BMJ: Diabetic ketoacidosis is the biggest threat to type ones

 

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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

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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.
References:
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. http://www.fda.gov/ NewsEvents/Newsroom/PressAnnouncements/ ucm226975.htm Accessed March 24, 2017.  
FDA website. FDA panel votes narrowly to modify Avandia restrictions, June 6, 2013. http://www.reuters.com/
American College of Cardiology Website. CVD-REAL Study: Lower Rates of Hospitalization For HF in New Users of SGLT-2 Inhibitors, March 19, 2017. http://www.acc.org/latest-in-cardiology/articles/2017/03/13/17/58/sun-2pm-cvd-real-study-lower-rates-of-hospitalization-for-hf-in-new-users-of-sglt-2-inhibitors-vs-other-glucose-lowering-drugs-acc-2017#sthash.4dPCw3Zu.dpuf.

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

BMJ: Continuous glucose monitoring in pregnant women halves adverse birth effects

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Adapted from the BMJ article by Susan Mayor 23 Sept 17

A study has shown beneficial effects in type one pregnant patients. One in two babies born to such women have complications such as prematurity, stillbirth, congenital anomalies, and being too big. These are due to high blood sugar levels in the womb and there has been no reduction in these in the last 40 years.
Denise Feig, the author of the study, based at the University of Toronto, says, “Keeping blood sugar levels in the normal range during pregnancy for women with type one diabetes is crucial to reduce risks for the mother and child. As insulin sensitivity varies through the pregnancy adjusting insulin accurately is complex. Since our results have come through we think that continuous blood sugar monitoring should be available to all type one women.”
In the international study 325 women who were planning a pregnancy or pregnant took part. Two thirds were randomised to get the monitors and the rest had standard treatment. Large newborns were halved and so was neonatal intensive care admissions and hypoglycaemia. Women had a small but significant reduction in HbA1c. They had more time in the normal blood sugar range and hypoglycaemia was not increased.
The extra cost of the monitors could be offset to some extent by the reduced cost of medical care after the birth.

Lifestyle changes add up to a longer life

Adapted from an article by James Hamilton in the Herald 14th October 2017

If you want to improve your life expectancy you can do the sums and see just how much extra time you can have according to Scottish researcher Dr Peter Joshi.
Obesity levels are now three times more than in the 1980s. At that time six percent of men and eight percent of women were affected. This has spurred an Edinburgh team to look into the genes affecting longevity in families and the lifestyle factors that affect life span in individuals. The old nature/ nurture debate again. Overall 600,000 people were tested and their family histories explored.
When it comes to longevity the balance comes down much more to lifestyle than your genes.
Educate yourself: add a year to every year educating yourself beyond school. That’s really like going to university for free. You get the time back at the other end!

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Get slim: add a year for every surplus stone you lose. Diabetes complications is the main factor in causing the reduced life expectancy.
Stop smoking or don’t start: add seven years to your life if you don’t smoke those 20 cigarettes a day.
Praise the parents: some people have a gene that improves their immune function giving an extra six months life expectancy.
Blame the parents: Addiction to drugs and alcohol are somewhat genetically based.
Blame the parents (again): A gene that affects cholesterol reduces lifespan by about eight months.

The full report is the journal Nature Communications.

Which medicines work most effectively for diabetic neuropathy?

What treatments can improve pain and quality of life?

This comprehensive report was first published in April 2017 by Diabetes in Control and discusses what old and new medicines work for diabetic neuropathy and importantly which ones don’t.

Pharmaceutical Products and Drugs
Diabetic neuropathy is a nerve disorder that the National Institute of Diabetes and Digestive and Kidney disease estimates affects about 60 to 70% of diabetic patients in some form, with the highest rates of neuropathy occurring in patients who have had diabetes for over 25 years.

Although diabetic neuropathy can affect almost any organ in the body, the most common type of diabetic neuropathy is peripheral neuropathy. Peripheral neuropathy, which is often worse at night, results in tingling, numbness, and pain occurring in the hands, arms, fingers, legs, feet, and toes.

The best way to prevent diabetic neuropathy is keeping glucose under control and maintaining a healthy weight, but for those who experience this painful condition, finding the best relief can often be difficult and confusing.
Building upon a previously published study from 2014, a new systemic review was conducted to “systemically assess the effect of pharmacological treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life” plus a search of PubMed and Cochrane Database of systemic reviews (reviews from 2011 – March 2016).
A total of 106 randomized controlled trials were used in the final systemic review, including trials analyzed by the previously published study. Only two medications, duloxetine and venlafaxine, had a moderate strength of evidence (SOE) compared to the low strength of evidence found with the remaining 12 study medications. As a class, serotonin-norepinephrine reuptake inhibitors (SNRIs) was found to be an effective treatment for diabetic neuropathy with the most commonly reported adverse effects of dizziness, nausea, and somnolence. Venlafaxine and tricyclic antidepressants were also determine to be effective at relieving pain compared to placebo using the previous analysis’ data.

Pregabalin was determined to be effective at reducing pain compared to placebo but found to have a low SOE due to the inclusion of four unpublished studies causing potential bias. Pregabalin, as well as the other anticonvulsants included, had adverse effects of dizziness, nausea, and somnolence.

Oxcarbazepine was also found to be an effective neuropathy pain reliever compared to placebo.
Atypical opioids have a dual mechanism of action, norepinephrine reuptake inhibition and mu antagonism, which aids in a class wide effective pain relief compared to placebo, and more specifically tramadol and tapentadol were found to be effective vs placebo. The most common adverse effects reported for opioids were constipation, somnolence, and nausea.

The last medication that was determined to be an effective pain reliever of diabetic neuropathy compared to placebo was botulinum toxin

Gabapentin, using five randomized controlled trials, was determined at two different doses to be ineffective at treating pain when compared to placebo. Other agents that were determined to be ineffective treatments for diabetic neuropathy were typical opioids (oxycodone), topical capsaicin 0.075%, dextromethorphan, and mexiletine.

Practice Pearls:
Pregabalin, oxcarbazepine, and tapentadol have shown to be effective vs placebo at relieving pain due to diabetic neuropathy and are also FDA approved for this indication.
Serotonin-norepinephrine reuptake inhibitors may be a good choice for relief of diabetic neuropathy pain and have the additional benefit of relieving depression that is commonly associated with diabetic neuropathy
Additional studies are needed to assess long-term pain relief effectiveness.

References:
“Nerve Damage (Diabetic Neuropathies) | NIDDK.” National Institutes of Health. U.S. Department of Health and Human Services. Web 05 April 2017
Julie M. Waldfogel, Suzanne Amato Nesbit, Sydney M. Dy, Ritu Sharma, Allen Zhang, Lisa M. Wilson, Wendy L. Bennett, Hsin-Chieh Yeh, Yohalakshmi Chelladurai, Dorianne Feldman, Karen A. Robinson. “Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life”. Neurology, 2017; 10.1212/WNL.0000000000003882 DOI: 10.1212/WNL.0000000000003882
 
Mark T. Lawrence, RPh, PharmD Candidate, University of Colorado-Denver, School of Pharmacy NTPD

 

 

 

BMJ: Continuity and individualised care matter more to patients than guidelines

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By Martin Rowland and Charlotte Paddison
Adapted from article in BMJ 18 May 2013
As the population rises more people are living with multiple medical conditions. These can be diabetes, rheumatoid arthritis, macular degeneration, depression, cancer, coronary heart disease and dementia among others.

These cause complex health, emotional and social problems which make their management difficult, especially in socioeconomically deprived areas. A new model of care is needed to manage patients optimally in these circumstances.
Although this seems obvious, care seems to be moving in the wrong direction for these patients.
Evidence based guidelines are really geared to patients with single conditions. They don’t cater to someone who has multiple conditions. Over treatment, and overly complex surveillance and assessment routines result. Older, less well educated and less affluent patients cope particularly poorly with these regimes. Guidelines also fail to recognise that patients get more frail as they age. The burdens of illness and treatment are different for a 100 year old compared to a 50 year old.
An individualised regime for each patient needs to be developed to focus on what matters most to each one.
Unfortunately doctors often feel that they can’t deviate from a guideline for fear of criticism and litigation. Perhaps guidelines should only be applied when they are clearly being used in the patient’s best interests, instead of the doctor’s? Exception reporting is a mechanism that allows doctors to deviate from guidelines and maybe should be used more.
Medical training does not as yet focus on this sort of individualised care. Medicine of old age comes the closest.
Listening to patients is the key thing that can help a doctor understand what their needs and goals are. The most appropriate care can then be built around that. The biggest barrier to this seems to be the over emphasis on single conditions.  This prevents rather than enhances goal oriented care.
Longer consultations are needed to help guide patients talk about their needs and think through complex decisions.
Satisfaction and outcomes are improved if this can be achieved. Despite this patients still often complain that they never see the same doctor twice both in hospital and primary care. It is also particularly difficult to provide a good quality of care when a doctor does not  know the patient and does not see the patient for follow up.
Young adults say they want to see the same doctor 52% of the time, but this increases to over 80% in those aged over 75.  More than a quarter of patients however say they struggle to see the doctor of their choice. This seems to be getting worse over time rather than better. Perhaps this is due to nurses taking over a lot of the care regarding chronic illness. Doctors are also increasingly working part time and may be involved in other tasks other than direct patient care. Shift systems in hospitals limit continuity a great deal.
In primary care, advanced access schemes give faster access but at the expense of continuity of care.
Older patients are particularly keen on waiting a few days longer to see the GP of their choice. Booking systems need to allow for both access and continuity.
This can be improved by receptionists attempting to book patients with their “own” doctor rather than simply the first available. Two or three doctors can share lists and try to see each other’s patients if one is not available.  E-mail booking of doctors directly can help. E-mail consultations can help.  Time for these must be built into the working day. The number of doctors who deal with  particularly complex needs may need to be restricted. Monitoring continuity of care can help. What gets monitored tends to get done more often after all.
As guidelines need to become less important for patients with multi-morbidity, a doctor’s clinical judgement becomes more critical.  There can be squads of other health care professionals involved in a patient’s care and deciding what ones are necessary and what ones are not is a useful task.  As the need for the traditional UK General Practitioner is increasing, sadly, their availability and time commitments to patient care seem to be decreasing.

BMJ: The PURE Study debunks the sat fat/heart disease hypothesis

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The PURE study: Eating fat is associated with lower cardiovascular disease

From BMJ 9 Sept 17
PURE is a five continent observational study in relation to cardiovascular disease in mortality in almost 150 thousand people. It found that high carbohydrate intake was associated with a higher risk of total mortality whereas total fat and individual types of fat were related to a lower total mortality.
Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, and the more saturated fat people ate the less strokes they had.
Like all observational studies correlation does not necessarily imply causation. The main message however is a series of negatives. There does not seem to be a connection between carbohydrate intake and cardiovascular disease, the association is with all- cause mortality. Perhaps high carbohydrate diets are simply a marker for poverty?
In contrast eating more fat, including saturated fat was associated with lower cardiovascular disease, meaning that we can abandon the saturated fat-cardiovascular disease hypothesis with some certainty.
So, what does “healthy food” look like?
A higher intake of fruit, vegetables and legumes was associated with a lower risk of non-cardiovascular and total mortality at three to four servings a day.
Great, says the author of this piece, Richard Lehman. His dream meal is cannelli beans and tuna salad with lots of olive oil, rib eye steak in butter, a salad, fruit, cheese and strawberries and cream.