HRT risks need to balanced with benefits

Adapted from Editorial BMJ 19 October 19 by Janice Rymer et al.

In the UK most women go through the menopause aged between 45 and 55. About half of them will get symptoms such as flushes, sweats, low mood, anxiety, joint and muscle pain, vaginal dryness, reduced sex drive, and hip fractures in later life. Hormone replacement therapy can turn these symptoms around.

Women’s health specialists are concerned that a meta-analysis published in the Lancet does not evenly show the benefits of HRT compared to the risks and think that the NICE guidance in 2015 looked more comprehensively at all the available evidence. They don’t want either women or doctors to stop HRT unnecessarily.

The Lancet showed that in the UK one in 16 women who have never taken HRT will develop breast cancer between the ages of 50 and 69.  If a woman of normal body mass index (under 25) starts HRT in her 40s or 50s the additional risk of getting breast cancer is one in 200 for oestrogen only HRT, one in 70 for daily oestrogen and progestogen for part of the month, and one in 50 for preparations with a mix of oestrogen and progesterone daily.  But body weight and alcohol have a greater effect on getting breast cancer than HRT. For instance, being overweight or obese will increase the rate of breast cancer six times compared to combined HRT.

The Lancet study looked at how many cases of breast cancer started but did not look at the mortality rate. A recent systematic review did. This showed that if a woman started HRT close to the menopause there was an apparent reduction in all cause mortality and cardiac death with no evidence of an increase in deaths from breast cancer.

The womens’ health specialists are concerned that the bone benefits and cardiac benefits, especially for women going through an early menopause, will be ignored if undue weight is put on the small increase in breast cancer diagnosis, over the symptomatic benefits and improvement in total mortality.

BMJ 2019;367:15928

 

Self caring during illness

Adapted from online presentation by Beverly Bostock ANP 7 May 2020

If you have diabetes you are more at risk of serious complications from Covid-19 and should seek medical advice early in the illness.

Any febrile illness can raise your blood sugars, including the prodromal phase when you don’t otherwise have symptoms. Once you are aware that you are coming down with something there are some useful ways of remembering how to monitor yourself.

Particularly for insulin users:

S – SUGAR – check your blood sugar more frequently than usual. For instance, if you would normally check your blood sugar every 5 hours during the day, double this to every 2.5 hours.

I – INSULIN – Adjust your insulin according to your blood sugars to keep within your target blood sugar level.

C – CARBOHYDRATE – If your blood sugar is low eat or drink more glucose or sugar/starch food items. If your blood sugar is high, drink plain water or more diet drinks.

K – KETONES – Use blood ketone stix or urine ketone stix to monitor your ketones if you are a type one diabetic every 4 hours or so. This is particularly important if you feel very ill, are nauseated, vomiting or have abdominal pain. If your ketones are high consider extra insulin, keep well hydrated and alert medical staff sooner rather than later.

Particularly for type twos:

It is important to keep well hydrated when you experience any illness but particularly an illness where you are febrile, or have  vomiting, limited oral intake, or severe diarrhea.

Some drugs can worsen your response to dehydrating illness and you may need to seek advice from a doctor, nurse or pharmacist about stopping certain drugs and when it is appropriate to restart them.

You can remember what they are with the mnemonic: SADMAN

SGLT2 inhibitors, ACE inhibitors, Diuretics, Metformin, ARBs, and Non- steroidal anti-inflammatory drugs.

 

 

 

Metformin reduces oesophageal cancer

Adapted from Wang QL et al. American Journal of Gastroenterology 1st January 2020

Metformin users were at a lower risk of developing oesophageal squamous carcinoma than non metformin users.

A growing number of observational studies have shown that metformin reduces overall cancer risk and a few specific cancer types such as colon, rectal, breast and stomach.

A population based cohort study included over 400,000 metformin and an equal number of non metformin users who were matched by age and sex.

There were 3.5 cases of oesophageal cancer in the metformin group per 100,000 person/years and 5.3 in the non metformin group. This finding was true for men, women and those in their sixties.  The odds ratio was 0.68 for metformin use.

Dr Aseem Malhotra: What is wrong with how we try to prevent cardiovascular disease

In part two of this series on cardiovascular disease Dr Aseem Malhotra, consultant cardiologist explains why putting faith in statins to resolve the cardiovascular disease epidemic is misguided. He explains that they only extend life by a matter of a few days yet need to be prescribed for years at considerable cost to the health service. Furthermore, he thinks that their side effects are not being explained to patients.

This is a medium length article which contains information on statins not readily seen in a single document.

https://www.europeanscientist.com/en/features/do-statins-really-work-who-benefits-who-has-the-power-to-cover-up-the-side-effects/

Dapagliflozin now approved for type ones in Scotland

From Scottish Medicines Consortium 9 September 2019

Dapagliflozin has been accepted for the treatment of inadequately controlled type one diabetes mellitus as an adjunct to insulin if their body mass index is at or above 27.

The combination significantly improves glycaemic control.

My comment: In my experience the combination is also good for weight control. These findings have been known for several years from USA research so it is good that Scottish doctors are being encouraged in its use.

 

Heartburn can be treated with Imipramine

From Cheong K et al. Low dose imipramine for refractory functional dyspepsia: a randomised double blind placebo controlled trial. Lancet Gastroenterology Hepatol. Oct 22 2018.

Heartburn is a miserable and very common symptom. It can be treated with antacids such as Peptac and Gaviscon and drugs such as Ranitidine and Omeprazole or Lansoprazole.  Domperidone, which increases gut motility can be used short term. But sometimes these don’t work.

Imipramine is an old anti depressant drug which was used in this recent drug trial for heartburn that had not responded to Esomeprazole and Domperidone.

107 patients entered the trial. The treatment arms were placebo or imipramine 25mg at night for two weeks, then 50mg a night for a total of 12 weeks.

In the Imipramine arm 63% of patients got a good reduction in symptom score compared to placebo’s 36.5%.

There was a higher rate of stopping the Imipramine, 18% versus 8% for the placebo. The side effects were dry mouth, constipation, drowsiness, insomnia, palpitations and blurred vision.

My comment: The re use of this old drug will be very helpful for patients who have run out of options for their heartburn. Many patients get an excellent effect when they go on a low carb diet too. The side effects of this are: slim down, lose belly fat, feel more energetic, clearer skin and for diabetics a great improvement in blood sugar control.

 

RCGP: Adapting diabetes medication for a low carb diet

Adapted from RCGP July 19 Adapting diabetes medication for low carbohydrate management of type two diabetes by C Murdoch et al.

This topic has been well covered in our book but has been reviewed in this article. 

Type two diabetes can be reversed by a low carb diet. Changes in medication need to keep pace with lowered blood sugar levels that result. A low carb diet can range from under 30g to 130g of carb a day.  Blood pressure medication also often needs to be reduced or stopped as lower blood pressure results from a reduction in insulin resistance.

Sulphonylureas, meglitinides and insulin all reduce blood sugar and if not reduced appropriately can result in hypoglycaemia.  It is reasonable to cut the dose of these by 50% when a low carb diet is started. Once the diet is stabilised the levels can be increased if this is necessary. If a patient has very high blood sugars eg HbA1C of 10% or more then a reduction of 30% can be considered initially. As more weight is lost or more carb is cut from the diet, further reductions can then be made. Some patients will be able to stop insulin and oral hypoglycaemics entirely as progress is made.

Some patients have latent autoimmune diabetes and although they can reduce their doses, their insulin must be maintained at some level. These patients can often be identified because they developed type two diabetes when they were thin.

Some patients who may need to stay on some insulin have had type two diabetes for many years and have ceased to make any pancreatic insulin. (Secondary beta cell failure).  My comment:  Users of sulphonylureas eg Gliclazide over five years are prone to this problem.

It is important to provide plenty of blood glucose testing strips to patients over the transition so they can let you know if they are experiencing hypos.

GPs can refer to endocrinologists for advice over patients who are giving concern.

Flozins also known as SGLT2 inhibitors increase the risk of ketoacidosis in patients who have significant pancreatic insufficiency.  The ketoacidosis is hard to recognise because the blood sugar is often normal or only very slightly raised. The person just feels ill and may vomit. My comment: in my experience this effect is difficult to predict but usually occurs in the first week or two of treatment. Low carb diets of below 30g-50g of carb a day also produce dietary ketones so can muddy the waters even more. Therefore is someone is on a flozin and starts a low carb diet it is best to suspend the flozin. They may not require it after a while on a low carb diet in any event.

Commonly used drugs that do not give any risk of hypoglycaemia include Metformin, Glutides, Glitazones, Gliptins and Acarbose.

About a quarter of people on metformin get diarrhea and need to go on the long acting version or stop it altogether.  Because acarbose is meant to help block starch and this is eliminated on a low carb diet, this drug can be stopped.  Glutides, Glitazones, Gliptins can be stopped when blood sugars are at a satisfactory level.  My comment: The target blood sugar will vary from patient to patient. You can see more about this in my PHC talk on you tube or in our book.

 

 

 

BMJ: Taking glucosamine long term may reduce cardiovascular disease risk

Adapted from BMJ18 May 19. Association of habitual glucosamine use with risk of cardiovascular disease. Ma h, Li X, Sun D et al. BMJ 2019:365:1628

Just over 466 thousand participants from the Biobank who did not have cardiovascular risk at that point completed a questionnaire about supplement use including glucosamine. Subjects were enrolled between 2006 and 2010 and were followed up in 2016.

After adjusting for age, sex, BMI, race, lifestyle factors, dietary habits, drug use and other supplement use, glucosamine was associated with a significantly lower risk of cardiovascular events. A limitation is that the association may not be causal. Perhaps those who use supplements are healthier than those who don’t.

The results they found were that there was a 15% less risk of total cardiovascular events.

There was a 22% lower risk of cardiovascular death, 16% less risk of ischaemic heart disease and a 9% lower risk of stroke.

My comment: I have been taking glucosamine regularly for the last 19 years because I have found that it completely solved the knee pain I had had for the previous five years. As I have a very strong family history of osteoarthritis of the knee and other joints I was keen to try it. Osteoarthritis is linked to inflammation in the joints, and we know that cardiovascular disease is linked to inflammation in the arterial walls and the bodies attempt to repair minute tears with cholesterol containing plaques. Thus there is a possible mechanism to explain the reduction in cardiovascular disease for those that take it. It is of course also possible that supplement takers take more exercise and I’m not sure to what extent the “lifestyle” factors were adjusted for. 

BMJ: Flu jag timing matters

From BMJ May 2019: Minerva BMJ 2019;365:1993

A review in Science indicates that vaccines for mumps, whooping cough and yellow fever lose their effectiveness more quickly than those for measles, diptheria, tetanus and flu.

The flu vaccine at best only protects about 60% of the people given it in any given year. Its effectiveness also declines after just a few months. If you are first in the queue to get it towards the end of September, much of its effects will be lost by January and February which are the peak months for flu infection.

My comment: Maybe you should plan to get the jag any time from mid November to mid December  if you are very keen on getting maximum effectiveness to prevent flu?

 

BMJ: Flozin effects in type one diabetes

 Adapted from BMJ 13 April19 Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type one diabetes Musso G, Gambino R. Cassader M, Pascheta E. BMJ 2019:365:1328

Flozins are increasingly used for patients with “double diabetes” in practice. The authors of this study searched for randomised controlled trials for the drug Sotagliflozin to find out how effective they were and what safety issues were apparent. Over three thousand patient responses were studied. There were six trials that were of moderate to good quality and they ran between four weeks and a year. The relative pluses and minus are listed.

lowered HbA1c by  0.34% (small)

reduced fasting and post meal blood sugars

reduced daily total, basal and meal insulins

reduced time in target blood sugar range

reduced body weight by 3%

reduced systolic blood pressure by 3 mmHg

reduced protein in the urine

reduced the number of hypoglycaemic events

reduced the number of severe hypoglycaemic events

On the other hand these factors were increased:

Ketoacidosis increased by a factor of x 2 to x 8 depending on the study looked at

genital tract infections increased by a factor of x 2 to x 4.5

diarrhea increased up to x 2

volume depletion events increased by up to x 4

Patients got better blood sugar results from the higher dose of 400mg Sotagliflozin compared to the 200mg dose without increasing the risk of adverse events.

Most DKA episodes occurred as the drug was being started and patients cut their insulin dose too much, in anticipation of reduced blood sugars.

My comment: The risk of DKA in type twos is not very common but is a known effect of flozins, so it is not that surprising that this is increased in type ones too. The reduction in hypoglycaemia events and severity is a new finding and suggests an increasing role for flozins in type one management.