Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways

There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression of peripheral cell-mediated activation, inflammation and induction of oxidative and nitrosative stress (IO&NS) pathways and of central microglial activation, decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple “co-morbidities” between depression and a large variety of a) brain disorders related to neurodegeneration, e.g. Alzheimer’s, Parkinson’s and Huntington’s disease, multiple sclerosis and stroke; b) medical disorders, such as cardiovascular disorder, chronic fatigue syndrome, chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, inflammatory bowel disease, irritable bowel syndrome, leaky gut, diabetes type 1 and 2, obesity and the metabolic syndrome, and HIV infection; and c) conditions, such as hemodialysis, interferon-α-based immunotherapy, the postnatal period and psychosocial stressors. The common denominator of all those disorders/conditions is the presence of microglial activation and/or activation of peripheral IO&NS pathways. There is evidence that shared peripheral and / or central IO&NS pathways underpin the pathophysiology of depression and the previously mentioned disorders and that activation of these IO&NS pathways contributes to shared risk. The IO&NS pathways function as a smoke sensor that detect threats in the peripheral and central parts of the body and signal these threats as melancholic, anxiety, and fatigue and somatic (F&S) symptoms. The presence of concomitant depression is strongly associated with a lower quality of life and increased morbidity and mortality in medical disorders. This may be explained since depression contributes to increased (neuro)inflammatory burden and may therefore drive the inflammatory and degenerative progression. It is concluded that the activation of peripheral and / or central IO&NS pathways may explain the co-occurrence of depression with the above disorders. This shows that depression belongs to the spectrum of inflammatory and degenerative disorders.

Chronic condition management and self-management in Aboriginal communities in South Australia : outcomes of a longitudinal study

OBJECTIVES: This paper describes the longitudinal component of a larger mixed methods study into the processes and outcomes of chronic condition management and self-management strategies implemented in three Aboriginal communities in South Australia. The study was designed to document the connection between the application of structured systems of care for Aboriginal people and their longer-term health status. METHODS: The study concentrated on three diverse Aboriginal communities in South Australia; the Port Lincoln Aboriginal Health Service, the Riverland community, and Nunkuwarrin Yunti Aboriginal Health Service in the Adelaide metropolitan area. Repeated-measure clinical data were collected for individual participants using a range of clinical indicators for diabetes (type 1 and 2) and related chronic conditions. Clinical data were analysed using random effects modelling techniques with changes in key clinical indicators being modelled at both the individual and group levels. RESULTS: Where care planning has been in place longer than in other sites overall improvements were noted in BMI, cholesterol (high density and low density lipids) and HbA1c. These results indicate that for Aboriginal patients with complex chronic conditions, participation in and adherence to structured care planning and self-management strategies can contribute to improved overall health status and health outcomes. CONCLUSIONS: The outcomes reported here represent an initial and important step in quantifying the health benefits that can accrue for Aboriginal people living with complex chronic conditions such as diabetes, heart disease and respiratory disease. The study highlights the benefits of developing long-term working relationships with Aboriginal communities as a basis for conducting effective collaborative health research programs.

Health-related quality of life and metabolic control in children with type 1 diabetes : a prospective cohort study

OBJECTIVE—To assess change in health-related quality of life (HRQOL) in children with diabetes over 2 years and determine its relationship to change in metabolic control.

RESEARCH DESIGN AND METHODS—In 1998, parents of children aged 5–18 years attending a tertiary diabetes clinic reported their child’s HRQOL using the Child Health Questionnaire PF-50. Those aged 12–18 years also self-reported their HRQOL using the analogous Child Health Questionnaire CF-80. HbA_1c levels were recorded. In 2000, identical measures were collected for those who were aged ≤18 years and still attending the clinic.

RESULTS—Of 117 eligible subjects, 83 (71%) participated. Parents reported no significant difference in children’s HRQOL at baseline and follow-up. However, adolescents reported significant improvements on the Family Activities (P < 0.001), Bodily Pain (P = 0.04), and General Health Perceptions (P = 0.001) scales and worsening on the Behavior (P = 0.04) scale. HbA1c at baseline and follow-up were strongly correlated (r = 0.57). HbA_1c increased significantly (mean 7.8% in 1998 vs. 8.5% in 2000; P < 0.001), with lower baseline HbA_1c strongly predicting an increase in HbA_1c over the 2 years (r² = 0.25, P < 0.001). Lower parent-reported Physical Summary and adolescent-reported Physical Functioning scores at baseline also predicted increasing HbA_1c. Poorer parent-reported Psychosocial Summary scores were related to higher HbA_1c at both times but did not predict change in HbA_1c.

CONCLUSIONS—Changes in parent and adolescent reports of HRQOL differ. Better physical functioning may protect against deteriorating HbA_1c, at least in the medium term. While the HRQOL of children with diabetes does not appear to deteriorate over time, we should not be complacent, as it is consistently poorer than that of their healthy peers.

Young women with type 1 diabetes' management of turning points and transitions

The authors used grounded theory to explore and develop a substantive theory to explain how 20 young women with type 1 diabetes managed their lives when facing turning points and undergoing transitions. The women experienced a basic social problem: being in the grip of blood glucose levels (BGLs), which consisted of three categories: (a) the impact of being susceptible to fluctuating BGLs, (b) the responses of other people to the individual woman’s diabetes, and (c) the impact of the individual women’s diabetes on other people’s lives. The women used a basic social process to overcome the basic social problem by creating stability, which involved using three interconnected subprocesses: forming meaningful
relationships, enhancing attentiveness to blood glucose levels, and putting things in perspective. Insights into the processes and strategies used by the women have important implications for provision of care and service delivery.

Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARß/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

Objective: To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.

Design: Skeletal muscle gene expression, mitochondrial protein content, oxidative capacity and lipid accumulation were measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.

Subjects: Ten obese type 2 diabetic patients and 10 obese normoglycemic controls matched for age and BMI.

Methods: Gene expression and mitochondrial protein content of complexes I–V of the respiratory chain were measured by quantitative polymerase chain reaction and Western blotting, respectively. Histochemical staining was used to quantify lipid accumulation and complex II succinate dehydrogenase (SDH) activity. Insulin sensitivity and substrate utilization were measured during a hyperinsulinemic–euglycemic clamp with indirect calorimetry.

Results: Skeletal-muscle mRNA of PGC-1a and PPARb/d – but not of other genes involved in glucose, fat and oxidative metabolism – was significantly lower in diabetic patients (Po0.01). Rosiglitazone significantly increased PGC-1a (B2.2-fold, Po0.01) and PPARb/d (B2.6-fold, Po0.01), in parallel with an increase in insulin sensitivity, SDH activity and metabolic flexibility (Po0.01). Surprisingly, none of the measured mitochondrial proteins was reduced in type 2 diabetic patients, nor affected by rosiglitazone treatment. No alterations were seen in muscular fat accumulation upon treatment.

Conclusion: These results suggest that the insulin-sensitizing effect of rosiglitazone may involve an effect on muscular oxidative capacity, via PGC-1a and PPARb/d, independent of mitochondrial protein content and/or changes in intramyocellular lipid.

Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid 1-3

Background: Dietary fatty acids may be associated with diabetes but are difficult to measure accurately.

Objective: We aimed to investigate the associations of fatty acids in plasma and diet with diabetes incidence.

Design: This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids.

Results: In plasma phospholipid, positive associations with diabetes were seen for stearic acid [OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001] and total saturated fatty acids [OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001], whereas an inverse association was seen for linoleic acid [OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001]. Dietary linoleic [OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002], palmitic [OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012], and stearic [OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030] acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls.

Conclusions: Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.

The mother-daughter guilt dynamic : effects of type 1 diabetes during life transitions

Aim. The aim of the study was to explore and describe the strategies young women with type 1 diabetes used to manage life transitions. The paper describes one aspect of how guilt dynamic often operates between mothers and daughters and how the women managed the guilt dynamic to create stability in their lives.
Background. When a child is diagnosed with diabetes, major transitional changes occur in the relationships between the mother and her child. The changes affect the psychological and social aspects of their lives and have a major impact on how young women manage their diabetes. A guilt dynamic between mothers and young women with diabetes emerged as a major theme in a larger study that investigated how young women with diabetes managed life transitions. Although the literature indicates that mothers of chronically ill children experience guilt feelings towards their children, little research was identified that addressed the emotional dynamics between mothers and daughters with diabetes.
Design. Using grounded theory method, interviews were conducted with 20 women with type 1 diabetes and five mothers during 2002 and 2003. Constant comparative analysis was used to analyse the data and develop an in-depth understanding of the experience of living with diabetes during life transitions.
Findings. The findings revealed that guilt feelings created a two-way dependency between mothers and their daughters with diabetes. The two-way dependency involved feelings of being a burden to each other, difficulty balancing responsibilities for diabetes management, difficulty relinquishing emotional and social dependency especially during life transitions. In addition, these issues were rarely discussed openly with each other or with health professionals. The findings provide additional information about the human experience of the mother–daughter relationship and the effect on coping with diabetes in the context of life transitions.
Conclusions. Understanding the impact diabetes has on the emotional and social well being of both women with type 1 diabetes and their mothers is critical in planning appropriate support for both groups. Most importantly, it is critical to understand the guilt dynamic that operates during young women with diabetes' life transitions when the daughters' dependency on their mother's control and responsibility for diabetes management undergo changes resulting in emotional responses, especially guilt feelings.
Relevance to clinical practice. Health professionals need to understand the emotional and social impact of the guilt dynamics between young women with type 1 diabetes and their mothers. Adequate and appropriate support can minimize the guilt feelings and enhance stability and quality of life for both mothers and their daughters, especially during major life transitions, such as motherhood.

Transitions : experiences of women with type 1 diabetes : Turning points and transitions as experienced by young women with type 1 diabetes in Australia

The relationship among psychosocial stress, coping and metabolic control has a key effect on diabetes clinical outcomes and mental health. Life transitions are peak times of major change within personal and social contexts, which add stress affecting on peoples? problem solving. The thesis describes young women with Type 1 diabetes? perspectives of the problems encountered and how they managed them when they faced turning points and made life transitions. The study identified the women?s health concerns and factors that enhanced or hindered their ability to manage turning points and transitions. A substantive theory that comprised a problem of ?being in the grip of blood glucose levels? (BGLs) and a process termed ?creating stability? to manage life transitions was developed. The state of being in the grip of BGLs was associated with the impact of fluctuating BGLs; responses of other people to the womens? diabetes and the impact of diabetes on other people?s lives. The women managed these problems by engaging in social and psychological strategies helping them to stabilised their lives and feel more in control during life transitions.

Psychological impact of DAFNE training in adults with Type 1 diabetes

This thesis investigated the psychological impact of an education intervention, Dose Adjustment for Normal Eating (DAFNE), in adults with type 1 diabetes. The results demonstrated that the education programme improved participants' subjective wellbeing, self-efficacy and reduced diabetes-related distress compared to a comparison group that engaged in usual care. The portfolio examined the use of mindfulness-based strategies, in particular Acceptance and Commitment Therapy (ACT) in four case studies which illustrated that the impact of the therapy is directly related to the the willingness of the client to engage in the practices.

Turning points and transitions : experiences of young women with Type 1 diabetes

This research explores young women with Type 1 diabetes' perspectives of the problems and how they manage them when facing turning points and making life transitions. The study presents a substantive theory of how the women tried to minimise the grip of blood glucose levels felt during transitions by creating stability in their lives.

Young adults’ management of Type 1 diabetes during life transitions

Aim. To identify life transitions likely to impact diabetes self-care among young adults with Type 1 diabetes and their coping strategies during transition events.
Background. Relationships among psychosocial stress, adjustment, coping and metabolic control affect clinical outcomes and mental health. Life transitions represent major change and are associated with stress that temporarily affects individuals’ problem-solving, coping abilities and blood glucose levels.
Design. A qualitative interpretive inquiry.
Method. Semi-structured interviews were conducted with 20 young adults with Type 1 diabetes and a constant comparative analysis method. Data and analysis was managed using QSR NVIVO 7 software.
Results. Participants identified two significant transition groups: life development associated with adolescence, going through the education system, entering new relationships, motherhood and the workforce and relocating. Diabetes-related transitions included being diagnosed, developing diabetes complications, commencing insulin pump treatment and going on diabetes camps. Participants managed transitions using ‘strategic thinking and planning’ with strategies of ‘self-negotiation to minimise risks’; ‘managing diabetes using previous experiences’; ‘connecting with others with diabetes’; ‘actively seeing information to ‘patch’ knowledge gaps’; and ‘putting diabetes into perspective’.
Conclusions. Several strategies are used to manage diabetes during transitions. Thinking and planning strategically was integral to glycaemic control and managing transitions. The impact of transitions on diabetes needs to be explored in larger and longitudinal studies to identify concrete strategies that assist diabetes care during life transitions.
Relevance to clinical practice. It is important for health professionals to understand the emotional, social and cognitive factors operating during transitions to assist young adults with Type 1 diabetes to achieve good health outcomes by prioritising goals and plan flexible, timely, individualised and collaborative treatment.