Aim
To assess the relationship between body mass index (BMI) classes and early COVID‐19 prognosis in inpatients with type 2 diabetes (T2D).
Methods
From the CORONAvirus‐SARS‐CoV‐2 and Diabetes ...Outcomes (CORONADO) study, we conducted an analysis in patients with T2D categorized by four BMI subgroups according to the World Health Organization classification. Clinical characteristics and COVID‐19–related outcomes (i.e. intubation for mechanical ventilation IMV, death and discharge by day 7 D7) were analysed according to BMI status.
Results
Among 1965 patients with T2D, 434 (22.1%) normal weight (18.5‐24.9 kg/m2, reference group), 726 (36.9%) overweight (25‐29.9 kg/m2) and 805 (41.0%) obese subjects were analysed, including 491 (25.0%) with class I obesity (30‐34.9 kg/m2) and 314 (16.0%) with class II/III obesity (≥35 kg/m2). In a multivariable‐adjusted model, the primary outcome (i.e. IMV and/or death by D7) was significantly associated with overweight (OR 1.65 1.05‐2.59), class I (OR 1.93 1.19‐3.14) and class II/III obesity (OR 1.98 1.11‐3.52). After multivariable adjustment, primary outcome by D7 was significantly associated with obesity in patients aged younger than 75 years, while such an association was no longer found in those aged older than 75 years.
Conclusions
Overweight and obesity are associated with poor early prognosis in patients with T2D hospitalized for COVID‐19. Importantly, the deleterious impact of obesity on COVID‐19 prognosis was no longer observed in the elderly, highlighting the need for specific management in this population.
Aims/hypothesis
Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear ...whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question.
Methods
The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes.
Results
A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 95% CI 1.19, 1.72,
p
<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 95% CI 1.17, 1.72,
p
<0.001) and 28 days (adjusted HR 1.30 95% CI 1.09, 1.55,
p
=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital.
Conclusions/interpretation
Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status.
Trial registration
ClinicalTrials.gov
NCT04324736
Graphical abstract
Lipohypertrophy (LH) is highly prevalent and is potentially harmful to insulin-injecting patients.
In this study, we assessed the impact of injection technique (IT) education, including use of a 4-mm ...pen needle on insulin-treated patients with clinically observed LH in a randomized, controlled, prospective multicenter study in France with follow-up of 6 months. Intensive education and between-visit reinforcement were given to the intervention group. Control patients received similar messages at study outset.
A total of 123 patients were recruited (age 52.1 ± 15.7 years; men 70.7%; body mass index >30 kg/m
: 34.2%; type 1: 53.7%; years with diabetes mellitus: 18.1 ± 10.5), of which 109 patients were included in the final analysis. The intervention group (n = 53) showed a significant decrease of total daily dose of insulin (average at baseline: 54.1 IU) at 3 months (T-3) and 6 months (T-6), reaching just over 5 IU versus baseline (P = 0.035). Corresponding, although not significant, decreases occurred in controls (n = 56); between-group differences were not significant. There were significant decreases in HbA1c (up to 0.5%) at T-3 and T-6 in both groups, with no significant differences between groups. A significant number of intervention patients improved their IT habits; about half achieved ideal IT habits by T-3 versus a quarter of control patients. By T-6, 2/3 of intervention patients achieved either ideal or acceptable IT habits, while only 1/3 of control patients did.
Our intervention was effective in both study arms, however, to a greater degree and more rapidly in the intervention group. Widespread application of this intervention could be highly cost-effective.
Context
The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism.
Aims
To describe main phenotype patterns and their evolution ...through life.
Design
Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2.
Results
Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations.
Conclusion
This large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.
Aim
To evaluate the effect of adding the dipeptidyl‐peptidase‐4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis.
Methods
Overall, ...65 insulin‐treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin‐insulin group) or to pursue their usual insulin regimen (insulin‐only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers.
Results
After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin‐insulin group compared with the insulin‐only group, although the between‐treatment difference was not statistically significant (mean difference CI 95%: −0.96 mmol/L −2.09; 0.18 vs. ‐0.29 mmol/L −1.29; 0.76, P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin‐insulin group versus the insulin‐only group (−0.6% −1.19; −0.1, P < 0.01), in the vildagliptin‐insulin group versus no change in the insulin‐only group (−130.6 μmol/L −271; 10.7 vs. +36.2 μmol/L −164.4; 236.9, P = 0.04 and − 5.9 IU/day −1.8; 7.1 vs. +1.1 IU/day −14.5; 16.6, P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events.
Conclusion
In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin‐sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.
Introduction: Type 2 diabetic patients (T2D) undergoing chronic dialysis are at very high cardiovascular risk, requiring optimization of insulin treatment.
Vildagliptin (Galvus), can be used in ...severe and terminal renal impairment (eGFR<30 or <15ml/min/1,73m²) and protects against hypoglycemia.
The aim of this study was to evaluate the efficacy and safety of vildagliptin (50 mg/d) on top of insulin in hemodialysed T2D.
Methods: Sixty-five patients treated with multiple daily insulin injections were randomized (group 1-G1, n=33-usual insulin regimen, group 2-G2, n=32-addition of vildagliptin) in a multicentric, prospective, controlled, open-label, 12 weeks- study. Glucose control was evaluated using Continuous Glucose Monitoring (CGM, I-Pro Medtronic) for 48h, at Week 1 (W1) and Week 12 (W12), HbA1c and daily insulin needs. Statistical analysis was performed in intention to treat.
Results: Both groups were comparable (G1 vs. G2) for age (71.3 ± 7.4 vs. 69.7 ± 9.6 years), BMI (32.1 ± 6 vs. 34.5 ± 6.4 kg/m²), daily doses of insulin (47.7 ± 29.2 vs. 51.3 ± 25.4 IU), HbA1c (7.3 ± 1.1 vs. 7.3 ± 1.1%), and mean glucose at W1 (using CGM, 167.6 ± 58.3 vs. 149.4 ± 76.1 mg/dl). At W12 compared to W1, mean glucose decreased significantly only in G2 (149.4 to 136.9 mg/dl, p <0.05). At W12 in G2 vs. G1, time in range (70-180 mg/dl) was greater (77.2 vs. 69.5%, p <0.05), time spent > 180 mg/dl was lower (21.27 vs. 39.03%, p <0.05), there was no difference in time spent <70 mg/dl (1.54 vs. 1.45%, NS). At W12, HbA1C and insulin requirements were respectively 6.9 ± 0.9% vs. 7.2 ± 1.1% (NS) and 49 ± 32 IU/d vs. 46 ± 23 IU/d (NS). There was no difference in adverse events between both groups. Overall, 8 symptomatic hypoglycemia occurred in G1 and 13 in G2.
Conclusion: Adding vildagliptin (50 mg/d) to insulin in hemodialysed T2D improves glycemic control by increasing time spent in normoglycemia and reducing time in hyperglycemia, without increasing time in hypoglycemia.
Disclosure
M. Munch: None. A. Smagala: None. L. Meyer: None. N. Meyer: None. O. Verier: None. D.I. Fleury: None. B. Guerci: None. T. Hannedouche: None. J. Cridlig: None. P. Baltzinger: None. D. Ducloux: None. S. Borot: Consultant; Self; Abbott, Animas Corporation, Johnson & Johnson Diabetes Institute, LLC., Medtronic, Roche Diabetes Care Health and Digital Solutions. K.W. Kunz: None. F. Alenabi: None. P. Winiszewski: Other Relationship; Self; Abbott, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Eli Lilly and Company, Sanofi. F. Chantrel: None. L. Kessler: None.
The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, ...compared with standard calorie and protein targets.
The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.
Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio HR 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032).
Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications.
French Ministry of Health.
PDF
