Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.
Health scenarios are constantly evolving, particularly in developing countries but little is known regarding the health status of indigenous groups in Malaysia. This study aims to elucidate the current health status in four indigenous populations in the country, who by and large been left out of mainstream healthcare developments.
Gestational diabetes (GD) is a common complication during pregnancy. Metabolic changes in GD affect fetal development and fetal glucose homeostasis. The present study utilized a rat model of GD to evaluate the effects of nicotinamide on diabetic parameters; antioxidant gene expression viz, superoxide dismutase (SOD) and catalase (CAT); reactive oxygen species (ROS) production by neutrophils and enhancement of lymphocyte mediated immune response. Nicotinamide (50, 100 and 200 mg/kg) was orally supplemented to gestational diabetic rats from days 6 through 20 of gestation. After GD induction, the control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes. The same doses of nicotinamide upregulated mRNA expressions of SOD and CAT genes in liver but reduced the oxidative burst activity of neutrophils in response to phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP) or E. coli activation. Nicotinamide (100 & 200 mg/kg) supplementation also increased expression of activated T helper (CD4+CD25+) cells and induced proliferation of splenocytes. These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.
The relationship of high and low molecular weight mannuronic acid (M)- and guluronic acid (G)-rich alginate nanoparticles as oral insulin carrier was elucidated. Nanoparticles were prepared through ionotropic gelation using Ca(2+) , and then in vitro physicochemical attributes and in vivo antidiabetic characteristics were examined. The alginate nanoparticles had insulin release retarded when the matrices had high alginate-to-insulin ratio or strong alginate-insulin interaction via OH moiety. High molecular weight M-rich alginate nanoparticles were characterized by assemblies of long polymer chains that enabled insulin encapsulation with weaker polymer-drug interaction than nanoparticles prepared from other alginate grades. They were able to encapsulate and yet release and have insulin absorbed into systemic circulation, thereby lowering rat blood glucose. High molecular weight G- and low molecular weight M-rich alginate nanoparticles showed remarkable polymer-insulin interaction. This retarded the drug release and negated its absorption. Blood glucose lowering was, however, demonstrated in vivo with insulin-free matrices of these nanoparticles because of the strong alginate-glucose binding that led to intestinal glucose retention. Alginate nanoparticles can be used as oral insulin carrier or glucose binder in the treatment of diabetes as a function of its chemical composition. High molecular weight M-rich alginate nanoparticles are a suitable vehicle for future development into oral insulin carrier.
BACKGROUND: We evaluated glycaemic response of a brown rice variant (BR) developed by cross-breeding. Subjects (n = 9) consumed 50 g carbohydrate equivalents of BR, white rice (WR) and the polished brown rice (PR) in comparison to 50 g glucose reference (GLU) in a cross-over design. Plasma glucose and insulin at 0, 15, 45, 60, 90, 120 and 180 min were measured and incremental area under the curve (IAUC) and indices for glucose (GI) and insulin (II) calculated.
RESULTS: BR compared to PR or WR produced the lowest postprandial glycaemia (GI: 51 vs 79 vs 86) and insulinaemia (II: 39 vs 63 vs 68) irrespective of amylose content (19 vs 23 vs 26.5%). Only BR was significantly different from GLU for both plasma glucose (P = 0.012) and insulin (P = 0.013) as well as IAUC(glu) (P = 0.045) and IAUC(ins) (P = 0.031). Glycaemic and insulinaemic responses correlated positively (r = 0.550, P < 0.001). Linear trends for IAUC(glu) and IAUC(ins) indicated a greater secretion of insulin tied in with a greater glycaemic response for WR (r(2) = 0.848), moderate for PR (r(2) = 0.302) and weakest for BR (r(2) = 0.122).
CONCLUSION: The brown rice variant had the lowest GI and II values but these advantages were lost with polishing.
Carum carvi L. (Apiaceae) is known as caraway, and its derivatives find wide medicinal use for health purposes, including for gastrointestinal problems and obesity. Since there is inconsistency among the reports on the safety of this plant in humans, this research was aimed at assessing the safety of a characterized caraway aqueous extract (CAE) in a randomized, triple-blind, placebo-controlled study. Seventy, overweight and obese, healthy women were randomly assigned into placebo (n = 35) and plant extract (n = 35) groups. Participants received either 30 ml/day of CAE or placebo. Subjects were examined at baseline and after 12 weeks for changes in heart rate, blood pressure, urine test, 25-item blood chemistries, and general health status. No significant changes of blood pressure, heart rate, urine specific gravity, and serum blood tests were observed between the two groups before and after treatment. However, in the complete blood count test, red blood cell levels were significantly (p
A survey was done to determine the prevalence of diabetes mellitus, hypertension and renal disease, as well as extent of diabetic control, amongst the workers of Malaysian Railways. The prevalence of diabetes was high at 6.6%, with 3.8% of these being insulin dependent diabetes. The highest prevalence was in Indians (16.0%) followed by Chinese (4.9%) and Malays (3.0%). Using HbA1 measurements, diabetic control was poor in 70.6% of the diabetics. Hypertension was found in 37% and proteinuria in 35%. Renal impairment was present in 30% of the diabetics. This survey shows that diabetes, hypertension and renal disease are high amongst the railway workers in Malaysia.
The paper presents the results of a health screening programme conducted in 10 major centers in Malaysia--Kuala Lumpur, Penang, Ipoh, Johor Bahru, Alor Star, Kuala Terengganu, Malacca, Kota Bahru, Kuching and Kota Kinabalu during the National Heart Weeks, 1995-1997. There were 6,858 participants of both sexes aged between 6 years to 81 years old. The parameters involved in the screening programme were body mass index, blood pressure, heart rate, cholesterol and glucose. The following are the results of the study:- 1. The mean and standard deviation for the body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), total cholesterol (TC) and non fasting (random) blood glucose (GL) of the volunteers studied were 24.3 +/- 4.0 kg/m2, 128.3 +/- 21.1 mmHg, 79.6 +/- 11.9 mmHg, 77.2 +/- 12.1 bpm, 5.33 +/- 1.37 mmol/l and 5.11 +/- 1.97 mmol/l respectively. 2. There was a rising trend for BMI, SBP, DBP, TC and GL with age. The HR was higher in the younger age group of those below 20 years. Males tended to have higher mean values than females except for HR which was similar in both sexes. 3. The Malays, Chinese and Indians seemed to have closely similar mean values for SBP, DBP and HR but the Indians possessed the highest BMI (25.62 +/- 3.90 kg/m2), TC (5.61 +/- 1.48 mmol/l) and GL (5.41 +/- 2.43 mmol/l) among the three major ethnic groups. While the Ibans had highest TC (6.07 + 1.09 mmol/l), their GL level was the lowest (4.76 +/- 1.15 mmol/l). The Kadazans had the lowest TC level (4.94 +/- 1.39 mmol/l) among all the ethnic groups. 4. Among the participants screened, 31.9% were overweight (BMI > or = 25), 7.6% were obese (BMI > or = 30); 26.8% had raised SBP (> or = 140 mmHg) and 19.3% had raised DBP (> or = 90 mmHg); 13.6% of the participants had increased HR (> or = 90 bpm), 22% had raised TC (> or = 6.20 mmol/l) and 2% had raised GL (> or = 11.00 mmol/l). There was a higher prevalence for abnormal values with increasing age until between the ages of 60 or 70 years, when the values began to fall. 5. Age was positively correlated with SBP (r = 0.41***, df = 4351), DBP (r = 0.27***, df = 4351), TC (r = 0.22***, df = 3303) and GL (r = 0.16***, df = 2442) but negatively correlated with HR (r = -0.13***, df = 4351). The BMI was positively correlated with SBP (r = 0.29***, df = 2769), DBP (r = 0.31***, df = 2769), TC (r = 0.16***, df = 2137) and GL (r = 0.11**, df = 1637) but there was no correlation with HR (r = 0.03NS, df = 2771). The SBP and DBP were highly correlated with each other (r = 0.75***, df = 4351) and they also showed highly significant positive correlation (r = 0.08***-0.13***, df = 2441-3301) with TC and GL. TC was positively correlated with GL (r = 0.05* df = 2319) but only at the 5% probability level.
Background: Tetrapleura tetraptera, a seasoning and nutritive spice is also used in western African folk medicine in the management of wide variety of diseases including diabetes, inflammation and hypertension. Flavonoids and saponins are some abundant secondary metabolic constituents in the fruits of this plant. This study aimed at evaluating the potential therapeutic action of the polyphenol-rich hydroethanolic extract (HET) of this fruit in experimentally induced obese and type 2 diabetic rats (T2DM) with characteristic metabolic syndrome (MetS).
Methods: MetS was induced in rats by high-carbohydrate, high-fat diet and administration of low-dose streptozotocin. Then different oral doses of HET (200 and 400 mg/kg) were administered to T2DM rats for 28 days. A standard antidiabetic drug, metformin (300 mg/kg), was used for comparison. The body weight, systolic blood pressure, oxidative stress and metabolic parameters were then assessed to evaluate the effect of HET on MetS.
Results: HET reduced weight gain, fasting blood glucose and plasma insulin levels as well as homeostasis model assessment of insulin resistance (HOMA-IR) and alleviated obesity and T2DM associated oxidative stress and hypertension in rats. Moreover, a significantly hypolipidemic property and an attenuation of liver injury and tissue steatosis was observed after HET administration. HET further demonstrated its anti-inflammation effect via down regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), leptin and an increase in adiponectin. The HET exhibited dose-dependent effects which were comparable to that of metformin.
Conclusions: The present study thereby demonstrates the anti-insulin resistance, antilipidemic, anti-obesity, hypotensive and anti-inflammatory properties of HET; hence it has the potential to be further developed for the management of MetS such as obesity, T2DM and hypertension.
Aims: Increased oxidative stress and oxidative damage are present in Type 2 diabetes mellitus (DM). The aim of this study was to assess the oxidative stress levels in the three major ethnic groups in Malaysia and to study the association between glycaemic control and oxidant-antioxidant levels in these patients.
Methods: Oxidative indices and glycaemic control were assessed in 650 Type 2 DM patients and 280 healthy age-matched controls by known established methods.
Results: Type 2 DM patients had significantly lower levels of antioxidant enzymes and non-enzymatic antioxidant (FRAP) and increased levels of HbA(1c), fasting blood glucose (FBG), malondialdehyde (MDA) and xanthine oxidase (XO) when compared with control subjects. Markers of oxidative stress were more apparent in Indian patients compared with Malay and Chinese patients. Correlation analysis of oxidant-antioxidant parameters as a function of HbA(1c) in each ethnic group revealed a strong association of HbA(1c) with oxidative indices.
Conclusions: The present study provides evidence for the possible contribution of XO to oxidative stress and the pathophysiology of diabetes. HbA(1c) remains an important marker of glycaemic control for the management of Type 2 DM, but other confounding factors that predispose or lead to oxidative stress should also be taken into consideration.
The effect of Ramadan fasting on fasting serum glucose (FPG) is still a matter of controversy. One hundred and fifteen healthy volunteers fasted for > or = 25 days during Ramadan. Blood samples were taken 1 week before Ramadan and on the 14th and 28th day of Ramadan. Serum glucose was determined by the glucose oxidase method. FPG decreased from 88.4 + 9.0 mg/dl to 62.9 +/- 7.7 mg/dl (p < 0.001). Men and women both experienced a significant drop in FPG. Calorie intake decreased in all groups (p < 0.001) and was positively correlated with decreasing FPG. FPG decreases with Ramadan fasting and has no serious adverse effect on fasting adults.
We determined the impact of a remote blood glucose telemonitoring program with feedback in type 2 diabetes mellitus patients fasting during Ramadan compared to conventional self-monitoring method. A twelve-week cluster randomised study, with 85 participants who wish to fast for at least 15 days during Ramadan was conducted. Self-measurement and transmission of blood glucose results were performed six times daily during Ramadan. Results were transmitted to a secure website for review with feedback from case manager if necessary. The control group received usual care. The main outcome was the number of participants experiencing hypoglycaemia during Ramadan and at the end of the study. During Ramadan, the number of participants reporting hypoglycaemia was significantly lower in the telemonitoring group [Odds ratio (OR): 0.186, 95% confidence interval: 0.04-0.936; p = 0.04]. Similarly, the proportion of participants reporting symptomatic hypoglycaemia at the end of the study was significantly lower in the telemonitoring group (OR: 0.257, 95% CI: 0.07-0.89; p = 0.03). A reduction of 1.07% in glycated haemoglobin levels was observed in the telemonitoring group compared to 0.24% in the control group (p
One of the most common types of adulteration of honey involves the addition of invert sugar syrups. A new method was developed to measure the stable isotope ratios of carbon and carbon-bound non-exchangeable (CBNE) hydrogen from specific molecular positions in fructose and glucose in honey. This was achieved through periodate oxidation of the sugars to produce formaldehyde, followed by reaction with ammonia to form hexamethylenetetramine (HMT). The preparation was simplified, optimized, and validated by isotopic analysis of replicate syntheses of HMT from fructose, glucose, sugar syrup and a representative authentic honey sample. The optimized method had a repeatability standard deviation from 1.5‰ to 3.0‰ and from 0.1‰ to 0.4‰ for δ2H and δ13C, respectively. This methodology has advantages over alternative isotopic methods, for measuring CBNE hydrogen isotope ratios in sugars, in terms of time, sensitivity and operability and offers a complementary method to differentiate authentic honey from invert sugar syrups.
Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered with metformin were changed to pre-combined glibenclamide-metformin tablets in the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to evaluate the differences in glycaemic control and treatment cost following the change. Eighty patients (60% females) with a mean age of 55 years old were studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p<0.01) and -0.83% (p<0.01) after three and six months respectively. Patients with baseline HbA1c > or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The treatment cost per month was reduced by 45% at 3 months (p<0.01)) and 44% at 6 months (p<0.01). The change to pre-combined glibenclamide-metformin tablets resulted in significant improvement in glycaemia and reduction in treatment cost.
The objective of this study was to evaluate the precursors of acrylamide formation in sweet potato (SP) (Ipomoea batatas L. Lam) chips and to determine the effect of different types of vegetable oils (VOs), that is, palm olein, coconut oil, canola oil, and soya bean oil, on acrylamide formation. The reducing sugars and amino acids in the SP slices were analyzed, and the acrylamide concentrations of SP chips were measured. SP chips that were fried in a lower degree of unsaturation oils contained a lower acrylamide concentration (1443 μg/kg), whereas those fried with higher degree of unsaturated oils contained a higher acrylamide concentration (2019 μg/kg). SP roots were found to contain acrylamide precursors, that is, 4.17 mg/g glucose and 5.05 mg/g fructose, and 1.63 mg/g free asparagine. The type of VO and condition used for frying, significantly influenced acrylamide formation. This study clearly indicates that the contribution of lipids in the formation of acrylamide should not be neglected.
Blood glucose concentration was measured in 100 children immediately before and during surgery. These children were randomly assigned to receive either lactated Ringer's (LR) solution or 5% dextrose in lactated Ringer's (5%D/LR) intraoperatively as maintenance and replacement fluids. Blood samples were taken immediately after induction of anaesthesia and at 1/2, 1, 1.5, 2 and subsequent hours. Blood glucose concentration was assayed by a reflectance meter. None of the patients was noted to be hypoglycaemic pre- and intraoperatively. Intraoperative blood glucose concentration increased significantly (p < 0.05) from preoperative levels for both groups of children but the increase in those that received 5%D/LR was significantly greater (p < 0.05) than those who received LR. The number of children who were hyperglycaemic during surgery was also greater in those who received 5% dextrose in lactated Ringer's as their intraoperative fluid. These data suggest that lactated Ringer's alone is a safe and appropriate fluid for intraoperative fluid therapy in children.
We describe the distribution of capillary blood glucose (BG) by age, sex and ethnicity in Malaysian adults. A national sample of 20,041 individuals aged 30 or older had usable data. They were selected by stratified 2-stage cluster sampling. BG was measured using reflectance photometer. Percentile tables and curves by age, sex and ethnicity are presented. The BG distribution was right skewed and showed the expected increase with age. Except in Indian, women had higher BG than men. There were also marked ethnic differences. Indian had the highest BG concentration, followed by Chinese, Malay and other indigenous ethnic group.
Study name: National Health and Morbidity Survey (NHMS-1996)
We determine the prevalence and determinants of clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and overweight in Malaysia. A national probability sample of 17,392 individuals aged 30 years or older had usable data. 61% of adults had at least one risk factor, 27% had 2 or more risk factors. The observed frequency of 4 factors cluster was 6 times greater than that expected by chance. Indian and Malay women were at particular high risk of risk factors clustering. Individuals with a risk factor had 1.5 to 3 times higher prevalence of other risk factors. Ordinal regression analyses show that higher income, urban residence and physical inactivity were independently associated with risk factors clustering, lending support to the hypotheses that risk factors clustering is related to lifestyle changes brought about by modernisation and urbanisation. In conclusion, risk factor clustering is highly prevalent among Malaysian adults. Treatment and prevention programme must emphasise the multiple risk factor approach.
Study name: National Health and Morbidity Survey (NHMS-1996)