RCGP: Adapting diabetes medication for a low carb diet

Adapted from RCGP July 19 Adapting diabetes medication for low carbohydrate management of type two diabetes by C Murdoch et al.

This topic has been well covered in our book but has been reviewed in this article. 

Type two diabetes can be reversed by a low carb diet. Changes in medication need to keep pace with lowered blood sugar levels that result. A low carb diet can range from under 30g to 130g of carb a day.  Blood pressure medication also often needs to be reduced or stopped as lower blood pressure results from a reduction in insulin resistance.

Sulphonylureas, meglitinides and insulin all reduce blood sugar and if not reduced appropriately can result in hypoglycaemia.  It is reasonable to cut the dose of these by 50% when a low carb diet is started. Once the diet is stabilised the levels can be increased if this is necessary. If a patient has very high blood sugars eg HbA1C of 10% or more then a reduction of 30% can be considered initially. As more weight is lost or more carb is cut from the diet, further reductions can then be made. Some patients will be able to stop insulin and oral hypoglycaemics entirely as progress is made.

Some patients have latent autoimmune diabetes and although they can reduce their doses, their insulin must be maintained at some level. These patients can often be identified because they developed type two diabetes when they were thin.

Some patients who may need to stay on some insulin have had type two diabetes for many years and have ceased to make any pancreatic insulin. (Secondary beta cell failure).  My comment:  Users of sulphonylureas eg Gliclazide over five years are prone to this problem.

It is important to provide plenty of blood glucose testing strips to patients over the transition so they can let you know if they are experiencing hypos.

GPs can refer to endocrinologists for advice over patients who are giving concern.

Flozins also known as SGLT2 inhibitors increase the risk of ketoacidosis in patients who have significant pancreatic insufficiency.  The ketoacidosis is hard to recognise because the blood sugar is often normal or only very slightly raised. The person just feels ill and may vomit. My comment: in my experience this effect is difficult to predict but usually occurs in the first week or two of treatment. Low carb diets of below 30g-50g of carb a day also produce dietary ketones so can muddy the waters even more. Therefore is someone is on a flozin and starts a low carb diet it is best to suspend the flozin. They may not require it after a while on a low carb diet in any event.

Commonly used drugs that do not give any risk of hypoglycaemia include Metformin, Glutides, Glitazones, Gliptins and Acarbose.

About a quarter of people on metformin get diarrhea and need to go on the long acting version or stop it altogether.  Because acarbose is meant to help block starch and this is eliminated on a low carb diet, this drug can be stopped.  Glutides, Glitazones, Gliptins can be stopped when blood sugars are at a satisfactory level.  My comment: The target blood sugar will vary from patient to patient. You can see more about this in my PHC talk on you tube or in our book.

 

 

 

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.