Autoimmune, insulin-dependent diabetes mellitus in man is an inherited disease . Many studies have demonstrated (reviewed in references 1, 2) that genes linked to the MHC of man contribute to the genetic susceptibility to diabetes . >90% of Caucasian patients suffering from type 1 diabetes express the DR3 and/or DR4 antigens as compared with a 60% expression in the total population . Interestingly, DR3/DR4 heterozygotes are particularly susceptible to the development of diabetes since up to 50% of type 1 diabetics possess this genotype as compared with only 5% of the general population . The fine specificity of the association of DR3 and DR4 with diabetes has recently been defined using HLA restriction endonuclease fragment length polymorphisms (3-5) and human T lymphocyte clones that define DR subtypes (6, 7).The autoimmune response in type 1 diabetes is characterized by insulitis, which is an inflammatory infiltrate affecting the islets of Langerhans . In a study of 60 recent-onset type 1 diabetics, insulitis was present in 78% of patients (8).A persistence of memory cells specific for insulin-producing a cells is suggested by the observation that long-term insulin-dependent patients receiving a pancreas transplant from an identical twin will still reject the islet tissue even though the original antigenic stimulus has been absent for years (9).Recently, two animal models exhibiting spontaneous diabetes mellitus have been identified . The BB rat (10, 11) and the nonobese diabetic (NOD)' mouse (12-16) both evidence the destructive autoimmune pancreatic insulitis that is characteristic of human type 1 diabetes . In the BB rat model, diabetes can be adoptively transferred with Con A-activated splenic lymphocytes obtained from diabetic BB rats (17,18). Further evidence supporting the autoimmune etiology of diabetes in the BB rat is that treatment of BB rats with a combination of immunosuppressive agents, which included cyclosporine A, glucocorticoids, and

Regular exercise is important for health, fitness and longevity in people living with type 1 diabetes, and many individuals seek to train and compete while living with the condition. Muscle, liver and glycogen metabolism can be normal in athletes with diabetes with good overall glucose management, and exercise performance can be facilitated by modifications to insulin dose and nutrition. However, maintaining normal glucose levels during training, travel and competition can be a major challenge for athletes living with type 1 diabetes. Some athletes have low-to-moderate levels of carbohydrate intake during training and rest days but tend to benefit, from both a glucose and performance perspective, from high rates of carbohydrate feeding during longdistance events. This review highlights the unique metabolic responses to various types of exercise in athletes living with type 1 diabetes.

Key points Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability. Low‐volume high‐intensity interval training (HIT) is a time‐efficient alternative to traditional moderate‐intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied. The applicability of current laboratory‐ and gym‐based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home‐HIT). This study is the first to show that 12 weeks of virtually supervised Home‐HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home‐based MICT and laboratory‐based HIT, while reducing many of the major barriers to exercise. Abstract This study investigated the effect of a novel virtually supervised home‐based high‐intensity interval training (HIT) (Home‐HIT) intervention in obese individuals with elevated cardiovascular disease (CVD) risk on capillarisation and muscle microvascular eNOS/NAD(P)Hoxidase ratio. Thirty‐two adults with elevated CVD risk (age 36 ± 10 years; body mass index 34.3 ± 5 kg m−2; V̇O2 peak 24.6 ± 5.7 ml kg min−1), completed one of three 12‐week training programmes: Home‐HIT (n = 9), laboratory‐based supervised HIT (Lab‐HIT; n = 10) or virtually supervised home‐based moderate‐intensity continuous training (Home‐MICT; n = 13). Muscle biopsies were taken before and after training to assess changes in vascular enzymes, capillarisation, mitochondrial density, intramuscular triglyceride content and GLUT4 protein expression using quantitative immunofluorescence microscopy. Training increased V̇O2 peak (P < 0.001), whole‐body insulin sensitivity (P = 0.033) and flow‐mediated dilatation (P < 0.001), while aortic pulse wave velocity decreased (P < 0.001) in all three groups. Immunofluorescence microscopy revealed comparable increases in total eNOS content in terminal arterioles and capillaries (P < 0.001) in the three conditions. There was no change in eNOS ser1177 phosphorylation (arterioles P = 0.802; capillaries P = 0.311), but eNOS ser1177/eNOS content ratio decreased significantly following training in arterioles and capillaries (P < 0.001). Training decreased NOX2 content (arterioles P < 0.001; capillaries P < 0.001), but there was no change in p47phox content (arterioles P = 0.101; capillaries P = 0.345). All measures of capillarisation increased (P < 0.05). There were no between‐group differences. Despite having no direct supervision during exercise, virtually supervised Home‐HIT resulted in comparable structural and endothelial enzymatic changes in the skeletal muscle mic...