Heartburn can be treated with Imipramine

From Cheong K et al. Low dose imipramine for refractory functional dyspepsia: a randomised double blind placebo controlled trial. Lancet Gastroenterology Hepatol. Oct 22 2018.

Heartburn is a miserable and very common symptom. It can be treated with antacids such as Peptac and Gaviscon and drugs such as Ranitidine and Omeprazole or Lansoprazole.  Domperidone, which increases gut motility can be used short term. But sometimes these don’t work.

Imipramine is an old anti depressant drug which was used in this recent drug trial for heartburn that had not responded to Esomeprazole and Domperidone.

107 patients entered the trial. The treatment arms were placebo or imipramine 25mg at night for two weeks, then 50mg a night for a total of 12 weeks.

In the Imipramine arm 63% of patients got a good reduction in symptom score compared to placebo’s 36.5%.

There was a higher rate of stopping the Imipramine, 18% versus 8% for the placebo. The side effects were dry mouth, constipation, drowsiness, insomnia, palpitations and blurred vision.

My comment: The re use of this old drug will be very helpful for patients who have run out of options for their heartburn. Many patients get an excellent effect when they go on a low carb diet too. The side effects of this are: slim down, lose belly fat, feel more energetic, clearer skin and for diabetics a great improvement in blood sugar control.

 

Type Ones get near normal blood sugars on very low carb diets

Adapted from Management of Type One Diabetes with a very low carbohydrate diet by Belinda S Lennerz et al. Pediatrics Volume 1 number 6, June 2018.

Exceptional glycaemic control of type one diabetes mellitus with low rates of adverse events was reported by a community of children and adults who consumed a very low carb diet. This study was done by recruiting patients via an online survey. Their medical records were then used to confirm their results.

Of the 316 respondents, just over a third were parents of diabetic children. The mean age of diagnosis was 16 years and the duration of diabetes was a mean of 11 years. The mean time of following a VLCD was just over 2 years. The mean daily carb intake was 36g. The mean HbA1c was 5.67%. Only 2% of the respondents reported diabetic hospitalisations. 4 admissions were for DKA and 2 for hypoglycaemia.

In the USA the average HbA1C for type one diabetics is 8.2%.  The ADA target to reduce complications is set at under 7.5% for children and under 7% for adults. Only 20% of children and 30% of adults reach these targets.

A major difficulty is achieving post meal blood sugar targets. The carbohydrate load has the greatest influence on this. A VLCD is regarded as between 20 and 50g of carb at each meal or between 5-10% of total meal calories from carbohydrate. Some practitioners worry about advising diabetics about VLCD because of concerns about DKA, hypos, lipid problems, nutrient deficiency, growth failure and sustainability.

The study was approved by the Boston Children’s Hospital.  The recruitment group were people who were following Dr Bernstein’s Diabetes Solution. They came from the USA, Canada, Europe and Australia. They were all confirmed as having type one diabetes from their medical records.

Symptomatic hypoglycaemia was reported by 69% of the participants but severe hypos were rare. Most people had 1-5 episodes of mild hypos a month.

Most people had the characteristic low triglycerides, high HDL, high total cholesterol and high LDL pattern.  The average trig/hdl ratio was 1:1 indicating excellent cardiometabolic health. BMI was also lower than population averages for age. The DCCT covered 1441 adolescents and young adults and the factors that showed the greatest effect on cardiovascular risk were: HbA1c, then trigs, then LDLc.

The commonly reported growth deceleration noted with type one diabetes is generally thought to be due to poor blood sugar control.  In this study group however the children’s height were modestly above averages for age and gender.

A few participants deliberately did not disclose their low carb diets to their health care providers due to concerns about being criticised, pressured to change behaviour or accused of child abuse. Although 49% of participants thought that their health care provider approved of VLCDs, a robust 82% of the health care providers said they did.

We don’t know how generalisable the findings in this study could be. This group may be particularly well motivated and may be pursuing other health related behaviours such as physical activity. None the less,  the level of glycaemic control and low rates of DKA and severe hypos revealed by this study break new ground in research into diabetes management for type one diabetes.

 

 

 

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.