Distress and Living with Diabetes: Defining Characteristics Through an Online Survey.

INTRODUCTION: There is considerable evidence for diabetes reducing quality of life. The impact of such a diagnosis on mental health is less well understood and was subsequently explored here. METHODS: Online PHQ-9 scores (which calculate the severity of depression), Diabetes Distress Screening Scale (DDSS) and EQ-5D-5L (quality-of-life) questionnaires were completed by patients with diabetes, followed by the extraction of data where possible from responders' clinical records. RESULTS: A total of 133 people submitted questionnaires. However, not all data items could be completed by each patient; 35% (45/130) had type I diabetes mellitus (T1DM); 55% (64/117) were women. The overall median age of 117 responders was 60 (IQR 50-68 years). The median aggregated response scores were: EQ-5D-5L 0.74 (IQR 0.64-0.85) (lower quality of life than UK population median of 0.83), DDSS 1.9 (IQR1.3-2.7) (≥ 2 indicates moderate distress) and PHQ-9 5 (IQR2-11) (≥ 5 indicates depression). Higher diabetes distress (DDSS)/lower quality of life EQ-5D-5L/higher depressive symptoms (PHQ-9) linked to female sex (DDSS 0.5/25% above median), younger age (< 50 years DDSS 0.7/35% above median), fewer years after diagnosis (< 10 years DDSS 0.8/40% above median), and obesity (BMI > 35 DDSS 0.6/30% above median). Additionally, a HbA1c reading of ≤ 48 mmol/mol was associated with higher DDSS scores, as did a reduction of more than 5 mmol/mol in HbA1c over the last three HbA1c measurements. The 30 individuals with a history of prescribed antidepressant medication also showed higher diabetes distress scores (DDSS 0.9, equating to 45% above the median). The DDSS score elevation came from an increase in emotional burden and regimen-related distress. DDSS scores were not significantly linked to diabetes type, insulin use, absolute level/change in blood glucose HbA1c. Physician-related distress showed a similar pattern. CONCLUSIONS: A low level of stress in relation to diabetes management may be associated with lower HbA1c. The larger impact of diabetes on mental health in younger women/people with shorter diabetes duration should be noted when considering psychosocial intervention/behavior change messaging. Physician-related distress is a potentially remediable factor. However, this sample was self-selecting, limiting generalization to other samples.

The experience of blood glucose monitoring in people with type 2 diabetes mellitus (T2DM).

BACKGROUND: Finger prick blood glucose (BG) monitoring remains a mainstay of management in people with type 2 diabetes (T2DM) who take sulphonylurea (SU) drugs or insulin. We recently examined patient experience of BG monitoring in people with type 1 diabetes (T1DM). There has not been any recent comprehensive assessment of the performance of BG monitoring strips or the patient experience of BG strips in people with T2DM in the UK. METHODS: An online self-reported questionnaire containing 44 questions, prepared following consultation with clinicians and patients, was circulated to people with T2DM. 186 responders provided completed responses (25.5% return rate). Fixed responses were coded numerically (eg not confident = 0 fairly confident = 1). RESULTS: Of responders, 84% were treated with insulin in addition to other agents. 75% reported having had an HbA1c check in the previous 6 months. For those with reported HbA1c ≥ 65 mmol/mol, a majority of people (70%) were concerned or really concerned about the shorter term consequences of running a high HbA1c This contrasted with those who did not know their recent HbA1c, of whom only 33% were concerned/really concerned and those with HbA1c <65 mmol/mol of whom 35% were concerned. Regarding BG monitoring/insulin adjustment, only 25% of responders reported having sufficient information with 13% believing that the accuracy and precision of their BG metre was being independently checked. Only 9% recalled discussing BG metre accuracy when their latest metre was provided and only 7% were aware of the International Standardisation Organisation (ISO) standards for BG metres. 77% did not recall discussing BG metre performance with a healthcare professional. CONCLUSION: The group surveyed comprised engaged people with T2DM but even within this group there was significant variation in (a) awareness of shorter term risks, (b) confidence in their ability to implement appropriate insulin dosage (c) awareness of the limitations of BG monitoring technology. There is clearly an area where changes in education/support would benefit many.

Chemical Characterization and Quantification of Circulating Intact PTH and PTH Fragments by High-Resolution Mass Spectrometry in Chronic Renal Failure.

BACKGROUND: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. RESULTS: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively). CONCLUSIONS: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.

HuR expression in adipose tissue mediates energy expenditure and acute thermogenesis independent of UCP1 expression.

The goal of this study was to define the functional role of adipocyte-specific expression of the RNA binding protein Human antigen R (HuR). Mice with an adipocyte-specific deletion of HuR (Adipo-HuR-/- ) were generated by crossing HuR floxed (HuRfl/fl ) mice with mice expressing adiponectin-driven cre-recombinase (Adipoq-cre). Our results show that Adipo-HuR-/- mice display a lean phenotype compared to wild-type littermate controls. HuR deletion results in a diet-independent reduction in percent body fat composition along with an increase in energy expenditure. Functionally, Adipo-HuR-/- mice show a significant impairment in acute adaptive thermogenesis (six hours at 4°C), but uncoupling protein 1 (UCP1) protein expression in brown adipose tissue (BAT) is unchanged compared to control. Pharmacological inhibition of HuR also results in a marked decline in core body temperature following acute cold challenge independent of UCP1 protein expression. Among the 588 HuR-dependent genes in BAT identified by RNA-seq analysis, gene ontology analysis shows a significant enrichment in mediators of calcium transport and signalling, almost all of which are decreased in Adipo-HuR-/- mice compared to control. In conclusion, adipocyte expression of HuR plays a central role in metabolic homoeostasis and mediates UCP1-independent thermogenesis in BAT, potentially through post-transcriptional control of intracellular calcium transport.Abbreviations: Adipo-HuR-/-: Adipocyte-specific HuR deletion mice; BAT: Brown adipose tissue; HuR: Human antigen R; UCP1: Uncoupling protein 1.

Development and Application of Mass Spectroscopy Assays for Nε-(1-Carboxymethyl)-L-Lysine and Pentosidine in Renal Failure and Diabetes.

BACKGROUND: Advanced glycation end products (AGEs) are formed via the nonenzymatic glycation of sugars with amino acids. Two AGEs, Nε-(1-carboxymethyl)-L-Lysine (CML) and pentosidine, have been observed to be elevated in subjects suffering from a multitude of chronic disease states, and accumulation of these compounds may be related to the pathophysiology of disease progression and aging. METHODS: We describe here the development and validation of a specific and reproducible LC-MS/MS method to quantify CML and pentosidine in human serum with lower limits of quantitation of 75 ng/mL and 5 ng/mL, respectively. The analyte calibration curve exhibited excellent linearity at a range of 0-10 900 ng/mL for CML and 0-800 ng/mL for pentosidine. High-low linearity of 5 serum pairs was assessed, with a mean recovery of 103% (range 94-116%) for CML, and 104% (range 97-116%) for pentosidine. RESULTS: Serum concentrations of CML and pentosidine were quantified in 30 control and 30 subjects with chronic renal insufficiency. A significant increase in both analytes was observed in renal failure compared to control subjects (2.1-fold and 8.4-fold, respectively; P < 0.001 for both). In a separate cohort of 49 control versus 95 subjects with type 2 diabetes mellitus (T2DM), serum CML but not serum pentosidine, was significantly elevated in the T2DM patients, and CML was also correlated with glycemic control, as assessed by hemoglobin A1c (r = 0.34, P < 0.001). CONCLUSIONS: These mass spectroscopy-based assays for serum CML and pentosidine should be useful in accurately evaluating circulating levels of these key AGEs in various disease states.

Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes.

The worldwide prevalence of type 2 diabetes (T2D) is increasing. Despite normal to higher bone density, patients with T2D paradoxically have elevated fracture risk resulting, in part, from poor bone quality. Advanced glycation endproducts (AGEs) and inflammation as a consequence of enhanced receptor for AGE (RAGE) signaling are hypothesized culprits, although the exact mechanisms underlying skeletal dysfunction in T2D are unclear. Lack of inducible models that permit environmental (in obesity) and temporal (after skeletal maturity) control of T2D onset has hampered progress. Here, we show in C57BL/6 mice that a onetime pharmacological intervention (streptozotocin, STZ) initiated in adulthood combined with high-fat diet-induced (HFD-induced) obesity caused hallmark features of human adult-onset T2D, including prolonged hyperglycemia, insulin resistance, and pancreatic ß cell dysfunction, but not complete destruction. In addition, HFD/STZ (i.e., T2D) resulted in several changes in bone quality that closely mirror those observed in humans, including compromised bone microarchitecture, reduced biomechanical strength, impaired bone material properties, altered bone turnover, and elevated levels of the AGE CML in bone and blood. Furthermore, T2D led to the premature accumulation of senescent osteocytes with a unique proinflammatory signature. These findings highlight the RAGE pathway and senescent cells as potential targets to treat diabetic skeletal fragility.

Can a 'consent to contact' community help research teams overcome barriers to recruitment? The development and impact of the 'Research for the Future' community.

BACKGROUND: Recruitment to health research remains a major challenge. Innovation is required to meet policy commitments to help patients take part in health research. One innovation that may help meet those policy goals is the development of 'consent to contact' systems, where people give generic consent to be contacted about research opportunities. Despite their potential, there are few empirical assessments of different ways of recruiting patients to such communities, or of the value of such communities to local research teams. MAIN TEXT: We describe the development of the 'Research for the Future'consent to contact community, outline the recruitment of patients to the community, and present data on their participation in research. DISCUSSION: Over 5000 people have been registered across 3 clinical areas. A range of recruitment strategies have been used, including direct recruitment by clinicians, postal invitations from primary care, and social media. In a 1 year period (2016-2017), the community provided over 1500 participants for a variety of research projects. Feedback from research teams has generally been positive. The 'Research for the Future'consent to contact community has proven feasible and useful for local research teams. Further evaluation is needed to assess the cost-effectiveness of different recruitment strategies, explore patient and researcher experience of its advantages and disadvantages, and explore how the community can be more reflective of the wider population.

Prioritising prevention: implementation of IGT Care Call, a telephone based service for people at risk of developing type 2 diabetes.

AIM: To design, deliver and evaluate IGT Care Call, a telephone service providing a 6 month lifestyle education programme for people with impaired glucose tolerance (IGT). METHODS: An observational study of IGT Care Call, a programme providing motivational support and education using electronic scripts. The service was delivered to 55 participants, all of whom completed the course (an information pack and at least five telephone calls over 6 months). Clinical measurements were undertaken in General Practice at baseline, on completion of the programme and one year later. RESULTS: Among the 40 participants for whom we have complete data available, one year after discharge, participants showed improvements in fasting plasma glucose (0.29 mmol/l, 95% CI 0.07 to 0.51), weight (2.81 kg, 95% CI 1.20 to 4.42) and BMI (1.06 kg/m(2), 95% CI 0.49 to 1.63). All differences were statistically significant (p < 0.01). CONCLUSION: Whilst an uncontrolled observational study with a small sample size, this pilot suggests IGT Care Call may be effective in promoting positive and sustained lifestyle changes to prevent type 2 diabetes, which warrants further investigation. A telephone method of service delivery was acceptable, convenient and may have improved self confidence in how to reduce risk of type 2 diabetes.

Behaviour change among people with impaired glucose tolerance: Comparison of telephone-based and face-to-face advice.

OBJECTIVES: To develop, implement and compare two lifestyle services for people at risk of developing type 2 diabetes. METHODS: Two localities were selected to implement two different service delivery models, telephone-based and face-to-face, supporting people at risk of developing type 2 diabetes. Impact was assessed by comparing weight, fasting plasma glucose and oral glucose tolerance test (OGTT) results at baseline and six months later. RESULTS: Both services were associated with an improvement in OGTT 2-h plasma glucose and weight. In the telephone intervention, 47.3% of participants who completed the project achieved both normal fasting plasma glucose (≤6.0 mmol/l) and normal plasma glucose levels (≤7.7 mmol/l). Participants had a mean weight loss of 3.3 kg (SD 4.3), equating to 3.4% of body weight (p < 0.001). In the face-to-face intervention, 46.3% of participants achieved normal plasma glucose (≤7.7 mmol/l) and a mean weight loss of 2.9 kg (SD 4.5), equating to 3.1% of bodyweight (p < 0.001). CONCLUSIONS: Local health providers can adapt existing service provision and tailor it to provide lifestyle programmes for people with impaired glucose tolerance. Both service delivery models offer effective diabetes prevention although each model may cater for different population needs and a choice of services might be the preferred option.

Back to Sleep: an educational intervention with women, infants, and children program clients.

OBJECTIVE: The incidence of sudden infant death syndrome (SIDS) is 2 to 3 times higher in the black population compared with the US population as a whole. Prone sleeping is also twice as prevalent in black infants. Standard modes of communication (media, brochures) regarding the Back to Sleep (BTS) campaign have been less effective with blacks. The objective of this study was to determine whether a 15-minute educational intervention is effective in changing sleep position practice among black parents. METHODS: A trained health educator led 15-minute sessions about safe infant sleep practices for groups of 3 to 10 parents of young infants who attended a Women, Infants, and Children clinic in Washington, DC. We performed pre- and postsession surveys, asking about sleep position, reasons for choosing a sleep position, and knowledge of the relationship between sleep position and SIDS. We then interviewed parents 6 months after the intervention and compared this group with a group of parents at a different Women, Infants, and Children site who did not receive the intervention. RESULTS: A total of 310 parents/caregivers participated in sessions from October 2001 to July 2002. Mothers comprised 84.5% of the participants, fathers 6.5%, and other relatives 9.0%. Parents had a mean age of 26.2 years (range: 15-64; standard deviation: 8.3), and 76.5% had graduated from high school. For 51%, this was their first child. Before the intervention, more than half (57.7%) of infants reportedly slept on their back, with the remainder sleeping back/side or side (15%) and prone (17.3%). Approximately 85% (266) of infants were sleeping in the same room as the parents. Only 28.1% of parents initially believed that prone sleeping definitely increases the risk of SIDS. Infants were more likely to be placed supine when previous children were placed supine or when parents had more than a high school education. Parents were also more likely to place infants supine when they believed that prone increases the risk of SIDS, they had previous knowledge of BTS, and they were aware that the American Academy of Pediatrics recommends supine position for infants. Sleep position was not affected by where the infant slept, number of parents in the home, presence of a grandmother in the home, or presence of smokers in the home. Immediately after the intervention, 85.3% planned to place infants on the back, and 55.7% now believed that prone definitely increases the risk of SIDS. When compared with a control group of parents 6 months after the intervention, parents who attended the educational intervention were more likely to place their infants on the back (75% vs 45%), less likely to bedshare (16% vs 44.2%), less likely to cite infant comfort as a reason for sleep position (14.5% vs 29.2%), and more likely to be aware of BTS recommendations (72.4% vs 38.9%). CONCLUSIONS: A 15-minute educational session with small groups of black parents is effective in informing parents about the importance of safe sleep position and in changing parent behavior. The effect of the intervention is sustained throughout the first 6 months of life, when the infant is at the highest risk for SIDS.

Use of safe cribs and bedroom size among African American infants with a high rate of bed sharing.

BACKGROUND: Impoverishment and crowding are associated with an increased risk of sudden unexpected death among infants. Bed sharing likely increases this risk, particularly among African American infants. OBJECTIVES: To compare the sleep environment of African American infants who bed share with that of infants who do not share sleep surfaces and to compare access to a safe crib, and the space available for it, in the sleeping rooms of both groups of infants. METHODS: Home visits were made at approximately age 2 weeks to the homes of serially enrolled African American infants born between July 15, 2001, and November 1, 2001. Questionnaires were used to survey sleep practices, especially sleep surface used. The area of the floor space of rooms used for sleeping was calculated. A portable crib was provided for infants lacking access to safe sleep surfaces. RESULTS: Of these infants, 42 (41%) usually bed shared and 60 (59%) slept alone. The areas of the floor spaces were similar (mean +/- SD, 13.8 +/- 3.3 m(2) for bed sharers vs 12.7 +/- 3.7 m(2) for those who slept alone; 95% CI for difference, -0.34 to 2.51 m(2)). Infants sleeping alone were much more likely to have access to a safe crib (51 of 60 vs 13 of 42; P<.001), and 53 cribs were provided. Follow-up telephone calls made at approximately age 7 months to 43.4% of recipients suggested that the cribs were used on most nights, were durable, and were enthusiastically received. CONCLUSIONS: Crowding is not a strong explanation for bed sharing among impoverished African American infants in St Louis, Mo, who often bed share because there is not a safe crib available. Providing safe cribs may reduce the prevalence of bed sharing.