The complete PCOS: Comprehensive, authoritative and up-to-date

Just published: Diagnosis and Management of Polycystic Ovary Syndrome (PCOS) is a clinical reference work for primary care physicians, internists, general endocrinologists, obstetricians, gynecologists and students. PCOS is a common but often misdiagnosed disease. Many symptoms can be alleviated by early intervention and effective management. Prominent endocrinologists have contributed recent data and current research on the pathogenesis, manifestations, diagnosis and treatment of PCOS.

The variety of medical issues presenting in PCOS patients result in late referrals or inappropriate advice. This book will be a tool in understanding the metabolic and genetic basis of PCOS, while providing management strategies.

Gestational Diabetes: Can we do better in the UK?

Are we risking the health of babies by testing pregnant women too late for diabetes?

Can brown fat fight obesity?

Research published recently has shown that brown fat cells (commonly found in babies) have the same parental cells as skeletal muscle cells. A second group of scientists has shed light on the origins of white fat cells.

New hope for diabetics

Zhou et al of Harvard University have been able to create cells with the characteristics of pancreatic beta cells, including their ability to secrete insulin. They did so by introducing three transcription factors into mouse exocrine pancreatic cells usually engaged in the secretion of digestive enzymes.

This work brings us closer to insulin-secreting cell replacement, as the Harvard group did not start with stem cells, but cells from the adult animal's own pancreatic cells. Although Zhou et al had to use carrier viruses to introduce the cocktail of transcription factors, they found that once the transformation of the cells was set in motion, they continue in their transformed state even in the absence of the loaded virus carrier.

The concern about using even disabled carrier viruses is that they may cause unanticipated inflammation in a few individuals in the short term or cancer long-term.

The Harvard group's finding raises the hope that, in the future, exocrine cells can be transformed into beta cells by direct injection of DNA or RNA corresponding to the transcription factors. Transcription factors are proteins that bind in the DNA encoding for specific genes to turn them on or off.

Nature October 2 2008 455:627-632.

Not all thyroid tablets are the same

The Endocrine Society (USA) has expressed concern that patients are being placed at risk when their sodium levothyroxine (L-T4) prescriptions are switched between brands, from a brand to a generic, or from one generic to another.

Explaining their position, they state "The most sensitive and clinically relevant measure of thyroid function is serum TSH concentration and not the level of thyroid hormone in the blood. With significant time and effort, doctors can stabilize TSH when treating patients with L-T4.

"They do so by testing different doses of one brand of medication and measuring the patient’s TSH levels over time. When the physician finds the dose and preparation that maintains TSH at ideal levels , it is critical that the patient not stray from this dose or preparation......

"Even a slight change in L-T4 dose - such as might be encountered when a patient is switched from one source of L-T4 to another - can alter TSH levels and adversely affect cardiac and brain function, among other things. These effects are even more pronounced in children, who can also suffer long-term developmental delay."

Designer thyroid hormone holds promise as a cholesterol lowering drug

An American- Swedish team lead by Professor John Baxter has shown that a designer thyroid molecule (KB 2115) is capable of lowering serum cholesterol in human subjects with moderately high cholesterol over a 14 day period. No side-effects were reported.

Splenda - not that splendid!

Splenda might sound like a good idea if you are counting calories (3 calories/gram instead of the 4 calories of sugar – and much sweeter) but reading the small script in the scientific literature shows that it might increase not only sugar cravings but appetite in general.

You need at least 7 hours of sleep to avoid being insulin resistant and keep healthy

Shortening the duration of the time you sleep to less than 6 hours is bad for your health and can lead to insulin resistance. And, according to Professor Eva van Auter of the University of Chicago, this can be brought about within a few days.

Metformin drug may prevent onset of cancer

Reviews of large groups of patients taking metformin for type 2 diabetes have suggested that the drug may prevent the onset of cancer.

Now, Ben Sahra and colleagues in France have showed that metformin added to the culture of prostate cancer cells as well as a similar collection of cells grafted under the skin of mice reduced both by 50%.

We are metformin enthusiasts

The gene dubbed LKB1 (now STK11) has been shown to be key to the role of metformin in insulin resistance and PCOS. An individual's response to metformin may be determined by the 'flavour' of the LKB1 gene they carry. However, Prof. Farid maintains that diet, exercise and other lifestyle measure can also modulate LKB1 and hence the response to metformin.

Have we got the final answer on pregnancy induction in PCOS?

A recent controlled trial(Legro et al) compared pregnancy rates over 6 months in women with PCOS treated with metformin alone, clomiphene alone and the combination of the two drugs. The rates of live birth were greater with clomiphene alone (22.5%), compared to metformin alone (7.2%). The combination of the two drugs resulted in live birth pregnancy rate of 26.8% although this figure was not statistically different form the rate on clomiphene alone. Clomiphene was associated with greater rates of multiple pregnancies.

However, according to Prof. Farid, "A crucial element missing in the recent studies comparing the efficacy of different drugs in enhancing ovulation and pregnancy rates in women with PCOS is diet."

Gut bacteria link to obesity

Some people swear they have only to look at food and they gain weight. and they maybe right. Aside from the fact that human populations have metabolisms with wide-ranging efficiencies or lack thereof, it turns out that bacteria that inhabit our bowels may also have something to say about this. The "diet " bacteria Bacteroidetes are not able to process fibre eaten to any large extent and thus do not contribute to their host's intake of carbohydrates, weight & insulin resistance. On the other hand, persons with a predominance of Firmicutes do put weight on easily. The "fattening" bacteria can break down dietary fibres and convert them into sugars that are then absorbed from the gut. The food eaten shows a higher GI than the host has reckoned on. The result is an increase in serum insulin on an ongoing basis setting up the stage for insulin resistance. To date nobody has come up with a scheme to change the gut's environment. It may, however, be possible. So watch this space!

How to stop failing our children

In the first survey of its kind, published on 14 February 2007, Unicef has accused the UK of failing its children. It comes at the bottom of a league table for child well-being across 21 industrialised countries. So what can we do?

Mice with a reduced core body temperature have an increased life span

Scientists have reported that genetically reducing the core body temperature of mice by 0.3-0.5 degrees C helps them to live 12-20% longer. The mice used in the study, published in the journal Science, were permitted to eat as much food as they wanted while their core body temperature was lowered. The experimental mice indirectly appeared to have increased metabolic efficiency, reported leads researcher Brian Conti of the Scripps Research Institute in La Jolla, California.

Subacute Thyroiditis

Recently, Prof. Farid has seen several patients with subacute Thyroiditis in recent weeks. He speculates that we have seen this cluster of cases because of the very hot summer that simulated the climatic conditions around the Great Lakes.

Link between metabolic stress and metabolic syndrome in mice

Scientists in the US have provided incontrovertible evidence that metabolic stress related to oxygen radicals results in the metabolic syndrome. In research, published in the prestigious Journal Proc. Natl Acad Science USA, the scientists created mice with an important gene known to protect the body against the ravages of oxygen radicals deleted. Much to the surprise of the authors the mice were very obese, had very high insulin levels, high cholesterol, fatty livers and high blood pressure. These are all the components of the Metabolic syndrome in humans.

Factors within the body and in the environment that generate these reactive oxygen radicals are associated with damage to the DNA, aging, cataracts and heart disease. The questions that we raise : does stress at work contribute in humans to this phenotype and do food and drugs with anti-oxidant activity protect us?

Health benefits of a pear shaped body

It has long been known that people with an apple shaped body are at higher risk of heart disease and diabetes than pear shaped people. 'Apples' tend to collect excess weight round their abdomens while 'pears' collect theirs around their hips and thighs.

Recent studies suggest that having a pear-shaped body might not only be less harmful, but beneficial to a person's health. One study at the University of Colorado, Denver suggests that fat on thighs can have a cardio-protective effect. Another study at the University of Pittsburgh Medical Center has shown that subjects with fatter thighs relative to their abdomen were less likely to have the metabolic syndrome. Finally, researchers in Seattle have found that higher waist-to-hip ratios are associated with impairments in memory and verbal fluency.

Increasing prevalence of obesity in Canada

Researchers in Canada have shown that the prevalence of overweight and obesity in Canada increased between 1985 and 2003. An adult with a body mass index (BMI, kg/m2) of 25 or greater is considered overweight, and obese if their BMI is 30 or greater. The study found that the prevalence of CLass III obesity (BMI of 40 or more) in Canada increased from 0.4% to 1.3% between 1990 and 2003, a 225% increase.

Cancer gene turns out key in how metformin works

Endocrinologists have known for some time that one of the principle ways in which metformin works is by turning on a switch on the cell surface known as AMPK, which in turn facilitates the influx of glucose into the cell and its utilization.

LKB1 is a gene that was found in 1998 to be mutated in persons with the familial form of bowel cancer. It was reckoned to be the causative genetic factor in that cancer. It now turns out that LKB1 works upstream from AMPK to regulate its activity, and without that interaction between LBK1 and AMPK, metformin cannot do its job. In other words, metformin only works if AMPK is switched on by LBK1. Indeed, researchers now think that LBK1's function in keeping cancer of the bowel at bay has to do with its effects on glucose metabolism.

This discovery may lead to new treatments of insulin resistance and some forms of cancers.

Genetic Screening

Recently, scientists have succeeded in putting together a panel of genes whose levels can be measured to enable the prediction of the effect of eating certain diets on the degree of weight gain, development of insulin resistance, the metabolic syndrome and, eventually, Type 2 diabetes in some individuals. Such a gene profile, based on a blood sample, would help predict the susceptibility of an individual to weight gain and its metabolic consequences. Read more

Diabetes drug aids IVF success

A recent study by researchers at Leeds General Infirmary has demonstrated the efficacy and safety of metformin in improving the fertility of women with PCOS. This approach has been used by Prof. Farid for many years. Mr Adam Balen's team at Leeds now gives metformin routinely to all women with PCOS undergoing IVF.