There is still no evidence to declare superiority of rapid-acting insulin analogues in the treatment of type 1 diabetes. These studies compared either insulin aspart (NovoLog) or insulin lispro (Humalog) with human insulin; no such study was available for glulisine (Apidra).

Based on average HbA1c values, patients treated with NovoLog had lower levels. However, statistical comparisons were so small that an effect on patients' health is not to be expected. It was also hypothesized that Humalog may prevent night time lows better than Apidra.

Even though patients have been treated with insulin analogues for 10 years, it is still unclear as to how these types of insulin affect long-term complications of type 1 diabetes. The long-term effects of insulin decisively increase the risk of heart disease and cancer, according to recent studies at Howard Hughs Medical Institute. Would you be surprised to learn that one of the insulin analogue manufacturers chose to withhold some of the results of their studies?

When blood sugar is falling, the stopper built into the body is the release of glucagon from the alpha cells of the pancreas which stimulates the release of glucose from the liver (but only if your adrenaline is flowing). However, when hypoglycemia is due to injected insulin - the stopper isn't entirely in place. Scientists explain how epinephrine (adrenaline) plays a major role in regulating glucose in times of low blood sugar and how this response could be adversely affected by the use of beta-blockers.

During insulin-induced hypoglycemia in dogs, the roles of adrenaline and glucagon were evaluated. The dogs fasted overnight to remove excess glucose from the blood. The dogs also had their adrenal glands removed. The adrenal glands are the source of adrenaline. Adrenaline is released into the bloodstream in response to physical or mental stress,to initiate the stimulation of glucose, among many other functions. Adrenaline and insulin were released at two different rates: a basal rate or a variable rate to simulate an adrenaline response. When the blood sugar fell to 42 mg/dL, the dogs in the basal rate group failed to release glucagon, but the simulated adrenaline response group increased normally. The liver response to releasing glucose fell in the basal group but increased in the simulated adrenaline response group. The researchers conclude that adrenaline must be responsible for this critical response to insulin-induced hypoglycemia.

Beta blockers are a common class of prescription drugs that counteract the stimulatory effects of adrenaline. Diabetics who inject insulin and take beta-blockers should be extra cautious of hypoglycemia. Hypoglycemic unawareness is already established for diabetics injecting GM insulin (genetically modified human insulin). Given the side effects of beta blockers, there is greater reason to be more aware of hypoglycemis unawareness -- yes, oxymoron. Those individuals who are on the brink of diabetes should avoid beta-blockers at all costs, according to a study in The Lancet (January 2007) beta-blockers used for hypertension increase a patient's risk of developing diabetes.

The discovery of insulin, in 1922, was a breakthrough in the treatment of diabetes and it produced a remarkable increase in the life expectancy of diabetic patients. Animal-derived insulins have been used to treat people with diabetes since insulin was first discovered and continuously subjected to various purification technologies. In 1973, Novo produced a purer type of insulin, called monocomponent insulin. This set a new standard in purity. In 1982, Human Monocomponent was the world's first insulin preparation identical to human insulin. It was actually pig insulin, modified by enzymes, to appear identical to human insulin.

When Novo tried to introduce monocomponent insulin into the USA, Lilly fought back with 'human' Humulin insulin. Before Humulin insulin became available, insulin had been produced from animal sources, pigs and cows. It is believed by some that the animal insulin provided the diabetic with better awareness of hypos, and it is certainly true that the long-acting animal insulin such as Ultralente are longer-acting than their 'human' equivalents. The fact that both pig and cow differ from human insulin by certain amino acids (1 in pig and 3 in cow) has lead the majority of physicians to recommend 'human' insulin. 'Animal' insulin became increasingly hard to find, particularly in the USA (see This Little Piggy Left the Market).

In the late 1990s Eli Lilly developed Lispro, brand name Humalog. This was approved for prescription use in the UK and the US by 1996. This insulin has a shorter activity curve than Regular. This means it can be injected closer to the meal time, even after it. Studies have shown that it does not improve control as measured by long-term indicators (Hba1c), but that it does decrease the number of hypos. Glargine, brand name Lantus, was approved for use in the US in 2004. It has become widely touted as better than other long-acting insulins because it has a plateau effect on glucose control that lasts for approximately 24 hours. Some people find it acts a little shorter (and some doctors don't believe that's possible!) So there you have it - the short and sweet version of the history of insulin. I strongly suggest anyone who wishes to fill the spaces between the discovery in 1922 and present day to pickup The Discovery of Insulin (Michael Bliss). I welcome all comments to fill-in the pivotal details I've failed to include.

Like a student driver -- the function of proinsulin (c-peptide) is as critically important as driver's education. The research was done, but because the information highway was just picking up speed (at the time back in '88) dissemination of such research was difficult, at best. Never fear - I found a good study to start things rolling.

Proinsulin (c-peptide) is made along with insulin in a 1 to 1 ratio from the beta cells. After a dose of proinsulin was administered - it took 5 to 10 minutes longer to lower a patient's blood sugar in comparison to insulin, alone. The rise of blood sugar following the lowest point was much slower, as well. In lay terms this means that insulin, coupled with proinsulin (c-peptide), results in a more controlled reaction. Kind of like the teenager with his permit to drive and Dad riding shotgun. The permit gives the kid the right to drive the car, but Dad is telling the kid when to accelerate and when to slow down. Insulin and proinsulin are quite similar in nature except we're talking about a life threatening hormone without the parental guidance.

The antilipolytic effect of proinsulin (tapping fat cells for energy and ANTI means this is stopped) was significantly stronger in comparison to insulin alone. Human proinsulin has a stronger effect on prevention of fat burning for energy in the absence of insulin (ketoacidosis). This seems logical because if you metabolize the glucose in your blood for energy - you will have little (if any) residual glucose to store as fat. Type 2 diabetics have a plethora of c-peptide in their body upon diagnosis but their blood sugar is also high. Looks like insulin and proinsulin reduces the risk of ketoacidosis and regulates fat metabolism.

Why did they decide to manufacture human synthetic insulin without it again? A personal experience pumping piggy proinsulin for 2 days now and I've seen definite control in my blood sugar fluctuations - less than 20 mg/dL in any testing window. It feels like the newly introduced highly purified porcine proinsulin came with a built-in continuous glucose monitor (i.e., C-peptide). More to come...

While patrolling the PubMed database this weekend, I came across a very interesting study that investigated the effects of new insulins on insulin and C-peptide antibodies, insulin dose, and diabetic control. Please note - this study was published in 1983. After reading -- I invite EVERYONE to let me know if it is possible to get purified pork insulin and whether or not you have been on it-- and if you have seen a difference in your diabetes control. Please?

24 diabetic patients using bovine (beef) insulin and possessing insulin antibodies underwent a study of the immunological and clinical consequences of changes in both purity and species of their insulin. The new insulin regimes tested were one of three: a) purified bovine insulin, b) highly purified porcine insulin, and c) semisythetic human insulin.

The patients underwent 3 consecutive 4-month periods on each insulin regimen. The average insulin antibody levels changed little on purified bovine (beef) insulin; actually increased on semi-synthetic human insulin but fell substantially on highly purified porcine insulin. Okay - so this means, in lay terms that the patient's insulin antibodies (the stuff killing your islets) remained relatively the same on beef insulin but became categorically HIGH on synthetic human insulin. And most importantly - to me-the highly purified porcine insulin actually DROPPED the insulin antibodies. Of course - it would cost big pharmaceutical companies more to manufacture highly purified porcine insulin.

C-peptide antibodies fell significantly and continuously throughout the study. The slower rate of fall in C-peptide antibody levels is likely to be due to the prolonged half-life of circulating exogenous proinsulin in the presence of insulin antibody. Although insulin dose remained constant the incidence of hypoglycaemic episodes did not increase and glycosylated haemoglobin levels rose significantly when patients were on porcine insulin. The deterioration in diabetic control may have been due to greater temporal mismatch between insulin needs and insulin availability with pork or human insulin than with beef insulins, and to reduced insulin antibody levels.

The use of purer insulins which more closely resemble the human form can cause a significant reduction in levels of insulin and C-peptide antibodies. These changes may not necessarily produce better diabetic control. Recent studies have shown that a depletion of C-peptide in the body results in a greater chance of microvascular complications associated with diabetes.

This study was published around the time when all of the synthetic human insulins were sweeping the Nation. I tried calling my local CVS Pharmacy on Saturday morning to see if I could get some purified porcine insulin. No such luck. Go figure. The big guys were successful at convincing the medical community and patients that no other insulin is better. Correction - no other insulin is cheaper to manufacture and that means it is better for them. And the importance of C-peptide was overlooked entirely - or was it? C-peptide prevents the complications associated with injecting insulin - but that sounds like another marketable drug. After all - synthetic human insulin doesn't have C-peptide. REAL HUMAN INSULIN does (the way it comes out of the beta cells, in natural form, it does)!!! And as long as your body is producing insulin antibodies - you NEED their synthetic insulin (conveniently -- the only kind you can buy). Best business model - customer for life!

Eli Lilly is introducing a unique insulin pen named the Memoir. It is the first on the market with a memory device to track doses administered. It is designed for use with Lilly's top-selling insulin, Humalog.

The battery-operated pen uses a computer chip to remember the last 16 insulin doses. And while insulin pens are popular in Europe and Asia, only about 800,000 of the 4 million U.S. diabetics who take injections use a pen-- most use syringes. It won't be too surprising if insurers and patients balk at the $100 sticker price for the pen alone. There is a separate fee for the insulin cartridges. I agree, it's a little pricey. Lilly plans to ignite the marketing campaign by offering a $45 coupon. Good start. This pen has been under development for seven years. Lilly plans to introduce two other pens this year to increase Humalog demand. I've got an idea (since nobody asked, but I was a former user). I traded up to Apidra because I became irate every time Humalog clogged my infusion set for my pump. Go back to the drawing board with that quandary while I'll work on my honey do list for product development.

Neither here nor there - my point is this: Eli Lilly you can be everything you want to be if you listen to your customers. The number of insulin-taking diabetics is rising along with the bar on product ingenuity. It's game day, Eli Lilly. I have more ideas to help bring out your A-game. Stay tuned...

In 2005, insulin cost state Medicaid programs $500 million. The diabetes epidemic is causing the government to question one of the big-ticket items on the shopping list - insulin. Insulin was developed over 20 years ago and many of these original forms are now off patent. This is a screaming opportunity for generic drug makers to prosper and government programs to save.

Two of the largest insulin makers, Novo Nordisk and Eli Lily, say they are opposed to any F.D.A. action that would approve generic insulin without clinical studies. Why the concern? The combined sales in the United States for Humulin and Novolin is about $1 billion. No wonder.

A drug maker needs to prove the generic version contains the same active ingredients, purity and quality, and provides equivalent delivery over time as the brand-name version. However the makers of generic drugs agree that the approval process for generic biologics, like insulin, would be more complex than the current shortened process for other generic drugs. Anybody have a guess as to what the hold up is for this much needed and overdue generic insulin explosion?