Understanding the Impact of Different Doses of Reducose® Mulberry Leaf Extract on Blood Glucose and Insulin Responses after Eating a Complex Meal: Results from a Double-Blind, Randomised, Crossover Trial.

Non-communicable diseases (NCDs) are becoming an increasingly important health concern due to a rapidly ageing global population. The fastest growing NCD, type 2 diabetes mellitus (T2DM), is responsible for over 2 million deaths annually. Lifestyle changes, including dietary changes to low glycemic response (GR) foods, have been shown to reduce the risk of developing T2DM. The aim of this study was to investigate whether three different doses of Reducose®, a mulberry leaf extract, could lower the GR and insulinemic responses (IR) to a full meal challenge in healthy individuals. A double-blind, randomised, placebo-controlled, repeat-measure, crossover design trial was conducted by the Oxford Brookes Centre for Nutrition and Health; 37 healthy individuals completed the study. Participants consumed capsules containing either 200 mg, 225 mg, 250 mg Reducose® or placebo before a test meal consisting of 150 g white bread and egg mayo filler. Capillary blood samples were collected at 15-min intervals in the first hour and at 30-min intervals over the second and third hours to determine glucose and plasma insulin levels. The consumption of all three doses of Reducose® resulted in significantly lower blood glucose and plasma insulin levels compared to placebo. All three doses of Reducose® (200 mg, 225 mg, 250 mg) significantly lowered glucose iAUC 120 by 30% (p = 0.003), 33% (p = 0.001) and 32% (p = 0.002), respectively, compared with placebo. All three doses of Reducose® (200 mg, 225 mg, 250 mg) significantly lowered the plasma insulin iAUC 120 by 31% (p = 0.024), 34% (p = 0.004) and 38% (p < 0.001), respectively. The study demonstrates that the recommended dose (250 mg) and two lower doses (200 mg, 225 mg) of Reducose® can be used to help lower the GR and IR of a full meal containing carbohydrates, fats and proteins.

Effectiveness of date seed on glycemia and advanced glycation end-products in type 2 diabetes: a randomized placebo-controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic medical condition affecting more than 95% of people with diabetes. Traditionally, some medicinal plants have been considered as an effective approach in management of T2DM. This trial evaluated the effects of date seed powder (DSP) on glycemia indices and oxidative stress in T2DM patients. METHODS: In this trail, 43 patients with T2DM were randomized to two groups: either 5 g/d of the DSP or placebo for 8 weeks. Levels of glycemic indices, lipolpolysaccharide (LPS), and soluble receptor for advanced glycation end products (s-RAGE), as well as other parameters associated with oxidative stress were assessed at baseline and after 8 weeks. Independent t-test and analysis of covariance (ANCOVA) were used for between-groups comparisons at baseline and the post-intervention phase, respectively. RESULTS: The results showed that supplementation with DSP significantly decreased HbA1c (-0.30 ± 0.48%), insulin (-1.70 ± 2.21 µU/ml), HOMA-IR (-1.05 ± 0.21), HOMA-B (-0.76 ± 21.21), lipopolysaccharide (LPS) (-3.68 ± 6.05 EU/mL), and pentosidine (118.99 ± 21.67 pg/mL) (P < 0.05, ANCOVA adjusted for baseline and confounding factors). On the other hand, DSP supplementation significantly increased total antioxidant capacity (TAC) (0.50 ± 0.26 mmol/L), superoxide dismutase (SOD) (0.69 ± 0.32 U/ml), and s-RAGE (240.13 ± 54.25 pg/mL) compared to the placebo group. FPG, hs-CRP, GPx, CML, and uric acid had no significant within- or between-group changes. CONCLUSION: Supplementation of DSP could be considered an effective strategy to improve glycemic control and oxidative stress in T2DM patients (Registration ID at www.irct.ir : IRCT20150205020965N10).

Effects of Satureja Khuzestanica supplementation on glycemic indices and lipid profile in type 2 diabetes patients: a randomized controlled clinical-trial.

BACKGROUND: Several studies showed the hypoglycemic and hypolipidemic effects of Satureja Khuzestanica (SK) in animal models. This study aimed to determine the effect of SK supplementation on glycemic and lipid outcomes of patients with type 2 diabetes mellitus (T2DM). METHODS: The study was designed as a double-blind, placebo-controlled, randomized clinical trial using block randomization. Seventy-eight T2DM patients were randomly assigned to intervention (n = 39) or placebo (n = 39) groups. They received SK or placebo in 500 mg capsules daily for 12 weeks. Anthropometric, blood pressure, liver enzymes, glycemic, and lipid outcomes were measured before and after the intervention. RESULTS: At baseline, there were no significant differences in age, sex, or glycated hemoglobin (HbA1c) levels between the groups. SK supplementation led to a significant decrease in FBS (-12.6 ± 20.7 mg/dl in the intervention group versus 3.5 ± 31.9 mg/dl; p = 0.007), HbA1c (-0.28 ± 0.45 in the intervention group versus 0.11 ± 0.54% in the placebo group; p = < 0.001), insulin (-1.65 ± 6.18 in the intervention group versus 2.09 ± 5.90 mIU/L in the placebo group; p = 0.03), total cholesterol (-14.6 ± 21.1 mg/dl in the intervention group versus 8.2 ± 30.9 mg/dl in the placebo group; p < 0.001), LDL-cholesterol (-4.6 ± 15.2 mg/dl in the intervention group versus 5.8 ± 14.6 mg/dl in placebo group; p < 0.001) levels, and significant increase in HDL-cholesterol (3.9 ± 4.9 mg/dl in the intervention group versus 0.9 ± 5.2 mg/dl in placebo group; p = 0.005). CONCLUSION: Based on the study results, SK supplementation may improve glycemic indices and lipid profile of patients with T2DM. Our findings may provide novel complementary treatments without adverse effects for diabetes complications. These results need to be further confirmed in clinical trials. REGISTRATION: This trial has been registered in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20190715044214N1, registration date: 21/02/2021).

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

The genetic association of the transcription factor NPAT with glycemic response to metformin involves regulation of fuel selection.

The biguanide, metformin, is the first-choice therapeutic agent for type-2 diabetes, although the mechanisms that underpin metformin clinical efficacy remain the subject of much debate, partly due to the considerable variation in patient response to metformin. Identification of poor responders by genotype could avoid unnecessary treatment and provide clues to the underlying mechanism of action. GWAS identified SNPs associated with metformin treatment success at a locus containing the NPAT (nuclear protein, ataxia-telangiectasia locus) and ATM (ataxia-telangiectasia mutated) genes. This implies that gene sequence dictates a subsequent biological function to influence metformin action. Hence, we modified expression of NPAT in immortalized cell lines, primary mouse hepatocytes and mouse tissues, and analysed the outcomes on metformin action using confocal microscopy, immunoblotting and immunocytochemistry. In addition, we characterised the metabolic phenotype of npat heterozygous knockout mice and established the metformin response following development of insulin resistance. NPAT protein was localised in the nucleus at discrete loci in several cell types, but over-expression or depletion of NPAT in immortalised cell models did not change cellular responses to biguanides. In contrast, metformin regulation of respiratory exchange ratio (RER) was completely lost in animals lacking one allele of npat. There was also a reduction in metformin correction of impaired glucose tolerance, however no other metabolic abnormalities, or response to metformin, were found in the npat heterozygous mice. In summary, we provide methodological advancements for the detection of NPAT, demonstrate that minor reductions in NPAT mRNA levels (20-40%) influence metformin regulation of RER, and propose that the association between NPAT SNPs and metformin response observed in GWAS, could be due to loss of metformin modification of cellular fuel usage.

Oat Polar Lipids Improve Cardiometabolic-Related Markers after Breakfast and a Subsequent Standardized Lunch: A Randomized Crossover Study in Healthy Young Adults.

It has been suggested that intake of polar lipids may beneficially modulate various metabolic variables. The purpose of this study was to evaluate the effect of oat polar lipids on postprandial and second meal glycemic regulation, blood lipids, gastrointestinal hormones, and subjective appetite-related variables in healthy humans. In a randomized design, twenty healthy subjects ingested four liquid cereal-based test beverages (42 g of available carbohydrates) containing: i. 30 g of oat oil with a low concentration (4%) of polar lipids (PLL), ii. 30 g of oat oil containing a high concentration (40%) of polar lipids (PLH), iii. 30 g of rapeseed oil (RSO), and iv. no added lipids (NL). The products were served as breakfast meals followed by a standardized lunch. Test variables were measured at fasting and during 3 h after breakfast and two additional hours following a standardized lunch. PLH reduced glucose and insulin responses after breakfast (0-120 min) compared to RSO, and after lunch (210-330 min) compared to RSO and PLL (p < 0.05). Compared to RSO, PLH resulted in increased concentrations of the gut hormones GLP-1 and PYY after the standardized lunch (p < 0.05). The results suggest that oat polar lipids have potential nutraceutical properties by modulating acute and second meal postprandial metabolic responses.

High-Protein, Low-Glycaemic Meal Replacement Decreases Fasting Insulin and Inflammation Markers-A 12-Month Subanalysis of the ACOORH Trial.

Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and obesity. Since insulin is the key weight regulator, we hypothesised that the addition of meal replacement to a lifestyle intervention reduces insulin levels more effectively than lifestyle intervention alone. In the international multicentre randomised controlled ACOORH (Almased Concept against Overweight and Obesity and Related Health Risk) trial, overweight or obese persons who meet the criteria for metabolic syndrome (n = 463) were randomised into two groups. Both groups received nutritional advice focusing on carbohydrate restriction and the use of telemonitoring devices. The intervention group substituted all three main meals per day in week 1, two meals per day in weeks 2-4, and one meal per day in weeks 5-26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline and after 1, 3, 6 and 12 months. All datasets providing insulin data (n = 446) were included in this predefined subanalysis. Significantly higher reductions in insulin (-3.3 ± 8.7 µU/mL vs. -1.6 ± 9.8 µU/mL), weight (-6.1 ± 5.2 kg vs. -3.2 ± 4.6 kg), and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and the highest amount of weight loss (-7.6 ± 4.9 kg) was observed in those participants with an insulin decrease > 2 µU/mL. These results underline the potential for meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin levels may serve as an indicator for adherence to carbohydrate restriction.

Khat chewing leads to increase in glycaemic parameters in patients with type 2 diabetes mellitus in Jazan region, Saudi Arabia and Yemen.

BACKGROUND: Khat is known to have a stimulating effect on the sympathetic nervous system by producing a temporary sensation of activeness and happiness, along with mood disturbance and anxiety. Despite growing evidence of the association between khat chewing and glycaemic control in patients with diabetes, the position of khat chewing in DM is not fully recognised. AIM: To evaluate the association of khat chewing with the risk of elevated blood glucose levels among patients with type 2 diabetes mellitus. METHOD: A web-based literature search was performed using the electronic databases PubMed, EMBASE and Google Scholar. Databases were searched for studies published about khat chewing and diabetes mellitus in the Jazan region, Saudi Arabia and Yemen. RESULT: Twenty-five published articles studying the relation between khat chewing and diabetes mellitus were identified, but only 10 studies reported an association between khat chewing and blood glucose levels and were included. CONCLUSION: Khat chewing increases fasting blood glucose, post-prandial blood glucose and HbA1c levels in patients with diabetes in the Jazan region, Saudi Arabia and Yemen.

Current concepts and clinical importance of glycemic variability.

BACKGROUND AND AIMS: Evolving evidence indicate that variations in blood glucose levels are likely to be an important factor in developing diabetic complications. Monitoring glucose fluctuations in patients remains as a therapeutic challenge and more evidence needs to be created in order to bring GV into limelight. This review encapsulates the most important findings conducted and discusses on them to provide readers a better understanding on this emerging subject. METHODS: Keyword-based comprehensive desktop search was conducted to gather the relevant literature. Triple-stage cascade type content analysis of the literature was conducted to draw relevant themes of discussions. RESULTS: High glycemic variability is associated with an increased risk of development of diabetic complications especially in cardiac conditions. The widely used and accepted metrics to determine the variations in blood glucose are Standard deviation (SD), MAGE (Mean amplitude of glycemic excursions) and MODD (Mean of daily differences). Occurrence of blood glucose variations affects at a molecular level thereby causing more harm than the occurrence of hyperglycemia alone. CONCLUSION: Available data suggest that Glycemic Variability should be used as an additional marker of glycemia. Additional research globally, and in India are required.

Glycemic benefits with adherence to testosterone therapy in men with hypogonadism and type 2 diabetes mellitus.

BACKGROUND: While previous studies have demonstrated testosterone's beneficial effects on glycemic control in men with hypogonadism and Type 2 Diabetes, the extent to which these improvements are observed based on the degree of treatment adherence has been unclear. OBJECTIVES: To evaluate the effects of long-term testosterone therapy in A1C levels in men with Type 2 Diabetes Mellitus and hypogonadism, controlling for BMI, pre-treatment A1C, and age among different testosterone therapy adherence groups. MATERIALS AND METHODS: We performed a retrospective analysis of 1737 men with diabetes and hypogonadism on testosterone therapy for 5 years of data from 2008-2018, isolating A1C, lipid panels, and BMI results for analysis. Subjects were categorized into adherence groups based on quartiles of the proportion of days covered (> 75% of days, 51-75% of days, 26-50% of days and 0-25% of days), with >75% of days covered considered adherent to therapy. RESULTS: Pre-treatment median A1C was 6.8%. Post-treatment median A1C was 7.1%. The adherent group, >75%, was the only group notable for a decrease in A1C, with a median decrease of -0.2 (p = 0.0022). BMI improvement was associated with improved post-treatment A1C (p = 0.007). When controlling for BMI, age, and pre-treatment A1C, the >75% adherence group was associated with improved post-treatment A1C (p < 0.001). DISCUSSION: When controlling for all studied variables, testosterone adherence was associated with improved post-treatment A1C. The higher the initial A1C at the initiation of therapy, the higher the potential for lowering the patient's A1C with >75% adherence. Further, all groups showed some reduction in BMI, which may indicate that testosterone therapy may affect A1C independent of weight loss. CONCLUSION: Even when controlling for improved BMI, pre-treatment A1C, and age, testosterone positively impacted glycemic control in diabetes patients with hypogonadism, with the most benefit noted in those most adherent to therapy (>75%).

Bread making with sourdough and intact cereal and legume grains - effect on glycaemic index and glycaemic load.

The concept of glycaemic index (GI) has led to efforts to develop low-GI foods. Bread contributes around one-quarter of carbohydrate intake in the Swedish diet. In this study, we sought to develop low-GI bread prototypes and examined the effects of bread making on content of total dietary fibre (TDF) and resistant starch (RS). Five bread prototypes were made in a commercial bakery, using sourdough fermentation and intact cereal and legume kernels. Predicted (p-GI) and in vivo GI values were determined, and TDF and RS were quantified. The p-GI value of the five prototypes was between 56 and 68. The confirmed in vivo GI value was 65 and 67 for two of the breads. The TDF content (≥17%) was not affected by bread making, but RS content was increased by three-fold. All breads were categorised as medium-GI, but with low glycaemic load (GL).

Musa paradisiaca L. leaf and fruit peel hydroethanolic extracts improved the lipid profile, glycemic index and oxidative stress in nicotinamide/streptozotocin-induced diabetic rats.

This study aimed to assess antihyperlipidemic, cardiac and antioxidant effects as well as mode of actions of Musa paradisiaca (M. paradisiaca) leaf and fruit peel hydroethanolic extracts in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Experimental diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), 15 min after intraperitoneal injection of NA (120 mg/kg body weight). NA/STZ-induced diabetic rats were orally supplemented with M. paradisiaca leaf and fruit peel hydroethanolic extracts in a dose of 100 mg/kg body weight/day for 28 days. The treatment of NA/STZ-induced diabetic rats with M. paradisiaca leaf and fruit peel extracts significantly decreased the elevated fasting and post-prandial serum glucose, total cholesterol, triglycerides, LDL-cholesterol and vLDL-cholesterol levels and significantly increased the lowered serum insulin level, liver glycogen content, serum HDL-cholesterol level, homeostasis model assessment-insulin resistance (HOMA-IS) and HOMA-ß cell function. The elevated cardiovascular risk indices in diabetic rats were significantly improved due to treatment with M. paradisiaca extracts. Concomitant with the increase in liver glycogen content, the glucose-6-phosphatase activity significantly decreased reflecting the decrease in hepatic glucose output. The heart function was potentially ameliorated as manifested by decrease in the elevated serum creatine kinase-MB, lactate dehydrogenase and aspartate aminotransferase activities after treatments of diabetic rats with M. paradisiaca extracts. The elevated liver lipid peroxidation and the decline in liver glutathione content and superoxide dismutase, glutathione peroxidase and glutathione-S-transferase activities were significantly reversed by treatments. Thus, it can be concluded that M. paradisiaca leaf and fruit peel hydroethanolic extracts may have antihyperlipidemic and cardioprotective potentials in NA/STZ-induced diabetic rats. These effects may be mediated via improvements in the glycemic state, ß-cell function, tissue insulin sensitivity, and antioxidant defense mechanism.

Effects of the Daily Consumption of Stevia on Glucose Homeostasis, Body Weight, and Energy Intake: A Randomised Open-Label 12-Week Trial in Healthy Adults.

Stevia is a non-nutritive sweetener, providing sweet taste with no calories. This randomised, controlled, open-label 2-parallel arm trial examined the effects of daily stevia consumption on glycaemia in healthy adults. Secondary endpoints included body weight (BW) and energy intake (EI). Healthy participants (n = 28; aged 25 ± 5y, body mass index 21.2 ± 1.7 kg/m2) were randomised into either the stevia group (n = 14)-required to consume a stevia extract daily-or to the control group (n = 14). At weeks 0 and 12, the glucose and insulin responses to an oral glucose tolerance test were measured; BW and EI were assessed at weeks 0, 6, and 12. There was no significant difference in the glucose or insulin responses. There was a significant main effect of group on BW change (F(1,26) = 5.56, p = 0.026), as the stevia group maintained their weight as opposed to the control group (mean weight change at week 12: -0.22 kg, 95%CI [-0.96, 0.51] stevia group, +0.89 kg, 95%CI [0.16, 1.63] control group). The energy intake was significantly decreased between week 0 and 12 in the stevia group (p = 0.003), however no change was found in the control group (p = 0.973). Although not placebo-controlled, these results suggest that daily stevia consumption does not affect glycaemia in healthy individuals, but could aid in weight maintenance and the moderation of EI.

Effects of Cynara scolymus L. on glycemic indices:A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Cynara scolymus L. (common artichoke) and its products have been considered as potential phytotherapeutic agents for various conditions, such as cardiovascular, hepatic and gastric diseases, among others. Until now, the effects of artichoke and artichoke products administration on glycemic indices have not been sufficiently appraised. The present study evaluated the effects of artichoke and artichoke products administration on the glycemic indices. METHODS: Clinical trials were identified in the Cochrane Library, PubMed, Embase and Scopus databases; to infinity until 15 March 2020. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. RESULTS: Pooled analysis of nine Randomized controlled trials (RCTs), demonstrated that the administration of artichoke and artichoke products led to a significant reduced fasting blood sugar (FBS) (WMD: -5.28 mg/dl, 95 % CI: -8.95, -1.61; p = 0.005). However, other glycemic indeces including fasting insulin (WMD: -0.45 µIU/dL, 95 % CI: -1.14, 0.25; p = 0.20), HOMA-IR (MD: -0.25, 95 % CI: -0.57, 0.07; p = 0.12) or Hemoglobin A1c (HbA1c) (WMD: -0.09, 95 % CI: -0.20, 0.02; p = 0.09) did not alter after the administration of artichoke and artichoke products. A subgroup analysis comparing the kind of intervention, revealed that just the supplementation of artichoke and artichoke products, in a noco-supplementation form, was efficacy for the reduction of Homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.52, 95 % CI: -0.85, -0.19; p = 0.002). CONCLUSIONS: The supplementation of artichoke and artichoke products can significantly reduce the FBS concentrations in humans. Moreover, these outcomes suggested that just the supplementation of artichoke and artichoke products is more effective in the reduction of HOMA-IR levels than the co-supplementation form. However, additional clinical trials with longer study periods are necessitated to obtain a robust conclusion for producing new guidelines as part of a healthy diet.

Starch composition, glycemic indices, antioxidant properties and carbohydrate hydrolyzing enzymes activities of African star apple fruit parts.

BACKGROUND: African star apple (Chrysophyllum albidum) is a traditonal fruit, which is predominant in tropical regions with the fruit parts consumed by the populace and used in folklore to manage diabetes. However, the likely activity mechanism is still undetermined. The current study examined and compared the inhibitory abilities of African star apple fruit parts on selected key enzymes related to diabetes mellitus in the pancreas tissue of rat. METHODS: Inhibitory effect of aqueous extract (1:10 w/v) of African star apple fruit parts (pulp, cotyledon, seed coat and pulp coat) on the activities of α-amylase, α-glucosidase, as well as their starch composition, phenolic constituents, estimated glycemic index, and antioxidant properties were assessed. RESULTS: The fruit parts showed low sugar, eGI, amylose, and amylopectin contents. The analysis also showed that the fruit parts inhibited α-glucosidase and α-amylase activities and exhibited antioxidant properties. Furthermore, the fruit parts contain high concentrations of beta-amyrin acetate, eleagine, epicatechin, epigallocatechin, skatole, stigmasterol and tetrahydro - 2- methylharman as revealed by HPLC-DAD. CONCLUSION: The fruit part low estimated glycemic indices, strong antioxidant properties, inhibition of α-amylase and α-glucosidase activities exhibited might be related to the bioactive compounds contained in the extract. This could also be a potential mechanism for the use in the prevention and management of type-2 diabetes. Nevertheless, the African star apple pulp coat displayed the highest property in comparison to other parts of the fruit.

Effect of Varying Molecular Weight of Oat ß-Glucan Taken just before Eating on Postprandial Glycemic Response in Healthy Humans.

To see if the molecular weight (MW) and viscosity of oat ß-glucan (OBG) when taken before eating determine its effect on postprandial glycemic responses (PPRG), healthy overnight-fasted subjects (n = 16) were studied on eight separate occasions. Subjects consumed 200 mL water alone (Control) or with 4 g OBG varying in MW and viscosity followed, 2-3 min later, by 113 g white-bread. Blood was taken fasting and at 15, 30, 45, 60, 90, and 120 min after starting to eat. None of the OBG treatments differed significantly from the Control for the a-priori primary endpoint of glucose peak-rise or secondary endpoint of incremental area-under-the-curve (iAUC) over 0-120 min. However, significant differences from the Control were seen for glucose iAUC over 0-45 min and time to peak (TTP) glucose. Lower log(MW) and log(viscosity) were associated with higher iAUC 0-45 (p < 0.001) and shorter TTP (p < 0.001). We conclude that when 4 g OBG is taken as a preload, reducing MW does not affect glucose peak rise or iAUC0-120, but rather accelerates the rise in blood glucose and reduces the time it takes glucose to reach the peak. However, this is based on post-hoc calculation of iAUC0-45 and TTP and needs to be confirmed in a subsequent study.