The effect of obesity pharmacotherapy on body composition, including muscle mass.

Obesity pharmacotherapy represents a promising approach to treating obesity and may provide benefits beyond weight loss alone. Maintaining or even increasing muscle mass during weight loss is important to overall health, metabolic function and weight loss maintenance. Drugs such as liraglutide, semaglutide, tirzepatide, and naltrexone/bupropion have shown significant weight loss effects, and emerging evidence suggests they may also have effects on body composition, particularly a positive influence on muscle mass. However, further research is needed to fully understand the mechanism of action of these drugs and their effects on muscle mass. Clinicians should consider these factors when developing an obesity treatment plan for an individual patient.

Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.

AIM: To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity. MATERIALS AND METHODS: This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal. RESULTS: Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels. CONCLUSION: Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity.

A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus.

Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient-practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.

The Effects of Bariatric Surgery on Pharmacokinetics of Drugs: a Review of Current Evidence.

PURPOSE OF REVIEW: Obesity constitutes a major public health concern and has been recognized as an epidemic. To date, bariatric surgery remains the most effective way for substantial long-lasting weight loss in severe obesity. The purpose of this review is to summarize how the pharmacokinetics of drugs are affected by the most common types of bariatric surgery, i.e., Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). RECENT FINDINGS: Limited data are available regarding the changes in pharmacokinetics of drugs after bariatric surgery. The lack of existing guidelines may lead patients to experience drug toxicity or therapeutic undertreatment. Pharmacokinetic parameters that need to be taken into consideration postoperatively include gastric motility, gastric volume, pH, surface area, bile secretions, carrier proteins, and first-pass metabolism. For drugs with a narrow therapeutic index, other factors need to be monitored closely, including plasma drug levels, patients' clinical outcomes, and laboratory markers. Patients should be followed up frequently and treated in accordance with their response to the drug therapy. Bariatric surgery may affect the pharmacokinetics of various drugs, due to the resultant anatomical changes and the substantial weight loss. Therefore, there is a need to identify those potential changes and adjust patients' medication doses in order to achieve higher efficacy and avoid toxicity.

Revisiting Resting Metabolic Rate: What is the Relation to Weight Fluctuations?

PURPOSE OF REVIEW: Despite the great progress in obesity-tackling strategies, a negative energy equilibrium between energy expenditure and energy intake remains the cornerstone in obesity management. The present review article aims to shed light on the complicated interrelations of resting metabolic rate to weight fluctuations. RECENT FINDINGS: Energy expenditure depends on body composition and is highly affected by weight changes, exerting a significant role in subsequent weight regain and underlining the metabolic resistance that people with obesity face when dealing with weight maintenance. The main tissue involved in energy expenditure is fat-free mass, as opposed to fat mass, which exerts a substantially lower impact. Although people with obesity display higher energy expenditures than their lean counterparts, these decrease substantially in the setting of weight loss. Metabolic adaptation is the difference between measured and predicted RMR after weight loss, either via lifestyle modification or after obesity surgery. Plausible explanations for this include differences in body composition, with loss of fat-free mass playing a significant role. This becomes especially apparent in the setting of rapid and massive weight loss, as in the case of bariatric surgery. A better understanding of energy expenditure pathophysiology may aid in further enhancing weight loss and promoting weight maintenance in people with obesity.

Circulating levels of all proglucagon-derived peptides are differentially regulated postprandially by obesity status and in response to high-fat meals vs. high-carbohydrate meals.

BACKGROUND & AIMS: We measured all proglucagon-derived peptides (PGDPs) levels in response to administration of three mixed meal tolerance tests (MMTs), examining differences in postprandial PGDP responses in subjects with leanness and obesity or between high-fat vs. high carbohydrate meals. METHODS: We designed three physiology interventional studies, administering MMTs over a 180-min period to individuals without diabetes after an overnight fast. In Study 1, a 450 kcal MMT was administered to n = 4 normal weight and n = 9 individuals with obesity. In Study 2, a 600 kcal high-fat MMT was administered to n = 15 normal-weight and n = 15 individuals with obesity. In Study 3, n = 32 participants with obesity were assigned to receive a 600-kcal high-fat (n = 15) or an isocaloric high-carbohydrate MMT (n = 17). Fasting and postprandial levels of c-peptide and PGDPs (proglucagon, GLP-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]) were assessed. RESULTS: In study 1, individuals with normal weight displayed elevated glicentin postprandial secretion compared with people with obesity (p = 0.002). Following a high-fat MMT with 33% higher energy content in study 2, all postprandial PGDPs levels were elevated (p-time<0.001), irrespective of weight status. In study 3, a prolonged postprandial upregulation of PGDPs during the high-fat MMT was observed in contrast with the acute, short-term (max 60 min) PGDP responses to a high-carbohydrate MMT (p-time∗meal<0.001). Across both studies 2 and 3, the postprandial responses of glucagon and MPGF were higher in subjects with male sex whereas glicentin was higher in subjects with female sex. CONCLUSIONS: Fat and carbohydrate content of a meal can substantially affect the postprandial levels of PGDPs. Circulating levels of PGDPs are influenced by the energy content of the meal, and additionally, the presence of leanness or obesity affects circulating levels of select PGDPs. These results, which are to be confirmed by additional studies, expand our understanding of PGDP physiology in leanness and obesity. CLINICALTRIALS: GOV REGISTRATION NUMBERS: (NCT04170010, NCT04430946, NCT04575194).

Low Dose Monacolin K Combined with Coenzyme Q10, Grape Seed, and Olive Leaf Extracts Lowers LDL Cholesterol in Patients with Mild Dyslipidemia: A Multicenter, Randomized Controlled Trial.

Certain nutraceuticals, mainly containing red yeast rice, might be considered as an alternative therapy to statins in patients with dyslipidemia, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing a low dose of monacolin K combined with coenzyme Q10, grape seed and olive tree leaf extracts in patients with mild hypercholesterolemia. In total, 105 subjects with mild hypercholesterolemia (low-density lipoprotein cholesterol LDL-C levels 140-180 mg/dL) and low CV risk were randomly assigned into three treatment groups: lifestyle modification (LM), LM plus a low dosage of monacolin K (3 mg), and LM plus a high dosage of monacolin K (10 mg) and treated for 8 weeks. The primary endpoint was the reduction of LDL-C and total cholesterol (TC). LDL-C decreased by 26.46% on average (p < 0.001) during treatment with 10 mg of monacolin and by 16.77% on average during treatment with 3 mg of monacolin (p < 0.001). We observed a slight but significant reduction of the triglyceride levels only in the high-dose-treated group (mean -4.25%; 95% CI of mean -11.11 to 2.61). No severe adverse events occurred during the study. Our results confirm the LDL-C-lowering properties of monacolin are clinically meaningful even in lower doses of 3 mg/day.

Circulating levels of proglucagon-derived peptides are differentially regulated by the glucagon-like peptide-1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6-month long interventional study.

AIM: To investigate the changes of circulating levels of all proglucagon-derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment. MATERIALS AND METHODS: Seventeen patients with obesity or with overweight and co-morbidities, but without diabetes, were assigned to receive once-daily oral naltrexone/bupropion 32/360 mg (n = 8) or once-daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3-month visits, participants underwent a 3-hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C-peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance-assessed liver steatosis and ultrasound-assessed liver stiffness were measured at each visit. RESULTS: Both medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight-independent increase in the levels of proglucagon (P < .001) and decreases in glucagon-like peptide-2 (GLP-2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon-like peptide-1 (GLP-1) levels in a weight-independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP-2 and glucagon (P < .01). PGDP levels at the 3-month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat-free mass, at both the 3- and 6-month visits. CONCLUSIONS: PGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP-1), and future studies should explore whether the addition of other PGDPs (e.g. GLP-2) could offer additional benefits.

Obesity Paradox: Fact or Fiction?

PURPOSE OF REVIEW: Obesity is related to several comorbidities such as type 2 diabetes mellitus, cardiovascular disease, heart failure, and various types of cancers. While the detrimental effect of obesity in both mortality and morbidity has been well established, the concept of the obesity paradox in specific chronic diseases remains a topic of continuous interest. In the present review, we examine the controversial issues around the obesity paradox in certain conditions such as cardiovascular disease, several types of cancer and chronic obstructive pulmonary disease, and the factors that may confound the relation between obesity and mortality. RECENT FINDINGS: We refer to the obesity paradox when particular chronic diseases exhibit an interesting "paradoxical" protective association between the body mass index (BMI) and clinical outcomes. This association, however, may be driven by multiple factors among which the limitations of the BMI itself; the unintended weight loss precipitated by chronic illness; the various phenotypes of obesity, i.e., sarcopenic obesity or the athlete's obesity phenotype; and the cardiorespiratory fitness levels of the included patients. Recent evidence highlighted that previous cardioprotective medications, obesity duration, and smoking status seem to play a role in the obesity paradox. The obesity paradox has been described in a plethora of chronic diseases. It cannot be emphasized enough that the incomplete information received from a single BMI measurement may interfere with outcomes of studies arguing in favor of the obesity paradox. Thus, the development of carefully designed studies, unhampered by confounding factors, is of great importance.

Nutritional Deficiencies Before and After Bariatric Surgery: Prevention and Treatment.

PURPOSE OF REVIEW: Bariatric surgery has the unique ability to drive substantial and sustainable weight loss in people living with obesity. Non-reversibility of these surgical techniques provides lifelong benefits but entails the need for continuous medical follow-up. The purpose of the current paper is to review and summarize current data on nutritional deficiencies in patients before and after bariatric surgery. RECENT FINDINGS: The cornerstone of preventing the emergence of disorders related to nutritional deficiencies is preoperative screening and correct supplementation since they may be exacerbated postoperatively. Following guidelines in conjunction to a lifelong personalized medical approach is of high importance. Bariatric surgery is a well-studied successful and durable means of weight loss that may lead to nutritional deficiencies. There is, thus, a medical need for careful monitoring and treatment of micro- and macronutrient deficiencies by an experienced multidisciplinary team.

Limb Salvage in Patients With Severe Critical Limb Ischemia (CLI) After Referral for a Second Opinion to a Dedicated CLI Center.

The complexity of critical limb ischemia (CLI) requires dedicated multidisciplinary teams of different care providers, who will supervise the full cycle of CLI care. Until CLI treatment is fully centralized, such dedicated teams may work as second-opinion tools before major amputation is undertaken in CLI patients. The aim of the study is to assess the effectiveness of a well-timed referral to a dedicated CLI-center of patients scheduled to major amputation elsewhere. A retrospective analysis of all CLI-patients treated in our department between January 2019 and March 2020 was conducted. Only patients scheduled for a major amputation elsewhere and referred to our clinic were included. Primary endpoint was amputation-free survival, whereas technical success, limb salvage, minor amputation rate, re-admission at 30 days, and frequency of medication change from other disciplines were the secondary endpoints. Sixteen patients with 19 treated limbs were identified and included in this analysis. The WIfI (wound, infection and foot ischemia) clinical stage on admission was 2 in 4 limbs (21%), 3 in 5 limbs (26%), and 4 in 10 limbs (53%). All patients underwent advanced endovascular revascularization. Minor amputation was performed in 8 patients (42%). Amputation-free survival at 6 months was 93% with limb salvage rate of 100%. Technical success and re-admission rates at 30 days was 95% and 6%, respectively. There was a medication adjustment from other specialties in 13 (81%) patients. Patients in severe stages of CLI scheduled to major amputation reached high limb salvage and survival rate, since they are referred for a second opinion to a dedicated multidisciplinary CLI team.

Interplay between baroreflex sensitivity, obesity and related cardiometabolic risk factors (Review).

The baroreflex represents a rapid negative feedback system implicated in blood pressure regulation, which aims to prevent blood pressure variations by regulating peripheral vascular tone and cardiac output. The aim of the present review was to highlight the association between baroreflex sensitivity (BRS) and obesity, including factors associated with obesity, such as metabolic syndrome, hypertension, cardiovascular disease and diabetes. For the present review, a literature search was conducted using the PubMed database until August 21, 2021. The searched terms included 'baroreflex', and other terms such as 'sensitivity', 'obesity', 'metabolic syndrome', 'hypertension', 'diabetes', 'gender', 'aging', 'children', 'adolescents', 'physical activity', 'bariatric surgery', 'autonomous nervous system' and 'cardiometabolic risk factors'. Obesity and its related metabolic disorders can influence baroreflex functionality and decrease BRS, mostly by potentiating sympathetic nervous system activity. Obesity induces inflammation, which can increase sympathetic system activity and lead to a higher incidence of cardiovascular events. Obesity also represents an important risk factor for hypertension through numerous mechanisms; in this setting, dysfunctional baroreceptors are not able to protect against constantly elevated blood pressure. Furthermore, diabetes mellitus and oxidative stress result in deterioration of BRS, whereas aging is also generally related to reduced cardiovagal BRS. Differences in BRS have also been observed between men and women, and overall cardiovagal BRS in healthy women is less intense compared with that in men. BRS appears lower in children with obesity compared with that in children of a healthy weight. Notably, physical exercise can increase BRS in both hypertensive and normotensive subjects, and BRS can also be significantly improved following bariatric surgery and weight loss. In conclusion, obesity and its related metabolic disorders may influence baroreflex functionality and decrease BRS, and baroreceptors cannot protect against the constantly elevated blood pressure in obesity. However, following bariatric surgery and weight loss, BRS can be significantly improved. The present review summarizes the role of obesity and related metabolic risk factors in BRS, providing details on possible mechanisms and shedding light on their interplay leading to autonomic neuropathy.

Gender Differences in Obesity-Related Cancers.

PURPOSE OF REVIEW: In this review, we summarize the role of obesity in carcinogenesis, providing details on specific cancer sites. Special emphasis is given to gender differences in obesity-related cancers and on the effect of bariatric surgery on cancer risk. RECENT FINDINGS: Accumulating evidence has highlighted the detrimental role of overweight/obesity in cancer, with almost 55% of cancers diagnosed in women and 24% diagnosed in men considered overweight- and obesity-related cancers. Sufficient data have shown that higher BMI is associated with risk of gynecologic malignancies (mainly breast and endometrial cancers) as well as cancers in sites such as the esophagus (adenocarcinoma), gastric cardia, colon, rectum, liver, gallbladder, pancreas, kidney, thyroid gland, and multiple myeloma. The main mechanisms underlying this relationship include the insulin/IGF1 system, the effect of sex hormones, and adipocytokines. Marked differences may be seen in specific cancer sites when comparing men to women. There is a higher overall incidence of obesity-related cancers among females (endometrial, ovarian, and postmenopausal female breast cancers), whereas cancers that concern both sexes show a higher incidence in males, particularly esophageal adenocarcinoma (male to female ratio: 9: 1 in the USA). Additionally, bariatric surgery has provided evidence of lowering overall cancer risk in patients with morbid obesity. Interestingly, bariatric surgery may lower overall cancer risk in women within the first 5 years after surgery due to the reduced risk of breast and endometrial cancer, and non-Hodgkin lymphoma. Obesity constitutes the base for marked metabolic, hormonal, and inflammatory alterations, including increased cancer risk in both men and women. Implementation of early obesity prevention strategies could ameliorate the continuously increasing incidence of cancer attributed to obesity.

How Important Is Eating Rate in the Physiological Response to Food Intake, Control of Body Weight, and Glycemia?

The link between eating rate and energy intake has long been a matter of extensive research. A better understanding of the effect of food intake speed on body weight and glycemia in the long term could serve as a means to prevent weight gain and/or dysglycemia. Whether a fast eating rate plays an important role in increased energy intake and body weight depends on various factors related to the studied food such as texture, viscosity and taste, but seems to be also influenced by the habitual characteristics of the studied subjects as well. Hunger and satiety quantified via test meals in acute experiments with subsequent energy intake measurements and their association with anorexigenic and orexigenic regulating peptides provide further insight to the complicated pathogenesis of obesity. The present review examines data from the abundant literature on the subject of eating rate, and highlights the main findings in people with normal weight, obesity, and type 2 diabetes, with the aim of clarifying the association between rate of food intake and hunger, satiety, glycemia, and energy intake in the short and long term.

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects.

OBJECTIVE: The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. METHODS: Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. RESULTS: In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. CONCLUSIONS: Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis.

PURPOSE: We aimed to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on postprandial glucose and lipid metabolism in addition to weight loss and fasting metabolic profile, in non-diabetic patients undergoing bariatric surgery. METHODS: Seventy-one patients were consecutively recruited and studied preoperatively, 3 and 6 months after surgery. Of these, 28 underwent RYGB (7 males, age 38 ± 9 years, BMI 46.9 ± 5.0 kg/m2), and 43 SG (9 males, age 38 ± 9 years, BMI 50.2 ± 7.0 kg/m2). A semi-liquid mixed meal was consumed, and blood samples were taken before, and every 30 min after meal ingestion up to 180 min postprandially, for measurement of glucose, insulin, and lipids. The overall postprandial response was assessed as area under the concentration-time curve (AUC). RESULTS: Baseline metabolic parameters were similar between RYGB and SG. Both groups experienced comparable weight loss, and a similar improvement in fasting glucose, insulin, and insulin resistance. Total and LDL cholesterol levels were lower at 6 months after RYGB compared to SG, while there was no difference in HDL cholesterol or triglycerides. Glucose AUC was lower after RYGB compared to SG at both 3 (p = 0.008) and 6 months (p = 0.016), without any difference in postprandial insulin response. Triglyceride AUC was also lower in RYGB vs. SG at 3 and 6 months (p ≤ 0.001). CONCLUSIONS: RYGB is superior to SG in improving postprandial glycaemia and lipaemia and cholesterol profile 6 months postoperatively in non-diabetic, severely obese patients. These findings imply procedure-specific effects, such as the malabsorptive nature of RYGB, and less likely a different incretin postoperative response.

Antihypertensive treatment in diabetic patients. Review of current data.

Thirty to 50% of diabetic patients suffer from hypertension, exhibiting increased cardiovascular risk. In the present article we review key studies regarding the current knowledge for blood pressure (BP) goals in people with diabetes, the treatment used and the possible diabetogenic effects of antihypertensive drugs, as well as the beneficial and non-beneficial combinations of antihypertensive drugs in diabetic patients. Early placebo controlled trials proved the beneficial outcome of BP lowering in diabetic patients with initially high BP levels. More recent trials examined the impact of intensive compared to less intensive BP goals in diabetic populations. However, initial BP goals had significant differences from final achieved BP levels. Accordingly, current data support initiation of antihypertensive drug treatment in all patients with diabetes and systolic BP ≥ 140 mmHg, with the aim to lower it consistently <140 mmHg, although how far below 140 mmHg the systolic BP goal should be is not clear. Available literature indicates that more than one drug is commonly used to achieve target BP. Drugs acting on the renin-angiotensin-aldosterone axis have been shown to act protectively on diabetic nephropathy, while ß-blockers and diuretics seem to have a diabetogenic effect. Interestingly, recent studies examining the role of combined use of available renin-angiotensin-aldosterone axis blockers versus its separate use exhibited an increased incidence of adverse outcome in diabetic patients who used combinations of drugs that act against renin-angiotensin-aldosterone system. More studies need to be conducted in order to establish the best combination therapy to reduce diabetic complications.

Improvement in cardiovascular indices after Roux-en-Y gastric bypass or sleeve gastrectomy for morbid obesity.

BACKGROUND: Morbidly obese patients display cardiac abnormalities which are partially reversed after weight loss. The aim of the present study was to assess the potential difference in cardiovascular disease indices between patients who underwent either gastric bypass surgery or sleeve gastrectomy. METHODS: Thirty-seven morbidly obese patients who underwent either Roux-en-Y gastric bypass (RYGB) (n = 14) or SG (n = 23) were examined before, 3 and 6 months after surgery. Indices of cardiac autonomic nervous system activity were evaluated, namely baroreflex sensitivity (BRS) and heart rate variability (HRV). A complete echocardiographic study was performed in a subgroup of 17 patients (RYGB 8, SG 9) preoperatively and 6 months after surgery, evaluating epicardial fat thickness, aortic distensibility, left ventricular (LV) Tei index, left atrium diameter, ejection fraction, and LV mass. RESULTS: All subjects experienced significant (p < 0.001) and similar weight loss independently of the type of operation. BRS and HRV indices improved significantly and to the same degree after surgery in both groups. In the echocardiographic study, all parameters improved significantly at 6 months in comparison with the baseline values. In addition, the RYGB group displayed significantly greater reduction in epicardial fat thickness (p = 0.007) and also tended to have a better LV performance as expressed by the lower values of the Tei index (p = 0.06) compared to the SG group 6 months after surgery. CONCLUSIONS: Both RYGB and SG exert comparable effects on weight loss and improvement of cardiovascular parameters. RYGB displays a more beneficial influence on epicardial fat thickness and left ventricular performance than SG.

In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls.

OBJECTIVE: To investigate liver enzymes in a cohort of women with Polycystic Ovary Syndrome (PCOS) and controls divided according to body mass index (BMI) and their association with features of the syndrome. DESIGN: Eighty-three PCOS women and 64 healthy women were studied. Patients and controls were subdivided into two groups, a lean subgroup (BMI <25kg/m(2)) and an overweight/obese subgroup (BMI >25kg/m(2)). Clinical history, height and weight were obtained and metabolic and hormonal parameters were determined. RESULTS: Serum fasting insulin, fasting glucose, HOMA-IR, triglycerides and total cholesterol were significantly higher (p<0.05) in women with PCOS compared to controls. No significant difference in serum liver enzymes levels between PCOS women and controls was detected. However, serum levels of alanine aminotransferase (ALT) (17.7 vs. 14.1 U/L, p<0.05) and gamma-glutamyl transpeptidase (gammaGT) (17.9 vs. 13.4 U/L, p<0.05) were significantly higher in overweight/obese PCOS women compared with overweight/obese controls. In overweight/obese PCOS patients and controls, ALT levels were positively correlated with free androgen index (FAI) (r=0.25 p<0.05) and total testosterone levels (r=0.33 p<0.01). CONCLUSIONS: The finding of elevated liver enzymes in overweight/obese PCOS women raises the question of screening for non-alcoholic fatty liver disease in this group.