Category: research

BMJ: Flozin effects in type one diabetes

kaitiscotland2 Comments

 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

kaitiscotland3 Comments

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

kaitiscotland1 Comment

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

kaitiscotland1 Comment

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

kaitiscotland4 Comments

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

kaitiscotland5 Comments

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

kaitiscotland2 Comments

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.

 

 

 

Dietary calcium doesn’t make your bones stronger after all

kaitiscotland5 Comments

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

kaitiscotland6 Comments

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.

When do you stop getting benefits from exercise?

kaitiscotland2 Comments

From Danielle Baron’s article in International Medical News 10 August 18

As with many different health interventions, there is a sweet spot between doing enough of it and doing too much of it. Too little, and it is not effective. Too much and you could cause unexpected negative repercussions.  The subject of exercise has been investigated regarding its effect on mental health.

Over 1.2 million USA citizens were asked about their exercise habits and their mental wellbeing between 2011 and 2015 by researchers at the Centers for Disease Control and Prevention.

All exercise types improved mental health but popular team sports were particularly effective in boosting mental health. The optimal duration of exercise was between 30 and 60 minutes a session, three to five times a week.

Sessions of longer than 90 minutes or done more than 23 times a month however, were related to WORSE mental health.

The authors conclude that blanket advice on exercise could be improved by being more specific about the types, durations and frequencies that were more likely to improve mental health and that further studies could be helpful.

Chekroud SR et al. Association between physical exercise and mental health in 1.2 million individuals in the USA between 2011 and 2015: a cross sectional study. Lancet Psychiatry. Published online 8 August 2018. doi: 10.1016/S2215-0366(18)30227-X

My comments: Oh dear! Well, I’ve got the duration right at 40 minutes but I hate team sports (because I’m useless at hand to eye or foot coordination) and I aim to exercise every day, which these researchers considered “excessive”.  Maybe the team sports were more beneficial because of the socialisation aspect as well as the physical aspect. Maybe less than 23 times a month made it something to look forward to and a dopamine hit , “I’ve achieved that” rather than a black mark ” I failed to do my exercise session”   as I tend to think about it. I can see the downsides of exercise addiction reflected in this piece of research.