Autoimmune Protocol Diet – the Secret Cure to Hashimoto’s Thyroiditis?

Within the past 5 years the autoimmune protocol diet (AIP, and sometimes referred to as the autoimmune paleo diet) has been hyped as the key to reversing the symptoms of autoimmune disorders, including hypothyroidism from autoimmune thyroiditis (AIT) a.k.a.Hashimoto’s Thyroiditis. The idea behind this diet is that it reduces the role of the intestine and inflammation, making intestinal inflammation a less likely cause of autoimmune symptoms. The AIP diet itself is much like a paleo diet in that it focuses on protein-rich foods. Like a paleo diet, the AIP recommends no grain or milk products and limits the amount of fruits (to limit fructose intake). Where the AIP differs from the paleo diet is that it also eliminates nuts, legumes and seeds.

But you may ask, what is the science? Well, that’s a good question.

The main theory surrounding the AIP diet and reducing HT symptoms is based on the association between celiac disease (CD) and autoimmune thyroiditis (AIT). Both are autoimmune disorders. It seems logical that if someone has auto-antibodies that are attacking one area of the body, they might be prone to have auto-antibodies attacking another area of the body. In fact, one review article cited ten articles that identified populations with AIT that were subsequently screened for CD. The rate of CD in these AIT populations ranged from 2% to 7.8%.1 This is much higher than the estimated general prevalence of CD which is approximately 1 in 133 people (around 0.7%).2

One study may shed light on how a gluten-free diet could help correct a thyroid disorder. An Italian study enrolled 241 adult patients with a new diagnosis of CD, and matched them to 212 control subjects (matched for age, sex, and ethnic origin).3 Investigators then drew thyroid assays (serum TSH, fT3, fT4, thyroid microsome antibodies [TM-Ab] and thyroperoxidase antibodies [TPO-Ab]) to ascertain thyroid function status. In total, 30.3% of the CD patients had a thyroid disorder, compared to 11.3% of controls (p<0.0005). When sex was taken into consideration, this difference was only significant for females (P<0.0005). Of the 73 patients with CD and a thyroid disorder, 31 were found to have hypothyroidism (10 were able to be identified as autoimmune in nature), 3 had hyperthyroidism, and 39 were euthyroid but with AIT detected. In the 24 subjects in the control group with a thyroid disorder, 9 had hypothyroidism (4 were autoimmune in nature), 7 hyperthyroid, and 8 euthyroid but with AIT detected. In a continuation of this study, 128 of the original 241 subjects with CD were instructed to maintain a gluten free diet. The results are highlighted in the table below. The interesting thing about the results is that a gluten-free diet resulted in half of the patients with autoimmune hypothyroidism and about A few things to note about this study as we apply it to all patients with HT. First and foremost, this was a study in patients with celiac disease. This study has not been replicated in a randomized controlled trial in the general population with thyroid disease (although many anecdotal successes exist on the internet). Furthermore, reversion to a euthyroid state was seen in patients with both autoimmune and non-autoimmune thyroiditis. If a gluten-free diet were to decrease autoimmune antibodies, one might expect to see the reversion to a euthyroid state in only the patients with auto-immune hypothyroidism. Finally, it should be noted that the two patients who remained with overt disease were still treated with pharmacotherapy.


Thyroid Function Patients Assessed (n) Outcome after Diet Trial (n)
Hypothyroid, autoimmune Overt (1)* Subclinical hypothyroidism (1)
Subclinical (5) Euthyroid (3)
Unchanged (2)
Hypothyroid, non-autoimmune Subclinical (14) Euthyroid (11)

Unchanged (3)

Hyperthyroidism Overt (1)* Subclinical hyperthyroidism (1)
Euthyroid with AIT detected (16) Normalization (3)

Unchanged (9)

Subclinical hypothyroidism (3)

Subclinical hyperthyroidism (1)

Normal (no thyroid disease detected during screen) (91) Non-autoimmune hypothyroidism (2)

Subclinical hyperthyroidism (1)

Euthyroid with AIT detected (2)

Normal (86)

Adapted from Sategna-Guidetti, et al.
*patients with over thyroid disease were also treated with drug therapy

A second study looked at TSH levels in subjects with hypothyroidism (HT) and lactose intolerance.4 The results showed that when these subjects adhered to a strict lactose-free diet, their TSH decreased (from 2.06 ± 1.02 IU/mL to 1.51 ± 1.1 IU/mL in euthyroid subjects and 5.45 ± 0.74 IU/mL to 2.25 ± 1.88 IU/mL in subclinical subjects). It should be noted that this same diet in subjects with HT but without lactose intolerance did not produce a similar decrease in TSH.4 This study was limited in the length of time of the lactose-free intervention was given.

Where should we go from here? We certainly need more randomized controlled trials on how diet can influence thyroid disease. The above mentioned articles were the only ones found with definitive evidence. There is a plethora of information on the internet regarding the AIP for HT, but these are anecdotal, and weak on evidence. Patients interested in an AIP diet for HT should be warned that it is an intense diet and can be difficult and frustrating to keep up with, and those with overt disease should be maintained on pharmacotherapy during their diet trial.


  1. Chin CL, Jones K, Kingham JGC. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007;5:184-92.
  2. Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 208;55:349-55.
  3. Sategna-Guidetti C, Volta U, Ciacci C, et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Castroenterol. 2001;96:751-7.
  4. Asik M, Gunes F, Binnetoglu E, et al. Decrease in TSH levels after lactose restriction in Hashimoto’s thyroiditis patients with lactose intolerance. Endocrine. 2013;46:279-84.

Single Payer Healthcare: Case study in running out of The People’s money

Currently there is significant and contentious debate about providing and paying for healthcare in America. In 2010, the Affordable Care Act (ACA) was passed by Congress and included a dozen different new taxes, a specific cadre of policy designs, and mandates for employer participation as well as mandates for individuals to carry insurance. Penalties went along with the mandates, of course. A full discussion of the ACA is beyond the scope of this blog, but suffice it to say that a major issue was how to pay for the expansion of healthcare services. Insurance companies signed up to provide healthcare policies to many individuals, Medicaid rolls were expanded in many states, and a unique provision was made to ‘bail out’ insurance companies if they sustained significant losses.

In short, with its continued funding of Medicare, and its role in partially funding Medicaid and [through bailouts] insurance companies, the extensive role of the federal government makes the United States almost a ‘pseudo’ single payer system with many of the provisions found in other single payer systems (SPSs).

While various factions continue to argue about the future of the ACA, and whether or not it was designed to devolve into a SPS, it would be prudent to look at well-established SPSs to see if there are lessons to be learned. The National Health Service (NHS) in the United Kingdom is a classic and longstanding example of a SPS. The NHS has separate bodies to handle the separate countries in the system. England, Wales, Ireland and Scotland each have separate, very complex organizational systems (1).

From the development of the NHS until now, the evolution of the system in England has devolved to decision-making bodies called Clinical Commissioning Groups, which are regional groups of general practitioners, nurses and consultants that plan and commission the best services for their local patients and population, and collectively have a fiduciary responsibility to the NHS in doing so. (1,2). Over the years, the National Institute for Health and Care Excellence (NICE) has evaluated new therapies and technologies to see if they are worthy to be reimbursed by the NHS. (3)

NICE is not known for readily adopting new medications and technologies. It withdrew NHS funding for newer and more expensive modalities that could potentially impact over 20,000 cancer patients, and more recently rationed treatments for Hepatitis C treatments (4,5,6,7)

No coverage for some products or rationing of others is just the tip of the iceberg in England. Surgery for cataracts is not permitted until the patient is nearly blind (x), knee and hip replacements are denied until “pain is so severe that it interferes with your quality of life and sleep….everyday tasks, such as shopping or getting out of the bath, are difficult or impossible.”(8, 9) And most recently, the “most severe [rationing] ever” by NHS, already adopted by several Clinical Commissioning Groups, is the ban of obese patients and smokers from ‘routine’ surgery. (10)

In addition to these specific issues, there is a movement within the NHS/NICE system to establish a new (lower) financial cap for costs per Quality Adjusted Life Year (QALY) as well as a potentially not approving any treatment that will cost the system more than 20 million pounds during the first three years. (10)

Rationing is the unseemly underbelly of Single Payer healthcare, and when discussed in abstract terms tends to lose its true meaning for the individual. If it is your mothers pain awaiting a new hip, your grandmothers inability to read her romance novels, or even your fathers heart attack while awaiting surgery because he is overweight or some other of the myriad possibilities these very real possibilities need to be discussed openly in light of what is going on with the NHS .

Despite these measures, the NHS is still several billions of dollars in the hole. Clearly these draconian measures are an attempt at slowing the rising healthcare debt, yet they haven’t cut any of the huge bureaucracy that adds to these costs. (12) Think the US government can do a better job? I have a bridge I’d like to sell you…

1. The organisation of the NHS in the UK: comparing structures in the four countries. Doheny S., National Assembly for Wales – Research Service. May 2015.

2. The NHS in England

3. NHS Commissioning

4. National Institute for Health and Care Excellence

5. Betrayal of 20,000 cancer patients: Rationing body rejects ten drugs (allowed in Europe) that could have extended lives

6. 25 cancer drugs to be denied on NHS

7. NHS ‘abandoning’ thousands by rationing hepatitis C drugs

8. Thousands of elderly are losing their sight as NHS rations cataract surgery

9. Pain-level rationing of hip and knee surgery due to cash crisis, admits NHS

10. Obese patients and smokers banned from routine surgery in ‘most severe ever’ rationing in the NHS

11. Daniel Zeichner MP: Proposed changes to NICE & NHS England must not be implemented without a real debate

12. Perspectives on the European Health Care Systems: Some Lessons for America

The Rodney Dangerfield of Cardiovascular Risk Factors in Diabetes

Some of you may remember the great comedian Rodney Dangerfield who passed away in 2004. While some may remember his roles in Caddy Shack or Back to School (my favorite), he was best known for his catchphrase “I don’t get no respect” which was the basis for many comedy monologues.

When we speak of cardiovascular risk in diabetes, we invoke cholesterol, chronic hyperglycemia, reactive oxygen species (ROS), AGE’s, the presence of kidney disease and perhaps others. But almost no one talks about, measures, or attempts to treat one risk factor that is well recognized and treatable (or at least the effects of it seem to be). Have you guessed it yet?

Haptoglobin (Hp) was first described in 1938. It is an α2-sialoglycoprotein coming mainly from hepatocytes in response to the secretion of cytokines such as IL-6, IL-1 and TNF. Haptoglobin is a tetrameric protein that structurally resembles immunoglobulins because it has two light chains (α) and two heavy chains (β) covalently bound to each other by disulfide bridges (S-S). Its main function is to rapidly bind free hemoglobin from intravascular hemolysis to keep it from oxidatively damaging the vascular endothelium. Although present in all vertebrates, in humans Hp is characterized by molecular heterogeneity caused by genetic polymorphism. In the 1940s and 1950s structural heterogeneity was establish when alleles of different structures and lengths were identified, categorized as Hp 1-1, Hp 2-1, and Hp2-2. While these variants can be found in patients without diabetes, much of the work on their role as risk factors has been done in the context of diabetes (both type 1 and type 2). Biologic functions of Hp include prevention of renal damage from intravascular hemolysis, protection against ‘toxic radicals’, and sparing of nitric oxide when unbound to hemoglobin. It has also been found to have a variety of different effects comprising an immune-modulating action. All of these effects seem to differ with the haptoglobin phenotype, and in general a protective role is seen in patients with the Hp 1-1 variant, and a lack of protective effect or more pathological role is seen with the Hp 2-2 variant. Approximately 40% of patients with diabetes carry the Haptoglobin 2-2 gene variant (1)

Increased oxidative stress in diabetic patients results from oxidation of glucose and the modification of low-density lipoproteins (LDL). These changes may stimulate the production of inflammatory cytokines that have been implicated in the morphological and pathological changes found in macrovascular and microvascular complications, and different degrees of susceptibility to the development of vascular problems have been observed in studies of the antioxidant properties of Hp. In diabetic patients, those with Hp 1-1 show better protection against complications than Hp 2-1 and Hp 2-2 individuals. The Hp 2-2 phenotype has been found more frequently in people developing type 2 diabetes (2). Hp 2-2 has been shown to be a major risk factor in diabetic vascular disease (3), an increased risk of Coronary Heart Disease (4) an increased cardiovascular mortality in type 1 diabetes (5), an increased risk of renal function decline (6), an increased risk of death following stroke (7), retinopathy (8) and many other risks of complications in people with diabetes.

Also, as many of you know, both type 1 and type 2 diabetes are associated with the so called ‘leaky gut’. In type 1 diabetes various antigens are presented to the maturing gut which can stimulate the development of activated T-cells which, over time, destroy pancreatic beta cells. In type 2 diabetes, the ‘leaky gut’ allows lipopolysaccharides into the circulation, releasing cytokines and adipokines causing inflammation, insulin resistance and eventually diabetes with loss of beta cell mass due to glucose and lipid toxicity. A major factor associated with ‘leaky gut’ is zonulin, discovered in 2000 by Fasano. Zonulin is pre-haptoglobin-2. (9) It is fascinating that the haptoglobin 2 allele (especially in those individuals who are homozygous [hp 2-2] would confer risk of diabetes, and risk within diabetes likely due to its role in gut permeability and ongoing inflammation…

The risk associated with the presence of the Hp 2-2 genotype can be mitigated with vitamin E treatment to a striking degree. While vitamin E has not been shown to affect surrogates of risk in individuals with Hp 1-1, its effect is clear for those with Hp 2-2. The summary abstract below speaks for itself:

Clinical trial data from the HOPE, ICARE, and WHS studies is presented showing a pharmacogenomic interaction between the Hp genotype and vitamin E on the development of CVD. Specifically, in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD. Cardioprotection by vitamin E in individuals with the Hp2-2 genotype appears to be mediated in part by an improvement in HDL functionality as demonstrated in three independent trials in both type 1 diabetes and type 2 diabetes. (10)

Despite this positive review, and others like it, over 300 articles in PubMed regarding haptoglobin in diabetes, and several presentations at ADA Annual meetings, the current ADA Standards of Medical Care don’t even mention haptoglobin.(11) It truly is the ‘Rodney Dangerfield of risk factors in diabetes’!

So my question to all of you is: With the clear role of haptoglobin genotype 2-2 in the risk of micro and macrovascular complications AND with the clear indication that treatment with Vitamin E can substantially reduce that risk…when was the last time you suggested obtaining a haptoglobin genotype for your patient with diabetes?

1) Changing the Face of Diabetic Care with Haptoglobin Genotype Selection and Vitamin E Nina S. Levy, Ph.D. and Andrew P. Levy, M.D., Ph.D. Rambam Maimonides Med J. 2011 Apr; 2(2): e0047

2) Shi X, et al. Haptoglobin 2-2 Genotype Is Associated with Increased Risk of Type 2 Diabetes Mellitus in Northern Chinese. Genetic Testing and Molecular Biomarkers 2012;16:563-568

3) Asleh R. and Levy AP. In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease. Vascular Health and Risk Management 2005;1:19–28

4) Cahill LE, et al. The Risk of Coronary Heart Disease Associated With Glycosylated Hemoglobin of 6.5% or Greater Is Pronounced in the Haptoglobin 2-2 Genotype. Journal of the American College of Cardiology 2015;66:1791-9

5) Costacou T. and Orchard TJ. The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes. J. Diabetes Complications. 2016;30:221-6

6) Costacou, T, et al. Haptoglobin Genotype and Renal Function Decline in Type 1 Diabetes. Diabetes 58:2904–2909, 2009

7) Ijas P, et al. Haptoglobin Hp2 Variant Promotes Premature Cardiovascular Death in Stroke Survivors. Stroke. 2017;48:1463-1469

8) Mukund R, et al. Haptoglobin2-2 phenotype is an additional risk factor of retinopathy in type 2 diabetes mellitus. Indian Journal of Human Genetic. 2013 Apr-Jun; 19(2): 154–8.

9) Fasano A., Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation. The American Journal of Pathology 2008;173:1243-1252

10) Hochberg I, et al. Interaction Between the Haptoglobin Genotype and Vitamin E on Cardiovascular Disease in Diabetes. Current Diabetes Reports 2017_online Jun 17

11) American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care 2017; 40: Supplement 1

Deintensification Discourse: Why are we still hesitant to pump the breaks on diabetes management?

It is well-established that the efficacy of diabetes therapy is frequently limited by clinical inertia, whether it be attributed to the patient, the clinician, or the health care system. The need for more frequent follow-up and education in the management of diabetes mellitus has created an area of opportunity for pharmacists, as we are more available to meet with patients and facilitate the initiation and acceleration of different therapies. Yet, we are often so concerned with adding on antihyperglycemic agents to getting our patients to goal that we often forget to pause and reassess if the patient really needs all of the medication they are prescribed.

In 2012, the American Diabetes Association (ADA) and European Association for the Study of Diabetes dismissed the one-size-fits-all-approach for glycemic targets and released a position statement describing the importance of individualizing treatment strategies, with an emphasis on patient-centered care and shared decision-making in the management of patients with type 2 diabetes.(1) This was based on literature that demonstrated intensive glycemic control (A1c <6–6.5%) may improve surrogate outcomes for microvascular complications and reduce cardiovascular events at the possible expense of all-cause mortality.(2-5) Factors such as disease duration, life expectancy, comorbidities, established vascular complications, patient preferences, available resources and support, along with risk for hypoglycemia and other adverse effects should be taken into consideration when establishing patient-specific glycemic targets.(6) As clinicians, we frequently assess these factors at diagnosis, but do we do the same for our aging patients with long-standing diabetes?

While we may think this isn’t a common problem, multiple studies have demonstrated possible overtreatment in vulnerable populations (7) and poor rates of treatment deintensification among patients with low HbA1c values or those at risk for hypoglycemia.(8, 9) A retrospective cohort study of data from the Veterans Health Administration examined rates of treatment deintensification among patients that were aged 70 years or older on active treatment for diabetes.(8) Of the 23,769 patients with moderately low HbA1c levels (6.0–6.4%) and the 12,917 patients with very low HbA1c levels (<6%), treatment deintensification was initiated in 20.9 and 27.0% of patients, respectively. Another retrospective analysis using OptumInsight data from 2004 through 2010 determined that antihyperglycemic therapy was deintensified in 18.3% of all patients with recently diagnosed type 2 diabetes mellitus.(9) Furthermore, treatment deintensification occurred in only 19.4% of patients with multiple comorbidities and 21.2% of those that met authors’ definition for frailty, regardless of glycemic control at baseline. This demonstrates the need for us as clinicians to step back and think, “does my patient actually need all of this medication?”

The widespread lack of treatment deintensification described by these studies demonstrates the need for further education among health care professionals and stakeholders. Patients that have not yet experienced a hypoglycemic event and are comfortable with their diabetes treatment are often empowered by their glycemic control, and therefore, patient preference serves as a barrier to deintensification. Providers may struggle identifying the need for and prioritizing diabetes treatment deintensification because what appears to be well-controlled diabetes may seem like the smallest obstacle in the road to comprehensive disease management, especially when patients present with a list of more active problems that require immediate attention. So, how can we better recognize the patient-specific transition of well-controlled to overcontrolled diabetes? How often do you assess an A1c goal in a well-controlled patient and consider their risk of hypoglycemia and falls along with their comorbid conditions to incorporate those factors into their treatment plan?

Just as pharmacists have demonstrated value in the implementation and optimization of antihyperglycemic therapy, their role in identifying those that would benefit from treatment deintensification and facilitating that process is equally important. That being said, what are some strategies you have used to identify the need for and to initiate deintensification of therapy in clinical practice?

Authored by Liz Van Dril, PharmD, PGY-1 Resident, Midwestern University

  1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364–79.
  2. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371:1392–406.
  3. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.
  4. Gerstein HC, Miller ME, Genuth S, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.
  5. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197–206.
  6. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–149.
  7. Lipska KJ, Ross JS, Miao Y, et al. Potential overtreatment of diabetes mellitus in older adults with tight glycemic control. JAMA Intern Med. 2015;175:356–362.
  8. Sussman JB, Kerr EA, Saini SD, et al. Rates of deintensification of blood pressure and glycemic medication treatment based on levels of control and life expectancy in older patients with diabetes mellitus. JAMA Intern Med. 2015;175:1942–1949.
  9. McAlister FA, Youngson E, Eurich DT. Treatment deintensification is uncommon in adults with type 2 diabetes mellitus: a retrospective cohort study. Circ Cardiovasc Qual Outcomes. 2017;10(4).
  10. National Committee for Quality Assurance. Healthcare effectiveness data and information set: comprehensive diabetes care. (accessed 2017 June 11).


A pharmacy business model that’s bad for pharmacy and bad for some patients

We’ve all heard about and experienced the impact of high medication costs in recent years ( While the ACA has increased the number of people who can obtain insurance, it has done nothing to help patients actually afford their medications. While there is no one person to blame, there is one piece of the puzzle that has a domino effect on medication costs.  The Pharmacy Benefit Manager (PBM) is a 4thparty in the mix of insurance that directly manages the prescription benefit for insurance companies.  It is the PBM who negotiates with manufacturers, insurance companies, and pharmacies. It is the PBM that offers different ‘formularies’ to health plans, in many cases disenfranchising patients who may need medications not on the ‘formulary’. A perfect example is the insulin marketplace.  (  Here is a good visual and explanation of how PBM’s work: )  I think they have created a perfect storm of healthcare inefficiency that costs patients access to medications and increases the overall cost of healthcare. Why?  I could list a bunch of reasons, but what do you think?

Metformin: Stepchild of Diabetes Care

The Merriam Webster definition of Stepchild is: “one that fails to receive proper care or attention”. We all know that metformin is pretty much a ‘given’ when we initiate care for diabetes based on nearly all type 2 diabetes treatment guidelines. We also know that metformin has been used effectively in diabetes prevention in patients with prediabetes with long-term effectiveness (1) and that this effect was dose and adherence related (2). Yet despite this, one survey suggested that only 36% of primary care providers prescribe metformin for patients with prediabetes at all (3). Combine this with the fact that we that there is a relationship of dose to the intensity of the hypoglycemic effect in diabetes in clinical trials (4) and that there is an association of glucose control in early treatment with ‘regression’ of pre-diabetes (5).

Guidelines are clear on the need to aggressively intensify therapy in patients with newly diagnosed type 2 diabetes to get to the A1C goal, but patients and physicians may feel less urgency early in the course of the disease, and ‘clinical inertia’ or lack of appreciation of the benefits of early control mean that many patients will be at increased risk of later cardiovascular complications from inadequate intensity of metformin dosing even in the few years subsequent to diagnosis (6). With more recent publications suggesting more flexibility in dosing metformin in patients with impaired renal function, we have even more reason to be comfortable with dosing this important medication (7). When was the last time you recommended metformin for a patient with prediabetes? When was the last time your reviewed your type 2 diabetes patients’ doses of metformin and pushed the envelope on dosing? Sounds like there’s a need to me!

1. Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study Lancet. 2009 November 14; 374(9702): 1677

2. The Diabetes Prevention Program Research Group. Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012;35:731

3. Mainous AG, et al. Prediabetes Screening and Treatment in Diabetes
Prevention: The Impact of Physician Attitudes. J Am Board Fam Med 2016;29:663

4. Hirst JA, et al. Quantifying the Effect of Metformin Treatment and Dose on Glycemic Control. Diabetes Care 2012;35:446

5. Perreault L, et al. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet 2012;379:2243

6. Svensson E, et al. Early Glycemic Control and Magnitude of HbA1c Reduction
Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators. Diabetes Care 2017;40_online April 17

7. Inzucchi, SE, et al. Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review. JAMA. 2014;312:2668

Laugh and the World Laughs With You… …Snore and You Sleep Alone!


Of course, all snoring isn’t necessarily bad (unless you are a sleep partner), but most of us have heard about Obstructive Sleep Apnea (OSA) and have pre-conceived notions about risk factors, prevalence and outcomes. It is safe to say, however, that obstructive sleep apnea is the  ‘elephant in the room’ of cardiovascular risk.  It is true that most individuals who have OSA are overweight or obese, as that is the most common risk factor.  We know that the upper airway collapses in some people who have more tissue in the upper airway (tonsils, adenoids, tongue, palate and uvula).  When the OSA sleeper lays in his/her back, gravity is not in their favor as muscles relax during sleep.  When the sleeper attempts to breath in, the tissue obstructs resulting in snoring or gasping sounds and either a decrease in flow (hypopnea) or a cessation of airflow into the lungs (apnea).  The more often this happens the more likely the sleeper is to develop the consequences of chronic intermittent hypoxia.  OSA affects men about 2-3 times more commonly than women. An older study suggested that roughly 26% of a primary care population was potentially at risk of OSA, yet screen was very rare (1,2). If we look at one specific population, among an estimated 14 million US commercial drivers, 17–28% or 2.4 to 3.9 million are expected to have OSA (3).  In this population the effects of sleep deprivation secondary to OSA can be disastrous.

A much more insidious and common occurrence of OSA is in people with diabetes.  If we look at the type 2 diabetes patient population, the proportion at risk is significantly higher, due to the higher prevalence of older patients, and those with obesity. A recent review suggested the overall prevalence of diagnosed OSA in diabetic patients is approximately 71% based on the average data from five studies including a total number of nearly 1200 patients with type 2 diabetes (4). In 2008, the IDF Taskforce on Epidemiology and Prevention released a consensus statement that recommended a targeted approach to “screen individuals with type 2 diabetes and obesity for sleep disordered breathing (SDB)”. Briefly, the IDF recommended that healthcare professionals should consider the possibility of OSA in patients with type 2 diabetes and work in tandem with the local ‘sleep service’ to provide a clinically appropriate process of assessment, referral and intervention (5).

Several screening tests are available and include the Berlin Questionnaire, the STOP-BANG Questionnaire, and the Epworth Sleepiness Scale.  This last screener may be less effective than the others primarily due to the fact that daytime sleepiness, while common, is not universal, and appears less often in women and in individuals with heart failure. I prefer the “Canadian modifications” of the STOP-BANG screening tool (6).  Further diagnostic tests include the ‘gold standard’ sleep study (polysomnography), and within the last several years more and more products have been introduced that can be used as home diagnostic tests (7).

Studies have shown that cardiac remodeling occurs In OSA patients and that the changes are similar to predisposing changes for heart failure.  There is a significant increase in cardiovascular risk from the downstream consequences of chronic intermittent hypoxia from repeated episodes of apnea or hypopnea during sleep: atherosclerosis, cardiovascular disease including conditions such as myocardial infarction, congestive heart failure, cerebrovascular accident, resistant hypertension, and cardiac arrhythmia, as well as cognitive dysfunction, depression, poor glucose control in diabetes and motor vehicle accidents to name just some of them.

So, the prevalence in people with diabetes is high, and the outcomes of cardiovascular morbidity and mortality are well described.  Yet, the screening rate is abysmally low (in one study around 5%).  Routine screening of diabetes patients should lead many more people to a diagnostic procedure and to CPAP as the most effective treatment.  An old saying about how to eat an elephant is “one bite at a time”.  In the case of OSA, I would submit that some of these bites are up to you.  Pharmacists, involved in screening for OSA you ask (?) Of course! In this era of patient-centered care, how could a credible “diabetes practitioner” [yes, that’s you…] NOT screen patients for Obstructive Sleep Apnea!

  1. Hiestand DM, Britz P, Goldman M, Phillips B. Prevalence of symptoms and risk of sleep apnea in the US population: results from the National Sleep Foundation sleep in America 2005 poll. Chest 2006; 130:780 – 6.
  2. Grover M, et al.  Identifying Patients at Risk for Obstructive Sleep Apnea in a Primary Care Practice. J Am Board Fam Med 2011;24:152–160
  3. Kales S, and Straubel,M. Obstructive Sleep Apnea in North American Commercial Drivers. Industrial Health 2014, 52, 13–24
  4. Pamidi S and Tasali E . Obstructive Sleep Apnea And Diabetes-IsThereALink_Pamidi FrontNeurol_2012_v3_Article128
  5. Seetho I, et al. Obstructive sleep apnoea in diabetes – assessment and awareness. British Journal of Diabetes  2014(3):105-108