John N. Harvey

Understanding Why People with Type 1 Diabetes Do Not Attend for Specialist Advice: A Qualitative Analysis of the Views of People with Insulin-dependent Diabetes Who Do Not Attend Diabetes Clinic:

Attendance at diabetes clinic is associated with improved medical outcome, however, significant numbers of people with type 1 diabetes choose not to attend. In order to understand the reasons underlying this decision, qualitative interviews were carried out with 12 long-term non-attenders. Three distinct groups emerged differing in terms of their cognitive and emotional responses to diabetes and their coping strategies: (1) the ‘High fear’ group; (2) the ‘Patient as expert’ group; and (3) the ‘Low motivation’ group. These differences should be recognized and suitable approaches developed to ensure that all people with diabetes are able to accept appropriate specialist support.

Using the IPQ and PMDI to predict regular diabetes care-seeking among patients with Type 1 diabetes

OBJECTIVES The objectives were, first, to identify factors associated with regular diabetes care-seeking and, second, to compare the performance of the Illness Perception Questionnaire (IPQ) and a modified version of the Personal Models of Diabetes Interview (PMDI) in predicting care-seeking. METHOD This was a cross-sectional study involving 42 patients who had not attended hospital diabetes clinic for a period of 18 months or more and 42 matched controls receiving specialist care. Differences in illness representations between clinic attenders and non-attenders were examined. Due to the variability in care-seeking between non-attenders (ranging from no contact with health professionals to regular general practitioners care), participants were then reclassified for further analyses into those receiving regular care from either hospital diabetes clinic or general practice (n = 52) and those receiving no regular care (n = 32). RESULTS Patients not seeking regular care held more negative views of the control, course and consequences of diabetes than those who received regular care. Regression analyses showed that the most important construct was treatment effectiveness. Treatment effectiveness (PMDI) and control (IPQ) dimensions were associated with clinic attendance. PMDI constructs of treatment effectiveness, threat and worries were associated with regular care-seeking. CONCLUSIONS IPQ and PMDI results were generally consistent. In order to understand diabetes care-seeking behaviour it is important to measure beliefs about the benefits of treatment recommendations in addition to those of the disease itself. Emotional and cognitive responses to diabetes should be assessed.

Continuity of care in the transition from child to adult diabetes services: a realistic evaluation study

Objectives: To identify the continuity mechanisms central to a smooth transition from child to adult diabetes care, the service components through which these can be achieved and their inter-relations in different contexts. Methods: A realistic evaluation study of five models of transition in England comprising: organizational analysis (semi-structured interviews with 38 health care professionals and selected observations); case studies of 46 young people under-going transition and 39 carers (three qualitative interviews over a 12-18 month period, medical record review and clinical interviews); surveys of 82 (32% response rate at least once and 11% response rate at two time points) young people in the population approaching, undergoing or less than 12 months post-transition, and their carers (questionnaires included psychosocial outcome measures); and a costs and consequences analysis. Results: Seven continuities contribute to smooth transition: relational, longitudinal, management, informational, flexible, developmental and cultural. Relational, longitudinal, flexible and cultural continuity are the most important. Models with high levels of relational, longitudinal, flexible and cultural continuity achieve smooth transition with relatively informal, low-cost informational and management continuity mechanisms. Models with low levels of relational and longitudinal continuity need to invest in more formal interventions to facilitate management, flexible and informational continuity so that smooth transition is not compromised. Conclusions: Focusing on continuity mechanisms, their inter-relations and the effectiveness of different constellations of service components in achieving smooth transition has furnished evidence to inform the development of innovative models which build on the logic of these findings but are sensitive to local context. Further studies are needed to confirm the quantitative findings from a broader range of services and patients.

Folate supplementation reduces serum Hsp70 levels in patients with type 2 diabetes

Abstract Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 μM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non–insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.

Mediation by illness perceptions of the effect of personality and health threat communication on coping with the diagnosis of diabetes

OBJECTIVES (1) To examine the relationship of personality traits and diabetes health threat communication (DHTC) to the coping strategies of newly diagnosed diabetes patients; (2) to determine to what extent these postulated effects are mediated by illness representations (IRs). DESIGN A longitudinal prospective study based on the common sense model. METHODS Patients were assessed shortly after diagnosis and 2 years after the diagnosis of diabetes. Personality traits (Mini-markers) were assessed at baseline. The DHTC Questionnaire was completed at baseline and 2 years. The Revised Illness Perception Questionnaire and the coping orientation to problems experienced were completed at 2 years. Mediation by IRs of the potential influence of personality and DHTC on coping behaviour was assessed by the method of Baron and Kenny. RESULTS Multiple regression analyses showed that educational level, agreeableness, openness/intellect, conscientiousness, and perceptions of a more reassuring health message since diagnosis were related to more adaptive coping (e.g., active coping, planning). The association of openness and perceived reassuring health message with active coping showed complete mediation by illness coherence and personal control. Openness led to seeking emotional support mediated by perceived personal control. Coherence associated with (partial mediation) the relation of openness to planning. Similarly, personal control and coherence mediated the relation of openness to positive reinterpretation and growth (PRG). Agreeableness had a direct relationship with active coping and PRG but led to planning and seeking instrumental support mediated by perceived treatment effectiveness. Perceptions of a threatening health message were associated with seeking instrumental and emotional support and this was mediated by symptom perception but threat had a direct relationship with planning. CONCLUSIONS Both personality traits and health threat communication predict the way individuals cope with diabetes. The relationships of these factors are largely mediated through measurable IRs. The results suggest targets for intervention to achieve greater problem-focused coping.

The role of illness perceptions, coping and evaluation in care-seeking among people with type 1 diabetes

Attendance at diabetes clinic is associated with improved medical outcome. In the present study, we used self-regulatory theory to identify factors associated with diabetes care-seeking. This article examines (i) differences in coping strategies and evaluation of coping success (general health, impact of diabetes on life and clinic satisfaction) between attenders and non-attenders, (ii) the relationships between personal models and coping strategies and (iii) the role of personal models and coping strategies in predicting diabetes care-seeking. The sample comprised of 42 non-attenders and 42 matched controls receiving specialist care. Attenders employed more effective coping strategies than non-attenders and reported higher levels of clinic satisfaction. Groups expressed similar views regarding health status and impact of diabetes. Participants were reclassified into ‘regular care’ (hospital or general practice) (n = 52) and ‘no regular care’ (n = 32) for further analysis. The results support the utility of self-regulatory theory. More positive personal models were associated with more effective coping strategies, which were in turn associated with regular care-seeking.

Alpha adrenoceptor agonist-induced microcirculatory oscillations are reduced in diabetic neuropathy.

In diabetic patients small fiber neuropathy has been associated with impairment of 0.1 Hz microvascular vasomotion. The aim of this study was (1) to investigate whether vasoconstriction-induced microvascular oscillations in the skin are reduced in diabetic patients with peripheral and/or autonomic neuropathy, and (2) whether this method could be used as a non-invasive surrogate marker to assess diabetic small fiber neuropathy. Four matched groups were studied: diabetic patients without neuropathy (D), with peripheral neuropathy (DPN), with peripheral and autonomic neuropathy (DAN), and non-diabetic controls (Ctrl). All participants were evaluated for peripheral and autonomic neuropathy, microvascular endothelial function, and metabolic syndrome indicators. Laser Doppler flowmetry was used to measure oscillations after iontophoresis of the alpha one selective agonist phenylephrine. approximately 0.1-Hz oscillations recorded at the foot were significantly attenuated in diabetic patients with peripheral and/or autonomic neuropathy (DPN and DAN groups) compared to diabetic patients without neuropathy or non-diabetic controls. In the forearm, microvascular oscillations were significantly reduced only in patients with autonomic neuropathy (DAN). Oscillation measures correlated significantly (P<0.001) with all markers of peripheral neuropathy but not with markers of measurements of microvascular endothelial function, or metabolic syndrome markers. In a logistic regression model, reduced microvascular oscillations at the foot were a strong predictor for the presence of peripheral neuropathy. The measurement of phenylephrine-induced approxiamtely 0.1-Hz microvascular oscillation may represent a useful non-invasive tool with which to study the effects of treatment strategies on the diabetic small fiber neuropathy.

Deterministic nonlinear features of cutaneous perfusion are lost in diabetic subjects with neuropathy

The aim of this study was to analyze and compare the deterministic nonlinear structure of cutaneous laser Doppler flowmetry signals obtained from the forearm and foot of normal subjects and diabetic patients without neuropathy (D), with peripheral neuropathy (DPN) and with combined autonomic and peripheral neuropathy (DAN). Flow oscillations were evaluated under baseline conditions, after local warming of the skin to 44 °C and after warming plus iontophoresis of phenylephrine. The presence of nonlinearity was investigated by three complementary approaches: (i) attractor reconstruction, (ii) calculation of largest Lyapunov exponents (LLEs), and (iii) correlation dimension analysis. Conclusions were validated against surrogate stochastic time series generated by randomizing the Fourier phase of the raw data. In the control and D groups, the combination of phenylephrine and warming unmasked flowmotion with a prominent component at 0.1 Hz. Attractor reconstruction revealed toroidal structure and estimated LLEs were positive. LLEs decreased to zero and dimension estimates increased for surrogate data, consistent with loss of determinism. In diabetic subjects with neuropathy estimates of LLE were not significantly different from zero and dimensions were unaffected by phase randomization. Evidence for nonlinear structure was also obtained under baseline conditions in normal and D subjects, but was lost on warming alone. We conclude that deterministic control mechanisms contribute to cutaneous flowmotion, particularly when pseudo-quasiperiodic behavior is enhanced by phenylephrine. Nonlinear analysis of laser Doppler signals may provide previously unrecognized insights into the effects of diabetic neuropathy on perfusion because it can identify loss of complexity independently of the amplitude of the signals recorded.

The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy

The changes in renal kallikrein synthesis through normal pregnancy and its relation to aldosterone excretion and the glomerular filtration rate was investigated. Overnight urinary kallikrein and aldosterone excretion rates and glomerular filtration rate were measured at 18 weeks, 34 weeks, term and postpartum in normal human pregnancy. Kallikrein excretion was raised at 18 weeks compared with the nonpregnant state (P < 0.001) but was significantly reduced at term. The reduction in renal kallikrein was not due to falling aldosterone concentration, which increased in the third trimester, compared with 18 weeks (P= 0.002) and remained elevated at term compared with the nonpregnant state (P < 0.001). Glomerular filtration rate remained elevated at term despite the reduced kallikrein excretion rate. These data are consistent with the hypothesis that increased aldosterone production is one factor responsible for increased kallikrein synthesis which contributes to elevated glomerular filtration rate in early pregnancy. Other factors clearly inhibit renal kallikrein production at term. In the face of plasma volume expansion associated with increased mineralo‐corticoid production, the effects of reduced kallikrein synthesis at term on glomerular perfusion and reabsorption of sodium by the distal tubule may predispose to blood pressure elevation in late pregnancy.

Polymorphisms in the Tropomyosin TPM1 Short Isoform Promoter Alter Gene Expression and Are Associated With Increased Risk of Metabolic Syndrome

BACKGROUND Inflammation contributes to the development of atherosclerotic lesions in the metabolic syndrome. Tropomyosin isoform expression is altered in this disease and has a role in inflammatory cell plasticity, motility, and insulin sensitivity. We determined the frequency of haplotype carriage of three single-nucleotide polymorphisms (SNPs) in the short isoform promoter of the TPM1 gene in 300 normal controls and 500 metabolic syndrome patients. The effect of each haplotype on tropomyosin gene expression was assessed. METHODS PCR-restriction fragment length polymorphism assays were developed for each polymorphism. Promoter activity was measured using luciferase assays in the insulin-sensitive human embryonic kidney (HEK) 293 and the monocyte THP-1 lines. RESULTS The SNPs -111(T/C), -426(T/C), and -491(A/G), relative to the TPM1 short isoform transcription start site, occurred in haplotypes ATT, GCT, GTT, and GTC, and were in strong linkage disequilibrium. ATT had a frequency of 66%. The presence of -491G, which conforms to a predicted binding site for transcription factor AML-1, caused a decrease in gene expression of 24% in the HEK 293 cells. In the THP-1 cells, haplotypes GTC and GTT gave 24% lower expression, whereas haplotype GCT gave expression at wild-type levels. The carriage of a -491G allele gave an odds ratio of 1.4 (95% CI 1.02-1.8) for the metabolic syndrome (P < 0.03). CONCLUSIONS A polymorphism in the TPM1 short isoform promoter region is predicted to alter transcription factor binding, alters gene expression and is associated with the metabolic syndrome. This could affect inflammatory cells and cytoskeleton-mediated insulin signaling.