Human Physiology, 14th edition (2016)

Regulation of Metabolism 683

As previously stated, 90% to 95% of diabetics have type

2 diabetes. The incidence of type 2 diabetes has tripled in the

past thirty years because of the increase in obesity. Indeed,

people who have a BMI (body mass index; section 19.2) of

30 have a five-times greater risk of type 2 diabetes than people

with a BMI of 25 or less. Because obesity decreases insulin

sensitivity, people who are genetically predisposed to insulin

resistance may develop type 2 diabetes mellitus when they

gain weight.

the liver can secrete into the blood, thereby contributing to the

hyperglycemia. The hyperglycemia of type 2 diabetes is thus due

to an increased hepatic secretion of glucose and to a decreased

uptake of plasma glucose into the skeletal muscles, liver, and

adipose tissue.

People who are prediabetic may have impaired glucose

tolerance, which is currently defined by the American Diabe-

tes Association as a repeatable fasting plasma glucose level of

100 to 125 mg/dL. This impaired glucose tolerance is accom-

panied by higher insulin secretion ( fig.  19.12 ), indicating a

state of insulin resistance. A repeatable fasting plasma glucose

level of 126 mg/dL or more, or a random fasting measure-

ment of 200 mg/dL or greater, indicates that the person has

diabetes.

People who are obese appear to have an increased mass

of beta cells in their pancreatic islets to compensate for their

insulin resistance. Also, there are increased beta cells during

pregnancy to compensate for the mother’s natural insulin resis-

tance during pregnancy (which can cause gestational diabetes;

chapter 11, section 11.6) and the needs of the fetus for glucose.

Those who are going to become diabetic have a genetic suscep-

tibility to b -cell failure under these conditions, where abnormal

function and apoptosis of b -cells eventually leads to an inability

of insulin secretion to compensate for the insulin resistance.

Figure 19.11 The consequences of an uncorrected insulin deficiency in type 1 diabetes mellitus. In this sequence

of events, an insulin deficiency may lead to coma and death.

Increased

hepatic glycogenolysis

Increased

hepatic gluconeogenesis

Increased

hepatic ketogenesis

Increased

lipolysis

Decreased

glucose utilization

Decreased

ketone utilization

Hyperglycemia Hyperketonemia

Osmotic diur esis

(water, sodium,

potassium, calcium,

phosphate)

Dehydration,

volume depletion,

hypotension

Metabolic

acidosis

Insulin deficiency

(decreased secretion, resistance, or both)

Clinical Investigation CLUES

The physician told Marty that he had a BMI of 34 and that

he was in danger of getting diabetes.

• What does the BMI measure, and what is the
  significance of Marty’s specific BMI measurement?


• How might a high BMI relate to the danger of
  developing diabetes?

Weight reduction, entailing a shrinking of visceral adipo-

cytes, reduces insulin resistance. Also, diets enriched in fiber

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