Metabolically 'extremely unhealthy' obese and non-obese patients with diabetes and the risk of cardiovascular events: a French nationwide cohort study.

BACKGROUND: Non-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities. MATERIALS AND METHODS: This was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio-renal-metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities. RESULTS: There were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22-1.61) and 1.48 (95% CI, 1.25-1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72-1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47-1.83)]. CONCLUSION: Both non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events.

3-Month Post-Operative Increase in FGF21 is Predictive of One-Year Weight Loss After Bariatric Surgery.

PURPOSE: The association between bariatric surgery outcome and blood levels of fibroblast growth factor 21 (FGF21) remains controversial. Many patients displayed stable or decreased FGF21 one year after bariatric surgery. Nevertheless, there is often an early increase FGF21 concentration in the post-surgery period. The aim of this study was to investigate the relationship between 3-month FGF21 response and percentage total weight loss at one year after bariatric surgery. MATERIALS AND METHODS: In this prospective monocentric study, a total of 144 patients with obesity grade 2-3 were included; 61% of them underwent a sleeve gastrectomy and 39% a Roux-en-Y gastric bypass. Data analysis was carried out to determine the relation between 3-month plasma FGF21 response and weight loss one year after bariatric surgery. Multiple adjustments were done including degree of weight loss after 3 months. RESULTS: FGF21 significantly increased between baseline and Month 3 (n = 144, p < 10-3), then decreased between Month 3 and Month 6 (n = 142, p = 0.047) and was not different from baseline at Month 12 (n = 142, p = 0.86). The 3-month-FGF21 response adjusted to body weight loss was not different between types of bariatric surgery. The 3-month-FGF21 response was associated to body weight loss at Month 6 (r = -0.19, p = 0.02) and Month 12 (r = -0.34, p < 10-4). After multiple regression analysis, only Month 12 body weight loss remained associated to 3-month FGF21 response (r = -0.3, p = 0.02). CONCLUSION: This study showed that the magnitude of changes in FGF21 at 3 months after bariatric surgery emerged as an independent predictor of one-year body weight loss irrespective of the type of surgery.

Type 2 diabetes and cardiorenal syndromes. A nationwide French hospital cohort study.

AIM: Type 2 diabetes mellitus (T2DM) is a risk factor for cardiac and renal complications; its effect on cardiorenal syndromes is unknown. METHODS: In a French nationwide cohort of 5,123,193 patients hospitalized in 2012 with ≥5 years of follow-up, we assessed the effect of T2DM on cardiorenal syndrome (CRS) (using cardiorenal, renocardiac, and simultaneous subtypes) incidence and outcomes using 1:1 propensity matching. RESULTS: Among 4,605,236 adults without cardiorenal syndrome, 380,581 (8.5%) with T2DM were matched to 380,581 adults without T2DM. During follow-up, CRS occurred in 104,788 patients: simultaneous n = 25,225 (24.0%); cardiorenal n = 51,745 (49.4%); renocardiac n = 27,818 (26.5%). T2DM doubled the risk of incident CRS (1.30% versus 0.65%/year; adjusted hazard ratio (HR) for any cardiorenal syndrome: 2.14 [95% confidence interval 2.10;2.19]; renocardiac: 2.43 [2.34;2.53]; cardiorenal: 2.09 [2.03;2.15]; simultaneous: 1.94 [1.86;2.03]. Among the 26,396 adults with CRS in 2012, 11,355 (43.0%) had T2DM and were younger than non-diabetic adults (77.4 ± 9.5 versus 82.3 ± 10.0); 8,314 patients with T2DM were matched to 8,314 patients without. T2DM increased risk of: end-stage kidney disease, adjusted HR 1.50 [1.39;1.62]; myocardial infarction 1.35 [1.19;1.53]; cardiovascular death 1.20 [1.13;1.27]; heart failure 1.17 [1.12;1.21]; and all-cause death 1.09 [1.06;1.13], but not ischemic stroke. CONCLUSION: Patients with T2DM represent almost half of patients with CRS and are younger than their non-diabetic counterparts. T2DM doubles the risk of CRS and increases the risk of death, cardiovascular outcome, and end-stage kidney disease but not ischemic stroke after CRS.

Prevalence and incidence of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: A nationwide French observational study of hospitalized patients.

BACKGROUND: Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) increase risks of cardiovascular (CV) and renal disease compared with diabetes-free populations. There are only a few studies comparing T1DM and T2DM for the relative risk of these clinical events. METHODS: All adult patients hospitalized in French hospitals in 2013 with at least 5 years of follow-up were identified and categorized by their diabetes status. A total of 50,623 patients with T1DM (age 61.4 ± 18.6, 53% male) and 425,207 patients with T2DM (age 68.6 ± 14.3, 55% male) were followed over a median period of 5.3 years (interquartile range: 2.8 - 5.8 years). Prevalence and event rates of myocardial infarction (MI), heart failure (HF), ischemic stroke, chronic kidney disease (CKD), all-cause death and CV death were assessed with age stratification of 10-year intervals. For clinical events during follow-up, we report hazard ratios (HRs) in T1DM relative to T2DM. RESULTS: The age and sex-adjusted prevalence of CV diseases was higher in T2DM for ages above 40 years whereas the prevalence of CKD was more common in T1DM between ages 18 and 70 years. During 2,033,239 person-years of follow-up, age and sex-adjusted HR event rates comparing T1DM, versus T2DM as reference, showed that MI and HF relative risks were increased above 60 years (1.2 and 1.4 -fold). HR of ischemic stroke did not markedly differ between T1DM and T2DM. Risk of incident CKD was 2.4-fold higher in T1DM above 60 years. All-cause death HR risk was 1.1-fold higher in T1DM after 60 years and the CV death risk was 1.15-fold higher in T1DM between 60 and 69 years compared to T2DM. CONCLUSIONS: Although the crude prevalent burden of CV diseases may be lower in T1DM than in T2DM, patients with T1DM may have a higher risk of incident MI, HF, all-cause death and CV death above 60 years of age, highlighting the need for improved prevention in this population.

Yearly Incidence of Stroke and Bleeding in Atrial Fibrillation with Concomitant Hyperthyroidism: A National Discharge Database Study.

Background: Hyperthyroidism is associated with atrial fibrillation (AF), and the latter is a major risk factor for stroke. Aim: We aimed to investigate the yearly incidence of stroke and bleeding in AF patients with and without concomitant hyperthyroidism from the French National Hospital Discharge Database. Methods: Admissions with AF between January 2010 and December 2019 were retrospectively identified and retrieved from the French national database. Incidence rates of ischaemic stroke and bleeding were compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by Cox regression. Results: Overall 2,421,087 AF patients, among whom 32,400 had concomitant hyperthyroidism were included in the study. During the follow-up (mean: 2.0 years, standard deviation SD: 2.2 years), the yearly incidence of ischaemic stroke was noted to be 2.6 (95% confidence interval CI: 2.5−2.8) in AF patients with concomitant hyperthyroidism, and 2.3 (95%CI: 2.3−2.4) in non-thyroid AF patients. Hyperthyroidism was noted as an independent risk factor for ischaemic stroke (adjusted hazard ratio aHR: 1.133, 95%CI: 1.080−1.189) overall, particularly within the first year of hyperthyroidism diagnosis (aHR 1.203, 95%CI 1.120−1.291), however, the association became non-significant in subsequent years (aHR 1.047, 95%CI 0.980−1.118). Major bleeding incidence was lower in the hyperthyroid AF group in comparison to the non-thyroid AF group (incidence ratio: 5.1 vs. 5.4%/year, p < 0.001). The predictive value of CHA2DS2VASc and HAS-BLED scores for ischaemic stroke and bleeding events, respectively, did not differ significantly between AF patients with or without concomitant hyperthyroidism. Conclusions: Hyperthyroidism seems to be an independent risk factor of ischaemic stroke in AF patients, particularly within the first year of hyperthyroidism diagnosis.

Metabolically healthy obesity and cardiovascular events: A nationwide cohort study.

AIM: To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. MATERIALS AND METHODS: All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE-HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS: In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted HR 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95% CI 1.31-1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30-1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87-0.98), ischaemic stroke (HR 0.93, 95% CI 0.88-0.98) and cardiovascular death (HR 0.99, 95% CI 0.93-1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12-1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49-0.99). CONCLUSIONS: In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new-onset HF and new-onset AF. However, notable differences were observed in men and women in the sex-stratified analysis.

Sex, age, type of diabetes and incidence of atrial fibrillation in patients with diabetes mellitus: a nationwide analysis.

BACKGROUND: There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. METHODS: All patients aged ≥ 18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). RESULTS: In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27-1.37) in women vs. 1.12(1.08-1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16-1.19) in women vs. 1.10(1.09-1.12) in men for type 2 diabetes. CONCLUSION: Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.

Impact of gender on relative rates of cardiovascular events in patients with diabetes.

AIM: To investigate whether diabetes confers higher relative risks of cardiovascular events in women compared with men using contemporary data and also whether such gender-differences are dependent on age. METHODS: All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and no history of major adverse cardiovascular events including heart failure (MACE-HF; heart failure, myocardial infarction, ischaemic stroke, cardiovascular death) were identified and categorized by diabetes status. Overall and age-stratified incidence rates, hazard ratios (HRs) and women-to-men ratios (WMRs) for MACE-HF leading to hospitalization were also calculated. Adjustments were then made for age and baseline characteristics according to cardiovascular risk factors and non-cardiovascular comorbidities. RESULTS: The study included 2,953,816 subjects, among whom 349,928 (11.9%) had diabetes. Of those with diabetes, the absolute rate of MACE-HF was higher in men than in women (96 vs 66 per 1000 person-years); corresponding absolute rates in men and women without diabetes were 44 vs 27 per 1000 person-years. Comparing those with and without diabetes, women had a higher unadjusted HR of MACE-HF (2.45, 95% CI: 2.42-2.47) than men (2.15, 95% CI: 2.14-2.17), with an adjusted WMR of 1.13 (95% CI: 1.12-1.15). HRs of MACE-HF related to diabetes were highest in women aged around 45 years and in the youngest men and decreased with advancing age in both these groups. However, HRs were higher in women of all ages > 40 years. After adjustment, this effect was more apparent for myocardial infarction (adjusted WMR: 1.43, 95% CI: 1.38-1.48) than for either ischaemic stroke (adjusted WMR: 1.10, 95% CI: 1.07-1.14) or heart failure (adjusted WMR: 1.13, 95% CI: 1.11-1.14). CONCLUSION: Although men have higher absolute risks of cardiovascular complications, the relative risks of cardiovascular complications associated with diabetes are higher in women than in men.