Metformin users have fewer knee and hip joint replacement than other type two diabetics

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A study published in the Journal of the Canadian Medical Association in Dec 2020, has found that type two diabetics who are on Metformin have about two thirds of the risk of having a hip or knee joint replacement compared to diabetics on other medications.

The study was undertaken by Dr Zhaohua Zhu from Zhujiang Hospital in Guangzhou in China. They compared the records of over twenty thousand patients in each group and compared the duration that they were on the diabetes medications and surgical outcomes.

As they found that Metformin use was associated with a significantly reduced risk of joint replacement, this suggests a potential therapeutic effect in patients who have osteoarthritis. They recommend that randomised controlled trials are undertaken to see if there is a beneficial effect in this group.

My comment: As Metformin has already been shown to reduce cancer incidence, is inexpensive, and reasonably well tolerated both by diabetics and non-diabetics, it would seem a good idea to me for such trials to be carried out.

New drug can delay the onset of type one diabetes

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Adapted from Medscape Nov 20 2022 by Miriam E Tucker a freelance journalist from Washington DC.

At last humans have caught up with mice!

Since my son was diagnosed with type one diabetes, some 28 years ago, it has been possible to reverse type one diabetes in mice. At last the huge effort to find a suitable agent to use in humans, and particularly children, has been approved by the FDA.

Thank you everyone who has contributed to this marvellous discovery. The Juvenile Diabetes Research Foundation was set up with this end point in mind and they have been successful in the development of the new drug which they helped fund. The thing is that now such an agent is available, we need to be able to find the people who would most benefit from taking the drug. Thus screening for early type one diabetes is going to become crucial.

The new drug is called Teplizumab-mzwv (Tzield, Provention Bio) and it is a anti-CD 3 monoclonal antibody. It was approved in Nov 17 21 and is the first human disease modifying therapy for impeding the prevention of type one diabetes. It delayed onset by around 2 years and longer in some subjects.

It is given by an intravenous infusion once daily for 14 days and costs around $200,000 dollars for the course of treatment.

It is licensed for children over the age of 8 years. The group it is targeting is those who are asymptomatic but who have raised blood sugar levels and at least two type one diabetes antibodies. Most of those screened are first degree relatives of type ones. The JDRF is offering a screening blood test for $55. But because 85-90% of people who do develop type one diabetes don’t have a first degree relative, screening will need to be developed further.

In Bavaria, Germany, screening of all schoolchildren for type one diabetes has been done, and the organisers said that a major benefit, was that education about the signs of diabetes occurred so that diagnosis occurred before Diabetic Ketoacidosis developed. This is known to cause deaths and wears out the pancreas much faster.

In another study 2 year olds and 6 year olds in the USA and western Europe were screened for islet autoantibodies and this detected almost all of those children who developed type one diabetes by mid adolescence.

Using a genetic risk score at birth has been suggested as more cost effective by Dr William Hagopian of the Pacific Northwest Research Institute in Seattle. 10% of newborns have HLA genes that can identify 80% of those who will get childhood type one diabetes.

My comment: I’m particularly pleased to see that the JDRF has been successful because if my son has offspring they have a one in three chance of developing type one diabetes in childhood. As time goes on, it is to be hoped that the interventions will become cheaper and more effective.

Co-enzyme Q10 in cardiovascular and metabolic disease

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Adapted from Co-enzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem, by Vladlena I Zozina et al. Current Cardiology Reviews 2018 Aug: 14(3) 164-174.

Co-enzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that it is tightly linked to cardiometabolic disorders. Supplementation can be useful in a variety of chronic and acute disorders. This review article discusses its role in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidaemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation.

CoQ10 is made in the inner membrane of the mitochrondia. These are the little batteries which power your cells. It exists as ubiquinone which is oxidised and ubiquinol which is does not have oxygen attached. It is a key component of electron transfer in ATP production, which is how cellular energy is generated.

It is also an intercellular anti-oxidant. It also plays a role in cell growth and differentiation. There are many diseases and degenerative states associated with CoQ10 deficiency such as type 2 diabetes, atherosclerosis, hypertension, dyslipidaemia, muscular dystrophy, Alzheimer’s disease and Parkinson’s disease.

Administration of selenium and CoQ10 in a group of elderly people over 4 years resulted in significantly reduced cardiovascular mortality over the next ten years. This new review aims to sum up current possibilities in a variety of conditions with an analysis of the impact on health and quality of life.

CoQ10 is found in all organs but the highest concentrations are in the heart, kidneys, liver and muscles.

Three out of four patients with heart disease have low levels of CoQ10, particularly in ischaemic heart disease and cardiomyopathy.

In 2010 31% of all adults had hypertension. This rate is rising, particularly in low income countries.

CoQ10 has a direct effect on the lining of blood vessels, the endothelium, which dilates the blood vessels in hypertensive people and so reduces blood pressure. It also has a blood pressure lowering effect via the angiotensin effect in sodium retention and lowers aldosterone. Blood pressure can be lowered as far as normal levels with CoQ10 and has been measured as reducing systolic bp by 11 mmHg and diastolic by 7mmHg.

Giving 300mg daily of CoQ10 has been shown to reduce inflammatory markers and raise anti-oxidant enzyme activity. It is well known that a pro-inflammatory effect is a major component of chronic disease.

In 2013 cardiovascular diseases were a worldwide leading cause of death causing about a third of all deaths. A randomised study showed that in patients with myocardial infarction and hyperlipidaemia, supplementation resulted in lower blood pressure and a beneficial rise in HDL. After primary angioplasty after a heart attack, patients with higher levels of CoQ10 had better ventricular performance at 6 months follow up.

In rat studies infusion of CoQ10 results in less cardiac damage when their cardiac vessels are occluded to provoke cardiac ischaemia.

Heart failure causes less blood to be pumped out of the heart with every heart beat. This can be from a combination of structural and functional heart problems. HF is the cause of a huge amount of hospitalisation and cardiac impairment. Deaths from HF range from 10% to 50% per year. The plasma level of CoQ10 has been found to predict mortality in HF patients. Supplementation has been found to be beneficial in raising the level and decreasing mortality rates.

CoQ10 helps the heart muscle beat with more power. 100mg given three times a day to HF patients showed a reduction in cardiovascular mortality (9% v 16%), all cause mortality (10% v 18%) and number f hospital stays. Exercise tolerance was improved at the end of 2 years observation.

In those patients on the waiting list for heart transplants, CoQ10 users had a significant improvement in functional status, clinical symptoms and quality of life. Although the drugs for HF are still essential, there can be some additional benefits to CoQ10 supplementation.

Atrial Fibrillation is increasing worldwide year on year and is associated with symptoms and mortality. Supplementation has been found to reduce arrhythmias after surgery or drugs to stimulate the heart muscle after surgery.

In mice studies survival rate was higher in those given CoQ10 than those who were not when they had viral myocarditis. In humans both CoQ10 and trimetazidine have been found to be effective.

Cardiomyopathy is associated with a high mortality and poor quality of life. It is linked to increased oxidative stress. Supplementation has been found to improve both cardiac structure and function. Fatigue and breathlessness improved. These studies have been done in both adults and children.

Cardiac toxicity is an unwelcome side effect for certain cancer drugs used in chemotherapy. CoQ10 and L-carnitine together have been found to be cardio-protective.

Supplementation has been found to reduce side effects of statins in heart failure patients. This is because statins deplete CoQ10 levels.

Although low CoQ10 has been found in type 2 diabetes patients, supplementation had no effect on glycaemic control, lipid profile or blood pressure. Triglyceride levels were reduced.

In patients with metabolic syndrome had a beneficial effect on insulin levels with supplementation.

Women with polycystic ovarian syndrome had a beneficial effect on glucose metabolism, and cholesterol levels with supplementation.

Studies have been done during and after cardiac surgery and in the management of post cardiac arrest care. In one study hypothermia plus supplementation resulted in considerably improved outcomes compared with hypothermia without supplementation. The three month survival was 68% v 29%.

Supplementation studies have shown a potential role in septic and haemorrhagic shock patients.

Further research needs to be done to establish the optimal doses to give for various conditions and situations.

Levels of 100 -300mg of CoQ10 per day seem to be effective for a wide range of problems.

Beta blockers and diuretics are not the best choices for hypertension

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Adapted from Medscape 2 Sept 2022. Hypertension: Real world efficacy of beta blockers versus other anti-hypertensives by Vinod Rane BS Pharm

Patients with hypertension who were treated with ACE inhibitors, Sartans and Calcium Channel blockers such as Amlodipine and Lercanipide had a lower risk of all- cause mortality than those treated with beta blockers.

The risk of all- cause mortality was no different between beta blocker users and those using diuretics.

Cardiovascular mortality was lowest in those treated with ACE inhibitors compared to beta blockers, Sartans, calcium channel blockers and diuretics.

Adapted from Sue Hughes Medscape August 26 2022 TIME: Cardiovascular events similar with evening or morning dose of blood pressure medications.

A five year trial looking at outcomes in those who took their blood pressure medications at night or in the morning showed no difference.

Previous studies have concluded that there could be a benefit to taking anti-hypertensives at night. Dundee researchers headed by Professor Tom MacDonald looked at hard outcomes which included vascular deaths, and non-fatal heart attacks and strokes.

They found “not a smidge of difference” between the two groups.

The study also showed that falls, fractures, or dizzy spells were no more common between the groups. The main thing he said was to take the medications every day at the same time and pick the time that suits you best.

The group tested had an average age of 65, 14% had diabetes,4% smoked,13% had prior CVD and the mean blood pressure at entry was 135/79. The patients were recruited from both primary and secondary care. The duration of follow up was between 5 and 9 years.

My comments: I am aware of the controversies regarding day and night time anti-hypertensives. Some doctors think that blood pressure control is better if drugs are taken at night and some think compliance is better if they are taken in the morning. I take my medication twice a day by splitting the dosage. That way I get good 24 hour coverage and if I forget a dose there is another one coming along in 12 hours or so.

NICE: SGLT2 inhibitors will have an increased role in type two diabetes management

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Adapted from BMJ 18 June 2022: Type 2 diabetes: summary of updated NICE guidance

When type 2 patients eventually get their diabetes checks, they can expect a few changes to management if their practices are keeping up with NICE guidelines.

Instead of looking at the 10 year risk for cardiovascular disease, type 2 diabetics over the age of 40 will be assessed for lifetime risk. This is usually a pathway to the initiation of statins, if they are not already being taken. If the cardiovascular risk is raised you will also be considered for an SGLT inhibitor.

If you have chronic heart failure or have already been diagnosed with atherosclerosis you will be considered for an SGLT2 inhibitor. These give a proven cardiovascular benefit.

SGLT2 inhibitors work well with Metformin if a glucose lowering drug is needed.

Modifiable risk factors for diabetic ketoacidosis should be assessed before prescribing SGLT2 inhibitors.

Such factors are: Alcohol limit above 14 units a week, use of illegal drugs, use of other medicines, concurrent illness, injury or planned surgery, very low carbohydrate or ketogenic diet.

There is a decision aid available at:

https://bit.ly/hba1c-nice

Dr Mark Cucuzella: Online resources for low carbing for patients and doctors

Adapting Medication for Type 2 Diabetes to a Low Carbohydrate Diet- Frontiers 2021

https://www.frontiersin.org/articles/10.3389/fnut.2021.688540/full

The above link gives the full paper from Dr Cucuzella about the medication adaptations, including insulin adaptations that need to be done if you are transitioning to a low carb diet. There is a helpful traffic light summary. Some medications do not need altered and these are discussed too.

Diet Doctor video on article “Why deprescription should be your new favorite word”

What your new diet will consist of and how to avoid unnecessary expense or complicated recipes is fully discussed in the following links. They are the same booklet but in different formats.

Our new “Low Carb on any Budget  – A Low-carb Shopping and Recipe Starter Begin a Life Free of Dieting and Indulge Yourself in Health” patient guide- Print and share with your patients

Pdf version

www.tinyurl.com/lowcarbanybudget

online flipbook

www.tinyurl.com/lowcarbanybudgetebook

For clinicians through guideline central

These booklets are quite complex and are for doctors who want to know more about low carb diets and fine tuning of medication and insulin. The first is in USA units and the second is the UK format. It does no harm for any diabetic or their carers to read these too but bear in mind that they do go into some depth.

-Guideline Central: Low-Carbohydrate Nutrition Approaches in Patients with Obesity, Prediabetes and  Type 2 Diabetes

http://eguideline.guidelinecentral.com/i/1180534-low-carb-nutritional-approaches-guidelines-advisory/0?

UK version – http://eguideline.guidelinecentral.com/i/1183584-low-carb-nutrition-queens-units/0? 

Vitamin D supplementation has been shown to reduce the development of autoimmune disease

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Adapted from BMJ 29 Jan 2022

This USA study looked at what happened after 5 years of vitamin D 3, omega 3 fatty acids and placebo to a group of over 12 thousand men and 13 thousand women. The men were at least 50 and the women 55 at the time of the start of the trial.

The groups were randomised to test out different combinations on the incidence of autoimmune diseases including rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, and psoriasis.

The results show that the vitamin D supplement group had the only statistically significant finding. This was a 22% reduction in autoimmune disease whether or not they took the vitamin D with omega three fatty acids or a placebo.

Although the doses are probably stated in the main paper, the summary from the BMJ did not contain this information.

Statin “deniers” take the Mail on Sunday to court for defamation

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Adapted from BMJ 26 March 2022.

Dr Malcolm Kendrick who is a GP, and Zoe Harcombe who is a PhD researcher, have raised a court action against the Mail on Sunday, because they think that their reputations have been damaged by being called “statin deniers whose deadly propaganda has endangered lives.” Their influence was described as “being worse than the MMR scare.”

Mr Justice Nicklin describes the case as a most significant piece of defamation litigation. The claimants assert that they have been accused of putting many thousands if not millions of people at a greater risk of a deadly or debilitating heart attack or stroke by misleading them into the false belief that statins do not work and/or have debilitating side effects.

Both Malcolm and Zoe write blog articles, have given lectures and written books. Malcolm writes, “Readers will know there is not one cause of heart disease. Equally, you are not going to protect yourself against heart disease doing one thing. You need to do many.”

Associated Newspapers who own the Mail on Sunday, say that their articles are substantially true, express an honest opinion and also say that they are protected by qualified privilege or by the defence of publication on a matter of public interest.

My comment: I was most concerned when I read about this case. There is a lot of controversy over the use of statins and the public should be able to hear both positive and negative information on health matters, so as to help them make up their own minds, or to stimulate further personal research. Dr Kendrick and Zoe Harcombe are both highly intelligent, well informed and well meaning people. They both support low- carbing for health care, and we have corresponded and met up personally and online at discussions and conferences of common interest. I am concerned that there is financial resource asymmetry here and that this case will be potentially ruinous for them. I await the court’s findings with interest and trepidation.

NICE: Semiglutide is the cavalry coming over the hill in the obesity battle

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Adapted from BMJ 12 Feb 2022

NICE are recommending that the anti diabetes drug Semiglutide is used for its anorexic properties in non diabetics who meet certain criteria.

Trials have found that patients given diet and exercise advice plus Semiglutide lost 12% more weight than lifestyle advice alone.

The drug is given in a weekly, self administered injection. My comment: I have used similar drugs with my type two patients and they were all surprised at how easy this was to do and how effective the drug was as an appetite suppressant.

To be considered for the treatment you have to have a BMI of at least 35 and have a related co-morbidity.

If you have a BMI between 30 and 34.9 you may be eligible for the drug if you are of South Asian, Chinese, black African or Caribbean family background or if you have been referred to a tier 3 weight loss service. This is because the drug is cheaper and safer than bariatric surgery and also because certain ethnic groups are more at risk of co-morbidity at lower BMIs than those of white European ancestry.

My comment: I can envisage that there will be huge market for this drug. One issue is that patients tend to regain weight on stopping and I understand that newcomers are expected to stay on the drug for two years.

Metformin improves side effects of steroid treatment

From Pernicova I et al. Lancet Diabetes Endocrinol 25 Feb 2020

Long-term glucocorticoids, most often prednisolone, are prescribed for about 3% of European adults. The long term exposure can raise metabolic, infectious and cardiovascular risks.

This was a trial of 53 adults who had inflammatory disease treated with prednisolone but did not have diabetes, who were given either 12 weeks of metformin or a placebo.

The dose of prednisolone was 20mg or more for the first month and then 10mg or more for the next 12 weeks. The dose of metformin given was up to 850mg three times a day.

What improved:

Facial fatness was in seen in 52% of the placebo group but only 10% in the metformin group.

Increased blood sugar was seen in 33% of the placebo group and none of the metformin group.

There was improvement in insulin resistance, beta cell function, liver function, fibrinolysis, carotid intima media thickness, inflammatory parameters and disease activity severity markers in the metformin group.

There were fewer cases of pneumonia, moderate to severe infections and all causes of hospitalisation for adverse events in the metformin group.

What got worse:

Diarrhea was worse in the metformin group.

What didn’t get better:

Visceral to subcutaneous fat ratio was unchanged between the groups.

My comment: Looks like a clear winner for adding metformin to long term prednisolone treatments.