Human Physiology, 14th edition (2016)

Rev.Confirming Pages

684 Chapter 19

microbiota into short chain fatty acids (acetate, proprionate,

and butyrate; chapter 18, section 18.4), which affects bacte-

rial metabolism in a way that’s beneficial to body metabolism.

Weight reduction and increased dietary fiber, together with exer-

cise, were shown in one study to decrease the risk of diabetes by

58% after four years.

Exercise is beneficial in two ways. First, by increasing

calorie expenditure, it helps a person lose weight and decrease

the size of the adipocytes, making them more sensitive. Sec-

ond, it improves the sensitivity of the skeletal muscle fibers

to insulin. This is partly because muscle contraction during

exercise, independent of insulin, increases the amount of

GLUT4 carriers in the plasma membrane that are needed for

the facilitative diffusion of glucose into the skeletal muscle

fibers. Exercise also enhances the ability of insulin to stim-

ulate skeletal muscle glucose uptake and utilization in other

ways, making the skeletal muscles better able to remove glu-

cose from the blood.

In the years preceding the development of hyperglycemia

in type 2 diabetes, the insulin resistance associated with obesity

can result in a compensatory increase in the number of b cells

in the islets. This produces an elevated secretion of insulin, but

there may be impaired glucose tolerance despite the increased

insulin. Insulin resistance can be associated with hypertension

and dyslipidemia (and thus with increased risk of cardiovascular

diseases), as discussed in the Clinical Application box on met-

abolic syndrome (see p. 672). Metabolic syndrome in obesity

may be caused by inflammation; the number of macrophages

in adipose tissue increases in proportion to the obesity, as do

inflammation markers in the blood such as C-reactive protein. In

obesity, adipose tissue (including adipocytes and macrophages)

secretes several pro-inflammatory adipokines, including tumor

necrosis factor alpha (TNF a ), interleukin-1, and resistin, that

also reduce the insulin sensitivity of target tissues (adipose tis-

sue, liver, and muscles). By contrast, the adipose tissue of lean

people releases an anti-inflammatory adipokine—adiponectin—

that increases insulin sensitivity and protects against metabolic

syndrome.

People with type 2 diabetes do not usually develop keto-

acidosis. The hyperglycemia itself, however, can be dangerous

on a long-term basis. In the United States, diabetes is the lead-

ing cause of blindness, kidney failure, and amputation of the

lower extremities. People with diabetes frequently have circu-

latory problems that increase the tendency to develop gangrene

and increase the risk for atherosclerosis. The causes of damage

to the retina and lens of the eyes and to blood vessels are not

well understood. It is believed, however, that these problems

result from a long-term exposure to high blood glucose, which

damages tissues through a variety of mechanisms.

The glycated hemoglobin (hemoglobin A1c) test is a

measure of the average blood glucose level over a few months

and does not require overnight fasting. An Alc measurement

of about 5% is normal, whereas an A1c of 5.7% to 6.4% indi-

cates prediabetes. An A1c level above 6.5% indicates diabetes;

diabetic control is considered good if the A1c measurement is

maintained at 7% or less.

help decrease insulin resistance. Dietary fiber includes insoluble

fiber (cellulose and lignin) and soluble fiber (oligosaccharides

of fructose or galactose). Reduced insulin resistance is believed

to result from the fermentation of soluble fiber by the intestinal

Figure 19.12 Oral glucose tolerance in prediabetes

and type 2 diabetes. The oral glucose tolerance test showing

( a ) blood glucose concentrations and ( b ) insulin values following

the ingestion of a glucose solution. Values are shown for people

who are normal, prediabetic, and type 2 (non-insulin-dependent)

diabetic. Prediabetics (those who demonstrate “insulin

resistance”) often show impaired glucose tolerance without

fasting hyperglycemia. Data from Simeon I. Taylor et al.,“Insulin

Resistance of Insulin Deficiency: Which is the Primary Cause of

NIDDM?” in Diabetes, vol. 43, June 1994, p. 735.

See the Test Your Quantitative Ability section of the Review

Activities at the end of this chapter.

100

50

150

250

350

450

0

200

300

400

500

Glucose (mg/dl)

Prediabetic

Normal

Type 2

(less severe)

Type 2

(more severe)

0231

Time (hours)

0

100

120

140

160

180

80

60

40

20

200

Insulin (U/ml)

Prediabetic

Normal

(b)

(a)

Type 2

(less severe)

Type 2

(more severe)

0231

Time (hours)

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