Eatwell plate advice doesn’t reduce cardiovascular disease



Adapted from  BMJ 27 Jan 2018 from a study reported in PLOS Med

The UK Food Standards Agency uses a scoring system of their own devising to determine whether a food is “healthy” or not.  Fruit, vegetables, fibre and protein get top marks and saturated fat, sugar and salt get a fail.

When 25 thousand participants in the European Prospective Investigation of Cancer study completed a seven day food diary at the start of the study, and their food choices were marked on perceived health benefits, there was no difference in the incidence of cardiovascular disease over the next 16 years.

Time to lay the Eatwell Plate advice in the bin?


BMJ: Adults are just as likely as children to get type one diabetes

Over 40% of new type one diabetics are over the age of 30 at the time of diagnosis.

Richard Oram from Exeter University said, “The assumption among many doctors is that adults presenting with the symptoms and signs of diabetes will have type two, but this misconception can lead to misdiagnosis which can have serious consequences”.

Clues to the person having type one can be failure to control blood sugar with tablets and the person being of a slim build.

The study was done by looking at the genetic biomarkers of over 13 thousand patients who had developed the disease before the age of 60.

BMJ 9 December 2017

A sleep expert tells us how to improve jet lag


Adapted from an article by Richard A. Friedman’s article, “Yes, your sleep schedule is making you sick” published in the New York Times March 10 2017

Jet lag makes everyone miserable and here is what you can do about it.


We have a circadian rhythm that is 25 hours long and it is almost in synchronicity with the 24 hour day. Jet lag messes this up big time. Everyone who has experienced it knows that jet lag makes you feel tired, out of sorts, renders concentration difficult and makes you moody.

If you are flying from New York to Rome for instance and arrive early in the morning Rome time,  the best way to reduce jet lag is to keep on eye shades in the plane and dark glasses on the ground till your New York 7am has been reached. This will be about lunch time in Rome.

Melatonin is also an important factor. As it starts getting dark your pineal gland starts to produce melatonin around 2 or 3 hours before your sleep time. If you take a melatonin supplement earlier than this is can become possible for you to fall asleep earlier than you otherwise would.

Surprisingly, if you take melatonin in the early morning, it can fool your brain into thinking it slept longer, at least to some extent, and does not make you more tired during the day.

So this is the fix for jet lag. Travel east and you’ll need morning light and evening melatonin. Go west and you’ll need evening light and morning melatonin. 

If you are a night owl, who can’t sleep at midnight because it’s too early for you, take a small dose of melatonin a few hours before the desired bedtime. They can also try exposure to bright lights at progressively earlier times in the morning, which also should make it easier to fall asleep earlier. You

should also avoid the blue light that smartphones and computers emit in the evenings. You can wear special glasses that block blue light if this is a problem.

Richard A. Friedman is a professor of clinical psychiatry and director of psychopharmacology clinic at the Weill Cornell Medical College.

Sulphonylureas increase cardiac deaths but are still recommended for use after Metformin in type two diabetics in Scotland


heart attackFrom Diabetes in Control May 2017. Cheapest treatment associated with increased risks of cardiovascular events and death.
After the cardiovascular issues with rosiglitazone, cardiovascular safety trials had to be conducted for all new anti-hyperglycemic agents. However, approval for older medications was based simply on evidence of a reduction in glucose parameters; cardiovascular safety was not a concern back then. But, data from the UKPDS trial shows that metformin reduces CV events, so, it was never in doubt. The ORIGIN trial has shown no increased harm with early initiation of insulin. However, some questions linger regarding the cardiovascular safety profile of sulfonylureas.

Data exist on the weight gain and risk of hypoglycemia associated with sulfonylureas, but the associated cardiovascular events have not been well-quantified. Sulfonylureas are used commonly across the world and are very effective in lowering HbA1C, but often the effect wears off, as shown in the ADOPT study.
Recent randomized trials have compared the newer antidiabetic agents to treatments involving sulfonylureas, drugs associated with increased cardiovascular risks and mortality in some observational studies with conflicting results. They reviewed the methodology of these observational studies by searching MEDLINE from inception to December 2015 for all studies of the association between sulfonylureas and cardiovascular events or mortality.
Sulfonylureas were associated with an increased risk of cardiovascular events and mortality in five of these studies (relative risks 1.16–1.55). Overall, the 19 studies resulted in 36 relative risks as some studies assessed multiple outcomes or comparators. Of the 36 analyses, metformin was the comparator in 27 (75%) and death was the outcome in 24 (67%). The relative risk was higher by 13% when the comparator was metformin, by 20% when death was the outcome, and by 7% when the studies had design-related biases.
The lowest predicted relative risk was for studies with no major bias, comparator other than metformin, and cardiovascular outcome (1.06 [95% CI 0.92–1.23]), whereas the highest was for studies with bias, metformin comparator, and mortality outcome.
In summary, sulfonylureas were associated with an increased risk of cardiovascular events and mortality in the majority of studies with no major design-related biases. Among studies with important biases, the association varied significantly with respect to the comparator, the outcome, and the type of bias. With the introduction of new antidiabetic drugs, the use of appropriate design and analytical tools will provide their more accurate cardiovascular safety assessment in the real-world setting.
So this study reviewed over 19 trials looking at sulfonylureas, specifically studying cardiovascular events and mortality. The problem with some studies is that they don’t take into account the duration of diabetes et cetera; so, they may end up comparing sicker patients with those who aren’t as sick. This group looked at potential biases such as exposure misclassification, time-lag bias, and selection bias, and, of the 19 studies, 6 did not have any of these biases. Of those 6 studies, 5 showed that sulfonylureas were associated with an increased risk of cardiovascular events and mortality, with relative risks ranging from 1.16 to 1.55.
It is not possible to tease out what the cause of the increase in events is based on this type of analysis. Is it hypoglycemia? Is it a direct drug effect? However, regardless of the mechanism, the consistent finding of increased cardiovascular risk may have an impact on selection of agents for our patients. Newer agents have been shown not to increase events, and recently some have even shown reduction in events. So, perhaps our algorithm of selecting medications for our patients may have to change to focus on the cardiovascular effects first and then the glycemic benefits because, in the end, our goal is preventing cardiovascular events from happening in our patients with diabetes.
Practice Pearls:
Sulfonylureas are associated with increased risks of cardiovascular events and death.
Sulfonylureas also associated with hypoglycemia events.
Data exist on the weight gain and risk of hypoglycemia associated with sulfonylureas.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
The ORIGIN Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med. 2012;367(4):319-328.
Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies. Diabetes Care 2017 May; 40(5): 706-714.
Sulfonylureas and the Risks of Cardiovascular Events and Death: A Methodological Meta-Regression Analysis of the Observational Studies. Diabetes Care. 2017 May;40(5):706-714. doi: 10.2337/dc16-1943.

My comments: The health issues of sulphonylureas have been known about for at least a decade or two, but because they are cheap and effective in blood sugar lowering they continue to be promoted as the next drug to use after Metformin for type twos.  The Scottish Government have produced a paper which I reviewed a few weeks ago. It is their “new” strategy to deal with diabetes. Mainly, they wanted to limit the expenditure on the newer gliptans eg Linagliptan, Sitagliptan, the flozins eg Empagliflozin  and the injectibles such as Victoza and Byetta. These are a lot more expensive than metformin and gliclazide. They propose that lifestyle measures are first line. This means promoting exercise and “Healthy Eating” first. Yes, this means  a high carb, low fat diet, with lots of starch, limited sugar, salt, and whatever fat you eat should be the good monounsaturated type and also the inflammatory vegetable oil/margarines.  As we know this actually increases obesity for most people and worsens diabetes control. You then get put on metformin and then before you get put on drugs that actually lower your weight, blood sugar and blood pressure and cardiovascular risk, you get put on a sulphonylurea which wears out your pancreas, makes you fatter, makes you more prone to hypos and increases your cardiovascular risk. In my view sulphonylureas should be AFTER the newer drugs and given as a choice if someone does not want to use insulin.  I put in my comments regarding diet to the editorial board but they have done nothing saying that the remit of the paper was really about drugs, not diet. Yet, without the right diet, diabetes management is doomed to failure.

BMJ: Regular, physical exercise is the miracle cure to ageing

Tai chi.jpg

Adapted from Scarlett McNally’s article in the BMJ 21 Oct 17

The NHS and social care are inextricably intertwined. The rising number of older people is frequently blamed. The rising social care costs in this age group can be modified however. NICE in 2015 said, “disability, dementia and frailty can be prevented or delayed”.
The need for relatives or paid carers arises when someone can no longer perform the activities of daily living such as washing, dressing and feeding themselves. For some people the ability to get to the toilet in time is the critical thing between having carers come to their own home twice a day and being admitted to a full time care facility.
The cost of care rises five times for those admitted to residential facilities. An average residential placement costs £32,600 a year and may be needed for months, years or decades.
A cultural change is needed so that people of all ages aspire to physical fitness as a way of maintaining independence into old age. There just doesn’t seem to be the local or national infrastructure to support this however.
Ageing is a normal, if unwelcome, biological process that leads to a decline in vision, hearing, skin elasticity, immune function and resilience, which is the ability to bounce back.
The decline in fitness with age starts around the age of 30 and accelerates after the age of 45. Things move downhill even faster if someone has a sedentary job that involves car driving and computer work. Diabetes, dementia, heart disease and some cancers become more common.
Some may think that fitness in old age is down to genes and luck but social strata differences exist with good nutrition and exercise as major factors in enhancing health and fitness into old age.
Apart from getting older, environment and lifestyle affect disease onset. At the age of 40, some forty percent of people have at least one long term condition and the rate goes up by ten percent each decade. As environmental and behavioural factors stack up over time, more people develop an increasing number of diagnoses. Yet, small habits such as cycling to work, can mitigate the effects of a sedentary job.
As time goes on, a person’s independence can be compromised by well -meaning carers and relatives doing more for their charges rather than letting them do things for themselves.
Genetics are thought to play only 20% of the part in the development of modern diseases. Lack of fitness has more of a part to play than disease and multiple morbidity.
Pain can lead people to limit their activity because they think it could make their illness worse, but strength, stamina, suppleness and balance training are usually needed more rather than less as you get older and accumulate illnesses.
These factors improve cognitive ability in midlife through to a person’s 80s. They can reduce the onset of dementia. Increasing independence results.
The Academy of Medical Royal Colleges go as far as describing exercise as “the miracle cure”. Improving the time to stand from sitting down, walking, and resistance training exercise all produce a dose response effect with the most frail benefitting the most. Any exercise or activity such as gardening that gets you slightly breathless and is done in ten minute bursts or longer counts as the 150 minutes minimum as recommended in the UK.
Stopping smoking and limiting alcohol are also worthwhile interventions. Gyms, walking groups, gardening, cooking clubs and volunteering have all been shown to improve the health and well- being of people of all ages with long term conditions.
When people are admitted to hospital they often experience a rapid decline in function. Patients are not allowed to move about or go to the toilet themselves in case they fall. The numbers of these are considered adverse incidents and are strongly discouraged. Thus the ambulant end up chair or bedbound. Most inpatients spend 80% of the time in bed and more than 60% come out with reduced mobility.
All patients should be encouraged to start an activity programme and gradually increase the frequency, intensity, and time that they do it.
The outdoor environment can be improved by even pavements, open spaces, tables and seating in public areas, safe cycle lanes and restriction in car use.
Money may need to be shifted from passive care and polypharmacy to activity and rehabilitation services.
People need to concentrate on being active every day. A quarter of women and a fifth of men do no activity whatsoever in a week never mind the minimum recommended 150 minutes a week.
In the UK the total social care bill is over £ 100 billion which is virtually the same as spent in the NHS.
The cost of care doubles between the ages of 65 and 75 and triples between 65 and 85. If everyone was just a bit fitter, the savings would add up.
Individuals need to see it as their responsibility to stay fit or improve their fitness. There needs to be more national coordination regarding the environment, transport and our working schedules so that we can all stay that bit functionally younger into old age. We could be making the difference between staying at home or depending on social and residential care.

BMJ: Diabetic ketoacidosis is the biggest threat to type ones



Adapted from BMJ Minerva 23 Sept 17 and BMJ Learning Module Clinical Pointers in Diabetic Emergencies Oct 17

Type ones under the age of 30 have a mortality rate three times that of their non- diabetic friends.
This rather shocking statistic was discovered by Welsh paediatricians who have been tracking their children with diabetes since 1995. Furthermore the death rate has not gone down over all this time despite improvements in monitoring and therapy. Ketoacidosis is the leading cause of death. Although microvascular and to a lesser extent macrovascular complications can occur, they do not affect mortality rates in this age group.
Out of a hundred or so type one adult diabetics approximately 3 or 4 will develop diabetic ketoacidosis each year. Currently 3-5% will die. Not all deaths will occur in hospital because not everyone is identified as having ketoacidosis prior to death. Recognition by relatives, friends, police and medical professionals would be an important factor to improve transfer to hospital.
Ketoacidosis is also be the presenting sign of diabetes in 6% of the total number of ketoacidosis patients. It may have been precipitated by a viral infection and can be confused by a variety of illnesses such as gastroenteritis, flu and alcohol intoxication and withdrawal.
Assuming a person can be recognised as ill and needing hospital assessment, recognition of DKA is improved by always checking a blood glucose in an acutely ill person in the A and E department.
If levels of glucose are high, and the characteristic symptoms are present eg dehydrated looking, tired, nausea, vomiting, abdominal discomfort and breathing rapidly, then the diagnosis can be further explored by checking the blood electrolytes.
The immediate treatment is re-hydration with a litre of normal saline and the administration of intravenous or subcutaneous insulin usually 0.1 u of insulin per kilogram body weight. As the potassium level can be affected, particularly a tendency to go too low after treatment has started to work, this needs monitored every hour or two. The problem is that irregularities of the heart beat can occur if the potassium level is not adjusted correctly.
It can be seen that management of DKA in the established case is tricky and time consuming. Therefore it is wise to seek medical advice while you or the one you are concerned about, is still relatively well and can for instance still tolerate oral fluids and give a coherent history.
Early recognition and treatment is the key to a good outcome in DKA.



Is there a new “magic bullet” for type two diabetes?

SLGT-2 Inhibitors Gaining Traction as a Class in Preventing Cardiovascular Consequences
April 15th, 2017 Diabetes in Control

Chest pain

Are we experiencing the next “magic bullet” in type 2 diabetes?
Cardiovascular mortality has long been established as the primary cause of death in patients with type 2 diabetes (T2D).

Cardiovascular effects of oral antidiabetic medications came to the forefront in 2007 with the landmark article in the New England Journal of Medicine, written by Dr. Steven Nissen.  In this publication, Dr. Nissen showed a strong association between use of rosiglitazone and increased incidence of cardiovascular complications and deaths.  In the years following, the FDA placed strong restrictions on the prescribing of rosiglitazone, sharply decreasing the market for Avandia.  Subsequent studies showed no correlation between the use of thiazolidinediones and adverse cardiovascular events, causing the FDA to reverse its stance on Avandia.  This class of agents was of particular interest because it was among the first of the oral agents that did not display the hypoglycemia seen with the sulfonylureas.  More importantly, this event caused the FDA to re-examine its approval process, and enforce that cardiovascular studies be done in all new drug presentation trials.
Until recently, there were no groundbreaking studies that suggested any class of oral hypoglycemic could significantly reduce CV risks associated with diabetes.  In January 2016, the European Heart Journal reported the results of EMPA-REG OUTCOME, a randomized placebo-controlled trial with over 7,000 subjects looked at empagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, which works by reducing glucose reabsorption at the renal tubule, thereby increasing glucose excretion. While a known effect is the reduction of hyperglycemia in T2D, there is also an increase in diuresis, weight loss, and reduction in blood pressure without associated tachycardia.  EMPA-REG OUTCOME showed that patients who received empagliflozin demonstrated significant declines in heart failure hospitalizations and cardiovascular deaths, without a rise in adverse effects, regardless of baseline heart failure state.  Based on these findings, Eli Lilly, the manufacturer of the Jardiance® brand of empagliflozin, saw a significant increase in their stock value, as their product was given preference over other available SGLT-2 inhibitors.
Earlier this month, the American College of Cardiology held the ACC.17, where the results of the CVD-REAL study were released .  CVD-REAL was a meta-analysis looking at over 364,000 patients from 6 different countries (United States, United Kingdom, Germany, Norway, Sweden, and Denmark), with T2D. Subjects were receiving either a SGLT-2 inhibitor or another glucose-lowering drug (oGLD) with even distribution across both arms in all six countries.  Of the patients studied, 3% had baseline heart failure, 13% had baseline cardiovascular disease, and 27% had baseline microvascular disease. The primary endpoint was hospitalization for heart failure, which showed a reduction strongly favoring the SGLT-2 inhibitors (hazard ratio [HR] 0.61; p < 0.001).  The secondary endpoints of all-cause mortality also favored the SGLT-2 inhibitors (HR, 0.49; p<0.001), as did heart failure hospitalizations and all-cause deaths in total (HR, 0.54; p<0.001).
Of important significance is the lack of population heterogeneity across the different countries, which suggests that the positive effects seen can be associated with the entire class of SGLT-2 inhibitors (which include dapagliflozin [Farxiga®] and canagliflozin [Invokana®]), and not just empagliflozin.

The investigators in CVD-REAL have come forth and stated that their findings do indeed line up with those from EMPA-REG OUTCOME.  The significance of this is there now exists an open market for SGLT-2 inhibitors, and that these once very costly medications may experience considerable cost reduction across the class, giving patients more affordable options.
As David Kliff, publisher of Diabetic Investor, recently stated, Dr. Nissen has received plenty of negative feedback from the community for his claims against rosiglitazone.  However, because of his initial findings and subsequent correction, the FDA has re-established its approach to the approval process for treatments of type 2 diabetes to include necessary studies of cardiovascular outcomes, much to the benefit of our patients, and that’s certainly a good thing.
Practice Pearls:
The significance of the fall and rise of rosiglitazone has had a tremendous impact on how type 2 diabetes treatments are evaluated.
EMPA-REG OUTCOME has demonstrated considerable positive effects on cardiovascular outcomes in T2D patients receiving empagliflozin, an SGLT-2 inhibitor.
The recent CVD-REAL study has strengthened the notion that all SGLT-2 inhibitors significantly reduce hospitalizations due to heart failure, as well as displaying a decline in cardiovascular deaths in the T2D population.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-71.
FDA website. FDA significantly restricts access to the diabetes drug Avandia. Press release, September 23, 2010. NewsEvents/Newsroom/PressAnnouncements/ ucm226975.htm Accessed March 24, 2017.  
FDA website. FDA panel votes narrowly to modify Avandia restrictions, June 6, 2013.
American College of Cardiology Website. CVD-REAL Study: Lower Rates of Hospitalization For HF in New Users of SGLT-2 Inhibitors, March 19, 2017.

Mark T. Lawrence, RPh,PharmD Candidate, University of Colorado-Denver, School of Pharmacy NTPD