Saturday, December 30, 2017

Dapsone: the essentials


Friday, December 29, 2017

Coffee consumption and atrial fibrillation: a meta analysis



Results: Among the 497 retrieved articles, we identified 2 cross-sectional and 9 prospective studies comprising a total of 339,692 individuals with 18,228 AF events. The highest category of coffee consumption (greater than or equal to 5 cups/day) was not associated with increased or decreased risk of AF (pooled RR, 0.98; 95% CI: 0.88-1.09; p less than 0.001; I2 = 59.21%), compared to the lowest category (1 cup/day).

Conclusions: We found no evidence that coffee consumption is associated with increased risk of AF.

Thursday, December 28, 2017

The campaign against daily labs in hospitalized patients



Routine daily laboratory testing of hospitalized patients reflects a wasteful clinical practice that threatens the value of health care.

Where’s the evidence of that claim?

Choosing Wisely initiatives from numerous professional societies have identified repetitive laboratory testing in the face of clinical stability as low value care.

Choosing Wisely recommendations are based on suggestions people have submitted. The relevance here is questionable, as there are few clinically stable patients who remain in the hospital.

Although laboratory expenditure often represents less than 5% of most hospital budgets, the impact is far-reaching given that laboratory tests influence nearly 60% to 70% of all medical decisions.

If this daily testing is influencing medical decisions isn’t it worth doing?

Good source of information about cystic fibrosis


Infections in cystic fibrosis and eligibility for lung transplantation


Form a review:

In cystic fibrosis (CF) patients with end-stage pulmonary disease, lung transplantation (LTx) remains a life-extending therapy with good outcome in most patients. Despite early concern about chronic pretransplantation infections in the context of posttransplantation immunosuppression, typical CF-associated organisms such as Pseudomonas aeruginosa turned out to be quite well manageable and associated with favorable outcomes in transplanted CF patients, even in patients with highly resistant strains. However, the situation is less evident with other pathogens.

Recent findings

Burkholderia cenocepacia is associated with reduced survival and regarded as a contraindication for LTx in most centers, other Burkholderia species are less problematic. Other resistant Gram-negative bacteria and methicillin-resistant staphylococcus aureus in CF patients are not regarded as a contraindication. Nontuberculous mycobacteria disease in CF patients does not preclude successful recovery after LTx, although postoperative complications can be expected in patients with Mycobacterium abscessus and specific management is indicated. Fungal species should be treated aggressively to limit morbidity after transplantation.

Saturday, December 23, 2017

Sleep and cardiovascular disease



Abstract:

Purpose of review: Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors.

Recent findings: Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities.

Summary: Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Friday, December 22, 2017

Cerebral T waves in ischemic stroke: what do they mean?



Transient, symmetric, and deep inverted electrocardiogram (ECG) T waves in the setting of stroke, commonly referred to as cerebral T waves, are rare, and the underlying mechanism is unclear. Our study aimed to test the hypothesis that cerebral T waves are associated with transient cardiac dysfunction. This retrospective study included 800 patients admitted with the primary diagnosis of hemorrhagic or ischemic stroke. ECGs were examined for cerebral T waves, defined as T-wave inversion of greater than or equal to 5 mm depth in greater than or equal to 4 contiguous precordial leads. Echocardiograms of those meeting these criteria were examined for the presence of left ventricular (LV) wall motion abnormalities. Follow-up evaluation included both ECG and echocardiogram. Of the 800 patients, 17 had cerebral T waves on ECG (2.1%). All 17 patients had ischemic strokes, of which 11 were in the middle cerebral artery distribution (65%), and 2 were cerebellar (12%), whereas the remaining 4 involved other locations. Follow-up ECG showed resolution of the T-wave changes in all 17 patients. Of these patients, 14 (82%) had normal wall motion, and 3 had transient wall motion abnormalities (18%). Two of these patients had Takotsubo-like cardiomyopathy with apical ballooning, and the third had globally reduced LV function. Coronary angiography showed no significant disease to explain the LV dysfunction. In summary, in our cohort of patients with acute stroke, cerebral T waves were rare and occurred only in ischemic stroke. Eighteen percent of patients with cerebral T waves had significant transient wall motion abnormalities. Patients with stroke with cerebral T waves, especially in those with ischemic strokes, should be assessed for cardiac dysfunction.

Thursday, December 21, 2017

Cardiometabolic risk factors for atrial fibrillation


From a recent review:

Purpose of review

Atrial fibrillation is the most common sustained cardiac arrhythmia, attributable to several factors that may be amenable through lifestyle modification. There is emerging evidence to suggest that the successful management of several cardiovascular risk factors [obesity, hypertension (HTN), diabetes mellitus, and obstructive sleep apnea (OSA)] can lead to fewer complications and atrial fibrillation prevention. However, the long-term sustainability and reproducibility of these effects have yet to be explored in larger studies. This review explores recent findings for exercise and lifestyle modifications to promote alternative strategies to interventional therapy for atrial fibrillation management.

Recent findings

Several studies have highlighted the impact of established modifiable risk factors on atrial fibrillation burden and the potential for effective risk management in a clinical setting. Higher SBP, HTN, pulse pressure, and antihypertensive treatment have been linked to alterations in left atrial diameter and dysfunction. Effective treatment of HTN has been shown to reduce all-cause mortality, cardiovascular mortality, and the overall risk of developing atrial fibrillation. Given the impact of obesity on the development of atrial fibrillation, diet has been identified as a modifiable risk factor for stroke. Maintenance of proper glycemic control through structured exercise training for prediabetes and continuous positive airway pressure utilization for OSA, have also been correlated with reductions in atrial fibrillation recurrence.

Summary

Early intervention of modifiable cardiometabolic factors leads to lifestyle and behavioral change, which has significant potential to evolve atrial fibrillation management in the coming years.

Wednesday, December 20, 2017

More on the asthma obesity connection



Recent findings

Insulin resistance is a possible factor contributing to the asthma–obesity relationship and the effect is independent of other components of the metabolic syndrome such as hypertriglyceridemia, hypertension, hyperglycemia, and systemic inflammation. Obesity has important effects on airway geometry, by especially reducing expiratory reserve volume causing obese asthmatics to breathe at low lung volumes. Furthermore, obesity affects the type of inflammation in asthma and is associated with reduced inhaled corticosteroids treatment responsiveness.

Summary

Obesity induces the development of asthma with a difficult-to-control phenotype. Treatment targeting insulin resistance may be beneficial in obese asthma patients, especially when they have concomitant diabetes. Systemic corticosteroids should be avoided as much as possible as they are not very effective in obese asthma and associated with side-effects like diabetes, weight gain, and osteoporosis.

Tuesday, December 19, 2017

Hospitalist “education” may have driven excessive narcotic use


Here are a couple of articles in Today’s Hospitalist from years ago. [1] [2]

These articles in effect said that pain was a vital sign, patients’ statements about pain should be taken at face value without too much analysis and that hospitalists’ concerns about the risks of narcotics were overblown.

I remember choking and gagging in response to the attempts to shove pain management pseudoscience down my throat at one of our national hospitalist meetings back in the early days. I wish I had kept the notes, but I didn’t.

Acute exacerbation of IPF


From a recent update:

Recent findings

Clinically, acute exacerbation-IPFs are highly relevant events with a mortality rate of approximately 50%. A 2016 working group on acute exacerbation-IPF has suggested the definition be widened to include any acute respiratory worsening with new widespread alveolar abnormality on high-resolution computed tomography of the chest not fully explained by cardiac failure or fluid overload. Management of acute exacerbation-IPF typically includes supportive care, high-dose corticosteroids and broad-spectrum antibiotics, despite the scarcity of data supporting the usefulness of these therapies. The effect of a number of novel therapeutic approaches is currently under investigation.

Summary

Acute exacerbation-IPF has recently been redefined. A standardized definition, similar to that of other chronic respiratory diseases, will likely facilitate the performance of highly needed studies in acute exacerbation of both IPF and other ILDs

Monday, December 18, 2017

More on opioid prescribing and the Joint Commission suit




If Joint Commission didn’t start the push for more narcotics, according to this report they jumped on board around the year 2000 which had the effect of converting a promotion into a standard.

Device and drug company payments to cardiologists



In conclusion, pharmaceutical and device manufacturers or group purchasing organizations continue to make substantial payments to cardiac practitioners with a significant variation in payments made to different cardiology subspecialists. The largest number and total payments are to general cardiologists, whereas the highest median payments are made to cardiac electrophysiologists. The impact of these payments on practice patterns remains to be examined.

Note the last sentence. Even if some studies have measured impacts on practice patterns (and there are soft data to that effect) we know very little about the impact on patient outcomes, good or bad.

Sunday, December 17, 2017

Saturday, December 16, 2017

Joint Commission sued over allegations about the opioid crisis


So who’s to blame for the opioid epidemic? How did we get where we are today? There's been a lot of finger pointing at the pharmaceutical industry and while it deserves a share of the blame there have been other factors. The Joint Commission had some pretty aggressive pain management standards starting back in the late 90s. Unless you’re in mid or late career (and didn’t have your head in the sand about 18 years ago) you wouldn’t remember this but I do. Oh, how well I remember it.

I remember our joint commission surveys with all the preparation we went through and how pain management was the hot topic of conversation. There were lots of documents from those days (old Joint Commission manuals and hospital committee records) that I'm sure folks would like to suppress and I can say the same thing for certain CME materials promulgated by our own professional societies who tried to shove this pseudoscience down our throats.

Fingers have been pointed at Joint Commission for a while now concerning this, so recently they issued a disclaimer. That vigorous attempt to deflect blame was recently called out by Skeptical Scalpel and I linked to the post here. From that post it would appear that Joint Commission cooperated with industry in pushing for expanded indications for narcotics while minimizing risks.

So the latest news is that four cities in West Virginia have sued the Joint Commission, claiming economic losses not only for the health care of victims but for the cost of efforts to stem the epidemic. This came out just last month (H/T EP monthly). Whether or not they prevail, this will shine light on the history of the problem by bringing old documents into public view that up to now would have been difficult to access. Joint Commission, in their denial that they contributed to the problem, correctly points out that they did not coin the phrase “fifth vital sign.” But, as the documentation shows, they did a great deal to propagate the idea.

Here are the introductory paragraphs from the court document:

1. In 2001, Defendant JCAHO, as part of its certification program for health care organizations, teamed with Purdue Pharma L.P. and its affiliates (“Purdue”), as well as other opioid manufacturers, to issue Pain Management Standards (or “Standards”) and other related documents that grossly misrepresented the addictive qualities of opioids and fostered dangerous pain control practices, the result of which was often the inappropriate provision of opioids with disastrous adverse consequences for individuals, families, and communities. These dangerous Standards, with minor modifications, exist to this day.

2. JCAHO zealously enforces these dangerous Standards through its certification program and has persisted in this course of action even after Purdue was found by the Food and Drug Administration to have misrepresented the quality of its opioid OxyContin in 2003, after Purdue pleaded guilty to felony criminal charges for making misrepresentations respecting OxyContin in 2007, and after warnings from health care professionals concerning the horrible impact wrought by the Standards.

Wow.

It then goes on to quote from past JC standards:

36. For the 2001 Standard RI.1.2.8, The Official Handbook provides “[e]xamples of Implementation of Standard RI.1.2.8,” the first of which is: “Pain is considered the ‘fifth’ vital sign in the hospital’s care of patients...”

46. The 2001 JCAHO Monograph stated: “Some clinicians have inaccurate and exaggerated concerns about addiction, tolerance and risk of death...”

62. The 2003 JCAHO Monograph stated:

a. “Clinicians’ misconceptions about pain treatments could include an exaggerated fear of addiction resulting from use of opioids; confusion about the differences between addiction, physical dependence, and tolerance; or unwarranted concerns about the potential for the side effect of respiratory depression.”…

c. “Many practices are faulty and outdated (e.g., promoting the idea that there is a high risk of addiction when opioids are taken for pain relief).”…

The pharmaceutical industry, our professional organizations and published articles promoted pseudoscientific dogma on pain management. Joint Commission made it a mandate.



Breath acetone as a biomarker in heart failure: something to follow?



Abstract

Background: Although breath analysis has emerged as a noninvasive tool in several clinical conditions, it is not widely used in cardiovascular disease yet. Exhaled acetone is one of the compounds expected as biomarkers for heart failure. However, it is unknown how exhaled acetone concentration changes in clinical course of heart failure.

Objective: To investigate time course of exhaled acetone concentration in acute decompensated heart failure.

Methods: This study included 19 patients with acute decompensated heart failure (ADHF group), and 14 stable patients (control group). Exhaled acetone was collected from these patients and the concentration was measured with gas chromatography.

Results: The ADHF group had higher heart rates (p = 0.020), higher levels of brain natriuretic peptide (p less than 0.001), and blood total ketone bodies (p = 0.003), compared with the control group. In ADHF group, exhaled acetone concentration was significantly decreased after treatment (median: 2.40 ppm vs. 0.92 ppm, p less than 0.001). On the other hand, in the control group, exhaled acetone concentration did not significantly change (median: 0.69 ppm vs. 0.62 ppm, p = 0.370, Table 1).

Conclusions: Exhaled acetone concentration in patients with acute decompensated heart failure was drastically decreased by treatment, and therefore, could be a novel noninvasive biomarker to evaluate the course of acute decompensated heart failure.

Ketosis reflects the neurohumeral response in heart failure. Breath acetone as a measure of ketosis is ultrasensitive, non invasive, low tech and with immediate results available at the point of care.


Friday, December 15, 2017

Atrial dissociation


Two independent atrial rhythms protected from each other by entrance and exit block. One usually associates this condition with heart transplants, but the case described had no history of such.

Thursday, December 14, 2017

Atrioesophageal fistula following a fib ablation



Methods and Results Electronic searches were conducted in PubMed and Embase for English scientific literature articles. Out of 628 references, 120 cases of AEF were identified using various ablation modalities. Clinical presentation occurred between 0 and 60 days postablation (median 21 days). Fever (73%), neurological (72%), gastrointestinal (41%), and cardiac (40%) symptoms were the commonest presentations. Computed tomography of the chest was the commonest mode of diagnosis (68%), although 7 cases required repeat testing. Overall mortality was 55%, with significantly reduced mortality in patients undergoing surgical repair (33%) compared with endoscopic treatment (65%) and conservative management (97%) (adjusted odds ratio, 24.9; P less than 0.01, compared with surgery). Multivariable predictors of mortality include presentation with neurological symptoms (adjusted odds ratio, 16.0; P less than 0.001) and gastrointestinal bleed (adjusted odds ratio, 4.2; P=0.047).

Wednesday, December 13, 2017

The association between aortic stenosis and ventricular conduction disturbances


The more severe the AS the wider the QRS (roughly) and the more likely the patient is to have RBBB or LBBB. This paper looks at the clinical implications.

Tuesday, December 12, 2017

Influenza activity



Abstract

Influenza activity in the United States was low during October 2017, but has been increasing since the beginning of November. Influenza A viruses have been most commonly identified, with influenza A(H3N2) viruses predominating. Several influenza activity indicators were higher than is typically seen for this time of year. The majority of influenza viruses characterized during this period were genetically or antigenically similar to the 2017-18 Northern Hemisphere cell-grown vaccine reference viruses. These data indicate that currently circulating viruses have not undergone significant antigenic drift; however, circulating A(H3N2) viruses are antigenically less similar to egg-grown A(H3N2) viruses used for producing the majority of influenza vaccines in the United States. It is difficult to predict which influenza viruses will predominate in the 2017-18 influenza season; however, in recent past seasons in which A(H3N2) viruses predominated, hospitalizations and deaths were more common, and the effectiveness of the vaccine was lower. Annual influenza vaccination is recommended for all persons aged greater than or equal to 6 months who do not have contraindications. Multiple influenza vaccines are approved and recommended for use during the 2017-18 season, and vaccination should continue to be offered as long as influenza viruses are circulating and unexpired vaccine is available. This report summarizes U.S. influenza activity* during October 1-November 25, 2017 (surveillance weeks 40-47).

Monday, December 11, 2017

Locums versus non-locums in terms of outcomes


It’s quite the thing nowadays to look at large administrative databases and compare outcomes in various categories of physicians (male versus female, FMG versus domestic, age categories, DO versus MD, and on and on). So it was inevitable that someone would compare locums docs versus non-locums docs. Make whatever you will of this:



Design, Setting, and Participants A random sample of Medicare fee-for-service beneficiaries hospitalized during 2009-2014 was used to compare quality and costs of hospital care delivered by locum tenens and non–locum tenens internal medicine physicians.



Exposures Treatment by locum tenens general internal medicine physicians.



Main Outcomes and Measures The primary outcome was 30-day mortality. Secondary outcomes included inpatient Medicare Part B spending, length of stay, and 30-day readmissions. Differences between locum tenens and non–locum tenens physicians were estimated using multivariable logistic regression models adjusted for beneficiary clinical and demographic characteristics and hospital fixed effects, which enabled comparisons of clinical outcomes between physicians practicing within the same hospital. In prespecified subgroup analyses, outcomes were reevaluated among hospitals with different levels of intensity of locum tenens physician use.



Results Of 1 818 873 Medicare admissions treated by general internists, 38 475 (2.1%) received care from a locum tenens physician; 9.3% (4123/44 520) of general internists were temporarily covered by a locum tenens physician at some point. Differences in patient characteristics, demographics, comorbidities, and reason for admission between locum tenens and non–locum tenens physicians were not clinically relevant. Treatment by locum tenens physicians, compared with treatment by non–locum tenens physicians (n = 44 520 physicians), was not associated with a significant difference in 30-day mortality (8.83% vs 8.70%; adjusted difference, 0.14%; 95% CI, −0.18% to 0.45%). Patients treated by locum tenens physicians had significantly higher Part B spending ($1836 vs $1712; adjusted difference, $124; 95% CI, $93 to $154), significantly longer mean length of stay (5.64 days vs 5.21 days; adjusted difference, 0.43 days; 95% CI, 0.34 to 0.52), and significantly lower 30-day readmissions (22.80% vs 23.83%; adjusted difference, −1.00%; 95% CI −1.57% to −0.54%).



Conclusions and Relevance Among hospitalized Medicare beneficiaries treated by a general internist, there were no significant differences in overall 30-day mortality rates among patients treated by locum tenens compared with non–locum tenens physicians. Additional research may help determine hospital-level factors associated with the quality and costs of care related to locum tenens physicians.



That first sentence is a little misleading. Hospital reimbursement for ordinary Medicare patients is not fee for service and hasn’t been since the Prospective Payment System was implemented in 1984.



A few more observations:



The physicians in both categories were, without a doubt, hospitalists.



Although there was no significant difference in mortality the locums docs had longer LOS. The part B spending referred to above would be their rounding and procedure fees, which may mean locums docs tended to code higher for their visits.


Saturday, December 09, 2017

Inflammatory markers in obese adolescents


Friday, December 08, 2017

Hospitalization with infection as a particular risk factor for VTE



Highlights

•Hospitalized infection appears to trigger VTE events.
•The triggering effect of infection on VTE decreases over time after an infection.
•VTE preventive measures may prevent VTE events in the peri-infection period.
•Hospitalized patients with an infection may be considered for VTE prophylaxis.

Wednesday, December 06, 2017

GIK for myocardial infarction


We refuse to give up on it but haven’t quite found a way to make it work, and it’s been 40 years now. The latest? If you couple it with tight glycemic control in NSTEMI, then maybe.

Tuesday, December 05, 2017

Should drug eluting (as opposed to bare metal) stents be used in patients with atrial fibrillation?


Another way of asking this might be “how long do you want to subject a patient to triple anti-thrombotic therapy?”

There is not a clear evidence based answer. This study looked at practice patterns and there is considerable variation.

Monday, December 04, 2017

Cefepime neurotoxicity


Here’s a systematic review on this increasingly recognized problem.

Sunday, December 03, 2017

Interatrial block aka Bayes syndrome: role in atrial fibrillation and stroke


Free full text review.

Saturday, December 02, 2017

Interatrial block: diagnosis and clinical significance


Free full text review here.

Friday, December 01, 2017

Hypokalemia and supraventricular ectopy: risk factors for stroke


Thursday, November 30, 2017

Hyperammonemic encephalopathy following bariatric surgery


You can add this one to two growing lists: bariatric surgery complications and non hepatic hyperammonemias. [1] [2]

Mechanisms? From the first reference:

The specific mechanisms driving the hyperammonemic state after RYGB may be multifactorial. As it has been almost exclusively observed in women, X-linked partial ornithine transcarbamylase (OTC) deficiency has been implicated (Figure 2). Previously asymptomatic heterozygous OTC-deficient women can present when faced with catabolic stressors, and biochemical profiling is consistent with impaired urea cycle function. Zinc deficiency has also been proposed to interfere with OTC function (5). Nongenetic mechanisms of increased ammoniagenesis have been considered, including portosystemic shunting, severe hepatic dysfunction, and overgrowth of intestinal flora. A profound catabolic state may also play a role, driving protein breakdown and accumulation of nitrogenous waste products.

Wednesday, November 29, 2017

HRCT scanning in the diagnosis of pulmonary diseases


In diffuse or multifocal parenchymal lung disease the HRCT may point to a specific diagnosis or place the disorder in a category, thus shortening the differential. Free full text review.

Tuesday, November 28, 2017

Monday, November 27, 2017

Hospitalists as housekeepers


Hospitalists write medication orders, take calls for “housekeeping” issues and do the discharge paperwork. With us, quality of care and patient satisfaction generally improve, and the surgeon isn’t being called at 2 a.m. with requests for Tylenol or laxatives. What’s not to like?


How did we get into this mess? By failing to set boundaries to limit the mission creep that moved us away from the original notion of hospitalists as clinicians within the original scope of their training, IMHO. Our professional organization didn’t help.

Sunday, November 26, 2017

Saturday, November 25, 2017

The hospital of tommorrow


Hospitalists will be obsolete as the hospital care team continues home care via telemedicine and putting patients to death will be considered patient centered. Read the rest.

Friday, November 24, 2017

Clinical status before and outcomes after admission to hospice



Background

Prior work has shown that symptoms leading to restrictions in daily activities are common at the end of life. Hospice is a Medicare benefit designed to alleviate distressing symptoms in the last 6 months of life. The effect of hospice on the burden of such symptoms is uncertain.

Methods

From an ongoing cohort study of 754 community-dwelling older persons, aged greater than or equal to 70 years, we evaluated 241 participants who were admitted to hospice from March 1998 to December 2013. A set of 15 physical and psychological symptoms leading to restricted activity (ie, cut down on usual activities or spend at least half the day in bed) were ascertained during monthly telephone interviews in the year before and 3 months after hospice admission.

Results

The prevalence and mean number of restricting symptoms increased progressively until about 2 months before hospice admission, before increasing precipitously to a peak around the time of hospice admission. After the start of hospice, both the prevalence and the mean number of restricting symptoms dropped markedly. For several symptoms deemed most amenable to hospice treatment, including depression and anxiety, the prevalence dropped to levels comparable to or lower than those observed 12 months before the start of hospice. The trends observed in symptom prevalence and mean number of symptoms before and after hospice did not differ appreciably according to hospice admission diagnosis or sex. The median duration of hospice (before death) was only 15 days.

Conclusion

The burden of restricting symptoms increases progressively several months before the start of hospice, peaks around the time of hospice admission, and decreases substantially after the start of hospice. These results, coupled with the short duration of hospice, suggest that earlier referral to hospice may help to alleviate the burden of distressing symptoms at the end of life.

Thursday, November 23, 2017

Hospitalists’ enthusiasm for MOC: less than overwhelming


Wednesday, November 22, 2017

Home NPPV



Question Does the addition of home noninvasive ventilation to home oxygen therapy prolong time to readmission or death for patients with chronic obstructive pulmonary disease and persistent hypercapnia following a life-threatening exacerbation?

Findings In this randomized clinical trial of 116 patients, the addition of home noninvasive ventilation significantly prolonged time to readmission or death from 1.4 months to 4.3 months.

Meaning The addition of home noninvasive ventilation to home oxygen therapy may improve outcomes in patients with severe chronic obstructive pulmonary disease and persistent hypercapnia following hospital admission.

Tuesday, November 21, 2017

An attempted classification to encompass the diverse phenotypes of diabetes


The different forms of diabetes no longer lend them selves to two simple categories. Various efforts to refine the classification have been met with controversy and complicated by evolving understanding. Here is my attempt to summarize the current thinking.

Type 1: caused by complete autoimmune destruction of the beta cells. A good practical definition is that patients require exogenous insulin in order to stay alive. That is, they will invariably develop ketoacidosis (DKA) when deprived of insulin, even in the basal state. It is important to specify the basal state, because patients with other forms of diabetes can go into DKA as well, but only in the presence of some stressor such as sepsis, MI, stroke, etc. This designation has changed little in recent decades and remains useful, though it has seen some tweaks as noted below.



Type 1b aka 1.5: These designations are no longer very useful for a variety or reasons. They originally (especially 1b) referred to a group of patients in certain ethnic groups with phenotypic characteristics of both type 1 and type 2 diabetes who seemingly transitioned from type 1 to type 2 and/or back, due to a non autoimmune mechanism: intermittent reversible severe beta cell failure due to an exaggerated form of glucotoxicity. This group has subsequently been found to be more heterogeneous than previously thought, both in terms of ethnicity and pathogenesis. To confuse things further, these terms (especially 1.5) have also been used to denote late autoimmune diabetes of adulthood (LADA), an unrelated condition. The terms were partially replaced in popular usage with ketosis prone type 2 diabetes but that too has been waning in popularity, largely abandoned. The ADA, recognizing that there are patients who develop DKA but lack antibodies, created the category of “idiopathic type 1 diabetes.” A more recently proposed category recognizes the heterogeneity in these patients (and subclassifies them accordingly) and is known as ketosis prone diabetes (see below). To confuse things a bit, KPD also incorporates patients who do not fit this phenotype, in order to encompass all diabetic patients who go into ketoacidosis apart from some severe stress. (Note: a very early designation for patients seemingly transitioning between the phenotypes of DM 1 and 2 was Flatbush diabetes).



Ketosis prone diabetes (KPD): This is a proposed designation to replace the category immediately above and adds some other mechanisms, attempting to encompass all patients who spontaneously develop DKA. It recognizes the heterogeneity of the phenotype above, specifically the fact that some forms have an autoimmune pathogenesis. Its 4 categories are based on the presence or absence of beta cell reserve and the presence or absence of autoimmunity.



Type 2: DM 2 is pretty well defined and I will not spend a great deal of time here other than to caution against defining it as any case of diabetes that does not develop DKA in the basal state. That is to say that some forms of diabetes, that don’t invariably cause DKA in the basal state, are not appropriately classified as DM 2 as will be discussed below. Although DM 2 is itself heterogeneous the patients have in common insulin resistance, gradual beta cell fatigue and the metabolic syndrome.



Type 3: Here’s where it gets even more confusing. While often a wastebasket there are some forms of diabetes that rightfully belong in this category though in current literature they have varied and sometimes quite limited degrees of acceptance. There are numerous subcategories. Here they are.

Type 3, no letter designation: This is a theoretical construct that Alzheimer disease is essentially diabetes (insulin resistance) localized to the brain and might be effectively treated with insulin sensitizing agents.

Additional categories of DM 3, designated by letter, were taken from this site:

Type 3 A refers to genetic defects in beta cells, essentially MODY. Inheritance is monogenic autosomal dominant as opposed to the polygenic inheritance of DM 2.

Type 3 B refers to severe genetically determined insulin resistance as seen in Donohue syndrome and related disorders.

Type 3 C is a more accepted category and denotes diabetes due to damage to the pancreas as a whole, eg pancreatitis, pancreatic cancer or pancreatic trauma. [1] [2]. This is important because it is usually misdiagnosed as DM 2 yet has unique treatment implications.

Type 3 D is DM caused by other endocrinopathies eg Cushing’s.

Type 3 E refers to DM caused by drugs such as corticosteroids.

Type 3 F refers to DM caused by infection. In the cite referenced above congenital rubella was given as the example. Would Hep C fit in here?

Type 3 G refers to diabetes associated with unusual autoimmune diseases, eg stiff person syndrome.

Type 3 H refers to diabetes associated with Down’s syndrome.

Note: Although all the entities mentioned above under type 3 are real I could find little or no independent support in the literature for the nomenclature except for the one with no letter designation (Alzheimer disease) and type 3C.



Type 4 This is a theoretical construct based on an animal model, attempting to explain some instances of apparent DM 2 in lean adults. This may not be an important entity in man if it exists at all and might be confused with LADA.



Miscellaneous forms:

Latent autoimmune diabetes in adults (LADA). It is sometimes been referred to as DM 1.5.

Double diabetes. You could be unlucky and have both 1 & 2. Or, in DM 1, if you treat overeating with more and more and more insulin and thereby gain of sufficient weight the characteristics of DM 2 could develop secondarily.