Control Of Postprandial Hyperglycemia Research Articles

Diphenolic boldine, an aporphine alkaloid: inhibitory effect evaluation on α-glucosidase by molecular dynamics integrating enzyme kinetics

Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase. A series of inhibition kinetics and spectrometry detections were conducted to analyze the α-glucosidase inhibition. Computational simulations of molecular dynamics/docking analyses were conducted to detect boldine docking sites’ details and evaluate the key binding residues. Boldine displayed a typical reversible and mixed-type inhibition manner. Measurements of circular dichroism and fluorescence spectrum showed boldine changed the secondary structure and loosened the tertiary conformation of target α-glucosidase. The computational molecular dynamics showed that boldine could block the active pocket site through close interaction with binding key residues, and two phenolic hydroxyl groups of boldine play a core function in α-glucosidase inhibition via ligand binding. This investigation reveals the boldine function on interaction with the α-glucosidase active site, which provides a new inhibitor candidate. Communicated by Ramaswamy H. Sarma

Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo.

In the context of the growing prevalence of type 2 diabetes (T2DM), control of postprandial hyperglycemia is crucial for its prevention. Blood glucose levels are determined by various factors including carbohydrate hydrolyzing enzymes, the incretin system and glucose transporters. Furthermore, inflammatory markers are recognized predictors of diabetes outcome. Although there is some evidence that isoflavones may exhibit anti-diabetic properties, little is known about to what extent their corresponding hydroxylated metabolites may affect glucose metabolism. We evaluated the ability of a soy extract before (pre-) and after (post-) fermentation to counteract hyperglycemia in vitro and in Drosophila melanogaster in vivo. Fermentation with Aspergillus sp. JCM22299 led to an enrichment of hydroxy-isoflavones (HI), including 8-hydroxygenistein, 8-hydroxyglycitein and 8-hydroxydaidzein, accompanied by an enhanced free radical scavenging activity. This HI-rich extract demonstrated inhibitory activity towards α-glucosidase and a reduction of dipeptidyl peptidase-4 enzyme activity. Both the pre- and post-fermented extracts significantly inhibited the glucose transport via sodium-dependent glucose transporter 1. Furthermore, the soy extracts reduced c-reactive protein mRNA and secreted protein levels in interleukin-stimulated Hep B3 cells. Finally, supplementation of a high-starch D. melanogaster diet with post-fermented HI-rich extract decreased the triacylglyceride content of female fruit flies, confirming its anti-diabetic properties in an in vivo model.

Recent Updates on Phytoconstituent Alpha-Glucosidase Inhibitors: An Approach towards the Treatment of Type Two Diabetes.

Diabetes is a common metabolic disorder marked by unusually high plasma glucose levels, which can lead to serious consequences such as retinopathy, diabetic neuropathy and cardiovascular disease. One of the most efficient ways to reduce postprandial hyperglycemia (PPHG) in diabetes mellitus, especially insulin-independent diabetes mellitus, is to lower the amount of glucose that is absorbed by inhibiting carbohydrate hydrolyzing enzymes in the digestive system, such as α-glucosidase and α-amylase. α-Glucosidase is a crucial enzyme that catalyzes the final stage of carbohydrate digestion. As a result, α-glucosidase inhibitors can slow D-glucose release from complex carbohydrates and delay glucose absorption, resulting in lower postprandial plasma glucose levels and control of PPHG. Many attempts have been made in recent years to uncover efficient α-glucosidase inhibitors from natural sources to build a physiologic functional diet or lead compound for diabetes treatment. Many phytoconstituent α-glucosidase inhibitors have been identified from plants, including alkaloids, flavonoids, anthocyanins, terpenoids, phenolic compounds, glycosides and others. The current review focuses on the most recent updates on different traditional/medicinal plant extracts and isolated compounds’ biological activity that can help in the development of potent therapeutic medications with greater efficacy and safety for the treatment of type 2 diabetes or to avoid PPHG. For this purpose, we provide a summary of the latest scientific literature findings on plant extracts as well as plant-derived bioactive compounds as potential α-glucosidase inhibitors with hypoglycemic effects. Moreover, the review elucidates structural insights of the key drug target, α-glucosidase enzymes, and its interaction with different inhibitors.

Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives

The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a–p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6–287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.

Glycemic control after switching to faster aspart in adults with type 1 diabetes

AimsPost-prandial hyperglycemia remains an unmet need in the management of type 1 diabetes (T1D). In randomized trials, faster insulin aspart (FIA) showed modest but significant reductions of glycemic spikes after meals. Whether such benefit is evident in routine clinical practice is unclear.MethodsWe analyzed data of patients with T1D at the time they switched from a prior bolus insulin to FIA and at the first available follow-up. The primary endpoint was the change in the time spent in hyperglycemia > 250 mg/dl during daytime from flash glucose monitoring (FGM). Secondary outcomes included the change in HbA1c, body weight, insulin dose and other FGM metrics.ResultsWe included 117 patients with T1D on multiple daily injections who switched to FIA, 57 of whom had data from FGM. Patients were 41-year-old, 51.3% men, with 19.3 years diabetes duration and a baseline HbA1c of 7.7% (60 mmol/mol). Mean observation time was 4.3 months. After switching to FIA, HbA1c declined by 0.1% (1 mmol/mol) only in patients with baseline HbA1c > 7.0% (53 mmol/mol). Time spent in hyperglycemia > 250 mg/dl during daytime was significantly reduced from 14.8 to 11.9% (p = 0.006). Time in range improved from 48.3 to 51.0% (p = 0.028). Results were consistent across various patient characteristics.ConclusionsUnder routine care, patients with T1D who switched to FIA experienced a reduction in the time spent in hyperglycemia > 250 mg/dl during daytime and an increase in time in range. These improvements may be due to better control of post-prandial hyperglycemia, as observed in trials.

Ganyong-kelor snack bar's glycemic index as a diet for diabetics

Background: Lack of insulin or the inability of cells to respond to insulin causes high blood glucose levels or hyperglycemia, a hallmark of diabetes. Consumption of foods with a low glycemic index and high fiber has been shown to provide the same benefits as pharmacological therapy in the control of postprandial hyperglycemia and can prevent the incidence of hypoglycemia in people with diabetes. Ganyong (Canna edulis) is a food source of carbohydrates and fiber. Kelor (Moringa oliefera) contains protein and some phytochemical compounds which have a hypoglycemic effect.Objectives: The objective of the study was to analyze the glycemic index of ganyong-kelor snack bars as a diet for diabetics.Materials and Methods: Ten respondents fasted for 10 hours and checked their fasting blood glucose levels, then consumed 105 grams of bread as the reference food. Every 30 minutes after eating, the blood glucose levels were checked. In the following week, after fasted, all respondents consumed 157 grams of a ganyong-kelor snack bar and checked their blood glucose levels every 30 minutes.Results: Every 100 grams of ganyong-kelor snack bar contains 230.13 kcal, 31.97 grams of carbohydrates, 9.25 grams of fat, and 4.75 grams of protein. In this study, bread was used as a reference food. If bread was corrected with glucose as a reference food, the glycemic index of the ganyong-kelor snack bar was 38.08. The calculation of the glycemic load used the converted-glycemic index and the total carbohydrates contained in 100 grams of the food. Ganyong-kelor snack bar had a glycemic load value of 12.10.Conclusions: Ganyong-kelor snack bar had good nutritional content and was categorized as food with a low glycemic index. The hypoglycemic effect of the ganyong-kelor snack bar came from its high fiber content. Ganyong-kelor snack bar can be consumed as a healthy snack for diabetic people.

Structure-Activity Relationship Study of Acyclic Terpenes in Blood Glucose Levels: Potential α-Glucosidase and Sodium Glucose Cotransporter (SGLT-1) Inhibitors.

Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an -glucosidase inhibitory effect and the second with an inhibition of the sodium–glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.

Antihyperglycemic activity of the leaves from annona diversifolia Safford. and farnesol on normal and alloxan-induced diabetic mice*

Background: Diabetes mellitus (DM) is a chronic disease characterized by high blood glucose levels resulting from insulin resistance or inadequate insulin secretion. In the world, DM is one of the most frequent non-contagious diseases that affect more than 371 million people. Objective: This study aimed to evaluate the antihyperglycemic properties of the ethanol extract, subsequent fractions, and farnesol obtained from the leaves of Annona diversifolia on alloxan-induced diabetic and normal mice. Materials and Methods: Bioassay-guided fractionation of the ethanol extract of the leaves of A. diversifolia (EELAd) was performed on alloxan-induced Type 2 diabetic and normoglycemic (NM) mice. Oral glucose tolerance test (OGTT), oral sucrose tolerance test (OSTT), and oral lactose tolerance test (OLTT) were performed in fast NM mice (FNM). Results: The EELAd, CHCl3 fraction, and farnesol induced a significant reduction of postprandial hyperglycemia in acute and subchronic tests using AITD mice. When EELAd, CHCl3 fraction, and farnesol were tested on NM in subchronic assays, these did not affect glycemic levels. In the case of acute test on NM, only CHCl3 fraction induced a hypoglycemic effect at 2 h after the treatment. OLTT and OSTT showed that the EELAd, CHCl3 fraction, and farnesol induced a significant reduction of hyperglycemia levels in FNM at 2 h after a lactose or sucrose load comparable to acarbose. In the case of OGTT was observed a significant reduction of hyperglycemia levels in FNM mice at 2 h after a glucose load comparable to canagliflozin. Conclusion: The EELAd and farnesol induced a significant reduction of postprandial hyperglycemia on AITD mice in acute and subchronic assays. Our results suggest that the control of postprandial hyperglycemia may be mediated by the regulation of absorption of glucose and inhibition of disaccharide digestion such as sucrose and lactose. Finally, the results explained the use of A. diversifolia in Mexican traditional medicine as an antihyperglycemic agent.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes in Asia

The improvement of glycemic control in patients with type 2 diabetes (T2D) is an urgent need in Asia. East Asian T2D patients have distinct characteristics, including relatively low body weight, early impairment of islet beta cell function with reduced insulin secretion and a marked increase in postprandial blood glucose levels. Control of postprandial hyperglycemia and beta cell preservation are key elements of the therapeutic strategy for these patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce HbA1c, fasting plasma glucose, and (in particular) postprandial glucose levels, and slow gastric emptying, while minimizing the risk of hypoglycemia and weight gain. Compared with long-acting GLP-1RAs, short-acting GLP-1RAs produce greater slowing of gastric emptying (which is a key factor driving the reduction of postprandial glycemia) and induce beta cell rest rather than promoting postprandial insulin secretion when used under physiological conditions. GLP-1RAs have greater efficacy in Asian than Caucasian patients. GLP-1RA add-on therapy provides clinically meaningful reductions in HbA1c and postprandial glucose in Asians with T2D inadequately controlled by oral antidiabetic drugs (OADs) or basal insulin ± OADs. Premixed insulin is often prescribed for T2D patients in China. A short-acting GLP-1RA plus basal insulin is an alternative to premixed insulin, resulting in better efficacy and a lower risk of hypoglycemia and weight gain. In conclusion, GLP-1RAs, especially short-acting GLP-1RAs, are a practical treatment option for East Asian patients with T2D inadequately controlled by OADs or basal insulin.Funding: Sanofi.

Efficacy of Alpha Glucosidase Inhibitor from Marine Actinobacterium in the Control of Postprandial Hyperglycaemia in Streptozotocin (STZ) Induced Diabetic Male Albino Wister Rats.

The current study was carried out to evaluate the in-vitro and in-vivo efficiency of alpha glucosidase inhibitor of marine actinobacteria in the control of postprandial hyperglycaemia. Soil samples were collected from salterns, coastal area in Kothapatnam, Ongole, Andhra Pradesh, India. Among the actinobacterial isolates tested for yeastα-glucosidase inhibitory activity, only three isolates showed prominent inhibition. The patient isolate was selected and identified as Streptomyces coelicoflavus SRBVIT13 using 16S r-RNA gene sequencing. In in-vitro studies, the chloroform extract of Streptomyces coelicoflavus SRBVIT13 showed significant enzyme inhibitory activity against yeast and mammalian α-glucosidaseenzymes. In animal studies, the oral ingestion of chloroform extract (600 mg/kg) of S. coelicoflavus SRBVIT13 in maltose and sucrose loaded diabetic rats, showed significant regulation of postprandial blood glucose by 82.25% and a 77.25% reduction, respectively. The lead compound from S. coelicoflavusSRBVIT13 was isolated, purified, characterized, and identified by stranded analytical techniques as 2-t-butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine-1-carboxylic acid, t-butyl ester. The results obtained in the present study are promising and the bioactive compound from S. coelicoflavusSRBVIT13 may be considered as a potential agent in regulating the postprandial hyperglycaemia.

α-Amylase Modulation: Discovery of Inhibitors Using a Multi-Pharmacophore Approach for Virtual Screening.

Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type II diabetes and obesity. In this study, a rational computer-aided approach was developed to identify novel α-amylase inhibitors. Three-dimensional pharmacophores were developed based on the binding mode analysis of six different families of compounds that bind to this enzyme. In a stepwise virtual screening workflow, seven molecules were selected from a library of 1.4 million. Five out of seven biologically tested compounds showed α-amylase inhibition, and the two most potent compounds inhibited α-amylase with IC50 values of 17 and 27 μm. The scaffold benzylideneacetohydrazide was shared by four of the discovered inhibitors, emerging as a novel drug-like non-carbohydrate fragment and constituting a promising lead scaffold for α-amylase inhibition.

Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

This work investigates the role of oleanolic acid (OA), isolated from the olive ( Olea europaea L.) leaf, as a radical scavenger and inhibitor of the hydrolyzing enzymes of dietary carbohydrates. New evidence is provided showing that OA may capture 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) and peroxyl radicals, and also exert a strong and non -competitive inhibition of α-glucosidase (IC 50 10.11 ± 0.30 μM). The kinetic and spectrometric analyses performed indicate that OA interacts with this enzyme inside a hydrophobic pocket, through an endothermic and non spontaneous process of a hydrophobic nature. These are two possible mechanisms by which OA may facilitate a better control of post-prandial hyperglycaemia and oxidative stress, so contributing to preserving insulin signalling. Obesity, insulin resistance and Type 2 Diabetes Mellitus are considered the first pandemics of the 21st century. In this sense, OA might be used in future preventive and therapeutic strategies, as an ingredient in new drugs and functional foods.

In vivo antihyperglycemic activity of a lanosteryl triterpene from Protorhus longifolia.

Control of postprandial hyperglycemia is crucial in the management of diabetes mellitus. Despite the use of the current hypoglycemic drugs, incidence of diabetes and related diseases continue to increase. This study aimed at evaluating the in vivo antihyperglycemic activity of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), a lanosteryl triterpene isolated, and characterized from Protorhus longifolia stem bark. Spectroscopic data analysis was used to establish and verify the structure of the triterpene. The antihyperglycemic activity of the triterpene was evaluated in an STZ-induced diabetes rat model. The experimental animals were orally administered with RA-3 (100 mg/kg body weight) daily for 14 days. An oral glucose tolerance test was also performed. The animals were euthanized and biochemical analysis of antioxidant status, some glycolytic enzymes and glycogen content were conducted on serum and liver samples, respectively. RA-3 exhibited hypoglycemic activity by reducing blood glucose levels by 37%. The triterpene also improved glucose tolerance in the diabetic rats. Relatively higher hepatic glycogen content, hexokinase and glucokinase activity with a decrease in glucose-6-phosphatase activity were observed in the triterpene-treated diabetic group when compared with the diabetic control group. The triterpene treatment further increased antioxidant status of the diabetic animals; increased activity of superoxide dismutase and catalase were observed along with a decrease in malondialdehyde content. The results indicate potential pharmaceutical effects of lanosteryl triterpene in the management of diabetes mellitus.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats.

BackgroundThe fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects.AimAbove mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats.MethodsTreated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests.Resultsd-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue.ConclusionOur findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and hyperglycemia with the preservation of β-cells in the progression of T2DM.

Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus.

Targets for Glycemic Control

Targets for Glycemic Control

Tighter control of postprandial hyperglycemia with mitiglinide/voglibose fixed-dose combination in Japanese patients with type 2 diabetes mellitus

Objective: The objective of this study was to compare the effects of mitiglinide, voglibose and its combination on metabolic responses after a test meal in Japanese patients with type 2 diabetes mellitus (T2DM).Research design and methods: This randomized crossover study consisted of four periods between August and November 2011. In the first period, all patients (n = 12) received water alone (control period). In the next three periods, the patients received 10 mg mitiglinide, 0.2 mg voglibose or a combination in a random order.Main outcome measures: Postprandial metabolite/hormone levels were then measured.Results: Plasma glucose and serum insulin reached peak levels by 60 – 90 and 90 min, respectively, after the test meal in the control group. The combination reduced postprandial glucose levels compared with mitiglinide or voglibose alone, particularly at 30 – 90 min, which significantly exceeded the effects of mitiglinide (p < 0.05). Mitiglinide and the combination restored early insulin response, whereas the combination provided an insulin-sparing effect compared with mitiglinide alone. The combination improved postprandial lipid profiles, combining the effects of both drugs.Conclusion: This study revealed marked differences in the postprandial metabolic effects of mitiglinide, voglibose and its combination in patients with T2DM. The combination therapy should enable tighter control of postprandial hyperglycemia compared with the individual drugs.

Fucoidan regulate blood glucose homeostasis in C57BL/KSJ m+/+db and C57BL/KSJ db/db mice

Type 2 diabetes mellitus is a multisystem disease that is characterized by hyperglycemia and is associated with the dysfunction and failure of various organs. The control of postprandial hyperglycemia is important in the prevention and intervention of type 2 diabetes. Fucoidan has several biological activities in vitro and in vivo. However, the effect of fucoidan on hyperglycemia in non-diabetic and diabetic mice has not been investigated. This study was undertaken to study the effects of different molecular weight forms (5kilodalton (k), 5–30k and crude) of fucoidan on oral glucose tolerance tests in non-diabetic mice and on food intake, weight gain, fasting blood glucose and blood biochemistry of db/db mice. Treatment with 200mg/mL 5k, 5–30k and crude fucoidan substantially prevented hyperglycemia according to oral glucose tolerance tests in non-diabetic mice. In addition, fucoidan fractions significantly reduced blood glucose levels in diabetic mice.

Effective and safe control of glycemia with insulin Apidra - the recipe for success of type 2 diabetes prophylaxis

Current possibilities for the use of ultra-short acting insulin analogs are discussed. The importance of control of postprandial hyperglycemia is emphasized.Pharmacological properties of insulin glulisine are described with special reference to its advantage over human ultra-short acting insulin.An important characteristic of glulisine is the possibility of its efficacious use for the treatment of obese patients. The results of GINGER and CHOinternational studies suggest high efficacy and safety of glulisine used for intensive insulin therapy according to both flexible and fixed regimens.