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BACKGROUND Despite being an unapproved method of insulin delivery, increasing numbers of people with type 1 diabetes (T1D) worldwide are choosing to use Loop, a Do-It-Yourself Automated Insulin Delivery system. OBJECTIVE We aimed to assess glycemic outcomes, safety and the perceived impact on quality of life (QOL), in a local Edmonton cohort of known Loop users. METHODS An observational study of adults with T1D using Loop was performed. Assessment of glycemic; HbA1c and time in range (TIR), and safety outcomes; hospital admissions and time below range (TBR), compared six months of Loop with the user’s prior regulatory approved insulin delivery method. QOL outcomes were assessed using INSPIRE, Diabetes Impact and Device Satisfaction (DIDS) measures (with maximum scores of 100, 10 and 10), and semi-structured interviews. RESULTS 24 adults with T1D, 66.7% female, median (IQR) age 33 (28-45), duration of diabetes 22 years (17-32), with duration of Loop 18 months (12-25). With Loop, median (IQR) HbA1c 7.1% (6.5-7.5), 54mmol/mol (48-58) and TIR 76.5% (64.6-81.9); a significant improvement from prior therapy (p=0.001 and p=0.005), with a non-significant reduction in time 3.0-3.9mmol/L (p=0.17) and CONCLUSIONS This local cohort of people with T1D, demonstrate a beneficial effect of Loop use on both glycemic control and QOL, with no safety concerns highlighted. CLINICALTRIAL N/A

IntroductionWe aimed to assess the current experience and attitudes towards Commercial and Do-it-yourself (DIY) automated insulin delivery (AID) systems among healthcare providers (HCP) across Canada.MethodsA cross-sectional study was performed through electronic distribution of an anonymous survey to HCP licensed to practice in Canada looking after people with type 1 diabetes (T1D).ResultsResponses included 204 HCP across the multi-disciplinary team; dieticians (32.8%), nurses (31.9%), and endocrinologists (28.4%), looking after adults (51%) and children (23%) mainly in urban areas (85.7%). Respondents reported a median 100-500 patients with T1D per practice, with a median 6-24 current users/practice of Commercial compared to a median 1-5 current users/practice of DIY AID. The majority of HCP (72.7%) were comfortable supporting Commercial AID, whereas only 21.6% reported comfort supporting DIY AID use. A significant, although moderate correlation between HCP experience and comfort was seen; Commercial r=0.57(pConclusionsDespite documented beneficial outcomes, AID systems are not widely used in the management of T1D in Canada. The need for both user and HCP education to improve familiarity with the systems, in addition to clarity in medico-legal guidance, have been identified as gaps, which if addressed, might enable the benefits of AID to be more widely available to people with T1D in Canada.

Introduction Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors. Pathophysiology of fha Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release. Implications for future treatment Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.

In the past century, since the discovery of insulin, methods of insulin delivery and glucose monitoring have advanced technologically. In particular, the introduction of insulin pumps, providing continuous subcutaneous insulin infusion (CSII), and continuous glucose monitors (CGMs) have been revolutionary for people living with type 1 diabetes. In this review, we have focussed on automated insulin delivery (AID) systems and discuss the implications of both approved and off-label options for the user and health-care providers. By pairing insulin pumps with CGM, AID systems facilitate automated adjustment in insulin delivery based on CGM readings. A subset of these have been developed commercially and were granted regulatory approval. In contrast, unregulated do-it-yourself AID systems, designed and set up by people living with type 1 diabetes and their families, have advanced rapidly and are gaining popularity worldwide. These patient-driven technologies have demonstrated impressive user self-reported improvements in glycemic control and quality of life, but have not been evaluated in any formal randomized controlled trials or by regulators. This presents challenging uncertainty for health-care providers, in addition to ethical and legal implications in supporting people with diabetes who wish to use these technologies. The current knowledge, opinions and practices relating to the use of AID systems across Canada are unknown. Gathering this information will highlight current practice and areas of knowledge gaps and concern and will assist in focussed education. This understanding is crucial to ensure people with type 1 diabetes using these systems have access to optimal, consistent and safe patient-centred care.

AIMS The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P

Aims Self-compassion is a modifiable characteristic, linked with psychological well being and intrinsic motivation to engage in positive health behaviours. We aimed to explore levels of self-compassion in individuals with type 2 diabetes (T2DM) and their association with levels of depression, diabetes-related distress and glycaemic control. Methods A cross-sectional study in 176 patients with T2DM in Leicester, UK, using three self-report questionnaires: the Self Compassion Scale (SCS); Patient Health Questionnaire (PHQ-9), and Diabetes Distress Scale (DDS-17). Demographic data, medical history and blood samples were collected. Results Majority of participants were male (n=120, 68.2%), with median [IQR] age and HbA1c of 66 [60, 71] years and 7.3 [6.7, 8.0] %, respectively. Multivariable analysis adjusting for age, gender, ethnicity and diabetes duration revealed significant association of all three scores with HbA1c: per one standard deviation increase of each score, a -0.16% reduction in HbA1c for SCS (p=0.027), 0.21% increase for PHQ-9 (p=0.012) and 0.33% increase for DDS-17 (p Conclusions Higher levels of self-compassion and lower levels of depressive symptoms were associated with significantly better long-term diabetes control. These results reinforce the importance of emphasis on psychological parameters, including self-compassion, in the multi-disciplinary management of T2DM. We identify this as a potential area for intervention in UK practice.

BACKGROUND & AIMS A causal association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and type 2 diabetes (T2DM) remains unproved. We aimed to quantify the likelihood of causality examining the sensitivity of observational associations to possible confounding. METHODS Studies investigating longitudinal associations of NAFLD with CVD or T2DM were searched on 5 June 2018. Study-specific relative risks (RRs) were combined in random-effects meta-analyses and pooled estimates used in bias analyses. RESULTS Associations of NAFLD with CVD and T2DM were reported in 13 (258 743/18 383 participants/events) and 20 (240 251/12 891) studies respectively. Comparing patients with NAFLD to those without, the pooled RR was 1.48 (95% CI: 0.96, 2.29) for CVD and 2.17 (1.77, 2.65) for T2DM. In bias analyses, for an unmeasured confounder associated to both NAFLD and CVD with a RR of 1.25, the proportion of studies with a true (causal) effect of NAFLD on CVD surpassing a RR of 1.10 (ie, 10% increased risk of CVD in participants with NAFLD) was 0.67 (95% CI: 0.42, 0.92) while for 75% increase, it was 0.36 (0.11, 0.62). Corresponding figures for T2DM were 0.97 (0.91, 1.00) for a 10% increased risk of T2DM in participants with NAFLD to 0.70 (0.49, 0.92) for a 75% increase. CONCLUSIONS The results of this study are strongly suggestive for a causal relationship between NAFLD and T2DM, while the evidence for a causal link between NAFLD and CVD is less robust. Therapeutic strategies targeting NAFLD are likely to reduce the risk of developing T2DM.

Aim Whether the relative risk of cancer incidence and mortality associated with diabetes has changed over time is unknown. Data synthesis On August 12th, 2020, we electronically searched for observational studies reporting on the association between diabetes and cancer. We estimated temporal trends in the relative risk of cancer incidence or mortality associated with diabetes and calculated the ratio of relative risk (RRR) comparing different periods. As many as 193 eligible articles, reporting data on 203 cohorts (56,852,381 participants; 3,735,564 incident cancer cases; 185,404 cancer deaths) and covering the period 1951–2013, were included. The relative risk of all–site cancer incidence increased between 1980 and 2000 [RRR 1990 vs.1980: (1.24; 95% CI: 1.16, 1.34); 2000 vs.1990: (1.23; 1.15, 1.31)] and stabilised thereafter at a relative risk of 1.2; the relative risk of all–site cancer mortality was constant at about 1.2 from 1980 to 2010. Both magnitudes and trends in relative risk varied across cancer sites: the relative risk of colorectal, female breast, and endometrial cancer incidence and pancreatic cancer mortality was constant during the observed years; it increased for bladder, stomach, kidney, and pancreatic cancer incidence until 2000; and decreased for liver while increased for prostate, colon and gallbladder cancer incidence after 2000. Conclusions Alongside the increasing prevalence of diabetes, the temporal patterns of the relative risk of cancer associated with diabetes may have contributed to the current burden of cancer in people with diabetes.

BACKGROUND AND PURPOSE Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality. DATA EXTRACTION AND DATA SYNTHESIS Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and LIMITATIONS Biases other than unmeasured confounding were not analytically assessed. CONCLUSIONS Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.