Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S adults. Rationale for the use of insulin therapy alone as the pharmacological treatment of type 2 diabetes. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Comparison of blood glucose, hba1c, and fructosamine, The hemoglobin a1c is an important part of long term blood glucose monitoring. Fructosamine – wikipedia, the free encyclopedia, Fructosamines are compounds that result from glycation reactions between a sugar (such as fructose or glucose) and a primary amine, followed by isomerization via the. Fructosamine to a1c conversion chart-wiki sucher, Hemoglobin a1c (hba1c) and fructosamine can be used to monitor glycemic control in diabetic patients with normal kidney function, but their validity in. Science, Technology and Medicine open access publisher.Publish, read and share novel research. 4.Effect of chronic administration of ethylacetate extract on body weights and hyperlipidaemia associated with diabetes Table 3. Hypoglycaemic and Hypolipidaemic Effects of an Ethylacetate Fraction of Artocarpus heterophyllus LeavesSureka Chackrewarthy1 and M.I. Fernando MR, Thabrew MI, Karunanayake EH.Hypoglycaemic activity of somemedicinal plants in Sri Lanka. Chandrika JG, Fernando WS, Wickremasinghe SMDN, Wedage WS.Effects of proanthocyanidine and flavanoid fractions of Artocarpus heterophyllus leaves on blood glucose levels in healthy amle Wistar rats. Chandrika UG, Wedage WS, Wickremasinghe SM, Fernando WS.Hypoglycaemic action of the flavonoid fraction of Artocarpus heterophyllus leaf.
The full text of this 2007 article provides a good comprehensive review of the role of iron in diabetes.
This 2007 full text comment on the above review adds important perspective to this discussion. In this study reported from China in 2010 the researchers st out "to investigate the relationship of gamma-glutamyl transferase to ferritin, and their interaction on the risk of type 2 diabetes." "A total of 436 men and 588 women were recruited. In 2006, these researchers reported a study of 490 Greek individuals with metabolic syndrome. In this 2007 study of a group of 944 individuals in France, and over a period of six years, both ferritin and transferrin levels were significantly associated to the development of metabolic syndrome. Figure 1—Age-adjusted ORs (95% CI) for the 6-year incidence of the IDF-defined metabolic syndrome according to high ferritin and transferrin levels (both above the upper tertiles) (A), lower ferritin and high transferrin levels (B), high ferritin and lower transferrin levels (C), and lower ferritin and lower transferrin levels (D).
In 2006, data from the above French study was analyzed to determine the association of ferritin and transferrin to glucose metabolism. Figure 1—Standardized ORs for the 3-year incidence of hyperglycemia (IFG or type 2 diabetes) according to baseline iron biomarkers and CRP (independent variables) after adjustment for baseline age, BMI, WHR, and glucose and insulin concentrations in the DESIR study.
In this 2005 Italian study of 269 metabolic syndrome and 210 control subjects, ferritin in metabolic syndrome subjects was significantly higher than in controls. In this 2008 study of a population of 110 women with diabetes from Kuwait, researchers found an association of elevated ferritin with diabetes, but not with metabolic syndrome. Figure 1 Serum ferritin levels in male (white boxes) and female (grey boxes) individuals discriminated according to the presence or absence of defining criteria of the insulin resistance syndrome (A–F). As in the study described directly above, this was a 2012 reported study from the large EPIC epidemiologic survey undertaken in Europe. This 2007 reported study of incident type 2 diabetes the researchers recruited participants from four clinical centers in the U.S.
This 2009 study was based on "a longitudinal population-based study of approximately 6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. In this 2010 study from Iran, serum ferritin was measured in 128 pregnant women (64 women with gestational diabetes and 64 age-matched controls). This 2011 study was reported by researchers from Division of Epidemiology, Statistics and Prevention at the National Institutes of Health.
In another study from Iran in 2008, serum ferritin measurements in 25 obese menstruating women and 25 non-obese menstruating women matched for age were obtained. In 2008 these researchers examined the expression of iron transport molecules in NAFLD patients with or without iron overload, in hemochromatosis patients and in controls. This 2003 review further differentiates iron loading in NAFLD patients from that observed in hemochromatosis patients, and discusses findings that patients with chronic hepatitis and the C282Y hemochromatosis genotype "are more likely to suffer from advanced hepatic fibrosis or cirrhosis and to do so at younger ages." and, "A role for modest iron overload in increasing severity of alcohol-induced liver disease has been well established from results of experimental studies.
This is an early study (2000) that explores insulin resistance in NASH and the role of iron. This 2009 research was reported in a study of 38 NASH patients, compared to 24 with simple steatosis (fatty liver) and 10 health subjects.
In this 2009 study, the researchers measured and compared markers of hepatic oxidative stress in 38 patients with non-alcoholic steatohepatitis (NASH), 24 simple steatosis (NAFLD or fatty liver disease) and 10 healthy subjects.Oxidative stress was significantly higher in NASH patients than in those with NAFLD, and was related to iron overload, glucose-insulin metabolic abnormalities, and severity of disease.
This 1999 study done in France characterized insulin resistance associated with hepatic iron overload. In this 2008-reported, large population based survey conducted in Beijing and Shanghai, 3,289 participants aged 50-70 years were examined for fasting plasma ferritin, glucose, insulin, lipid profile, glycohemoglobin, inflammatory markers, adipokines; and dietary profile were collected. This 1997 research was first to characterize this syndrome of unexplained hepatic iron overload and normal transferrin saturation.
In a 2011 study of 65 NASH patients in Turkey the investigators measured iron metabolism markets and inflammatory cytokines. In a paper published in 1999, this research team in France examined 161 non-C282Y homozygous patients (i.e. This 2010 paper presents a possible molecular explanation for the accumulation of iron in NASH patients.
This 2005 review describes the interaction of alcohol with increased iron absorption in alcoholic liver disease patients.
This review discusses several other factors that are likely contributors to the accumulation of iron in alcohol liver disease. This animal (rat) study provides more insight into alcoholic liver disease and the mechanism of iron accumulation in hepaocytes.
Objectives: The present cross-sectional community-based study was conducted to assess the prevalence and risk factors for coronary artery disease (CAD) in an urban community in Tenali, Andhra Pradesh. Conclusions: Observations from our community based study indicate that prevalence of CAD in urban Andhra Pradesh is alarmingly high as observed in other parts of India and urgent steps are to be taken to adopt life style changes and to control risk factors. While studying the prevalence of CAD and its risk factors in Tenali town (A.P), the opportunity is utilized to increase the awareness of risk factors of the ongoing epidemic of CAD among general public and propagating the preventive measures against the modifiable risk factors like smoking, abdominal obesity, control of diabetes, hypertension, dyslipidemia, sedentary life style and faulty dietary habits etc. Tenali is a major Municipal town with a population of 1,54,740 (2001 census) in Guntur District of Andhra Pradesh. CAD was diagnosed based on a past history of documented MI or ECG evidence of Q-waves (Minnesota codes 4-1 to 4-2), ST segment depression (Minnesota codes 1-1-1 to 1-1-7). All the persons in the houses responded for our request for examination and investigations (response rate was 100%).
Of the 29 cases with CAD (18 males) detected during the survey 19 were known to have CAD and 10 additional asymptomatic cases were detected freshly to have CAD (Table 3). There is a scarcity of reliable community based epidemiological data on the prevalence of CAD from Andhra Pradesh and even less is known regarding the prevalence of CAD in the community setting. As observed in the present study, clustering of various cardiovascular risk factors was reported in Asian Indians.6 Total serum cholesterol and LDL cholesterol are considered to be important risk factors for CAD in some studies and hypertriglyceridemia with low HDL is reported to be the major risk-factor in other studies.
In the present study 86 persons were known to have diabetes mellitus and 12 persons were freshly detected to have diabetes mellitus. Additionally 17 persons were detected freshly to have impaired glucose tolerance based on WHO consultation group criteria. It is well known that Asian Indians have low HDL cholesterol levels which could be one of the risk factors for premature CAD in this ethnic group.
The present study is a community based study, utilizing specific well defined criteria including laboratory testing. Mohan V, Deepa R, Shantirani S, Premalatha G, prevalence of Coronary Artery disease and its relationship to lipids in a selected population in South India. Gopinath N, Kaul V, Chandhan SL, etal, Asymptomatic coronary heart disease detected in epidemiological survey of urban population of Delhi. This continues to pose a real challenge to physicians as the prevalence of this disease in the United States continues to rise. The focus of this review will be the management of patients with type 2 diabetes using one or more of the five available classes of oral hypoglycemic agents: sulfonylureas, meglitinides, biguanides, thiazolidinediones and alphaglucosidase inhibitors (Table 1). Metformin (Glucophage) is currently the only agent in this antidiabetic class available in this country. Food and Drug Administration (FDA) included troglitazone (Rezulin), rosiglitazone (Avandia) and pioglitazone (Actos). Alpha-glucosidase inhibitors act by inhibiting the enzyme alpha-glucosidase found in the brush border cells that line the small intestine, which cleaves more complex carbohydrates into sugars. Reasonable combinations of agents include a sulfonylurea plus metformin, a sulfonylurea plus an alpha-glucosidase inhibitor, a sulfonylurea plus a thiazolidinedione, metformin plus repaglinide, biguanide plus alpha-glucosidase inhibitor, and metformin plus a thiazolidinedione. The effects of ethylacetate (EtAc), methanol and water fractions of A.heterophyllus leaves on fasting blood glucose levels of normoglycaemic rats.
Thabrew2[1] Department of Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Kelaniya, Thalagolla Road, Ragama, Sri lanka[2] Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka1.
A comparative study on phenolic profiles and antioxidant activities of legumes as affected by extraction solvents.
Thiolysis-HPLC characterization of apple procyanidins covering a large range of polymerization states.
The authors introduce their discussion as follows: "In this review, we discuss the role tissue iron and elevated body iron stores play in causing type 2 diabetes and the pathogenesis of its important complications, particularly diabetic nephropathy and cardiovascular disease (CVD). According to levels of GGT and ferritin, they were divided into three groups in each gender of each geological location (Urban or Rural), that is, Group 1 (both GGT and ferritin < median values), Group 2 (only GGT or ferritin ? median values), and group 3 (both GGT and ferritin ? median values). The researchers noted, "This is the first prospective study associating ferritin and transferrin with the metabolic syndrome and its components. High and low levels were defined according to the three groups: men, premenopausal women, and postmenopausal women (DESIR). The investigators stated aim was "to determine, in a cohort of men and women, whether ferritin and transferrin were associated with glucose metabolism and whether they were predictive of the onset of hyperglycemia (impaired fasting glycemia or type 2 diabetes) after 3 years of follow-up. Geometric mean values of serum ferritin are shown for premenopausal women (black bar), postmenopausal women (white bar), and men (gray bar).
The researches concluded, "This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. 1 Odds ratios and 95% CIs for the association of clinically raised ferritin (group 5) vs ferritin in the normal range (groups 1–4) with incident diabetes in men and women, with adjustment for factors as stated (described in methods).
The investigators, "examined the association between serum ferritin concentration and the risk of diabetes. Researchers in Sweden "investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk." "We conducted a prospective cohort study of 3,158 pregnant women.
Serum ferritin and markers of lipid peroxidation were significantly higher in the obese women. The researchers first noted,"cardiorespiratory fitness (CRF) and physical activity (PA) are inversely related to the occurrence of type 2 diabetes (T2D). At that time it was noted that, "Excess hepatic iron may occur in insulin resistance-associated iron overload (IRHIO), characterized by hyperferritinemia with normal to mild increases in transferrin saturation. Iron reduction using phlebotomy significantly reduced oxidative stress in NASH patients and resulted in concomitant reduction in liver serum transferase. Sixty-five patients with high ferritin concentrations, similar to hemochromatosis, but normal transferrin saturation, unlike hemochromatosis.
In patients with iron overload of more than 50% above the upper-normal threshold, greater liver damage was noted (including advanced hepatic fibrosis),and a diagnosis of NASH. They attribute the process to enhanced expression of transferrin receptors and hyperdynamic state of retinoid (vitamin A) metabolism.
A total of 534 people aged 20 years and above in randomly selected houses in each street of the 2 localities were examined. The prevalence of CAD doubled to 3 to 4% in rural India and quadrupled to 9 to 11% in urban India over the past four decades.
In community-based study, we attempted to document the prevalence of CAD in an urban population in Andhra- Pradesh state and look at its relationship to certain risk factors. Waist and hip were measured and the mean of two measurements was taken for calculating the waist to hip ratio (WHR). The prevalence rates obtained from the study were age-standardized to minimize the effect of age groups in the study population.
In this study, age, total cholesterol and LDL cholesterol were found to be risk factors for CAD on univariate analysis.
This study shows 11.3% of patients with diabetes mellitus have CAD while 3% of normal glucose tolerance only had CAD thus confirming that subjects with glucose intolerance have a greater risk of CAD (Table 1).
Forty nine known patients with diabetes mellitus were found to have their lipid levels within normal limits. Sixty three persons were known to have hypertension, of whom only 24 were found to have their blood-pressure under control.
Therefore these results may reflect the true burden of CAD and its risk factors in the community at large.
Effect of potentially modifiable risk factors associated with myocardial infraction in 52 countries (The interheart study). Significant lipid, adiposity and metabolic abnormalities amongst 4535 Indians from a developing region of rural Andhra Pradesh.
The prevalence and determinants of hypertension in the urban population of Jaipur in Western India.


Type 2 diabetes is defined as a syndrome characterized by insulin deficiency, insulin resistance and increased hepatic glucose output.
Metformin works by reducing hepatic glucose output and, to a lesser extent, enhancing insulin sensitivity in hepatic and peripheral tissues.
Subsequently, in March 2000, the FDA asked the manufacturer (Parke-Davis, Warner-Lambert) of troglitazone, the first agent in this class to receive labeling approval, to remove the product from the market.
Because they inhibit the breakdown and subsequent absorption of carbohydrates (dextrins, maltose, sucrose and starch; no effect on glucose) from the gut following meals, the largest impact of these drugs is on postprandial hyperglycemia. Effect of chronic administration of ethylacetate extract on fasting blood glucose levels of sterptozotocin-induced diabetic rats Table 2. Mohamed, Pharmacognostical standardization and antidiabetic activity of Artocarpus heterophyllus leaves.
In addition, we emphasize that iron overload is not a prerequisite for iron to mediate either diabetes or its complications.
Odds ratios for T2D in group 2-3 compared with group 1 were analyzed by multiple logistic regressions.
Among 360 new cases of diabetes, serum ferritin measured the study baseline was higher in cases than in controls (in men 96.6 vs.
Ferritin serves as an antioxidant by binding excess iron, and elevated serum ferritin is a well-established risk factor for future type 2 diabetes.
The green, yellow, and pink regions correspond to the low-, medium-, and high-risk strata, respectively. The figure shows the incidence rate of diabetes for male study participants in the four serum ferritin (SF) level quartiles. Note that the subjects with hereditary hemochromatosis (HH) have significantly higher ferritin and transferrin saturation levels than the subjects with NAFLD and high iron.
Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH." The researchers concluded, "Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. OR and 95% confidence interval (CI) for metabolic syndrome (A), type 2 diabetes (B), and IFG (C) according to joint classification of ferritin and CRP concentrations. OR and 95% confidence interval (CI) for type 2 diabetes according to joint classification of metabolic syndrome (MetS) and ferritin concentrations. The research team stated that ferritin levels elevated to this degree are "an independent predictor of advanced hepatic fibrosis among patients with NAFLD." The researchers concluded, "(Serum ferritin 50% or more above the upper normal laboratory range) is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. All of them underwent oral glucose tolerance test and lipid profile estimation and a 12-lead electrocardiogram. All persons aged 20 years and above in randomly selected houses in each street of the two localities of the town namely Gandhinagar and Nazarpet which comprise people from upper, middle as well as low income groups were examined. Blood pressure (BP) was recorded in the sitting position in the right arm with a mercury sphygmomanometer (Diamond Deluxe BP apparatus, Pune, India) by a physician who was unaware of the clinical status of the subject.
Past medical records of treatment for myocardial infarction (MI) and revascularization procedures were verified. For analysis of cardiovascular risk factors, CAD was diagnosed based on documented MI or the presence of Q-waves or ST segment changes in ECG. Z-test for comparison of means and proportions were used for comparing the mean and frequencies between cases and controls. Another 11 (6 of whom underwent coronary artery bypass grafting) were taking lipid modifying drugs regularly. Only 5 persons out of 86 known diabetics were taking lipid modifying drugs (3 know cases of CAD and one case of post CABG). The remaining 130 persons were detected freshly to have hypertension during the survey (24.3%). Medications used to treat type 2 diabetes are designed to correct one or more of these metabolic abnormalities. It is of particular concern with agents that are metabolized to an active metabolite with significant renal excretion. Pharmacognosy of Diabetes MellitusDiabetes mellitus type II (T2DM) is a global public health crisis that threatens the economies of all nations, particularly developing countries. The results showed "(1) The prevalence of glucose abnormalities increased across the three groups of female subjects. The line through the box is the median, and the error bars are the 5th and 95th percentiles.
Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline.
Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. The results from the study were adjusted using Bayes’ law to reflect the observed 5-year incidence of 5.7% among the 3,032 at-risk individuals in Inter99 (A). Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors." "Dietary heme iron intake was positively and significantly associated with GDM risk. Increased SF concentration is considered a contributing factor for developing T2D." The researchers "investigated 5,512 adult participants enrolled in the Aerobics Center Longitudinal Study (ACLS) between 1995 and 2001.
HH patients are not protected from high levels of iron, yet they generally do not load macrophage iron and tend to have significantly lower levels of triglycerides and LDL cholesterol. Adjusted for age, sex, region, residence, BMI, smoking, drinking, physical activity, education levels, dietary factors, and family histories of chronic diseases (A) or family histories of diabetes (B and C). The ORs were adjusted for age, sex, region, residence, BMI, smoking, drinking, physical activity, education levels, dietary factors, and family histories of diabetes. Furthermore, elevated SF is independently associated with higher NAS (a fibrosis scoring system), even among patients without hepatic iron deposition. The cohort included a high prevalence of (HFE) compound heteroyzgotes who had slightly greater iron burden. Two readings were taken 5 minutes apart and the mean of the two was taken as the blood pressure measurement. Stepwise multiple logistic regression analysis was performed using CAD as the dependent variable and age, BMI, systolic and diastolic blood pressures, fasting blood sugar, serum HDL, serum LDL and total serum cholesterol as independent variables. Among risk factors, 6 persons had diabetes mellitus, 8 persons were hypertensive and 3 persons had both diabetes mellitus and hypertension.
Among 12 freshly detected diabetics 6 persons were found to have dyslipidemia and the other 6 persons were having their lipids within normal limits. Thus hypertension was found to be more prevalent than diabetes mellitus at Tenali in the present study. Currently, there are five distinct classes of hypoglycemic agents available, each class displaying unique pharmacologic properties. These agents include chlorpropamide (Diabinese) and glyburide, both of which should be avoided in the setting of impaired renal function and used with caution in elderly patients.
Most of the related side effects (including metallic taste, gastrointestinal discomfort and nausea) are transient and commonly reported only during initiation of therapy.
Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity.
Correspondingly, MDA levels (a lipid peroxidation product) were also higher in group 3 than other groups. Significance levels were determined by the Mann–Whitney U-test and are indicated in the figure. The increased risk of newly diagnosed diabetes was concentrated among participants with transferrin saturations < 45%. On the left axis, absolute risk is indicated, and relative risk is shown on the right axis. A fasting blood sample was collected after an overnight fast of at least 10 hours for biochemical investigations. Among 17 cases of freshly detected impaired glucose tolerance, 9 cases have dyslipidemia indicating abnormal lipids may precede the development of overt diabetes mellitus. These classes are the sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
Unlike the commonly used sulfonylureas, the meglitinides have a very short onset of action and a short half-life. Therapy with acarbose has been linked to elevations in serum transaminase levels and the use of this agent is contraindicated in patients with liver cirrhosis. According to the International Diabetes Federation [1], diabetes affects at least 285 million people worldwide, and that number is expected to reach 438 million by the year 2030, with two-thirds of all diabetes cases occurring in low- to middle-income countries. Karthikeyan, Antidiabetic activity of Feronia limonia and Artocarpus heterophyllus in STZ induced diabetic rats.. All multiple linear regression coefficients between ferritin concentration and concentrations of insulin, glucose, and glycosylated hemoglobin were positive and significant for both men and women." The investigators concluded, " "Elevated serum ferritin concentration was associated with an increased risk of diabetes.
After adjusting for confounders, women reporting the highest heme iron intake levels (?1.52 vs. All biochemical parameters were carried out on Merck Biochemistry auto analyzer, using kits.
In the other, 17 persons whose lipid levels were within normal limits, 9 were taking lipid modifying drugs (4 cases of post CABG + 5 cases of old MI). In patients for whom diet and exercise do not provide adequate glucose control, therapy with a single oral agent can be tried. All sulfonylureas have been associated with weight gain and thus, may not be the optimal first choice for obese patients.Unfortunately, not all patients treated with a sulfonylurea will have an adequate response. Taking the drug with meals may also lessen the severity of the gastrointestinal side effects.
Patients treated with pioglitazone have displayed mean decreases in triglyceride levels, mean increases in HDL cholesterol levels, and no consistent mean changes in LDL and total cholesterol levels.20,21Because these agents do not increase insulin secretion, hypoglycemia does not pose a risk when thiazolidinediones are taken as monotherapy. The number of adults with impaired glucose tolerance will rise from 344 million in 2010 to an estimated 472 million by 2030. Moutounet, Quantitative fractionation of grape proanthocyanidins according to their degree of polymerization.J. Fasting and 2 hour plasma glucose estimations (glucose oxidase and peroxidase method), serum cholesterol (CHOD-PAP method) and serum triglycerides (GPO PAP method) were measured. When choosing an agent, it is prudent to consider both patient- and drug-specific characteristics.
Treatment failure with sulfonylurea therapy can be divided into two categories: primary and secondary. If a meal is omitted throughout the day, patients should be instructed to skip the corresponding dose to prevent hypoglycemia. Because metformin does not affect insulin secretion, it is not associated with hypoglycemia when used as monotherapy, but can potentiate hypoglycemia when used in combination with a sulfonylurea or insulin. Other contraindications include patients with inflammatory bowel disease or a history of bowel obstruction.32Therapy should be initiated with the lowest effective dose and titrated slowly over intervals of two to four weeks. Jayasekera, Evaluation of hypoglycaemic and hypolipidaemic effects of an ethylacetate fraction of Artocarpus heterophyllus leaves in STZ-induced diabetic rats.
Aruoma, Characterization of the phenolic constituents in Mauritian endemic plants as determinants of their antioxidant activities in vitroJ. The researchers concluded, "GGT and ferritin were correlated with each other, and had synergistic effect on the risk of T2D in women. In more recent research reported on this page and on our Iron Reduction Therapy page the condition of relatively normal transferrin with elevated ferritin has been shown to be a combination of moderate iron overload accompanied by inflammation. High Density Lipoprotein (HDL) cholesterol was estimated by phosphotungstate method after precipitating low density lipoprotein and chylomicrons by the addition of phosphotungstic acid in the presence of magnesium ions and very low density lipoprotein.
In 2 cases of post CABG, lipid levels were abnormal in spite of taking drugs, hence adjustment of dosage of lipid modifying drugs was advised by us. If adequate blood glucose control is not attained using a single oral agent, a combination of agents with different mechanisms of action may have additive therapeutic effects and result in better glycemic control. Primary failure results when a patient exhibits an initial poor response to sulfonylurea therapy (a decrease in FPG levels of less than 20 mg per dL [1.1 mmol per L]).
Likewise, if an extra meal is added throughout the day, the patient should add a dose to cover that meal.
It is well documented that insulin sensitivity and glucose tolerance can be modulated by use of traditional medicines that are mainly derived from plants [3-5]. Reaven, From plant to patient: an ethnomedical approach to the identification of new drugs for the treatment of NIDDM. This combination of factors has been described in other conditions including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and insulin resistant hepatic iron overload (IR-HIO).
Stratification of the at-risk Inter99 subpopulation by fasting plasma glucose status (B) and by DRS risk stratum (C). Conclusion: Lower SF concentration was associated with lower risk of developing T2D in those regularly participating in CRF.
6 cases of known CAD were not taking lipid modifying drugs and were advised to take suitable drugs. Repaglinide can be titrated to a dosage of 4 mg before each meal (maximum dosage of 16 mg per day). Natural antidiabetic agents with fewer side effects from readily available medicinal plants offer great potential in the discovery of new antidiabetic drugs.Pharmacognosy (the study of the medicinal properties of materials of natural origin) has played an important role in the management of diabetes mellitus since ancient times. Most of the research on the remainder of this page and in our other Science Library pages is focused on the independent predictive value of either ferritin or GGT in relation to diabetes, heart disease and other diseases of aging. The use of thiazolidinediones should be avoided in these patients.As referred to earlier, of greatest concern are the reports of an idiosyncratic drug reaction with troglitazone. Although hypoglycemia is not typically associated with monotherapy with the alpha-glucosidase inhibitors, it can occur in combination with other drugs. Indeed, it has been estimated that more than 800 herbal or plant-derived products have been used for the management of T2DM across geographically and culturally diverse populations worldwide [6-9].


Also, Health-e-Iron concurs with the recommendation that regular fitness activities will lower serum ferritin, but suggests that in conjunction with a fitness routine, participants should consider blood donation or therapeutic phlebotomy as an effective way to more quickly reduce and maintain optimal ferritin levels. Most of the hypoglycemic effects of the sulfonylureas will be observed at one half of the maximum dose recommended for a specific agent.
At least one week should be allowed between dosage adjustments to adequately assess blood glucose response.
This reaction is initially characterized by increased serum transaminase levels, which in some cases progressed to hepatitis, hepatic failure and death. World Health Organization (WHO) recommendations [10] on the use of alternative medicines for treating diabetes mellitus provide an impetus for research in this area. Unfortunately, not many people who commit to a regular fitness routine are able to maintain it for more than a relatively short period of months or years.
In patients undergoing contrast studies, metformin therapy should be withheld for approximately 48 hours following the procedure or until it has been determined that renal function has returned to baseline. Preliminary attempts (before troglitazone was withdrawn from the market in March 2000) to prevent such incidents included a request by the FDA that Parke-Davis strengthen the drug's labeling and require stringent monitoring of transaminase levels in patients taking this agent. Currently, the focus of research includes discovering newer antidiabetic agents as well as isolating the active compounds from herbal sources that have been documented to have antidiabetic properties as have been described in ancient texts. In March 1999, the FDA's Endocrine and Metabolic Drugs Advisory Committee reviewed the status of troglitazone and the potential toxicities and recommended continued availability in a select group of patients: those who are not well controlled with other antidiabetic agents.
The active components of a number of plant-derived antidiabetic compounds have been identified, and amongst these are flavonoids, alkaloids, glycosides, polysaccharides, peptidoglycans, hypoglycans, guanidine, steroids, carbohydrates, glycopeptides, terpenoids and amino acids.
Since then, it has been determined that patients requiring the use of an insulin sensitizer should be treated with one of the alternative agents.
Potentially beneficial effects on the rate of food digestion, glucose transport, potentiation of insulin release, inhibition of insulin clearance, insulin-mimetic effects, reduced gluconeogenesis, and ?-cell protection have been attributed to these agents [11]. Although results from pre-marketing trials revealed no evidence of hepatotoxicity with the newer agents (rosiglitazone and pioglitazone), two recent case reports demonstrated that rosiglitazone may be associated with hepatic failure following just 14 days of therapy, although a true cause-and-effect relationship has not been established.26,27The FDA recommends that serum transaminase levels be monitored every other month for the first year in all patients receiving a thiazolidinedione. Type 2 diabetes (T2DM) is a disease characterized by a dual defect: 1) by insulin resistance which prevents cells from using insulin properly and 2) degrees of reduced pancreatic insulin secretion.
Following one year of therapy with the newer agents, the incidence of serum transaminase elevations has been reported to be similar to placebo.The time to achieve a desired effect with the thiazolidinediones is somewhat longer than the other classes of hypoglycemic agents discussed thus far.
It is a progressive disease that shows a consistent deterioration in glycemic control over time. Intervals of at least three to four weeks should be allowed before increasing the dosage of these agents.
While the pathophysiology and pathogenesis of the T2DM is not fully understood, it is clear that impaired glucose tolerance (IGT) often develops into T2DM.
Smaller dosages can be initiated if used as part of a combination regimen with a sulfonylurea or a sulfonylurea plus metformin. Interventions that may delay or prevent the progression of IGT to T2DM are desperately needed.
Hyperlipidaemia is a secondary complication in diabetes and there is a growing interest in plants with both hypoglycaemic and hypolipidemic properties since they have a potential to be developed further for effective treatment for diabetes specially associated with a hyperlipidaemic state.
Overview of Artocarpus heterophyllusArtocarpus heterophyllus Lam (family Moraceae), commonly known as jakfruit is one of the most significant trees in tropical homegardens and perhaps the most widespread tree in the genus Artocarpus. It is a medium-size evergreen tree typically reaching 8–25 m (26–82 ft) in height with evergreen, alternate, glossy and leathery leaves to 22.5 cm (9 in) in length. Jackfruit's place of origin is believed to be indigenous to the rainforests of the Western Ghats. Today, it is cultivated at low elevations throughout India, Sri Lanka, Myanmar, southern China, Malaya, East Indies, Queensland, Mauritius, Kenya, Uganda and former Zanzibar, Pacific islands and Brazil [12].Many parts of the plant including the bark, roots, leaves, and fruit are attributed with medicinal properties. It is reported in Ayurveda (a traditional medicine system in Sri Lanka and India) to possess antibacterial, anti-inflammatory, antidiabetic, antioxidant and immunomodulatory properties. It is an important source of compounds like morin, dihydromorin, cynomacurin, artocarpin, isoartocarpin, cyloartocarpin, artocarpesin, oxydihydroartocarpesin, artocarpetin, norartocarpetin, cycloartinone, betulinic acid, artocarpanone and heterophylol which have therapeutic properties [13].The root is a remedy for skin diseases and asthma and the extract is taken in cases of fever and diarrhea.
The ashes of the leaves, burned together with corn and coconut shells are used alone or mixed with coconut oil to heal ulcers.
Mixed with vinegar, the latex promotes healing of abscesses, snakebite and glandular swellings.
The seed starch is given to relieve biliousness and the roasted seeds are regarded as aphrodisiac. Aim of the chapterAlternative systems of medicine such as Ayurveda is widely used in Sri Lanka and India.In Ayurveda diabetes falls under the term Madhumeha [14]. Various types of herbal preparations such as decoctions (boiled extracts), Swaras (expressed juices), Asav-Arisht (fermented juices), and powders have been used for the treatment of Madhumeha [14].Hot water extracts of A. This traditional claim was first scientifically validated by the investigations carried out by Fernando et.
This preliminary work has been followed by many other studies which have provided insights into the efficacy, safety, mechanisms of action and the presence of other bioactivities of therapeutic potential in A. This chapter is based on the investigations carried out by Chackrewarthy et al [18] to evaluate the hypoglycaemic and hypolipidaemic potential of an ethylacetate fraction of A.
Phytochemical screening and standardized extractionPlant extracts used in traditional medicine are chemically complex and may contain one or more structurally related active compounds that produce a combined effect.
Standardization and phytochemical screening are essential measurements of ensuring quality control of herbal drugs.Phytochemical screening of the aqueous extract of the leaves has revealed the presence of a range of polyphenols such as flavanoids, anthocyanins, tannins and polysaccharides as constituents [19]. In a more recent study of the aqueous extract of leaves, the presence of proteins, saponins, sterols, glycosides and lipids have been revealed in addition to the compounds mentioned [20]. In general, the solvent system used for the extraction plays a significant role in the solubility of the active principles of plant materials which in turn influence the bioactivities of the fractions [21]. To concentrate and obtain polyphenol rich fractions before analysis, strategies including sequential extraction is commonly used. Generally, waxy and lipoid substances are extracted into hexane and DCM and polyphenols are extracted into more polar solvents such as ethylacetate, methanol and water. In particular, methanol has been generally found to be more efficient in extraction of sugars, organic acids and lower molecular weight polyphenols while the higher molecular weight flavanols are better extracted with ethylacetate [24-27]. Effects on fasting blood glucose levelsThe hypoglycemic potential of fractions separated from A. The ethylacetate (EA) fraction and the water fraction were found to exert the highest hypoglycemic effects compared to the controls treated with distilled water (Fig 2).
This demonstrates that both these fractions contain the active principals mediating the hypoglycaemic effect in varying proportions.
Methanol fraction also had significant activity similar to the aqueous fraction, but the initial hypoglycaemic effect (+1 hr) was more prominent in the aqueous fraction (30% vs 16%). Further, purification and fractionation results in an enhancement of bioactivity by eliminating the unwanted material which could exert inhibitory effects on the bioactivity of interest. Since the ethylacetate fraction has been shown to contain a high content of flavanoids by phyotochemical screening [19,28,29], the hypoglycaemic activity of this fraction could be attributed to a high molecular weight flavanoid which has a higher solubility in ethylacetate than in water. Effects on glucose tolerance Impaired glucose tolerance is a pre-diabetic state which may precede T2DM.
The oral glucose tolerance test (OGTT) was used as a screening method for acute antihyperglycemic activity since the results give the overall effect of the test material on the handling of an external glucose load [30].Glucose tolerance studies with normoglycaemic rats, receiving the ethylacetate fraction showed a significant improvement in their ability to utilize the external glucose load compared to the control group (Fig.
Reductions in blood glucose levels were statistically significant between the control curve and test curves at all time intervals. These data provide confirmatory evidence for the presence of antidiabetic principals in the leaf extract and validate its use in the treatment of diabetes by traditional medical practitioners. Animal models of diabetes mellitusNon-insulin-dependent forms of diabetes can be produced by administration of a low dose of Streptozotocin (STZ) or alloxan [32]. These kinds of models of diabetes are considered a screening step in the search for drugs for the treatment of diabetes [33].
Streptozotocin (STZ) is an antibiotic derived from Streptomyces achromogenes and structurally is a glucosamine derivative of nitrosourea.
Its structural similarity to glucose allows it to enter the pancreatic beta-cell via a glucose transporter-GLUT-2 and causes alkylation of deoxyribonucleic acid (DNA).
Furthermore, STZ induces activation of poly-adenosine diphosphate ribosylation and nitric oxide release. Although high-dose STZ severely impairs insulin secretion mimicking type 1 diabetes, low-dose STZ has been known to induce a mild impairment of insulin secretion which generate an impairment in glucose metabolism leading to glucose intolerance and mild, moderate or severe hyperglycaemia [36, 37].
Further, it also affects the lipid metabolism which leads to hyperlipidaemia which closely mimic the natural course of pathogenesis of T2DM [36-39]. The potential problem with STZ is that its toxic effects are not restricted to pancreatic beta-cells since it may cause renal injury [40], oxidative stress, inflammation and endothelial dysfunction [41]. As in the glibenclamide-treated rats, in rats receiving the ethylacetate fraction also, the fall in the blood sugar level continued progressively till the end of the fifth week. The fall in fasting blood sugar has continued progressively during the period of treatment with the extract.
In another study conducted by Mohana Priya et al [29] using a similar protocol, chronic administration of an ethylacetate fraction of the A.
Histopathological analysis of pancreas of streptozotocin induced diabetic rats chronically treated with an ethylacetate fraction of A.
Insulin increases the receptor mediated removal of LDL cholesterol and activates lipoprotein lipase for the hydrolysis of triacylglycerols in lipoproteins.
Therefore, reduced activity if insulin in diabetes causes hypercholesterolaemia and hypertriglyceridaemia. This is cleary demonstrated in the diabetic controls of the present study by the increased levels of serum total cholesterol (TC) and triacylglycerols (TG) in diabetic rats when compared to normal control rats (Table 3). This effect on diabetic hypertriglyceridemia in ethylacetate fraction treated rats could be due to improved glycemic control.
Further, stimulation of insulin secretion in response to the treatment with the extract could increase the uptake of low density lipoprotein (LDL) cholesterol by extrahepatic tissues contributing to the cholesterol lowering effects of the ethylacetate fraction. However, to obtain confirmatory evidence of these views, further studies on the effects of the ethylacetate fraction on LDL and high density lipoprotein (HDL) cholesterol levels and their clearance need to be investigated. Loss of body weight in diabetic rats is due to increased muscle wasting and loss of tissue proteins [57].
As evident from Table 3, the ethylacetate fraction had an improving effect on the BW (11%) of diabetic rats, which was restored to near normal levels. This may be a reflection of improved health resulting from the effects of the ethylacetate fraction on insulin release.5. ToxicityThe use of herbal medicines for the treatment or prevention of a variety of diseases has increased markedly. This coupled with lower costs compared with conventional medications is the major attraction to these treatments. The active ingredients of plant extracts are chemicals similar to those in purified medications, and they have the same potential to cause serious side effects. The usefulness of any drug depends not only on its therapeutic efficacy but also on its lack of toxicity or adverse side effects. Therefore, toxicological investigations have to be carried out before any drug can be considered as safe.
This is specially important in the case of antidiabetic drugs, which have to be administered over a relatively long period of time to obtain their pharmacological potency. An in vivo study using Sprague Dawley rats carried out by Fernando and Thabrew [58] has demonstrated that an aqueous extract of mature leaves of A. Investigations carried out by Chandrika et al [28] also have revealed that the chronic administration of the ethylacetate fraction of A. No significant differences had been observed in the liver function tests and the histology of various body organs between the test and the control groups. Further, no effects of the extract have been observed on the intestinal glucose absorption in experimental rats.In vitro investigations carried out by Kotowaroo et al [60], on the mechanism of action have revealed that aqueous leaf extract of A. Further, enzyme kinetic studies using the Michaelis-Menten and Lineweaver-Burk equations have established that the aqueous leaf extract of A.
However, this finding does not agree with the fact that the leaf extract significantly improves the glucose tolerance by improving the ability to handle an external glucose load, which has been consistently demonstrated in both animal and human studies conducted so far. However, the possibility exists, that the leaf extract could exert its hypoglycaemic effects through more than one mechanism. Furthermore, avialable evidence indicates that the active principals mediating the antidiabetic effect in A. There is evidence that flavonoids, can increase the viability of beta-cells exposed to STZ or other oxidative stress conditions and improve beta-cell function [61-64]. Increased oxidative stress due either to fasting or postprandial hyperglycemia is accepted as a participant in increased beta-cell damage contributing to the development and progression of diabetes [65].
There is also evidence that the antioxidant defense system is under-expressed in pancreatic cells [66] and flavonoid-rich extracts administration to diabetic animal models has been shown to increase expression of enzymes like catalase and superoxide dismutase as well as glutathione peroxidase system [67, 68]. Therefore, there is a strong possibility of a pancreatic mechanism either by induction of insulin secretion or by recovery of beta-cell mass through which the hypoglycaemic activity of the leaf extract could be exerted. Chronic administration of the ethylacetate fraction to STZ-induced diabetic rats resulted in a significant improvement in the hyperlipidaemia associated with diabetes leading to a significant lowering of serum total cholesterol and triglycerides.
The effects of the improved glycaemic control was evident in the improvement of body weights in diabetic rats under chronic treatment with the ethylacetate fraction. Isolation and characterization of the active principals in the ethylacetate fraction followed by further pharmacological and clinical studies would provide with a novel herbal drug for T2DM therapy.



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Comments

  1. 05.07.2014 at 15:36:23


    Mg/dL at two hours, and less than 140.

    Author: iceriseherli
  2. 05.07.2014 at 20:36:18


    When a person's cells become resistant to the it's possibly just related to that but I think if it goes above.

    Author: BRIQADIR
  3. 05.07.2014 at 14:11:56


    Low blood sugar, which test results are useful for identifying health.

    Author: Jin