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Background: An “obesity paradox” for mortality has been shown in chronic disorders such as diabetes, and attributed to methodological bias, including the use of body mass index (BMI) for obesity definition. This analysis investigated the independent association of BMI versus surrogate measures of central adiposity with all-cause mortality in individuals with type 2 diabetes. Methods: The Renal Insufficiency And Cardiovascular Events Italian Multicentre Study is a prospective cohort study that enrolled 15,773 patients in 19 Italian centres in 2006–2008. Exposures were BMI and the surrogate measures of central adiposity waist circumference (WC), waist-to-height ratio (WHtR), and A Body Shape Index (ABSI). Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%), Results: Age- and sex-adjusted hazard ratios and 95% confidence intervals were significantly higher in BMI-based underweight (1.729 [1.193–2.505), P = 0.004), moderately obese (1.214 [1.058–1.392), P = 0.006) and severely obese (1.703 [1.402–2.068), P < 0.0001), lower in overweight (0.842 [0.775–0.915), P < 0.0001) and similar in mildly obese (0.950 [0.864–1.045), P = 0.292), compared to normal-weight individuals. When further adjusting for smoking, physical activity (PA), and comorbidities, risk was lower also in mildly obese versus normal-weight patients. The BMI-mortality relationship did not change after sequentially excluding ever smokers, individuals with comorbidities, and those died within two years from enrollment and when analyzing separately participants below and above the median age. Conversely, a paradox relationship was observed among inactive/moderately inactive, but not moderately/highly active patients. Mortality risk adjusted for age, gender, smoking, PA and comorbidities was significantly higher in the highest tertile of WC (1.279 [1.089–1.501], P = 0.003), WHtR (1.372 [1.165–1.615], P < 0.0001), and ABSI (1.263 [1.067–1.495], P = 0.007) versus the lowest tertile.

Background: Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods: On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with < 3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with > 3 drugs or controlled with > 4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results: Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P < 0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P = 0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P = 0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values < 120/7

Background: Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods: On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with < 3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with > 3 drugs or controlled with > 4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results: Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P < 0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P = 0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P = 0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values < 120/7

Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification.Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped

Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification.Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped

Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.Methods: Serial (3-5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke