Two weeks of acarbose treatment shows no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study.

Aim: The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D. Methods: Faecal samples were collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57-85 years, HbA1c 40-74 mmol/mol, BMI 23.6-34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a 6-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing. Results: The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (ß-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp. and Escherichia coli (P < 0.05) were observed after acarbose treatment. Conclusion: In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only minor effects on GM as seen in increased relative abundances of Klebsiella spp. and Escherichia coli.

Exploring chalcone-sulfonyl piperazine hybrids as anti-diabetes candidates: design, synthesis, biological evaluation, and molecular docking study.

To address the escalating rates of diabetes mellitus worldwide, there is a growing need for novel compounds. The demand for more affordable and efficient methods of managing diabetes is increasing due to the inevitable side effects associated with existing antidiabetic medications. In this present research, various chalcone-sulfonyl piperazine hybrid compounds (5a-k) were designed and synthesized to develop inhibitors against alpha-glucosidase and alpha-amylase. In addition, several spectroscopic methods, including FT-IR, 1H-NMR, 13C-NMR, and HRMS, were employed to confirm the exact structures of the synthesized derivatives. All synthesized compounds were evaluated for their ability to inhibit alpha-glucosidase and alpha-amylase in vitro using acarbose as the reference standard and they showed excellent to good inhibitory potentials. Compound 5k exhibited excellent inhibitory activity against alpha-glucosidase (IC50 = 0.31 ± 0.01 µM) and alpha-amylase (IC50 = 4.51 ± 1.15 µM), which is 27-fold more active against alpha-glucosidase and 7-fold more active against alpha-amylase compared to acarbose, which had IC50 values of 8.62 ± 1.66 µM for alpha-glucosidase and 30.97 ± 2.91 µM for alpha-amylase. It was discovered from the Lineweaver-Burk plot that 5k exhibited competitive inhibition against alpha-glucosidase. Furthermore, cytotoxicity screening assay results against human fibroblast HT1080 cells showed that all compounds had a good level of safety profile. To explore the binding interactions of the most potent compound (5k) with the active site of enzymes, molecular docking research was conducted, and the results obtained supported the experimental data.

Phytochemical Profile, Antioxidant, Enzyme Inhibition, Acute Toxicity, In Silico Molecular Docking and Dynamic Analysis of Apis Mellifera Propolis as Antidiabetic Supplement.

This study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti-diabetic activity through inhibition of α-amylase (α-AE), α-glucosidase(α-GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13 mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94 µg/ml). This study found that AMPE displayed promising α-AE and α-GE inhibition through in vitro study. Based on LC-MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α-AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α-GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7-Dihydroxy-1-(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene and 3(3-(3,4-Dihydroxybenzyl)-7-hydroxychroman-4-one as novel inhibitors of α-AE and α-GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100 ns simulations. The in vivo acute toxicity assay reveals AMPE as a practically non-toxic product with an LD50 value of 16,050 mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.

A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 µM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

Reactive hypoglycemia owing to an intrahepatic congenital portosystemic shunt in an older patient.

An 85-year-old woman was admitted to our hospital because of hypoglycemia and impairment of consciousness several hours after breakfast. Because the hypoglycemia predominantly occurred 2-4 h after meals, we diagnosed reactive hypoglycemia. An oral glucose tolerance test showed prolonged hyperinsulinemia following the postprandial hyperglycemia, with a subsequent rapid decrease in blood glucose concentration. The post-stimulus plasma C-peptide concentration was relatively low compared to the plasma insulin concentration. Abdominal computed tomography revealed an intrahepatic congenital portosystemic shunt (CPSS). On the basis of these findings, we concluded that the reactive hypoglycemia was induced by the CPSS, via a reduction in hepatic insulin extraction. Treatment with an alpha-glucosidase inhibitor resolved the reactive hypoglycemia. CPSS comprises anomalous vascular connections between the portal vein and the systemic venous circulation, and reactive hypoglycemia is a rare complication of this malformation, which has most frequently been reported in children, with only a few cases reported in adults. However, this case indicates that even in adult patients, imaging studies should be conducted to rule out CPSS as the cause of the reactive hyperglycemia.

Discovery of the new alpha-glucosidase inhibitor with therapeutic potential in type 2 diabetes mellitus by a novel high-throughput virtual screening and free energy evaluation.

Type 2 diabetes can cause a variety of complications, significantly affecting people's health. Given their ability to suppress carbohydrate digestion, alpha-glucosidase inhibitors are effective treatments for diabetes. However, the current approved glucosidase inhibitors' side effects of abdominal discomfort limit their use. We used the compound Pg3R from the natural fruit berry as a reference, screening against a large database of 22 million compounds to identify potential health-friendly alpha-glucosidase inhibitors. Ligand-based screening enables us to identify 3968 ligands that exhibit structural similarity compared to the natural compound. These lead hits were used for LeDock, and their binding free energies were evaluated by MM/GBSA. Among the top-scoring candidates, ZINC263584304 exhibited the strongest binding affinity to alpha-glucosidase, with a "low-fat" structural characteristic. Its recognition mechanism was further investigated by microsecond MD simulations and free energy landscapes, exhibiting novel conformational changes during the binding process. Our study provided a novel alpha-glucosidase inhibitor with the potential to treat type 2 diabetes.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

AIMS: The alpha-glucosidase inhibitor acarbose is an antidiabetic drug delaying assimilation of carbohydrates and, thus, increasing the amount of carbohydrates in the distal parts of the intestines, which in turn increases circulating levels of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1). As GLP-1 may suppress bone resorption, acarbose has been proposed to potentiate meal-induced suppression of bone resorption. We investigated the effect of acarbose treatment on postprandial bone resorption in patients with type 2 diabetes and used the GLP-1 receptor antagonist exendin(9-39)NH2 to disclose contributory effect of acarbose-induced GLP-1 secretion. METHODS: In a randomised, placebo-controlled, double-blind, crossover study, 15 participants with metformin-treated type 2 diabetes (2 women/13 men, age 71 (57-85 years), BMI 29.7 (23.6-34.6 kg/m2), HbA1c 48 (40-74 mmol/mol)/6.5 (5.8-11.6 %) (median and range)) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. At the end of each period, circulating bone formation and resorption markers were assessed during two randomised 4-h liquid mixed meal tests (MMT) with infusions of exendin(9-39)NH2 and saline, respectively. Glucagon-like peptide 2 (GLP-2) was also assessed. RESULTS: Compared to placebo, acarbose impaired the MMT-induced suppression of CTX as assessed by baseline-subtracted area under curve (P = 0.0037) and nadir of CTX (P = 0.0128). During acarbose treatment, exendin(9-39)NH2 infusion lowered nadir of CTX compared to saline (P = 0.0344). Neither parathyroid hormone or the bone formation marker procollagen 1 intact N-terminal propeptide were affected by acarbose or GLP-1 receptor antagonism. Acarbose treatment induced a greater postprandial GLP-2 response than placebo treatment (P = 0.0479) and exendin(9-39)NH2 infusion exacerbated this (P = 0.0002). CONCLUSIONS: In patients with type 2 diabetes, treatment with acarbose reduced postprandial suppression of bone resorption. Acarbose-induced GLP-1 secretion may contribute to this phenomenon as the impairment was partially reversed by GLP-1 receptor antagonism. Also, acarbose-induced reductions in other factors reducing bone resorption, e.g. glucose-dependent insulinotropic polypeptide, may contribute.

Production of α-glucosidase inhibitor in the intestines by Bacillus licheniformis.

We selected Bacillus licheniformis NY1505 by screening a strain capable of producing α-glucosidase inhibitors in both aerobic and anaerobic environments in vitro and spore formation. To confirm whether this strain proliferates in the intestine and produces α-glucosidase inhibitor, the spores of this strain were administered to mice orally. As the results, it was confirmed that 107 cells and about 300 units of α-glucosidase inhibitor per 1 g feces were excreted in the feces after three weeks of administration as spores. And after two weeks of stopping administration, Bacillus licheniformis NY1505 in the intestine are cleared. This means that Bacillus licheniformis NY1505 steadily proliferated in the intestine and produced α-glucosidase inhibitors and excreted in the feces. Also, it has an advantage in its use as it can easily eliminate Bacillus licheniformis NY1505 from the intestine. This method of ingesting only microorganisms is a more efficient and new method than the existing method of administering an α-glucosidase inhibitor that consumes a large amount of purified product. This method shows a process in which microorganisms capable of proliferating in the intestine directly produce and supply specific secondary metabolites in the intestine.

A cross-sectional study of the correlation between diabetic therapy and serum zinc concentrations.

AIM: Zinc, an essential trace element, has various functions in humans. Zinc deficiency is associated with the elderly, patients with diabetes, and patients with frailty, a common geriatric syndrome. As few studies have reported the effects of anti-diabetic medication on zinc levels, we examined serum zinc concentrations in patients with diabetes and their correlation with anti-diabetic medications, especially in the elderly and patients with frailty, in Japan. METHODS: This cross-sectional study was conducted in 2014 and included 1033 patients with diabetes. Blood samples were taken, and a survey for the 8-item Short Form Health Survey of the Medical Outcomes Study was conducted. RESULTS: Because of renal dysfunction (with an estimated glomerular filtration rate of < 60 mL/min/1.73 m2), 337 patients out of 1033 were excluded. Hypozincemia was observed in 43.8% of the patients with diabetes. In 177 elderly patients with a low physical component summary score, multivariable logistic regression analysis revealed two anti-diabetic medications associated with hypozincemia: GLP-1RA (multivariable-adjusted odds ratio [OR] 0.08, 95% confidence interval [CI] 0.010-0.657, p = 0.019) and metformin (OR 0.415, 95% CI 0.222-0.774, p = 0.006). In addition, metformin had a dose-dependent correlation with zinc levels (R = 0.3067, p < 0.0001). CONCLUSIONS: Oral administration of metformin in the elderly with diabetes and non-progressive renal dysfunction was not associated with hypozincemia, even at high doses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00521-6.

The 4-(dimethylaminoalkyl)piperazine inhibitors of α-glucosidase: allosteric enzyme inhibition and identification of interacting chemical groups.

In continuation of our interest in identifying new α-glucosidase inhibitors with potential to become antidiabetic drugs, this work focuses on the study of 4-(dimethylaminoalkyl)piperazine-1-carbodithioate derivatives as α-glucosidase inhibitors. The eight heterocyclic piperazine-dithiocarbamate complexes studied in this work contain a variety of substitutions on their benzene ring exhibiting potent, noncompetitive inhibition of α-glucosidase. Dithiocarbamate and piperazine moieties are important pharmacophores with promising therapeutic prospects featuring facilitated drug delivery due to their lipophilic nature in addition to their α-glucosidase inhibitory activity. Enzyme kinetics, molecular dynamics simulations, and docking studies revealed that the target compounds bind to a new allosteric site that is located near the active site of α-glucosidase. Majority of molecular interactions of the compounds with the enzyme are mediated by hydrophobic contacts in addition to a number of important polar interactions. The current work identifies a number of chemical groups in the compounds that are responsible for potent inhibition of α-glucosidase. Moreover, it also provides new insights into understanding α-glucosidase inhibition by dithiocarbamate and piperazine-containing compounds that can be promising for development of new antidiabetic drugs.

Management of Diabetes Mellitus in Patients With CKD: Core Curriculum 2022.

The most common cause of kidney failure in the United States and across the world is diabetes mellitus (DM). Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in persons with diabetes, and chronic kidney disease (CKD) further increases overall CVD risk. It is important to individualize glycemic targets for patients to maintain glucose levels that will reduce the development and progression of complications while avoiding hypoglycemia. CKD alters the relationship of glucose levels to measures of long-term control, such as hemoglobin A1c. Medications used to treat DM may need dose adjustments as CKD progresses. Some medications have particular characteristics in patients with CKD. Insulin and sulfonylureas increase the risk of hypoglycemia, some glucagon-like peptide 1 receptor agonists reduce the risk of CVD outcomes, and most sodium/glucose cotransporter 2 inhibitors reduce the risk of CKD and CVD outcomes. Therefore, for the individual patient, changes in medication types and doses may need constant attention as CKD progresses.

Clinical characteristics of patients with pneumatosis intestinalis.

BACKGROUND: Several theories explaining the development of pneumatosis intestinalis (PI) have been reported, but a substantial portion of cases have been idiopathic. Additionally, predictors of bowel ischaemia in PI have not been fully investigated, while PI with bowel ischaemia has deteriorated overall outcomes of PI. METHODS: Sixty-four patients diagnosed with PI (2009-2019) were allocated to two groups: with (group 1; n = 15 (23%)) and without (group 2; n = 49 (77%)) bowel ischaemia. Fourteen patients underwent emergency surgery, and bowel ischaemia was identified in nine (64%). Six patients in group 1 were diagnosed with bowel ischaemia, and were treated palliatively. On medical charts, we determined underlying conditions of PI, compared the characteristics and outcomes between the groups, and identified the predictors of bowel ischaemia. RESULTS: Group 1 patients more commonly showed abdominal pain, lower base excess, higher C-reactive protein concentrations, higher white blood cell counts and higher neutrophil-to-lymphocyte ratios, and more frequent comorbid ascites, free air and hepatic portal vein gas. Of nine bowel ischaemia surgery patients, three (33%) died; all because of anastomotic leak. All except three patients in group 2, who presented with aspiration pneumonia, responded to treatment. Only one patient had an unknown cause (1/64, 1.6%), and various underlying conditions in secondary PI were confirmed. CONCLUSION: Idiopathic PI may be identified rarely using current imaging and knowledge, but outcomes in PI patients with bowel ischaemia remain unsatisfactory. Earlier identification of bowel ischaemia by various specialists in accordance with predictors of bowel ischaemia could improve overall outcomes in PI patients.

Reduced postprandial bone resorption and greater rise in GLP-1 in overweight and obese individuals after an α-glucosidase inhibitor: a double-blinded randomized crossover trial.

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

Correction: Sartorius et al. "Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects" Nutrients 2019, 11, 1700.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.

Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice.

Type 2 diabetes mellitus and its related insulin resistance are known to increase the risk of cancer. Anti-diabetic agents can improve insulin resistance and may lead to the suppression of carcinogenesis. This study aimed to investigate the preventive effects of the alpha-glucosidase inhibitor voglibose on the development of azoxymethane-induced colorectal pre-neoplastic lesions in obese and diabetic C57BL/KsJ-db/db mice. The direct effects of voglibose on the proliferation of colorectal cancer cells were also evaluated. Mice were injected with azoxymethane to induce colorectal pre-malignancy and were then administered drinking water with or without voglibose. At the end of the study, the administration of voglibose significantly suppressed the development of colorectal neoplastic lesions. In voglibose-treated mice, serum glucose levels, oxidative stress, as well as mRNA expression of the insulin-like growth factor-1 in the colon mucosa, were reduced. The proliferation of human colorectal cancer cells was not altered by voglibose. These results suggested that voglibose suppressed colorectal carcinogenesis in a diabetes- and obesity-related colorectal cancer model, presumably by improving inflammation via the reduction of oxidative stress and suppressing of the insulin-like growth factor/insulin-like growth factor-1 receptor axis in the colonic mucosa.

Pneumatosis cystoides intestinalis induced by the alpha-glucosidase inhibitor complicated from sigmoid volvulus in a diabetic patient.

INTRODUCTION: We present the case of a diabetic patient on treatment with acarbose who had presented a sigmoid volvulus with localized cystic pneumatosis of the sigmoid colon. CASE REPORT: A 72-year-old patient with a medical history of atrial fibrillation, DNID in treatment since 10 years by acarbose. The patient was admitted to the emergency for abdominal pain and occlusive syndrome since 48 h without fever or nausea or vomiting. A CT scan was performed that showed a dolichocolon with a sigmoid volvulus. The colonic wall was thickening as well as submucosal and subserosal gas, without extra digestive air or collections. A rectosigmoidoscopy was achieving that showed a sigmoid volvulus with multiple small projections like a submucosa gas bubbles. A laparoscopic non-oncologic sigmoidectomy with primary termino terminal colorectal anastomosis was performed. During the surgical procedure, an aspect of PCI of the sigmoid colon was found. The sigmoid colon was long like a dolichocolon, dilated, and partially twisted. DISCUSSION: PCI is a rare condition characterized by the presence of multiple pneumokystes at different layers of the colonic wall. In emergency setting, the presence of colonic pneumatosis precludes the differential diagnosis between the PCI and mesenteric ischemia or ischemic colitis. It can be the cause of unnecessary explorative laparotomy. CONCLUSION: PCI is rare disease, in emergency setting, we had to consider in differential diagnosis with colonic vascular disorders.

Discovery of novel pyrido-pyrrolidine hybrid compounds as alpha-glucosidase inhibitors and alternative agent for control of type 1 diabetes.

A new library of pyrido-pyrrolidine hybrid compounds were designed, developed and screened for their antidiabetic property with α-glucosidase. The design is based on preliminary screening of key fragments identified from literature reported α-glucosidase inhibitors and antidiabetic compounds. The most active fragments were stitched to provide a pyrido-pyrrolidine hybrid molecule as a new motif. A library of these compounds were synthesized and screened against a series of α-glycosidases. Subsequently, compound 3k was the most efficacious analog with IC50 of 0.56 µM. Photoluminescence study and circular dichroism experiments indicated that compound 3k modulates the primary and secondary structure of the enzyme. It successfully brings down the fasting blood glucose level for streptozotocin (STZ, 70 mg/kg, Intraperitoneal) induced type I diabetic male Sprague-Dawley rats (250-320 g). At lower concentration, compound 3k slightly stimulates proliferation of BRIN-BD11 (α-glucose responsive beta cells from rat pancreas islets that secretes insulin) cells.

Alpha Glucosidase Inhibitory Activities of Plants with Focus on Common Vegetables.

Type-2 diabetes mellitus is one of the most prevalent metabolic diseases in the world, and is characterized by hyperglycemia (i.e., high levels of glucose in the blood). Alpha-glucosidases are enzymes in the digestive tract that hydrolyze carbohydrates into glucose. One strategy that has been developed to treat type-2 diabetes is inhibition of the activity of alpha-glucosidases using synthetic drugs. However, these inhibitors are usually associated with gastrointestinal side effects. Therefore, the development of inhibitors from natural products offers an alternative option for the control of hyperglycemia. In recent years, various studies have been conducted to identify alpha-glucosidases inhibitors from natural sources such as plants, and many candidates have transpired to be secondary metabolites including alkaloids, flavonoids, phenols, and terpenoids. In this review, we focus on the alpha-glucosidases inhibitors found in common vegetable crops and the major classes of phytochemicals responsible for the inhibitory activity, and also as potential/natural drug candidates for the treatment of type-2 diabetes mellitus. In addition, possible breeding strategies for production of improved vegetable crops with higher content of the inhibitors are also described.

Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes.

BACKGROUND: Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. METHODS: We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. RESULTS: Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67-0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89-1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. CONCLUSIONS: Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.

Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.