TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

When proteins change their structure and clump together, formation of amyloid fibrils and plaques may occur. Such 'misfolding' and 'protein aggregation' processes damage cells and cause diseases such as Alzheimer's and type 2 diabetes. A team of scientists from the Technical University of Munich (TUM) headed by Professor Aphrodite Kapurniotu have now developed molecules that suppress protein aggregation and could pave the way for new treatments to combat Alzheimer's, type 2 diabetes and other cell-degenerative diseases.

The scientists designed and studied 16 different peptide molecules in order to find out which of them are able to impede the 'clumping' of the proteins amyloid beta (Aß) and islet amyloid polypeptide (IAPP), which are associated with Alzheimer's and type 2 diabetes.

The molecules were designed on the basis of scientific work that shows that the Aß and IAPP proteins interact with each other, and that this 'cross-amyloid interaction' suppresses their clumping. The researchers selected short sequences of the IAPP protein that correspond to the key regions involved in the interaction with the Alzheimer's protein. These "hot segments" were then chemically linked to each other by using specific peptide segments as 'linkers' in order to mimic and optimize the IAPP cross-amyloid interaction surface.

Ref : http://www.tum.de/en/about-tum/news/press-releases/short/article/32611/

TUM scientists develop molecules that could pave way for new treatments to fight Alzheimer's, diabetes

Promising preliminary results for AKB-9778 in diabetic macular oedema

AKB-9778, a small molecule competitive inhibitor of vascular endothelial-protein tyrosine phosphatase (VE-PTP), has a good safety and efficacy profile in patients with diabetic macular oedema, suggests a preliminary dose-escalation study. 

By blocking VE-PTP, AKB-9778 promotes the activation of Tie2, a protein involved in the regulation of vascular permeability, explain the researchers. In preclinical studies, AKB-9778 has been shown to suppress vascular leakage as well as neovascularisation of the retina and choroid, they add.

In this phase Ib trial, four groups of six patients were treated with open-label AKB-9778 self-administered twice daily via subcutaneous injections at doses of 5.0 mg, 15.0 mg, 22.5 mg or 30.0 mg for 4 weeks.

Participants treated with the higher 22.5 mg and 30.0 mg doses, but not those given the 5.0 mg and 15.0 mg doses, experienced headache, dizziness and vasovagal events such as presyncope or syncope – adverse events that are consistent with the anticipated vasodilatory activity of AKB-9778, say the researchers.

“Modest decreases” in resting systolic blood pressure were also observed in the 22.5 mg and 30.0 mg groups, they report, adding that these effects and the adverse events were “transient” and “generally resolved” shortly after dosing.

At 4 weeks, best-corrected visual acuity (BCVA) improved from intake in the 15.0 mg, 22.5 mg and 30.0 mg groups; of 18 participants, 10 achieved an improvement of five to 10 letters, one improved by 11 letters and two by over 15 letters.

Moreover, seven patients who received AKB-9778 at doses of 15.0 mg or more showed decreases in study eye central subfield thickness (CST) from baseline, with reductions of over 100 μm in five patients and of 50 to 100 μm in two patients.

Promising preliminary results for AKB-9778 in diabetic macular oedema

Fish Oil Pills Might Cut Diabetes Risk....

Supplements, also known as omega-3 fatty acids, increase levels of a hormone called adiponectin that's linked to insulin sensitivity, Harvard researchers found. Higher levels of this hormone in the bloodstream have also been linked to a lower risk for heart disease.

"While prior animal studies found fish oil increased circulating adiponectin, whether similar effects apply in humans is not established," the study's lead author, Jason Wu, from the Harvard School of Public Health, said in a news release from the Endocrine Society.

For their study, the researchers conducted a "meta-analysis" of 14 clinical trials. A meta-analysis reviews existing research and attempts to find a consistent pattern. In this case, the studies that were reviewed were all randomized, placebo-controlled trials, which is considered the gold standard in research.

"By reviewing evidence from existing randomized clinical trials, we found that fish oil supplementation caused modest increases in adiponectin in the blood of humans," Wu explained.

Overall, the new study looked at 682 people who took fish oil supplements, and 641 who were given placebos such as sunflower or olive oil.

Among the people treated with fish oil, adiponectin levels increased by 0.37 micrograms per milliliter of blood. This hormone plays a beneficial role in processes that affect metabolism, such as blood sugar regulation and inflammation.

Because the effects of fish oil varied significantly in the studies analyzed, the researchers suggested that omega-3 fatty acids could have a stronger effect in certain groups of people. The investigators concluded that more research is needed to determine which people would benefit most from fish oil supplements.

"Although higher levels of adiponectin in the bloodstream have been linked to lower risk of diabetes and coronary heart disease, whether fish oil influences glucose [blood sugar] metabolism and development of type 2 diabetes remains unclear," Wu said.

More - Read at

Fish Oil Pills Might Cut Diabetes Risk, Researchers Say - Drugs.com MedNews

Popular diabetes drug does not improve survival rates after cancer

In continuation of my update on metformin

Despite previous scientific studies that suggest diabetes drug metformin has anti-cancer properties, a new, first-of-its-kind study from Women's College Hospital has found the drug may not actually improve survival rates after breast cancer in certain patients.

The study, published in the journal Diabetes Care, failed to show an improved survival rate in older breast cancer patients with diabetes taking the drug metformin, a first-line treatment for diabetes. However, the authors caution further research is necessary to validate the study's findings.

"Metformin is a drug commonly used by diabetic patients to control the amount of glucose in their blood," said the study's lead author Dr. Iliana Lega, a research fellow at Women's College Research Institute. "Although existing scientific literature suggests that drug may prevent new cancers and death from breast cancer, our study found the drug did not significantly impact survival rates in our patients."

Scientific research has found metformin is associated with an up to 30 per cent reduction in new cancers and a reduction in tumour growth in non-diabetic breast cancer patients treated with the drug, Dr. Lega notes in the study.

To test the drug's anti-cancer properties, the authors examined 2,361 women, aged 66 or older who were treated with the drug and diagnosed with breast cancer between April 1, 1997 and March 31, 2008. The women were followed from their date of breast cancer diagnosis until their death or until March 30, 2010. The researchers found no significant statistical correlation between cumulative use of metformin and death from all causes or a significant reduction in deaths due to breast cancer.

"What makes our study so unique is that while the effects of metformin have been well documented, previous research has not examined the cumulative effects of the drug on patients, particularly breast cancer patients with diabetes," Dr. Lega said. "This is important given that diabetic patients may switch drugs over the course of their treatment."

The authors note a lack of data on body mass index, breast cancer stage and a short followup period for breast-cancer specific deaths, limit interpretation of their findings. Further research is necessary in a younger population of patients with breast cancer and diabetes.

"Understanding the effects of metformin on breast cancer patients is critical in helping address the gap in cancer outcomes in patients with and without diabetes," she added. "The findings will help physicians inform treatment plans for patients with diabetes."

Ref : http://care.diabetesjournals.org/content/early/2013/04/30/dc12-2535

Popular diabetes drug does not improve survival rates after cancer

Reduced melatonin levels linked to greater diabetes risk - Life Extension Update

In continuation of my update on Melatonin....

"Melatonin receptors have been found throughout the body in many tissues including pancreatic islet cells, reflecting the widespread effects of melatonin on physiological functions such as energy metabolism and the regulation of body weight," Ciaran McMullan and colleagues at Brigham and Women's Hospital noted in their introduction to the article. "Loss-of-function mutations in the melatonin receptor are associated with insulin resistance and type 2 diabetes. Additionally, in a cross-sectional analysis of persons without diabetes, lower nocturnal melatonin secretion was associated with increased insulin resistance."

The researchers matched 370 women who developed diabetes while enrolled in the Nurses' Health Study with 370 nondiabetic participants. Morning urine samples obtained upon enrollment in 2000 were analyzed for the ratio of 6-sulfoxymelatonin (the major metabolite of melatonin) to creatinine in order to estimate overnight melatonin secretion.

Women with diabetes had a 6-sulfatoxymelatonin to creatinine ratio that was significantly lower than that of the control group. Among those whose ratio was among the lowest of the participants, the adjusted risk of developing diabetes was more than twice that of women whose ratio was among the highest group.

"This is the first time that an independent association has been established between nocturnal melatonin secretion and type 2 diabetes risk," announced Dr McMullan, who is a researcher in the Renal Division and Kidney Clinical Research Institute at BWH. "Hopefully this study will prompt future research to examine what influences a person's melatonin secretion and what is melatonin's role in altering a person's glucose metabolism and risk of diabetes."

"It is interesting to postulate from these data, in combination with prior literature, whether there is a causal role for reduced melatonin secretion in diabetes risk," the authors remark. "Further studies are needed to determine whether increasing melatonin levels (endogenously via prolonged nighttime dark exposure or exogenously via supplementation) can increase insulin sensitivity and decrease the incidence of type 2 diabetes."

Ref : http://jama.jamanetwork.com/article.aspx?articleid=1674239

Reduced melatonin levels linked to greater diabetes risk - Life Extension Update

Metformin more effective than sulfonylurea in controlling type 2 diabetes

In continuation of my update on Metformin

A Vanderbilt study examining the impact of the two most commonly prescribed oraldiabetes medications on the risk for heart attack, stroke and death has found the drug metformin has benefits over sulfonylurea drugs.

It was important to examine the cardiovascular impact of the more commonly used diabetes drugs after recent controversy surrounded another diabetes medication, rosiglitazone, because it was associated with an increased cardiac risk, said lead author, Christianne L. Roumie, M.D., MPH, assistant professor of Internal Medicine and Pediatrics. Smaller studies pointed to a potential advantage of taking the drug metformin but this study confirms this in a large population.

"We demonstrated that for every 1,000 patients who are using metformin for a year there are two fewer heart attacks, strokes or deaths compared with patients who use sulfonylureas. I think this reinforces the recommendation that metformin should be used as the first medication to treat diabetes," Roumie said.

The researchers looked at the charts of more than 250,000 veterans receiving care in Veterans Health Administration hospitals throughout the United States.

More...

Metformin more effective than sulfonylurea in controlling type 2 diabetes

Diabetes Drug Could Be a Promising Therapy for Traumatic Brain Injury

In continuation of my update on Exendin-4

Research commissioned by the United States Air Force, Prof. Chaim Pick of Tel Aviv University's Sackler Faculty of Medicine and Dr. Nigel Greig of the National Institute of Aging in the US have discovered that Exendin-4, an FDA-approved diabetes drug, significantly minimizes damage in TBI animal models when administered shortly after the initial incident. Originally designed to control sugar levels in the body, the drug has recently been found effective in protecting neurons in disorders such as Alzheimer's disease.

Prof. Pick's collaborators include his TAU colleagues Dr. Vardit Rubovitch, Lital Rachmany-Raber, and Prof. Shaul Schreiber, and Dr. David Tweedie of the National Institute of Aging in the US. Detailed in the journal Experimental Neurology, this breakthrough is the first step towards developing a cocktail of medications to prevent as much brain damage as possible following injury....

American Friends of Tel Aviv University: Diabetes Drug Could Be a Promising Therapy for Traumatic Brain Injury

First combination drug to treat type 2 diabetes and high cholesterol receives FDA approval

In continuation of my update on Simvastin

The U.S. Food and Drug Administration recently approved Juvisync (sitagliptin and simvastatin), a fixed-dose combination (FDC) prescription medication that contains two previously approved medicines in one tablet for use in adults who need both sitagliptin and simvastatin.....

More....

New class of anti-diabetic compound established

New class of anti-diabetic compound established

Liraglutide as Additional Treatment in Type 1 Diabetes

In continuation of my update on Liraglutide...

 Results of a small, observational study conducted at the University at Buffalo suggest that liraglutide (below structure) , an injectable medication used to treat type 2 diabetes, also helps type 1 diabetics on insulin achieve optimal control of their blood glucose levels.

More....

Lyxumia®, as an add-on to basal Insulin, shows significant positive phase III results

Sanofi  announced today that new results from a Phase III study showed that the investigational product Lyxumia® (lixisenatide see structure above), when used as an add-on therapy to basal insulin (in association with or without metformin), achieved its primary efficacy endpoint of significantly reducing HbA1c versus placebo for patientswith type 2 diabetes without significantly increasing their risk of hypoglycemia...

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Chillies for diabetes: Study

In continuation of my update on diabetes and its treatment,  I find the following study interesting.  In fact, I had a blog article  , where in the authors claim that Capsaicin may cause weight loss and I think these findings are of great significance........

Chillies for diabetes: Study

 

New evidence that drinking coffee may reduce the risk of diabetes

In continuation of my update on benefits of coffee....

New evidence that drinking coffee may reduce the risk of diabetes

Salsalate may be useful for the treatment of patients with type 2 diabetes .....

We know that Salsalate (see structure; source Drugs.com)  is a  non-steroidal anti-inflammatory drug (NSAID) belonging to salicylates. It is used in the treatment of Osteo Arthritis and  Rheumatoid Arthritis. 

Now researchers from Harvard Medical School, lead by Dr. Allison Goldfine, have come up with interesting finding, i.e., Salsalate may be useful for the treatment of patients with type 2 diabetes as well. In a three-month trial of people with type 2 diabetes ,  those who took the drug showed significantly improved blood glucose levels. 

Starting off, the patients all had levels of hemoglobin A1C (a standard measurement that reflects blood sugar levels over several months) in the range of 7.0 to 9.5%. A significant number of those who took salsalate saw this number drop by 0.5%, a result that is in the range of several recently released diabetes therapeutics. Other tests related to glucose levels also showed substantial improvement.  

Overall the drug appeared to be safe and to be tolerated well by patients. The study included 108 individuals, aged from 18 to 75 years, at 17 clinical sites around the United States. Patients were randomly divided into four; three groups were each given differing amounts of salsalate in three daily doses, while the fourth received placebos. All patients continued with their current regimes for managing diabetes.

Though these preliminary findings  suggests  that,   salsalate may provide an effective, safe and inexpensive new avenue for diabetes treatment, however the researchers  want to complete the ongoing  additional studies so that they can further substantiate their claim........

Ref : March 16 in the Annals of Internal Medicine

FDA approves Liraglutide for Type 2 Diabetes, with a warning.....

Liraglutide, marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, Now the same drug has been approved  by the FDA.

The interesting part of this approval lies in the fact that, Liraglutide was reviewed by an FDA advisory panel which expressed serious concerns that the drug may cause thyroid tumors. Whereas based on the studies and consistent with the relevant literature it is obvious that the rodent C-cell tumors induced by dosing of liraglutide were caused by a non-genotoxic, specific receptormediated mechanism to which rodents are particularly sensitive whereas non-human primates and humans are not. Liraglutide improves control of blood glucose.  It reduces meal-related hyperglycaemia (for 12 hours after administration) by increasing insulin secretion, delaying gastric emptying, and suppressing prandial glucagon secretion.

As per the claim by the company, the advantages are:

a) acts in a glucose-dependent manner, and  stimulate insulin secretion only when blood glucose levels are

    higher than normal. Consequently, it shows negligible risk of hypoglycemia;

b) has the potential for inhibiting apoptosis and stimulating regeneration of beta cells;

c) decreases appetite and maintains body weight, as shown in a head-to-head study versus glimepiride;

d) lowers blood triglyceride levels and only mild and transient side effects, mainly gastrointestinal &
e) has a half-life after subcutaneous injection of 11–15 hours and hence once-daily GLP-1 derivative.

But the FDA, warned that the once-daily injection shouldn't be used as an initial (first-line) treatment until additional studies are completed, since the drug may cause thyroid tumors or a rare disease called medullary thyroid cancer. People at risk for this type of cancer shouldn't use the drug, the FDA stressed. Hope the further studies will rule out the possibility of the drug causing thyroid tumors..

For details, one can read the press release....

Encouraging results from first phase III clinical trials of Balaglitazone (an anti-diabetic drug)......

Balaglitazone (CAS-199113-98-9),5-[[4-[3-methyl-4-oxo-3,4-dihydro-2-quinazolinyl] methoxy]phenyl-methyl]thiazolidine-2,4-dione, (see structure) is a novel partial agonist of PPAR-gamma, which elicits only 52% of the PPAR-gamma activation observed with both pio- and rosiglitazone.

            

Pre-clinical studies have indicated that besides robust glucose lowering ability, balaglitazone results in lower body fluid accumulation, lower fat accumulation, less heart enlargement and no reduction of bone formation, indicating that Balaglitazone may be able to displace the balance between desired and side effects, and thus show a better safety profile than full agonists of PPAR-gamma.

 Now Reddy's Lab, has come up with interesting results from its  Phase III clinical trial programme.The study explored the impact of adding placebo, Balaglitazone 10mg, Balaglitazone 20mg or Pioglitazone 45mg to a background treatment regimen of stable insulin therapy for a period of 26 weeks. The primary endpoint was HbA1c reduction, while several secondary endpoints including fasting plasma glucose, oedema, weight gain, and body composition were considered.

In all, 409 patients were randomized in roughly equal proportions across the four arms of the study. All three active arms (Balaglitazone 10mg, 20mg and Pioglitazone 45mg) showed similar levels of efficacy with respect to both HbA1c and fasting plasma glucose.

All three active arms showed good tolerability and adverse event profile, with Balaglitazone 10mg demonstrating less water retention, less fat accumulation, lower weight/BMI gain and less bone loss when compared to the Pioglitazone arm.

Encourged by these results both companies (Dr. Reddy's & Rheoscience) are planning for detailed studies required for registration of  Balaglitazone.

Type 2 diabetes is a major cause of morbidity and mortality in the industrialized world, with cardiovascular disease as the leading cause of death, accounting for almost 50% of all T2D deaths. Furthermore, the number of T2D patients is increasing rapidly, and the number of patients is expected to reach between 300 and 380 million by 2025, thereby placing an enormous economical burden on global healthcare. Hope new drugs will take care of this problem.



Ref : http://www.drreddys.com/media/popups/jan4_2010.html

Metformin - safe for patients with advanced heart failure and diabetes mellitus

In continuation of my update on Metformin,   I am sharing herewith  something interesting info,  about the same drug. Now researchers from David Geffen School of Medicine at UCLA,  have found that metformin, a drug often used in the treatment of diabetes mellitus, is safe for use in treating patients who have both diabetes and advanced heart failure. 

Diabetes increases not only the risk of developing heart failure, but also the risk of death among heart failure patients. This is due in large part to the fact that diabetes, because it increases the amounts of sugar and fat circulating in the bloodstream, accelerates the onset of coronary atherosclerosis. This hardening and thickening of blood vessels is the hallmark of atherosclerotic heart disease, the most common cause of death. The optimal treatment for high glucose and fat blood levels among heart failure patients has not been demonstrated.

The new study involved 401 patients of an average age of 56, with type II diabetes and advanced systolic heart failure. This patient cohort was followed for 14 years in a comprehensive heart failure management program.

The study results suggest that, in patients with both advanced heart failure and diabetes, use of metformin is safe, and may be associated with better heart failure survival.

Interestingly, the diabetes drug metformin previously carried a "black box warning" from the FDA against its use in treating diabetes in heart failure patients and that is why most many physicians have been reluctant to use metformin and other similar medications to treat this patient group. However, analysis by the researchars, shows that using metformin to treat diabetes in patients with advanced, systolic heart failure is not only safe, but may also play a role in improving outcomes compared to conventional diabetes care. As per the claim by Dr Gregg Fonarow, coresearcher,  metformin improves myocardial function via activation of a signaling mechanism (AMP-activated protein kinase) independent of antihyperglycemic effects. Together, these studies suggest that metformin may be cardioprotective by augmenting heart function at the molecular level, and should be further investigated as a treatment for heart failure, irrespective of diabetes....

Ref : http://www.newsroom.ucla.edu/portal/ucla/ucla-study-demonstrates-that-metformin-150497.aspx

New target for diabtes type 2 treatment ?

Mitochondria provide energy for cellular activity. Mitochondrial damage causes people with type 2 diabetes to lose insulin-producing cells, a finding that could lead to new treatments, researchers say.

The researchers (Dr. E. Dale Abel, chief of the endocrinology and metabolism division at the University of Utah School of Medicine in Salt Lake City) found that when insulin-producing beta cells in the pancreas can't respond to circulating insulin, it triggers a "molecular cascade" that damages the normal action of a certain molecular receptor on the surface of the mitochondria. The damaged mitochondria then begin to destroy adenosine triphosphate, the prime fuel for cellular activity. As a result, the beta cells die.

The study provides novel insights into the role of insulin signaling in the regulation of the BAD/GK complex, glycolytic enzyme activity and mitochondrial metabolism in pancreatic β-cells. Ser112-BAD_S and its upstream kinases may be potential targets for the maintenance of the BAD/GK complex that is necessary for normal mitochondrial function and the regulation of β-cell survival....

Source : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007983

Statins as anticancer and anti diabetic agents ?

We know that statins are widely used as cholesterol lowering drugs. They act by inhibiting HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway that leads to the synthesis of farnesyl pyrophosphate, a precursor for cholesterol synthesis and the source of lipid moieties for protein prenylation. But researchers from University of Gothenburg, have found that statins might be useful as anticancer and antidiabetic too.

Statins lower cholesterol by blocking certain enzymes involved in our metabolism. However, they have also been shown to affect other important lipids in the body, such as the lipids that help proteins to attach to the cell membrane (known as lipid modification). Because many of the proteins that are lipid-modified cause cancer, there are now hopes that it will be possible to use statins in the treatment of cancer.

Studies show that statins can have a dramatic inhibitory effect on growth and development. As the researchers managed to identify the enzyme involved, they can also explain how the effect arises at molecular level. Not least that they can prevent the growth of cancer cells caused by lipid-modified proteins, but also that they can be effective in the treatment of diabetes and neurological disorders such as Parkinson's. In one of my earlier blog, I have mentioned about the simvastin (Simvastatin prevents progression of Parkinson's Disease ?).

So in the days to come statins may be useful as anticancer, anti diabetic and even to treat Parkinsons disaese....


Source : http://www.science.gu.se/english/News/News_detail/Cholesterol-lowering_medicines_may_be_effective_against_cancer.cid898016

Vegetables Can Protect Unborn Child Against Diabetes

Expecting mothers who eat vegetables every day seem to have children who are less likely to develop type 1 diabetes, a new study from the Sahlgrenska Academy has revealed......


More......Vegetables Can Protect Unborn Child Against Diabetes