Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up.

Left ventricular diastolic dysfunction (DD) is a subclinical cardiac abnormality in patients with type 2 diabetes mellitus (T2DM) that can progress to heart failure (HF) and increase cardiovascular risk. This prospective study evaluated the DD in T2DM patients without atherosclerotic cardiovascular disease after one year of incretin-based drugs added to standard treatment. Of the 138 enrolled patients (49.30% male, mean age 57.86 ± 8.82, mean T2DM history 5 years), 71 were started on dipeptidyl peptidase-4 inhibitor sitagliptin/saxagliptin, 21 on glucagon-like peptide-1 receptor agonist exenatide, and 46 formed the control group (metformin and sulphonylurea/acarbose). At baseline, 71 patients had grade 1 DD, another 12 had grade 2 and 3 DD, and 15 had indeterminate DD. After one year, DD was evidenced in 50 cases. Diastolic function improved in 9 cases, and 27 patients went from grade 1 to indeterminate DD. The active group benefited more, especially patients treated with exenatide; their metabolic and inflammation profiles also improved the most. An in-depth analysis of echocardiographic parameters and paraclinical results in the context of literature data justifies the conclusion that early assessment of diastolic function in T2DM patients is necessary and the benefits of affordable incretin-based treatment may extend to subclinical cardiovascular manifestations such as DD.

Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease-Current Background, Hopes, and Perspectives.

Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease worldwide, reaching one of the highest prevalences in patients with type 2 diabetes mellitus (T2DM). For now, no specific pharmacologic therapies are approved to prevent or treat NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are currently evaluated as potential candidates for NAFLD treatment in patients with T2DM. Some representatives of this class of antihyperglycemic agents emerged as potentially beneficial in patients with NAFLD after several research studies suggested they reduce hepatic steatosis, ameliorate lesions of nonalcoholic steatohepatitis (NASH), or delay the progression of fibrosis in this population. The aim of this review is to summarize the body of evidence supporting the effectiveness of GLP-1RA therapy in the management of T2DM complicated with NAFLD, describing the studies that evaluated the effects of these glucose-lowering agents in fatty liver disease and fibrosis, their possible mechanistic justification, current evidence-based recommendations, and the next steps to be developed in the field of pharmacological innovation.

Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is the hepatic expression of metabolic syndrome. The development of non-invasive methods for the diagnosis of hepatic steatosis and advanced fibrosis in high-risk patients, especially those with type 2 diabetes mellitus, is highly needed to replace the invasive method of liver biopsy. Elastographic methods can bring significant added value to screening and diagnostic procedures for NAFLD in patients with diabetes, thus contributing to improved NAFLD management. Pharmacological development and forthcoming therapeutic measures that address NAFLD should also be based on new, non-invasive, and reliable tools that assess NAFLD in at-risk patients and be able to properly guide treatment in individuals with both diabetes and NAFLD. This is the first review aiming to outline and discuss recent studies on ultrasound-based hepatic elastography, focusing on NAFLD assessment in patients with diabetes.

Association of Inflammatory and Metabolic Biomarkers with Mitral Annular Calcification in Type 2 Diabetes Patients.

(1) Background: Type 2 diabetes mellitus (T2DM) contributes to cardiovascular disease and related mortality through the insidious effects of insulin resistance and chronic inflammation. Mitral annular calcification (MAC) is one such degenerative process promoted by T2DM. (2) Methods: This is a post hoc analysis of insulin resistance, inflammation, and hepatic steatosis markers in T2DM patients without atherosclerotic manifestations, but with incidental echocardiographic detection of mild MAC. (3) Results: 138 consenting patients were 49.3% men, 57.86 years old, with a history of T2DM of 6.16 years and HbA1c 8.06%, of whom sixty had mild MAC (43.47%). The statistically significant differences between patients with/without MAC were higher HOMA C-peptide and C-peptide index for insulin resistance, higher TNF-α for inflammation, and lower estimated glomerular filtration rate. High-sensitive C-reactive protein (hsCRP) was significantly associated with insulin resistance and the strength of the relationship was higher in the MAC group. Predictive of MAC were TNF-α, HOMA C-peptide, and especially hepatic steatosis and hypertension. (4) Conclusions: MAC was more prevalent than reported in the literature. Insulin resistance and inflammation were predictive of MAC, but significant markers differ across studies. Widely available routine tests and echocardiographic assessments are useful in the early identification of mitral annular calcifications in diabetes patients.

New Insights into Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease: The Liver-Heart Axis.

Non-alcoholic fatty liver disease (NAFLD) represents the hepatic expression of the metabolic syndrome and is the most prevalent liver disease. NAFLD is associated with liver-related and extrahepatic morbi-mortality. Among extrahepatic complications, cardiovascular disease (CVD) is the primary cause of mortality in patients with NAFLD. The most frequent clinical expression of CVD is the coronary artery disease (CAD). Epidemiological data support a link between CAD and NAFLD, underlain by pathogenic factors, such as the exacerbation of insulin resistance, genetic phenotype, oxidative stress, atherogenic dyslipidemia, pro-inflammatory mediators, and gut microbiota. A thorough assessment of cardiovascular risk and identification of all forms of CVD, especially CAD, are needed in all patients with NAFLD regardless of their metabolic status. Therefore, this narrative review aims to examine the available data on CAD seen in patients with NAFLD, to outline the main directions undertaken by the CVD risk assessment and the multiple putative underlying mechanisms implicated in the relationship between CAD and NAFLD, and to raise awareness about this underestimated association between two major, frequent and severe diseases.

Self-Reported Satisfaction to Treatment, Quality of Life and General Health of Type 2 Diabetes Patients with Inadequate Glycemic Control from North-Eastern Romania.

Type 2 diabetes mellitus (T2DM) undermines health and quality of life (QoL). This cross-sectional study surveyed 138 consenting T2DM patients from North-Eastern Romania with regard to their satisfaction with treatment, diabetes-related impact on QoL, and general health. The Romanian versions of Diabetes Treatment Satisfaction Questionnaire (DTSQ), Audit of Diabetes Dependent Quality of Life (ADDQoL-19), and 36-Item Short Form Health Survey (SF-36) questionnaires were used. Self-reports were analyzed in conjunction with clinical and metabolic profiling. The patients were 57.86 ± 8.82 years old, 49.3% men, treated with oral glucose-lowering drugs, presenting with inadequate glycemic control but without cardiovascular manifestations. The mean DTSQ and ADDQoL scores were 25.46 ± 0.61 and -2.22 ± 1.2, respectively. Freedom to eat, holidays, journeys, leisure, physical health, sex life, freedom to drink, and feelings about the future scored below average. The mean SF-36 physical and mental health scores were 47.78 ± 1.03 and 50.44 ± 1.38, respectively. The mean SF-6D score was 0.59 ± 0.04 (generated retrospectively using SF-36 data). Negative associations were significant between ADDQoL, age (r = -0.16), and body mass index (r = -0.23), p < 0.01. Overall scores did not correlate with diabetes duration (except DTSQ, r = -1.18, p = 0.02) or HbA1c. The results confirm other researchers' findings in Europe and nearby countries. Our patients seemed satisfied with treatment despite glycemic imbalance and viewed diabetes as a burden on QoL and especially freedom to eat.

Association of Antihyperglycemic Therapy with Risk of Atrial Fibrillation and Stroke in Diabetic Patients.

Type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Atrial fibrillation (AF) and stroke are both forms of CVD that have major consequences in terms of disabilities and death among patients with diabetes; however, they are less present in the preoccupations of scientific researchers as a primary endpoint of clinical trials. Several publications have found DM to be associated with a higher risk for both AF and stroke; some of the main drugs used for glycemic control have been found to carry either increased, or decreased risks for AF or for stroke in DM patients. Given the risk for thromboembolic cerebrovascular events seen in AF patients, the question arises as to whether stroke and AF occurring with modified incidences in diabetic individuals under therapy with various classes of antihyperglycemic medications are interrelated and should be considered as a whole. At present, the medical literature lacks studies specifically designed to investigate a cause-effect relationship between the incidences of AF and stroke driven by different antidiabetic agents. In default of such proof, we reviewed the existing evidence correlating the major classes of glucose-controlling drugs with their associated risks for AF and stroke; however, supplementary proof is needed to explore a hypothetically causal relationship between these two, both of which display peculiar features in the setting of specific drug therapies for glycemic control.

The Mediterranean Diet: From an Environment-Driven Food Culture to an Emerging Medical Prescription.

The Mediterranean diet originates in the food cultures of ancient civilizations which developed around the Mediterranean Basin and is based on the regular consumption of olive oil (as the main source of added fat), plant foods (cereals, fruits, vegetables, legumes, tree nuts, and seeds), the moderate consumption of fish, seafood, and dairy, and low-to-moderate alcohol (mostly red wine) intake, balanced by a comparatively limited use of red meat and other meat products. A few decades ago, the Mediterranean diet drew the attention of medical professionals by proving extended health benefits. The first reports ascertained cardiovascular protection, as multiple large-scale clinical studies, starting with Ancel Keys' Seven Countries Study, showed a marked reduction of atherosclerotic clinical events in populations with a Mediterranean dietary pattern. Ensuing trials confirmed favorable influences on the risk for metabolic syndrome, obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. While its health benefits are universally recognized today by medical professionals, the present state of the Mediterranean diet is challenged by major difficulties in implementing this protective dietary pattern in other geographical and cultural areas and keeping it alive in traditional Mediterranean territories, also tainted by the unhealthy eating habits brought by worldwide acculturation.

Pregnancy and recurrence rates in infertile patients operated for ovarian endometriosis.

AIM: The study deals with the preoperative ultrasound diagnosis of ovarian endometriosis, postoperative ultrasound reassessment, laparoscopic surgical resolution of ovarian endometriosis, estimation of recurrence risk 12 months after surgery by ultrasound, reappearance of clinical symptoms (such as pain) or second-look laparoscopy, and pregnancy rate 2 years after surgery. MATERIAL AND METHODS: 140 patients with en- dometriosis and infertility admitted to the Iasi "Cuza-Voda" Clinical Hospital of Obstetrics and Gynecology between the years 2009-2011 were included in the study. The patients were divided into 2 groups: group 1-59 cases that refused in vitro fertilization procedures, did not afford in vitro fertilization (IVF) or had minimal endometriosis and young ages and thus a possibility of delaying treatment, and group 2--62 cases which underwent IVF procedures immediately after surgery. RESULTS: No significant differences in the chance of becoming pregnant were found between the two groups (χ2 = 2.06, p = 0.0891, 95% CI); in group 1, 11.86% pregnancies were obtained while in group 2 the pregnancy rate was 11.29%. Based on the nonparametric method of analysis of contingency tables we could estimate the odds of becoming pregnant in the study groups, obtaining an odds ratio (OR = 1.16, CI: 1.04-2.23, 95% CI). This result indicated that in group 1 the odds of becoming pregnant was not significantly higher, and the estimation was made for a confidence interval of 95%. The study had in view the assessment of pregnancies obtained in the study groups and the time interval (number of weeks) from the time of intervention until the occurrence of pregnancy. The Kaplan-Meier analysis enabled the assessment of the mean value and the median value of the number of weeks until becoming pregnant, and these values did not show significant differences (χ2 = 1.55, p = 0.212, 95% CI). CONCLUSIONS: For endometriosis associated with infertility, hormonal suppression does not improve fertility, and therefore surgery followed by controlled ovarian hyperstimulation and intrauterine insemi- nation (IUI), provided the anatomy of the pelvis is preserved in early cases or in vitro fertilization in severe cases is preferred.

GnRH Antagonist IVF Protocol in PCOS.

The aim of the present study was to compare the GnRH agonist long protocol with the flexible GnRH antagonist protocol in infertile PCOS women undergoing COS in terms of clinical pregnancy rate (CPR), with special reference to the incidence of OHSS. Materials and Methods. The study was conducted at the Hospital Obstetrics and Gynecology Cuza Voda Iasi and Fertility Reproductive Medical Center Omini Clinic Iasi from June 1, 2010, to September 31, 2012. PCOS as defined by the Rotterdam 2003 consensus, i.e. presence of two of the following three features: presence of oligo- and/ or anovulation, clinical and/or biochemical signs of hyperandrogenism, polycystic ovaries and exclusion of other endocrinopathies. Results. No differences were observed in clinical pregnancy rate (CPR) in the agonist and antagonist protocols, respectively. Incidence of OHSS was lower in the antagonist compared with agonist group (4% versus 28%). Duration of stimulation (13,80 + 1,4 vs 11,85 + 2,4 p < 0,001) and total gonadotrophin required (2435,5 + 884,5 versus 2005, 5 + 545,5 IU p < 0.003) were also lower in the antagonist compared with agonist protocol. Conclusions. The current study suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF.