Ketosis

I’ve talked about Ketosis in a number of posts and I felt that a little bit more clarity of this key metabolic process was necessary. More so, since there are a number of ignorant health care providers, who get scared of the term, and will pass on their ignorance and their fears to us. If you will care to note, everywhere I’ve mentioned the term, I’ve referred to it as “Nutritional Ketosis”. That because, Nutritional ketosis is very different to “Ketoacidosis” which is what many would confuse this state with - mostly doctors (yes doctors). So let’s look at what is so different between them and why Ketosis is such a beneficial state for us to be in.

Our chemical energy is derived from the substance known as ATP (adenosine triphosphate). ATP is mostly produced and used in a metabolic pathway known as The Citric Acid Cycle or The Kreb’s cycle. This process takes place within our cell mitochondria. To do that, first, our macro nutrients must be broken down into a 2 carbon fragment known as acetyl CoA or Acetyl Coenzyme A. This acetyl CoA can be derived from Carbs (glucose), Proteins (amino acids) or Fats (fatty acids). However, the pathways of converting either of these into ATP are quite different and unique from each other. And so are the consequences.

In the absence of glucose to be used as energy, our liver starts to break down free fatty acids into ketones. These are eventually converted into the acetyl CoA, and further into ATP. This metabolic process is known as beta-oxidation. When we use this process (beta-oxidation) for deriving energy, naturally, some ketones are found floating in blood plasma, and also in urine. The body only has a 24 hour store of glucose and therefore, this is nature’s way of ensuring survival by utilizing stored fat in times of exigency. This is Nutritional Ketosis, and we try to deliberately induce it for gaining control on Blood Sugar, Obesity, Hypertension, Cholesterols and what not.

What ignorant doctors confuse this with is Diabetic Ketoacidosis (DKA). DKA is a life threatening diabetic condition for insulin dependent patients. In this case, if the patient does not receive adequate insulin, the body goes into a starvation mode, and starts to use ketones for energy. Same as in ketosis, BUT, the absence of insulin, allows for a continuous production of ketones, without stopping. Eventually, the cascading process goes out of hand, and the blood acidity levels rise to critical. If the situation is not corrected within time, the person will tend to go into a coma or death may result. This is not possible in people who can produce even small amounts of insulin.

So, on the one hand of the spectrum lies, controlled benign Nutritional Ketosis and on the other extreme is DKA. But do not ever confuse the two. Such extreme outcomes are true of any process, metabolic or not. Nutritionally, it is even possible to die with an abnormal excessive consumption of water. DKA is not possible unless you are a diabetic, only dependent on exogenous insulin, have excessively high blood sugar levels, and lack the insulin dosage as and when required. Any other aberration our body corrects preemptively. After all it likes balanced homeostasis.     

Glucotoxicity

In a recent mailer, I referred to the term – “glucotoxicity” and left it at that, without offering any further explanation. Literally, it would mean – the damage (or extent thereof) arising out of the poisonous effect/s of glucose (breakdown). Surely, in times to come, we all will hear a lot of this term, at least I hope that we do. And I do hope that after reading this post, you will take it more seriously and think about how much of it you are willing to tolerate.

Glycolysis, the breakdown of glucose, for conversion to ATP (adenosine-tri-phosphate) takes place in the cell cytosol (fluid within) & partly within the cell mitochondria. The process of the actual breakdown & conversion to newer substances creates by-products which are toxic (poisonous). Yes, you read it right. Glycolysis results in the formation of a glucotoxic substance known as methylglyoxal (hereinafter MG).

That MG is toxic is a non issue. Everyone agrees on that. MG can find its way into the body through many sources. MG in the body exists within cells (as above) and in blood circulation. MG in serum (blood) is tolerable to certain extent, as is the case with most toxins. It’s the intracellular MG that we are concerned with here. That is the problem.

A recent study showed the directly proportionate link between levels of blood glucose & MG. This was not an observational or associative study, but relied on direct measurements of the stuff to propose the relationship. So in other words it proved that if your blood glucose levels were higher, your MG levels were higher as well. Diabetics, are you listening ? It also found that levels of MG were much higher in Type 1s than that of T2s. Probably poor control & roller coaster fluctuations were at the root of this observation.

The way I see it, the best inference to be drawn from this is that using medication or artificial methods to control BG may give us the good numbers & “control” but it is the dependence on glucose that still remains the problem. Sure enough, anyone relying on glucose for energy is making a lot of MG & that is bad news.

Non diabetics, where do you see the harm in this approach for yourself. Your systems are the same as ours. Metabolize a lot less glucose & save yourself from the harmful effects of MG, and who knows what else. We should all be thankful that an alternate energy system does exist, which has none of these terrible side effects. Yes, KETOSIS, where ketones are consumed for energy from fatty acids.

Almost 95% of the body cells can rely on ketones and are quite happy making that switch. The other 5% (RBC, some nerve & brain cells) can find their glucose from many sources other than carbs. The liver is very happy doing that service for them. So keep a close watch on your glucose throughput – the sum total of glucose being used up within the body. Make ketosis your dietary focus.         

BG Testing

When diagnosed as a diabetic, it becomes mandatory to test your blood sugars at various times during the day. Ideally the tests should be carried out when (1) Fasting (FA) the first thing in the morning upon waking up. (2) Before meals (BL/BD) (3) Postprandial or after meals (PL/PD) (4) Before and/or after exercise (EX). (5) Randomly (RA) during anytime in the day.

I keep getting a lot of queries on BG tests, testing methods and related questions. I'll try to throw light on some of the things that are important and should be kept in mind during testing. Obviously, testing has to have purpose. Even a cheap home test should tell you something that you want to know. It must reveal some meaningful insight into your 24 hour BG profile.

First, let's begin by talking about meters. There are many companies who have introduced scores of meters in the market. This business is also gaining momentum like the cell phone business, with companies introducing newer models every few months. With an ever expanding consumer base the business is now worth billions of dollars. By law, meters are allowed to be +/- 20% off accuracy. A more accurate system would be cumbersome to manage in terms of size and costs. Hence we make do with the next best. At least meters now are very handy, inexpensive and some Nano models can be carried around in the pocket. But, meters can only keep you informed of your BG “range” and not the exact number at a given time. As the BG level rises, so does the error margin in the accuracy.

Laboratories test for BG out of the blood plasma. Plasma is the watery part of the blood, while home meters test the “whole” blood, which consists of the plasma + everything else (mostly red blood cells). Science tells us that there is a difference between BG of the plasma & BG of whole blood. Some estimates put this at 20 mg/dl, others at 12%, but my feeling is that even this difference varies at differing levels. The inbuilt software in the meter converts your whole blood reading into the plasma BG and then displays it. Since the circulating blood within the body is not homogeneous, the BG number from different parts of the body will also differ. Try taking two readings from two different fingers, one from each hand and see the difference for yourself. BG also changes from moment to moment, it is not a static number, as with all the other health parameters and markers in the body.

Strips are coated with reagents and these are also highly susceptible to corruption by the environment, especially heat. Keep them in a cool place in the house, but not the refrigerator. The meter that I use works by checking for the color change in the strip with IR light before and after the blood is applied and calculating the BG based on the color change. Use strips before the end of expiry date, but sometimes they do work pretty well even beyond.

Wash your hands before every test. Doctors may use an alcohol swab to wipe your finger before pricking, but soap and water works just as fine. If you are the only user of your “lancet” (the pricking device) there is no need for the needle to be changed very frequently. Sometimes I forget to change my needle even after months of use. After extended use the needles do tend to get blunt and will tell you when it is time to change. Do not use your needle for anyone else and do not use the needle used by anybody else. Do not starve the strip for blood. Give it the drop of adequate size. If you have difficulty in getting a good blood flow out of your fingers, try snapping them a few times before the blood draw, or try jerking the hand rapidly, a few times before the prick.

Coming to the tests themselves, as I wrote above, every test ought to have a purpose. Let me tell you how, what and why I tested in the initial stages of my diabetes education. I would test (1) FASTING (the first thing upon waking up) (2) BEFORE every meal to know if I had reached my base line BG before I put any food in my mouth and make it go up again. (3) AFTER meals I would test at 30, 60 & 120 minutes to see what “that” food was doing to my BG. For that I usually had to limit food menus to a single item or a combination of max 2 things at a time. (4) I would check for the effect of EXERCISE on my BG before and then 30 and 60 minutes after the work out. I would check for different forms, duration and intensity of exercise. (5) I even checked the various combinations of foods and exercise put together. (6) Sometimes I checked at RANDOM times just for the heck of it.

If you can predict your BG to within +/- 3 points, it means that you are getting a hang of your own system and becoming your own master bit by bit. When testing like that, it would be quite OK to carry out 15-20 tests a day. “Obsessive” for sure, but you must know your system, before you can begin to treat it. Once enough data has been collected and your BG profile becomes predictable, you need not test aggressively anymore.

If you happen to test like that, you will need a good spreadsheet or logging system to record all that data. Because you have to collate it and then analyze it, for it to have any meaning. If any of you need, I could send you a sample of my excel sheet to help you further.

The take home lesson from all of this is that "The meter is your best friend". It will answer most of your questions. If you want to take control of your blood sugar & take charge of your life, "test, test, test."

Diabetes

The precursor to diabetes is defined as IGT or Impaired Glucose Tolerance. As the name suggests, in this condition, the body is unable to "tolerate" glucose, and cannot metabolize it in a "normal" manner. The glucose therefore remains in circulation and the result is elevated Blood Glucose (BG). So Diabetes can be thought of as an advanced "beyond the IGT stage" of dysfunctional glucose metabolism. There are many types and forms of diabetes. Unfortunately, in India, many doctors are unaware of some of these types, and often end up with a mis-diagnosis. This can be dangerous because each type has it's own cause, effect and requires a different treatment approach. Treating every diabetic case, the same way without proper investigation, could have drastic consequences. Let's briefly look at each type & their characteristics.

Impaired Glucose Metabolism : The presence of glucose in the body, requires the pancreas to secrete the hormone insulin. Insulin is more particularly secreted by the beta-cells of the "islets of Langerhans" located in the pancreas. The secreted insulin, acts as a carrier for the glucose, and supplies it to all of the body cells, to be used as a source of energy. When there is a malfunction of this normal metabolic process, the pancreas reduce or completely stop creating and secreting insulin. Alternatively, there is some or normal secretion of insulin, but the cells become Insulin Resistant, and refuse to accept the insulin, and in turn the glucose that it is carting. In either case, or even in a combination of the above scenarios, the glucose remains un-utilized and circulating in the blood. This causes the BG (Blood Glucose) to rise and remain elevated in affected individuals.    

Gestational Diabetes (GD) : This is the type of diabetes that strikes about 8-10 % of women during pregnancy. The treatment could include preferably insulin or oral pills if the BG (Blood Glucose) does not normalize. High blood sugar in the mother is very dangerous for the growing fetus, as it depends solely on the mother's blood supply for its own nourishment. Usually GD resolves soon after the delivery on it's own. Once the big "D" rears it's ugly head during pregnancy, the woman can be considered to be at potential risk for getting the full blown version later in life. Even the babies born from such pregnancies are considered to be susceptible to the disease during their lifetime.

Type 1 Diabetes (T1) : is also known as Juvenile Diabetes, because it usually strikes during the childhood years. This is an Auto-Immune disease, in which the Auto Immune System of the body, malfunctions and causes the onset of T1. Usually the afflicted children come under some kind of viral attack. The make up of the virus/es is similar to that of the beta cells of the pancreas. In a case of mistaken identity, the auto immune system not only attacks the invading virus but also the pancreatic beta cells. The attacked beta cells degenerate and are not able to make and secrete insulin for the remainder of the life cycle. T1s have therefore to rely on exogenous insulin injections to survive.

Type 2 Diabetes (T2) : This form of diabetes is also known as Mature Onset diabetes and normally strikes a person in the middle ages - mostly after the late 30s. This form of diabetes is more common and is mostly a combination of reduced insulin secretion capacity and (IR) Insulin Resistance. Where and which cells within the body have IR and to what extent, determines the person's diabetic imprint, and response to therapy. In majority of the cases, the BG can be well managed with lifestyle changes and sometimes oral medication. In extreme cases, a combination therapy or exclusive use of injected insulin is advised.

Type 1.5 (LADA) : Off late, 2 mid-way strains of diabetes have evolved. These forms of diabetes are understood to lie between T1 & T2, and therefore designated as T1.5. LADA stands for "Latent Auto Immune Diabetes in Adulthood". LADA, is also an Auto-Immune disease, but it lies dormant during childhood and begins to appear only late in life. In simpler words LADA is T1 appearing in adult years. As opposed to T2, these persons also cannot secrete any insulin just like the T1s and have to depend on exogenous insulin to manage BG.

Type 1.5 (MODY) : Just like LADA, this is a variety thought to lie in between T1 & T2. MODY stands for "Mature Onset of Diabetes in the Young". These cases are that of young people getting afflicted by T2 diabetes very early in life. They suffer from part faulty insulin secretion and part IR just like the T2s. Most cases can be managed by lifestyle changes and oral medication. In some rare cases insulin needs to injected. Due to their young age, these type of patients can many times cause a dramatic reversal of their conditions, provided that their lifestyle and/or medical intervention is maintained. An increasing number of youngsters have been joining the MODY group off late, indicating the fast pace at which diabetes variants are spreading in the global population.

Symptoms : There are many ways that high blood sugars start to show up. The most common symptoms are  - excessive thirst and urination. Small wounds not healing well. Fungal and yeast infections on the body. Problems with visibility. Sudden unexplained weight loss. Sensations like hot/cold/tingling/pain or fatigue in the legs and/or hands. Many times there are no symptoms at all. High diabetic levels of blood sugar appear only after years of metabolic damage within the body. After the age of 35, it is a good idea to keep an annual check on your blood sugars.

Diagnosis : In India BG is measured in mg/dL or milligrams per deciliter. Normal levels are 60-100 mg/dL at fasting (morning) or before meals and Postprandial (after meals) levels of 140 mg/dL at 2 hrs after meals. Though all efforts should be made to keep the PP numbers at 140 at 1 hr & 120 by 2 hrs. Fasting readings of 100-125 mean that your metabolic challenge has started and it is time something should be done about it. Doctors may make one undergo an OGTT - Oral Glucose Tolerance Test. A sugary drink containing 75 gms of glucose is to be had and the blood sugar levels are checked over time. At 1 hr one should be below 200 mg/dL & at 2 hr below 140 mg/dL to escape the Diabetic tag. 

Insulin is bound with another pancreatic protein secretion known as C-peptide. Insulin secretion capacity can be evaluated by measuring the levels of C-peptide in the blood. T1s & T1.5s who are under constant attack by their Immune system also have antibodies in their blood. These are known as GAD antibodies, and the GAD-65 antibodies test can determine their presence. These tests help in better type determination.   

For diabetics, I'd recommend reading from our site www.diabetic.pub

Insulin Resistance

On the previous post we touched on Insulin Resistance (IR) a little bit. On a blog devoted to metabolic disorders, IR is too important a subject not to have its own independent post or page. IR is of critical importance as it is the primary cause of weight gain & Obesity and has strong associations with chronic diseases like Diabetes, Hypertension and Coronary Heart Disease (CHD) and many many more. But there is much more to IR that is important to us. IR as a subject is very vast to be covered fully under the scope of this post, but nevertheless let’s take a very brief look into some aspects.

As the name suggests, IR basically means that the cells of the body become resistant to accepting the circulating hormone Insulin. That is a cause for concern, as Insulin’s primary role is to cart the glucose in the blood supply and deliver it to the cells for further metabolic processing and conversion to energy (ATP). So with IR the blood glucose starts to remain underutilized & gets elevated. This signals the pancreas to release more Insulin as it sees that glucose levels are still high. This only compounds the problem. IR also means that Insulin itself remains in circulation for extended periods, and causes its own harm. It is definitely a pro inflammatory hormone and causes the advent of chronic low level inflammation within the blood vessels. You can imagine the consequences of chronic inflammation within your vascular system.

To understand IR better, let’s first look at the action of Insulin, or at least actions that have been studied and understood till now. Insulin primarily (1) delivers glucose to the muscle tissue to be converted to ATP and used as energy (2) encourages the conversion and storage of glucose into glycogen by the liver and discourages its release back into the blood as glucose. (3) pushes glucose into adipose (fat) cells to be stored as fat (that is how weight is gained) AND blocks its release and use as energy.

Now, with IR the above three roles of Insulin get blocked and the resulting consequences would be something like this.

1.   If insulin resistance is strictly of the muscle tissues, insulin and sugar will both rise. Since the liver is still responding normally to insulin, glycogen stores will be filled from the ample glucose in the blood based on the "signal" of the also elevated insulin in the blood. When the muscles - which are starving not because the glucose isn't circulating right in front of them but because they cannot utilize it - signal that they are starving and need glucose, the liver (still responsive) can respond with additional glucose from its ample glycogen stores. This further elevates blood sugar, especially after long periods of fasting and at dawn. Exercise would play a critical role in controlling blood sugar & circulating insulin levels as it would strike at the core problem.

2.    Hepatic (liver) IR will lead to the over production of glucose by the liver. Recent studies indicate that this seems to be the larger problem with Type 2 diabetics, as the pancreas is still able to generate some Insulin. Because of IR, the liver doesn't get the signal from the pancreas to stop glucose production. For the type 2 diabetics, the liver dumps far too much glucose into the blood stream than for a non-diabetic both in the post-meal and in the fasted state. And in either 1 or 2 if the fat tissue is still responding normally to insulin, weight gain which is very "stubborn" and difficult to reverse - is the obvious result.

3.   Scenario 3 is true for mostly leaner people with metabolic disorders. In diabetics mostly Types 1 or LADA suffer from this kind of IR. These types of people would suffer from elevated glucose but not lose or gain weight easily. In either of scenarios 2 & 3 exercise will not help much unless the timing & type of exercise has been carefully thought out.

It is highly unlikely that IR will strike in either of the scenarios in isolation. In all likelihood it manifests as a combination of two or all three of the above. Assessing what type/s of IR affects one, can only come about by a lot of self testing and observation, or possibly through carefully timed/devised serum insulin tests. Once the type and quantum/stage of IR is understood, devising a plan for resolving the metabolic challenge is possible.

3 studies on centenarians (100 year + old persons) could not find much in common amongst them. They have high cholesterol and low cholesterol, some exercise and some don't, some drink / smoke, some don't. But they all have low sugar, for their age. They all have low triglycerides for their age. And they all have relatively low insulin. Insulin is the common denominator in everything associated with poor health. High Insulin levels are found in people suffering from obesity, hypertension, diabetes, osteoporosis, cancer etc. The best way to treat virtually all the so-called chronic diseases of aging is to treat insulin itself. And is there any better and safer way to do it, than “Nutritional Ketosis”. I doubt it.

Blood Sugar

Everywhere on the blog we’ve referred to Blood Sugar as (BG) Blood Glucose, which is the more technically correct term. Table sugar as we know it consists of glucose + fructose in equal measure. Glucose is metabolized in all the cells of the body, fructose though is metabolized only in the liver. It is the glucose that circulates in the blood, hence BG. I use the term blood sugar here, because of it’s popularity among the general public.

Of all the general health parameters, Blood Sugar is probably THE MOST IMPORTANT one. Other parameters like weight, BMI, temperature, cholesterol or blood pressure pale in comparison as health indicators. Blood Sugar should be ideally kept within a narrow 30-40 point limit (80-120 mg/dl) throughout the entire day. Glucose concentrations in blood beyond 20 points on either side of the range are fraught with dangers. It disrupts the homeostatic (balanced) metabolism and that can give rise to all sorts of problems and disease including cancer. Barring traumatic accidents or inborn genetic disorders, all health issues begin with a dysfunctional metabolism, hence it’s value as an indicator.

Wellness practitioners often use analogies in explaining body function and processes, especially to those who do not possess a scientific disposition. It is one of my favourite tools as well. I use the firemen analogy to explain the irrelevance of cholesterol (on it’s own) as a cardiovascular risk factor. A fire naturally requires firemen to come & douse the fire. It is natural to expect a few of them to lose their lives, every once in a while. Where there is fire, there are bound to be firemen. But are they to be blamed for starting the fire? Such is the relation between cholesterol & cardiovascular problems. I also liken drugs that suppress symptoms to cutting off the red warning lights on your car’s dashboard. Symptoms are like those red warning lights that indicate problems within the bonnet. Getting rid of the warning light is not really the right therapeutic approach. When drugs are required, they are, but most times they do not serve purpose, and are prescribed with gay abandon, without so much as a thought to their side effects & other consequences.

To explain the glucose metabolism and blood sugar related issues I came up with an analogy that I would like to share with you. Let’s use a BUSINESS model to understand this one. Imagine RAW MATERIALS being used by a FACTORY to manufacture a PRODUCT. It then requires a WAREHOUSE to store the product until it is released in the market. Suppose this business uses a door to door model and thus employs many SALESMEN to distribute / deliver the product to its CONSUMERS. If the business were to misjudge the product’s demand and keep on over producing it, very soon there would be a GLUT in the market. Consumers would point blank refuse to have any more of it. Salesmen would be roaming with unsold stock, getting frustrated in the process, and would start to negatively affect the business. If this keeps up for long, a total COLLAPSE would follow and the business would have to shut down.

Now in the above scenario replace the capitalized words as follows ;

You (BUSINESS),

Carb rich food (RAW MATERIALS),

Digestive system (FACTORY),

Glucose (PRODUCT),

Liver (WAREHOUSE),

Insulin (SALESMEN),

Cells (CONSUMERS),

Insulin Resistance (GLUT) &

Metabolic Syndrome (COLLAPSE).

Get the picture ? 

Insulin

I was recently invited to give a talk to a group of savvy corporate youngsters which was titled as "The Healthy Weigh of Life". The latter half of the title was chosen because the group consisted mostly of women, eager to shed a few kilos and inches. The spear-head of the talk was high carbohydrate consumption and its proportionate Insulin response within the body and subsequent problems. I called Insulin the “nectar of life”. Insulin, and its action are the titles of many a voluminous biological textbook. But here we are looking at the hormone in a snapshot review. For those who were not present, here’s what I meant.

Insulin is secreted by the (beta) b-cells within the “islets of Langerhans” - a region of the Pancreas. They are so named because of their discoverer Dr. Paul Langerhans. Apart from the b-cells, the islets also contain (alpha) a-cells & (gamma) g-cells which have other secretions which we will not go into at this time. The secretion of Insulin begins as soon as any food is ingested, probably even before that with the smell, sight or thought of food.

Insulin’s preliminary role in carb, lipid and protein metabolism is that of distribution and storage. That is why it is so essential to life. Primarily it distributes glucose to target cells for energy metabolism. Beyond that it encourages the storage of glucose as glycogen and also its further conversion to triglyceride and storage as fat in adipose tissue. In fact it is the primary regulator of fat deposit in the body. On a lesser scale it also plays a role in the storage of several key minerals in the body. These events are essential for normal growth and development and for normal homeostasis.

Once at the target site insulin signaling & reception results in a large array of biological outcomes. Understanding these mechanisms and pathways is the subject matter of a large number of studies under way. These studies could lead to a better understanding of the pathophysiology of insulin resistance which is associated with obesity and type 2 diabetes. Insulin Resistance is dealt with in more detail on the next post, but it should be said that Insulin is also a pro-inflammatory hormone. Excessive amounts of Insulin could therefore result in abundance of free radicals which cause extensive damage wherever and whenever they get a free run.

In my humble opinion Insulin is certainly the hormone of life. It is a sort of time keeper of our metabolic age. Because we have become so accustomed to a carb loaded diet, we use more and more of Insulin on a daily basis & that is why we are ageing much faster. After all AGE (advanced glycation end-products) is the cause of age. For confirmation all you need to do is compare the advent of puberty in children these days with that of 30-40 years ago. And that is why I say that the “Fast Food” label is a half-truth. Not food but certainly fast. So to live a longer, fuller & healthier life watch your Insulin. Keep the clock ticking slower & longer. After all THE IDEA IS TO DIE YOUNG AS LATE AS POSSIBLE.     

Healthy Regards.