Lower verbal intelligence is associated with diabetic complications and slower walking speed in people with Type 2 diabetes: the Maastricht Study

This study was designed to see if there was a correlation between verbal intelligence, Type 2 diabetes, and walking speed.  They had each participant take the Groningen Intelligence Test which tested their vocabulary and then were assigned a score.  This score was then compared to indicators if Type 2 diabetes like A1C and glucose levels.  This vocabulary score was also compared to other diabetic health complications like chronic kidney disease, cardiovascular disease, and neuropathic pain.  Lastly, they assessed this vocabulary score with the speed at which the individual walked.  They tried to minimize confounding variables like age or gender.

In total, only 228 patients were fully assessed on all three tests.  When the verbal score was compared to the indicators of Type 2 diabetes (A1C, LDL, glucose, etc.) there was no association between the two.  The verbal score was also not associated with kidney disease.  Lower verbal scores did show an association with increased cardiovascular disease and neuropathic pain and decreased walking speed.

They noted that the lower verbal intelligence might be correlated with some diabetic functions because they aren’t as educated and have a lesser understanding of their disease state.  But I’d like to pose the question that if they don’t understand their disease state, then why isn’t there a correlation between low intelligence and out-of-range A1C, LDL, etc.  I also wonder why low intelligence was associated with slower walking.  It would be very interesting to see why exactly they chose to compare these three very different assessments and compared them to each other.  The walking speed especially seems unrelated.

 

Tang JYM, Wong GHY, Ng CKM, et al. Lower verbal intelligence is associated with diabetic complications and slower walking speed in people with Type 2 diabetes: the Maastricht Study. J Am Geriatr Soc. 10.1111/jgs.13938 (1 March 2016).

Effect of Metformin Added to Insulin on Glycemic Control Among Obese Adolescents with Type 1 Diabetes

Studies currently show that 24% of children and adolescents with Type 1 Diabetes are overweight and 15% are obese. The need for high doses of insulin may further promote weight gain. Additionally, insulin resistance has been associated with increased risk for cardiovascular risk factors. Metformin lowers glucose and was associated with low insulin doses without having an effect on A1C.

A trial was conducted using patients aged 12 to 19 diagnosed with Type 1 Diabetes for at least one year who had an insulin pump or administered at least 3 injections of insulin each day. The patients had an A1C between 7.5% and 9.9% and were in the 85th percentile for BMI. The patients were given 500 mg of metformin that was titrated over 4 weeks to reach 2000mg daily. The rest of the patients were given a placebo.

The baseline A1C was 8.8% in each both groups. At 13 weeks, the mean change in the metformin group was -0.2% and 0.1% in the placebo group. However at 26 weeks, the mean change in the metformin group was 0% and 0.3% in the placebo group. There was no significant difference for glycemic control. However, the patients in the metformin group used less insulin throughout the 26 weeks than the patients on the placebo and more patients in the metformin group maintained or lost weight.

In conclusion, metformin did not improve glycemic control in children or adolescents with Type 1 Diabetes. A few outcomes were favored but not significantly. Additionally, taking metformin increases the risk of GI adverse effects. Therefore, it is not indicated to prescribe metformin to this patient population.

This is interesting because many people do not fully understand the difference between Type 1 and Type 2 Diabetes and the medications to treat each. It is important to know what medications are indicated for each to educate children and parents. Thoughts on another oral medication that may be better suited for this patient population?

JAMA. 2015;314(21):2241-2250. 

Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study

When prescribing medications for the initiation of  a new therapy in patients with multiple chronic diseases, physicians often look to guidelines to determine their recommended treatment option.  While this is considered good practice, it is important to not look at the disease state as a singular entity when choosing a therapy for the patient to follow due to the effects that certain conditions have on one another. This study looked to analyze the association between guideline recommended drugs and death in older adults with multiple chronic disease states. To do this, 8578 adults aged 65 and older were monitored though three years of treatment. Patients involved in the study had a variety of disease states including but not limited to atrial fibrillation, chronic kidney disease, depression, diabetes,  and hyperlipidemia. Results from the study showed that over 50% of the participants received guideline recommended drugs without the consideration of other disease states. Although 15% of the patients died during the course of the study, researchers were able to determine that cardiovascular medications were associated with a decrease in mortality. Other guideline medications analyzed in the study did not show an association with reduced mortality. Overall, it was determined that choosing medication therapy for patients should only be done after fully analyzing the patients other conditions.

I believe this study is important due to the fact that guideline recommended medications are commonly dispensed in the pharmacy setting. It is thus important for us to understand how guideline drugs interact with each other to protect a patient at the point of treatment initiation. By doing this, we will be able to avoid adverse drug effects that can result due to medication interactions. I believe that this is one of the most important roles of a pharmacist because it helps promote patient well-being and increases the likelihood of medication regiment adherence. The goal of our profession is to protect patients and advise them on how to find ways to live a healthy lifestyle. The easiest way to do this is by starting at the roots of the solution.

Tinoetti M, McAvay G, Trentalange M, et al. Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study. BMJ 2015; 351: h4984

Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).

This study compared the diagnosis of diabetes and it’s relationship to depression in men.  It was a cross-sectional study of 5462 men between the age of 70-89 years old.  The rate of these men’s depression was based on the Geriatric Depression Scale and diabetes was measured with fasting blood glucose levels.  There is a “J-shaped” curve relationship between depression and age with men with diabetes.  That means that depression increases as the men get older.  Although some other factors most likely play a pivotal role.

I was interested in this article because these disease states are treated by medications that pharmacists deal with on a daily basis.  To me, this emphasizes the importance of the pharmacist role in patient’s lives.  The better the patient’s diabetes is managed, the better their related depression might be treated.  if the diabetes is under control, the depression will not occur hopefully and therefore, there will not be a need for additional medical treatment.  The less medication needed, the better the life of the patient.

Almeida OP, McCaul K, Hankey GJ, et al.  Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS). 2016; 86: 3-9

New front opens in battle against stroke – Medicinal approach cuts recurrence risk by 24 percent in stroke patients

Medical scientists discovered that an already-known drug showed to reduce the risk of stroke or heart attack by almost a quarter in patients who had previously suffered a stroke or mini-stroke!  The drug is pioglitazone, which some of you know is used to treat diabetes.  Pioglitazone works by making the body less insulin resistant, and researchers found that insulin resistance puts you at a risk for heart attack and stroke.

The typical drugs to treat stroke are blood thinners and anticoagulants.  Statins and blood pressure medications may also help in some cases.  It is unusual for a diabetes drug to be used to treat heart attack or stroke.

Blood thinners, statins, and blood pressure management medications have all been shown to significantly reduce the risk for stroke.  However, researchers wanted to explore another risk factor:  insulin resistance, also called “pre diabetes.”

Researchers showed that insulin resistance was associated with a higher risk of stroke and heart attack.  Therefore, they tested pioglitazone, a diabetes drug that can help reduce insulin resistance.

The results of the five-year, double-blind trial of pioglitazone versus a placebo, was that the team found that patients receiving the drug had 24% fewer incidents of either stroke or heart attack.  This is important because pioglitazone may now be used to prevent diabetes as well as heart attack / stroke.

My question is:  Knowing the side effects of pioglitazone, would you been willing to reccommend this medication as a preventative measure? For example, if the patient has a family history of heart attack / stroke, but has not had one?  Do you think the side effects outweigh the benefit of taking the drug as a preventative measure?

 

 

Walter N. Kernan, Catherine M. Viscoli, Karen L. Furie, Lawrence H. Young, Silvio E. Inzucchi, Mark Gorman, Peter D. Guarino, Anne M. Lovejoy, Peter N. Peduzzi, Robin Conwit, Lawrence M. Brass, Gregory G. Schwartz, Harold P. Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A. Ford, Dawn Kleindorfer, John R. O’Leary, Mark W. Parsons, Peter Ringleb, Souvik Sen, J. David Spence, David Tanne, David Wang, Toni R. Winder. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal of Medicine, 2016; 160217112012002 DOI: 10.1056/NEJMoa1506930

PPI–clopidogrel interaction a concern after stent placement

The goal of this study was to determine if there was an increased risk of adverse cardiac events in patients with DM2 who were using clopidogrel and a PPI concomitantly following drug-eluting stent placement(DES).

There were roughly 10,000 patients in this study, with the clinical endpoints of the study being whether patients with DES who were either using clopidogrel alone or in combination with a PPI experienced acute coronary syndrome and readmission to the hospital due to revascularization after 3,6, or 12 months.

The researchers found that patients using the combination of drugs had a 6 month hazard ratio of 1.63 and a 12 month hazard ratio of 1.37. Patients who had previous history of acute coronary syndrome who received the drug combination were at a higher risk of ACS following stent placement(1.55 times more likely) than those who received clopidogrel alone.

I think this study is very interesting because many patients will be using a PPI while also using an anti-platelet drug such as clopidogrel. What is also concerning is that if patients are not counseled on the increased risk of ACS when combining these two drugs, patients can elect to purchase an OTC PPI on their own, and may unknowingly subject themselves to this risk. I think that this drug interaction may be an important point for pharmacsists to counsel on when first dispensing clopidogrel to patients.

Link to Article

Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus

In an observation study published in the Annals of Internal Medicine, a group of researchers compared the outcomes of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor versus a sulfonylurea to metformin therapy. The study occurred in Taiwan and used the country’s National Health Insurance Research Database to study patients between 2009 and 2012. It included patients taking metformin who were later additionally prescribed either a DPP-4 inhibitor or sulfonylurea, but excluded patients who were also taking any other medications to manage their diabetes. Outcomes considered were mortality, MACEs (a measure of hospitalizations from stroke, myocardial infarction, and heart failure), and hospitalization for hypoglycemia. The study ended up examining 10,131 DPP-4 inhibitor users, 60,209 sulfonylurea users, and 10,890 propensity score-matched pairs.

Among the patients included in the study, 563 (5.6%) DPP-4 inhibitor users and 4425 (7.3%) sulfonylurea users died before the follow-up. Using the propensity score-matched pairs, it was observed that DPP-4 inhibitor users had lower risks of all-cause death, MACEs, and hypoglycemia. Risks for myocardial infarction and hospitalization for heart failure were not significantly different between the two groups.

The data gathered from this study can be very beneficial for choosing which medication is best for a patient. In patients at greater risk for cardiovascular events, it may be best to prescribe a DPP-4 inhibitor over a sulfonylurea if they are already taking metformin. I also wonder how this data might be translated into practice. Since all the data is from Taiwan, I had to wonder if there are any genetic differences between this group of people and others that could affect the outcomes of treatment. I’m curious to see future studies that compare the outcomes of DPP-4 inhibitors and sulfonylureas in other populations to see how it compares to this study’s findings.

Ann Intern Med. 2015;163:663-672.

Effect of ranibizumab on the decision to drive and vision function relevant to driving in patients with diabetic macular edema

Diabetic macular edema (DME) is a condition that affects a person’s eyesight that can happen after a diabetic patient develops retinopathy. A major issue with this condition is that it often affects the patient’s ability to drive because of their loss of visual acuity (VA). One medication, ranibizumab, is said to significantly lower the risk for substantial visual acuity either by itself or in combination with laser treatment compared to observation alone or macular laser alone. This study was done to specifically analyze and evaluate the impact that ranibizumab can have on the ability of DME patients to drive. There were three different methods involved: RESTORE, RIDE, and RISE. In RESTORE, patients were deemed eligible for laser surgery and had a VA letter score between 78 and 39. They were then either given ranibizumab monotherapy, ranibizumab combination therapy (with laser therapy), or laser monotherapy. In RIDE and RISE, patients either got sham injection, 0.3 mg ranibizumab, or 0.5 mg ranibizumab. Macular laser could be used in any arm as long as the participant met the requirements. In all the trial types, each patient only had one eye treated with the experimental treatment while the other one was treated with the standard of care.

Compared with sham or macular laser therapy in all three of the methods, ranibizumab therapy allowed patients with visual impairment due to DME to report at a greater frequency that they were driving at 12 or 24 months if they were not driving at the onset of treatment. Those using ranibizumab treatment reported less difficulty with driving during the daytime in familiar places, driving at night, and driving in difficult conditions, such as bad weather, during rush hour, on the freeway, or in city traffic. This study ultimately shows that a patient treated for DME with ranibizumab is more likely to be driving 24 months after they start taking the medication. This article made me happy that medication is advancing to allow patients to better manage other disease that come along with diabetes. There are so many complications that occur with this one disease that it is nice to see more and more improvements with them. It is amazing that medication can bring a patient’s eyesight that was almost totally gone back to where they can see well enough to drive. This type of improvement must be amazing for the patient.

 

Bressler NM, Varma R, Mitchell P, et al. Effect of ranibizumab on the decision to drive and vision function relevant to driving in patients with diabetic macular edema. JAMA Opthalmol. 2016;134:160-66.

Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses

According to the new guidelines for treatment of hypertension, it is recommended to initiate pharmacological treatment in diabetic patients when their blood pressure goes above 140/90. This recommendation is one of many that come from JNC 8, a trusted guideline by pharmacists and doctors all over the world. One issue with the JNC treatment guidelines, however, is that while they give extensive and thorough recommendations about the initiation of antihypertensive therapy, they offer little to no recommendations about when antihypertensives should be continued or stopped after a goal blood pressure has been reached.

 

In this review article that looked at 49 randomized controlled trials, it was determined that further treatment of diabetes patients with anti-hypertensives after they were below goal blood pressure actually increased risk of cardiovascular death as well as correlated to an increase towards all types of mortality. This surprised me because it seems counterintuitive that antihypertensive medications could ever increase the possibility of a cardiovascular death, even in a patient with healthy blood pressure.

 

I think this article may shed some light on the “if it ain’t broke don’t fix it” attitude of many doctors towards maintenance medications. Many doctors will keep their patients on anti-hypertensives or statins even if the patient’s blood pressure or lipid levels are at goal. This attitude, as shown by this review article, could have some negative effects on patient outcomes. What do you think? Should patients be discontinued on medications when they reach their goals? Or is this review finding specific to patients with both hypertension and diabetes?

 

Brunström M. & Carlberg, B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: Systematic review and meta-analyses. Bmj 2016;352:I717.

Comparison of Incretin Based Drugs and Sulfonylureas and the Risk of Pancreatic Cancer in Diabetic Patients

Incretin based medications is an umbrella term for some newer antidiabetic agents including dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists. These medications are approved to treat type 2 diabetes. Researchers in this study want to know if these medications are associated with an increased risk in pancreatic cancer compared to the sulfonylurea drug class. This study was conducted as a retrospective cohort study involving data from multiple countries. The researchers looked at 972,384 patients who were just beginning non-insulin antidiabetic therapy with the aforementioned medications. During the follow-up period, which ranged from 1.3 years to 2.8 years, 1221 patients were diagnosed with pancreatic cancer. The results concluded that there was no significant increased risk of pancreatic in incretin based drugs compared with sulfonylureas.

While this study was interesting, I think that more long term effects, included the incidence of pancreatic, should be studied in incretin based medications. This is still a relatively newer group of medications, so long term studies are necessary to determine their overall safety compared to other medications that have been used for longer periods of time. However, this study was definitely a great first step in determining the safety of incretin medications.

Azoulay L, Filion KB, Platt RW, et al. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. BMJ. 2016;352:i581. (Published 17 February 2016).