Chapter 50
Diabetes Mellitus and the
Metabolic Syndrome
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Glucose, Fats, and Protein
• Energy needs in the body
• The liver with hormones from the endocrine pancreas that
regulates energy production
• Glucose is metabolized to CO2 and H2O.
– 4 kcal/g
• Fat is metabolized to glycerol and fatty acids.
– 9 kcal/g
• Protein is metabolized to amino acids.
– 4 kcal/g
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Tissue Types and Functions
of the Pancreas
• The acini
– Secrete digestive juices into the duodenum
• The islets of Langerhans
– Secrete hormones into the blood
– Composed of beta cells that secrete insulin, alpha
cells that secrete glucagon, and delta cells that
secrete somatostatin
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Actions of Insulin and Glucagon
on Glucose
• Insulin
– Increases glucose transport into skeletal muscle and
adipose tissue
– Increases glycogen synthesis
– Decreases gluconeogenesis
• Glucagon
– Promotes glycogen breakdown
– Increases gluconeogenesis
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Actions of Insulin on Glucose,
Fats, and Protein
• Anabolic in nature
• Promotes glucose uptake by target cells and provides for
glucose storage as glycogen
• Prevents fat and glycogen breakdown
• Inhibits gluconeogenesis and increases protein synthesis
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Actions of Glucagon on Glucose,
Fats, and Protein
• Catabolic in nature
• Increases transport of amino acids into hepatic cells
• Increases breakdown of proteins into amino acids for use
in gluconeogenesis
• Increases conversion of amino acids into glucose
precursors
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Other Hormones Affecting Blood Glucose
• Catecholamines
– Epinephrine and norepinephrine
– Help to maintain blood glucose levels during periods
of stress
• Growth hormone
– Increases protein synthesis in all cells of the body,
mobilizes fatty acids from adipose tissue, and
antagonizes the effects of insulin
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Other Hormones Affecting Blood Glucose
(cont.)
• Glucocorticoids
– Critical to survival during periods of fasting and
starvation
– Stimulate gluconeogenesis by the liver
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Question
• Insulin is _______________ and glucagon is
______________.
− A. catabolic
− B. anabolic
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Answer
• Insulin is anabolic and glucagon is catabolic.
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Types of Diabetes
• Type 1 results from
– Loss of beta cell function
– An absolute insulin deficiency
• Type 2 results from
– Impaired ability of the tissues to use insulin
– A relative lack of insulin or impaired release of insulin
in relation to blood glucose levels
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Diabetes Mellitus
• Prediabetes—impaired fasting plasma glucose and
impaired glucose tolerance
• Disorder of carbohydrate, protein, and fat metabolism
– Results from an imbalance between insulin
availability and insulin need
• Can represent
– An absolute insulin deficiency
– Impaired release of insulin by the pancreatic beta
cells
– Inadequate or defective insulin receptors
– Production of inactive insulin or insulin that is
destroyed before it can carry out its action
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Question
• Hyperglycemia is a complication of ________________.
− A. diabetes type 1
− B. diabetes type 2
− C. both
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Answer
• C. both
• Rationale: Hyperglycemia is a complication of both
conditions, but is thought to be causative in type 2, and
transient in type 1.
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Subdivisions of Type 1 Diabetes
• Type 1A
– Immune-mediated diabetes
• Type 1B
– Idiopathic diabetes
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Factors Involved in the Development
of Type 1A Diabetes
• Genetic predisposition (diabetogenic genes)
• A hypothetical triggering event that involves an
environmental agent that incites an immune response
• Immunologically mediated beta cell destruction
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Idiopathic Type 1B Diabetes
• Those cases of beta cell destruction in which no evidence
of autoimmunity is present
• Only a small number of people with type 1 diabetes fall
into this category; most are of African or Asian descent.
• Type 1B diabetes is strongly inherited.
• People with the disorder have episodic ketoacidosis due
to varying degrees of insulin deficiency with periods of
absolute insulin deficiency that may come and go.
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Metabolic Abnormalities Contributing
to Hyperglycemia in Type 2 Diabetes
• Impaired beta cell function and insulin secretion
• Peripheral insulin resistance
• Increased hepatic glucose production
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Causes of Beta Cell Dysfunction
in Patients with Diabetes
• An initial decrease in the beta cell mass
• Increased beta cell apoptosis/decreased regeneration
• Long-standing insulin resistance leading to beta cell
exhaustion
• Chronic hyperglycemia can induce beta cell
desensitization (“glucotoxicity”).
• Chronic elevation of free fatty acids can cause toxicity to
beta cells (“lipotoxicity”).
• Amyloid deposition in the beta cell can cause
dysfunction.
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Metabolic Syndrome and Type 2 Diabetes
• Metabolic syndrome
– Triglycerides
– HDL
– Hypertension
– Systemic inflammation
– Fibrinolysis
– Abnormal function of the
vascular endothelium
• Obesity and insulin
resistance
• Increased resistance to
the action of insulin
• Impaired suppression of
glucose production by the
liver
• Hyperglycemia and
hyperinsulinemia
– Macrovascular disease
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Question
• Metabolic syndrome is most often related to
__________________.
− A. diabetes type 1
− B. diabetes type 2
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Answer
• B. diabetes type 2
• Rationale: Due to the high levels of glucose and the
increased appetite for carbohydrates
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The Three Polys of Diabetes
• Polyuria
– Excessive urination
• Polydipsia
– Excessive thirst
• Polyphagia
– Excessive hunger
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Other Symptoms of Hyperglycemia
• Weight loss
• Recurrent blurred vision
• Fatigue
• Paresthesias
• Skin infections
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Blood Tests
• Fasting blood glucose test
• Casual blood glucose test
• Capillary blood tests and self-monitoring of capillary
blood glucose levels
• Glycated hemoglobin testing
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Treatment Plans for Diabetes
• Nutrition therapy
• Exercise
• Anti-diabetic agents
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Oral Antidiabetic Agents
• Sulfonylureas
• Repaglinide and nateglinide
• Biguanides
• α-Glucosidase Inhibitors
• Thiazolidinediones
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Three Principal Types of Insulin
• Short-acting
• Intermediate-acting
• Long-acting
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Acute Complications of Diabetes
• Diabetic ketoacidosis
– Hyperglycemia
– Ketosis
– Metabolic acidosis
• Hyperosmolar hyperglycemic state
• Hypoglycemia
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Definitive Diagnosis of DKA
• Hyperglycemia (blood glucose levels >250 mg/dL)
• Low bicarbonate (<15 mEq/L)
• Low pH (<7.3)
• Ketonemia (positive at 1: 2 dilution)
• Moderate ketonuria
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Characteristics of Hyperosmolar
Hyperglycemic State (HHS)
• Hyperglycemia (blood glucose >600 mg/dL)
• Hyperosmolarity (plasma osmolarity >310 mOsm/L)
• Dehydration
• The absence of ketoacidosis
• Depression of the sensorium
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Factors Contributing to Hyperglycemia
• Increased resistance to the effects of insulin
• Excessive carbohydrate intake
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Chronic Complications of Diabetes
• Disorders of the microvasculature
– Neuropathies, nephropathies, and retinopathies
– Distal symmetric neuropathy and foot ulceration
• Macrovascular complications
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Pathologic Changes Observed with
Diabetic Peripheral Neuropathies
• Thickening of the walls of the nutrient vessels that supply
the nerve
– Leading to the assumption that vessel ischemia plays
a major role in the development of neural changes
• Segmental demyelinization process that affects the
Schwann cell
• Accompanied by a slowing of nerve conduction
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Classification of Diabetic Peripheral
Neuropathies
• Somatic
– Polyneuropathies (bilateral sensory)
– Mononeuropathies
– Amyotrophy
• Autonomic
– Impaired vasomotor function
– Impaired gastrointestinal function
– Impaired genitourinary function
– Cranial nerve involvement
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