HNF-4α controlling many genes involved in liver function such as the GLUT2 and L-PK genes.
Evidence on the mode of action of metformin shows that it improves insulin sensitivity by increasing insulin receptor tyrosine kinase activity and enhancing glycogen synthesis in hepatocytes, and by increasing recruitment and transport of GLUT4 transporters to the plasma membrane in adipose tissue. In addition to its effects on hepatic glucose and lipid homeostasis and adipose tissue lipid homeostasis, metformin exerts effects in the pancreas, vascular endothelial cells, and in cancer cells.
Diabetics all differ from person to person because everyone has to take various things into consideration such as weight, height, health and family medical history as well as their gender, males may need more of a calorie intake to get through the day versus a female and an elderly person who doesn’t get much exercise may be able to get through the day with a lower blood glucose reading than one that gets out and about all the time and is really active.
It is hard for some doctor’s to pinpoint what a normal range for blood glucose may be or for a normal range fasting blood glucose but for many they throw it all out there and have a standard chart that they go by, which is standard normal range for everyone. While diabetics need to be careful and monitor their normal range for blood glucose levels carefully and make sure that they don’t get hypoglycemic, which is low blood sugar and can cause hunger, fainting, shaking, etc. Healthy people, diabetics and everyone else needs to monitor for a normal range cholesterol. By keeping yourself healthy so that you can have a normal range cholesterol and also a normal range for blood glucose is an important part of living a long and healthy life. What is the difference between type 1 and type 2 diabetes (and what if I don't fit either type)?
As you can see in the preceding graph, every day starting at about 3am this person’s glucose levels started to go up.
One colourful term for the liver’s tendency to release glucose into the blood overnight is a liver leak.
Rebounding (the so-called Somogyi phenomenon) is commonly cited by diabetes health care practitioners as a cause of high morning blood glucose readings. Gee, I could get writer’s cramp listing every possible cause for erratic blood glucose readings. It is important to be aware that A1C levels are measured in different units and on a different scale than is blood glucose; hence an A1C level of 7 is not the same as saying that your average blood glucose is 7. Typically, type 1 diabetes in children, adolescents or teenagers and require immediate institution of insulin. Typically, type 2 diabetes develops in middle-aged or older persons who are overweight and can – at least initially - be managed with lifestyle therapy and non-insulin medications. There are also a large number of adults who, based on their age (and, often, based on their body size) are thought to have type 2 diabetes, but who don’t get their blood glucose levels down despite usual therapy with lifestyle and non-insulin medications and, soon after diagnosis, require insulin therapy.
One helpful way to distinguish type 1 from type 2 diabetes is to do a blood test for a special protein called a GAD antibody.
As you can see, if you have type 2 diabetes then at the time you were diagnosed your pancreas was only making ½ of the insulin it was supposed to and, as time passes, it progressively loses more and more of its ability to make insulin. If you have type 2 diabetes and are on insulin therapy you still have type 2 diabetes, not type 1 diabetes.
ACE inhibitors and ARBs (I list the various types below) are medications that were created years ago to help control high blood pressure, but medical research subsequently discovered that even if a person with diabetes does not have high blood pressure, taking an ACE inhibitor or ARB will still reduce the risk of having a heart attack or stroke if you are at high risk for these complications. Statins are medicines that improve cholesterol levels in your blood and they do this very well indeed. The real story is that the number, size, and density of cholesterol particles in your blood (LDL-P and HDL-P) are far better predictors of heart disease risk. The best way to measure your heart disease risk through LDL cholesterol is to measure the number of LDL particles in your blood, or LDL-P, which you never get checked unless you have a fancy test called a lipid nuclear magnetic resonance test – or NMR test for short. You can look at particle size.  As a general rule (this is NOT always the case, however), the larger the LDL particles, for a given LDL-C, the fewer the particles (which is what we want).
Below is graph of my overall change in changes in HDL-C, LDL-C, and TG, along with the ratio of my TG to HDL-C, based on the “standard” cholesterol panel.


As I stated above, a better marker of risk with respect to LDL is particle number, LDL-P – the fewer particles, the better; and you can estimate this by measuring particle size, or through concentration of ApoB.
Unfortunately, I only started doing regular VAP testing about a year ago, over one year into my “experiment” of progressive carbohydrate restriction.  Hence, I can’t show my progress as longitudinally with VAP as I can with standard cholesterol testing.
Below is figure showing the change in my VAP panel over a seven month period, between January and July 2011. Keep in mind how my diet changed between January and July – I reduced carbohydrate intake from approximately 150 grams per day of “good” carbs to less than 50 grams per day.  I also increased, dramatically, my intake of fat, including saturated fats. Despite the amount of time I’ve expended on explaining all of these nuances of “cholesterol” numbers, I am not entirely convinced that I am healthier today because my cholesterol numbers are better.  I wonder if I’m healthier today because of something else, and that whatever else is making me healthier is also correcting my cholesterol problem? If I had to guess what is really making me healthier today, besides being less fat, I believe it is the combination of how sensitive I’ve become to insulin and how much less inflammation I have in my body, especially in and around my arteries.
As I mentioned above, findings #1, 2, and 4 are almost universal in folks who abandon carbohydrates, while finding #3 is somewhat variable. Which of these is most important?  This is an obvious and important question, but one I don’t really know the answer to (nor does anyone else, for that matter).  If I had to guess, I believe observation #4 is the most important because insulin resistance is the underpinning of metabolic syndrome. People have said things to me like, “Well it’s great that you’ve reduced your risk of all diseases associated with metabolic syndrome, but wouldn’t it be funny if you got hit by a car tomorrow!”  All kidding aside, this misses the point. Another exenatide-related drug is Bydureon® which is a once-a-week injectable form of exenatide. A more recent addition to the GLP-1 receptor agonist family of diabetes drugs is Trulicity® (dulaglutide) manufactured by Eli Lilly and Co.
Additionally, it has been shown that metformin affects mitochondrial activities dependent upon the model system studied.
The latter effects of metformin were recognized in epidemiological studies of diabetic patients taking metformin versus those who were taking another anti-hyperglycemia drug. High cholesterol can stem from many things such as eating too high fatty foods, too much grease, too much junk food, etc.
The dawn phenomenon is the rise in blood glucose levels in the dawn (that is, the morning) due to excessive release of glucose from the liver into the blood.
This individual, like so very many others living with diabetes who have high blood glucose levels first thing in the morning, blamed themselves and attributed their elevated morning blood glucose to having overeaten or snacked the night before. Not so! This is particularly likely to be the case if you are taking NPH insulin at supper or Levemir insulin (only) in the morning. If you are rebounding it means that you had a very low blood glucose overnight, slept through it, and your liver poured out so much glucose into your blood to bring your blood glucose back up that it ended up making too much and overshot the mark and as a result your blood glucose was high when you awakened.
The idea is that a certain amount of carbohydrates is likely to raise your blood sugar level by a predictable amount and thus, you can take an amount of insulin proportional to your carb intake to prevent this rise in blood glucose from occurring.
Indeed, there are many middle-aged people who develop type 1 diabetes and there are increasing numbers of children who develop type 2 diabetes. Such people often have a form of type 1 diabetes called LADA (Latent Autoimmune Diabetes in Adults). This antibody is almost always present if a person has type 1 diabetes and is almost always absent if someone has type 2 diabetes.
Well, often it doesn’t, but there is at least one situation where it does; that is, the instance where a person with LADA is unsuccessfully treated with oral medicine after oral medicine in a fruitless attempt to control their blood glucose levels when what they really need is insulin! Well, there are two: what can I actually measure that predicts my risk of heart disease, and how does diet affect these these things I can measure? Basically it’s a test to measure how much insulin a person needs to keep their glucose level constant, despite the addition of glucose.  The less insulin one requires, the more insulin sensitive one is. Metformin has a mild inhibitory effect on complex I of oxidative phosphorylation, has antioxidant properties, and activates both glucose-6-phosphate dehydrogenase, G6PDH and AMP-activated protein kinase, AMPK.


The usual best way to deal with the dawn phenomenon is to take a dose of NPH, Lantus, or Levemir insulin at bedtime. There is always a reason for erratic blood glucose levels and if you’re having this problem, you and your health care providers need to play Sherlock Holmes and find out what is the cause!
But if stress is part and parcel of your life (as it is of so many lives) your blood glucose levels can still be well controlled so long as your treatment program is tailored appropriately to your needs. Therefore, even if you aren't yet at the target A1C (and indeed even if you never reach target) it is important that you know that any reduction in your blood glucose (and, hence, your A1C) will substantially reduce your risk of diabetes damaging your body.
But, if you don't keep a log book then you are not going to be able to recognize trends and patterns in your readings. Carbohydrate counting is essential if you are using an insulin pump and is often of major value if you are taking injections of rapid-acting (Humalog, NovoRapid, Apidra) before meals; especially if you have type 1 diabetes. The importance of AMPK in the actions of metformin stems from the role of AMPK in the regulation of both lipid and carbohydrate metabolism (see AMPK: Master Metabolic Regulator for more details).
If that number gets too high then you are putting yourself in harm’s way and taking the chance or risks of a heart attack or stroke. If you are already taking one of these insulins at bedtime then it may be that your dose needs to be adjusted.
Except that recent medical studies suggest this doesn’t actually happen and that rebounding doesn’t even exist! If you are able, try to have a straight shift (regardless whether this is days, nights, or something else). So if your A1C was 10 and you get it down to 9 pat yourself on the back; you've just reduced your risk of eye and kidney damage by almost 40%! Speak to your diabetes educators (in particular, your dietitian) to see if this would be a helpful technique for you.
In adipose tissue, metformin inhibits lipolysis while enhancing re-esterification of fatty acids. My strong expectation is that within the next few years we will have conclusive evidence for the non-existence of rebounding. If this is not possible, your blood glucose control can still be maintained but your insulin schedule may need to be overhauled.
It reveals the patterns and provides the clues as to what changes to make to your therapy, be they dietary, insulin or otherwise.
The activation of AMPK by metformin is likely related to the inhibitory effects of the drug on complex I of oxidative phosphorylation.
My preferred strategy for my patients with type 1 diabetes who perform shift work is for them to use an insulin pump or, failing that, using Lantus (or Levemir) insulin once daily (given at the one time of day they are always certain to be awake) and a rapid-acting insulin (Apidra, Humalog, or NovoRapid) before meals (whenever those meals happen to be for a particular shift).
A log book is not meant to simply be a historical record and it is most definitely not a report card. This would lead to a reduction in ATP production and, therefore, an increase in the level of AMP and as a result activation of AMPK. It is an interactive tool to assist you in deciding how much insulin to give every time you are due for an insulin injection. In fact, since the cells of the gut will see the highest doses of metformin they will experience the greatest level of inhibited complex I which may explain the gastrointestinal side effects (nausea, diarrhea, anorexia) of the drug that limit its utility in many patients.



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Comments

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    Author: PLAY_BOY
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  4. 12.09.2015 at 15:27:18


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