Sandro Gentile

A randomized controlled trial of acarbose in hepatic encephalopathy

BACKGROUND & AIMS Hepatic encephalopathy in cirrhosis is contributed to by toxic products deriving from the proteolytic bacterial flora-related degradation of dietary nitrogen substances. Acarbose is a novel hypoglycemic agent acting through the inhibition of glucose absorption in the gut and the promotion of intestinal saccharolytic bacterial flora at the expense of proteolytic flora. We assessed whether acarbose exerts a beneficial effect on hepatic encephalopathy and on postprandial hyperglycemia in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus. METHODS One hundred seven cirrhotic patients with grade 1-2 hepatic encephalopathy and type 2 diabetes mellitus were randomized to acarbose 100 mg 3 times daily or placebo for 8 weeks; after a 2-week washout period, treatments were switched, and patients were followed for 8 more weeks. Ammonia blood levels, Reitans number connection test, intellectual function, fasting and postprandial glucose levels, glycated hemoglobin values, and C peptide values were determined 2 weeks before and 4, 8, 11, 14, and 18 weeks after treatment. RESULTS (1) Acarbose significantly decreased ammonia blood levels and improved Reitans test score and intellectual function score compared with placebo (P < .01). (2) Acarbose caused a 33% decrease in fasting glucose level and an approximately 50% decrease in postprandial glucose level compared with placebo (P < .01). (3) Acarbose significantly lowered glycated hemoglobin values and postprandial C peptide compared with baseline values, whereas placebo did not. (4) No change in biochemical parameters of liver function was observed after acarbose treatment. CONCLUSIONS Acarbose is a safe and effective drug in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus.

Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial.

OBJECTIVE To provide evidence-based options on how to intensify basal insulin, we explored head-to-head prandial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1–3 oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS Patients were randomized to lixisenatide once daily or insulin glulisine given once or thrice daily, added to glargine, with or without metformin, if HbA1c remained ≥7 to ≤9% (≥53 to ≤75 mmol/mol) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization. Coprimary end points at 26 weeks were 1) noninferiority (95% CI upper bound <0.4% [<4.4 mmol/mol]) in HbA1c reduction with lixisenatide versus glulisine once daily, and either 2a) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b) superiority in body weight change for lixisenatide versus glulisine thrice daily. Fasting and postprandial plasma glucose, composite efficacy/safety end points, and adverse events were also assessed. RESULTS Baseline characteristics were similar between arms (n = 298, diabetes and basal insulin duration of 12.2 and 3.2 years, respectively; BMI 32.2 kg/m2). HbA1c improved from 8.5% to 7.9% (69 to 63 mmol/mol) with glargine optimization and further to 7.2%, 7.2%, and 7.0% (55, 55, and 53 mmol/mol) with lixisenatide and glulisine once daily and thrice daily, respectively; all coprimary end points were met. Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisine patients. More gastrointestinal events occurred with lixisenatide. CONCLUSIONS Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.

Cardiovascular risk assessment beyond Systemic Coronary Risk Estimation: A role for organ damage markers

Background: Cardiovascular risk assessment in the clinical practice is mostly based on risk charts, such as Framingham risk score and Systemic Coronary Risk Estimation (SCORE). These enable clinicians to estimate the impact of cardiovascular risk factors and assess individual cardiovascular risk profile. Risk charts, however, do not take into account subclinical organ damage, which exerts independent influence on risk and may amplify the estimated risk profile. Inclusion of organ damage markers in the assessment may thus contribute to improve this process. Objective: Our aim was to evaluate the influence of implementation of SCORE charts with widely available indexes of organ damage, with the purpose to ameliorate individual risk assessment. Methodology: We searched www.Pubmed.gov for evidence about the predictive value of left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU) and metabolic syndrome on different risk profiles estimated by SCORE. Interventional and observational trials including at least 200 patients and published after 2000 were selected. Results: The presence of organ damage as well as the number of abnormal parameters indicating organ damage is associated with increased cardiovascular risk, independently of SCORE. In the area of high risk, the impact of different markers of organ damage is heterogeneous. Combined risk models of SCORE and subclinical organ damage have major impact on risk stratification and may impact on recommendation in primary prevention in all SCORE categories. Conclusion: Available evidence suggests a tangible clinical advantage of adding the evaluation of simple organ damage markers to risk charts in cardiovascular risk prediction.

Sex Disparities in the Quality of Diabetes Care: Biological and Cultural Factors May Play a Different Role for Different Outcomes A cross-sectional observational study from the AMD Annals initiative

OBJECTIVE To investigate the quality of type 2 diabetes care according to sex. RESEARCH DESIGN AND METHODS Clinical data collected during the year 2009 were extracted from electronic medical records; quality-of-care indicators were evaluated. Multilevel logistic regression analysis was applied to estimate the likelihood of women versus men to be monitored for selected parameters, to reach clinical outcomes, and to be treated with specific classes of drugs. The intercenter variability in the proportion of men and women achieving the targets was also investigated. RESULTS Overall, 415,294 patients from 236 diabetes outpatient centers were evaluated, of whom 188,125 (45.3%) were women and 227,169 (54.7%) were men. Women were 14% more likely than men to have HbA1c >9.0% in spite of insulin treatment (odds ratio 1.14 [95% CI 1.10–1.17]), 42% more likely to have LDL cholesterol (LDL-C) ≥130 mg/dL (1.42 [1.38–1.46]) in spite of lipid-lowering treatment, and 50% more likely to have BMI ≥30 kg/m2 (1.50 [1.50–1.54]). Women were less likely to be monitored for foot and eye complications. In 99% of centers, the percentage of men reaching the LDL-C target was higher than in women, the proportion of patients reaching the HbA1c target was in favor of men in 80% of the centers, and no differences emerged for blood pressure. CONCLUSIONS Women show a poorer quality of diabetes care than men. The attainment of the LDL-C target seems to be mainly related to pathophysiological factors, whereas patient and physician attitudes can play an important role in other process measures and outcomes.

Sex Disparities in theQuality of DiabetesCare: Biological and Cultural FactorsMayPlay a Different Role for DifferentOutcomes

OBJECTIVE To investigate the quality of type 2 diabetes care according to sex. RESEARCH DESIGN AND METHODS Clinical data collected during the year 2009 were extracted from electronic medical records; quality-of-care indicators were evaluated. Multilevel logistic regression analysis was applied to estimate the likelihood of women versus men to be monitored for selected parameters, to reach clinical outcomes, and to be treated with specific classes of drugs. The intercenter variability in the proportion of men and women achieving the targets was also investigated. RESULTS Overall, 415,294 patients from 236 diabetes outpatient centers were evaluated, of whom 188,125 (45.3%) were women and 227,169 (54.7%) were men. Women were 14% more likely than men to have HbA1c >9.0% in spite of insulin treatment (odds ratio 1.14 [95% CI 1.10–1.17]), 42% more likely to have LDL cholesterol (LDL-C) ≥130 mg/dL (1.42 [1.38–1.46]) in spite of lipid-lowering treatment, and 50% more likely to have BMI ≥30 kg/m2 (1.50 [1.50–1.54]). Women were less likely to be monitored for foot and eye complications. In 99% of centers, the percentage of men reaching the LDL-C target was higher than in women, the proportion of patients reaching the HbA1c target was in favor of men in 80% of the centers, and no differences emerged for blood pressure. CONCLUSIONS Women show a poorer quality of diabetes care than men. The attainment of the LDL-C target seems to be mainly related to pathophysiological factors, whereas patient and physician attitudes can play an important role in other process measures and outcomes.

Correlates of diabetes-related distress in type 2 diabetes: Findings from the benchmarking network for clinical and humanistic outcomes in diabetes (BENCH-D) study.

OBJECTIVE To evaluate correlates of high diabetes-related distress (HD) among individuals with type 2 diabetes mellitus (T2DM). METHODS The study involved a sample of patients with T2DM who filled in the Problem Areas in Diabetes questionnaire (PAID-5); a score ≥ 40 indicates HD. Additional instruments included: SF12 health survey (SF12), Well-Being Index (WHO-5), Diabetes Empowerment Scale-Short Form (DES-SF), Patient Assessment of Chronic Illness Care-Short Form (PACIC-SF), Health Care Climate-Short Form (HCC-SF), Global Satisfaction with Diabetes Treatment (GSDT), Summary of Diabetes Self-Care Activities (SDSCA-6); Barriers to Medications (BM), Perceived Social Support (PSS). Clinical data were extracted from computerized medical records. Multivariable logistic regression analyses were performed to identify correlates of HD. RESULTS Of 2374 patients (mean age 65.0±10.2 years, diabetes duration 14.0±15.3 years, 59.9% males), 1429 (60.2%) had HD. Compared to patients with a PAID-5 score<40 those with HD were more often female, living alone, had a lower level of education, higher HbA1c levels, a greater perceived impact of hyperglycemic and hypoglycemic symptoms, a greater number of diabetes-related complications, lower scores of WHO-5, DES-SF, PSS, GSDT, SF-12 PCS, SDSCA-healthy diet and physical activity subscales, higher scores of BM and SDSCA-SMBG component. Multivariable analyses confirmed the relationship between HD and symptoms of hyperglycemia, levels of empowerment, global satisfaction with treatment, perception of barriers to medication, and psychological well-being. Conclusion HD is extremely common among people with T2DM, affecting almost two-thirds of patients. High levels of distress are associated with worse clinical and psychosocial outcomes and should be considered as a key patient-centered indicator.

Interplay among patient empowerment and clinical and person-centered outcomes in type 2 diabetes. The BENCH-D study

OBJECTIVE We evaluated empowerment in T2DM and identified its correlates. METHODS A sample of individuals self-administered the Diabetes Empowerment Scale-Short Form (DES-SF) and other 9 validated instruments (person-centered outcomes). Correlates of DES-SF were identified through univariate and multivariate analyses. For person-centered outcomes, ORs express the likelihood of being in upper quartile of DES-SF (Q4) by 5 units of the scale. RESULTS Overall, 2390 individuals were involved. Individuals in Q4 were younger, more often males, had higher levels of school education, lower HbA1c levels and prevalence of complications as compared to individuals in the other quartiles. The likelihood of being in Q4 was directly associated with higher selfreported self-monitoring of blood glucose (SDSCA6-SMBG) (OR=1.09; 95% CI: 1.03-1.15), higher satisfaction with diabetes treatment (GSDT) (OR=1.15; 95% CI: 1.07-1.25), perceived quality of chronic illness care and patient support (PACIC-SF) (OR=1.23; 95% CI: 1.16-1.31), and better person-centered communication (HCC-SF) (OR=1.10; 95% CI: 1.01-1.19) and inversely associated with diabetes-related distress (PAID-5) (OR=0.95; 95% CI: 0.92-0.98). Adjusted DES-SF mean scores ranged between centers from 69.8 to 93.6 (intra-class correlation=0.10; p<0.0001). CONCLUSIONS Empowerment was associated with better glycemic control, psychosocial functioning and perceived access to person-centered chronic illness care. Practice of diabetes center plays a specific role. PRACTICE IMPLICATIONS DES-SF represents a process and outcome indicator in the practice of diabetes centers.

Management of newly diagnosed patients with type 2 diabetes: what are the attitudes of physicians? A SUBITO!AMD survey on the early diabetes treatment in Italy.

Early intensive therapy in type 2 diabetes can prevent complications. Nevertheless, metabolic control is often sub-optimal in newly diagnosed patients. This web-based survey aimed to evaluate opinions of physicians about treatment, priorities, and barriers in the care of patients first referred to diabetes clinics. Data on physician attitudes toward therapeutic preferences for two clinical case models (same clinical profile, except HbA1c levels of 8.6 and 7.3% at the first access, respectively) were collected. Participants were asked to rank from 1 (most important) to 6 (least important) a list of priorities and barriers associated with the care of new patients. Overall, 593 physicians participated. In both case models, metformin and education were primary options, although their combination with other classes of drugs varied substantially. Main priorities were “to teach the patient how to cope with the disease” and “to achieve HbA1c target”; main barriers were “lack of time” and “long waiting list”. At multivariate analyses, physicians from the South of Italy had a twofold higher likelihood to attribute a rank 1–2 to organizational barriers than those operating in the North (South vs. North: OR: 2.4; 95% CI 1.4–4.1; Center vs. North: OR: 2.4; 95% CI 0.9–3.2). In the absence of a widely accepted evidence-based therapeutic algorithm driving the therapeutic choices according to the patient characteristics, prescriptions vary according to physician preferences. Education is perceived as a key-strategy, but organizational barriers and geographic disparities are an obstacle. These findings can drive new strategies to reduce clinical inertia, attitudes variability, and geographic disparities.

Predictors of chronic kidney disease in type 2 diabetes: A longitudinal study from the AMD Annals initiative

AbstractThe identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus.We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m2 and normoalbuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; and eGFR <60 mL/min/1.73 m2 and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m2 and albuminuria. Measurements: eGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index.Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m2, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m2), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m2), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome.Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that different mechanisms are involved in the development of these 2 components of diabetic kidney disease.

Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of short‐acting and other glucagon‐like peptide‐1 receptor agonists

A substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti‐diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short‐acting glucagon‐like peptide‐1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed.