Tag Archives: insulin

History of Diabetes: Elizabeth Hughes, Insulin Pioneer

One of the very first users of insulin injections lived to be 73.  That amazes me since most of her life was lived before we could keep close track of blood sugar levels with home glucose monitoring.  She died of pneumonia in 1981.  She was a type 1 diabetic since age 11.

Insulin was discovered in Canada

Her name was Elizabeth Hughes, daughter of a New York governor.  She was started in insulin around 1922. 

I read about her in Nutrition Journal earlier this year.  Most of the article was about the use of starvation diets for diabetics in the pre-insulin era .  Ever heard of the Joslin Clinic, a preeminent U.S. diabetes center?  Elliott Joslin was once an advocate of these starvation diets.  Insulin changed that.

The article notes that before insulin therapy was available, the standard diabetic diet was low-carbohydrate, avoiding sugars and starches, sometimes called the “animal diet.”

I also learned that urine became easily testable for sugar in the early part of the 20th century, if not earlier.  Before this, many cases of diabetes (mostly type 2) were undetectable or misdiagnosed.

Even today, type 1 diabetes is a hard row to hoe.  Before 1922, it was even worse.  As bad as it can get.

Steve Parker, M.D.

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Book Review: Why We Get Fat

Gary Taubes’s new book, Why We Get Fat: And What To Do About It, comes on the market later this month.  I give it five stars per Amazon.com’s ranking system (I love it).

♦   ♦   ♦

At the start of my medical career over two decades ago, many of my overweight patients were convinced they had a hormone problem causing it.  I carefully explained that’s rarely the case.  As it turns out, I may have been wrong.  And the hormone is insulin.

Mr. Taubes wrote this long-awaited book for two reasons: 1) to make the ideas in his 2007 masterpiece (Good Calories, Bad Calories) more accessible to the public, and 2) to speed up the process of changing conventional wisdom on overweight.  GCBC was the equivalent of a college-level course on nutrition, genetics, history, politics, science, physiology, and biochemistry. Many nutrition science geeks loved it while recognizing it was too difficult for the average person to digest.

Paradigm Shift

The author hopes to convince us that “We don’t get fat because we overeat; we overeat because we’re getting fat.”  We need to think of obesity as a disorder of excess fat accumulation, then ask why the fat tissue isn’t regulated properly.  A limited number of hormones and enzymes regulate fat storage; what’s the problem with them?

Mr. Taubes makes a great effort convince you the old “energy balance equation” doesn’t apply to fat storage.  You remember the equation: eat too many calories and you get fat, or fail to burn up enough calories with metabolism and exercise, and you get fat.  To lose fat, eat less and exercise more.  He prefers to call it the “calories-in/calories-out” theory.  He admits it has at least a little validity.  Problem is, the theory seems to have an awfully high failure rate when applied to weight management over the long run.  We’ve operated under that theory for the last half century, but keep getting fatter and fatter.  So the theory must be wrong on the face of it, right?  Is there a better one?

So, Why DO We Get Fat?

Here is Taubes’s explanation.  The hormone in charge of fat strorage is insulin; it works to make us fatter, building fat tissue.  If you’ve got too much fat, you must have too much insulin action.  And what drives insulin secretion from your pancreas?  Dietary carbohydrates, especially refined carbs such as sugars, flour, cereal grains, starchy vegetables (e.g., corn, beans, rice, potatoes), liquid carbs.  These are the “fattening carbs.”  Dozens of enzymes and hormones are at play either depositing fat into tissue, or mobilizing the fat to be used as energy.  It’s an active process going on continously.  Any regulatory derangement that favors fat accumulation will CAUSE gluttony (overeating) or sloth (inactivity).  So it’s not your fault. 

What To Do About It

Cut back on carb consumption to lower your fat-producing insulin levels, and you turn fat accumulation into fat mobilization.

Before you write off Taubes as a fly-by-night crackpot, be aware that he’s received three Science-in-Society Journalism Awards from the National Association of Science Writers.  He’s a respected, professional science writer.  Having read two of his books, it’s clear to me he’s very intelligent.  If he’s got a hidden agenda, it’s well hidden.

One example  illustrates how hormones control growth of tissues, including fat tissue.  Consider the transformation of a skinny 11-year-old girl into a voluptuous woman of 18. Various hormones make her grow and accumulate fat in the places we now see curves.  The hormones make her eat more, and they control the final product.  The girl has no choice.  Same with our adult fat tissue, but with different hormones. If some derangement is making us grow fatter, it’s going to make us more sedentary (so more energy can be diverted to fat tissue) or make us overeat, or both.  We can’t fight it.  At not least very well, as you can readily appreciate if look at the people around you at any American shopping mall.

This’N’That

Taubes’s writing is clear and persuasive.  He doesn’t beat you over the head with his conclusions. He lays out a logical series of facts and potential connections and explanations, helping you eventually see things his way.  If insulin controls fat storage by building and maintaining fat tissue, and if carboydrates drive insulin secretion, then the way to reduce overweight and obesity is carbohydrate-restricted eating, especially avoiding the fattening carbohydrates.  I’m sure that’s true for many folks, perhaps even a majority.

If you’re overweight and skeptical about this approach, you could try out a very-low-carb diet for a couple weeks or a month at little expense and risk (but not zero risk).  If Mr. Taubes and I are right, there’s a good chance you’ll lose weight.  At the back of the book is a university-affiliated low-carb eating plan.

If cutting carb consumption is so critical for long-term weight control, why is it that so many different diets—with no focus on carb restriction—seem to work, if only for the short run?  Taubes suggests it’s because nearly all diets reduce carb consumption to some degree, including the fattening carbs.  If you reduce your total daily calories by 500, for example, many of those calories will be from carbs.  Simply deciding to “eat healthy” works for some people: stopping soda pop, candy bars, cookies, desserts, beer, etc.  That cuts a lot of fattening carbs right there.

Losing excess weight or controlling weight by avoiding carbohydrates was the conventional wisdom prior to 1960, as documented by Mr. Taubes.  Low-carb diets for obesity date back almost 200 years.  The author attributes many of his ideas to German internist Gustav von Bergmann (1908).   

Taubes discusses the Paleolithic diet, mentioning that the average paleo diet derived about a third of total calories from carbohdyrates (compared to the standard American diet’s 55% of calories from carb).  My prior literature review  found 40-45% of paleo diet calories from carbohydrate.  I’m not sure who’s right.

Minor Bone of Contention RE: Coronary Heart Disease

Mr. Taubes provides numerous scientific references to back his assertions.  I checked out one in particular because it didn’t sound right.  Some background first. 

Reducing our total fat and saturated fat consumption over the last 40 years was supposed to lower our LDL cholesterol, thereby reducing the burden of coronary heart disease, which causes heart attacks.  Instead, we’ve experienced the obesity epidemic as those fats were replaced by carbohydrates.  Taubes mentions a 2009 medical journal article by Kuklina et al, in which Taubes says Kuklina points out the number of heart attacks has not decreased as we’ve made these diet changes.  Kuklina et al don’t say that.  In fact, age-standardized heart attack rates have decreased in the U.S. during the last decade. 

Furthermore, autopsy data document a reduced prevalence of anatomic coronary heart disease in people aged 20-59 from 1979 to 1994, but no change in prevalence for those over 60. The incidence of coronary heart disease decreased in the U.S. from 1971 to 1998 (the latest reliable data).  Death rates from heart disease and stroke have been decreasing steadily over the last 40 years in the U.S.; coronary heart disease death rates are down by 50%.  I do agree with Taubes that we shouldn’t credit those improvements to reduced total and saturated fat consumption.  [Reduced trans fat consumption may play a role, but that’s off-topic.] 

I think Mr. Taubes would like to believe that coronary artery disease is either more severe or unchanged in the last few decades because of low-fat, high-carb eating.  That would fit nicely with some of his theories, but it’s not the case.  Coronary artery disease is better now thanks to a variety of factors, but probably not diet (setting aside the trans-fat issue).

Going Forward

Low-carb dieting was vilified over the last half century partly out of concern that the accompanying high fat consumption would cause premature heart attacks, strokes, and death.  We know now that total dietary fat and saturated fat have little to do with coronary heart disease and atherosclerosis (hardening of the arteries), which sets the stage for a resurgence of low-carb eating.  

I advocate Mediterranean-style eating as the healthiest, in general.  It’s linked with prolonged life and lower risk of heart disease, stroke, dementia, diabetes, and cancer.  On the other hand, obesity is a strong risk factor for premature death and development of heart disease, stroke, diabetes, and cancer.  If consistent low-carb eating cures the obesity, is it healthier than the Mediterranean diet?  Maybe so.  Would a combination of low-carb and Mediterranean be better?  Maybe so.  I’m certain Mr. Taubes would welcome a decades-long interventional study comparing low-carb with the Mediterranean diet.  But that’s probably not going to happen in our lifetimes. 

Gary Taubes rejects the calories-in/calories-out theory of overweight that hasn’t done a very good job for us over the last 40 years.  Taubes’s alternative ideas deserve serious consideration.

Steve Parker, M.D.

Update December 18, 2010: I found Mr. Taubes’s reference for stating that Paleolithic diets provide about a third of calories from carbohydrate (22-40%), based on modern hunter-gatherer societies).  See References below.   

References:
Coronary heart disease autopsy data:  American Journal of Medicine, 110 (2001): 267-273.
Reduced heart attacks:  Circulation, 12 (2010): 1,322-1,328.
Reduced incidence of coronary heart disease:  www.UpToDate.com, topic: “Epidemiology of Coronary Heart Disease,” accessed December 11, 2010.
Death rates for coronary heart disease:  Journal of the American Medical Association, 294 (2005): 1,255-1,259.

Cordain, L., et al.  Plant-animal subsistance ratios and macronutrient energy estimations in worldwide hunter-gatherer dietsAmerican Journal of Clinical Nutrition, 71 (2000): 682-692.

Disclosure:  I don’t know Gary Taubes.  I requested from the publisher and received a free advance review copy of the book.  Otherwise I received nothing of value for this review.

Disclaimer:   All matters regarding your health require supervision by a personal physician or other appropriate health professional familiar with your current health status.  Always consult your personal physician before making any dietary or exercise changes.

Update April 22, 2013

As mentioned above, WWGF was based on Taubes’ 2007 book, Good Calories, Bad Calories. You may be interested in a highly critical review of GCBC by Seth at The Science of Nutrition.

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Drug Review: Insulin

Insulin is life-saving for type 1 diabetics.  Many type 2 diabetics will eventually, if not at the outset, need to take insulin for adequate control of blood sugars, which should help prevent diabetes complications.

My comments here are simply a brief review of insulins used by type 2 diabetics.  Anyone taking insulin must work closely with a physician or diabetes nurse educator on proper dosing, injection technique, and recognition and management of hypoglycemia (low blood sugar).

This is NOT an insulin rig! Modern insulin injections barely hurt, if at all.

Insulin’s Mechanism of Action
 

 

 

Insulin is made by the pancreas to keep blood sugars from rising above a fairly strict range: 70-140 mg/dl or 3.89-7.78 mmol/l.  [It has many other actions that I won’t bother to outline here.]  When we eat a meal containing carbohydrates (and proteins to a lesser extent), blood sugar starts to rise as we digest the carbs.  Insulin drives the sugar into our body’s cells for use as immediate energy or conversion to fat as stored energy.  About half of the insulin produced by a healthy body is “basal,” meaning it’s secreted into the bloodstream in a steady, low-volume amount, to keep the liver from making too much sugar (glucose) and controlling fasting sugar levels.  The other half is secreted in to the bloodstream in response to meals.

In type 2 diabetes, the body’s tissues, at first, are resistant to the effect of insulin.  So the pancreas has to secrete more than usual (hyperinsulinism). As the illness progresses, the pancreas cannot keep up with demand for more insulin and starts to “burn out,” producing less insulin.  This is when many type 2 diabetics need to start insulin injections.  [These are generalities; there are exceptions.]

Types of Insulin

Specific names of insulins vary by manufacturer and by country.  By convention, I capitalize only the brand names below, plus NPH and NPL.

We could break them down into two types: human (identical in structure to human insulin) and analogs (minor molecular modifications to the usual human insulin molecule).  But most people don’t care about that.  It’s more helpful to distinguish them by the timing of their action:

  • Rapid acting:  lispro (e.g., Humalog), aspart (e.g., Novolog), glulisine (e.g., Apidra)
  • Short acting:  regular (e.g., Novolin R, Humulin R)
  • Intermediate to long acting:  NPH, glargine (e.g., Lantus), detemir (e.g., Levemir), degludec (e.g., Tresiba), NPL (neutral protamine lispro)

Rapid-acting insulins have onset of action between 5 and 15 minutes, peak effect in 30 to 90 minutes, and duration of action of 2 to 4 hours.

Short-acting “regular insulin” has  onset in 30 minutes, peaks in 2 to 4 hours, and works for 5 to 8 hours.

Intermediate to long-acting insulins start working in 2 hours, don’t have a well-defined peak of action, and may keep working for 20 or more hours (glargine), for 6 to 24 hours (detemir), or 30 to 42 hours (degludec).

All these times are gross approximations.  Once the insulin is injected into the fat below the skin, it has to be absorbed into the bloodstream and transported to the tissues where it does its magic.  Lots of factors affect this process. For instance, the thicker the fat tissue at the injection site, the slower the absorption.  Absorption tends to be  faster from the abdominal wall, slower from the arms, even slower from the thighs or buttocks.  Absorption can vary from day to day in an individual even when injection site and technique are identical.

As you might have guessed, the short- and rapid-acting insulins are usually injected before a meal in anticipation of blood sugar rising as food is digested.  The intermediate- and long-acting insulins imitate the healthy body’s “basal” insulin.

Manufacturers also supply premixed insulins, combining intermdiate or long-acting insulin with a short- or rapid-acting insulin.  Examples are Humalog 75/25, Humulin 70/30, and Novolog 70/30.

Dose and Selection of Insulin

See your physician or diabetes nurse educator for details.  Many type 2 diabetics get started just with an intermediate or long-acting insulin once or twice daily, with or without diabetes drugs by mouth. Nearly all type 1’s will need a long-acting “basal” insulin (one-third to one-half of their total daily insulin requirement, plus meal-time “bolus” dosing with a rapid-acting insulin. Insulin pumps are a topic for another day.

Side Effects

By far the most common and worrisome is hypoglycemia.

Steve Parker, M.D.

Last update: August 1, 2016

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London’s Low-Carb Diet Fad of 1865

Dr. Robert Atkins didn’t invent low-carb dieting.  William Banting (1797-1878) sparked a low-carb diet craze in London with his low-carb weight-loss diet, first published in 1863.  Even that probaby wasn’t the first low-carb diet.

According to Wikipedia, Banting was a distant relative of Frederick Banting, the co-discoverer of insulin in 1921.

Mr. Banting attributes his successful program design to a “medical gentleman,” Mr. Harvey, of Soho Square, London. 

Click to read Mr. Banting’s 1865 “Letter on Corpulence” at Internet Archive.

Steve Parker, M.D.

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Review: Gestational Diabetes

You can't tell if she has it just by looking

You can’t tell if she has it just by looking

Ever heard of gestational diabetes?  It’s when a when a woman develops diabetes during pregnancy.  It usually goes away soon after the baby is born.  All pregnancies are characterized by some degree of insulin resistance and high insulin levels: they are necessary for the baby.  Nevertheless, healthy pregnant women run blood sugars 20% lower than when they are not pregnant.

In the U.S., gestational diabetes occurs in 5% of pregnancies, affecting more than 240,000 births annually.  Compared to caucasians, gestational diabetes mellitus (GDM) occurs more often in blacks, native Americans, Asians, and Latinos.

So What’s the Big Deal?

Numerous problems are associated with GDM, for both the mother and the baby:

  • dangerously high blood pressure (preeclampsia)
  • excessive amount of amniotic fluid (the baby in the uterus floats in this fluid)
  • delivery requiring an operation
  • early or premature delivery
  • death of the baby
  • birth trauma, such as broken bones or nerve injury
  • metabolic problems in the baby (low blood sugar, for example)
  • abnormally large baby (macrosomia, a major problem)

Diabetic ketoacidosis—a life-threatening complication of diabetes—is rare in GDM.

How Is GDM Diagnosed?  (section updated December 28, 2013)

Most women should undergo a screening test around the 24th to 28th week of pregnancy.  Screen earlier if undiagnosed type 2 diabetes is suspected or if risk factors for diabetes are present.  The American Diabetes Association (2014 guidelines) recommends either one of two screening tests.

  • “One-step test.” It’s a morning oral glucose tolerance test after at least eight hours of fasting. Fasting blood sugar is tested then he woman drinks 75 grams oral of glucose.  Blood sugar is tested again one and two hours later.  This blood sample is obtained by a needle in a vein, not by finger prick.  Gestational diabetes is diagnosed if any of the following apply: 1) fasting glucose is 92 mg/dl (5.1 mmol/l) or higher, 2) 0ne-hour level is 180 mg/dl (10.0 mmol/l) or higher, or 3) two-hour level is 153 mg/dl (8.5 mmol/l) or higher.
  • “Two-step test.” This is a nonfasting test with only one needle-stick. The woman drinks 50 grams of glucose; plasma glucose is tested one hour later. But if it’s over 140 mg/dl (10.0 mmol/l), that’s a flunk and a three-hour 100-gram oral glucose tolerance test in the fasting state must be done (step two). Gestational diabetes is present if the three-hour glucose is 140 mg/dl (7.8 mmol/l) or higher. Other experts say the diagnosis requires two or more of the following:
    • fasting blood sugar > 95 mg/dl (5.3 mmol/l)
    • 1-hour blood sugar > 180 mg/dl (10 mmol/l)
    • 2-hour blood sugar > 155 mg/dl (8.6 mmol/l)
    • 3-hour blood sugar > 140 mg/dl (7.8 mmol/l)

You’ll find that various expert panels have proposed different criteria for the diagnosis. The National Institutes of Health in the U.S. published their consensus statement in 2013

There’s no need for the screening test if a random blood sugar is over 200 mg/dl (11.1 mmol/l) or a fasting sugar is over 126 mg/dl: those numbers already define diabetes, assuming they are confirmed with a second high reading.  A random blood sugar over 200 mg/dl (11.1 mmol/l) should probably be repeated for confirmation.  Gestational diabetes can be diagnosed at the first prenatal visit if fasting blood sugar is 92 or over mg/dl (5.1 mmol/l or over) but under 126 mg/dl (7 mmol/l), or if hemoglobin A1c at the first prenatal visit is 6.5% or greater.

Women with diabetes in the first trimester have overt diabetes, not gestational diabetes.

What’s the Treatment for Gestational Diabetes?

Briefly: diet, exercise, blood glucose self-monitoring,  and insulin if needed.  The immediate goal is to achieve normal blood sugars.

A registered dietitian is involved in teaching diet modification.  The standard recommendation is to reduce carbohydrate consumption to 35-40% of total calories.  [By comparison, the standard American diet provides about 55% of calories as carbohydrates.]  Protein and fat are about 20% and 40%, respectively.  Total calorie recommendations are based on the mother’s ideal body weight.  Insulin resistance is greatest in the morning, so breakfast is small.  Complex carbohydrates are favored over simple sugars.  Most women will achieve normal glucose (blood sugar) levels with diet modification.

Moderate exercise also helps control blood sugars, partially by increasing sensitivity of body tissues to insulin.

How often should blood sugar be monitored by the mother?  Ideally, at least four times daily: fasting (on an empty stomach before breakfast) and one hour after the first bite of each meal.

Insulin therapy should be seriously considered when fasting glucose is over 90–95 mg/dl (5.0–5.3 mmol/l) or 1-hour-after-meal glucose is over 120-130 mg/dl (6.7–7.2 mmol/l).  Fifteen percent of mothers with GDM will need insulin injections.  If elevated fasting glucose is the only problem, NPH insulin before bedtime is prescribed.  If sugar levels one hour after meals are elevated, then use rapid-acting insulin aspart or insulin lispro just before meals.  In some cases, both NPH and rapid-acting insulin are both necessary.

Outside the U.S., glucose-lowering pills are sometimes used: glyburide and/or metformin most commonly.

What About After Delivery?

Having had gestational diabetes, the mother is at high risk of developing typical non-pregnant diabetes in the future. She should be screened for the development of diabetes and prediabetes at least every three years. Regular exercise and loss of excess weight decrease the risk substantially.

Steve Parker, M.D.

Sources:  UpToDate.com article on gestational diabetes, accessed March, 2010 and October, 2011.  American College of Obstetrics and Gynecology position paper published in 2001.  Diabetes Care, vol. 34, 2011: supplement 1: S62.  Blood sugar levels on the 3-hour 100-gram glucose tolerance test are from the Fourth International Workshop-Conference on Gestational Diabetes, published in 2000. For gestational diabetes diagnosis: American Diabetes Association’s Standards of Care in Diabetes – 2014.

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You Know About Insulin. And Now, the REST of the Story . . .

When we digest carbohydrates, blood sugar rises.  If it goes too high it causes problems.  Everybody knows that insulin lowers blood sugar levels, right?  Less well-known is that regulation of blood sugar is the result of complex interactions of multiple hormones, not just insulin.

[As is my habit, I will use “sugar” and “glucose” interchangeably in this post.] 

Allow me to review the main hormones involved in blood glucose regulation:

1. Insulin is made and stored in pancreas beta cells.  As a meal is digested, blood sugar rises; the pancreas releases insulin to bring blood sugar back down by driving it into cells.

2. Amylin is also made and stored in pancreas beta cells and works to reduce blood sugar levels.  Blood levels of amylin rise and fall in concert with insulin levels.  Amylin slows emptying of the stomach, reduces food consumption, and regulates another hormone—glucagon—after meals.

3. Glucagon is from pancreas alpha cells.  It works to raise blood sugar by promoting the liver’s breakdown of glycogen into glucose, and by promoting the liver’s manufacture of new glucose molecules.

4. Glucagon-like peptide -1 (GLP-1) is produced in small intestine cells and it’s main action is to promote insulin secretion by the pancreas beta cells after absorption of food, which lowers blood sugar levels.  GLP-1 (like amylin) also inhibits emptying of the stomach, inhibits glucagon release, and inhibits appetite, all of which would tend to keep a lid on blood sugar levels. 

5. Gastric inhibitory polypeptide (GIP) promotes secretion of insulin following absorption of food.  GIP is also known as glucose-dependent insulinotropic polypeptide.

You can see that some hormonal mechanisms raise glucose levels; others lower glucose levels.  Homeostasis is all about reaching a happy medium between the two, without wild swings one way or the other.  In healthy people, eating food leads to release of gastrointestinal peptides (GLP-1 and GIP), insulin, and amylin.  The interaction among them keeps blood sugar levels in a fairly level low range.  In diabetes, one or more malfunctions in the system leads to abnormally high blood sugars.

The good news is that scientists have used this knowledge to devise new, effective treatments for diabetes.  Examples are GLP-1 analogues and DPP-4 inhibitors.

Steve Parker, M.D.

PS:   In lab animals, GLP-1 stimulates formation of new pancreas beta cells, so it hold promise in halting the progressive beta cell failure characteristic of type 2 diabetes.

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Lipid Overload as the Cause of Type 2 Diabetes

An up-and-coming theory to explain type 2 diabetes suggests that abnormal lipid metabolism, not glucose/sugar metabolism, is the primary metabolic defect.  Roger H. Unger, M.D., writes about this in the March 12, 2008, issue of the Journal of the American Medical Association.

Early in the writing of this blog entry, I realized it is much too technical for many readers.  I’m writing this to solidify my own understanding of a new theory.  If you are not interested in physiology, you can quit reading now. 

Still with me? 

Definitions and Physiology

Diabetes is defined by high blood glucose (sugar) levels. 

The lipid family includes triglycerides (fats and oils), sterols (e.g., cholesterol), and phospholipids (e.g., lecithin, a major cell membrane component).  Fats are almost entirely composed of trigylcerides.  When fats are broken down, fatty acids are produced.  On the other hand, fatty acids can be joined together, along with glycerol, to form triglycerides. 

Glycogen is a storage form of glucose in liver and muscle tissue. 

Insulin is a protein hormone produced by pancreatic beta cells.  Insulin:

  1. lowers blood glucose levels by driving glucose into cells 
  2.  inhibits breakdown of glycogen into glucose
  3. inhibits formation of new glucose molecules by the body
  4. stimulates glycogen formation
  5. promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation)
  6. promotes formation of fatty acids (triglyceride building blocks) by the liver
  7. inhibits breakdown of stored triglycerides
  8. supports protein synthesis. 

Fatty acids in muscle tissue block the uptake of glucose from the bloodstream by muscle cells.  Fatty acids in liver tissue impair the ability of insulin to suppress breakdown of glycogen into glucose, and impair the ability of insulin to suppress production of new glucose molecules.  In other words, an “excessive fatty acid” environment in liver and muscle tissue promotes elevated glucose levels.

Got that?  [This is very difficult material.]  Now on to . . .

 The Lipocentric Theory of Type 2 Diabetes

Type 2 diabetes may be caused by:

  1. Eating too many calories, leading to…
  2. High insulin levels, leading to…
  3. Stimulation of fat production, leading to…
  4. Increased body fat, leading to…
  5. Deposition of lipids in cells where they don’t belong (that is, not in fat cells), leading to…
  6. Resistance to insulin’s effects on glucose metabolism, leading to…
  7. Lipid accumulation in pancreatic beta cells, damaging them, leading to…
  8. Elevated blood glucose levels, i.e., diabetes.

Perhaps the key to understanding this is to know that “insulin resistance” refers to insulin having less ability to suppress glucose production by the liver, or less ability of various tissues to soak up circulating glucose.  Insulin resistance thereby leads to elevated glucose levels.  But insulin’s effect of “producing fats” (lipogenesis) continues unabated.  Excessive fats, actually fatty acids, accumulate not only in fat cells, but also in liver cells, muscle cells, pancreatic beta cells, and others.  This lipid overload can damage those cells.

If This Theory Is Correct, So What?

Steps #1 and 2 of the lipocentric theory involve excessive caloric intake and high circulating insulin levels, leading to problems down the road.  So overweight people should restrict calories and try to lose at least a modest amount of weight.  Particularly if already having type 2 diabetes or prone to it.

And what about people with type 2 diabetes who have insulin resistance and have poorly controlled glucose levels?  Most of these have high insulin levels already, contributing to a fat-producing state.  Adding more insulin, by injection, would not seem to make much sense.  The extra insulin would bring glucose levels down, but might also cause lipid overload with associated cellular damage.  Effective clinical strategies according to Dr. Unger would include 1) caloric restriction, which helps reduce weight, high insulin levels, and fat production, and 2) if #1 fails, add anti-diabetic drugs that reduce caloric intake (exenatide?), that reduce lipid overload (which drug?), or that do both.  Dr. Unger suggests consideration of bariatric surgery, for caloric restriction and cure of diabetes.

Compared with dietary fats and proteins, carbohydrates generally cause higher circulating insulin levels.  And type 2 diabetics taking insulin shots need higher doses for higher intakes of carbohydrate. So it makes sense to me to consider preferential reduction of carbohydrate intake if someone is going to reduce caloric intake.

Dr. Unger and I agree that reduction of excessive food intake and excess body fat is critically important for overweight people with type 2 diabetes.

Steve Parker, M.D.

References: Unger, Roger H.  Reinventing Type 2 Diabetes: Pathogenesis, Treatment, and Prevention.  Journal of the American Medical Association, 299 (2008): 1185-1187.

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