Type 2 Diabetes Could Be a Cause of Erectile Dysfunction


Type 2 diabetes may be a causal factor in the development of erectile dysfunction (ED), with insulin resistance a likely mediating pathway, results of a large-scale genomic analysis suggest. The data also uncovered a genetic locus linked to ED.

Jonas Bovijn, MD, DPhil, Big Data Institute at the University of Oxford, United Kingdom, and colleagues gathered data on more than 220,000 men across three cohorts, of whom more than 6000 had ED.

The researchers initially showed that a region on chromosome 6 is linked to the development of ED. The location suggested that the condition is associated with dysregulation of the hypothalamus.

Next, they performed a Mendelian randomization analysis, which examined the relationship between gene mutations known to be associated, in this case, with cardiometabolic factors and the outcome of ED.

The research, published online December 20 in the American Journal of Human Genetics, showed that a genetic predisposition to type 2 diabetes increased the risk for ED. The risk was driven primarily by susceptibility to insulin resistance.

Bovijn said in a release: “We know that there is observational evidence linking erectile dysfunction and type 2 diabetes, but until now there has not been definitive evidence to show that predisposition to type 2 diabetes causes erectile dysfunction.”

“Further research is needed to explore the extent to which drugs used in the treatment of type 2 diabetes might be repurposed for the treatment of ED,” the team notes.

Co–senior author Anna Murray, PhD, University of Exeter Medical School, United Kingdom, said in the release that “until now little has been known” about the cause of ED.

Previous studies have suggested there is a genetic basis for ED. The new study goes further by demonstrating that a genetic predisposition to type 2 diabetes is linked to ED, according to Murray.

“That may mean that if people can reduce their risk of diabetes through healthier lifestyles, they may also avoid developing erectile dysfunction,” she said.

Michael Holmes, MD, PhD, of the Nuffield Department of Population Health at the University of Oxford, who was one of the senior authors, agreed.

“Our finding is important, as diabetes is preventable, and indeed one can now achieve ‘remission’ from diabetes with weight loss, as illustrated in recent clinical trials.

“This goes beyond finding a genetic link to erectile dysfunction to a message that is of widespread relevance to the general public, especially considering the burgeoning prevalence of diabetes,” Holmes said.

Large Studies Key

Although the prevalence of ED is known to increase with age, rising to 20% to 40% among men aged 60 to 69 years, the genetic architecture of the condition remains poorly understood. This is at least in part due to a lack of well-powered studies.

The researchers therefore conducted a genome-wide association study (GWAS) using data on 199,362 individuals from the UK Biobank cohort and 16,787 people from the Estonian Genome Center of the University of Tartu (EGCUT) cohort, both of which are population based.

In addition, they included information on 7666 participants in the hospital-recruited Partners HealthCare Biobank (PHB) cohort.

The prevalence of ED, which was determined on the basis of self- or physician-reported ED, the use of oral ED medication, or a history of ED surgical intervention, was 1.53% in the UK Biobank, 7.04% in EGCUT, and 25.35% in PHB.

The researchers believe that the difference in prevalence rates between the cohorts may relate to the older average age for men in PHB, at 65 years, vs 59 years in the UK Biobank and 42 in EGCUT. In addition, the prevalence in the UK Biobank cohort may have been affected by a “healthy volunteer” selection bias and a lack of primary care data.

GWAS on the UK Biobank data indicated that there was a single genome-wide significant locus at 6q16.3 between the MCHR2 and SIM1 genes, with rs57989773 the lead variant.

Pooled meta-analysis of the combined cohorts indicated that rs57989773 was associated with ED at an odds ratio of 1.20 per C-allele (P = 5.71 × 10-14).

Synthesizing previous research on SIM1, which is highly expressed in the hypothalamus, in both human and rodent models, the team found that rs57989773 is associated with syncope, orthostatic hypotension, and urinary incontinence.

Moreover, the common risk variant for ED at 6q16.3 is linked to blood pressure and adiposity, as well as male sexual behavior in mice.

The researchers, therefore, suggest that a potential mechanism for the effect of the MCHR2-SIM1 locus on ED could be the hypothalamic dysregulation of SIM1.

The team also performed Mendelian randomization analyses to examine the potential causal role of cardiometabolic traits in ED risk.

Factors included type 2 diabetes, insulin resistance, systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol levels, smoking heaviness, alcohol consumption, body mass index, coronary heart disease, and educational attainment.

The analysis revealed that type 2 diabetes was causally implicated in ED, with the risk for ED increased 1.11-fold with each 1-log higher genetic risk for type 2 diabetes (P = 3.5 × 10-4).

Insulin resistance was found to be a likely mediating pathway for the relationship, with an odds ratio for ED of 1.36 per 1 SD genetic increase in insulin resistance (P = .042).

SBP also had a causal effect on ED risk, at an odds ratio of 2.34 per 1 SD increase in SBP (P = .007).

LDL cholesterol was found to have a minor impact on the risk for ED, at an odds ratio of 1.07 per 1 SD increase in levels (P = .113). There was no association between ED and either smoking heaviness or alcohol use.

Source:Medscape.com

Curcumin reduces the effects of a high-fat diet


Image: Curcumin reduces the effects of a high-fat diet

Diets high in fat are known as major contributors to many health diseases, such as heart disease, and cancer. Researchers at Jawaharlal Institute of Postgraduate Medical Education and Research in India discovered that taking curcumin supplements minimizes the damage caused by a high-fat diet.

In their study, the researchers looked at the beneficial effects of curcumin on inflammation, oxidative stress, and insulin resistance in high-fat-fed rats. They examined two groups of rats: one group fed with a high-fat diet only and another group given a high-fat diet with 200 milligrams per kilogram (mg/kg) body weight of curcumin every day for 10 weeks.

The researchers measured the rats’ food intake, body weight, and biochemical parameters at the start and the end of the study. After 10 weeks, they also measured the oxidative stress parameters in skeletal muscle and liver triglyceride levels.

The results revealed that the high-fat diet increased the body weight and liver fat. It also increased the levels of plasma glucose, insulin, insulin resistance, total cholesterol, triglycerides, and very low-density lipoprotein cholesterol (VLDL-c), and decreased high-density lipoprotein (HDL) cholesterol.

The high-fat diet also increased inflammation and oxidative stress in skeletal muscles. It also increased liver triglyceride content and caused fat buildup in the liver.

However, the supplementation with curcumin significantly improved these changes. Curcumin supplementation significantly reduced body weight, liver adipose tissue, glucose, insulin, and insulin resistance. In addition, it decreased plasma levels of total cholesterol, triglycerides, VLDL-c, and inflammatory markers, and increased HDL cholesterol. Moreover, it reduced oxidative stress, hepatic triglyceride content, and liver fat deposition.

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With these findings, the researchers concluded that curcumin could improve lipid levels, oxidative stress, inflammation, and insulin resistance caused by a high-fat diet.

Curcumin and turmeric

Curcumin is the active ingredient of the spice called turmeric and is responsible for most of the spice’s health benefits. It takes up about two to eight percent of most turmeric preparations and gives turmeric its distinct color and flavor.  Here are some health benefits of turmeric and curcumin backed up by scientific evidence:

  • Cancer: One of the most notable benefits of turmeric and curcumin is their ability to prevent cancer. Turmeric and curcumin may help prevent cancer by reducing the activity of colon and other cancer cells. A new study published in the Proceedings of the National Academy of Sciences revealed that curcumin inhibits to the DYRK2 enzyme. Inhibiting this enzyme stops protein complexes known as proteasomes that contribute to cancer development. This action interrupts the proliferation of cancer cells, reducing tumors, and slowing cancer’s growth. This is beneficial for preventing proteasome-addicted cancers, such as triple-negative breast cancer and multiple myeloma.
  • Antibacterial: Turmeric and curcumin have powerful antibacterial effects. They have been reported to inhibit the growth of many disease-causing bacteria.
  • Antifungal: Studies have also reported that turmeric and curcumin have antifungal effects. They can disrupt fungal cell membranes and could be used with other fungal medicines for better effect.
  • Diabetes: Turmeric and curcumin can improve blood sugar metabolism and potentially reduce the effects of diabetes in the body.
  • Heart disease: As mentioned in the Indian study, curcumin reduced bad LDL cholesterol and triglycerides. These effects, which were also seen in earlier studies, can cut the risk of heart disease.
  • Liver health: Turmeric and curcumin can also protect the liver from damage caused by oxidative stress.
  • Obesity: Research has shown that turmeric and curcumin may inhibit the inflammatory pathway related to obesity and may help control body fat.
  • Osteoarthritis: Plant compounds in turmeric, including curcumin, can decrease inflammatory markers and relieve osteoarthritis symptoms, such as pain and stiffness.

Both high, low gestational weight gain influence childhood adiposity


Gaining too much weight or too little during pregnancy can lead to increased childhood cardiometabolic risk factors, including adiposity, hypertension and insulin resistance, according to findings published in Diabetologia.

Ronald C.W. Ma

“The risk of obesity and diabetes increase in offspring of mothers who have obesity or diabetes. This intergenerational cycle of diabetes and obesity may be an important contribution to the escalating obesity and diabetes seen in many parts of the world,” Ronald C.W. Ma, MD, professor and head of the division of endocrinology and diabetes in the department of medicine and therapeutics at The Chinese University of Hong Kong, told Endocrine Today. “Prospective mothers who plan to become pregnant need to be aware of the risks and long-term impact of gaining excessive weight during pregnancy. ‘Eating for two’ is a myth that needs to be dismissed.”

Ma and colleagues examined data from 905 mother-child pairs of Chinese ancestry that reached full-term pregnancies and used 2009 Institute of Medicine recommendations for gestational weight gain to determine when participants gained too much or too little during pregnancy. Self-reported weight was used to calculate BMI before pregnancy, and medical records provided weight at delivery. The participants returned 7 years after delivery to record the anthropometric indices of the children. These assessments took place between 2009 and 2013.

The researchers noted a mean BMI of 20.9 kg/m2 for participants before pregnancy. Weight gain after delivery averaged to 15.2 kg, with 41.8% of the women meeting the Institute of Medicine guidelines (n = 378), 41% exceeding recommended weight gain (n = 371) and 17.2% falling below (n = 156).

In models adjusted for child sex, age and height, significantly higher BMI (P = 1.3 x 10-7), diastolic blood pressure (P = 1.4 x 10-3), diastolic BP percentile (P = 9.7 x 10-4), systolic BP percentile (P = .0185), fasting plasma insulin (P = .0146), 2-hour insulin (P = 1.2 x 10-3), homeostatic model assessment of beta-cell function (P = 4.2 x 10-4), HOMA-insulin resistance (P = .039) and pancreatic beta-cell function (P = 6.6 x 10-4) and Matsuda insulin sensitivity index (P = 6 x 10-4) were found among the children born to mothers who gained more weight than recommended compared with those who met recommendations. Children born to mothers with inadequate gestational weight gain also had higher diastolic BP percentile (P = .0186), 2-hour insulin area under the curve (P = .0158), pancreatic beta-cell function (P = 7.9 x 10-3) and Matsuda insulin sensitivity index (P = .0477) compared with those with recommended amount of weight gain.

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“Our findings suggest that the effect of maternal [gestational weight gain] on childhood cardiometabolic risk is not confined to the upper and lower extremes of [gestational weight gain], but rather this relationship is a U-shaped continuum,” the researchers wrote.

“It is often too late to try to intervene during pregnancy,” Ma said. “It is best to try to optimize body weight before pregnancy in order to achieve the best outcome. Young women need greater awareness of the importance of healthy diet and lifestyles and the health risks of obesity.”

Conclusions from the study have limitations, especially as it pertains to the Chinese population, the researchers wrote. The Institute of Medicine recommendations are based on “standard BMI thresholds,” which have yet to be determined in China.

Wing Hung Tam

“The definition based on prepregnant BMI for overweight and obesity in [Asia] is different,” Wing Hung Tam, MD, professor in the department of obstetrics and gynecology at The Chinese University of Hong Kong, told Endocrine Today. “We need [a] large population study to tell what kinds of weight gain is most appropriate for the underweight, normal weight, overweight and obese mothers.” – by Phil Neuffer

Many Faces of Insulin Resistance


Insulin resistance is a state where cells cannot take properly sugar from blood to use it as an energy source. Cells become resistant to the action of insulin. It therefore takes more insulin to keep blood sugar in balance. People with insulin resistance syndrome will consequently have normal blood sugar levels but elevated insulin level

There is no single test that would reliably measure insulin resistance. The diagnosis can be made through clinical symptoms and some laboratory tests. The insulin fasting value is an essential test but it is not the only one. The insulin values may temporarily vary without being insulin resistant. Another indicative laboratory test is The Triglyseride-to-HDL Cholesterol Ratio. In insulin resistance triglycerides start to rise and HDL decrease. The more important is TG/HDL-C ratio must be less than 2 in US values and in countries who use mmol/l like Europe, Australia and Canada TG/HDL-C less than 0.87. Normal official fasting values of serum insulin are 2–20mU/L, but I think that’s too high. It should be less than 5mU/L

We know that continuing insulin resistance leads to metabolic syndrome and thus prediabetes but it leads to many other diseases as well. According to studies 70% those who have prediabetes develop type 2 diabetes if significant lifestyle changes aren’t made.

Symptoms include elevated blood pressure. Insulin Resistance in the early stages may develop a skin condition known as Acanthosis Nigrircans. This condition creates dark patches often on the back of the neck, groin, and armpits. Other symptoms are, feeling hungry even after meal, craving carbohydrate-rich food and sugar, sugar addiction, compulsive overeating, hormone imbalance, PCOS, female androgenic alopecia, swollen ankles and general swollenness, complexion problems, lethargy, sleepiness after a meal, difficulty concentrating (brain fog), poor memory and impairing learning abilities, mental fatigue, anxiety, mental swings, depression. It’s a long list of all kind of symptoms, what is not rightly understood, that all may be due to the same reason. Usually these patients have a long list of different medicines targeted only to various symptoms. Excessive fatigue and other mental disorders are due to chronic hypoglycaemia, which is one of the earliest sign of Insulin Resistance. Weight gain or even severe obesity is typical among these patients but not for all. Patients may have normal weight but the excess fat is visceral fat.

There is increasing evidence that insulin resistance leads to many diseases like high blood pressure, heart disease, stroke, fatty liver, fat metabolism disorders, dementia and even cancer. Using the old phrase. Insulin resistance is “the mother of all diseases”

The main stream medicine has totally ignored the basic role of insulin in all that affects the metabolic balance. All symptoms are treated with medicines, which is typical of medicalisation. Insulin resistance is not treated with medicines but with lifestyle changes, which does not cost anything. We can call this approach a lifestyle medicine that is the future.

Many may ask why this has not been previously discussed. Knowledge has existed but it is guided to the siding. Many are aware of the role of money in the medicine. Lifestyle changes are free and do not benefit anybody else. In a world where everything is for sale, this is simply not acceptable. A good example of this is Helsinki Policemen Study, where the effect of insulin on cardiac diseases was studied. The study lasted 22 years and the study showed that those with the highest levels of insulin had nine times heart attack compared to those with the lowest values.  It was a staggering result. None of the research related to cholesterol has not been able to present such results. Finland is a small country. When the global food and pharmaceutical industry supported the country’s cholesterol party, which also supported the interests of the nation’s medical elite, all was forgotten. A few years later, the doctor responsible for the study nominated to a doctor of the year. It was little comfort to him but a great sorrow to us.

The Journal of Clinical Endocrinology & Metabolism published August 2001 an article “Insulin Resistance as a Predictor of Age-Related Diseases” The study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. The graphic tells more than words

           3 groups median follow up time 6 years.

1. Low insulin 2. Moderate 3. High

HT:    Hypertension
CA:    Cancer
CHD: Heart disease
Type: 2 DM
CVA:  Stroke

The group 1 had been healthy throughout the follow-up period. The group 2 has created Hypertension and Cancer and some Heart Disease. The group 3 got whole scale all diseases, Hypertension, Cancer, Heart disease, Type 2 Diabetes and Stroke.

It is interesting to notice that the primary problem of Insulin Resistance is not Type 2 Diabetes but Hypertension and Cancer. Group 3 had Hypertension and Cancer as much as the group 2. It is therefore reasonable to assume that Hypertension and Cancer are the first diseases caused by insulin resistance. Diabetes is not the first problem. No wonder cancer has increased in the world. The official side erroneously blames being overweight and diabetes for the problem when the real cause is insulin resistance. That’s why the official conception leads completely to fraudulent treatments. One study tells that nonobese people with hyperinsulinemia were at higher risk of cancer mortality than those without hyperinsulinemia and suggests that improvement of hyperinsulinemia may be an important approach for preventing cancer regardless of the presence or absence of obesity. Fatty Liver Disease(NAFLD) is a result of insulin resistance and is significantly associated with colon cancer in men, and breast cancer in women

The only way solve this complex problem is to identify the early symptoms of insulin resistance and the treatment is a lifestyle change. Drugs do not help but lead to the wrong illusion that things are in order. It is vital to detect all these warning signs so early as possible. The possibility of insulin resistance should be assessed for each patient with hypertension. The same applies to all of the above-mentioned symptoms that often lead to numerous medications. This research has also been silenced but it does not matter. Many patients are frustrated when they know that they have been misled. Old Greek wisdom says: “if you want to change the world so start it yourself.” It is also the core of Insulin Resistance treatment.

The process of eating a high-sugar, high-refined carbohydrate diet day in and day out pressures your pancreas to secrete more and more insulin in the attempt to lower your blood sugar. Over time, your cells start to become resistant, or numb, to so much insulin. This is when insulin resistance develops.  Some drugs like statins increase insulin resistance, which raises a lot of questions if we look at things from this perspective.

The only drug, which improves insulin sensitivity, is metformin. Drugs are not a solution. Conventional diabetes medicines decrease blood glucose, which is meaningless in insulin resistance. Nutrition is the solution and the only way substantially change the situation. Exercise is helpful and supports the diet but alone, exercise is of no use. Aerobic exercise can be disadvantageous because it adds cortisol, which is very bad in this case. The best type exercise is anaerobic exercise like HIIT and weight lifting. The combination of diet and for example HIIT gives fast results. The diet is naturally Low Carb or an extreme form Ketogenic diet. We can see the whole situation as some form of carbohydrate sensitivity because not everybody gets problems of insulin even they eat sugar. It is a bit same that one can smoke without any harm or drink alcohol without being an alcoholic. It is difficult to estimate how many people are sensitive to carbohydrates. According to assessment Joseph Kraft60%-70% of the population are sensitive to carbohydrates. It’s a lot. If this were to be understood by an official side, it would bring radical change to everything that concerns nutrition and medicines. Most have T2DM because they have developed progressive insulin resistance over decades as a result of diets that are to high in sugar and carbohydrates and too low in fat and protein.

There are many versions of the Low Carb diet. Some address meat and some not. It’s about fat diet. Too much protein is harmful and exacerbates insulin resistance. Everyone can build their own version of the of the Low Carb diet. Simple rule is to leave sugar and starch and use good fats like extra virgin olive oil and coconut oil. I recommend a diet which is based on lots of vegetables. Unprocessed vegetables contain a great deal of micronutrients that are of great importance to the health of the body. There is a lot of research information about how vegetable micronutrients inhibit inflammation, protects against oxidative stress and have a positive influence on the genetic level. Diet without vegetables is always unhealthy. Unfortunately, many fruits have been processed to be too sugar-rich. Berries are a better option

Unfortunately, researchers in the Western world have not studied the potential benefits of herbs to a significant extent. Most studies are oriented in the direction of developing chemicals that can be patented. That’s why I encourage people to avoid processed food and make their own food. Many of the plants used in Asia are exotic and difficult to find in an average food store. But now we know that many ordinary plants have the same features. Turmeric is a very potent herb that inhibits quite effectively the glycosidase enzyme but also a direct effect on muscles by improving insulin resistance.

Food quality is very important for several reasons. It should be as nutritionally dense as possible. Many of these nutrients protect the body from the harmful effects of sugar. Asian countries have a long history of diabetes nutrition therapy. Many of the herbs taken for example in China balance blood sugar. People have learned how to use herbs without knowing how they affect the body. Today we know how these herbs and plants counteract the effects of diabetes. The nutrients in plants inhibit the alpha glucosidase enzyme, which breaks down starch and disaccharides into glucose.

The inhibition of the enzyme slows down the absorption of sugars. Enzyme inhibitors mainly reduce the increase in postprandial plasma glucose. Among patients with non-insulin-dependent diabetes mellitus, these inhibitors can decrease postprandial plasma glucose by 40 to 50 mg/dL (2.2 to 2.8 nmol) and hemoglobin A1C by 0.5% to 1.0%. Herbs are remarkably effective in the treatment of diabetes.

All plants and herbs contain anthocyaninspolyphenolsflavonoids, terpenoids and, of course, curcuminoids. That essentially means that all spices, herbs, berries, fruit and vegetables are useful for diabetics. My favourite is marjoram. There is a potent antioxidant called pygcocenol, a French maritime pine bark extract, which is a member of the anthocyanidin family. In the old days in northern Europe, people added powdered pine bark to flour when there was a shortage of grains. People were healthy in those days; this all turned upside down when wheat was introduced.

Some mushrooms also inhibit the glucosidase enzyme. The most studied mushrooms are Maitake, Reishi, Shitake mushrooms, but I believe that many other mushrooms have same effect. Ganoderma lucidum is an old Chinese medicinal mushroom. It has also been used in Siberia and in Finland for many other purposes as well. The Chaga mushroom (Inonotus obliquus) is a traditional Russian folk remedy, which helps fight cancer and also helps prevent the formation of the glucosidase enzyme. Chaga mushrooms are quite popular today among health-conscious people in Finland.  Chaga mushrooms grow on birch trees. Birch trees also grow in the north states of the US and in Canada.

Epigenetics is future. Epigenetics will revolutionize everything that concerns nutrition. It is a method to find out how food affects our genes. The Spanish olive oil study best shows what is expected in the future. The study included three groups (A, B, and C). A got traditionally produced olive oil and B got processed olive oil. C was a control group. After 3 months expression of the genes related to atherosclerosis were significantly reduced compared to other groups.

Could diabetes drugs curb our dementia epidemic?


There may be a connection between tau proteins, which are linked to Alzheimer’s, and insulin resistance.

People with lifestyle-related diabetes are at an increased risk of developing dementia and, with both conditions on the rise, scientists are scrambling to understand their connection in the hope of finding new treatments. 

There are 54 million people in Europe living with lifestyle-related – or Type 2 – diabetes and the numbers are soaring, fuelled by the obesity epidemic. Alzheimer’s, the most common form of dementia, affects around 10.5 million Europeans and this number is forecast to hit 18.7 million by 2050 as a result of population ageing.

People with Type 2 diabetes have higher levels of sugar in their blood because their cells have become resistant to insulin which normally regulates blood sugars. Insulin resistance in the brain has been linked to dementia in large, long-term studies but the exact mechanism behind the phenomenon is still being teased out.

‘There is growing evidence from epidemiological studies suggesting that Type 2 diabetes is a risk factor for dementia, particularly Alzheimer’s disease,’ said Dr Shreyasi Chatterjee at the University of Southampton, UK. ‘Therefore, we want to know more about the relationship between insulin resistance seen in diabetes and the protein build-up associated with Alzheimer’s.’

Protein tangles

Key to solving these puzzles are two proteins associated with memory loss in Alzheimer’s – amyloid-beta, which accumulates in plaques that trigger brain cell death, and tau proteins, which cause tangles in the brain.

‘Insulin resistance in the brain can make it difficult for Alzheimer’s patients to process the sugar which is needed to fuel brain cells,’ said Dr Chatterjee. ‘It disrupts normal signalling pathways in the brain and can also hamper the brain’s natural mechanism for clearing misfolded proteins that trigger memory loss.’

As part of the EU-funded AlzDiabetes project, Dr Chatterjee is focusing on the role of tau proteins in fruit flies that have been genetically programmed to mimic the kind of neurodegeneration seen in Alzheimer’s disease.

Fruits flies are often used in genetic research as they have around 75 % of the genes that cause human disease and they are easy to work with thanks to their short breeding times. Dr Chatterjee worked with a population of fruit flies bred to have excessive tau proteins, and experimented with adding insulin receptor substrate (IRS) – a key player in processing insulin.

‘We could reduce the likelihood that people with Type 2 diabetes will develop Alzheimer’s.’

Prof Yifat Miller, Ben-Gurion University of the Negev in Israel

She found that adding IRS gave the fruit flies better memories and longer lifespans, whereas knocking out the gene that produces it increased the level of tau proteins. This new observation is the most direct evidence to date of a direct connection between insulin resistance seen in diabetes and the tau tangles seen in Alzheimer’s disease.

Her team also observed that when the flies were insulin resistant their brains were unable to clear away the toxic tau proteins, providing an explanation of why people with Type 2 diabetes might develop Alzheimer’s.

Curbing dementia risk

As scientists learn more about how insulin resistance affects the brain, researchers hope that controlling blood sugar in diabetic patients will curb their dementia risk.

‘We already know that treating Alzheimer’s disease with inhaled insulin (a diabetes medication) reduces cognitive impairment,’ said Dr Chatterjee. ‘Other diabetes drugs are now in clinical trials to test whether they could slow the progression of dementia.’

In addition to having a higher risk of Alzheimer’s, diabetes patients are also more likely than the average person to develop Parkinson’s disease. Professor Yifat Miller at the Ben-Gurion University of the Negev in Israel has explored the relationship between diabetes, Alzheimer’s and Parkinson’s as part of the EU-funded AbetaAlphasynTau project.

Her team used computer simulations to model the interactions at the molecular level between the amyloid-beta protein, which is associated with Alzheimer’s, alpha-synuclein, which builds up in the brains of Parkinson’s patients, and amylin, a hormone produced by the pancreas. The project pinpointed crucial fragments of these proteins that make them stickier when they interact.

We are now developing molecules that would inhibit these interactions,’ Prof. Miller said. ‘The new molecules will prevent the interactions between these proteins so that they will not clump together. Consequently, we could reduce the likelihood that people with Type 2 diabetes will develop Alzheimer’s and Parkinson’s later in life.’

Using their detailed molecular knowledge of these brain diseases, Prof. Miller’s team is designing molecules that could break the link between these three diseases. However, this is still in the early stages of drug design and several new medicines may be needed.

‘The inhibitor we are working on is not a single molecule but a cocktail of molecules,’ she said. ‘It’s very challenging but we are excited about laying the foundation for understanding how these diseases are connected.’

Source:horizon-magazine.eu

Omega-3 fatty acid supplementation does not affect insulin resistance in PCOS


Women with polycystic ovary syndrome likely receive no benefit from daily omega-3 fatty acid supplementation, according to a meta-analysis of three randomized controlled trials.

“Reducing the levels of serum insulin and increasing insulin sensitivity are considered to be of paramount importance for therapeutic targets in PCOS,”Alirez Sadeghi, of the department of cellular and molecular nutrition at the School of Nutritional Sciences and Dietetics at Tehran University of Medical Sciences, Iran, and colleagues wrote. “Omega-3 fatty acids may lead to insulin sensitivity by producing and secreting anti-inflammatory adipokines, such as adiponectin, and also through reducing inflammation and proinflammatory cytokines. Although it is said that omega-3 fatty acids have positive effects on insulin resistance, various studies have indicated contradictory results.”

Sadeghi and colleagues analyzed data from three studies that measured the association between oral omega-3 supplementation and insulin resistance inwomen with PCOS. Studies were conducted in Australia, Iran and the United States, and included 72 women with PCOS and 73 controls. All studies were double blind and published between 2009 and 2012 with follow-up between 6 and 8 weeks. In all three studies, PCOS groups received 1.2 g to 3.6 g daily omega-3 supplementation containing eicosapentaenoic acid and docosahexaenoic acid (median, 2.7 g); control groups received an oral placebo (olive oil, soybean oil or other placebo). Researchers assessed plasma fatty acid composition in one study; participants maintained their usual diet during intervention in two of the studies; daily energy intake was assessed at baseline and end of intervention in two studies.

In women with PCOS, researchers found that omega-3 fatty acid supplementation did not affect insulin plasma level (mean difference: 6.018; 95% CI, –3.347 to 15.382) or homeostasis model assessment of insulin resistance (HOMA-IR; mean difference: 0.276; 95% CI, –1.428 to 1.981), with high heterogeneity observed for both. The researchers noted that samples sizes in the included studies were low, and further, high-quality randomized controlled trials are needed to validate the findings. – by Regina Schaffer

The Relationship Between Vitamin D and Insulin Resistance


Vitamin D is a steroid hormone that influences virtually every cell in your body, which is why maintaining a healthy level is so important. Low vitamin D levels are widely known to harm your bones, leading them to become thin, brittle, soft or misshapen.

Vitamin D and Diabetes

Story at-a-glance

  • Vitamin D is a steroid hormone that influences virtually every cell in your body. Low levels are linked to poor bone health, as well as heart, brain, immune and metabolic dysfunction
  • Animal studies have shown vitamin D is a foundational factor necessary for normal insulin secretion, and that vitamin D improves insulin sensitivity
  • Atypical antipsychotics such as quetiapine, a bipolar medication, can increase your risk of hyperglycemia and diabetes. Research suggests vitamin D3 may counteract these effects

But vitamin D is equally important for your heart, brain, immune function and much more. For example, there’s an important connection between insufficient vitamin D and insulin resistance and/or diabetes, both type 11 and type 2.

Vitamin D Deficiency May Influence Your Type 2 Diabetes Risk

According to recent research, vitamin D deficiency affects your glucose metabolism and may actually be more closely linked to diabetes than obesity. In a study of 118 people, those with low vitamin D levels were more likely to have type 2 diabetes, pre-diabetes or metabolic syndrome, regardless of their weight.

Among obese people, those without metabolic disorders had higher levels of vitamin D than those with such disorders, and among lean people, those with metabolic disorders were more likely to have low levels of vitamin D. According to one of the study’s authors:2

“The study suggests that vitamin D deficiency and obesity interact synergistically to heighten the risk of diabetes and other metabolic disorders. The average person may be able to reduce their risk by maintaining a healthy diet and getting enough outdoor activity.”

It’s not the first time vitamin D has been shown to play a role in diabetes. One Indian study found that vitamin D and calcium supplementation, in combination with exercise, can prevent pre-diabetes from progressing into full-blown diabetes.

For every unit increase in vitamin D levels, the risk of progression to diabetes in people with pre-diabetes went down by 8 percent.3

Another study4 published in 2013 found that type 2 diabetics given 50,000 IUs of oral vitamin D3 per week for eight weeks experienced “a meaningful reduction” in fasting plasma glucose and insulin. Other research showing this link includes but is not limited to the following:

  • Animal studies have shown vitamin D is a foundational factor necessary for normal insulin secretion5,6 and that vitamin D improves insulin sensitivity7,8
  • One study involving nearly 5,680 individuals with impaired glucose tolerance showed that vitamin D supplementation increased insulin sensitivity by 54 percent9
  • The mechanisms by which vitamin D reduces insulin resistance include its effect on calcium and phosphorus metabolism and by upregulating the insulin receptor gene10

Vitamin D May Lower Risk of Hyperglycemia in Those Taking Atypical Antipsychotics

Certain drugs can raise your risk of metabolic dysfunction. For example, statin drugs can trigger drug-induced diabetes. Atypical antipsychotics such as quetiapine, a bipolar medication, have also been linked to an increased risk of hyperglycemia and diabetes.

In the latter case, research suggests vitamin D3 may counteract these effects. As reported by The American Journal of Managed Care:11

“Atypical antipsychotics have long been associated with an increased risk of hyperglycemia — which can lead to new-onset diabetes, diabetic ketoacidosis, coma and even death.

Some proposed mechanisms for this effect include weight gain, decreased insulin secretion from pancreatic beta cells and insulin resistance.

To determine whether there were any medications that could decrease this likelihood of hyperglycemia, researchers analyzed the FDA’s Adverse Event Reporting (FAERS) system — a database that logs self-reported adverse effects or medication errors submitted by patients.

By cross-referencing atypical antipsychotics and hyperglycemia, the study authors found that patients who had been simultaneously prescribed to take vitamin D and quetiapine were somehow less likely to have hyperglycemia.”

Subsequent animal studies produced similar results. Mice given vitamin D and quetiapine had significantly lower blood sugar levels compared to mice given quetiapine alone. According to lead author Takuya Nagashima, vitamin D inhibits quetiapine from reducing an enzyme that causes hyperglycemia.

Based on these results, the authors suggest combining antipsychotics with vitamin D supplementation to “efficaciously safeguard against antipsychotic-induced hyperglycemia accompanied by insulin resistance.”

Other Benefits of Vitamin D

Researchers have pointed out that raising levels of vitamin D among the general population could prevent chronic diseases that claim nearly 1 million lives throughout the world each year.

Incidence of several types of cancer could also be slashed in half, or more. Recent research reveals raising your serum 25-hydroxyvitamin D to 40 ng/ml can slash your risk of invasive cancers by 67 percent!

In the interview above, Dr. Michael Holick — a well-known vitamin D researcher — expands on these and many other health benefits of vitamin D. For instance, optimizing your vitamin D levels can help protect against:

Cardiovascular disease

Vitamin D is very important for reducing hypertension, atherosclerotic heart disease, heart attack and stroke. According to Holick, one study showed that vitamin D deficiency increased the risk of heart attack by 50 percent.

 

Autoimmune diseases

Vitamin D is a potent immune modulator, making it very important for the prevention of autoimmune diseases, like multiple sclerosis (MS) and inflammatory bowel disease (IBD).

Infertility

Vitamin D may help stimulate the production of hormones including testosterone and progesterone, and has been shown to boost fertility in both men and women.

Vitamin D is also associated with semen quality in men and may improve menstrual frequency in women with polycystic ovary syndrome (PCOS).12

DNA repair and metabolic processes

One of Holick’s studies showed that healthy volunteers taking 2,000 international units (IUs) of vitamin D3 per day for a few months upregulated 291 different genes that control up to 80 different metabolic processes.

Some of these processes help improve DNA repair and boost immune function, while others affect autoxidation (oxidation that occurs in the presence of oxygen and /or UV radiation, which has implications for aging and cancer, for example).

Migraine

Recent research also suggests vitamin D can play a role in migraines. Researchers at Cincinnati Children’s Hospital Medical Center found that many who suffer from migraines have deficiencies in vitamin D, riboflavin (B2) and coenzyme Q10 (CoQ10).13

Girls and women who suffered migraines were particularly prone to having CoQ10 deficiency, while boys and men were more likely to be deficient in vitamin D. Those with chronic migraines were more likely to have CoQ10 and riboflavin deficiencies, compared to those with episodic migraines.

Neurological/psychological/mental disorders

Vitamin D also plays a major role in neurotransmission, and vitamin D deficiency has been associated with a number of neurological and brain disorders, including cognitive dysfunction and Alzheimer’s disease (in one study, those who were most vitamin D deficient had a 31 percent increased relative risk of suffering neurocognitive decline), schizophrenia, Parkinson’s disease, stroke, epilepsy and depression.

Cold and flu

Vitamin D has potent infection-fighting abilities, and can be beneficial for both the prevention and treatment of tuberculosis, pneumonia, colds and flu.

What’s the Best Way to Optimize Your Vitamin D Level?

There is no doubt that vitamin D is imperative for good health and disease prevention. It may even help counteract some of the deleterious metabolic effects caused of certain drugs. But there’s no lack of controversy when it comes to the issue of how to optimize your vitamin D. Most of the researchers specializing in vitamin D agree that sensible sun exposure is the ideal way though.

First of all, vitamin D3 supplements do not confer the identical effects as the vitamin D your skin generates in response to UV exposure. Secondly, sun exposure has additional health benefits that are unrelated to vitamin D production.

For example, UVA exposure produces nitric oxide (NO), which has a blood pressure-lowering effect. In fact, the entire solar spectrum is important for optimal health. We’re not dependent solely on the narrowband wavelength of about 295 nanometers (nm), which is where vitamin D is made.

However, unless you make a concerted effort, chances are you’re simply not getting enough sun exposure to raise your vitamin D level. As noted in a recent British study, adolescent Britons are not getting enough sun exposure even in the middle of summer to elevate their vitamin D to a healthy level, prompting the authors to suggest changes to the U.K.’s vitamin D guidelines.

As reported by Endocrine Today,14 “more than one-quarter of the adolescents in the study had inadequate vitamin D levels even during summer, the period when participants spent the most time outdoors.” According to the authors:

“Current U.K. national guidance on vitamin D acquisition assumes those aged 4 to 64 years gain their vitamin D requirements from sunlight alone, thus there is no recommended nutrient intake. Meanwhile, substantial proportions of the global population, including the U.K., are reported to have low vitamin D status, and rickets has returned as a clinical concern …

As U.K. current sun exposure patterns do not provide an adequate source of vitamin D, amendments are required to recommendations on vitamin D acquisition in this age group. While wider skin surface area exposure to sunlight might safely increase vitamin D status, oral vitamin D supplements may be beneficial during this critical time for bone development.”

When to Take a Vitamin D3 Supplement

Indeed, while sun exposure is the ideal route, it can be difficult for many to achieve an optimal vitamin D level this way. Your lifestyle, location, age, ethnicity, time of year, weather conditions and a number of other factors influence how much vitamin D your skin will make in response to sun exposure. The fact that vitamin D insufficiency and deficiency is widespread even in sundrenched areas like India attests to this difficulty.

In some cases, making changes to your routine in order to get more regular sun exposure may do the trick. Key points to remember is that you need to expose large areas of skin to the sun, and on a frequent basis (ideally daily). However, under ideal conditions you may not need more than a few minutes of exposure.

The worst thing you could do is to bake in the sun for hours on end on the weekends. You definitely want to avoid burning your skin, as this will only cause skin damage that could potentially increase your risk for skin cancer.

If sensible sun exposure is either not feasible or isn’t sufficient to raise your vitamin D to a healthy level, then taking an oral vitamin D3 supplement is a wise choice. If you decide to supplement with vitamin D please consider using one that also has vitamin K2, as it works synergistically with vitamin D to maximize the benefits.

The only way to know how your sun exposure is affecting your vitamin D level is to get your vitamin D tested. I recommend doing this twice a year, in January and June/July, to get a reading on your lowest and highest levels. This will tell you whether you might be in need of a supplement. It will also guide you in terms of dosage.

In short, your ideal dosage is one that will help you maintain a clinically relevant vitamin D level of 40 to 60 ng/ml year-round. For some this may be 2,000 IUs a day. For others, it could be 8,000 IUs a day or more.

The Role of Vitamin D in Disease Prevention

A growing body of evidence shows that vitamin D plays a crucial role in disease prevention and maintaining optimal health. There are about 30,000 genes in your body, and vitamin D affects nearly 3,000 of them, as well as vitamin D receptors located throughout your body.

According to one large-scale study, optimal Vitamin D levels can slash your risk of cancer by as much as 60 percent. Keeping your levels optimized can help prevent at least 16 different types of cancer, including pancreatic, lung, ovarian, prostate, and skin cancers.

AUA: Low-Carb Diet Quells ADT Effects


Trial misses insulin-resistance endpoint but may have potential.

A very low-carbohydrate diet failed to prevent insulin resistance in men taking androgen deprivation therapy for prostate cancer, but led to significant weight loss and preserved bone health, a small trial showed.

The dietary intervention led to a significant reduction in homeostatic model assessment (HOMA) of insulin resistance at 3 months, as compared with a control group, but not at 6 months, the primary endpoint. Men on the very low-carbohydrate diet had significant reductions in weight and percent body fat and stable bone mineral content (BMC) versus weight and body fat increases and a reduction in BMC in the control group.

Though the trial missed its primary endpoint, a follow-up study has already begun to test the oncologic benefits of the very low-carbohydrate diet, Stephen Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, reported here at the American Urological Association (AUA) meeting.

“Carbohydrate restriction is a promising tool to prevent androgen deprivation therapy (ADT) -induced metabolic side effects,” said Freedland. “Given that weight loss is generally anticancer, coupled with animal data that this diet slows prostate cancer growth, studies evaluating oncological efficacy and safety are ongoing.”

The diet would pose an adherence challenge for many men, but the challenge has to be weighed against the reality of the disease, said Benjamin Davies, MD, of the University of Pittsburgh.

“These are men who have recurrent cancer,” said Davies, who moderated an AUA press briefing where Freedland discussed the study. “If you tell them that there is preliminary data that this may help them with their physiology and their health, you might be more apt to induce them to follow a proactive approach to change their lifestyle. Whereas if this were just a regular guy without the kind of medical challenge, you can see where there might be some reluctance.”

“Usually, people are more apt to change their lifestyles when their health is at risk,” he added. “I think that gives me some hope that we could actually do that for patients. Obviously, it’s challenging. I don’t know that I could do it … actually, I know that I couldn’t.”

For decades, hormonal therapy, or ADT, has represented standard of care for advanced prostate cancer. Multiple studies have demonstrated survival benefits with ADT. However, recent investigations have documented major side effects, especially metabolic effects (weight gain, insulin resistance, dyslipidemia), in addition to hot flashes, loss of libido, erectile dysfunction, memory loss, and bone mineral loss and osteoporosis.

“Hormonal therapy for prostate cancer increases the risk of diabetes by 40%,” said Freedland. “Diabetes is a problem controlling blood sugar levels. We wondered, what happens if you don’t eat sugar?”

Low-carbohydrate diets have demonstrated the potential to achieve significant weight loss and improve diabetes control, he continued. In animal models, low-carbohydrate diets have been associated with slowing of prostate cancer growth. Such a diet has never been evaluated in a randomized trial involving patients with cancer.

Investigators hypothesized that a very low-carbohydrate diet could prevent insulin resistance and other metabolic side effects in men initiating hormonal therapy for advanced prostate cancer. To test the hypothesis, Freedland and colleagues conducted a prospective, randomized trial, comparing a very low-carbohydrate diet versus usual diet in men initiating ADT.

Men randomized to the intervention arm followed a diet that limited daily carbohydrate consumption to 20 g, similar to the Atkins diet, said Freedland. They also were instructed to exercise 30 minutes a day, 5 days a week. Men assigned to the control arm continued their usual practices regarding diet and exercise.

Investigators randomized 42 patients, and 40 completed the baseline assessment. Subsequently, 14 men in the intervention arm and 20 in the control group completed the 6-month trial. Complete data were available for 11 men in the very low-carbohydrate group and 18 in the control group, and those 29 patients formed the basis for data analysis.

The primary endpoint was change in HOMA at 6 months. The intervention group had a mean change in HOMA of -4 compared with an increase of 36 in the control group (P=0.127). The 3-month values showed a significant difference in favor of the intervention arm (-19 versus +7, P=0.015).

The dietary intervention was not expected to affect PSA values, and the change from baseline (in response to hormonal therapy) ranged from -97% to -99% in both arms at 3 and 6 months. Men in the very low-carbohydrate arm had weight loss that averaged about 15 lbs at 3 months, increasing to 20.5 lbs at 6 months. In the control group, men had gained almost a pound at 3 months and almost 3 lbs at 6 months (P<0.001 versus intervention group at both time points).

Bone mineral content remained unchanged at 6 months in the intervention group as compared with a reduction of 2.3% in the control group (P=0.025). Percent body fat decreased by 16.2 % at 6 months in the intervention group and increased by 11% in the control group (P=0.002).

Phospholipids affect obesity, insulin resistance in young adults


Sphingomyelins, lysophosphatidylcholines and phosphatidylcholines appear to be associated with obesity and insulin resistance independent of LDL and HDL cholesterol levels in young adults, according to recent findings.

The children born to the women in the study were followed serially and were aged 20 years at the time of the current study. A total of 175 lipid metabolites of 1,011 participants were included in the analysis.

Researchers found significant correlations between waist circumference and concentrations of sphingomyelins, lysophosphatidylcholines and phosphatidylcholine. Seven sphingomyelins and five diacylphosphatidylcholines were positively associated with waist circumference, and two lysophosphatidylcholines were negatively associated with waist circumference.

Patients with high homeostasis model assessment of insulin resistance (HOMA-IR) values had decreased levels of two diacylphosphatidylcholines and increases in one lysophosphatidylcholine and one diacylphosphatidylcholine.

In participants with overweight or obesity, no significant associations were seen between metabolites and log-HOMA concentrations; however, a trend toward decreased lysophosphatidylcholine levels was seen. No significant interaction was seen between sex and metabolite concentration.

“Even though the pathways are not very well understood to date, the results presented here suggest that [sphingomyelins], [phosphatidylcholine] and [lysophosphatidylcholine] are associated with obesity and [insulin resistance] independent of LDL- and HDL-cholesterol,” the researchers wrote. “The underlying mechanism for the elevated [sphingomyelin] and [phosphatidylcholine] levels in human plasma could be explained by the hypothesis of lipotoxicity.” – by Jennifer Byrne

Vitamin D dose does not affect insulin resistance in older adults with overweight


Older adults assigned high-dose vitamin D supplementation for 1 year showed no differences in measures of insulin resistance when compared with older adults assigned a lower dose of vitamin D, according to recent study findings presented at The American Society for Bone and Mineral Research Annual Meeting.

“High dose vitamin D did not improve insulin resistance in elderly overweight individuals,” Ghada El-Hajj Fuleihan, MD, MPH, of American University of Beirut-Medical Center in Lebanon, and colleagues wrote. “Regardless of vitamin D dose, an unexpected rise in fasting glucose, that correlated with the rise in [vitamin D levels], and exceeded the anticipated rise in [fasting blood sugar] in an aging, overweight population, was observed.”

Ghada El-Hajj Fuleihan, MD, MPH

Ghada El-Hajj Fuleihan

Fuleihan and colleagues analyzed data from 222 adults (mean age, 71 years; mean BMI, 30 kg/m²; 55% women) without diabetes participating in a 1-year, double-blind, randomized controlled trial. Researchers randomly assigned participants to 1,000 mg calcium citrate and the equivalent of either 600 IU or 3,500 IU vitamin D3 daily.

Hormone levels and serum 25-hydroxyvitamin D were measured at baseline, 3, 6, and 12 months.

Within the cohort, 69% of participants had impaired fasting glucose or abnormal HbA1c; 45% of participants were taking antihypertensive medications; 30% were taking lipid-lowering medications. After 1 year, vitamin D levels in the low-dose group rose from 20 ng/mL to 26 ng/mL; levels in the high-dose group rose from 20.9 ng/mL to 35.9 ng/mL. Researchers noted a significant rise in fasting g glucose within each group, which was not explained by either statins or a drift in laboratory performance over the study period.

“There were no detectable differences in [fasting blood glucose], nor in any of the indices of insulin resistance, between the two groups at 1 year,” the researchers wrote. “In the multivariate analyses, BMI, but not vitamin D treatment or age, predicted insulin sensitivity indices at 1 year.” – by Regina Schaffer