Glycemic Reduction Research Articles

Early Response to Preventive Strategies in the Diabetes Prevention Program

Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. 3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program. Independent variables were weight loss at 6 and 12months; fasting glucose (FG) at 6months; hemoglobin A1c (HbA1c) at 6months; and post-load glucose at 12months. The main outcome was time to diabetes diagnosis. After 6months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95% CI) 0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15 (0.07-0.30) for 0-<3%, 3-<5%, 5-<7%, 7-<10%, and ≥10% weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted >60% lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038). Weight and glucose at 6 and 12months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes.

Antioxidant and antidiabetic profiles of two African medicinal plants: Picralima nitida (Apocynaceae) and Sonchus oleraceus (Asteraceae).

BackgroundDiabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia generally associated with oxidative stress. The present study aims at evaluating the antioxidant and antidiabetic potential of methanol and hydroethanol extracts of the stem bark and leaves of Pricralima nitida and the Sonchus oleraceus whole plant respectively.MethodsThe in vitro antioxidant activity was assessed using 1,1-Diphenyl-2-picrilhydrazyl (DPPH) for free radical-scavenging properties of the extracts, and the Folin-Ciocalteu method in determining their phenol contents. The antidiabetic activity was tested in mice following streptozotocin diabetes induction, and selected oxidative stress markers (Malondialdehyde, Hydrogen peroxides and Catalase) were measured in order to evaluate the level of oxidative stress in treated animals.ResultsThe in vitro antioxidant activity using DPPH showed IC50 ranging from 0.19 ± 0.08 to 1.00 ± 0.06 mg/mL. The highest activity was obtained with the hydroethanol extracts of S. oleraceus (0.19 mg/mL and P. nitida (0.24 mg/mL). Polyphenol contents ranged from 182.25 ± 16.76 to 684.62 ± 46.66 μg Eq Cat/g. The methanol extract of P. nitida showed the highest activity, followed by the hydroethanol extract of S. oleraceus (616.89 ± 19.20 μEq Cat/g). The hydroethanol extract of whole plants (150 mg/Kg) and methanol leave extract of P. nitida (300 mg/Kg) exhibited significant antidiabetic activities with 39.40% and 38.48% glycaemia reduction, respectively. The measurement of stress markers in plasma, liver and kidney after administration of both extracts showed significant reduction in MDA and hydrogen peroxide levels, coupled with a substantial increase in catalase activity.ConclusionsThese findings suggest that S. oleraceus whole plant and P. nitida leaves possess both antidiabetic and antioxidant properties, and therefore could be used as starting point for the development of herbal medicines and/or source of new drug molecules against diabetes.

Effect of infliximab on metabolic disorders induced by Walker-256 tumor in rats

BackgroundThe purpose of this study was to investigate the effect of infliximab, an anti-tumor necrosis factor a (TNFα) mono-clonal antibody, on the progression of cachexia and several metabolic parameters affected by the Walker-256 tumor in rats. MethodsInfliximab (0.5mg/kg) was ip administered, twice a day, beginning at the day in which the Walker-256 tumor cells were in-oculated. After 12 days of treatment, the tumor growth, some parameters of cachexia/anorexia, the blood levels of triacylglycerol, glucose, lactate and urea, the peripheral response to insulin and the hepatic glycolysis and gluconeogenesis were investigated. The pe-ripheral response to insulin was evaluated by the insulin tolerance test and the glycolysis and gluconeogenesis in isolated perfused liver. ResultsThe treatment with infliximab did not alter the growth of the Walker-256 tumor, but attenuated (p<0.05) the reduction of body weight and prevented (p<0.05) the loss of retroperitoneal adipose tissue induced by the tumor. Moreover, treatment with in-fliximab tended to minimize the loss of gastrocnemius muscle, the reduction in food intake, the peripheral response to insulin and the liver gluconeogenesis from alanine, as well as the increased blood triacylglycerol, caused by the tumor. In contrast, treatment with infliximab did not attenuate the reduction in hepatic glycolysis and glycemia, nor did it minimize the rise in blood levels of lactate and urea induced by the tumor. ConclusionThe treatment with infliximab ameliorated some changes associated with cachexia, such as the reduction of adipose tissue and body weight, suggesting that TNFα plays a significant role in mediating these changes induced by the tumor. In addition, in-fliximab tended to improve or had no effect on other metabolic parameters affected by the Walker-256 tumor, suggesting that other mediators or tumor-related events are involved in these disorders.

Effects of alternate-day fasting on high-fat diet-induced insulin resistance in rat skeletal muscle

AimsThe purpose of this study was to investigate the effects of alternate-day fasting (ADF) on insulin-stimulated glucose transport activity in skeletal muscle in rats fed a high-fat diet. Main methodsMale Wistar rats were placed on a high-fat diet (n=24) or standard chow diet (Chow, n=12) for 10weeks. Rats fed the high-fat diet were separated into two groups after 4weeks. One group was subjected to ADF for the subsequent 6weeks (HF-ADF, n=12), and the other group was maintained on an ad libitum diet (HF-AL, n=12). After the 10-week dietary intervention, measurements of insulin-stimulated glucose uptake and insulin tolerance test (ITT) were performed. Key findingsWhereas the total intra-abdominal fat mass in the HF-AL group was significantly higher than in the Chow and HF-ADF groups, there was no significant difference between the Chow and HF-ADF groups. However, insulin-stimulated glucose uptake in skeletal muscles was significantly lower in both high-fat fed groups than in the Chow group. Muscle GLUT-4 protein content in HF-AL is significantly lower (~30%) than in Chow, and further reduction (~42%) was observed in the HF-ADF group rats. The HF-ADF and HF-AL group rats had less reduction in glycemia than did the Chow group rats during ITT. SignificanceADF was unable to eliminate high-fat diet-induced muscle insulin resistance, despite a substantial decrease in total intra-abdominal fat mass. This might have resulted from a reduction in GLUT-4 protein in both HF-AL and HF-ADF rats compared to the Chow group.

Antidiabetic Effect of theChrysobalanus icacoL. Aqueous Extract in Rats

Chrysobalanus icaco L. is a medicinal plant popularly known in Brazil as "Grageru" or "Abageru." It is used in African and American continents as medicinal food in the treatment of several diseases, including diabetes. This study used phytochemical screening to determine the antioxidant and α-amylase inhibitor activities of the aqueous extract (AECI) of C. icaco, and evaluated its antidiabetic potential in rodents. Phytochemical screening was performed using colorimetric tests with specific reagents. The in vitro antioxidant activity was evaluated by the scavenging activity of 2,2-diphenyl-1-picril-hydrazyl. The lethality test and behavioral screening was performed using an oral administration of 5 g/kg of AECI. The antidiabetic potential of AECI was evaluated through the oral glucose tolerance test (OGTT) and chronic hypoglycemic test at the doses of 100, 200, and 400 mg/kg (orally). Metformin was used as a reference drug in all tests. Diabetes was induced by injection of alloxan (40 mg/kg; intravenously). Phytochemical screening showed the presence of various compounds, including tannins, flavones, triterpenoids, steroids, saponins, and alkaloids. The in vitro antioxidant test demonstrated that AECI presented potent antioxidant activity. The lethality test and behavioral screening did not show lethality signs. In the OGTT test, AECI administration was not able to inhibit the elevation of glycemia. However, chronically administrated, it was able to cause a significant (P<.05) reduction of glycemia from 335±27 up to 197±15 mg/dL. These results demonstrate that the AECI presents a potential beneficial effect for diabetes.

Abstract 62: The Effect of ETC-1002 on Low Density Lipoprotein-Cholesterol and Additional Risk Factors in Patients With Type 2 Diabetes

Background Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular (CV) disease and over half do not achieve LDL-C goal. Statins lower CV risk by reducing LDL-C and inflammation, but have been associated with worsening glycemic control and new onset diabetes, resulting in class label warnings for all statins. ETC-1002 is an oral investigational drug in Phase 2 development to treat dyslipidemia and other cardio-metabolic risk factors through dual adenosine monophosphate-activated protein kinase activation and adenosine triphosphate-citrate lyase inhibition. Methods Sixty T2DM patients received either ETC-1002 (80 mg for 2 weeks followed by 120 mg for 2 weeks) or placebo (PBO) for 4 weeks following a 4 week T2DM drug washout and 1 week PBO run-in. Results ETC-1002 lowered LDL-C by 43% (PBO corrected mean -39%; p&lt;.0001) and non-HDL-C by 32% (PBO corrected mean -31%; p&lt;.0001). Median reductions in high sensitivity C-reactive protein (hsCRP) were 41% and 11% for ETC-1002 and PBO (p=.0011). Post hoc analyses showed additional benefits of ETC-1002. An LDL-C goal of &lt;100 mg/dL was achieved by 88% of ETC-1002 (21/24) and 4% of PBO subjects (1/24) not at baseline goal (p&lt;.0001 versus PBO). Reductions in post-prandial hyperglycemia following standard meal challenge were observed which were significant in a subgroup of patients with BMI ≥ 30 kg/m 2 (p=.0246 versus placebo). Using continuous glucose monitoring, ETC-1002 treatment resulted in significant peak glycemic reduction between hours 6-12 and a trend between hours 12-18 and 18-24. A weight loss trend was observed with ETC-1002. In patients with 24 hour diastolic ambulatory blood pressure (DBP) &gt; 80 mmHg, a 7 mmHg reduction versus PBO was observed (p=.0474). ETC-1002 was safe and well tolerated with no drop-outs, dose limiting side effects or serious adverse events, and no liver function tests &gt;2 times upper limit normal. Conclusion In patients with T2DM and dyslipidemia, ETC-1002 produced statin-like reduction in LDL-C, robust reduction in hsCRP and was associated with modest to significant improvement of blood pressure, glucose control and weight loss. The novel mechanism of action of ETC-1002 may provide unique benefit to these patients.

Glucoprivation of hypothalamic neurons elicits the counter‐regulatory response in rats

Whether the sympathetic counter‐regulatory response to hypoglycaemia is activated by glucose sensing neurons in the fore‐or hind‐brain remains controversial, since systemic hypoglycaemia excites neurons located in both areas. Here, we hypothesize that neurons in the perifornical hypothalamus (PeH), but not in the rostral ventrolateral medulla (RVLM), sense the reduction in glycaemia and increase the adrenal sympathetic nerve activity (ASNA). Experiments were conducted in anaesthetized (urethane, 1.2 g/kg i.v.), paralysed (pancuronium bromide, 1 mg/kg i.v.), and artificially ventilated male Sprague‐Dawley rats. Local glucopaenia, induced by bilateral microinjections of 2‐deoxy‐D‐glucose (2DG; 15 ng/50 nl) into the PeH, increased ASNA (101±1% vs 175±11%, N=10; P&lt;0.05) and blood glucose (6.6±0.3 vs 7.6±0.3 mmol/l, N=9; P&lt;0.05). A higher dose of 2DG (150 ng/50 nl) further increased ASNA (157±7% vs 280±59%, N=6; P&lt;0.05) and blood glucose (7.5±0.5 vs.9.6±0.5 mmol/l, N=4; P&lt;0.05). Microinjections of 2DG (15 ng/50 nl) into the RVLM (N=6) neither changed ASNA (101±1% vs 84±14%) nor blood glucose (6.4±0.1 vs 6.9±0.1 mmol/l). Subsequent intravenous infusion of 2DG (250 mg/kg) increased ASNA (101±1% vs 183±8%; P&lt;0.05). The results indicate that neurons in the PeH, but not in the RVLM, are glucose sensitive and their excitation produces adrenaline release in response to glucoprivation.

Influence of &lt;i&gt;Moringa oleifera&lt;/i&gt; leaves on atherogenic lipids and glycaemia evolution in HIV-infected and uninfected malnourished patients

Objectives: The study evaluated mineral composition of “Togolese ecotype” of Moringa oleifera leaves and its effect on anthropometric parameters, atherogenic lipids and glycaemia during nutritional recovery in HIV negative and HIV positive malnourished patients after daily use of the leaves powder. Methodology and results: Patients aged from 12 months to 8 years, consumed every day for 15 weeks the leaves powder. Results showed that powder is rich in proteins, micronutrients and induced BMI increase in both patients (p C 0.001). Biochemical parameters determination showed decrease in total cholesterol, triglycerides, LDL-cholesterol (p C 0.01), atherogenicity index (AI) correlated with HDL-cholesterol increase (p C 0.001) in HIV negative. Increase in triglycerides, LDL-cholesterol, AI (p C 0.001) correlated with HDLcholesterol decrease (p C 0.001) is observed in HIV positive. Total cholesterol decreased more in HIV positive asymptomatic and increased in patients treated with ARV drugs (p C 0.0001). Glycaemia level is decreased in both patients of the study. Conclusion and application of findings: This study confirms higher concentrations of proteins, micronutrients, hypolipidemic potential and hypocholesterolemic activity of M. oleifera leaves. This explained nutritional recovery and reduction of atherogenic lipids. Positive effect of the powder on cholesterol metabolism is due to beta-sitosterol, bioactive phytoconstituent of the leaves which fixed LDL particles and thought to be through the lowering significantly of their plasma concentrations. Reduction of glycaemia in both patients confirms also hypoglycemic properties of leaves with high concentration of polyphenols and antioxydants. The lowering of atherogenic risk and glycaemia after regular consumption of M. oleifera leaves powder is more significant in HIV negative than HIV positive patients. Results of this study bring information which will make it possible to pediatrics and nutritionists to adapt better use of M. oleifera leaves to combat malnutrition and the follow-up of HIV positive persons and in particular those on antiretroviral treatment. Key words: Moringa oleifera , malnutrition, atherogenic lipids, glycaemia, HIV/AIDS.

Combretum lanceolatum flowers extract shows antidiabetic activity through activation of AMPK by quercetin

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500mg/kg of metformin and diabetic treated with 250 or 500mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50μg/mL of ClEtOH, similarly to the incubation with metformin (50μg/ mL) or quercetin (10μg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin.

Pharmaceutical consultation as a tool to improve health outcomes for patients with type 2 diabetes

This study develops and evaluates a pharmaceutical consultation program (PCP) to improve treatment for Type 2 diabetes patients (T2DP) and reduce risk factors for diabetic complications with possible application in other chronic diseases. We recruited T2DP receiving conventional medical treatment but with fasting glycemia &gt;140mg/dl and/or glycated hemoglobin &gt;7%. The PCP includes strategies obtained from Dader's method, the PWDT (Pharmacist's Workup of Drug Therapy method) model of pharmaceutical care, the SOAP (Subjective data, Objective data, Assessment, and Plan of care) method, and concepts based on a nursing care model. The PCP evaluated lifestyle, pharmacotherapy and monitoring it using laboratory tests, vital signs, and anthropometry. These procedures were repeated every 4 months for 1 year. Data obtained in each consultation were used to provide patient education focusing on healthy lifestyles and medications. Fifty patients completed the PCP. There were reductions in glycemia (P&lt;0.0001), glycated hemoglobin (P=0.0022), cholesterolemia (P=0.0072), triacylglycerolemia (P=0.0204) and blood pressure (P&lt;0.0001). Increased concordance with drug treatment and correction of drug-related problems contributed to improved treatment. We can therefore conclude that our PCP was suitable for improving health outcomes in T2DP by reducing risk factors for diabetic complications.

Resistant starch

Resistant starch represents a diverse range of indigestible starch-based dietary carbohydrates. Resistant starch has been investigated in the past for its effects on bowel health (pH, epithelial thickness, and apoptosis of colorectal cancer cells); reduction in postprandial glycemia; increased insulin sensitivity; and effects on the gut microbiome. This review highlights advances as resistant starch gains clinical relevance as a potential treatment/preventive tool for diseases such as colorectal cancer (CRC) and diabetes. Recent articles have evaluated the comparative physiological effects of different types of resistant starch and investigated the effects of resistant starch on blood lipids, body weight, and defining resistant starch-induced changes to the micriobiome that may be important in health and disease. The most novel and relevant recent data describe a role for resistant starch in ameliorating inflammation; the use of resistant starch for optimal bowel health and prevention of CRC; and, further, that the systemic effects of resistant starch may be important for the treatment of other forms of cancer, such as breast cancer. This review describes advances in resistant starch research highlighting the gastrointestinal effects that are now being linked to systemic, whole body effects with clinical relevance. These effects have important implications for overall health and the prevention or amelioration of various chronic diseases.

Resistance Versus Aerobic Exercise

OBJECTIVEIn type 1 diabetes, small studies have found that resistance exercise (weight lifting) reduces HbA1c. In the current study, we examined the acute impacts of resistance exercise on glycemia during exercise and in the subsequent 24 h compared with aerobic exercise and no exercise.RESEARCH DESIGN AND METHODSTwelve physically active individuals with type 1 diabetes (HbA1c 7.1 ± 1.0%) performed 45 min of resistance exercise (three sets of seven exercises at eight repetitions maximum), 45 min of aerobic exercise (running at 60% of Vo2max), or no exercise on separate days. Plasma glucose was measured during and for 60 min after exercise. Interstitial glucose was measured by continuous glucose monitoring 24 h before, during, and 24 h after exercise.RESULTSTreatment-by-time interactions (P < 0.001) were found for changes in plasma glucose during and after exercise. Plasma glucose decreased from 8.4 ± 2.7 to 6.8 ± 2.3 mmol/L (P = 0.008) during resistance exercise and from 9.2 ± 3.4 to 5.8 ± 2.0 mmol/L (P = 0.001) during aerobic exercise. No significant changes were seen during the no-exercise control session. During recovery, glucose levels did not change significantly after resistance exercise but increased by 2.2 ± 0.6 mmol/L (P = 0.023) after aerobic exercise. Mean interstitial glucose from 4.5 to 6.0 h postexercise was significantly lower after resistance exercise versus aerobic exercise.CONCLUSIONSResistance exercise causes less initial decline in blood glucose during the activity but is associated with more prolonged reductions in postexercise glycemia than aerobic exercise. This might account for HbA1c reductions found in studies of resistance exercise but not aerobic exercise in type 1 diabetes.

Fish oil supplementation for two generations increases insulin sensitivity in rats

We investigated the effect of fish oil supplementation for two consecutive generations on insulin sensitivity in rats. After the nursing period (21 days), female rats from the same prole were divided into two groups: (a) control group and (b) fish oil group. Female rats were supplemented with water (control) or fish oil at 1 g/kg body weight as a single bolus for 3 months. After this period, female rats were mated with male Wistar rats fed on a balanced chow diet (not supplemented). Female rats continued to receive supplementation throughout gestation and lactation periods. The same treatment was performed for the next two generations (G1 and G2). At 75 days of age, male offspring from G1 and G2 generations from both groups were used in the experiments. G1 rats did not present any difference with control rats. However, G2 rats presented reduction in glycemia and lipidemia and improvement in in vivo insulin sensitivity (model assessment of insulin resistance, insulin tolerance test) as well as in vitro insulin sensitivity in soleus muscle (glucose uptake and metabolism). This effect was associated with increased insulin-stimulated p38 MAP kinase phosphorylation and lower n-6/n-3 fatty acid ratio, but not with activation of proteins from insulin signaling (IR, IRS-1 and Akt). Global DNA methylation was decreased in liver but not in soleus muscle. These results suggest that long-term fish oil supplementation improves insulin sensitivity in association with increased insulin-stimulated p38 activation and decreased n-6:n-3 ratio in skeletal muscle and decreased global DNA methylation in liver.

Investigation of the mechanisms contributing to the compensatory increase in insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques

Dexamethasone has well-described effects to induce insulin resistance and increase insulin secretion. Herein, we examined potential contributors to the effect of dexamethasone to increase insulin secretion in rhesus macaques. Six male rhesus macaques received daily injections of either saline or dexamethasone (0.25 mg/kg i.m. for 7 days) in random order with 3 weeks between treatments. At the end of the treatment period, animals were fasted overnight and underwent a feeding study the next day, during which blood samples were taken before and for 60 min after a meal in order to assess islet hormone and incretin secretion. Dexamethasone induced marked increases in fasting plasma insulin, glucagon, leptin, and adiponectin concentrations (P<0.05). Surprisingly, the glycemic response after meal ingestion was decreased twofold during dexamethasone treatment (P<0.05). Dexamethasone-treated animals exhibited a significant increase in both insulin and glucose-dependent insulinotropic polypeptide (GIP) secretion during the feeding study (P<0.05). However, glucagon-like peptide-1 secretion was significantly lower in dexamethasone-treated animals compared with controls (P<0.01). Fasting and meal-stimulated pancreatic polypeptide concentrations (an index of the parasympathetic input to the islet) did not differ between saline and dexamethasone treatments. However, the proinsulin:insulin ratio was decreased throughout the feeding study with dexamethasone treatment suggesting an improvement of β-cell function (P<0.05). In conclusion, the maintenance of euglycemia and reduction of postprandial glycemia with short-term dexamethasone treatment appears to be due to the marked elevations of fasting and meal-stimulated insulin secretion. Furthermore, increases in postprandial GIP secretion with dexamethasone treatment appear to contribute to the effect of dexamethasone treatment to increase insulin secretion.

Comment on Marciano et. al.: Effects of type 2 diabetes mellitus on coronary microvascular function and myocardial perfusion in patients without obstructive coronary artery disease

Dear Sir, I recently read with interest the article by Marciano et al. about the effect of diabetes mellitus on coronary microvascular diseases. I was quite puzzled by the analysis of the data shown in Fig. 2. The author states in the results that there is a significant correlation between CPT-CF and fasting glycaemia. Visual inspection of the graphs would appear to reveal a different conclusion, as the two quantities look disconnected. Anscombe [1] explained the importance of looking not only at the correlation coefficient value but also at the data distribution. He provided, as examples, four different datasets, each characterized by the same mean and variance along X and Y, the same regression line and the same (extremely statistically significant) correlation coefficient (0.816 with n011). In only one of these four examples were the correlation coefficient and the regression line indeed indicative of a “correlation” as commonly understood. Specifically, the fourth dataset shows a situation representative of the situation shown in Fig. 2 of the aforementioned article [2]. Anscombe shows that taking ten points with no correlation at all and one outlier very far from all the other ones gives a very high correlation coefficient. This, of course, is not indicative of a relationship, nonetheless linear, between the variables! A more formal analysis could reveal clearly the mathematical hypothesis that is violated when computing a correlation coefficient and its p value from data with such a distribution. Therefore, I would say that the statement that “a significant inverse correlation was found between fasting glycaemia and endothelium-dependent vasodilatation” is not correct. In fact the analysis of only diabetic patients does not support this finding. With the exception of a small number of outliers (4 out of 49 total patients), all of the points seems to lie inside a perfect circle, the very shape used to describe uncorrelated variables. If the point corresponding to the patient with a fasting glycaemia of 300 mg/dl and a CPT-CF ratio of about 1.3 were removed the correlation coefficient would drop to about zero. That would also happen with a reduction of fasting glycaemia and an increase in CPT-CF ratio, within the boundaries of the precision of the two measurements. The fasting glycaemia values and CPT-CF ratios of the three other “outlier” points suggest that these probably represent just the three most healthy nondiabetic patients.

Reducing cardiovascular disease risk in type 2 diabetes: is the focus on glycaemia warranted?

Cardiovascular disease remains a major source of morbidity and mortality in type 2 diabetes mellitus. This article examines the recent evidence from trials and related meta-analyses on the effects of glycaemic control on cardiovascular disease (and, to a lesser extent, microvascular outcomes) in diabetes, and compares this with evidence accrued from blood pressure and statin trials. On the basis of such evidence, as well as pragmatic considerations, it is clear that clinicians should place stronger emphasis on lipid and blood pressure management to lessen cardiovascular risks. At the same time, cardiovascular disease benefits of glycaemia reduction appear less pronounced, with patient characteristics critically influencing risk to benefit ratio. Recent guidelines now reflect recent observations on glycaemic control (with relaxed targets in specific patient groups), whereas future guidelines should encourage physicians to prioritize lipid-lowering and blood pressure management in patients with diabetes.

Effect of an aqueous extract of Cucurbita ficifolia Bouché on the glutathione redox cycle in mice with STZ-induced diabetes

Ethnopharmacological importanceCucurbita ficifolia is used in Mexican traditional medicine as an anti-diabetic and anti-inflammatory agent and its actions can be mediated by antioxidant mechanisms. Disturbance in the homeostasis of glutathione has been implicated in the etiology and progression of diabetes mellitus and its complications. Material and methodsIt was evaluated, the effect of an aqueous extract of Cucurbita ficifolia on glycemia, plasma lipid peroxidation; as well as levels of reduced (GSH) and oxidized (GSSG) glutathione and activities of enzymes involved in glutathione redox cycle: glutathione peroxidase (GPx) and glutathione reductase (GR) in liver, pancreas, kidney and heart homogenates of streptozotocin-induced diabetic mice. ResultsIncreased blood glucose and lipid peroxidation, together with decreased of GSH concentration, GSH/GSSG ratio and its redox potential (Eh), and enhanced activity of GPx and GR in liver, pancreas and kidney were the salient features observed in diabetic mice. Administration of the aqueous extract of Cucurbita ficifolia to diabetic mice for 30 days, used at a dose of 200mg/kg, resulted in a significant reduction in glycemia, polydipsia, hyperphagia and plasma lipid peroxidation. Moreover, GSH was increased in liver, pancreas and kidney, and GSSG was reduced in liver, pancreas and heart, therefore GSH/GSSG ratio and its Eh were restored. Also, the activities involved in the glutathione cycle were decreased, reaching similar values to controls. ConclusionsAn aqueous extract of Cucurbita ficifolia with hypoglycemic action, improve GSH redox state, increasing glutathione pool, GSH, GSH/GSSG ratio and its Eh, mechanism that can explain, at least in part, its antioxidant properties, supporting its use as an alternative treatment for the control of diabetes mellitus, and prevent the induction of complications by oxidative stress.

Treatment evaluation of liraglutide in type 2 diabetes

Liraglutide is a Glucagon like Peptide-1 (GLP-1) receptor agonist, which stimulates GLP-1 receptors and consequently leads to various cardio-metabolic and glycemic improvements in individuals with Type 2 Diabetes Mellitus (T2DM). It is administered once daily as a subcutaneous injection and has been extensively studied in randomized placebo and active comparator studies demonstrating favorable effects on glycemic control and weight reduction. This short review summarizes the role and practical use of this agent in the context of efficacy and safety information obtained during clinical trials.

Glucose and blood pressure lowering effects of Pycnogenol® are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy

Diabetic cardiomyopathy shows ECG alterations related to cardiac repolarization and manifested by increased duration of QT interval. Although the mechanism is unknown, it is widely believed that the reduction of hyperglycaemia might prevent such alterations. To test this hypothesis, we used the standardized extract of French pine bark – Pycnogenol® (PYC) with hypoglycaemic and antioxidant properties in 8–9 week old rats with experimentally (streptozotocin) induced diabetes mellitus (DM). PYC was administered orally for 6 weeks in three different doses (10, 20, and 50mg/kg b.w., resp.). Experimental DM was manifested by hyperglycaemia (four to six-fold increase in plasma glucose concentration; p<0.05) and significantly increased mean arterial blood pressure (by 19%; p<0.05) measured using catheterization of carotid artery in vivo. Both abnormalities were dose-dependently reduced by PYC. In addition, diabetic cardiomyopathy was associated with a significant increase in left ventricular weight to body weight ratio (by 21%; p<0.05) and a significant decrease of the width of cardiomyocytes (by 23%; p<0.05) indicating cardiac edema on the one side, and hypotrophy of cardiomyocytes on the other. Both of these changes were not affected by PYC. Consequently to metabolic and hemodynamic alterations, significant prolongation of QT interval (by 20%; p<0.05) was present in diabetic rats, however, PYC failed to correct it. Conclusively, PYC fails to correct QT prolongation in spite of dose-dependent reduction of glycaemia and high blood pressure in streptozotocin-induced diabetic cardiomyopathy.

Effects of Psidium guajava on the metabolic profile of Wister rats

The consumption of a diet rich in fruits, vegetables, seeds and whole foods contributes to reduce the risk factors for chronic disorders such as insulin resistance, high blood pressure and dyslipidemia. The objective of this study was to evaluate the effect of the consumption of the pulp and seeds of guava (Psidium guajava) on the metabolic profile of Wistar rats. The animals were divided into a control group, G1, and two treatment groups: G2 – fed with guava pulp juice, and G3 – fed with rat food containing guava seeds. The duration of the treatment was 40 days. A significant reduction in glycemia and in the levels of triacylglycerides and total cholesterol, and augmented levels of High-density lipoproteincholesterol (HDL-c) were observed in the animals fed with guava pulp juice and seeds. The levels of alanine aminotransferase (AST) and alanine aminotransferase (ALT) enzymes were also reduced. These findings indicate that the use of guava (Psidium guajava) pulp and seeds, the latter considered agroindustrial wastes, contribute significantly to the control of biochemical variables involved in the incidence of chronic degenerative disorders in the population. Key words: Psidium guajava, glycemia, cholesterol, Wistar rats.