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 Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial

In this interesting study the researchers looked to see if degludec /liraglutide was noninferior to continued titration of glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin. The study occurred at 75 sites in 10 countries with 557 participants with A1Cs of 7% to 10%.  The study measure A1c over a 26 week period with a nonineriority margin of 0.3%. This study is very important because even with insulin therapy, managing blood glucose is a very difficult task in patients with type 2 diabetes.

The study ended up showing the two medications did not show a reasonable difference in achieve A1c after 26 week. However, both medications showed reduction in A1c over the 26 weeks. The researchers did call for more long term studies to determine long term efficacy and safety. These findings could be very important in the future treatment of type 2 diabetes and as the authors said it is very difficult to achieve glycemic control in patients with type 2 diabetes.

With so many people getting diagnosed with type 2 diabetes and it being so difficult to control I wonder how much of it has to do with the patient and how much of it has to do with the medical providers and medication. Diet and personal health plays a role in type 2 diabetes so that much is on the patient. Also I have the feeling that patients with type 2 diabetes don’t see the severity of the disease in comparison to patients with type 1 which leads to adherence problems. On the other hand is the drug therapy not effective enough or the medication being prescribed for individual patients not effective enough?  Either way I hope medical providers will find a way to effectively control type 2 diabetes in the majority of patients.

Lingvay I, Manghi FP, Garcia-Hernandez P, et al. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial. JAMA. 2016;315(9):898-907.

JAMA. 2016;315(9):898-907.

Ranolazine for T2DM and Angina

Greiner and colleagues did a literature review to examine the effects of ranolazine in glycemic control of patients with type II diabetes. Ranolazine is a cardiovascular agent used for the treatment of chronic angina and additionally has been show to reduce A1C levels. This becomes an important drug therapy because it could afford a means of treating type II diabetes and reduce the cardiovascular complications or events associated with type II diabetes.

Clinical studies examined in the trial have shown that ranolazine decrease A1C levels without resulting in hypoglycemia and as a dose-dependent affect on A1C. The authors note that the most common adverse effects related to the administration of ranolazine was nausea, constipation, headache, and dizziness. The authors additionally referenced an animal study that suggested that ranolazine’s ability to reduce A1C levels could be related to preserving the function of beta pacreatic cells. As a conclusion, the authors state that the first line of treatment for patients with type II diabetes should be lifestyle modifications and that metformin should still be considered as the first pharmacological intervention. They state that because of ranolazine’s ability to reduce A1C, it could be considered a new therapeutic agent for individuals with type II diabetes.

I found this study to be very interesting because it is the first time I have become aware of a drug that could be used to treat both type II diabetes and chronic angina related to cardiovascular disease. Because type II diabetes and cardiovascular disease are so closely related, the idea of having a single drug that can help treat both chronic conditions it an exciting prospect. It could reduce the number of adverse events related to drug-drug interactions and it could be an easier treatment option for the patient.

Greiner L, Hurren K, Brenner M. Ranolazine and Its Effects on Hemoglobin A1C. Ann Pharmacother. 2016 Feb 25.

http://aop.sagepub.com.pitt.idm.oclc.org/content/early/2016/02/24/1060028016631757.full.pdf+html

Use of Fenugreek in Maintenance of Type II Diabetes Mellitus

As the industry in production of these natural supplements grows, there are more questions being raised about their effectiveness and different uses. Since there is not a ton of literature that supports their efficacy, it is difficult on the part of the pharmacist to recommend these with any sort of confidence. Here fenugreek was evaluated for its use in assisting with maintenance of type II diabetes mellitus (T2DM).

Fenugreek has already been used in foreign countries in patients with uncontrolled blood glucose levels. It is thought to work by delaying gastric emptying, slow carbohydrate absorption, and act to increase insulin sensitivity in tissues. The fenugreek seeds increase glucose dependent insulin secretion. It does have issues with blood thinning and may cause hypokalemia. It may decrease the absorption of some medications since it is rich in fiber, thus its use should be spaced out by at least 2 hours from other medications.

There have been mixed results regarding its effectiveness in treatment of T2DM. One study showed a significant decrease in A1C of 1.13% in use of the supplement over time while it did not show any effect on fasting blood glucose level. Another study did show a decrease in fasting levels of -0.96 mmol/L and 2 hour levels of -2.19 mmol/L. This study also showed a decrease in A1C of 0.85%.

Fenugreek was showed to be a supplement that may have some use in the maintenance of T2DM. However, there are definitely some reasons why not to recommend its use for this indication. The issue with its interference with the absorption of other orally administered medications could prove to be problematic in its usefulness since many of antidiabetic medications must be taken before meals. More studies are needed to determine its place in T2DM therapy but due to its ability to lower blood sugar, this should be encouraging to the scientific community to investigate more of these herbal supplements in an attempt to determine if they may have a place in modern medicine.

Reference

Smith J, Clinard V. Natural products for the management of type 2 diabetes mellitus and comorbid conditions. J Am Pharm Assoc. 2014; 54(5): 304-21

J Am Pharm Assoc. 2014; 54(5):304-21

Prevalence of Sugar-Sweetened Beverage Intake Among Adults — 23 States and the District of Columbia, 2013

The 2015-2020 Dietary Guidelines for Americans states that only 10% of a person’s daily calories should come from added sugar. They identified sugar-sweetened drinks as one of the most significant sources of sugar in the U.S., and frequently consuming these types of beverages is associated with many health conditions such as Type 2 diabetes, obesity, and cardiovascular disease. In an NHANES study, it was found that 50.6% of U.S. adults drink at least one sugar-sweetened beverage per day, and in certain regions of the country, such as the Northeast and South, this intake was even higher, reaching 68.4% and 66.7%, respectively. When looking at specific states, Louisiana, Mississippi, and West Virginia have the highest rate of sugar-sweetened beverage consumption. When looking at other factors that cause an increase in sugar consumption, the highest prevalence was seen in adults ages 18-24 years old, in men, in non-Hispanic African Americans, in unemployed adults, and in people with less than a high school education. The intake of these high sugar-content beverages was also found to be an effective biomarker for inflammation and insulin resistance that can then lead to cardiovascular disease and diabetes. Public health actions that should be taken to reduce the intake of these sugary beverages include education and awareness initiatives, increasing the access to healthier food options, food service guidelines being more readily accessible, and the promotion of drinking water in schools and in the general population. In addition, health care providers can screen patients’ sugar content and provide counseling on how to reduce their intake and give resources to help support them in this change.

MMWR Morb Mortal Wkly Rep.2016;65(Early Release):169-174

I chose this article because obesity and diabetes are two extremely common illnesses facing the American population. Food and beverages that contain high levels of additives, including sugar, are a major source of these problems. As this survey has shown, this problem affects a high percentage of our population and this will only increase if we do not take action. Making healthier options, such as fruit, vegetables, and water more available to the public, especially is the Northeastern and Southern regions of the country, will help reduce the prevalence we are seeing. Pharmacists counsel patients everyday on the numerous medications that are available for these conditions associated with high sugar intake, but we should also be counseling the patient on life-style changes. What good is the medication if the person does not change the behavior that is the core of the problem? I believe we need to shift our focus from purely talking about the side effects of these types of medications to informing the public that these medications are actually side effects of their high-sugar intake, and although the medications are helpful, they should not be seen as the solution. As health care providers, we need to start motivating people to change their dietary behaviors to prevent these conditions from occurring, and to prevent people from taking additional and unnecessary medications.

 

 

 

A New Possible Type 2 Diabetes Injection: IDegLira

As we learn more about diabetes and the huge impacts it can have on patients’ everyday lives, it is almost natural to wonder why treatment has not become easier or safer or perhaps more importantly, more convenient. A massive aspect of medication adherence is the convenience, especially when focusing on diabetes. Most patients do not understand that nonadherence to one diabetes medication however can lead to the addition of more and therefore a further inconvenience to the patient. Patients also understandably dislike the adverse effects that typically accompany diabetes medications, such as hypoglycemia and weight gain. Hopefully, a new drug may be able to diminish this growing issue.

IDegLira is an injectable diabetes management medication that is a combination of basal insulin and GLP-1RA, or liraglutide. The medication is injected once daily and tackles two different physiological deficits in patients with type 2 diabetes. The basal insulin reduces fasting blood glucose while the GLP-1RA keeps postprandial glucose values under control. A study with patients already on basal insulin was completed to see if adding insulin aspart or liraglutide would control their glucose levels better. The addition of liraglutide was recorded to be more effective as well as less hindering, as it had lower rates of hypoglycemia and weight loss in patients as opposed to weight gain.

Positive results have been seen in several clinical trials involving the combination drug of insulin basal and GLP-1RA. Hopefully this more convenient, effective, and safe medication will come out on the market soon to aid those with type 2 diabetes.

Do you think patients would truly be more adherent to this medication, a single injection, than metformin, a single oral tablet per day? Even if this is more effective, will patients choose an injection over a pill?

Reference: Hughes E. IDegLira: Redefining insulin optimisation using a single injection in patients with type 2 diabetes. Primary Care Diabetes. Article in Press. https://www-clinicalkey-com.pitt.idm.oclc.org/#!/content/journal/1-s2.0-S1751991815001837

Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial

Metabolic syndrome is defined by the following risk factors: abdominal obesity, elevated blood pressure, dyslipidemia, abnormal glucose regulation. Prolonged metabolic syndrome increases a persons risk of developing cardiovascular disease and type 2 diabetes. As we have learned a lot during our first and second semesters of pharmacy school, not all populations have equal risk of developing diseases. Many are determined by socioeconomic status. Vulnerable populations to metabolic syndrome include the Hispanic population and those with lower socioeconomic status including education and household income. This study aimed to assess the efficacy of lifestyle interventions to reduce the rate and severity of metabolic syndrome in these populations. They recruited low income, minority participants (less than $20,000). The participants must have 3 of the following: high waist circumference, high triglyceride levels, high HDL levels, hypertension, and impaired fasting glucose to be considered to have metabolic syndrome. The interventions were tailored to the community by translating the educational materials to Spanish, delivering the healthcare meetings in Spanish should the patient be comfortable with that, and providing culturally relevant examples and dietary recommendations. Overall the intervention showed a significant reduction in weight especially in female participants. Additionally the fasting blood glucose level was significantly reduced. There was no reduction in cholesterol, abdominal obesity, or number of patients qualifying for metabolic syndrome. The educational materials being translated showed an effect on how well the materials were received.

J Behav Med. doi: 10.1007/s10865-016-9721-2 (published 04 February 2016).

This study shows just how important it is to keep the community we serve in mind when creating treatments for patients. Healthcare and treatment regimens are not universal, as we see in guidelines like JNC 8 where certain populations are given different treatments for hypertension. Further studies could be done to emphasize the importance of creating differential treatments for patients for all kinds of disease states according to population.

Gene Identification associated with Epigenetics of Type 2 Diabetes

Type 2 Diabetes is the most prevalent type of diabetes accounting for 90% of all cases.  The disease is also a major risk factor for cardiovascular events.  In a recent study, researchers discovered an epigenetic mechanism that occurs when regulating blood sugar levels.  Epigenetic mechanisms such as DNA methylation has been associated with several processes such as aging or pathologies.  This study provides evidence that DNA methylation of the TXNIP gene is associated with type 2 diabetes.  As many people know, this disease has a genetic component as well as environmental factors.  Many of the environmental factors have been studied in the past, so researchers are beginning to focus on the epigenetics of diabetes.

This study’s aim was to associate type 2 diabetes with DNA methylation.  The setup of the experiment was a two cohort approach which included comparing non-diabetes patients with patients with diabetes, as well as two different groups of diabetics based on their control of blood glucose levels (well-controlled or poorly controlled).  As a result, a new methylation was associated with diabetes and A1C levels.

The study concluded that there is a binding correlation with glucose import and chaperone binding.  Methylation differences in where they bind may alter the regulation of genes which correlate with glucose exposure.  The expression of the TXNIP gene for glucose-responsiveness is elevated in the muscle of pre-diabetics and diabetic patients.  DNA methylation may be able to modulate the expression and work as a biomarker of altered glucose levels.

This article demonstrates the importance of genomics in disease.  Identifying possible genetic components invested in prominent diseases such as diabetes can be a step in the right direction for a cure.  How could pharmacists use these types of studies in their practice?  Pharmacogenomics is a hot topic these days, how could this study benefit diabetes drug development?

Carolina Soriano-Tárraga, Jordi Jiménez-Conde, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M. Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer. Epigenome-wide association study identifiesTXNIPgene associated with type 2 diabetes mellitus and sustained hyperglycemia. Human Molecular Genetics, 2016; 25 (3): 609 DOI: 10.1093/hmg/ddv493

Long-term Exposure to Antipsychotics in Youth and Type 2 Diabetes

Over the years, antipsychotic use in youth has become increasingly popular. Most youth are prescribed second generation antipsychotic or SGAs. When SGAs were first approved for youth they were restricted to those that were on the schizophrenia spectrum. Since then, they have been approved for diseases such as Tourette syndrome and some autistic characteristics such as bipolar mania and irritability. The issue with SGAs being prescribed to the youth now is that they are being prescribed for a broad range of off label indications. These indications are impulsivity, mood, aggression, depression, and anxiety.

SGAs differ from first generation antipsychotics (FGAs) because of their fewer neuromotor side effects. Although SGAs do not cause many neuromotor adverse effects they do cause cardiometabolic side effects. These side effects include weight gain and other disease states that can lead to type 2 diabetes mellitus (T2DM). The article focuses on the concern that these cardiometabollic adverse effects are present at low dosages, and are more severe in the youth, concerning   that long-term expose can only worsen the adverse effects.

The study concluded that the highest risk for development of T2DM was in the antipsychotic exposed group of approximately 1000 patients. The mean age of the patients was 14 years old with almost two-thirds being males. The patients were The incidence rate of developing T2DM from exposure to SGAs was found to be 0.5% , and is very statistically significant. This shows that long-term exposure of the youth to antipsychotics increased the possible development of T2DM and that antipsychotics should be monitored and used for as short of a duration as possible in the youth.

I find this study to be very interesting because it calls into question not only the adverse effects that can develop in the antipsychotic exposed youth, but also the control in prescribing these medications. Specifically, I wonder what we can do to better control the prescribing of antipsychotics to youth, who present with more side effects? Or what other changes in diet or exercise we can supplement the youth with who are on antipsychotic treatment long-term?

 

Galling B, Roldan A, Nielsen R, et al. Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2015.2923(published January 20, 2016)

Link to Article