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: 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.




Type ones on low carb diets experience less hypoglycaemia

Adapted from Why low carb diets for type one patients? Jun1 2019 by Emma Kammerer Pharmacy Doctorate Candidate Bradenton School of Pharmacy originally published in Diabetes in Control.

Both Dr Jorgen Neillsen and Dr Richard Bernstein have shown that insulin users have fewer attacks of hypoglycaemia and that the attacks are less severe.  A new randomised controlled study by Schmidt et al confirms this finding.

Studies have shown that when a high carb diet is consumed there 20% greater error in carbohydrate estimation compared to when a low carb diet is chosen. This then affects the insulin dose administered, and thus the resulting blood sugars.

Schmidt wanted to look at the long term effects on glycaemic control and cardiovascular risk in type one patients on a low carb diet compared to a high carb diet.

The study was a randomised open label crossover study involving 14 adults who had had diabetes for more than 3 years, to eliminate the honeymoon effect. The patients went on one diet for 12 weeks, had a washout period of another 12 weeks, and then took up the other diet.  This was done so that the glycated haemoglobin levels would not be carried over from one diet to the next.

A low carb diet was defined as less than 100g carb a day and a high carb diet as over 250g per day.

Patients were given individualised meal plans and education on how to eat healthy carbs, fats and proteins. They all were experienced insulin pump users. They were asked to record total carbohydrate eaten but not the food eaten. Measurements were taken on fasting days on the first and last day of the study periods.

Blood glucose levels were downloaded from continuous glucose monitoring devices.

Four patients dropped out of the study so ten completed the test which was considered satisfactory by the statistician involved.

Results showed that the time spent in normal blood sugar range 3.9 to 10 mmol/L ( USA 56-180) was not significantly different for each diet.

The time spent in hypoglycaemia, below 3.9 (USA 70) was 25 minutes less a day on the low carb diet, and six minutes less a day below 3.0 (USA 56).

On the low carb diet glycaemic variability was lower and  there were no reports of severe hypoglycaemia.

On the high carb diet, significantly more insulin was used, systolic blood pressure was higher and weight gain was more.

There was no relevant changes in factors for cardiac risk between the two study arms.

The study showed that a low carb diet can confer real advantages to type one patients but education on how to conduct a low carb diet and manage the lower doses of insulin is required.

Schmidt, Signe et al. Low versus high carbohydrate diet in type 1 diabetes: A 12 week randomised open label crossover study. Diabetes, Obesity and Metabolism. 2019 March 26.



Vitamin D shown to improve blood sugar control in gestational diabetes

From Ojo O et al. The effect of vitamin D supplementation in women with gestational diabetes mellitus. A systemic review and meta-analysis of randomised controlled trials. Int J Environ Res Public Health. 2019:16(10)

A meta-analysis has indicated that various factors relevant to improved blood sugar control are likely to be improved by vitamin D supplementation in  a total of 173 women with gestational diabetes.

Fasting blood glucose decreased by a mean of 0.46 mmol/L

Glycated haemoglobin decreased by a mean of 0.37%

Serum insulin reduced by a mean of 4.10 uIU/mL.

 My comment: Although the improvements are small, vitamin D supplements are inexpensive, easy to take and do not have the side effects of other medications.



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.

Higher blood pressure is linked to LESS cognitive decline

From Streit S et al. Ann Fam Med 1 March 2019 and reported by Sarfaroj Khan UK Clinical Digest 13 March 2019

In my GP career treatment of blood pressure for the general population has become more intensive as time has gone on. This hasn’t always resulted in better long term outcomes overall. Indeed, the target systolic blood pressure, the upper measurement, has been moved from 130 to 140 in the last few years because of this.

A Dutch study of over a thousand patients over the age of 75 showed that those with a systolic blood pressure under 130 showed more cognitive decline than those with a blood pressure over 150 when they had mental functioning tests a year later.

Those with higher blood pressures had no loss of daily functioning or quality of life.

As aggressive blood pressure control in those with diabetes is standard treatment, it is worth knowing this. Perhaps further studies in this subgroup of patients would be worth doing. I have seen reports of impaired kidney function when blood pressure levels are “optimal” but low too.

Another study regarding blood pressure management reported in the British Journal of Sports Medicine indicates that blood pressure reduction of almost 9mm Hg in hypertensive patients when regular structured exercise is undertaken. This is of a degree similar to most anti-hypertensive medications. (Reported in BMJ 5 Jan 2019)



Eating carbs last gives lower blood sugar spikes

From IDDT newsletter December 2018

A report in BMJ Open Diabetes Research and Care Sept 2017 shows that in type two diabetes, eating sugar and starch later in the meal halved the blood sugar spike after the meal compared with those who ate the sugar and starch first.

This study was done on 16 people who ate test meals of protein, vegetables, bread and orange juice. Those who were instructed to eat the bread and juice last also had 40% lower post meal glucose levels compared to those who ate all of the meal components in a mixed fashion.

My comment: This is a small study but easily reproducible with yourself and your blood glucose meter. If you do wish to eat sugar and starch best have these last, unless you are treating a hypo.