DPP4 inhibitors: From sitagliptin monotherapy to the new alogliptin-pioglitazone combination therapy

Diabetes mellitus (DM) is currently considered to be an epidemic disease. A safe and effective treatment has long been sought by scientists. Incretin mimetics and dipeptidyl peptidase-4 (DPP4) inhibitors represent a new class of agents that have recently been included as antidiabetic drugs. Although only a limited number of studies exist regarding the treatment of DM based on the incretin effect, DPP4 inhibitors have so far proved to be safe and effective, both when administered alone or in combination with other antidiabetic medication. This review focuses on incretin-effect physiology, as well as the DPP4 inhibitors, from sitagliptin to the new alogliptin-pioglitazone combination agent, given as monotherapy and in combination with other antidiabetic agents. © 2009 Springer Healthcare Communications

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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

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. Summary: 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. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature

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. Summary: 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. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

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 β-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. © 2013 Elsevier Ireland Ltd

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. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

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. Copyright © 2018, Georg Thieme Verlag KG. All rights reserved

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/m2) and an overweight/obese subgroup (BMI >25kg/m2). 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 γ-glutamyl transpeptidase (γGT) (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