Change in cardio-protective medication and health-related quality of life after diagnosis of screen-detected diabetes: Results from the ADDITION-Cambridge cohort.

AIMS: Establishing a balance between the benefits and harms of treatment is important among individuals with screen-detected diabetes, for whom the burden of treatment might be higher than the burden of the disease. We described the association between cardio-protective medication and health-related quality of life (HRQoL) among individuals with screen-detected diabetes. METHODS: 867 participants with screen-detected diabetes underwent clinical measurements at diagnosis, one and five years. General HRQoL (EQ5D) was measured at baseline, one- and five-years, and diabetes-specific HRQoL (ADDQoL-AWI) and health status (SF-36) at one and five years. Multivariable linear regression was used to quantify the association between change in HRQoL and change in cardio-protective medication. RESULTS: The median (IQR) number of prescribed cardio-protective agents was 2 (1 to 3) at diagnosis, 3 (2 to 4) at one year and 4 (3 to 5) at five years. Change in cardio-protective medication was not associated with change in HRQoL from diagnosis to one year. From one year to five years, change in cardio-protective agents was not associated with change in the SF-36 mental health score. One additional agent was associated with an increase in the SF-36 physical health score (2.1; 95%CI 0.4, 3.8) and an increase in the EQ-5D (0.05; 95%CI 0.02, 0.08). Conversely, one additional agent was associated with a decrease in the ADDQoL-AWI (-0.32; 95%CI -0.51, -0.13), compared to no change. CONCLUSIONS: We found little evidence that increases in the number of cardio-protective medications impacted negatively on HRQoL among individuals with screen-detected diabetes over five years.

Are changes in glycaemic control associated with diabetes-specific quality of life and health status in screen-detected type 2 diabetes patients? Four-year follow up of the ADDITION-Cambridge cohort.

BACKGROUND: Interventions that improve HbA1c levels do not necessarily improve health-related quality of life (QoL). This issue may be particularly relevant in asymptomatic diabetes patients detected earlier in the course of the disease. METHODS: HbA1c , diabetes-specific QoL (ADDQoL) and health status were measured in 510 screen-detected diabetes patients from the ADDITION-Cambridge trial at 1 and 5 years post diagnosis. Multivariable logistic/linear regression was used to quantify the longitudinal association between change in HbA1c from 1 to 5 years and ADDQoL and health status at 5 years, adjusting for age, sex, education and trial group; alcohol consumption, smoking, physical activity, plasma vitamin C, HbA1c , ADDQoL or health status at 1 year, and glucose-lowering medication at 5 years. RESULTS: From 1 to 5 years, median HbA1c interquartile range increased from 6.3% (5.9-6.8) to 6.8% (6.4-7.4); the median ADDQoL score and mean health status physical health summary score decreased from -0.4 (-1 to -0.08) to -0.5 (-1.08 to -0.09) (suggesting an adverse impact of diabetes on QoL) and by -0.79 (8.94) points, respectively. Increases in HbA1c were independently associated with reporting a negative impact of diabetes on QoL (OR = 1.38, 95% CI: 1.03 to 1.85) but not with the health status summary scores. CONCLUSIONS: Increases in HbA1c from 1 to 5 years post-diagnosis were independently associated with increased odds of reporting a negative impact of diabetes on QoL. While our results suggest that efforts to reduce HbA1c do not adversely affect health-related QoL, large numbers of participants still report a negative impact of diabetes on their QoL 5 years post-diagnosis.

Healthy behaviours and 10-year incidence of diabetes: a population cohort study.

OBJECTIVE: To examine the association between meeting behavioural goals and diabetes incidence over 10 years in a large, representative Swedish population. METHODS: Population-based prospective cohort study of 32,120 individuals aged 35 to 55 years participating in a health promotion intervention in Västerbotten County, Sweden (1990 to 2013). Participants underwent an oral glucose tolerance test, clinical measures, and completed diet and activity questionnaires. Poisson regression quantified the association between achieving six behavioural goals at baseline - body mass index (BMI) <25 kg/m(2), moderate physical activity, non-smoker, fat intake <30% of energy, fibre intake ≥15 g/4184 kJ and alcohol intake ≤20 g/day - and diabetes incidence over 10 years. RESULTS: Median interquartile range (IQR) follow-up time was 9.9 (0.3) years; 2211 individuals (7%) developed diabetes. Only 4.4% of participants met all 6 goals (n=1245) and compared to these individuals, participants meeting 0/1 goals had a 3.74 times higher diabetes incidence (95% confidence interval (CI)=2.50 to 5.59), adjusting for sex, age, calendar period, education, family history of diabetes, history of myocardial infarction and long-term illness. If everyone achieved at least four behavioural goals, 14.1% (95% CI: 11.7 to 16.5%) of incident diabetes cases might be avoided. CONCLUSION: Interventions promoting the achievement of behavioural goals in the general population could significantly reduce diabetes incidence.

Do improvements in dietary behaviour contribute to cardiovascular risk factor reduction over and above cardio-protective medication in newly diagnosed diabetes patients?

BACKGROUND/OBJECTIVES: A healthy diet is an integral component of successful diabetes management. However, the comparative importance of adopting a healthy diet for cardiovascular risk factor reduction over and above medication use among newly diagnosed diabetes patients remains unclear. SUBJECTS/METHODS: We computed a dietary score consistent with American Diabetes Association and Diabetes UK recommendations in 574 newly diagnosed diabetes patients by summing standardised values for the intake of total energy, saturated fat, sodium, fibre and plasma vitamin C. In linear regression analyses, stratified by cardio-protective medication use (yes/no), we quantified the comparative longitudinal associations of baseline diet and change in diet over 1 year with change in blood pressure, HbA1c and lipids. RESULTS: Baseline diet was generally not predictive of change in cardiovascular risk factor levels at 1 year. In contrast, dietary change over 1 year among patients prescribed and not prescribed cardio-protective medication after baseline was associated with comparative (p-interaction all ⩾0.95) reductions in diastolic blood pressure (-2.38 vs -2.93 mm Hg, respectively) and triglycerides (-0.31 vs -0.21 mmol/l, respectively), independent of potential confounding factors and change from baseline to follow-up in physical activity and smoking status. CONCLUSIONS: Modest dietary change over the first year following diagnosis of diabetes was associated with reductions in blood pressure and triglycerides, over and above the effects of cardio-protective medication. Our findings support the notion that dietary change should be viewed as an integral component of successful diabetes self-management, irrespective of medication use.

Revealing mechanisms underlying variation in malaria virulence: effective propagation and host control of uninfected red blood cell supply.

Malaria parasite clones with the highest transmission rates to mosquitoes also tend to induce the most severe fitness consequences (or virulence) in mammals. This is in accord with expectations from the virulence-transmission trade-off hypothesis. However, the mechanisms underlying how different clones cause virulence are not well understood. Here, using data from eight murine malaria clones, we apply recently developed statistical methods to infer differences in clone characteristics, including induction of differing host-mediated changes in red blood cell (RBC) supply. Our results indicate that the within-host mechanisms underlying similar levels of virulence are variable and that killing of uninfected RBCs by immune effectors and/or retention of RBCs in the spleen may ultimately reduce virulence. Furthermore, the correlation between clone virulence and the degree of host-induced mortality of uninfected RBCs indicates that hosts increasingly restrict their RBC supply with increasing intrinsic virulence of the clone with which they are infected. Our results demonstrate a role for self-harm in self-defence for hosts and highlight the diversity and modes of virulence of malaria.

Partitioning regulatory mechanisms of within-host malaria dynamics using the effective propagation number.

Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.

Parasite genetic diversity does not influence TNF-mediated effects on the virulence of primary rodent malaria infections.

The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) is associated with malaria virulence (disease severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled for, a greater day 7 TNF-alpha response was induced by infection with more virulent P.c.c. clones. Since many functions of TNF-alpha are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c. infections induced significantly different plasma interferon gamma (IFN-gamma), interleukin 6 (IL-6) and interleukin 10 (IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-alpha is a key mediator of weight loss, independent of parasite load and across parasite genotypes.