Nathalie C. Leite

Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus.

Background/Aims: Diabetic patients have an increased prevalence and severity of non‐alcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence and the factors associated with the presence of ultrasonographic NAFLD in type‐2 diabetic individuals.

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM.

Microvascular degenerative complications are associated with increased aortic stiffness in type 2 diabetic patients

OBJECTIVE Diabetes is a risk factor for increased arterial stiffness; however, few studies had investigated its associated factors. The aim was to evaluate the correlates of increased arterial stiffness in type 2 diabetes, particularly the relationships with microvascular complications. METHODS 482 type 2 diabetic patients without peripheral arterial disease were evaluated in a cross-sectional study. Clinical (including tests of cardiovascular dysautonomy), laboratory, ECG, echocardiographic and 24h ambulatory blood pressure monitoring data were obtained. Arterial stiffness was assessed by carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocity (PWV) measurements. Statistics included multivariate linear and logistic regressions to investigate the independent correlates of increased arterial stiffness. RESULTS No diabetes-related variable was associated with peripheral arterial stiffness. 148 patients (31%) had increased aortic PWV (>12m/s). On multiple linear regression, retinopathy and nephropathy, besides age, heart rate, 24h pulse pressure, diabetes duration, dyslipidemia and number of antihypertensive drugs in use, were independently associated with aortic PWV. On multivariate logistic regression increased aortic stiffness was associated with retinopathy (odds ratio: 3.83, 95% confidence interval [CI]: 2.24-6.56, p<0.001) and peripheral neuropathy (odds ratio: 1.79, 95%CI: 1.06-3.02, p=0.03) after adjusting for possible confounding variables. Other variables associated with increased aortic stiffness were older age, heart rate, diabetes duration, 24h pulse pressure, dyslipidemia and physical inactivity. CONCLUSIONS In type 2 diabetic patients, increased central arterial stiffness is associated with the presence of microvascular complications independent of other established determinants of aortic stiffness.

Prognostic Impact of Aortic Stiffness in High-Risk Type 2 Diabetic Patients The Rio de Janeiro Type 2 Diabetes Cohort Study

OBJECTIVE The prognostic importance of carotid-femoral pulse wave velocity (PWV), the gold standard measure of aortic stiffness, has been scarcely investigated in type 2 diabetes and never after full adjustment for potential confounders. The aim was to evaluate the prognostic impact of carotid-femoral PWV for cardiovascular morbidity and all-cause mortality in a cohort of 565 high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS Clinical, laboratory, ambulatory blood pressure (BP) monitoring, and carotid-femoral PWV data were obtained at baseline. The primary end points were a composite of fatal and nonfatal cardiovascular events and all-cause mortality. Multiple Cox survival analysis was used to assess the associations between carotid-femoral PWV, as a continuous variable and categorized at 10 m/s, and the end points. RESULTS After a median follow-up of 5.75 years, 88 total cardiovascular events and 72 all-cause deaths occurred. After adjustments for potential cardiovascular risk factors, including micro- and macrovascular complications, ambulatory BP, and metabolic control, carotid-femoral PWV was predictive of the composite end point but not of all-cause mortality both as a continuous variable (hazard ratio 1.13 [95% CI 1.03–1.23], P = 0.009 for increments of 1 m/s) and as categorized at 10 m/s (1.92 [1.16–3.18], P = 0.012). On sensitivity analysis, carotid-femoral PWV was a better predictor of cardiovascular events in younger patients (<65 years), in those with microvascular complications, and in those with poorer glycemic control (HbA1c ≥7.5% [58.5 mmol/mol]). CONCLUSIONS Carotid-femoral PWV provides cardiovascular risk prediction independent of standard risk factors, glycemic control, and ambulatory BPs and improves cardiovascular risk stratification in high-risk type 2 diabetes.

Pattern of 24-Hour Ambulatory Blood Pressure Monitoring in Type 2 Diabetic Patients with Cardiovascular Dysautonomy

The pathophysiological mechanisms linking cardiovascular dysautonomy to mortality are unclear. The aim of this study was to investigate the pattern of 24-h ambulatory blood pressure (BP) monitoring (ABPM) in diabetic patients with cardiovascular autonomic neuropathy (CAN). We evaluated 391 type 2 diabetic patients in a cross-sectional study. Five clinical tests of CAN were performed: heart-rate variation during deep breathing, the Valsalva maneuver, and standing, and BP variation during handgrip and standing. Patients were considered to have initial CAN if one heart-rate test was abnormal or two were borderline, and to have definite or severe CAN if at least two tests were abnormal. Differences between patients with and without CAN were assessed by bivariate tests and ANCOVA. Of the 391 patients, 230 (59%) presented clinical CAN, of whom 53 had definite or severe involvement. Patients with CAN were older, had diabetes of longer duration, and had an equal prevalence of hypertension but used more antihypertensive drugs than those without CAN. On ABPM, patients with definite or severe CAN had higher systolic BP (SBP) and pulse pressures (PP) than those without CAN, particularly in the nighttime (SBP: 128±18 vs. 117±16 mmHg, p=0.007; PP: 58±13 vs. 50±11 mmHg, p=0.003) and early morning (SBP: 140±18 vs. 131±17 mmHg, p=0.05) after adjustment for potential confounders, as well as a higher prevalence of the systolic nondipping pattern (75.5% vs. 50.9%, p=0.021). In conclusion, type 2 diabetic patients with more severe CAN have higher SBP and PP, especially during the nighttime and early morning, as well as a higher prevalence of nondipping status. This unfavorable 24-h ABPM pattern may contribute to the increased cardiovascular risk of diabetic patients with dysautonomy.

Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2 diabetes are at a particularly high risk for developing the progressive forms of NAFLD, non-alcoholic steatohepatitis and associated advanced liver fibrosis. Moreover, diabetes is an independent risk factor for NAFLD progression, and for hepatocellular carcinoma development and liver-related mortality in prospective studies. Notwithstanding, patients with NAFLD have an elevated prevalence of prediabetes. Recent studies have shown that NAFLD presence predicts the development of type 2 diabetes. Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients. The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods, although histopathological evaluation is still considered the gold standard diagnostic method. An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking. We sought to outline the published data including epidemiology, pathogenesis, diagnosis and treatment of NAFLD in diabetic patients, in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.

Correlates of Aortic Stiffness Progression in Patients With Type 2 Diabetes: Importance of Glycemic Control The Rio de Janeiro Type 2 Diabetes Cohort Study

OBJECTIVE The correlates of serial changes in aortic stiffness in patients with diabetes have never been investigated. We aimed to examine the importance of glycemic control on progression/regression of carotid-femoral pulse wave velocity (cf-PWV) in type 2 diabetes. RESEARCH DESIGN AND METHODS In a prospective study, two cf-PWV measurements were performed with the Complior equipment in 417 patients with type 2 diabetes over a mean follow-up of 4.2 years. Clinical laboratory data were obtained at baseline and throughout follow-up. Multivariable linear/logistic regressions assessed the independent correlates of changes in cf-PWV. RESULTS Median cf-PWV increase was 0.11 m/s per year (1.1% per year). Overall, 212 patients (51%) increased/persisted with high cf-PWV, while 205 (49%) reduced/persisted with low cf-PWV. Multivariate linear regression demonstrated direct associations between cf-PWV changes and mean HbA1c during follow-up (partial correlation 0.14, P = 0.005). On logistic regression, a mean HbA1c ≥7.5% (58 mmol/mol) was associated with twofold higher odds of having increased/persistently high cf-PWV during follow-up. Furthermore, the rate of HbA1c reduction relative to baseline levels was inversely associated with cf-PWV changes (partial correlation −0.11, P = 0.011) and associated with reduced risk of having increased/persistently high aortic stiffness (odds ratio 0.82 [95% CI 0.69–0.96]; P = 0.017). Other independent correlates of progression in aortic stiffness were increases in systolic blood pressure and heart rate between the two cf-PWV measurements, older age, female sex, and presence of dyslipidemia and retinopathy. CONCLUSIONS Better glycemic control, together with reductions in blood pressure and heart rate, was the most important correlate to attenuate/prevent progression of aortic stiffness in patients with type 2 diabetes.

Prognostic impact of clinic and ambulatory blood pressure components in high-risk type 2 diabetic patients: the Rio de Janeiro Type 2 Diabetes Cohort Study.

Background: The prognostic importance of tight clinic blood pressure (BP) control is controversial in diabetic patients. The objective was to investigate the prognostic impact of clinic and ambulatory BPs for cardiovascular morbidity and mortality in type 2 diabetes. Methods: In a prospective cohort study, 565 type 2 diabetic patients had clinical, laboratory and ambulatory BP monitoring (ABPM) data obtained at baseline and during follow-up. The primary endpoints were a composite of fatal and nonfatal cardiovascular events and all-cause mortality. Multivariable Cox survival and splines regression analyses assessed associations between each BP component [SBP, DBP and pulse pressure (PP)] and the endpoints. Results: After a median follow-up of 5.75 years, 88 total cardiovascular events and 70 all-cause deaths occurred. After adjustments for cardiovascular risk factors, clinic SBP and DBPs were predictive of the composite endpoint but not of all-cause mortality, whereas all ambulatory BP components were predictors of both endpoints. Ambulatory systolic and PPs were the strongest predictors and achieved ambulatory BPs during follow-up improved risk prediction in relation to baseline values. When categorized at clinically relevant cut-off values, risk began only at clinic BPs at least 140/90 mmHg, whereas for ambulatory BPs it began at lower values (≥120/75 mmHg for the 24-h period). Conclusion: ABPM provides more valuable information regarding cardiovascular risk stratification than office BPs and should be performed, if possible, in every high-risk type 2 diabetic patient. Achieved 24-h ambulatory BPs less than 120/75 mmHg are associated with significant cardiovascular protection and, if confirmed by other studies, may be considered as BP treatment targets.

Factors associated with carotid intima-media thickness and carotid plaques in type 2 diabetic patients.

Objective: Factors associated with carotid atherosclerosis are unclear in type 2 diabetic patients. The aim was to investigate the independent correlates of carotid intima-media thickness (IMT) and plaques in these individuals. Methods: In a cross-sectional study, we measured carotid IMT at three sites (common carotid, bifurcation and internal carotid artery) and the severity of extracranial carotid artery (ECCA) atherosclerosis by plaque score in 441 type 2 diabetic patients. Nontraditional cardiovascular risk factors [ambulatory blood pressures (BPs), aortic stiffness, C-reactive protein and ankle–brachial index) were obtained. Multivariate linear and logistic regressions assessed the independent correlates of carotid IMT and ECCA plaque score. Results: Patients with greater carotid IMT or plaque scores had worse clinical and laboratory profile than those with lower IMT and plaque scores, including higher BPs, aortic stiffness and prevalences of diabetic complications. On multivariate analysis, carotid IMT and plaques were mainly associated with older age, male sex, current–past smoking and ambulatory BPs, but not with clinic BPs. Night-time pulse pressure was the most important modifiable determinant of increased carotid IMT. No microvascular complication was independently associated with carotid atherosclerosis, except retinopathy for plaque score. Additionally, internal carotid IMT and plaque score were associated with ankle–brachial index in the subgroup of patients without macrovascular diseases. Conclusion: In type 2 diabetic patients, older age, male sex, smoking status and ambulatory BPs, particularly night-time pulse pressure, were the main independent correlates of ultrasonographic carotid atherosclerosis. This finding reinforces the importance of ambulatory BP monitoring in type 2 diabetes management.

Thresholds of ambulatory blood pressure associated with chronic complications in type 2 diabetes.

BACKGROUND Diagnostic cut-off values for ambulatory blood pressure monitoring (ABPM) in diabetic patients are not established. The aim was to investigate associations between office and ambulatory blood pressures (BPs) and diabetic chronic complications and to establish optimal threshold ambulatory BP values regarding the likehood of having microvascular complications in type 2 diabetes. METHODS In a cross-sectional design, clinical, laboratory, and 24-h ABPM data were obtained in 550 type 2 diabetic patients. Multivariate logistic regression assessed the associations between office and ambulatory BPs and diabetic micro and macrovascular complications. Optimal threshold values for ambulatory BPs (daytime, night-time, and 24 h) were established by examining the best combination of systolic (SBP) and diastolic BP (DBP) that maximized the odds ratios (ORs) of having each microvascular complication. RESULTS After multivariate adjustment for all potential confounders, ambulatory SBPs were more strongly associated with diabetic complications than office BPs, except for retinopathy and nephropathy, in which both were equivalent. In general, night-time BPs were stronger correlates than daytime BPs. The optimal threshold ambulatory BP values were 125/75 mm Hg for daytime, 110/65 mm Hg for night-time, and 120/75 mm Hg for the 24-h period, with odds ranging from 1.7- to 2.3-fold of having each microvascular complication. CONCLUSIONS Except for retinopathy and advanced nephropathy, ambulatory BPs are better correlates of chronic complications than office BPs in type 2 diabetes. The association of microvascular complications with lower ambulatory BP levels than those reported as normal for nondiabetic patients may indicate that lower cut-off values for ambulatory BPs might be considered in type 2 diabetic patients.