BMJ: Varicoceles can be a marker for metabolic syndrome and type two diabetes

Nancy Wang from Stanford University is a urologist and says, “Varicoceles which are varicose veins of the spermatic cords, are associated with low testosterone. This in turn makes men more likely to develop metabolic risks and heart disease. No one has connected the dots before now”.

These men have higher risks of heart disease, diabetes, and hyperlipidaemia.

My comment: Varicoceles feel just  like a bag of worms in the scrotum. Up to one in 5 men will develop these over their lifetime. 

BMJ: Bariatric surgery best done before a BMI of 50

More than a third of patients who had bariatric surgery got back to a BMI of 30 or less after one year. Some patients respond better than others, and some operations are more effective than others.

Having a BMI of less than 40 made it more likely for the person to reach their goal weight. Obviously, they had less to lose. Only one out of ten patients who had a BMI of 50 or over got down to a BMI of 30, which corresponds to the limit between being considered overweight and being considered obese.

Sleeve gastrectomy, gastric bypass or duodenal switch operations were the most effective. Adjustable gastric bands were less effective.

BMJ  9 Dec 2017 from JAMA Surg 2017

Canagliflozin reduces onset of cardiac failure compared to other anti-diabetic drugs

 

Adapted from BMJ 10 Feb 18

A large population based cohort study showed that patients who started canagliflozin had a markedly reduced risk of being admitted to hospital with cardiac failure compared to three other types of anti-diabetes drugs.  There was no increase in heart attacks or stroke.

The study was based in the USA and the comparative drugs were DPP-4 inhibitors such as Victoza and Byetta, Gliptans such as Linagliptan and Sitagliptan, and sulphonylureas such as Gliclazide.   There was a 30-49% decrease in hospitalisations for cardiac failure.

None of the patients had a history of cardiac failure or cardiovascular disease at the start of the study and the patients were compared to others with the same HbA1C to ensure a fair comparison.

The reduction in cardiac failure could be a class effect of the Flozin drugs but further studies would be needed to find out. No other Flozins were used in the study as comparators.

Between 17,354 and 20,539 pairs of patients were matched for each comparison making this a very large study indeed.

Eatwell plate advice doesn’t reduce cardiovascular disease

UPDATED_Eatwell_guide_2016_FINAL_MAR23-01

 

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

melatonin.jpg

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.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)07019-6/fulltext
The ORIGIN Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia. N Engl J Med. 2012;367(4):319-328. http://www.nejm.org/doi/full/10.1056/NEJMoa1203858
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. http://care.diabetesjournals.org/content/40/5/706
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. https://www.ncbi.nlm.nih.gov/pubmed/28428321

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.