Excessive Insulin Production by Reduced Number of Beta Cells
Beta Ceil Burnout
Fig. 1-1. The vicious circle of insulin resistance.
related to genetics (see Chapter 12, "Weight Loss, If You're Over weight"),a substantial portion ofthe populationhasthe potentialwhen overweight to become sufficiently insulin-resistant that the increased demands on the pancreas burn out the beta cells that produceinsulin.
These people enterthe vicious circle depictedin Figure 1-1.Note in the figure the crucial role of dietarycarbohydrate in the development and progression of this disease.
This is discussed in detailin Chapter 12.
Insulin resistance appears to be caused at least in part by inheri tance and in part by high levels of fat , in the form of triglycerides released from abdominal fat , in the branch of the bloodstream that feeds the liver. (Transient insulin resistance can be created in labora-
Diabetes: TheBasics 41
toryanimals byinjecting triglycerides , fat , directly intotheir liver's blood supply.)* Abdominal fat is associated with systemic inflamma tion, another cause of insulin resistance, as areinfections.
Insulin resis tance by its very nature increases the body's need for insulin, which therefore causes the pancreas to work harder to produce elevated in sulin levels (hyperinsulinemia), which can indirectly cause high blood pressure and damage the circulatory system.
High levels of insulin in the blood down-regulate the affinity for insulin thatinsulin receptors alloverthe body havenaturally.
This"tolerance" to insulin causes even greaterinsulin resistance.
So, to simplifysomewhat, inheritance plus inflammation plus fat in the blood feeding the liver causes insulin resistance, which causes ele vated serum insulin levels, which cause the fat cells to build even more abdominal fat, which raises triglycerides in the fiver's blood supply and enhances inflammation, which causes insulin levels to increase because of increased resistance to insulin.
If that sounds circular, it is.
But note that the fat that is the culprit here is not dietary fat.
Triglycerides are in circulation at some level in the bloodstream at alltimes.
High triglyceride levels are not so much the result of intake of dietary fat as they are of carbohydrate consumption and existing body fat. (We will discuss carbohydrates, fat, and insulin resistance more in Chapter 9, "The Basic Food Groups") The culprit is actually a particular kind of body fat.
Visceral obesity is a type of obesity in which a special kind of fat is concentrated around the middle of the body, particularly surrounding the intestines (the viscera).A man who is viscerally obese has a waist of greater circumference than his hips.
A woman who is viscerally obese will have a waist at least 80 percent as big around asher hips.
All obese individuals and especially those with visceralobesity areinsulin-resistant.
The ones who eventually become diabetic arethose who cannot make enough extrainsulin to keep their blood sugars normal.
Though treatment has many similar elements , and many of the adverse effectsof elevated blood sugar are the same, type 2 diabetes differs from type 1 in several important ways.
The onset of type 2 diabetes is slowerand more stealthy, but even in its earliest stages the abnormal blood sugar levels, though not sky-
New evidence demonstrates a role for fat contained in muscle cells (intramy- ocyte fat) as another important factor in causing insulin resistance.
42 Before You Start
high, can cause damage tonerves, blood vessels, heart, eyes, andmore.
Type 2diabetes isoften called the silent killer, and it isquite frequently discovered through oneof itscomplications, such ashypertension, vi sualchanges, or recurrent infection.* Type 2 diabetes is, at the beginning, a less serious disease , pa tients don't melt away into sugarwaterand die in a few months' time.
Type 2, however, can through chronically but less dramatically ele vated blood sugars be much more insidious.
Because so many more people areaffected, it probably causes more heartattacks, strokes, and amputations than the more serious type 1 disease.
Type 2 is a major cause of hypertension, heart disease, kidney failure, blindness, and erectile dysfunction.
That these serious complications of type 2 dia betescan progress is no doubt because it is initially milder and is often left untreated or treated more poorly.
Individuals with type 2 still make insulin, and most will never re quire injected insulin to survive, though if the disease is treated poorly, they can eventually burn out their pancreatic beta cells and require insulin shots.
Because of their resistance to the blood sugar- lowering effects of insulin (though not its fat-building effects), many overweight type 2 diabetics actually makemore insulin than slim non diabetics.
BLOOD SUGARS: THE NONDIABETIC VERSUS THE DIABETIC
Since high blood sugar is the hallmark of diabetes, and the cause of every long-term complication of the disease, it makes sense to discuss where blood sugar comes from and how it is used and not used.
Our dietary sources of blood sugar are carbohydrates and proteins.
One reason the taste of sugar , a simple form of carbohydrate , de lights us is that it fosters production of neurotransmitters (principally serotonin) in the brain that relieve anxiety and can create a sense of well-beingor even euphoria.
This makes carbohydrate quite addictive to certain people whose brains may have inadequate levels of or sensi tivity to these neurotransmitters, the chemicalmessengers with which the brain communicates with itself and the rest of the body.
When
A common early sign of mild chronic blood sugar elevation in women is re current vaginalyeastinfections that causeitchingor burning.
Diabetes: TheBasics 43
blood sugar levels are low, the liver, kidneys, and intestines can, through aprocess we will discuss shortly, convert proteins into glucose, butvery slowly andinefficiently.
The body cannot convert glucose back into protein, nor can it convertfat into sugar.
Fat cells, however, with the helpof insulin, do transform glucose into saturatedfat.
The taste of protein doesn't excite us as much as that of carbohy drate , it would be thevery unusual child who'd jump up and down in the grocery store and beg his mother for steak or fish instead of cookies.
Dietary protein gives us a much slower and smaller blood sugar effect,which, as you will see,we diabetics can use to our advan tage in normalizingblood sugars.
The Nondlabetic In the fasting nondiabetic,and evenin most type 2 diabetics, the pan creasconstantlyreleases a steady, lowlevel of insulin.
This baseline, or basal, insulin level prevents the fiver, kidneys, and intestines from in appropriately converting bodily proteins (muscle, vital organs) into glucose and thereby raising blood sugar, a process known as gluco- neogenesis.
The nondiabetic ordinarily maintains blood sugar im maculatelywithin a narrow range , usuallybetween80 and 100mg/dl (milligrams per deciliter),* with most peoplehoveringnear 85 mg/dl.
There are times when that range can briefly stretch up or down , as high as 160 mg/dl and as low as 65 , but generally, for the nondia betic, such swings are rare.
Youwill note that in some literature on diabetes, "normal" may be defined as 60-120 mg/dl, or even as high as 140 mg/dl.
This "normal" is entirely relative.
No nondiabetic will have blood sugar levelsas high as 140 mg/dl except after consuming a lot of carbohydrate. "Normal" in this case has more to do with what is considered "cost-effective" for the average physician to treat.
Since a postmeal (postprandial) blood sugar under 140 mg/dl is not classified as diabetes,and since the indi vidual who experiences such a value will usually still have adequate in sulin production eventually to bring it down to reasonable levels, many physicians would seeno reason for spending their valuabletime on treatment.
Such an individual may be sent off with the admonition to watch his weight or her sugar intake.
Despite the designation "nor-
A deciliter is one-tenth of a liter, or a little over 3 ounces. A milligram is one one-thousandth of a gram, or about one three-thousandth of the weight of sugar in a levelteaspoon.
44 Before You Start
mal,"an individual frequendydisplaying ablood sugar of 140mg/dl is a good candidate for full-blown type 2 diabetes.
I have seen"nondia betics"with sustainedblood sugars averaging 120 mg/dl develop dia betic complications.
Let's take a look at how the average nondiabetic body makes and uses insulin.
Suppose that Jane, a nondiabetic, arises in the morning and has a mixed breakfast,that is, one that contains both carbohydrate and protein.
On the carbohydrate side, she has toast with jelly and a glass of orange juice; on the protein side, she has a boiled egg.
Her basal (i.e., before-meals) insulin secretion has kept her blood sugar steadyduring the night, inhibiting gluconeogenesis.
Shortly after the sugar in the juiceor jellyhits her mouth, or the starchy carbohydrates in the toast reach certain enzymes in her saliva and intestines, glucose beginsto enterher bloodstream.
The mere presence of food in her gut as well as the rise in Jane's blood sugar signal her pancreas to release the granules of insulin it has stored in order to offset a jump in blood sugar (see Figure 1-2).
This rapid release of stored insulin is called phase I insulin response.
It quicklycorrects the initialblood sugar in crease and can prevent further increase from the ingested carbohy drate.
As the pancreas runs out of stored insulin, it manufactures more, but it has to do so from scratch.
The insulin released now is known as the phase II insulin response, and it's secreted much more slowly.
As Jane eats her boiled egg, the small amount of insulin of phase II can cover the glucose that, over a period of hours, is slowly produced from the protein of the egg.
Insulin acts in the nondiabetic as the means to admit glucose , fuel, into the cells.
It does this by activating the movement of glu cose"transporters" within the cells.
These specialized protein mole cules protrude from the cytoplasm of the cellsand their outer surfaces to grab glucose from the blood and bring it to the interiors of the cells.
Once inside the cells, glucose can be utilized to power energy- requiring functions.
Without insulin, the cells can absorb only a very smallamount of glucose, not enoughto sustain the body.
As glucose continues to enter Jane's blood, and the beta cells in her pancreas continue to release insulin,some of her blood sugar is trans formed to glycogen, a starchy substance stored in the muscles and liver.Once glycogen storagesites in the muscles and liver are filled, ex cess glucose remaining in the bloodstream is converted to and stored as saturated fat.
Later, as lunchtime nears but before Jane eats, if her blood sugar drops slightlylow,the alpha cells of her pancreas will re-
Diabetes: The Basics 45
• Phase 1 Phase II
1 -J C 3 W c
a E CO
a. '<- Baseline - ^- Baseline ' Start of Meal Digestion Finished
Terry Eppndge
Fig. 1-2.Phase I and phaseII insulin response in a normal, nondiabetic person.