Evaluation of a Stepped Care Approach to Manage Depression and Diabetes Distress in Patients with Type 1 Diabetes and Type 2 Diabetes: Results of a Randomized Controlled Trial (ECCE HOMO Study).

INTRODUCTION: Depression is a common and serious complication of diabetes. Treatment approaches addressing the specific demands of affected patients are scarce. OBJECTIVE: The aim of this work was to test whether a stepped care approach for patients with diabetes and depression and/or diabetes distress yields greater depression reduction than treatment-as-usual. METHODS: Two-hundred and sixty patients with diabetes and elevated depressive symptoms (CES-D ≥16) and/or elevated diabetes distress (PAID ≥40) were randomized to stepped care for depression or diabetes treatment-as-usual. The primary outcome was the rate of meaningful depression reduction at the 12-month follow-up according to the HAMD (score <9 or reduction by ≥50%). Secondary outcomes were changes in depression scores (HAMD/CES-D), diabetes distress (PAID), diabetes acceptance (AADQ), well-being (WHO-5), quality of life (EQ-5D/SF-36), self-care behavior (SDSCA/DSMQ), HbA1c, and biomarkers of inflammation. RESULTS: One-hundred and thirty-one individuals were assigned to stepped care and 129 to treatment-as-usual. Overall, 15.4% were lost to follow-up. Meaningful depression reduction was observed in 80.2 versus 51.2% in stepped care versus treatment-as-usual (p < 0.001, intention-to-treat analysis). Of the secondary measures, the HAMD (∆ -3.2, p < 0.001), WHO-5 (∆ 1.5, p = 0.007), and AADQ (∆ -1.0, p = 0.008) displayed significant treatment effects, while effects on CES-D (∆ -2.3, p = 0.065), PAID (∆ -3.5, p = 0.109), and SDSCA (∆ 0.20, p = 0.081) were not significantly different. Both groups showed comparable changes in EQ-5D/SF-36, DSMQ, HbA1c, and biomarkers of inflammation (all p ≥ 0.19). CONCLUSIONS: The stepped care approach improved depression, well-being, and acceptance. The results support that increasing treatment intensity on demand is effective and can help provide more optimal treatment. The inclusion of diabetes-specific interventions may be beneficial for patients with diabetes and elevated depression.

Association between pro- and anti-inflammatory cytokines and depressive symptoms in patients with diabetes-potential differences by diabetes type and depression scores.

Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 ± 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 ± 8 years). Subclinical depression was examined using three questionnaires (Center for Epidemiologic Studies Depression [CES-D], Patient Health Questionnaire-9 [PHQ-9], 5-item World Health Organization Well-Being Index [WHO-5]). In T1D, levels of interleukin-1 receptor antagonist (IL-1RA) were positively associated with two depression scores (CES-D, PHQ-9), and high-sensitivity C-reactive protein (hsCRP) was positively associated with depression for one score (WHO-5) after adjustment for age, sex, body mass index, diabetes duration, metabolic variables, medication and comorbidities (P = 0.008-0.042). In T2D, IL-18 and IL-1RA were positively associated with depression for two scores (IL-18: PHQ-9, WHO-5; IL-1RA: CES-D, WHO-5), hsCRP was associated with one depression score (PHQ-9), and adiponectin showed an inverse association with one depression score (PHQ-9) after adjustment (P = 0.006-0.048). No associations were found for IL-6 and CC-chemokine ligand 2 (CCL2). In conclusion, we observed associations between hsCRP, IL-1RA and depressive symptoms in patients with diabetes. In T2D, there was additional evidence for associations of IL-18 and (inversely) adiponectin with depressive symptoms. The strength of the associations appeared to depend on diabetes type and the method used to asssess depressive symptoms.

Longitudinal associations between biomarkers of inflammation and changes in depressive symptoms in patients with type 1 and type 2 diabetes.

BACKGROUND: Depressive disorders represent a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical inflammation increases the risk of depressive symptoms in the general population, but the relationship appears complex and bidirectional, and longitudinal data from patients with diabetes are lacking. Therefore, this study aimed to analyse associations between changes in depressive symptoms and changes in biomarkers of inflammation in patients with T1D and T2D and to investigate the hypothesis that higher baseline levels of biomarkers of inflammation are related to a less pronounced reduction of depressive symptoms over time. METHODS: Depressive symptoms and systemic levels of six biomarkers of inflammation were assessed in 168 individuals with T1D and 103 individuals with T2D who participated in baseline and 1-year follow-up examinations. Data were obtained from two matching randomised controlled trials addressing diabetes distress and depressive symptoms. Longitudinal associations between biomarkers and depressive symptoms were estimated using linear regression models adjusting for multiple confounders. RESULTS: In patients with T2D, reductions in depressive symptoms were associated with reductions in high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-18 and IL-1 receptor antagonist (IL-1RA) (P ≤ 0.016), whereas no associations were seen for IL-6, CCL2 and adiponectin. Higher CCL2 levels at baseline were associated with lower subsequent reduction in depressive symptoms (P = 0.018). Neither baseline levels nor changes in biomarkers in subclinical inflammation were associated with changes in depressive symptoms in patients with T1D. CONCLUSIONS: Reductions of depressive symptoms were longitudinally associated with reductions in biomarkers of inflammation in patients with T2D. Higher baseline CCL2 levels were related with lower reduction of depressive symptoms in this group. No such associations were observed in patients with T1D, suggesting that risk factors and pathomechanisms linking inflammation and depression may differ between diabetes types.

Measurement of psychological adjustment to diabetes with the diabetes acceptance scale.

AIMS: To develop a psychometric measure of diabetes acceptance. METHODS: An item pool was developed and pilot-tested using a sample of 220 people with diabetes; item selection resulted in the 20-item 'Diabetes Acceptance Scale (DAS)'. 606 people with diabetes were then cross-sectionally assessed with the DAS to evaluate its reliability, validity and clinical utility; concurrent measurements included diabetes-related coping (FQCI), diabetes distress (PAID-5), depressive symptoms (PHQ-9), quality of life (EQ-5D), self-management (DSMQ), glycaemic control (HbA1c) and complications. RESULTS: Internal reliability was high (Cronbach's α = 0.96). Factorial and criterion-related results supported validity. Higher diabetes acceptance scores correlated with more functional coping styles, lower distress and depression levels, higher treatment adherence, better glycaemic control and better quality of life (all P < .001). Persons with low diabetes acceptance (22% of the sample) were four times more likely to have HbA1c values over 9.0% (75 mmol/mol), two times more likely to be diagnosed with long-term complications and each over two times more likely to have had episodes of severe hypoglycaemia and ketoacidosis in the past year; the prevalence of major depression in this group was fivefold increased (all P < .05). CONCLUSIONS: The DAS is a reliable and valid tool to measure diabetes acceptance. It may help identify patients with significant problems of accepting diabetes, a putative high-risk group in need of tailored care and support.

Reduction of depressive symptoms predicts improved glycaemic control: Secondary results from the DIAMOS study.

AIMS: Evidence from randomised trials analysing effects of depression treatment on glycaemic control in group comparisons is inconsistent. The aim of this study was to test if the reduction of depressive symptoms would explain improved glycaemic control irrespective of treatment groups. METHODS: The DIAMOS study tested effects of cognitive-behavioural therapy (CBT) versus usual care on depressive symptoms in a 12-month prospective trial; HbA1c was a secondary outcome. Since the results suggested superiority of CBT for improving depressive symptoms, but not HbA1c, we conducted this secondary analysis to test if reduction of depressive symptoms could explain improved glycaemic control when assessed irrespective of treatment group affiliation. Reduction of depressive symptoms was assessed using baseline-to-follow-up changes in the Center for Epidemiologic Studies Depression Scale (CES-D). We used multiple regression analyses, adjusting for baseline HbA1c and depression, group affiliation and covariates, to assess associations between reduction of depressive symptoms and follow-up HbA1c. RESULTS: 181 participants provided eligible data. Depressive symptoms decreased between baseline and follow-up by averagely -5.1±11.8 CES-D points. Greater reduction of depressive symptoms predicted greater improvement of HbA1c at follow-up, while adjusting for baseline HbA1c and covariates (Beta=-0.24, P=0.004). Additionally, patients with greater reduction of depressive symptoms were more likely to reach in-target HbA1c (<7.5%) at follow-up (adjusted OR=1.04, 95% CI 1.01-1.08, P=0.023). CONCLUSIONS: The findings suggest that reduction of depressive symptoms can explain improved glycaemic control. Behavioural treatments might aim to improve both affective and glycaemic outcomes.

Reduction of diabetes-related distress predicts improved depressive symptoms: A secondary analysis of the DIAMOS study.

OBJECTIVE: Depressive symptoms in people with diabetes are associated with increased risk of adverse outcomes. Although successful psychosocial treatment options are available, little is known about factors that facilitate treatment response for depression in diabetes. This prospective study aims to examine the impact of known risk factors on improvement of depressive symptoms with a special interest in the role of diabetes-related distress. METHODS: 181 people with diabetes participated in a randomized controlled trial. Diabetes-related distress was assessed using the Problem Areas In Diabetes (PAID) scale; depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic and linear regression analyses were used to assess associations between risk factors for depression (independent variables) and improvement of depressive symptoms (dependent variable). Reliable change indices were established as criteria of meaningful reductions in diabetes distress and depressive symptoms. RESULTS: A reliable reduction of diabetes-related distress (15.43 points in the PAID) was significantly associated with fourfold increased odds for reliable improvement of depressive symptoms (OR = 4.25, 95% CI: 2.05-8.79; P<0.001). This result was corroborated using continuous measures of diabetes distress and depressive symptoms, showing that greater reduction of diabetes-related distress independently predicted greater improvement in depressive symptoms (ß = -0.40; P<0.001). Higher age had a positive (Odds Ratio = 2.04, 95% CI: 1.21-3.43; P<0.01) and type 2 diabetes had a negative effect on the meaningful reduction of depressive symptoms (Odds Ratio = 0.12, 95% CI: 0.04-0.35; P<0.001). CONCLUSIONS: The reduction of diabetes distress is a statistical predictor of improvement of depressive symptoms. Diabetes patients with comorbid depressive symptomatology might benefit from treatments to reduce diabetes-related distress.

The affective and somatic side of depression: subtypes of depressive symptoms show diametrically opposed associations with glycemic control in people with type 1 diabetes.

AIMS: While depression has been linked to serious adverse outcomes in diabetes, associations with glycemic control are not conclusive. Inconsistencies could be due to the complex symptomatology of depression. Aim of this study was to analyze the associations of depressive subtypes with glycemic control in people with type 1 and type 2 diabetes. METHODS: Patients completed the Center for Epidemiological Studies-Depression scale which comprises affective, somatic, and anhedonic symptoms. These subtypes were analyzed in a joint linear regression analysis with glycemic control as a dependent variable. Subtype scores were calculated as mean item scores. Separate analyses for people with type 1 and type 2 diabetes were conducted. All analyses were controlled for demographic and medical confounders. RESULTS: The sample comprised 604 patients with type 1 and 382 patients with type 2 diabetes. In people with type 1 diabetes, the somatic and affective subtype showed diametrically opposed associations with glycemic control (somatic: ß =+0.23, p < .05; affective: ß = -0.23, p < .05). Anhedonia was not significantly associated with glycemic control. In people with type 2 diabetes, none of the depressive subtypes was significantly associated with glycemic control. CONCLUSIONS: For people with type 1 diabetes, the distinction of subtypes offered a detailed picture of the associations of depressive symptoms with glycemic control. However, due to the cross-sectional design, inferences about the direction of these associations cannot be made. In clinical practice, instead of focusing on overall depression, healthcare providers should examine the nature of depressive symptoms and how they might be related to having diabetes.

Depression is linked to hyperglycaemia via suboptimal diabetes self-management: A cross-sectional mediation analysis.

OBJECTIVE: To analyse if the association between depressive symptoms and hyperglycaemia is mediated by diabetes self-management. METHODS: 430 people with diabetes (57.7% type 1, 42.3% type 2) were cross-sectionally assessed using validated self-report scales for depressive symptoms (Center for Epidemiologic Studies Depression Scale (CES-D)) and diabetes self-management (Diabetes Self-Management Questionnaire (DSMQ)); HbA1c was analysed simultaneously in a central laboratory. Structural equation modelling was used to test if the association between depressive symptoms and hyperglycaemia (HbA1c) was mediated by suboptimal self-management in people with type 1 and type 2 diabetes. RESULTS: The hypothesised model of depressive symptoms, diabetes self-management and hyperglycaemia fit the data well for both diabetes types (SRMR≤0.04, TLI≥0.99, CFI>0.99, RMSEA≤0.02 for both models). In both the type 1 and type 2 diabetes group, higher depressive symptoms were associated with lower self-management (P<0.001) and lower self-management was associated with higher HbA1c (P<0.001). Results indicated that the association between depressive symptoms and hyperglycaemia was significantly mediated by suboptimal diabetes self-management in both type 1 and type 2 diabetes patients (P<0.001). Significant direct associations between depressive symptoms and hyperglycaemia, not mediated by self-management, could not be observed. CONCLUSIONS: This study provides good evidence supporting that depression is linked to hyperglycaemia via suboptimal diabetes self-management in both major diabetes types.

Assessing Diabetes Self-Management with the Diabetes Self-Management Questionnaire (DSMQ) Can Help Analyse Behavioural Problems Related to Reduced Glycaemic Control.

AIM: To appraise the Diabetes Self-Management Questionnaire (DSMQ)'s measurement of diabetes self-management as a statistical predictor of glycaemic control relative to the widely used SDSCA. METHODS: 248 patients with type 1 diabetes and 182 patients with type 2 diabetes were cross-sectionally assessed using the two self-report measures of diabetes self-management DSMQ and SDSCA; the scales were used as competing predictors of HbA1c. We developed a structural equation model of self-management as measured by the DSMQ and analysed the amount of variation explained in HbA1c; an analogue model was developed for the SDSCA. RESULTS: The structural equation models of self-management and glycaemic control showed very good fit to the data. The DSMQ's measurement of self-management showed associations with HbA1c of -0.53 for type 1 and -0.46 for type 2 diabetes (both P < 0.001), explaining 21% and 28% of variation in glycaemic control, respectively. The SDSCA's measurement showed associations with HbA1c of -0.14 (P = 0.030) for type 1 and -0.31 (P = 0.003) for type 2 diabetes, explaining 2% and 10% of glycaemic variation. Predictive power for glycaemic control was significantly higher for the DSMQ (P < 0.001). CONCLUSIONS: This study supports the DSMQ as the preferred tool when analysing self-reported behavioural problems related to reduced glycaemic control. The scale may be useful for clinical assessments of patients with suboptimal diabetes outcomes or research on factors affecting associations between self-management behaviours and glycaemic control.

Development of a New Tool to Assess Bolus Calculation and Carbohydrate Estimation.

BACKGROUND: Carbohydrate estimation and bolus calculation are two important skills for handling intensive insulin therapy and effectively using bolus calculators. Structured assessment of both skills is lacking. A new tool for the assessment of skills in carbohydrate estimation and bolus calculation was developed and evaluated. MATERIALS AND METHODS: A new assessment tool (SMART) was developed that included 10 items for bolus calculation and 12 items for carbohydrate estimation. In total, 411 patients on intensive insulin treatment were recruited. Different parameters of glycemic control were used as validity criteria. RESULTS: The SMART tool achieved good reliability for the assessment of bolus calculation (Cronbach's α = 0.78) and sufficient reliability for the assessment of carbohydrate estimation (Cronbach's α = 0.67). A good bolus calculation skill was significantly associated with lower glycated hemoglobin values (r = -0.27), lower mean blood glucose levels (r = -0.29), and higher fluctuation of blood glucose control (r = -0.43). A good carbohydrate estimation skill was significantly associated with a lower frequency of severe hyperglycemia (r = -0.27) and a higher frequency of euglycemia (r = 0.26). CONCLUSIONS: SMART is a reliable and valid tool for the assessment of both skills. Bolus calculation as well as carbohydrate estimation was associated with glycemic control. With the help of SMART, important skills for the management of intensive insulin therapy can be assessed separately. Thus, in clinical practice patients in need of assistance from a bolus calculator can be identified.

Negative association between depression and diabetes control only when accompanied by diabetes-specific distress.

Evidence of the negative impact of depression on glycaemic control is equivocal, and diabetes-related distress has been proposed as potential mediator. 466 diabetes patients were cross-sectionally assessed for depression (Center for Epidemiologic Studies Depression Scale), diabetes-related distress (Diabetes Distress Scale), and glycaemic control (HbA1c). We distinguished the associations of depression and diabetes distress with glycaemic control using analysis of variance and multiple regression. Neither patients with depression only nor diabetes distress only differed significantly from controls regarding HbA1c. However, HbA1c was substantially increased when both conditions were present (9.2 vs. 8.6 %, P = 0.01). As in previous studies, we observed a significant association between depression and hyperglycaemia (P < 0.01). However, a mediation analysis revealed that this association in fact depended on the presence of diabetes distress (P < 0.01). Depression seems to be associated with hyperglycaemia particularly when accompanied by diabetes distress, suggesting that adjusting clinical procedures regarding diabetes distress may facilitate the identification and care of high-risk patients.

Effect of local heating on postprandial blood glucose excursions using the InsuPad device: results of an outpatient crossover study.

The InsuPad is a medical device to accelerate insulin resorption by applying local heat at the insulin injection site. This crossover study examined the impact of the InsuPad use on postprandial glucose excursions under daily life conditions. In 1 study phase, diabetic patients used the InsuPad when injecting bolus insulin before breakfast and dinner and measured their blood glucose 5 times daily (before breakfast, lunch, and dinner and after breakfast and dinner). In the other study phase, blood glucose measurements were maintained without using the InsuPad. The order of the study phases was randomized. Twenty patients with a high insulin demand took part (30% type 1 diabetes, age 53.7 ± 8.9 years, diabetes duration 14.9 ± 7.4 years; HbA1c 8.3 ± 0.8%; total daily insulin demand 0.97 ± 0.32 IU per kg). Postprandial glucose excursion was reduced by 15.4 mg/dl (95% CI 9.7-21.2 mg/dl; P = .011) after breakfast and dinner if InsuPad was used. The mean blood glucose was lower by 8.8 mg/dl (95% CI 0:3-18:0 mg/dl; P = .099) when using the InsuPad. Safety parameters and the percentage of hypoglycemic (< 60 mg/dl) or hyperglycemic (> 300 mg/dl) blood glucose measurements were not negatively affected by InsuPad use (hypoglycemic values 1.4% vs 1.5%, P = .961; hyperglycemic values 2.6% vs 4.0%, P = .098). Local heating of the insulin injection site by use of the InsuPad device is an effective and safe method to reduce postprandial blood glucose excursions under daily life conditions without negative side effects on the occurrence of low or high blood glucose values.