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.

 

 

 

Lower cholesterol may not better if you have neuropathy

From Jende JME et al. Peripheral nerve damage in patients with type 2 diabetes. JAMA Netw Open. 2019;2(5);e194798

In type two patients who had diabetic neuropathy affecting the legs, low total cholesterol and low density lipoprotein cholesterol had more nerve lesions, impaired nerve conduction and more pain and disability than those with higher cholesterol levels.

Almost all type two diabetics will be advised to take statins to keep the cholesterol level down as this is generally accepted as improving the outlook for cardiac and circulatory conditions.

One hundred participants with type two diabetes were tested using magnetic resonance neurography. 64 had diabetic neuropathy and 36 did not.

My comment: Although this was not discussed in the abstract, I wonder whether those people with more advanced complications were being more intensively treated all round and thus had more/higher doses of statins, and so the relationship between low cholesterol and neuropathy severity was simple association, or whether there is a causative factor here. I am aware that statin neuropathy is believed to exist.

Dietary calcium doesn’t make your bones stronger after all

Although it is current practice to prescribe vitamin D and calcium together, particularly in post menopausal women, a six year study shows that the added calcium has no value.

The women were all over the age of 65 and had osteopenia. This is the stage before osteoporosis. 1,994 women were randomised to take zolendronic acid or placebo.  Bone mineral density was measured at the spin, total hip, femoral neck and total body three times at intervals.

The baseline BMD was unrelated to dietary calcium after controlling for age, height, weight, physical activity, alcohol intake, smoking and past HRT use when a cross section of women were studied.

Loss of BMD over the next six years was not related to the amount of dietary calcium ingested.

Bristow SM et al. Dietary Calcium intake and bone loss over six years in osteopenic post menopausal women. J Clin Endocrinol Metab. 2019 Mar 21.

My comment: Maybe time to ditch the calcium?

And while we are on the subject of bones, I’m pleased to say that another study has shown that high dose vitamin D supplementation does NOT increase kidney stone risk.

Over just over 3 years of taking 100,000 iu of vitamin D3 each month did not increase excess calcium in the blood or the onset of kidney stones in adults aged between 50 and 84 years.

This dose is equivalent to 3300 iu vit D3 a day, similar to what many of us in the know take.

158 people took part in the randomised trial. The number of people developing kidney stones was similar in each group and no one in the intervention group developed hypercalcaemia.  The groups self reported stones. No ultrasound was done which the authors say could have been more accurate.

Malihi Z et al. Monthly high dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomised controlled trial. Am J Clin. Nutr. 2019 Apr 21

 

Liraglutide can improve fatty liver damage as well as blood sugars

Adapted from Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option. 

Gauri Dhir and Kenneth Cusi  Endocrinology/Metabolism Review Volume 66 Issue 1 2018

Obesity is a major risk factor for type two diabetes and a cluster of metabolic factors that lead to poor cardiovascular outcomes.  The amount of fat stored in the liver tissue closely mirrors insulin resistance and metabolic health.

Non alcoholic fatty liver disease (NAFLD) is now the commonest form of liver disease in the western world and can lead progressively to non alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma.

NAFLD is present in two thirds of obese people and promotes type two diabetes.  NASH is present in half of these. NAFLD is expected to become the most common cause of liver transplantation by 2020.

Pioglitazone and the newer drugs such as Liraglutide (Victoza) can be used, as well as various dietary therapies.

If a weight loss of 10% can be achieved, there is a significant improvement in the inflammatory process that results in cell death and fibrosis in NASH. But weight loss is difficult to achieve and maintain.  Pioglitazone can improve  NASH in two thirds of non- diabetic patients and by around half in those with diabetes or pre-diabetes.  Vitamin E has also been shown to have some success in non diabetic patients.

Liraglutide and drugs of the same class affect insulin secretion in response to meals, beta cell proliferation, inhibition of glucagon secretion, delayed gastric emptying, and making you feel fuller with less to eat.

These effects result in worthwhile clinical outcomes in overweight or obese patients whether they have diabetes or not. Body weight is reduced by at least 5% in 30% of patients and by at least 10% in 30% of patients. Over three years this can result in complete remission of the diabetes or pre-diabetes in 30% of the patients. Cardiovascular outcomes are also improved.

Triglyceride accumulation in the liver cells is the mechanism that has been recently shown to cause insulin resistant adipose tissue.  After 48 weeks of high dose Liraglutide (1.8 mg a day), resolution of NASH was seen on biopsy samples in 39% of the treated group compared to 9% in the placebo group.

The main side effects are nausea and diarrhea.  There could possibly be more gallstone development but no increase in pancreatitis.

Drugs Trial for Diabetic Retinopathy Medication

I’d kill for her eyelashes… Picture from Max Pixel.

Once more, dear friends, I’m putting my body to good use—a drugs trial where I hope my small part contributes to better outcomes for other people with diabetes.

Last year, when I received one of my six-monthly invites to the retinal screening clinic, an invite popped out of the envelope. Did I wish to take part in a trial for a drug aimed at preventing the progression of diabetic retinopathy? Not ‘alf. I’m keen to hang onto my eyesight for the rest of my life, especially as I’m a voracious reader.

I do have diabetic retinopathy. The changes to my eyes happened years ago, I’m screened regularly and while the letters that follow my appointments tell me there is more evidence of minor changes so far I’ve not needed treatment. And long may that happy state continue.

Cholesterol reducing

The drug I’ve been taking is a fenofibrate. I say that as if I have any idea of what that means. I don’t, apart from it belonging to the fibrate class of medications and it also has cholesterol reducing properties. I’ve now taken it for seven weeks.

If you are not familiar with drugs trial protocol, if a person is judged suitable for a trial after tests, they take the drug for a run-in period. Further tests are done—blood pressure, height, weight and bloods—and then you are put in one of two groups. One takes the real drug, the other takes a placebo and that’s you for two years.

I’ve done the run-in and now I’m about to do the two years around with the other thousand or so people who have been recruited to take part. Exciting to think our participation might shape treatments for years to come, and here’s hoping the drug proves effective not just for me but for anyone else at risk of losing their eyesight.