Wednesday, March 20, 2013

Another Diabetic Discussion

I'm currently involved in training as part of a Care Management team approach, which will help prepare me for the implementation of the Patient Centered Medical Home. This is the concept that...wait for it...wait for it....physicians actually ask the patient what we as clinicians can do to help them care for themselves better. Call me crazy but doctors are actually being taught they have to talk to their patients and then really, truly actually listen to what they have to say...A concept whose time, ummmmm, should've already come.

This weeks discussion was on diabetes and I had alot to say, but kept it short, for, uh, brevity's sake. First off, who is brevity and second off, it wasn't short....

Enjoy!

Remember, my blog posts are for informational purposes only and are not intended to diagnose, treat or cure any diseases. However, they are intended to hopefully eradicate the nutritional ignorance of the medical profession...



Diabetes Forum;

As a family physician with a profound concern for the diagnosis and correct treatment of diabetes, and having been directly involved with the management and care of thousands of diabetics over my 20 years of practice; I can state without reservation that the current standards of care for diabetics is wrong. Unfortunately, organizations like the American Diabetes Association, American Dietetic Association, American Heart Association, American Cancer Society, the National Institutes of Health, the National Heart Lung & Blood Institute, the Surgeon General, TV personalities such as Dr. Oz and even the White House’s new My Plate campaign, all have it wrong as far as the correct way to eat is concerned.

My direct clinical experience has taught me that in order to correctly treat diabetics, carbohydrate  (carb) restriction is mandatory. The current ADA guidelines recommend that diabetics go no lower than 139 grams of carbs per day. This is wrong. Experience has shown me that when I reduce the carb count to 20 to 40 grams of carbs a day, dramatic sugar control becomes immediately apparent. Yes, you read that correctly; I did state that I reduce my diabetic pt’s carb intake to 20 to 30 grams a day.

This reduction is simple in a newly diagnosed Type 2 diabetic who is not on any medications; but if I get a diabetic already diagnosed on meds, the clinical approach needs to change. For instance, if I see a diabetic who is on insulin (and this can be a type 1 or 2 ) and I get the impression that they are serious about lowering their carbs to help lower their meds; I will immediately stop any short acting insulin (e.g. Humulog) and cut in half the long acting insulin they may be on. Also, meds like Byetta (a hormonal incretin analog which increases GLP-1 secretion) and Januvia (a dipeptidyl peptidase type 4 inhibitor which allows incretin analogs to stay in system longer) will be stopped as will any sulfonylurea (e.g. glimeprimide and glipizide, which work by stimulating an already fatigued pancreas to secrete more insulin hence facilitating B cell burnout and the eventual need for insulin).

The insulin can be stopped and adjusted and the meds can be d/c’ed because once a diabetic reduces their carb amount these meds are no longer needed. I have a big issue with any Type 2 being started on any sulfonylurea due to their mechanism of action. As a side note, if anyone has seen the black box warnings on sulfonylureas it includes ‘increased risk of cardiovascular mortality’ and that it ‘should not be used for prolonged therapy,’ a fact that most clinicians have either forgotten or had no idea about, because I still get diabetics in my office on these meds; usually for many years.

Getting back to adjustments and d/cing of meds, when one dramatically lowers their carb intake there will not be a large increase in post prandial serum blood sugar; therefore the short acting insulin (which is used to lower post prandial blood glucose) will not be needed. Meds like Byetta & Januvia also work by helping lower postprandial blood glucose and they will not be needed as there will be no large increase in post prandial blood glucose because of the carb lowering. The most dangerous of these meds are the sulfonylureas. These meds need to be stopped immediately once a pt implements low carbs. This is because the sulfonylureas will continue to force the pancreas to secrete insulin, irrespective of the blood glucose readings and dangerous life-threatening hypoglycemia can result. I have counseled many a pt who started a low carb regimen on their own, without stopping the sulfonylurea, and subsequently woke up in the hospital after their syncopal event. What’s even worse is that the ER doctor or nutritionist who sees the patient tells the patient they should never have lowered their carb intake; not understanding that is the wrong approach and the pt should have stopped the medicine, not increased their carb intake. Why? Because the pt was no longer consuming large amounts of carbs and does not need the med any longer. This would also be true of Byetta, Januvia, and short acting insulins.

Let’s take some time to discuss insulin and its role in the treatment of diabetics. There are four types of diabetics; Type 1 DM whose pancreas’s no longer can make insulin so they need to take it exogenously; the Type 2 DM whose pancreas is actually hyper-secreting insulin and represents the most common type. This hyper-secretion can go on for years which is why eventually the B cells can burn out (a process facilitated by sulfonylureas and assuaged somewhat by the use of exogenous insulin). This hyper-secretion is also the reason the cellular insulin receptors become resistant due to receptor down regulation as one of the contributors; and this is also the main reason we should never, ever use a sulfonylurea to treat a type 2 diabetic, as their pancreas is already overworking and these meds facilitate its demise. There is also a less recognized type of diabetes known as type 1 and a half or type 3 diabetes. This type of diabetic is one who is insulin requiring, but now has developed resistance to exogenous insulin, a situation we are seeing more of as more clinicians are using insulin in the initial treatment of even type 2 diabetics (a treatment I do agree with but with some caveats). The fourth type is gestational diabetes and these pts do very well with carb restriction which is safe in pregnancy, so long the pt is eating more fat, cholesterol and protein. Some authors have argued there are at least two more types (drug induced diabetes as one sees with steroid use and Juvenile onset type 2 diabetes, which is self-explanatory) but for brevity’s sake we’ll limit our discussion to the 4 types above.

Now let’s get back to insulin. We all learned in nursing or medical school that insulin helps to lower serum blood sugar. This is done via a second messenger system specifically the Inositol 1-4-5 triphosphate, e.g. IP3 and the diacylglycerol or DAG molecules. This fact was learned when we took biochemistry but unfortunately was quickly forgotten. Analyzing this second messenger system further and looking specifically at the DAG molecule, we need to note that one of the ‘acyl’ groups is arachidonic acid which when metabolized releases pro-inflammatory mediators (Click Here for more on Arachidonic Acid). It is these mediators that can and do cause a cellular apoptosis. What’s even more of a concern is that some of these mediators have been shown to be oncogenic. The possible end result of allowing our cells to see too much insulin is the eventual death of the cell. Said another way, not only does the elevated blood sugar cause cellular damage, but so too insulin can cause cellular damage or death (culminating in organ damage) and this is a point missed by most clinicians. Therefore I disagree with the intensive insulin therapy and do agree with lowering the carb intake in our 60 yo female pt.

While some may be thinking it difficult to lower the carb intake so strictly, I must state that the majority of my patients are very happy to have this option to treat, an option too few doctors even know about. As far as motivational interviewing is concerned it really is a treatment that sells itself. Most pts do not want to take meds and they especially do not want to take insulin as this requires a needle. I have successfully treated thousands of diabetics with a low carb approach with success nothing short of miraculous. The only problem is that most clinicians, dieticians, nutritionists, and politicians do not even understand the correct way to eat.

I want to get back to insulin a little while longer because it is such an important hormone to understand. When a healthcare professional is asked to describe the effects of insulin secretion, all will correctly state that it helps lower serum blood sugar; but insulin has many more effects biochemically which I want to discuss further, as it directly affects diabetes care. Insulin also increases the activity of HMG Coenzyme reductase as well as acetyl Coenzyme A carboxylase. The first enzyme catalyzes the rate limiting step in cholesterol biosynthesis; the second enzyme catalyzes the start of the biosynthesis of fatty acids. Therefore, any increase in the secretion of insulin which occurs via the consumption of carbs, will also increase the biosynthetic rate of both cholesterol and fatty acid synthesis. The end result is progression of atherosclerosis, elevation of triglycerides, lowering of HDL, and increases in weight all of which contribute to the manifestation of ‘the metabolic syndrome’ which culminates in development of overt type 2 diabetes. In fact, the treatment and reversal of not only type 2 diabetes but of the entire metabolic syndrome is so easy; it should be an embarrassment to the medical community that we haven’t been able to do this yet on a widespread scale. As a side note, there is a website that lists doctors who understand the importance of low carbs in the treatment of disease, just go to LowCarbDoctors.com

Now it is easy to say we need to dramatically lower our carb intake to experience better and ultimate sugar control, but we aslo have to analyze further what exactly carbs are and this is where it can become controversial. Everyone knows that cakes and candies are bad for us as well as the white starchy foods; but what about whole grains, muti-grains, whole wheat pasta, brown rice, yogurt, oatmeal and fruit? Are these foods safe for a diabetic to eat? Well, let’s analyze those foods further. Diabetics are often told that they can eat whole grains and the like, and that fruit is fine to eat too. This is false. Whole grains are complex carbs and as such contain many sugar molecules (one grain contains 6 x 10 exponent 1017 molecules which is a 6 times 10 to the 1017 power!) and one slice of whole grain bread may contain even more carbs (even after subtracting the fiber) than its white counterpart. The body will break down these complex carbs into simple sugars and that’s where the trouble starts. One may not see an immediate rise in blood sugar for an hour or so after consuming complex carbs, but it will happen if one keeps checking blood glucose levels. Another side note is that blood sugar should always be normal, it should never be elevated. This sounds like a tautology but let me explain further. I use a normal range of 80-100 and I warn my diabetics they should always be in that range. That any increase in blood sugar will create cell damage and is dangerous to their organs. I am confused as to why the ADA allows a post-prandial increase in blood sugar and considers this to be ‘normal.’ It is not and any rise above 100 should be evaluated. In fact, I tell my patients who are going to get their labs drawn to not fast, as fasting is cheating and changes the blood chemistry into what it truly isn’t and we want to see what the blood normally looks like. Another fact is that a simple 6 hour fast (and a lot of clinicians tell their pts to fast 12-14 hours) can normalize blood sugars and triglycerides, and the clinician will not know a pt is over consuming carbs and cannot counsel the pt effectively. Another reason blood sugar should always remain normal is that the attachment of glucose molecules to cells in our organs occurs via a nonenzymatic pathway, referred to as nonenzymatic glycosylation. What this means is that glucose attaches to the cells in a concentration dependent manner and no intermediaries are needed for this to happen. This glycosylation process is what leads eventually to end organ damage and the only way to prevent this is by having normal blood sugars all the time.

Getting back to the whole grains (and this goes for any grain, oatmeal etc.) once they are metabolized to simple sugars, insulin will be secreted form the pancreas and this will facilitate persistent insulin resistance as well as increase the biosynthesis of cholesterol, free fatty acids, help to lower HDL, encourage weight gain, & create pro-inflammatory mediators via the second messenger system. This cascade of events will occur with any glucose molecule. The glucose released from complex carbs is not ‘special’ in any sense. To think that at the level of the cell a cell can ‘recognize’ a glucose molecule as being from whole grains, oatmeal, white starchy food or a chocolate bar is wrong. Cells are not cognizant of where a glucose molecule comes from, they just do biochemically what they’re programmed to do when glucose enters them; make us fatter, create plaque forming deadly cholesterol and of course elevate blood glucose serum levels.

And now a word about fruit. I tell my diabetics that fruit is a poison and they should stay away from it. Any diabetic who actually checks their blood sugar level after eating fruit knows this. I am utterly confused as to why the organizations as delineated above refuse to understand this. Another biochemical fact is our cells use both glucose and fructose to make cholesterol and fat and that fructose is actually transformed into cholesterol & fat faster than glucose. This means that when one eats a piece of candy and piece of fruit, the fructose in the fruit will be converted more quickly into fat & cholesterol, than the glucose in the piece of candy will be. This is a biochemical fact. Why? Quite simply because fructose enters the glycolytic pathway about a third of the way in and needs to be modified less than glucose. So, no, diabetics should not be eating fruits as allowed by the ADA guidelines.

I want to take time out now to dispel a few myths about glucose. Glucose is not the primary energy source of the body. I know this is a controversial statement but let me explain further.  The fact is that our skeletal muscles, renal cortex and myocardium all prefer free fatty acids for fuel, not glucose. Also, when given the choice the brain prefers ketone bodies for fuel over glucose. Interestingly enough, the breakdown products of fatty acid metabolism (in a process referred to as beta-oxidation) are ketone bodies. Another interesting point is that some will claim that the only way glycogen can be stored (in the liver and muscles) is by the consumption of carbs, which allows glucose to be stored as glycogen. This is not true. We can also make glucose from the glucogenic amino acids as well as the glycerol backbone chain found in triglycerides. The utilization of free fatty acids for energy comes from shuttling 2 carbon acetyl fragments into the Kreb’s cycle then onto the oxidative phosphorylation pathway, not by creating glucose (this is the beta oxidative pathway).

Another misconception I wish to clear up is the whole ‘burning of fat’ or ‘burning of calories’ notion. When we catabolize or breakdown macronutrients (fat, carbohydrates or protein) this is not a combustion process, it is a digestive process. For example, the breakdown of carbohydrates begins when a carb is ingested. If it is a complex carb, it will be acted upon by different enzymes (mono & disaccharidases) to release a glucose molecule(s). This glucose molecule will then enter the cell and be shuttled into the glycolytic pathway. The end result of this pathway is the creation of a molecule (actually 2) of pyruvate which then will be transformed to Acetyl CoA. I often refer to Acetyl CoA as a pivotal biomolecule because its fate depends upon how much carbohydrate one has consumed. If there is an overabundance of carbs ingested, the Acetyl CoA will be shuttled into the cholesterol and fatty acid biosynthetic pathway. If there is not an overabundance of carbs consumed it (Acetyl CoA) will then move into the Kreb’s cycle and then finally into the oxidative phosphorylation pathway (the final step in the oxidation of glucose.) It is important to stress that nothing is burned because it creates a misunderstanding of what really is happening biochemically. Glucose is metabolized to create either ATP (the energy currency of our bodies) or is used to make cholesterol or fat, there is no actual burning. The same is true of fat and protein digestion, they are not combustion processes. This is so germane to a diabetic (and anyone) because we are told to count calories. This is wrong. We often hear the phrase ‘I need to burn up my calories,’ and this, too, is wrong. We are not burning any calories or fat. We metabolize fat, protein and/or carbs to either create biomolecules and/or to create ATP. Again, there is no combustion going on here.

Now the process to determine how many calories are in an item of food is indeed a combustion process. We’ve all come across the calorimeter; a cylindrical metal device containing water, a thermometer, a lid and a heat source. To determine the amount of calories we simply place an item of food inside, heat it to reduce it to carbon, and record the temperature rise of the thermometer. The temperature rise is how we actually measure calories. In fact, the definition of a calorie takes all this into account; i.e. a calorie is the amount of heat needed to raise the temperature of 1 gram of water by 1 degree Celsius. All this is very important to understand when caring for a diabetic. Only by realizing that the calorie is irrelevant in human nutrition, that the burning of anything from a nutritional standpoint is a fallacy, can we better care for our diabetics. The bottom line is that we need to be counting grams of carbs, not calories. Also, by focusing on calories and suggesting they be lowered, will often deprive the pt of important sources of fat & cholesterol in the diet.

With this introduction I will now move onto the questions for this week’s forum;

1)    What might you assume is causing the patient’s blood sugar variability?

We have here a 60 yo female suffering from diabetes for 8 years, stated as non-compliant, with concomitant diagnoses of CVA, HTN and depression; she’s also stated to be ‘maxed’ out on oral meds. My first encounter with this pt would consist of an in depth discussion with the pt about her diabetes, determine exactly why pt is experiencing difficulty with blood sugar control and ascertain how much her depression contributes to her ‘non-compliance.’ I put non-compliance in quotes because I have seen many a pt whose sole reason for non-compliance was a lack of understanding about their disease and not a voluntary attempt to disregard the advice of the physician or nurse.

I would also address the 2 other medical conditions (HTN & CVA) and discuss with pt that many people experience depression with having only one medical condition e.g. diabetes, but she is dealing with 2 more, greatly increasing her risk for depression. I would then add that many pts can get depressed from the simple act of taking meds on a daily basis; this increased risk of depression (& frustration) increases the more meds one has to take. It also needs to be ascertained exactly what type of CVA pt suffered and if (depending on area of brain involved) the location of CVA is contributing to depression e.g. deep limbic system, pre-fontal cortex, anterior cingulate gyrus, basal ganglia &/or temporal lobes. It should be noted that evidence based studies have shown antidepressants to be ‘modestly beneficial’ with ‘adverse events significantly more common.’ (Hackett, Anderson, House; Cochrane Database Syst Review 2008.)  Also, psychotherapy was shown to have ‘no evidence of benefit.’ (Ibid). Another trial revealed ‘that a care management program, which included depression education, antidepressant treatment guided by algorithm, and monitoring of therapy was more effective than usual care’ i.e. discretionary use of antidepressants. (Stroke. 2007;38(3):998) Further studies go on to state an ‘eight-week psychosocial-behavioral intervention plus antidepressant therapy was superior to antidepressant treatment alone.’ (Stroke. 2009;40(9):3073) With all this conflicting data it is easy to see why the treatment of depression of this pt that’s post-CVA can be a challenge. That said, a care management approach, which is exactly what these tutorial sessions are teaching us, appears to be the best approach.

After discussing with pt her individual med conditions and assessing where her knowledge base is at, I would then go over her medications with her, again asking what she takes and how she takes it. For my own edification, I also review the med list from a pharmacodynamic and pharmacokinetic perspective.

The med list appears to only list the diabetic meds and it immediately became apparent to me that meds the pt may be taking for her HTN or CVA could be contributing to her depression; for brevity’s sake I will only focus on the diabetic meds. The first med listed is metformin. This is a safer med for diabetics to take as its mechanism of action is to help increase a cell’s sensitivity to insulin and also decreases gluconeogenesis in the liver; this has the effect of more effective utilization of circulating insulin and diminished ‘dumping’ of blood sugar into the serum. This is a medication that does not (usually) cause a precipitous drop in blood glucose, so I can safely allow my pts to continue this drug when starting a low carb regimen. Both glimeprimide & glipizide are sulfonyl ureas and stimulate an already overworked pancreas to secrete even more insulin. As mentioned above, but it bears reiterating, this will have the effect of increasing insulin resistance (despite the package insert’s contradictory comments), increasing the likelihood of beta-cell burnout, increasing the intracellular production of both cholesterol & triglycerides (which directly increased cardiovascular morbidity & mortality), increasing cellular apoptosis via the use of the second messenger system, and slowing down and/or preventing weight loss by its inhibitory action on hormone sensitive lipase; this is not an exhaustive list but I will stop here.

Now the next 2 meds, Byetta and Januvia are an interesting combination and it appears the prior physician was using them for their complimentary actions. Januvia was the dipeptidyl peptidase type 4 inhibitor which interestingly enough,  would prevent the Byetta from being metabolized, allowing Byetta to exert its physiological effects longer (increasing glucose dependent insulin secretion, decreasing glucagon secretion, slowing gastric emptying…) As a side noted, studies have shown Byetta to reduce the HgA1c by 0.5-1%,( immediate release) to 1.5-1.9% (sustained release), which would reduce our pt’s HgA1c to 12.0 (sustained release), which is a negligible lowering of average blood sugar. In addition, post-marketing studies have shown increased risk of pancreatitis with Byetta use.

After review of her med list. I would immediately begin counseling on carb counting and would gauge pt’s motivation for starting. If I sensed she would seriously consider starting to lower her carbs, I would stop the glimepiride, glipizide, Byetta and Januvia.

I agree with the start of Insulin therapy, but I would need clarification of what ‘intensive insulin therapy’ means. The orders do not reveal if we are adding Insulin in addition to or are we eliminating any meds once starting insulin? These orders immediately reminded me of a study I read a few years back which suggested that tight HgA1c control (<6 .5="" 3="" about="" all="" am="" amp="" and="" answer="" as="" associated="" be="" better="" blood="" bolt="" came="" certainly="" death="" disease="" end-organ="" equates="" finally="" greater="" i="" in="" into="" less="" me="" morbidity="" morning="" mortality.="" of="" one="" over="" read="" regulation="" researchers="" sat="" seeing="" so.="" so="" study.="" study="" style="mso-bidi-font-style: normal;" sugar="" sure="" t="" taught="" that="" the="" this="" tissue="" to="" upright="" was="" wasn="" we="" were="" weren="" why="" with="" would="">the increased morbidity & mortality was not due to the tight control of the HgA1c
, it was due to all the meds the pts were on to get the HgA1c lower. The pt’s blood sugars were not being controlled through the correct way to eat, but through the use of these medications and the pts were suffering because of this.
Getting back to my pt, I would stop the meds as described and start solely on long acting insulin (assuming pt allows), and yes, using the pens makes it much easier (some insurances wont allow), discuss the importance of low carbs, and have the pt call my office on a daily basis with blood sugar results. Now some may immediately become concerned at me stopping 4 PO meds and starting on just long-acting insulin stating (correctly) that the pt’s blood glucose will almost certainly rise. That is correct, but it is OK. Hypoglycemia is more dangerous in the short term than hyperglycemia, so I’m ok allowing my pt to run a little higher as we figure out the correct dose of insulin. Another couple points about insulin. Once we take more than 20 units at once (some authors say 10 units), there can be erratic absorption so it is best to ‘split’ the dose above, say, 30 units; i.e. give 20 units SQ in one area and 10 units SQ in another. Also, we run the risk of creating more insulin resistance by using increasing doses of insulin; thus the pt runs the risk of developing type 3 diabetes. This is where metformin is helpful because it helps maintain insulin sensitivity.

In 1 week pt will return with both a sugar and food diary (remember she was in contact with me daily all week) and we will discuss the results.

As far as what’s causing the blood reading variability, it is because pt most likely received inadequate diabetic teaching (or more importantly, the incorrect diabetic training) and may possibly be ‘afraid’ to use the insulin; this is why it’s important to have pt come back with not only a sugar diary, but a food diary as well and we would want to ask exactly how she is taking insulin.

Looking at pt’s labs reveals a diabetic nephropathy as microalbuminuria is elevated with an elevated Cr. I would like to stress that the correct approach is to not restrict protein intake, but encourage increased consumption of protein, fat and cholesterol and to lower the carb intake. What is happening in diabetic nephropathy (as well as all the other end-organ damaging effects) is that the aforementioned non-enzymatic glycosylation is occurring at the glomerular level and this impairs the filtration mechanism of the nephron. This impaired filtering mechanism, with the subsequent increased proteinuria, is not from the consumption of protein, but from the overconsumption of sugar. Eating more protein will not create more kidney damage as is commonly thought. In fact it’s beneficial. I have seen microalbuminurias in the 100 range (highest 800) revert to normal upon eating the correct way. This is a reversal of the nephropathy. In addition, other end organ damage (eye and nerve) can also reverse when a pt begins to eat the correct way. A quick note about the lipid profile; the triglycerides are elevated. These will also lower once the pt lowers their carbs and begins to eat more fat, cholesterol & protein.

2)    What would your next steps include in care-managing this pt?

A full discussion of diabetes including the correct way to eat; recommended reading: my favorite is Dr. Bernstein’s Diabetes Solution by Richard K. Bernstein (2007).; I would have anyone on my care management team read this book and keep it as a handy reference; training of my support staff as to the correct way to eat for counseling our pts….

I have so much more to say, but I think this is a good primer for continued study J