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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Clinical trials have shown that bariatric surgery (BS) is associated with better glycemic control and diabetes remission in patients with type 2 diabetes (T2D) compared with routine care.We conducted a real-world population-based study examining the impact of BS on glycemic control and medications in patients with T2D.This was a retrospective, matched, controlled cohort study conducted between January 1, 1990, and January 31, 2018, using IQVIA Medical Research Data, a primary care electronic records database. Adults with body mass index (BMI) ≥30 kg/mA total of 1126 patients in the surgical group and 2219 patients in the control group were analyzed. Mean (standard deviation) age was 50.0 (9.3) years, 67.6% were women, baseline glycocylated hemoglobin (HbA1C) was 7.8% (1.7 mmol/mol), and diabetes duration was 4.7 years (range, 2.0-8.4 years). Over a median (interquartile range) follow-up of 3.6 years (1.7-5.9 years), a higher proportion of patients in the surgical group achieved an HbA1C of ≤6.0% than the control group (65.8% versus 22.8%). The surgical group showed a decrease in mean HbA1C of 1.5% (95% confidence interval [CI]: 1.4%-1.7%), 1.4% (1.2%-1.5%), and 1.3% (1.1%-1.5%) at 1-, 2-, and 3-year follow-up, respectively, whereas HbA1C increased in the control group. The proportion of patients receiving glucose-lowering medications decreased in the surgical group (92.2% to 66.5%) but increased in the control group (85.3% to 90.2%).BS is associated with significant improvement in glycemic control, achievement of normal HbA1C levels, and reduced need for glucose-lowering therapy in patients with T2D.

Purpose of ReviewThis review offers a critical narrative evaluation of emerging evidence that sodium-glucose co-transporter-2 (SGLT2) inhibitors exert nephroprotective effects in people with type 2 diabetes.Recent FindingsThe SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes. Randomised clinical trials and ‘real world’ observational studies, mostly involving type 2 diabetes patients, have noted that use of an SGLT2 inhibitor can slow the decline in glomerular filtration rate (GFR), reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria.SummaryThe nephroprotective effects of SGLT2 inhibitors are class effects observed with each of the approved agents in people with a normal or impaired GFR. These effects are also observed in non-diabetic, lean and normotensive individuals suggesting that the mechanisms extend beyond the glucose-lowering, weight-lowering and blood pressure-lowering effects that accompany their glucosuric action in diabetes patients. A key mechanism is tubuloglomerular feedback in which SGLT2 inhibitors cause more sodium to pass along the nephron: the sodium is sensed by macula cells which act via adenosine to constrict afferent glomerular arterioles, thereby protecting glomeruli by reducing intraglomerular pressure. Other effects of SGLT2 inhibitors improve tubular oxygenation and metabolism and reduce renal inflammation and fibrosis. SGLT2 inhibitors have not increased the risk of urinary tract infections or the risk of acute kidney injury. However, introduction of an SGLT2 inhibitor in patients with a very low GFR is not encouraged due to an initial dip in GFR, and it is prudent to discontinue therapy if there is an acute renal event, hypovolaemia or hypotension.

People with pre-diabetes are at high risk of progressing to type 2 diabetes. This progression is not well characterised by ethnicity, deprivation and age, which we describe in a large cohort of individuals with pre-diabetes.A retrospective cohort study with The Health Improvement Network (THIN) database was conducted. Patients aged 18 years and over and diagnosed with pre-diabetes [HbA1c 42 mmol/mol (6.0%) to 48 mmol/mol (6.5%) were included]. Cox proportional hazards regression was used to calculate adjusted hazard rate ratios (aHR) for the risk of progression from pre-diabetes to type 2 diabetes for each of the exposure categories [ethnicity, deprivation (Townsend), age and body mass index (BMI)] separately.Of the baseline population with pre-diabetes (n = 397,853), South Asian (aHR 1.31; 95% CI 1.26-1.37) or Mixed-Race individuals (aHR 1.22; 95% CI 1.11-1.33) had an increased risk of progression to type 2 diabetes compared with those of white European ethnicity. Likewise, deprivation (aHR 1.17; 95% CI 1.14-1.20; most vs. least deprived) was associated with an increased risk of progression. Both younger (aHR 0.63; 95% CI 0.58-0.69; 18 to30 years) and older individuals (aHR 0.85; 95% CI 0.84-0.87; ≥65 years) had a slower risk of progression from pre-diabetes to type 2 diabetes, than middle-aged (40 to65 years) individuals.South Asian or Mixed-Race individuals and people with social deprivation had an increased risk of progression from pre-diabetes to type 2 diabetes. Clinicians need to recognise the differing risk across their patient populations to implement appropriate prevention strategies.

The past 50 years have seen a growing ageing population with an increasing prevalence of type 2 diabetes mellitus (T2DM); now, nearly half of all individuals with diabetes mellitus are older adults (aged ≥65 years). Older adults with T2DM present particularly difficult challenges. For example, the accentuated heterogeneity of these patients, the potential presence of multiple comorbidities, the increased susceptibility to hypoglycaemia, the increased dependence on care and the effect of frailty all add to the complexity of managing diabetes mellitus in this age group. In this Review, we offer an update on the key pathophysiological mechanisms associated with T2DM in older people. We then evaluate new evidence relating particularly to the effects of frailty and sarcopenia, the clinical difficulties of age-associated comorbidities, and the implications for existing guidelines and therapeutic options. Our conclusions will focus on the effect of T2DM on an ageing society.

Introduction To assess if in adults with COVID‐19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM‐NC) and those without diabetes. Methods Service‐level data was used from 996 adults with laboratory confirmed COVID‐19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM‐NC, and non‐diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. Results Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM‐NC and 597 (59.9%) non‐diabetes. There were 309 (31.0%) in‐hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM‐NC and 170 (17.0%) non‐diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM‐NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95–2.03, p = 0.093) and 1.18 (95% CI 0.90–1.54, p = 0.226) in DM+C and DM‐C, respectively. Conclusions Those with COVID‐19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study., As people with diabetes are disproportionately affected by COVID‐19, there is a need to identify diabetes sub‐groups who could be at high risk of adverse outcomes when presenting to hospitals.Our real world study of people with diabetes and laboratory confirmed diagnoses of COVID‐19 uses service level data including biochemical markers for initial assessment. We compared these values and mortality levels in people with and without diabetes and hyperglycaemic complications.We found people with COVID‐19 and diabetes with existing complications presented with a more severe clinical and biochemical profile.However, the association between diabetic/hyperglycemic state in COVID‐19 and all cause‐mortality was not statistically significant in this study.

Summary Background Diabetes leads to a wide range of established vascular and metabolic complications that has resulted in the implementation of diverse prevention programmes across high-income countries. Diabetes has also been associated with an increased risk of a broader set of conditions including cancers, liver disease, and common infections. We aimed to examine the trends in a broad set of cause-specific hospitalisations in individuals with diabetes in England from 2003 to 2018. Methods In this epidemiological analysis, we identified 309 874 individuals 18 years or older with diabetes (type 1 or 2) in England from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data from 2003 to 2018. We generated a mixed prevalent and incident diabetes study population through serial cross sections and follow-up over time. We used a discretised Poisson regression model to estimate annual cause-specific hospitalisation rates in men and women with diabetes across 17 cause groupings. We generated a 1:1 age-matched and sex-matched population of individuals without diabetes to compare cause-specific hospitalisation rates in those with and without diabetes. Findings Hospitalisation rates were higher for all causes in persons with diabetes than in those without diabetes throughout the study period. Diabetes itself and ischaemic heart disease were the leading causes of excess (defined as absolute difference in the rate in the populations with and without diabetes) hospitalisation in 2003. By 2018, non-infectious and non-cancerous respiratory conditions, non-diabetes-related cancers, and ischaemic heart disease were the most common causes of excess hospitalisation across men and women. Hospitalisation rates of people with diabetes declined and causes of hospitalisation changed. Almost all traditional diabetes complication groups (vascular diseases, amputations, and diabetes) decreased, while conditions non-specific to diabetes (cancers, infections, non-infectious and non-cancerous respiratory conditions) increased. These differing trends represented a change in the cause of hospitalisation, such that the traditional diabetes complications accounted for more than 50% of hospitalisation in 2003, but only approximately 30% in 2018. In contrast, the proportion of hospitalisations due to respiratory infections between the same time period increased from 3% to 10% in men and from 4% to 12% in women. Interpretations Changes in the composition of excess risk and hospitalisation burden in those with diabetes means that preventative and clinical measures should evolve to reflect the diverse set of causes that are driving persistent excess hospitalisation in those with diabetes. Funding Wellcome Trust.

Introduction: COVID-19 infection in people with diabetes is associated with a disproportionately increased risk of complications and mortality.1 Diabetic ketoacidosis (DKA) is an acute complication of diabetes.2,3 Little is known about DKA in the presence of COVID-19 infection. This study aimed to explore the effects of COVID-19 infection on presentation, clinical course and outcome in patients presenting with DKA. Methods: This retrospective cohort study included all patients treated for DKA between 1 March and 30 May 2020 at University Hospitals Birmingham. Patients were categorised as COVID-positive or negative based on PCR swab test. A pre-COVID group was established as external control. Data regarding demographics, diabetes type, admission pH, bicarbonate, lactate, glucose, serum electrolytes, urea, creatinine, time to resolution of acidosis and ketosis, complications and outcome were collected. DKA onset was defined as the presence of hyperglycaemia (serum glucose >11 mmol/L), ketosis (serum ketones >3 mmol/L or urine ketone >+++) and metabolic acidosis (pH 7.3 or bicarbonate >15 mmol/L) as per national guidelines in the UK.4 Results: A total of 88 episodes were included in the final analysis (20 COVID-positive, 31 COVID-negative, 37 pre-COVID). These were further sub-classified into type 1 (five COVID-positive, two COVID-negative, 29 pre-COVID) and type 2 diabetes (15 COVID-positive, two COVID-negative, eight pre-COVID). There was no significant difference in the severity of DKA at presentation (median for COVID positive, COVID negative and pre-COVID groups): pH (7.15 vs 7.2 vs 7.2), bicarbonate (11.4 mmol/L vs 11 mmol/L vs 13.3 mmol/L), glucose (25.85 mmol/L vs 30.9 mmol/L vs 29.1 mmol/L), lactate (2.7 mmol/L vs 3.2 mmol/L vs 2.8 mmol/L), serum osmolality (314.6 mmol/L vs 323.1 mmol/L vs 316.2 mmol/L). There was also no significant difference between the groups for the duration of DKA (from the time of admission to resolution of DKA: 12.5 hours vs 14.9 hours vs 17.9 hours for COVID-positive, COVID-negative and pre-COVID groups, respectively; Fig 1). COVID-positive patients with type 1 diabetes were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was a significantly higher incidence of type 2 diabetes in COVID-positive patients than in pre-COVID or COVID-negative groups. COVID-negative patients had more episodes of hypokalaemia and hyperkalaemia during DKA compared to other two groups. There was no significant difference between the number of episodes of hypokalaemia in the COVID-positive compared to the pre-COVID group. In patients with type 2 diabetes, hypokalaemia was more common in COVID-negative patients. Conclusion: COVID infection appears to influence the natural history of DKA differently in type 1 and type 2 diabetes. Infection was associated with increased hyperglycaemia in type I diabetes and greater acidosis on presentation with DKA. People with type 2 diabetes were presenting unusually in DKA when infected with COVID. These patients also had higher mortality rates. There is need for a multi-centre approach to conduct larger cohort studies in this area.

Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA1c) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators. Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis. Subjects received subcutaneous semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine, dulaglutide 0.75 or 1.5 mg). The main endpoint was a composite of ≥1.0% HbA1c reduction and ≥5.0% weight loss at end of treatment. Results: Significantly greater proportions of subjects achieved the composite endpoint with semaglutide 0.5 (25 to 38%) and 1.0 mg (38 to 59%) versus comparators (2 to 23%). More subjects treated with semaglutide versus comparators achieved ≥1.0% HbA1c reductions (58 to 77% and 75 to 83% for semaglutide 0.5 and 1.0 mg versus 12 to 68%) and ≥5.0% weight loss (37 to 46%, 45 to 66% versus 4 to 30%). Proportions of subjects achieving targets were significantly higher with semaglutide 1.0 versus 0.5 mg in four of five trials. Semaglutide was well tolerated, with a safety profile similar to other GLP-1 receptor agonists. Conclusion: Significantly more subjects achieved both ≥1.0% HbA1c reduction and ≥5.0% weight loss with once-weekly subcutaneous semaglutide treatment versus comparators in the SUSTAIN trials. A dose-dependent effect was observed with semaglutide. Abbreviations: AE = adverse event; CV = cardiovascular; ER = extended release; GLP-1 = glucagon-like peptide 1; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HbA1c = glycated hemoglobin; OAD = oral antidiabetic drug; sc = subcutaneous; T2D = type 2 diabetes

Introduction The increasing prevalence of type 2 diabetes (T2DM) in the UK imposes a significant burden on the National Health Service (NHS). Despite the availability of effective treatments, the loss of glycaemic control over time results in significant comorbidities, including nephropathy, neuropathy and retinopathy. The cost of treating these microvascular complications has not been well documented, and this study aimed to provide an accurate assessment of the healthcare resource utilisation (HCRU) associated with managing T2DM and its complications. Methods This retrospective cohort study utilised electronic medical records from patients with T2DM from the Heart of England Foundation Trust (HEFT), which captures data from patients using secondary care services. Patients were diagnosed with microvascular complications based on ICD-10 or OPCS codes. HCRU over a 2-year period was based on NHS Tariffs for healthcare services for inpatient, accident and emergency, and dialysis clinic usage. Results The study cohort comprised 26,629 patients with T2DM who used HEFT services during the study period, 22.6%, 20.8% and 3.1% of whom had comorbid nephropathy, retinopathy or neuropathy, respectively. While the prevalence of diabetes in the overall HEFT population was reported to be 7% in 2012, diabetes and its associated complications accounted for more than 30% of secondary care costs. Furthermore, while patients with diabetes represent only 17% of HEFT inpatients, they account for more than 20% of service usage. The economic burden of microvascular complications increased substantially with the severity of the condition, with the overall cost exceeding £70 million over the 2-year period. Conclusion This study of patients with T2DM in a typical secondary care provider in the UK showed that avoiding the progression of microvascular complications could provide substantial cost savings through targeted interventions that improve outcomes and lower resource use. Funding Merck Sharp & Dohme Limited. Electronic supplementary material The online version of this article (10.1007/s13300-018-0548-4) contains supplementary material, which is available to authorized users.

South Asians constitute approximately 1.6 billion people from the Indian subcontinent, comprising Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka; and make up the largest diaspora globally. Compared to the White European population, this group is at a higher risk of developing type 2 diabetes along with cardiovascular, renal and eye complications. Over the recent years, a number of new therapies for type 2 diabetes have become available for which cardiovascular outcome trials (CVOTs) have been published. The recent ADA/EASD consensus guidelines on diabetes, pre-diabetes and cardiovascular diseases' offer a transitional shift in type 2 diabetes management. The new consensus recommendations are based on recent CVOTs, many of which had a representation of South Asian cohorts. In light of this new evidence, there is urgent need for an integrated, evidence-based, cost-effective and individualised approach specific for South Asians. This review takes into consideration the evidence from these CVOTs and provides best practice recommendations for optimal management of South Asian people with type 2 diabetes, alongside the previously published consensus report from South Asian Health Foundation in 2014 [1].

Objective COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA. Design Retrospective cohort study. Methods All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected. Results A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups. Conclusion COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9–60.0) vs 31.4 mmol/L (28.0–39.1) vs 24 mmol/L (20.2–33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results.

BACKGROUND Remission of type 2 diabetes following bariatric surgery is well established, but identifying patients who will go into remission is challenging. PURPOSE To perform a systematic review of currently available diabetes remission prediction models, compare their performance, and evaluate their applicability in clinical settings. DATA SOURCES A comprehensive systematic literature search of MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. The search was restricted to studies published in the last 15 years and in the English language. STUDY SELECTION All studies developing or validating a prediction model for diabetes remission in adults after bariatric surgery were included. DATA EXTRACTION The search identified 4,165 references, of which 38 were included for data extraction. We identified 16 model development and 22 validation studies. DATA SYNTHESIS Of the 16 model development studies, 11 developed scoring systems and 5 proposed logistic regression models. In model development studies, 10 models showed excellent discrimination with area under the receiver operating characteristic curve ≥0.800. Two of these prediction models, ABCD and DiaRem, were widely externally validated in different populations, in a variety of bariatric procedures, and for both short- and long-term diabetes remission. Newer prediction models showed excellent discrimination in test studies, but external validation was limited. LIMITATIONS While the key messages were consistent, a large proportion of the studies were conducted in small cohorts of patients with short duration of follow-up. CONCLUSIONS Among the prediction models identified, the ABCD and DiaRem models were the most widely validated and showed acceptable to excellent discrimination. More studies validating newer models and focusing on long-term diabetes remission are needed.

OBJECTIVE To assess the impact of bariatric surgery (BS) on incident microvascular complications of diabetes-related foot disease (DFD), sight-threatening diabetic retinopathy (STDR), and chronic kidney disease (CKD) in patients with type 2 diabetes and obesity. RESEARCH DESIGN AND METHODS A retrospective matched, controlled population-based cohort study was conducted of adults with type 2 diabetes between 1 January 1990 and 31 January 2018 using IQVIA Medical Research Data (IMRD), a database of primary care electronic records. Each patient with type 2 diabetes who subsequently had BS (surgical group) was matched on the index date with up to two patients with type 2 diabetes who did not have BS (nonsurgical group) within the same general practice by age, sex, preindex BMI, and diabetes duration. RESULTS Included were 1,126 surgical and 2,219 nonsurgical participants. In the study population 2,261 (68%) were women. Mean (SD) age was 49.87 (9.3) years vs. 50.12 (9.3) years and BMI was 46.76 (7.96) kg/m2 vs. 46.14 (7.49) kg/m2 in the surgical versus nonsurgical group, respectively. In the surgical group, 22.1%, 22.7%, 52.2%, and 1.1% of patients had gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and duodenal switch, respectively. Over a median follow-up of 3.9 years (interquartile range 1.8–6.4), BS was associated with reduction in incident combined microvascular complications (adjusted hazard ratio 0.53, 95% CI 0.43–0.66, P < 0.001), DFD (0.61, 0.50–0.75, P < 0.001), STDR (0.66, 0.44–1.00, P = 0.048), and CKD (0.63, 0.51–0.78, P < 0.001). Analysis based on the type of surgery showed that all types of surgery were associated with a favorable impact on the incidence of composite microvascular complications, with the greatest reduction for RYGB. CONCLUSIONS BS was associated with a significant reduction in incident diabetes-related microvascular complications.

Background: COVID-19 in people with diabetes is associated with poorer outcomes. Diabetic Ketoacidosis (DKA) is an acute complication of diabetes with a mortality rate of 0·67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients with DKA. Methods: This retrospective cohort study included all patients with DKA between 01 March 2020 and 30 May 2020. Patients were categorised as COVID-positive or COVID-negative. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as control. Data regarding demographics, diabetes type, admission pH, bicarbonate, lactate, glucose, serum electrolytes, urea, creatinine, time to DKA resolution, complications, and outcome were collected. Findings: A total of 88 episodes (20 COVID-positive, 31 COVID-negative and 37-pre-COVID) were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive type 1 diabetes (T1DM) were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of type 2 diabetes (T2DM) in COVID-positive patients than in pre-COVID or COVID-negative groups. Interpretation: COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. In patients with T1DM, infection was associated with more hyperglycaemia and acidosis on presentation with DKA. Patients with T2DM were unusually presenting in DKA when infected with COVID-19. These patients were also more likely to need ITU with higher mortality rates. There is a need for a collaborative, multi-centre approach in order to conduct larger cohort studies to provide more definitive results. Funding: No funding was received for this work. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was registered as a retrospective audit and was approved by the hospital governance team with no further ethical input needed.

Aim: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. Materials and methods: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c

Aims To estimate the risk of developing long-term major cardiovascular and renal complications in relation to levels of body mass index (BMI) in a population of White European (WE), African-Caribbean (AC), and South Asian (SA) patients with type 2 diabetes mellitus (T2DM). Materials and methods Patients with new diagnosis of T2DM, aged ≥ 18 years from January 2000 (n = 69,436) and their age-sex-ethnicity matched non-diabetic controls (n = 272,190) were identified from UK primary care database. Incidence rates ratios (IRRs) for non-fatal major cardiovascular events (MACE) and chronic kidney disease (CKD) in patients with T2DM compared to controls were estimated using multivariate Mantel-Cox model. Results Among normal weight patients with T2DM, WEs had significantly higher prevalence of cardiovascular multi-morbidity (95% CI 9.5, 11.3), compared to SAs (95% CI 4.8, 9.5). AC and SA overweight and obese patients had similar prevalence, while obese WEs had significantly higher prevalence. During a median 7 years of follow-up, risk of MACE was significantly higher for overweight (95% CI of IRR 1.50, 2.46) and obese (95% CI of IRR 1.49, 2.43) SAs compared to their WE counterparts. However, similar risk levels were observed for normal weight WEs and SAs, respectively. Risk of CKD was higher and uniform for BMI ≥ 25 kg/m2 amongst WEs and ACs, whereas only overweight patients had significantly higher risk of CKD amongst SA [IRR 2.08 (95% CI 1.49, 2.93)]. Conclusion Risk of MACE/CKD varies over levels of BMI within each ethnic group, with overweight SAs having a disproportionate risk of CKD. Electronic supplementary material The online version of this article (10.1186/s12933-018-0712-1) contains supplementary material, which is available to authorized users.

Introduction To assess the real-life clinical benefits and cost implications of switching from another basal insulin to insulin degludec (degludec) in patients with type 1 diabetes (T1D) on basal–bolus regimens with recurrent hypoglycemia and/or hypoglycemia unawareness. Methods Patients with T1D who were aged ≥ 18 years, were on a basal–bolus regimen, and had switched to degludec plus bolus insulin for at least 6 months were included. Patients had to have switched to degludec as a result of recurrent hypoglycemia and/or hypoglycemia unawareness. Results Six months of follow-up data were available for 42 patients. At 6 months, there was a significant reduction in median (interquartile range) HbA1c, from 8.6 (8.0–9.3)% [70 (64–78) mmol/mol] to 8.4 (7.9–8.9)% [68 (63–74) mmol/mol]; p

The prevalence of type 2 diabetes in adolescents and young adults is dramatically increasing. Similar to older-onset type 2 diabetes, the major predisposing risk factors are obesity, family history, and sedentary lifestyle. Onset of diabetes at a younger age (defined here as up to age 40 years) is associated with longer disease exposure and increased risk for chronic complications. Young-onset type 2 diabetes also affects more individuals of working age, accentuating the adverse societal effects of the disease. Furthermore, evidence is accumulating that young-onset type 2 diabetes has a more aggressive disease phenotype, leading to premature development of complications, with adverse effects on quality of life and unfavourable effects on long-term outcomes, raising the possibility of a future public health catastrophe. In this Review, we describe the epidemiology and existing knowledge regarding pathophysiology, risk factors, complications, and management of type 2 diabetes in adolescents and young adults.

We examined the relationship between weight changes after preoperative glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment and weight changes from the start of medical weight management (MWM) until 12 months after bariatric surgery in patients with type 2 diabetes in a retrospective cohort study. A total of 45 patients (64.4% women, median [interquartile range] age 49 [45-60] years) were included. The median (interquartile range) weight loss from start of MWM until 12 months post-surgery was 17.9% (13.0%-29.3%). GLP-1RA treatment during MWM resulted in 5.0% (1.9%-7.7%) weight loss. Weight loss during GLP-1RA treatment predicted weight loss from the start of MWM until 12 months post-surgery, but not postoperative weight loss after adjustment. The proportion of weight loss from start of MWM to 12 months post-surgery attributed to GLP-1RA treatment was negatively associated with that attributed to surgery, after adjustment. In conclusion, weight change after GLP-1RA treatment predicted the weight loss achieved by a combination of MWM and bariatric surgery, but not weight loss induced by surgery only. Failure to lose weight after GLP-1RA treatment should not be considered a barrier to undergoing bariatric surgery.

Aims To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non-diabetic controls in a multi-ethnic population. Materials and methods This was a case-control study of 90 367 patients with incident diabetes and 362 548 age-sex-ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated. Results Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m2 at diagnosis (32.2 kg/m2) compared to the matched controls (27.4 kg/m2). White Europeans (n = 79 270), African-Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m2, respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m2 (38%) than White Europeans (26%) and African-Caribbeans (29%) (all P

Background: Diabetes mellitus is the most common cause of end-stage renal disease, which is associated with increased morbidity and mortality. The impact of bariatric surgery on chronic kidney disease is unclear. Objectives: Our primary aim was to assess the impact of bariatric surgery on estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients. Our secondary aim was to compare the impact of bariatric surgery versus routine care on eGFR in patients with T2D. Setting: University Hospital, United Kingdom. Methods: A retrospective cohort analysis of adults with T2D who underwent bariatric surgery at a single center between January 2005 and December 2012. Data regarding eGFR were obtained from electronic patients records. eGFR was calculated using the Modification of Diet in Renal Disease formula. Data regarding patients with T2D who did not undergo bariatric surgery ("routine care") were obtained from patients attending the diabetes clinic at the same center from 2009 to 2011. Results: One hundred sixty-three patients were included (mean age 48.5±8.8 yr; baseline body mass index 50.8±9.1 kg/m2) and were followed for 3.0±2.3 years. Bariatric surgery resulted in an improvement in eGFR (median [interquartile range] 86.0 [73.0-100.0] versus 92.0 [77.0-101.0] mL/min/1.73 m2 for baseline versus follow-up, respectively; P = .003), particularly in patients with baseline eGFR≤60 mL/min/1.73 m2 (48.0 [42.0-57.0] versus 61.0 [55.0-63.0] mL/min/1.73 m2; P = .004). After adjusting for baseline eGFR, glycated hemoglobin (HbA1C), body mass index, age, and gender, bariatric surgery was associated with higher study-end eGFR compared with routine care (B = 7.787; P< .001). Conclusion: Bariatric surgery results in significant improvements in eGFR in T2D patients, particularly those with an eGFR≤60 mL/min/1.73 m2, while routine care was associated with a decline in eGFR.

Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality.A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/mA total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8- 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group.Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.Estudios de cohortes han mostrado que la cirugía bariátrica puede reducir la incidencia de enfermedad cardiovascular (cardiovascular disease, CVD) y la mortalidad, pero los estudios basados en datos del mundo real son limitados. Este estudio examinaba el impacto de la cirugía bariátrica (bariatric surgery, BS) en la incidencia de CVD, hipertensión, fibrilación auricular (FA) y mortalidad por cualquier causa. MÉTODOS: Se realizó un estudio retrospectivo de cohortes, controlado por emparejamiento, a partir de la base de datos de atención primaria del The Health Improvement Network (THIN) (1/1/1990 y 31/1/2018) (aproximadamente el 6% de la población del Reino Unido UK). En el grupo de exposición, se incluyeron adultos con un índice de masa corporal (IMC) ≥ 30 kg/mSe incluyeron un total de 5.170 sujetos expuestos y 9.995 participantes controles. La edad media (DE) fue 45,3 (10,5) años, 21,5% (n = 3.265) tenían T2D. La mediana de seguimiento era de 3,9 años (rango intercuartílico 1,8- 6,4). La media ± desviación estándar del % de pérdida de peso fue del 20,0 ± 13,2% en el grupo BS versus 0,8 ± 9,5% en los grupos control. Globalmente, la BS no se asoció con una CVD significativamente más baja (cociente de riesgos instantáneos ajustados, adjusted hazard ratio, HR 0,80; i.c. del 0,62- 1,02, P = 0,074). Solo en el grupo del bypass gástrico se observó un impacto significativo en CVD (0,53, 0,34- 0,81, P = 0,003). BS se asoció con una reducción significativa en la mortalidad de cualquier causa (0,70; i.c. Del 95% 0,55- 0,89, P = 0,004), hipertensión (0,41; 0,34- 0,50, P 0,001), e insuficiencia cardiaca (0,57, 0,34- 0,96; P = 0.033). Los resultados fueron similares en aquellos pacientes con y sin T2D (expuesto versus control) excepto en la FA incidental que se redujo en el grupo T2D.La práctica de BS se asoció con una reducción del riesgo de insuficiencia cardiaca y mortalidad.

Studies on the influence of a modern lifestyle in abetting Coronary Heart Diseases (CHD) have mostly focused on deterrent health factors, like smoking, alcohol intake, cheese consumption and average systolic blood pressure, largely disregarding the impact of a healthy lifestyle in mitigating CHD risk. In this study, 30+ years' World Health Organization (WHO) data have been analyzed, using a wide array of advanced Machine Learning techniques, to quantify how regulated reliance on positive health indicators, e.g. fruits/vegetables, cereals can offset CHD risk factors over a period of time. Our research ranks the impact of the negative outliers on CHD and then quantifies the impact of the positive health factors in mitigating the negative risk-factors. Our research outcomes, presented through simple mathematical equations, outline the best CHD prevention strategy using lifestyle control only. We show that a 20% increase in the intake of fruit/vegetable leads to 3-6% decrease in SBP; or, a 10% increase in cereal intake lowers SBP by 3%; a simultaneous increase of 10% in fruit-vegetable can further offset the effects of SBP by 6%. Our analysis establishes gender independence of lifestyle on CHD, refuting long held assumptions and unqualified beliefs. We show that CHD risk can be lowered with incremental changes in lifestyle and diet, e.g. fruit-vegetable intake ameliorating effects of alcohol-smoking-fatty food. Our multivariate data model also estimates functional relationships amongst lifestyle factors that can potentially redefine the diagnostics of Framingham score-based CHD-prediction., 10 pages, 7 tables, 2 figures together with a detailed online supplementary section including another 9 tables and 4 figures

Background: Early onset of type 2 diabetes (T2DM) is associated with prolonged exposure to hyperglycaemia and increased propensity to chronic complications. The aim of this study was to characterize and compare the phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes (T2DMY). Methods: One hundred young adults (White European [WE], South Asian [SA] and African-Caribbean [AC]) diagnosed with T2DM before the age of 40 years were recruited. Demographics, family history, diabetes related complications, co-morbidities, anthropometry (body mass index [BMI], body composition), physical activity and biochemistry (HbA1c, lipid profile, liver and renal function) and autoantibodies (anti GAD, anti islet cell) were collected for all participants. Data were analysed for the most represented ethnic groups: (WE, N = 36 and SA, N = 53) using SPSS version 23. Results: Mean (± standard deviation) age at diagnosis was 32.5 ± 5.5 years and mean diabetes duration was 7.7 ± 3.8 years. Overweight/obesity was present in 95% of participants, history of maternal diabetes in 68%, deprivation 75%, low physical activity 40%, polycystic ovarian disease 29% (in females), acanthosis nigricans 12% and non-alcoholic fatty liver 11%. There was considerable clustering of risk factors within the cohort with over 75% of all subjects having three or more of the above risk factors and 52% required insulin within 3 years of diagnosis. Two-thirds of the patients had evidence of at least one diabetes related microvascular complication. Conclusion: T2DMY is characterized by a high burden of commonly associated risk factors for both the disease and its long-term complications.

Diabetes mellitus is a highly prevalent chronic disease, with an associated heavy personal and public health burden of disability, morbidity and mortality. The focus of care for older patients with diabetes is prevention of functional decline, with early intervention rather than attempting to recover function later. Diabetes doubles the risk of frailty. An important contributor towards physical frailty is sarcopaenia, which manifests as an age-related loss of skeletal muscle volume and power. Frailty is not an inevitable consequence of the ageing process; it is a dynamic and potentially reversible condition that highlights the importance of early recognition and intervention. In this review, we examine the evidence for linking diabetes to frailty and sarcopaenia and how the emergence of these conditions should lead to changes in clinician behaviour in terms of assessment of function and goal setting. High-quality, focused research in this area is now mandatory. Sin financiación 0.14 SJR (2016) Q3, 111/144 Internal Medicine; Q4, 307/375 Cardiology and Cardiovascular Medicine, 199/244 Endocrinology, Diabetes and Metabolism, 23/25 Endocrine and Autonomic Systems UEM

Rare gene knockouts in adult humans On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within individuals. Narasimhan et al. investigated LOF in a Pakistani population with high levels of consanguinity. Examining LOF alleles that were identical by descent, they found, as expected, an absence of homozygote LOF for certain protein-coding genes. However, they also identified many homozygote LOF alleles with no apparent deleterious phenotype, including some that were expected to confer genetic disease. Indeed, one family had lost the recombination-associated gene PRDM9 . Science , this issue p. 474

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control ( n = 28) or intervention ( n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile–monitored type 2 diabetes patients ( n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day ( p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol ( p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients ( n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day ( p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol ( p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.