Aims/hypothesis
Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a ...major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.
Methods
We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.
Results
The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m
2
; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA
1c
, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 1.10, 1.47). On admission, dyspnoea (OR 2.10 1.31, 3.35), as well as lymphocyte count (OR 0.67 0.50, 0.88), C-reactive protein (OR 1.93 1.43, 2.59) and AST (OR 2.23 1.70, 2.93) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 1.74, 3.53), treated obstructive sleep apnoea (OR 2.80 1.46, 5.38), and microvascular (OR 2.14 1.16, 3.94) and macrovascular complications (OR 2.54 1.44, 4.50) were independently associated with the risk of death on day 7.
Conclusions/interpretations
In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.
Trial registration
clinicaltrials.gov
NCT04324736.
Summary Background Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of ...the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. Methods This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00802503. Findings We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% SD 18% of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% 27%). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43–0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (−0·42 −0·79 to −0·05; p=0·0248). Interpretation Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. Funding Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.
Aims/hypothesis
This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic ...factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19).
Methods
The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days.
Results
We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th–75th percentile) 28.4 (25.0–32.4) kg/m
2
. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5–14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors.
Conclusions/interpretation
In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period.
Trial registration
Clinicaltrials.gov
identifier: NCT04324736
Graphical abstract
Summary Background & aims Sarcopenia is a well-known complication of protein energy wasting in hemodialysis patients. Its diagnosis requires measurements of muscle mass and muscle function. Few ...studies have reported its prevalence in hemodialysis patients. In this study, we report the prevalence of sarcopenia in this population and evaluate the performance of other parameters for its diagnosis. Methods In this observational cross-sectional study, data from hemodialysis patients from our nephrology department were recorded. Body composition measured by bioimpedancemetry analysis and muscle strength measured by handgrip were recorded. Normal values for sarcopenia were those recommended by the European Working Group on Sarcopenia in Older People (EWGSOP). Results The median age (interquartile range) of the 111 patients was 77.5 (70.8–84.8) years. A large majority of 88.3% (n = 98) of patients had a low muscle strength; a low muscle mass index was present in 33.3% (n = 37) of the population. Finally, 31.5% (n = 35) of patients had sarcopenia. These latter were older, had longer dialysis vintage, lower BMI, mid-arm circumference and mid-leg circumference, and a lower prealbumin. The best parameter predicting sarcopenia was BMI (ROC curve AUC of 0.79 0.68–0.91 (p < 0.001) in men and 0.81 0.68–0.93 (p = 0.003) in women). Mid-arm circumference predicted sarcopenia, but was less accurate than BMI. Mid-leg circumference predicted sarcopenia only in men. Predialysis creatinine or creatinine index could not predict sarcopenia. Conclusions We report a 31.5% prevalence of sarcopenia in hemodialysis patients. The diagnosis of sarcopenia was mainly driven by muscle mass measurement because muscle strength is low in the large majority of hemodialysis patients.
Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 ...diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age ≥ 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities.
There is a paucity of global data on cardiovascular disease (CVD) prevalence in people with type 2 diabetes (T2D). The primary objective of the CAPTURE study was to estimate the prevalence of ...established CVD and its management in adults with T2D across 13 countries from five continents. Additional objectives were to further characterize the study sample regarding demographics, clinical parameters and medication usage, with particular reference to blood glucose-lowering agents (GLAs: glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) with demonstrated cardiovascular benefit in randomized intervention trials.
Data were collected from adults with T2D managed in primary or specialist care in Australia, China, Japan, Czech Republic, France, Hungary, Italy, Argentina, Brazil, Mexico, Israel, Kingdom of Saudi Arabia, and Turkey in 2019, using standardized methodology. CVD prevalence, weighted by diabetes prevalence in each country, was estimated for the overall CAPTURE sample and participating countries. Country-specific odds ratios for CVD prevalence were further adjusted for relevant demographic and clinical parameters.
The overall CAPTURE sample included 9823 adults with T2D (n = 4502 from primary care; n = 5321 from specialist care). The overall CAPTURE sample had median (interquartile range) diabetes duration 10.7 years (5.6-17.9 years) and glycated hemoglobin 7.3% (6.6-8.4%) 56 mmol/mol (49-68 mmol/mol). Overall weighted CVD and atherosclerotic CVD prevalence estimates were 34.8% (95% confidence interval CI 32.7-36.8) and 31.8% (95% CI 29.7-33.8%), respectively. Age, gender, and clinical parameters accounted for some of the between-country variation in CVD prevalence. GLAs with demonstrated cardiovascular benefit were used by 21.9% of participants, which was similar in participants with and without CVD: 21.5% and 22.2%, respectively.
In 2019, approximately one in three adults with T2D in CAPTURE had diagnosed CVD. The low use of GLAs with demonstrated cardiovascular benefit even in participants with established CVD suggested that most were not managed according to contemporary diabetes and cardiology guidelines. Study registration NCT03786406 (registered on December 20, 2018), NCT03811288 (registered on January 18, 2019).
Immune cell infiltration of expanding adipose tissue during obesity and its role in insulin resistance has been described and involves chemokines. However, studies so far have focused on a single ...chemokine or its receptor (especially CCL2 and CCL5) whereas redundant functions of chemokines have been described. The objective of this work was to explore the expression of chemokines in inflamed adipose tissue in obesity. Human and mouse adipocytes were analyzed for expression of chemokines in response to inflammatory signal (TNF-α) using microarrays and gene set enrichment analysis. Gene expression was verified by qRT-PCR. Chemokine protein was determined in culture medium with ELISA. Chemokine expression was investigated in human subcutaneous adipose tissue biopsies and mechanism of chemokine expression was investigated using chemical inhibitors and cellular and animal transgenic models. Chemokine encoding genes were the most responsive genes in TNF-α treated human and mouse adipocytes. mRNA and protein of 34 chemokine genes were induced in a dose-dependent manner in the culture system. Furthermore, expression of those chemokines was elevated in human obese adipose tissue. Finally, chemokine expression was reduced by NF-κB inactivation and elevated by NF-κB activation. Our data indicate that besides CCL2 and CCL5, numerous other chemokines such as CCL19 are expressed by adipocytes under obesity-associated chronic inflammation. Their expression is regulated predominantly by NF-κB. Those chemokines could be involved in the initiation of infiltration of leukocytes into obese adipose tissue.
Abstract Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a ...more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.
Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain ...chronic diseases like type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the effect of supplementation with standardized poplar propolis extract powder (PPEP) on insulin homeostasis in non-diabetic insulin-resistant volunteers with obesity. In this randomized, controlled, crossover trial, nine non-diabetic insulin-resistant volunteers with obesity, aged 49 ± 7 years, were subjected to two periods of supplementation (placebo and PPEP) for 3 months. Blood samples and anthropomorphic data were collected at baseline and at the end of each phase of the intervention. PPEP supplementation improved insulin sensitivity by significantly decreasing the percentage of insulin-resistant subjects and the insulin sensitivity Matsuda index (ISI-M). According to this study, supplementation with standardized PPEP for 3 months in non-diabetic insulin-resistant volunteers with obesity led to an improvement in insulin homeostasis by its effect on insulin resistance and secretion. This study suggests that poplar propolis has a preventive effect on the physiopathological mechanisms of T2DM and, therefore, that it can help to prevent the development of the disease.
The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior ...myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice.
A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan-Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death.
From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome.
THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5-6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 ( http://www.ENCEPP.eu ).
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