Unfolding Novel Mechanisms of Polyphenol Flavonoids for Better Glycaemic Control: Targeting Pancreatic Islet Amyloid Polypeptide (IAPP)

Type 2 diabetes (T2D) is characterised by hyperglycaemia resulting from defective insulin secretion, insulin resistance, or both. The impact of over-nutrition and reduced physical activity, evidenced by the exponential rise in obesity and the prevalence of T2D, strongly supports the implementation of lifestyle modification programs. Accordingly, an increased consumption of fruits and plant-derived foods has been advocated, as their intake is inversely correlated with T2D prevalence; this has been attributed, in part, to their contained polyphenolic compounds. Over the last decade, a body of work has focussed on establishing the mechanisms by which polyphenolic compounds exert beneficial effects to limit carbohydrate digestion, enhance insulin-mediated glucose uptake, down-regulate hepatic gluconeogenesis and decrease oxidative stress; the latter anti-oxidative property being the most documented. Novel effects on the inhibition of glucocorticoid action and the suppression of amylin misfolding and aggregation have been identified more recently. Amyloid fibrils form from spontaneously misfolded amylin, depositing in islet cells to elicit apoptosis, beta cell degeneration and decrease insulin secretion, with amyloidosis affecting up to 80% of pancreatic islet cells in T2D. Therefore, intervening with polyphenolic compounds offers a novel approach to suppressing risk or progression to T2D. This review gives an update on the emerging mechanisms related to dietary polyphenol intake for the maintenance of glycaemic control and the prevention of T2D

Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial.

Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time.Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms.The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity.Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure.Australian New Zealand Clinical Trials Registry ACTRN12615000596505

Prevalence of Pre-Diabetes across Ethnicities: A Review of Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) for Classification of Dysglycaemia

Prediabetes can be defined by the presence of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), or glycated haemoglobin (HbA1c) to identify individuals at increased risk of developing type 2 diabetes (T2D). The World Health Organization (WHO, 1999) and the American Diabetes Association (ADA, 2003) utilise different cut-off values for IFG (WHO: 6.1–6.9 mmol/L; ADA: 5.6–6.9 mmol/L) but the same cut-off values for IGT (7.8–11.0 mmol/L). This review investigates whether there are differences in prevalence of IFG, IGT, and combined IFG&IGT between ethnicities, in particular Asian Chinese and European Caucasians. In total, we identified 19 studies using the WHO1999 classification, for which the average proportional prevalence for isolated (i)-IFG, i-IGT, and combined IFG&IGT were 43.9%, 41.0%, and 13.5%, respectively, for Caucasian and 29.2%, 49.4%, and 18.2%, respectively, for Asian. For the 14 studies using ADA2003 classification, the average proportional i-IFG, i-IGT, and combined IFG&IGT prevalences were 58.0%, 20.3%, and 19.8%, respectively, for Caucasian; 48.1%, 27.7%, and 20.5%, respectively, for Asian. Whilst not statistically different, there may be clinically relevant differences in the two populations, with our observations for both classifications indicating that prevalence of i-IFG is higher in Caucasian cohorts whilst i-IGT and combined IFG&IGT are both higher in Asian cohorts

Fatty Pancreas and Cardiometabolic Risk: Response of Ectopic Fat to Lifestyle and Surgical Interventions

Ectopic fat accumulation in non-adipose organs, such as the pancreas and liver, is associated with an increased risk of cardiometabolic disease. While clinical trials have focused on interventions to decrease body weight and liver fat, ameliorating pancreatic fat can be crucial but successful intervention strategies are not yet defined. We identified twenty-two published studies which quantified pancreatic fat during dietary, physical activity, and/or bariatric surgery interventions targeted at body weight and adipose mass loss alongside their subsequent effect on metabolic outcomes. Thirteen studies reported a significant decrease in body weight, utilising weight-loss diets (n = 2), very low-energy diets (VLED) (n = 2), isocaloric diets (n = 1), a combination of diet and physical activity (n = 2), and bariatric surgery (n = 5) including a comparison with VLED (n = 1). Surgical intervention achieved the largest decrease in pancreatic fat (range: −18.2% to −67.2%) vs. a combination of weight-loss diets, isocaloric diets, and/or VLED (range: −10.2% to −42.3%) vs. diet and physical activity combined (range: −0.6% to −3.9%), with a concurrent decrease in metabolic outcomes. While surgical intervention purportedly is the most effective strategy to decrease pancreas fat content and improve cardiometabolic health, the procedure is invasive and may not be accessible to most individuals. Given that dietary intervention is the cornerstone for the prevention of adverse metabolic health, the alternative approaches appear to be the use of weight-loss diets or VLED meal replacements, which are shown to decrease pancreatic fat and associated cardiometabolic risk

Does a Higher Protein Diet Promote Satiety and Weight Loss Independent of Carbohydrate Content? An 8-Week Low-Energy Diet (LED) Intervention

Both higher protein (HP) and lower carbohydrate (LC) diets may promote satiety and enhance body weight (BW) loss. This study investigated whether HP can promote these outcomes independent of carbohydrate (CHO) content. 121 women with obesity (BW: 95.1 ± 13.0 kg, BMI: 35.4 ± 3.9 kg/m2) were randomised to either HP (1.2 g/kg BW) or normal protein (NP, 0.8 g/kg BW) diets, in combination with either LC (28 en%) or normal CHO (NC, 40 en%) diets. A low-energy diet partial diet replacement (LEDpdr) regime was used for 8 weeks, where participants consumed fixed-energy meal replacements plus one ad libitum meal daily. Four-day dietary records showed that daily energy intake (EI) was similar between groups (p = 0.744), but the difference in protein and CHO between groups was lower than expected. Following multiple imputation (completion rate 77%), decrease in mean BW, fat mass (FM) and fat-free mass (FFM) at Week 8 in all was 7.5 ± 0.7 kg (p < 0.001), 5.7 ± 0.5 kg (p < 0.001), and 1.4 ± 0.7 kg (p = 0.054) respectively, but with no significant difference between diet groups. LC (CHO×Week, p < 0.05), but not HP, significantly promoted postprandial satiety during a preload challenge. Improvements in blood biomarkers were unrelated to LEDpdr macronutrient composition. In conclusion, HP did not promote satiety and BW loss compared to NP LEDpdr, irrespective of CHO content

Variation with treatment in overall gastric emptying times determined by the wireless motility capsule in six healthy females.

<p>There were no significant differences in gastric emptying times between placebo (glucose solution) and solutions containing either lactulose and mannitol, aspirin or blackcurrant juice with the transformed data. However the emptying of the solution containing ascorbic acid was significantly slower (P = 0.005) on ANOVA than that containing lactulose and mannitol. * indicates the outlier in the pH data after the consumption of the placebo drink.</p

CONSORT flow diagram of the progress through each phase of the study.

<p>CONSORT flow diagram of the progress through each phase of the study.</p

Half-hourly percentage urinary recovery of ingested dose of mannitol (A&B) and lactulose (C&D) in 40 healthy female volunteers following dosage with placebo (A&C) or aspirin (B&D).

<p>*The classification of the data into periods (<i>I, 0–2 </i><i>h</i>, corresponding to the passage of probes from the stomach to the SI; <i>II, 2½-4 </i><i>h,</i> corresponding to passage from the SI to the colon; <i>III, 4½-6 </i><i>h,</i> corresponding to the passage from the proximal to distal colon) was based on the early peak in mean % recovery of mannitol and on the later peak in mean % recovery of lactulose viewed in conjunction with the data from SmartPill (see text). Arrows on X axis indicate the time of passage of the SmartPill into subsequent segments of the gut. Dots indicate the mean ±SE of the % half hourly recoveries of the sugars. Horizontal bars indicate the temporal range of the peak in % recovery of each of the sugars between subjects.</p

Simple linear regressions of pooled half-hourly percentage urinary recoveries of mannitol and lactulose against time, during period II and period III after dosage with placebo or aspirin, in forty healthy female volunteers.

<p>Vertical bars are standard errors.</p

Variation in pH during two consecutive halfs of the time taken for the SmartPill to transit the colon after the consumption of various drinks.

<p>Results expressed as Mean ± SEM.</p><p>LM = lactulose mannitol BC = blackcurrant extract AA = ascorbic acid.</p><p>Differences between the symbols (♦, ●), denote that the mean pH is significantly different (P < 0.05) between the proximal and distal colon.</p><p>Variation in pH during two consecutive halfs of the time taken for the SmartPill to transit the colon after the consumption of various drinks.</p