Reversal of type 2 diabetes to normal metabolic control by either bariatric surgery or hypocaloric diet allows for the time sequence of underlying pathophysiologic mechanisms to be observed. In reverse order, the same mechanisms are likely to determine the events leading to the onset of hyperglycemia and permit insight into the etiology of type 2 diabetes. Within 7 days of instituting a substantial negative calorie balance by either dietary intervention or bariatric surgery, fasting plasma glucose levels can normalize. This rapid change relates to a substantial fall in liver fat content and return of normal hepatic insulin sensitivity. Over 8 weeks, first phase and maximal rates of insulin secretion steadily return to normal, and this change is in step with steadily decreasing pancreatic fat content. The difference in time course of these two processes is striking. Recent information on the intracellular effects of excess lipid intermediaries explains the likely biochemical basis, which simplifies both the basic understanding of the condition and the concepts used to determine appropriate management. Recent large, long-duration population studies on time course of plasma glucose and insulin secretion before the diagnosis of diabetes are consistent with this new understanding. Type 2 diabetes has long been regarded as inevitably progressive, requiring increasing numbers of oral hypoglycemic agents and eventually insulin, but it is now certain that the disease process can be halted with restoration of normal carbohydrate and fat metabolism. Type 2 diabetes can be understood as a potentially reversible metabolic state precipitated by the single cause of chronic excess intraorgan fat.
Some medical professionals use an Oral Glucose Tolerance Test (OGTT) to test for diabetes. If you’ve ever been pregnant and had to drink the sickeningly sweet sugar cocktail and then have blood drawn, you are familiar with this one. Basically, a patient is given 50-75 grams of glucose in concentrated solution and his blood sugar response is measured. I’m not a fan of this test because no one should be ingesting that much concentrated glucose, and the test is not a completely accurate measure. (Just a side note: if you are a drinker of the “Big Gulp” drinks or large amounts of soda, you are putting your body through a similar test each day! Eventually, your body will respond, probably with something like “Fine, you want diabetes, I’ll show you diabetes!)
Storage of liver fat can only occur when daily calorie intake exceeds expenditure. Sucrose overfeeding for 3 weeks has been shown to cause a 30% increase in liver fat content (37). The associated metabolic stress on hepatocytes was reflected by a simultaneous 30% rise in serum alanine aminotransferase (ALT) levels, and both liver fat and serum ALT returned to normal levels during a subsequent hypocaloric diet. Superimposed upon a positive calorie balance, the extent of portal vein hyperinsulinemia determines how rapidly conversion of excess sugars to fatty acid occurs in the liver. In groups of both obese and nonobese subjects, it was found that those with higher plasma insulin levels have markedly increased rates of hepatic de novo lipogenesis (2,38,39). Conversely, in type 1 diabetes the relatively low insulin concentration in the portal vein (as a consequence of insulin injection into subcutaneous tissue) is associated with subnormal liver fat content (40). Initiation of subcutaneous insulin therapy in type 2 diabetes brings about a decrease in portal insulin delivery by suppression of pancreatic insulin secretion and, hence, a decrease in liver fat (41). Hypocaloric diet (42), physical activity (43), or thiazolidinedione use (23,44) each reduces insulin secretion and decreases liver fat content. Newly synthesized triacylglycerol in the liver will be either oxidized, exported, or stored as hepatic triacylglycerol. Because transport of fatty acid into mitochondria for oxidation is inhibited by the malonyl-CoA produced during de novo lipogenesis, newly synthesized triacylglycerol is preferentially directed toward storage or export. Hence, hepatic fat content and plasma VLDL triacylglycerol levels are increased.
Many manufacturers offer pen delivery systems. Such systems resemble the ink cartridge in a fountain pen. A small, pen-sized device holds an insulin cartridge (usually containing 300 units). Cartridges are available for the most widely used insulin formulations. The amount of insulin to be injected is dialed in, by turning the bottom of the pen until the required number of units is seen in the dose-viewing window. The tip of the pen consists of a needle that is replaced with each injection. A release mechanism allows the needle to penetrate just under the skin and deliver the required amount of insulin.
Physical activity is an important part of controlling diabetes and preventing complications such as heart disease and high blood pressure. "We know that exercise is a very effective way to help bring blood sugars under control for someone with type 2 diabetes," says Kenneth Snow, M.D., Acting Chief, Adult Diabetes, Joslin Clinic. Try for 30 minutes of moderate exercise, like brisk walking, on most days. Joslin's Why WAIT? and Easy Start exercise programs are great resources for developing a safe weight loss program.
There are many promising studies suggesting chromium supplementation may be effective, but they are far from conclusive. For example, a small study published in the journal Diabetes Care compared the diabetes medication sulfonylurea taken with 1,000 mcg of chromium to sulfonylurea taken with a placebo. After 6 months, people who did not take chromium had a significant increase in body weight, body fat, and abdominal fat, whereas people taking the chromium had significant improvements in insulin sensitivity.
The diabetes looks better, since you can only see the blood sugars. Doctors can congratulate themselves on a illusion of a job well done, even as the patient gets continually sicker. Patients require ever increasing doses of medications and yet still suffer with heart attacks, congestive heart failure, strokes, kidney failure, amputations and blindness. “Oh well” the doctor tells himself, “It’s a chronic, progressive disease”.
As of now, diabetes is classified as either Type I or Type II. New research suggests there are several more types of diabetes, which all require different treatment approaches, but that’s a developing area of knowledge. On an episode of Bulletproof Radio, Dr. Steven Masley explains why doctors are starting to view Altzheimer’s disease as “type III diabetes” and picks apart the relationship between insulin and brain degeneration. Listen to it on iTunes.
Big pharma are in the early stages of developing their own cell therapy approaches for diabetes. Novo Nordisk, one of the largest providers of diabetes treatments, is bidding for stem cells and an encapsulation device, stating that the first clinical trial could take place in the “next few years.” Sanofi, also a big name in diabetes, is working with the German Evotec in a beta cell replacement therapy for diabetics.
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.