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.

 

 

 

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.

 

 

More fat = more kidney failure

From BMJ 12th January 2019

Chang AR et al The CKD Prognosis Consortium BMJ 2019;364:k5301

Between 1970 and 2017 a huge number of people were assessed for fatness using body mass index, waist circumference and waist to height ratio. The outcome was that the fatter you get, the more your kidney function declines. This was true whether you started off  with normal or impaired kidney function.

The lowest kidney disease was seen in those with a BMI of 20 and this barely changed till a BMI of 25 was reached. After this was a linear progression. By the time your BMI is 40, you have double the risk of kidney function impairment.

The results were adjusted for age, sex, race and current smoking.

My comment: This is a new risk factor for obesity as far as I know.

 

 

 

Hypoglycaemia: the neglected complication

Adapted from Hypoglycaemia: the neglected complication by Sanay Kalra et al.

Indian J Endocrinol Metab. 2013 Sep-Oct; 17(5): 819-834

Hypoglycaemia is an important complication of glucose lowering therapy in patients with diabetes mellitus. Attempts made at intensive glycaemic control invariably increases the risk of hypoglycaemia. A six fold increase in deaths due to diabetes has been found in patients with severe hypoglycaemia compared to those not experiencing severe hypoglycaemia.

Repeated episodes can lead to hypoglycaemia unawareness. Complications  of hypoglycaemia include stroke, heart attacks, cognitive dysfunction, retinal cell death and loss of vision. Apart from this there are the effects on quality of life regarding sleep, driving, employment, exercise and travel.

To maintain good glycaemic control, minimize the risk of hypoglycaemia and thereby prevent complications, there are steps that need to be taken: recognise risk factors for hypoglycaemia, use appropriate self monitoring of blood sugar, select treatment regimens that have little or no risk of incurring hypoglycaemia and teach health care professionals and patients how to avoid hypoglycaemia.

Although the DCCT showed that complications were reduced when blood sugars were brought under a HbA1C of 7%, other trials have noted a three fold risk of hypoglycaemia when the level is reduced under 6.5%. This tends to negate any improvements in long term complications.

Insulin users are most at risk. Those who have had diabetes for more than 15 years are particularly at risk. The DARTS study showed that the risk of severe hypoglycaemia was 7.1% for type one patients, 7.3% for type two patients and 0.8% for type twos on sulphonylureas. This causes increased cost for their healthcare as hospitalisation for around a week is needed in the average case.

The majority of hypos are due to medications but there are other potential causes such as: pancreatic or islet cell tumours, dietary toxins, alcohol, stress, infections, sepsis, starvation and excessive exercise.

In diabetics not eating enough food was the most common cause. Others were physical exercise, insulin miscalculation, stress, overtreating a high blood sugar, and impaired glycaemic awareness.

Nocturnal hypoglycaemia is seen in half of diabetic children, particularly under the age of 7. Dead in bed syndrome causes 5-6% of all deaths in type one youngsters.  Contributory factors are increased exercise that day or delayed meals.

In type two patients additional causative factors are alcohol ingestion and liver disease and duration of insulin over ten years. As in type ones there tends to be more hypoglycaemic unawareness as the person ages. In type twos  there is a 9 fold increase in deaths in those with hypoglycaemic unawareness.

Severe hypos in elderly patients increase the risk of dementia, functional brain failure and cerebellar ataxia. There are clear signs of neuronal death in specific brain areas at post mortem in these patients and a history of fits make these more extensive.

Hypos in elderly patients promote cardiac ischaemia. Arrhythmias are more likely due to catecholamine release during hypos. Prolonged QT intervals lead to increased heart rate, fibrillation and sudden cardiac death.  Inflammatory cytokines are released during hypos, abnormalities of platelet function and the fibrinolytic system occur.

Hypos can cause double vision, blurred vision and dimness of vision.  Blindness can occur due to retinal cell death.

Recurrent hypos make people feel powerless, anxious and depressed. Acute hypos cause mood swings, irritability, stubbornness and depression.  Quality of life scores are worse in patients with recurrent hypos.

Driving ability is affected by hypos. The affected driver can inadvertently cross lanes and speed and generally drive worse.

Hypos at night may be recognised by sleep disturbance, morning headaches, chronic fatigue and mood changes. In young children fits and bed wetting may occur.

Hypos at work can be awkward, embarrassing and frightening. Hypos are particularly dangerous for those who work at heights, underwater, on railway tracks, oil rigs, coal mines, handling hot metals or heavy machines.

Expert medical advice and planned action counselling can help workers. So can self blood glucose testing, healthy food options in canteens, flexible meal times, arrangements to carry and use emergency glucose/sugar, storage and disposal sites for medications and sharps, and time off for medical appointments. Work time and productivity due to hypos can be reduced and nocturnal hypos can also have a knock on effect the next day.

Hypos in children tend to be increased in summer months when they are more active. In adults, intense prolonged exercise following an episode of recent severe hypoglycaemia can damage skeletal muscle and the liver and can cause severe neurological symptoms.

Travelling long distances, particularly over times zones can cause insomnia, tiredness, stress, reduced appetite, nocturia,  gastric disturbance, muscle aching and headaches. Psychological symptoms include low mood, irritability, apathy, malaise, poor concentration. These deficits in both physical and mental performance can profoundly affect decision making.

The fear of hypos can affect patients more profoundly than the fear of long term complications.  Withholding of insulin can occur. Sometimes patients refuse to start it when they need it and sometimes they miss out their doses.

About 30% of type one patients are affected by hypoglycaemia unawareness and under 10% of type two patients are thus affected. Duration of insulin use is the main common factor.

Educating patients about how to detect, treat and prevent hypoglycaemia must be understandable to the patient and their family.

In 2013 the ADA recommended that insulin users test their blood sugars 6-8 times a day.

Basal insulin needs to be matched to the patients needs. If hypos persist, particularly overnight, switching to pump therapy may help.

Newer diabetic medications, which do not cause low blood sugars such as the gliptans and gliflozins, may be preferable in type two patients who have multiple co-morbidities, are elderly,  who live alone, are at high risk of falls, and who have hypoglycaemia unawareness or who otherwise could not effectively deal with a hypo.