major Depressed Individuals.

Background: The cooccurrence of major depression and dyslipidaemia is associated with negative cardiovascular outcome, which seems to justify a better identification of the factors favouring the development of dyslipidaemia in major depressed individuals. In the literature, there are arguments in favour of a special relationship between dyslipidaemia and alexithymia. However, despite a high prevalence of alexithymia in major depressed individuals, no study has investigated the impact of this personality trait on the lipid profile in this particular subpopulation. Given these elements, the aim of this study was therefore to investigate the risk of dyslipidaemia associated with alexithymia in major depressed individuals to allow better cardiovascular prevention in this subpopulation. Subjects and Methods. Demographic and polysomnographic data from 242 major depressed individuals recruited from the clinical database of the sleep laboratory were analysed. Only individuals with a diagnosis of dyslipidaemia according to the diagnostic criteria of the International Diabetes Federation at admission were included in the "dyslipidaemia" group. Logistic regression analyses were used to determine the risk of dyslipidaemia associated with alexithymia in major depressed individuals. Results: The prevalence of dyslipidaemia was 43.8% in our sample of major depressed individuals. After adjusting for the main confounding factors, multivariate logistic regression analyses demonstrated that alexithymia was a risk factor for dyslipidaemia in major depressed individuals. Conclusions: In this study, we found that alexithymia is a risk factor for dyslipidaemia in major depressed individuals, which seems to justify better identification and adequate management of this personality trait in order to allow a better lipid profile in this subpopulation at high cardiovascular risk.

Nonremission After Electroconvulsive Therapy in Individuals With Major Depression: Role of Borderline Personality Disorder.

OBJECTIVES: The aim of the present study was to investigate the risk of nonremission following electroconvulsive therapy (ECT), as associated with borderline personality disorder, in individuals with major depression in the context of the contradictory data available in the literature. METHODS: We analyzed demographic and clinical data from 210 individuals with major depression who were treated with ECT. Study participants were recruited from the medical records database of the Psychiatry Department at Erasme Hospital. Only individuals with major depression who were in remission, as demonstrated during the systematic psychiatric interview performed at the end of ECT (ie, with a >60% reduction in their 24-item Hamilton Depression Rating Scale score, combined with a score of <10), were included in the "remission" group. Logistic regression analyses were used to determine the risk of nonremission following ECT. RESULTS: Nonremission following ECT occurred frequently (42.9%) in our sample. Moreover, after adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that borderline personality disorder was a risk factor for nonremission following ECT in individuals with major depression. CONCLUSIONS: We demonstrated that borderline personality disorder was associated with a higher risk of nonremission following ECT in individuals with major depression. This finding seems to justify more systematic screening as well as more adequate management of this personality disorder in individuals with major depression who are treated with ECT to allow for attaining better remission rates in this subpopulation.

Association of Amlodipine with the Risk of In-Hospital Death in Patients with COVID-19 and Hypertension: A Reanalysis on 184 COVID-19 Patients with Hypertension.

Association between calcium channel blockers (CCBs) or functional inhibitors of acid sphingomyelinase (FIASMAs) use and decreased mortality in people with COVID-19 has been reported in recent studies. Since amlodipine is both a CCB and a FIASMA, the aim of this study was to investigate the association between chronic amlodipine use and the survival of people with hypertension infected with COVID-19. This retrospective cohort study used data extracted from the medical records of adult inpatients with hypertension and laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged from hospital or deceased) from Erasme Hospital (Brussels, Belgium). We re-analyzed the data of the retrospective cohort study using only the 184 patients (103 males, 81 females) with a mean age of 69.54 years (SD = 14.6) with hypertension. The fifty-five participants (29.9%) receiving a chronic prescription of amlodipine were compared with the 129 patients who did not receive a chronic prescription of amlodipine. Univariate and multivariate logistic regressions were used to explore the relationships between mortality and sex, age, comorbidities, smoking, and amlodipine status. Out of the 184 participants, 132 (71.7%) survived and 52 (28.3%) died. The mortality rates were, respectively, 12.73% (n = 7) and 34.88% (n = 45) for the amlodipine and non-amlodipine groups. Multivariate logistic regression was significant (Chi square (5) = 29.11; p < 0.0001). Chronic kidney disease and malignant neoplasm were significant predictors as well as amlodipine status. For chronic kidney disease and malignant neoplasm, the odds ratio with 95% confidence interval (95% CI) were, respectively, 2.16 (95% CI: 1.04−4.5; p = 0.039) and 2.46 (95% CI: 1.01−6.01; p = 0.047). For amlodipine status the odds ratio was 0.29 (95% CI: 0.11−0.74; p = 0.009). The result of the present study suggests that amlodipine may be associated with reduced mortality in people with hypertension infected with COVID-19. Further research and randomized clinical trials are needed to confirm the potential protective effect of amlodipine in people with hypertension infected with COVID-19.

Difficulty in Repurposing Selective Serotonin Reuptake Inhibitors and Other Antidepressants with Functional Inhibition of Acid Sphingomyelinase in COVID-19 Infection.

The rapid spread of COVID-19 has become a health emergency causing an urgent need for drug treatments to control the outbreak, especially in more vulnerable individuals. This is reinforced by the fact that prophylactic vaccines and neutralizing monoclonal antibodies may not be fully effective against emerging variants. Despite all efforts made by the scientific community, efficient therapeutic options currently remain scarce, either in the initial, as well as in the advanced forms of the disease. From retrospective observational studies and prospective clinical trials, selective serotonin reuptake inhibitors (SSRIs), and other antidepressants with functional inhibition of acid sphingomyelinase (FIASMAs), have emerged as potential treatments of COVID-19. This has led to some prematurely optimistic points of view, promoting a large prescription of fluvoxamine in patients with COVID-19, that we think should be reasonably tempered.

Cardiovascular risk associated with co-morbid insomnia and sleep apnoea (COMISA) in type 2 diabetics.

Objective: In the general population, co-morbid insomnia and sleep apnoea (COMISA) is associated with higher risk of cardiovascular diseases (CVD). However, despite a high prevalence of COMISA in type 2 diabetics, no study has investigated its potential implication in the negative cardiovascular outcome of this particular subpopulation. The aim of this study was therefore to examine the risk of CVD associated with COMISA in type 2 diabetics. Methods: Data from 471 type 2 diabetics recruited from the clinical database of the Erasme Hospital sleep laboratory were analysed. Only type 2 diabetics with SCORE index ≥5% were included in the group at high risk of CVD. Logistic regression analyses were conducted to examine the risk of CVD associated with COMISA in type 2 diabetics. Results: A high risk of CVD was present in 32.9% of type 2 diabetics. After adjustment for the main confounding factors associated with cardiovascular risk, multivariate logistic regression analysis revealed that unlike obstructive sleep apnoea syndrome or insomnia alone, only COMISA was associated with higher risk of CVD in type 2 diabetics. Discussion: In our study, we have demonstrated that unlike its components alone, only COMISA was associated with higher risk of CVD in type 2 diabetics, which highlights the importance of the central role played by the negative synergistic effect of COMISA on the cardiovascular outcome in this particular subpopulation. Thus, given these elements, more systematic research and adequate therapeutic management of COMISA seem to be necessary to allow better cardiovascular prevention in type 2 diabetics.

The association between type 2 diabetes and anhedonic subtype of major depression in hypertensive individuals.

Given the limited data in the literature, the aim of this study was to investigate the association between type 2 diabetes and anhedonic subtype of major depression in hypertensive individuals. Demographic and polysomnographic data from 323 hypertensive individuals recruited from the database of the Erasme Hospital Sleep Laboratory were analysed. Only individuals with a diagnosis of type 2 diabetes according to the diagnostic criteria of the American Diabetes Association at admission were included in the "diabetes group". Logistic regression analyses were used to study the association between type 2 diabetes and anhedonic subtype of major depression in hypertensive individuals. The rate of type 2 diabetes was 18.9% in our sample of hypertensive individuals. After adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that unlike the non-anhedonic subtype of major depression, only the anhedonic subtype of major depression was significantly associated with higher likelihood of having type 2 diabetes in hypertensive individuals. In this study, the authors demonstrated that the anhedonic subtype of major depression is significantly associated with type 2 diabetes in hypertensive individuals, which could potentially open up new perspectives for the development of therapeutic strategies complementary to conventional treatments for type 2 diabetes in this subpopulation at high risk of complications related to the co-occurrence of this metabolic disorder.

Risk of current suicidal ideations associated with lifelong anhedonia and recent change of anhedonia in individuals with insomnia: A cross-sectional study.

BACKGROUND: Individuals with insomnia are a subpopulation at high-risk of suicide. However, despite the elements in favour of an implication of anhedonia in the occurrence of current suicidal ideations (SI), no study has investigated the role played by this affective symptom in the occurrence of current SI in individuals with insomnia. The aim of this study was to investigate the risk of current SI associated with lifelong anhedonia and recent change of anhedonia in individuals with insomnia. METHOD: Demographic and polysomnographic data from 493 individuals with insomnia selected retrospectively from the clinical database of the Erasme Hospital Sleep Laboratory were analysed. Current SI were considered present if the score in item 9 of the Beck Depression Inventory (BDI-II) was ≥1 and/or if they were highlighted during the systematic psychiatric assessment conducted on admission to the Sleep Laboratory. Logistic regression analyses were used to determine the risk of current SI associated with anhedonia in individuals with insomnia. RESULTS: The prevalence of current SI was 21.5% in our sample of individuals with insomnia. After adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that unlike lifelong anhedonia, only recent change of anhedonia was a risk factor for current SI in individuals with insomnia. CONCLUSION: In this study, we demonstrated that in individuals with insomnia, recent change of anhedonia is a risk factor for current SI, which seems to justify more systematic research and adequate therapeutic management of this condition to allow better prevention in this particular subpopulation at high-risk of suicide.

The association between type 2 diabetes and major depression in apnoeic individuals.

Given the few studies available in the literature, the aim of this study was to investigate the association between type 2 diabetes and major depression in a large sample of apnoeic individuals. Demographic and polysomnographic data from 395 apnoeic individuals recruited from the clinical database of the Erasme Hospital Sleep Laboratory were analysed. Only individuals with a diagnosis of type 2 diabetes according to the diagnostic criteria of the American Diabetes Association at admission were included in the "diabetes" group. Logistic regression analyses were used to study the association between type 2 diabetes and major depression in apnoeic individuals. The prevalence of type 2 diabetes was 19.7% in our sample of apnoeic individuals. After adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that unlike remitted major depression and mild major depression, only moderate to severe major depression was significantly associated with higher likelihood of type 2 diabetes in apnoeic individuals. In our study, we found that moderate to severe major depression is significantly associated with type 2 diabetes in apnoeic individuals, which seems to justify more systematic screening and adequate therapeutic management of this psychiatric disorder to allow better glycaemic control in this subpopulation at high risk of diabetic micro/macrovascular complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-021-00359-0.