Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. METHODS: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. RESULTS: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. CONCLUSIONS: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

Independent association of history of diabetic foot with all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study.

BACKGROUND: Foot ulcers and/or infections are common long-term complications of diabetes and are associated with increased mortality, especially from cardiovascular disease, though only a few studies have investigated the independent contribution of these events to risk of death. This study aimed at assessing the association of history of diabetic foot with all-cause mortality in individuals with type 2 diabetes, independent of cardiovascular risk factors, other complications, and comorbidities. METHODS: This prospective cohort study enrolled 15,773 Caucasian patients in 19 Italian centers in the years 2006-2008. Prior lower extremity, coronary, and cerebrovascular events and major comorbidities were ascertained by medical records, diabetic retinopathy by fundoscopy, diabetic kidney disease by albuminuria and estimated glomerular filtration rate, cardiovascular risk factors by standard methods. All-cause mortality was retrieved for 15,656 patients on 31 October 2015. RESULTS: At baseline, 892 patients (5.7%) had a history of diabetic foot, including ulcer/gangrene and/or amputation (n = 565; 3.58%), with (n = 126; 0.80%) or without (n = 439; 2.78%) lower limb revascularization, and revascularization alone (n = 330; 2.09%). History of diabetic foot was associated with all-cause death over a 7.42-year follow-up (adjusted hazard ratio, 1.502 [95% confidence interval, 1.346-1.676], p < 0.0001), independent of confounders, among which age, male sex, smoking, hemoglobin A1c, current treatments, other complications, comorbidities and, inversely, physical activity level and total and HDL cholesterol were correlated independently with mortality. Both ulcer/gangrene and amputation alone were independently associated with death, with a higher strength of association for amputation than for ulcer/gangrene (1.874 [1.144-3.070], p = 0.013 vs. 1.567 [1.353-1.814], p < 0.0001). Both ulcer/gangrene/amputation and lower limb revascularization alone were independently associated with death; mortality risk was much higher for ulcer/gangrene/amputation than for revascularization (1.641 [1.420-1.895], p < 0.0001 vs. 1.229 [1.024-1.475], p = 0.018) and further increased only slightly for combined ulcer/gangrene/amputation and revascularization (1.733 [1.368-2.196], p < 0.0001). CONCLUSIONS: In patients with type 2 diabetes, an history of diabetic foot event, including ulcer/gangrene, amputation, and lower limb revascularization, was associated with a ~ 50% increased risk of subsequent death, independent of cardiovascular risk factors, other complications and severe comorbidities, which were also significantly associated with mortality. The association with mortality was greatest for amputation, whereas that for revascularization alone was relatively modest. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Association between age at diagnosis and all-cause mortality in type 2 diabetes: the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.

AIMS: It is unclear whether type 2 diabetes diagnosed in young adulthood is associated with increased severity than that occurring later in life beyond longer lifetime exposure to hyperglycemia. This study aimed at assessing the independent association of age at type 2 diabetes diagnosis with all-cause mortality. METHODS: This prospective cohort study enrolled 15,773 Caucasian patients with type 2 diabetes in 19 Italian centers in 2006-2008. Cardiometabolic risk profile and presence of complications and comorbidities were assessed at baseline and participants were stratified by quartiles of age at diabetes diagnosis. All-cause mortality was verified on 31 October 2015. RESULTS: Valid information on vital status was retrieved for 15,656 participants (99.3%). Patients in the lowest quartile had the longest diabetes duration, the worst glycemic control and the highest prevalence of insulin treatment, obesity, atherogenic dyslipidemia, and smoking habits. All complications were inversely associated with age at diabetes diagnosis after adjustment for age and sex, but not after further adjustment for diabetes duration. Percentages of death, Kaplan-Meier estimates, and unadjusted hazard ratios and mortality rates increased from the lowest to the highest quartile. In contrast, when adjusting for age and sex, participants falling in the lowest quartile, showed the highest mortality risk [hazard ratio 1.321 (95% confidence interval 1.196-1.460), P < 0.0001]. However, differences among quartiles disappeared after adjustment for diabetes duration, complications/comorbidities, or other cardiovascular risk factors. CONCLUSIONS: Type 2 diabetes onset in young adulthood is associated with increased mortality that is mainly driven by longer diabetes duration favoring the development of complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Relationship between degree of risk factor control and all-cause mortality in individuals with type 2 diabetes: A prospective cohort study.

AIMS: To assess whether and to what extent excess risk of all-cause death is reduced in individuals with type 2 diabetes by achieving optimal control of traditional cardiovascular risk factors. METHODS: This observational, prospective, cohort study enrolled 15,773 Caucasian patients in 19 Italian centres in 2006-2008. Participants were stratified according to the number of the following risk factors outside target: haemoglobin A1c, blood pressure, micro/macroalbuminuria, current smoking, LDL cholesterol, and triglycerides. All-cause mortality was retrieved for 15,656 patients (99.3 %) on 31 October 2015. RESULTS: Age-adjusted mortality rates and hazard ratios were significantly higher in the whole RIACE cohort (by ∼20 %) and in patients with (by ∼100 %) but not in those without prior cardiovascular disease (CVD), as compared with the coeval Italian general population. In all patients and in those without prior CVD, the relationship with mortality according to the number of risk factors outside target was J-shaped, an effect that was attenuated after either excluding "overtreated " patients, i.e., those with haemoglobin A1c ≤6.0 % on anti-hyperglycaemic agents causing hypoglycaemia and/or systolic blood pressure ≤120 mmHg on anti-hypertensive agents, or adjusting for "overtreatment". Conversely, in patients with prior CVD, mortality remained higher than in the general population in all categories and increased progressively from +70 % to +314 %, without J-effect. CONCLUSIONS: In patients with type 2 diabetes, optimal treatment of traditional cardiovascular risk factors completely eliminated the excess mortality risk versus the general population, provided that they were not "overtreated". However, this effect was observed only in participants without history of CVD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July 2008.