Cardiovascular disease contributes significantly to global morbidity and mortality and is particularly prevalent among individuals with Type 2 diabetes, which is thought to in part be due to the association between diabetes and the metabolic syndrome. Traditional cardiovascular risk prediction scores perform well in the general population but their use in people with Type 2 diabetes is limited as they are thought to underperform in high risk groups. Indeed, the use of any risk prediction in people with Type 2 diabetes is a point of discussion among clinicians as people with diabetes are thought by some to be at immediate high risk of CVD, whereas others view them as having a degree of modifiable risk which can be addressed using risk prediction. In the general population, novel markers such as cIMT and carotid plaque, as well as other potential biomarkers of cardiovascular risk, have been explored as possible adjuncts to risk scores in the prediction of cardiovascular disease. The evidence for their use in general populations has been established, although there have been no firm conclusions with regard to recommendations for their use, which is partly due to the high degree of variability in cIMT measurement. However, the evidence for their use in people with Type 2 diabetes is sparse, despite the use of such markers as surrogate CV endpoints in clinical trials. This thesis aimed to describe the frequency, distribution and change of cIMT and carotid plaque, as well as to explore the relationship of cIMT and carotid plaque with cardiovascular risk factors, prevalent cardiovascular disease and future cardiovascular events in older people with Type 2 diabetes. The association between cIMT, carotid plaque and other novel risk markers was also explored. The analysis was performed using data from the Edinburgh Type 2 Diabetes Study (ET2DS). This study is a large, prospective cohort study of 1066 men and women with Type 2 diabetes, aged 60-75 years at recruitment, living in Edinburgh and the Lothians. cIMT and carotid plaque were measured at year 1 follow up of the study. Variables concerning cardiovascular risk factors used in this thesis were obtained from the data collection performed at baseline and year 1. A mean of 3.5 years of follow up was available for analysis and is complete for the baseline cohort as data linkage was performed. Mean values of cIMT in the ET2DS were comparable with other studies of cIMT in people with Type 2 diabetes and may indeed be higher than cIMT in the general population. Measurement of cIMT by the sonographer was comparable with computer aided measurements. Increasing cIMT was independently associated (although only modestly) with increasing age, male sex and raised systolic blood pressure. Mean cIMT was associated with prevalent vascular disease and was predictive of incident global cardiovascular events and coronary artery events (but not stroke) over and above UKPDS risk factors, although the clinical impact of this on the reclassification of vascular risk (as demonstrated by net reclassification index (NRI)) was limited. There was a high prevalence of carotid plaque, and in particular “high risk” plaque, in the ET2DS. Different measures of carotid plaque were independently associated with several cardiovascular risk factors. Carotid plaque thickness was independently associated, albeit modestly, with increasing age, male sex, duration of diabetes and hypertension, plaque score with increasing age, hypertension, smoking and low BMI, and high risk plaque with hypertension and low BMI. All measures of carotid plaque were associated with prevalent vascular disease. However, despite these associations, carotid plaque did not have any additional predictive value for incident cardiovascular events over and above UKPDS risk factors. Finally, measures of cIMT and carotid plaque in the ET2DS were associated with the biomarkers ankle brachial index (ABI) and NTproBNP. In addition these markers were significantly higher in those individuals with prevalent vascular disease, suggesting a more extensive exploration of the association of these markers in relation to cardiovascular disease in the ET2DS may be warranted. cIMT and carotid plaque are modestly associated with traditional cardiovascular risk factors and prevalent cardiovascular disease in older adults with Type 2 diabetes. cIMT has been shown to be predictive of incident events while carotid plaque was not, in people with Type 2 diabetes, over and above traditional cardiovascular risk factors, although its impact on risk reclassification may only be small. Further evidence is required from the longer follow up of the ET2DS before firm conclusions can be drawn on the usefulness of cIMT and carotid plaque as risk markers in people with Type 2 diabetes. In addition, large collaborative studies could be used to further explore the relationship of carotid plaque, and change in cIMT with incident cardiovascular events, as well as exploring the additive effect of cIMT and plaque on risk prediction.

STUDY 1. INTRODUCTION. Insufficient physical activity is a major risk factor for developing type 2 diabetes. Using isotemporal substitution models, the influence of replacing modest durations of sedentary time with physical activity on diabetes risk scores can be studied. The aims of this study were to examine the relationship between diabetes risk scores, sedentary time and physical activity measured using wrist worn accelerometry, and to model the changes in risk scores by reallocating movement behaviours from lower to a higher intensity. METHODS. Data from 251 (93 males; aged 56.7 ± 8.8) participants from a mixed ethnicity cohort from Leicestershire, UK were selected for analysis. The relationship between diabetes risk (using the Leicester Diabetes Risk Assessment Score), physical activity and sedentary time was identified using multiple linear regressions and isotemporal substitution analysis. Models were calculated for main effects and also adjusted for peak oxygen uptake (VO2) and accelerometer wear time. RESULTS. Both unadjusted and adjusted models revealed that diabetes risk was inversely related to sedentary time, and positively related to light and moderate to vigorous physical activity (MVPA) (p < 0.0005). Unadjusted, the replacement of sedentary time with 10 minutes of either light or MVPA resulted in a reduction in diabetes risk score of -0.22 and -0.54, respectively. There was an eight to nine times greater reduction in risk for the same MVPA replacement models when the least active participants were compared to the pooled analysis (3.601 unadjusted). CONCLUSION. Diabetes risk is associated with sedentary time and physical activity estimated from wrist worn accelerometry. The replacement of sedentary time with MVPA is most beneficial for the least active individuals. STUDY 2. INTRODUCTION. Most associations between physical behaviours and health are assessed using intensity and duration based estimations; however, individuals accrue physical activity in differing ways and behavioural profiles have been linked with varying cardiometabolic risk factors. The frequency or regularity of behaviour may hold additional relationships with health, but have not been extensively explored. Accelerometers provide researchers with a large stream of raw data to analyse. The aim of this paper was to calculate a novel method of behavioural regularity called sample entropy from wrist worn accelerometry and to ascertain whether there are associations with cardiometabolic risk factors in adults. METHODS. Data from 290 (107 males; aged 57.0 ± 8.8) participants from a mixed ethnicity cohort from Leicestershire, UK were selected for analysis. Entropy scores were calculated using 60-second count data within MATLAB. The relationship between entropy scores, physical activity, sedentary time and cardiometabolic risk factors was identified using multiple linear regressions. Models were calculated for main effects and also adjusted for age, sex, accelerometer wear time and body mass index (BMI). RESULTS. Sample entropy scores were significantly related to high-density lipoprotein (HDL) cholesterol (b = 0.148, p = 0.042), triglycerides (b = -0.293, p = 0.042) and glycated haemoglobin (HbA1c) (b = -0.225, p = 0.006), even after adjustment for confounding variables. Traditional intensity estimates of physical activity were not associated; however, the frequency of breaks in sedentary time were significantly related to entropy scores (b = 0.004, p = 0.002). CONCLUSION. Using a novel measure of signal complexity, associations have been revealed with cardiometabolic risk factors; however further analysis in a larger, more diverse dataset is required to ascertain the utility of this technique within behavioural research and if so, what constitutes typical/average levels of entropy within a population. STUDY 3. INTRODUCTION. Acute physiological changes such as reductions in postprandial glucose excursions have been demonstrated within experimental studies that have compared being physically active to sedentary conditions. However, for this information to be truly useful, the coupling of behaviour and glucose data in a free-living environment needs to be achieved. The aim of the study was to ascertain if there is a relationship between objectively measured physical activity, sedentary time and glucose variability using glucose monitoring in an adult population. METHODS. Data from 29 participants recruited from a mixed gender sample from Leicestershire, UK were selected for analysis. Physical activity, sedentary time and interstitial glucose was measured continuously over 14 days using an accelerometer and the Freestyle Libre flash glucose monitor. Daily time (minutes) spent sedentary, and in light activity and moderate to vigorous physical activity (MVPA) were regressed against glycaemic variability indices including daily mean (average) glucose, standard deviation and mean amplitude of glycaemic excursions (MAGE). Generalised Estimating Equations were calculated between behaviour and glycaemic variability variables. Models were calculated for main effects and also adjusted for age, gender and accelerometer wear time. RESULTS. Physical activity and sedentary time were associated with measures of glucose variability, however low fitness individuals showed a stronger relationship between MVPA and MAGE (MAGE: whole sample b = -0.002, low fitness b = -0.012. Additionally, after adjustment for covariates, sedentary time was positively associated with a higher daily mean glucose (b = 0.001, p = 0.001) and MAGE (b = 0.002, p < 0.0005) for the low fitness group. MVPA was negatively associated with mean glucose (b = -0.004, p < 0.0005) and MAGE (b = -0.012, p < 0.0005); however, standard deviation of glucose was not associated with behaviour of any intensity. The magnitudes of the relationships were small, although participants were non-diabetics and exhibited relatively good glucose control i.e. minimal fluctuations in daily glucose variability. CONCLUSION. This study shows that sedentary time, physical activity and glucose variability are related. Despite supporting the previous laboratory research, it is uncertain whether any changes in glucose will reliably occur in all individuals. MVPA confers the largest reductions in glucose variability indices, yet as one of the few studies to couple behaviour and glucose data, more research is needed on larger and more diverse samples.

An accumulating evidence-base indicates that internalizing mental health disorders in adulthood are causally associated with cardiovascular diseases (CVD) and type-2 diabetes (T2DM). It is plausible, however, that the relationship between mental and cardiometabolic ill-health becomes established long before adulthood, and that externalizing problems (the other central domain of common psychopathology) are also involved. These questions, as well as questions on the mechanisms that underlie the relationships, have been insufficiently investigated. The overarching goal of this dissertation was to expand current knowledge on how common mental health problems increase cardiometabolic risk over the life course. First, the prospective association between childhood internalizing (emotional problems) and externalizing problems (hyperactivity and conduct problems) with CVD and T2DM risk in adolescence was assessed in data from the Avon Longitudinal Study of Parents and Children (ALSPAC, N=7,730). Results showed that hyperactivity problems were associated with insulin resistance (high HOMA-IR); that hyperactivity and conduct problems were each associated with high triglyceride levels; and that emotional problems were inversely associated with high triglyceride levels. These results suggest that childhood externalizing problems are an early life risk factor for CVD and T2DM and that childhood internalizing problems are not a risk factor or, that risk in these children does not become apparent until after adolescence. Second, the mechanisms underlying the prospective association of childhood hyperactivity and conduct problems with high levels of triglycerides in adolescence were investigated using causal mediation methods. Results showed that despite being associated with hyperactivity and with conduct problems, body mass index and lifestyle health behaviors including sleep, diet, physical activity, alcohol, and smoking, together these variables, as measured, mediated only 19.6 % and 19.3% of the associations of hyperactivity and conduct problems with triglycerides, respectively. These results would suggest that mechanisms other than body adiposity and unhealthy behaviors are also involved and that those mechanisms have a larger role in mediating these relationships. Alternatively, It is possible that the observed small role of health behaviors is due to error in measurement and therefore improving measurements for health behaviors should be a central focus of future work. Third and last, a systematic review of the literature on the relationship between childhood externalizing problems with CVD and T2DM risk was conducted. Studies were graded for propensity to bias. Evidence was summarized and assessed for consistency. Results strongly supported positive associations of externalizing problems with insulin resistance, T2DM, and with increased blood lipids among children and adolescents. Evidence suggested that associations are at least partly independent of body adiposity. Evidence provided mix support for the associations with T2DM and blood lipids in adults and with other outcomes in children or adults. Studies in children tended to be cross-sectional and to use valid and reliable assessment methods, whereas studies of adults tended to be prospective and to rely on less-valid, less reliable assessment methods. These results warrant more research, specifically prospective studies that track children into young adulthood, that employ well-validated measures of externalizing behaviors, that rely on repeated assessments of T2DM and CVD risk throughout follow-up, and that investigate mechanisms other than body adiposity and health behaviors. Overall, this dissertation has found that childhood externalizing problems are prospectively associated with elevated CVD and T2DM risk, specifically with elevated risk of increased levels of blood lipids and insulin resistance. Unlike studies in adults, this dissertation does not support a role of internalizing problems as risk factors. Among children with externalizing problems, risk becomes evident before adolescence and appears to be largely driven by pathways independent of unhealthy behaviors and body adiposity. Implications of this research’s findings for health practice were proposed. This dissertation identified several gaps and methodological shortcoming in the extant literature. Recommendations were made for future research, including fundamental next questions to investigate, and study designs and methodologies that are best suited to tackle those questions.

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Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798–808, 2017—Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline.

Aim To examine the risk factor of coronary artery calcium (CAC) in individuals with diabetes and those without diabetes in Central Appalachia. Methods Study population included 2479 asymptomatic participants who underwent CAC screening between August 2012 and November 2016. CAC score was classified into four categories [0 (no plaque), 1–99 (mild plaque), 100–399 (moderate plaque), and ≥400 (severe plaque)]. Multinomial logistic regression analyses were conducted to test the association between CAC and cardiovascular disease (CVD) risk factors among participants with diabetes, age and gender matched controls, and randomly selected controls. Results 13.6% of total participants had diabetes. Around 69%, 59.8%, and 57.7% of the participants with diabetes, matched controls, and randomly selected controls had CAC score ≥1, respectively. Participants with diabetes had higher prevalence of all CVD risk factors than controls. Among participants with diabetes, hypertension and physical inactivity increased the odds of CAC = 100–399, while among those without diabetes, hypertension and hypercholesteremia increased the odds of having CAC = 1–99 and CAC ≥ 400. Conclusion Half of study participants had subclinical atherosclerosis (i.e., CAC), and individuals with diabetes had higher CAC scores. This study suggests that individuals with diabetes in Central Appalachia might benefit from screening for CAC.

[Truncated abstract. Please see the pdf format for the complete text.] The discovery of the C282Y mutation and its role in the development of hereditary haemochromatosis has allowed a greater understanding into the effects of iron overload and its involvement in other conditions such as diabetes and heart disease. It has also allowed the better classification of heterozygotes, who were previously only diagnosed through the use of family studies. There are however, areas of conflict between phenotyping and genotyping methods. My research involved examining the relationship between Haemochromatosis and certain diseases such as diabetes and heart disease; genotyping versus phenotyping discrepancies and the possible interaction of secondary mutations. In Chapter 3 a population study was undertaken with the aim of comparing genotyping versus phenotyping methods as well as increasing general practitioner awareness regarding hereditary haemochromatosis and its diagnosis. It was determined that a minimum of 5000 subjects would be required to give the study sufficient power. Individuals were to be between the ages of 20—40 years, and thus presumably presymptomatic. Participation was entirely voluntary and a consent form was to be signed. Recruitment of subjects proved to be difficult and there was a selective bias towards individuals already displaying symptoms of haemochromatosis. In total less than a 100 subjects were recruited for the study. There were several issues encountered in the implementation of this study. Firstly the number of GPs participating was probably insufficient to recruit the subjects required. A more extensive campaign was probably required to enroll more GPs. Secondly it is very difficult for a busy GP to find the time necessary to explain the study to each of his patients and to get them to sign the consent form. Finally a bias developed in some of the requests. The subjects participating in this study were supposed to be random but in many cases the GPs had enrolled them in the study because they had symptoms of iron overload. In effect the biggest obstacle this study faced was the recruitment of subjects. Due to the small number of subjects little statistical data could be obtained from this study. It was noted, however, that genotyping methods detected two individuals who were homozygous for the C282Y mutation. Both also had increased transferrin saturation levels. Phenotyping detected 5 individuals with increased transferrin saturation. The three others detected via phenotyping were C282Y heterozygotes. Haemochromatosis has long been though to be related to the development of diabetes due to the effect of iron overload on the pancreas. If this is so it would be logical to assume that the prevalence of haemochromatosis would be higher in a diabetic population. Chapter 4 examined the possibility that diabetics have a higher frequency of the C282Y mutation. A population group consisting of 1355 diabetics was genotyped for the C282Y mutation and iron studies were performed on all heterozygotes and C282Y homozygotes. Initial findings indicated that there was a significant difference between the diabetic and control population. However, this finding was the opposite of what was expected, there seemed to be a decreased frequency of the Y allele in the diabetic population rather than an increased one. The control and diabetic populations were not matched in terms of ethnicity. The removal of the ethnic bias in the diabetic population altered the statistics so there was no longer a significant difference between the two groups. This study highlighted the importance of using appropriate control populations as comparison groups. The final results of the study indicated that there was no significant difference between the diabetic population and the control population. This would seem to indicate that there is not an increased occurrence of the C282Y mutation in the diabetic population when compared to the control group. Chapter 5 considered the possible association between C282Y heterozygosity and cardiovascular disease as well as the potential for early mortality. Several recent studies have indicated that C282Y heterozygosity may be a risk factor for the development of atherosclerosis, possibly on the basis of increased iron loading. Using a control population and a population of individuals with known coronary events the incidence of the C282Y mutation was compared against other risk factors. C282Y heterozygosity did not appear to be a risk factor for atherosclerosis. There was however, a statistically significant link between increased ferritin in women and carotid plaques. A population of elderly women was genotyped in order to examine the effects of C282Y heterozygosity on longevity. The first hypothesis addressed in chapter 5 was that C282Y heterozygosity was a risk factor for the development of coronary heart disease.

Background. With increasing personal affluence and changes in lifestyle, there is rising prevalence of type 2 diabetes mellitus in Hong Kong. Approximately 60% of diabetic subjects in Hong Kong are asymptomatic and previously undiagnosed. Since diabetes carries significant mortality and morbidity risk, it is important to diagnose these subjects early for intervention. There are many known factors associated with development of type 2 diabetes. Some are remediable such as obesity, dyslipidaemia, hypertension, while some are non-remediable such as age and past history of gestational diabetes. Identifying high-risk subjects will increase the yield and cost-effectiveness of screening program for diabetes and related risk factors and provide useful epidemiological information on the natural history of these diseases. / Methods. I used data from several cross-sectional and prospective studies of which I was the principal investigator or one of the co-investigators to test these hypotheses. The studies include mainly the following: (1) A public utility company workforce survey on cardiovascular risk factors in 1990 (n=1513). (2) Chinese subjects with risk factors for diabetes who underwent 75 gram oral glucose tolerance test (OGTT) screening at the Prince of Wales Hospital (PWH) between 1988 and 1995 (n=3718). (3) The 'United Christian Nethersole Community Health Service' (UCNCHS) primary health screening program database in 1997 (n=17764). / Objectives & hypothesis. I aimed to study the various factors associated with the development of type 2 diabetes in Hong Kong Chinese. With this information, I can design a screening method to early identify those subjects who are at high-risk for diabetes. I hypothesize the following: (1) Many risk factors for diabetes in Caucasians are also applicable to Hong Kong Chinese. (2) The presence of multiple factors increases the risk of diabetes in a linear fashion. (3) Chinese subjects are at risk of developing diabetes at a lower threshold of obesity, which is one of the most important risk factors for type 2 diabetes. / Results. Based on a cohort of 1513 asymptomatic subjects from a workforce survey, those in the top quartile of body mass index (BMI), as compared to those in the lowest quartile, had a 4 to 10-fold increased risk of diabetes and a 2.5 to 5-fold increased risk of impaired glucose tolerance (IGT) for men and women. (Abstract shortened by UMI.) / Ko Tin Choi. / "May 2005." / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0173. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 264-283). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Thesis (M. Nursing Science) --University of Limpopo, 2018 / Introduction: Diabetes mellitus has become a worldwide problem that is continuing to rise resulting in morbidity and mortality in developing countries.Finland developed the FINDRISC tool. Canada uses the Finnish Diabetes Risk Score (FINDRISC) tool and the Canadian Diabetes Risk Questionnaire (CANRISC), Germany has developed the German Diabetes Risk Score (GDRS). These risk scores are all self-assessment tools meant for assessing the risk of diabetes. They cover variables such as age, waist circumference, height, history of hypertension, physical activity, consumption of alcohol, coffee, whole grains and red meat (Buijsse, Simmons, Griffin & Schulze, 2010). Aim: To determine the feasibility of Home-Based Carers (HBCs) on the use of the FINDRISC tool to assess diabetes mellitus (DM) patients at Ga-Dikgale Village, South Africa. Methodology: A quantitative, descriptive cross–sectional design has been used to describe knowledge and practices of HBCs in using FINDRISC tool to assess the Diabetes Mellitus patient at the Dikgale village. Fifty two (52) HBCs have been assessed and homogeneous purposive convenience sampling has been used. A modified (tool) has been used by the HBCs to assess the risk status of people to determine diabetes risk status while the researcher scored the HBCs on the utilisation of modified FINDRISC tool after they have demonstrated all sections of the risk assessment tool. Data analysis has been done using (Statistical Package for Social Sciences) IBM ABSTRACT vii SPSS version 24 software and Microsoft excel sheet. Results: This study has found that HBCs can play in important role in the assessment of patients at risk of developing diabetes in the communities by using the assessment tool. The knowledge and skills of the HBCs that have been acquired throughout the years can be augmented by strengthening the primary health care re-engineering programme and in-service training that can be tailored for proper functioning of the HBCs within the health care team. Conclusion and recommendation: The burden of DM can be alleviated through the use of FINDRISC tool by determining diabetes risk status and employ necessary precautions to assist people who are at risk. This study recommend that the FINDRISC tool be modified in order to be relevant to the African perspective by validating of the tool through taking blood samples from people who are at risk . Keywords: diabetes mellitus, home-based carers, Finnish diabetes risk score tool, feasibility, assessment of patients at risk.

Exercise has a wide range of benefits for patients with type 1 diabetes, including improvements in body composition, cardiovascular risk profile and glycaemic control. Unfortunately, exercise also increases the risk of hypoglycaemia in children with type 1 diabetes, both at the time of exercise and for many hours afterwards. The availability of clear, evidence-based guidelines regarding appropriate adjustments in carbohydrate intake or insulin doses may help to prevent this exercise associated hypoglycaemia. However, current guidelines regarding exercise in children with type 1 diabetes rely heavily on adult literature or the consensus of experts. Therefore, further studies are needed in young people with diabetes to document the metabolic responses during and following exercise. In particular, the mechanisms underlying hypoglycaemia occurring many hours after exercise require further exploration. In addition, as children often exercise in the afternoon, studies performed at this time of the day are more likely to be transferrable to a real life situation. For this reason, we studied adolescents with type 1 diabetes to investigate physiological responses to exercise, focusing on afternoon activity and employing a novel variation of the euglycaemic insulin clamp technique. The core experiments involved studying diabetic adolescents on two occasions in a counterbalanced, paired design during and after afternoon exercise. Insulin was infused at a constant rate based on the subjects' usual daily insulin dose and glucose was infused to maintain euglycaemia. At 1600 hrs subjects either exercised at a moderate intensity (95% of their lactate threshold) for 45 minutes on a cycle ergometer (exercise study), or sat on the ergometer without exercising (rest study). Using this experimental design, it was found that glucose infusion rates (GIR) to maintain euglycaemia were elevated during and shortly following exercise and again from 7-11 hours after exercise compared with the rest study. Counterregulatory hormone levels were similar between the exercise and rest studies except for peaks in noradrenaline, cortisol and growth hormone levels at the end of exercise. Glucagon and adrenaline levels did not increase with exercise. The observed biphasic increase in glucose requirements paralleled the observed clinical risk of hypoglycaemia immediately during exercise and the delayed risk of hypoglycaemia which often occurs overnight.