Metformin attenuates the postprandial fall in blood pressure in type 2 diabetes.

Metformin has been shown to modulate the cardiovascular response to intraduodenal glucose in patients with type 2 diabetes (T2DM), and may have the capacity to regulate postprandial blood pressure (BP), which is often inadequately compensated in T2DM, resulting in postprandial hypotension. In the present study, we evaluated the acute effects of metformin on the BP and heart rate (HR) responses to oral glucose in patients with T2DM. Ten diet-controlled T2DM patients were evaluated on two occasions in a double-blind, randomized, crossover design. Participants received either metformin 1 g or saline (control) intraduodenally 60 minutes before ingesting a 50 g glucose drink labelled with 150 mg 13 C-acetate. BP, HR, plasma glucagon-like peptide-1 (GLP-1) and gastric emptying (breath test) were evaluated over 180 minutes. Systolic and diastolic BP decreased and HR increased after oral glucose (P < 0.001 for all) on both days. Metformin attenuated the fall in systolic BP (P < 0.001), increased plasma GLP-1 concentrations (P < 0.05) and slowed gastric emptying (P < 0.05) without significantly affecting diastolic BP or HR. In conclusion, metformin acutely attenuates the hypotensive response to oral glucose, associated with augmented GLP-1 secretion and delayed gastric emptying, effects potentially relevant to its favourable cardiovascular profile.

Comparative effects of proximal and distal small intestinal administration of metformin on plasma glucose and glucagon-like peptide-1, and gastric emptying after oral glucose, in type 2 diabetes.

AIMS: The gastrointestinal tract, particularly the lower gut, may be key to the anti-diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM). MATERIALS AND METHODS: Ten diet-controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg 13 C-acetate. "Arterialized" venous blood and breath samples were collected over 3 hours for measurements of plasma glucose, GLP-1, insulin and glucagon, and GE, respectively. RESULTS: Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP-1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin. CONCLUSIONS: In diet-controlled T2DM patients, glucose-lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP-1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose-lowering capacity of metformin.

Assessing and addressing barriers towards MDI use in acute asthma exacerbations at a tertiary pediatric ED in the United Arab Emirates.

Asthma is one of the most common causes of emergency department (ED) visits in children. Therapy delivered through a meter dose inhaler with spacer (MDI + S) is equally as effective as nebulization in mild and moderate asthma exacerbations but was not routinely prescribed in the ED at the largest tertiary center for pediatrics in the United Arab Emirates (UAE). Phase 1 of this cohort study involved a validated survey to evaluate physicians' knowledge, attitudes and perceptions towards MDI therapy. While 62% of physicians reported that MDI + S was equally effective as nebulizers and 82% believed that they had sufficient knowledge with regard to its use, only 28% prescribed it. Perceived barriers to change of practice included: Lack of clinical practice guidelines (CPG), poor knowledge amongst nurses and physicians, caregivers' reluctance and a difficult prescription process. Phase 2 consisted of administering the same survey after completing interventions to address the aforementioned barriers. Comparisons were made between the subgroups within phase 1 and statistically significant differences were noted with a p value < .05. The number of physicians who prescribed MDI + S increased from 28% to 41% (p value = .046). Moreover, physicians who believed that convincing parents to use MDI + S therapy would be easy, increased from 35% to 66% (p value < .0001). In conclusion, more physicians reported prescribing MDI + S in Phase 2 while concerns about barriers that exist to change in practice remained similar in both phases showing that consistent and prolonged advocacy is required to achieve long-term compliance.

Potential for Gut Peptide-Based Therapy in Postprandial Hypotension.

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.

Gastrointestinal Mechanisms Underlying the Cardiovascular Effect of Metformin.

Metformin, the most widely prescribed drug therapy for type 2 diabetes, has pleiotropic benefits, in addition to its capacity to lower elevated blood glucose levels, including mitigation of cardiovascular risk. The mechanisms underlying the latter remain unclear. Mechanistic studies have, hitherto, focused on the direct effects of metformin on the heart and vasculature. It is now appreciated that effects in the gastrointestinal tract are important to glucose-lowering by metformin. Gastrointestinal actions of metformin also have major implications for cardiovascular function. This review summarizes the gastrointestinal mechanisms underlying the action of metformin and their potential relevance to cardiovascular benefits.

Agricultural irrigation of vine crops from desalinated and brackish groundwater under an economic perspective. A case study in Siggiewi, Malta.

Maltese agriculture faces great challenges due to the severe scarcity of water. Sufficient water resources, in quantity and quality, are necessary to cover the demand in the production of wine grape, one of the most important crops in Maltese agriculture. But also, economic efficiency is essential in the grape cultivation. A Cost-Benefit Analysis (CBA) is defined for Maltese vineyards in the Siggiewi region, considering two irrigation scenarios, irrigation with groundwater or "do-nothing", compared with the "use non-conventional waters" from mixing water from a small desalination plant and groundwater. For the alternative 'mixing desalinated water with groundwater' it is possible to improve water availability and quality for vine crops, while increasing economic benefits for farmer. The results indicate a profitable project from a minimum area of 1 ha, but final benefit is highly dependent on the irrigated surface extension according to water price. Desalination, compared with other type of non-conventional water is considered the best option in this assessment with a small reverse osmosis (RO) desalination plant (120 m3/day) for covering the irrigation needs.

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes.

OBJECTIVE: Nutrient "preloads" given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a (13)C-octanoate-labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated. RESULTS: Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P < 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P < 0.05 each). CONCLUSIONS: In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia.