Amy Kennedy

What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review

Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.

Hypoglycaemia is associated with increased length of stay and mortality in people with diabetes who are hospitalized.

Diabet. Med. 29, e445–e448 (2012)

Does exercise improve glycaemic control in type 1 diabetes? A systematic review and meta-analysis.

Objective Whilst regular exercise is advocated for people with type 1 diabetes, the benefits of this therapy are poorly delineated. Our objective was to review the evidence for a glycaemic benefit of exercise in type 1 diabetes. Research Design and Methods Electronic database searches were carried out in MEDLINE, Embase, Cochrane’s Controlled Trials Register and SPORTDiscus. In addition, we searched for as yet unpublished but completed trials. Glycaemic benefit was defined as an improvement in glycosylated haemoglobin (HbA1c). Both randomised and non-randomised controlled trials were included. Results Thirteen studies were identified in the systematic review. Meta-analysis of twelve of these (including 452 patients) demonstrated an HbA1c reduction but this was not statistically significant (standardised mean difference (SMD) −0.25; 95% CI, −0.59 to 0.09). Conclusions This meta-analysis does not reveal evidence for a glycaemic benefit of exercise as measured by HbA1c. Reasons for this finding could include increased calorie intake, insulin dose reductions around the time of exercise or lack of power. We also suggest that HbA1c may not be a sensitive indicator of glycaemic control, and that improvement in glycaemic variability may not be reflected in this measure. Exercise does however have other proven benefits in type 1 diabetes, and remains an important part of its management.

Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögrens syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.

Attitudes and Barriers to Exercise in Adults with Type 1 Diabetes (T1DM) and How Best to Address Them: A Qualitative Study

Background Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM. Methodology A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme. Principal findings Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise). Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise. Significance Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in increasing activity in patients with T1DM.

Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a study protocol for a pilot randomized controlled trial

BackgroundExercise has a beta cell preserving effect in patients with type 2 diabetes. This benefit of exercise has not been examined in type 1 diabetes. Significant beta cell function is present at the time of diagnosis of type 1 diabetes and therefore studies of beta cell preservation are ideally conducted immediately after diagnosis.Many of the variables required to design and power such a study are currently unknown. The aim of EXTOD is to obtain the information required to design a formal study of exercise and beta cell preservation in newly diagnosed patients with type 1 diabetes.MethodsBarriers to exercise will initially be assessed in a qualitative study of newly diagnosed patients. Then, sixty newly diagnosed adult type 1 diabetes patients will be randomized to either conventional treatment or exercise, stratified on beta cell function and fitness. The exercise group will be encouraged to increase their level of activity to a minimum of 150 minutes of moderate to vigorous intensity exercise per week, aiming for 240 minutes per week of exercise for 12 months. Beta cell function will be measured by meal-stimulated C peptide. Primary outcomes are recruitment, adherence to exercise, loss to follow-up, and exercise levels in the non-intervention arm (contamination). The secondary outcome of the study is rate of loss of beta cell function.DiscussionThe outcomes of the EXTOD study will help define the barriers, uptake and benefits of exercise in adults newly diagnosed with type 1 diabetes. This information will enable design of a formal study to assess the effect of exercise on beta cell preservation in newly diagnosed patients with type 1 diabetes.Trial registrationCurrent controlled trials ISRCTN91388505

Inter-Individual Differences in RNA Levels in Human Peripheral Blood

Relatively little is known about the range of RNA levels in human blood. This report provides assessment of peripheral blood RNA level and its inter-individual differences in a group of 35 healthy humans consisting of 25 females and 10 males ranging in age from 50 to 89 years. In this group, the average total RNA level was 14.59 μg/ml of blood, with no statistically significant difference between females and males. The individual RNA level ranged from 6.7 to 22.7 μg/ml of blood. In healthy subjects, the repeated sampling of an individual’s blood showed that RNA level, whether high or low, was stable. The inter-individual differences in RNA level in blood can be attributed to both, differences in cell number and the amount of RNA per cell. The 3.4-fold range of inter-individual differences in total RNA levels, documented herein, should be taken into account when evaluating the results of quantitative RT-PCR and/or RNA sequencing studies of human blood. Based on the presented results, a comprehensive assessment of gene expression in blood should involve determination of both the amount of mRNA per unit of total RNA (U / ng RNA) and the amount of mRNA per unit of blood (U / ml blood) to assure a thorough interpretation of physiological or pathological relevance of study results.

Exercise to preserve β‐cell function in recent‐onset Type 1 diabetes mellitus (EXTOD) – a randomized controlled pilot trial

Residual β‐cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this β‐cell function reduces complications. We hypothesized that exercise preserves β‐cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis.

Attitudes and barriers to exercise in adults with a recent diagnosis of type 1 diabetes: a qualitative study of participants in the Exercise for Type 1 Diabetes (EXTOD) study

Objectives To explore attitudes and barriers to exercise in adults with new-onset type 1 diabetes mellitus (T1DM). Design Qualitative methodology using focus group (n=1), individual face-to-face (n=4) and telephone interviews (n=8). Thematic analysis using the Framework Method. Setting Nineteen UK hospital sites. Participants Fifteen participants in the Exercise for Type 1 Diabetes study. We explored current and past levels of exercise, understanding of exercise and exercise guidelines, barriers to increasing exercise levels and preferences for monitoring of activity in a trial. Results Five main themes were identified: existing attitudes to exercise, feelings about diagnosis, perceptions about exercise consequences, barriers to increasing exercise and confidence in managing blood glucose. An important finding was that around half the participants reported a reduction in activity levels around diagnosis. Although exercise was felt to positively impact on health, some participants were not sure about the benefits or concerned about potential harms such as hypoglycaemia. Some participants reported being advised by healthcare practitioners (HCPs) not to exercise. Conclusions Exercise should be encouraged (not discouraged) from diagnosis, as patients may be more amenable to lifestyle change. Standard advice on exercise and T1DM needs to be made available to HCPs and patients with T1DM to improve patients’ confidence in managing their diabetes around exercise. Trial registration number ISRCTN91388505; Results

Humpback whale "super-groups" - A novel low-latitude feeding behaviour of Southern Hemisphere humpback whales (Megaptera novaeangliae) in the Benguela Upwelling System

Southern Hemisphere humpback whales (Megaptera novaeangliae) generally undertake annual migrations from polar summer feeding grounds to winter calving and nursery grounds in subtropical and tropical coastal waters. Evidence for such migrations arises from seasonality of historic whaling catches by latitude, Discovery and natural mark returns, and results of satellite tagging studies. Feeding is generally believed to be limited to the southern polar region, where Antarctic krill (Euphausia superba) has been identified as the primary prey item. Non-migrations and / or suspended migrations to the polar feeding grounds have previously been reported from a summer presence of whales in the Benguela System, where feeding on euphausiids (E. lucens), hyperiid amphipods (Themisto gaudichaudii), mantis shrimp (Pterygosquilla armata capensis) and clupeid fish has been described. Three recent research cruises (in October/November 2011, October/November 2014 and October/November 2015) identified large tightly-spaced groups (20 to 200 individuals) of feeding humpback whales aggregated over at least a one-month period across a 220 nautical mile region of the southern Benguela System. Feeding behaviour was identified by lunges, strong milling and repetitive and consecutive diving behaviours, associated bird and seal feeding, defecations and the pungent “fishy” smell of whale blows. Although no dedicated prey sampling could be carried out within the tightly spaced feeding aggregations, observations of E. lucens in the region of groups and the full stomach contents of mantis shrimp from both a co-occurring predatory fish species (Thyrsites atun) and one entangled humpback whale mortality suggest these may be the primary prey items of at least some of the feeding aggregations. Reasons for this recent novel behaviour pattern remain speculative, but may relate to increasing summer humpback whale abundance in the region. These novel, predictable, inter-annual, low latitude feeding events provide considerable potential for further investigation of Southern Hemisphere humpback feeding behaviours in these relatively accessible low-latitude waters.