Diabetes Mellitus

Etiology and Pathophysiology

Theories link causes of diabetes singly or in combination to genetic, autoimmune, and environmental factors. Diabetes is a disorder of glucose metabolism related to absent or insufficient insulin supply and/or poor utilization of the insulin that is available.

Normal Insulin Metabolism Insulin is a hormone produced by Beta cells in the islets of Langerhans of the pancreas o Insulin helps move glucose from the bloodstream across cell membrane, into the cytoplasm of the cell. o Insulin is an anabolic hormone (storage hormone) The release of insulin lowers blood glucose and facilitates a stable, normal glucose range (70-120mg/dL) Counterregulatory hormones work to increase blood glucose levels by stimulating glucose production and output by the liver and by decreasing the movement of glucose into the cells o Abnormal production of insulin or counterregulartory hormones may be present in diabetes Insulin and counterregulatory hormones provide a sustained but regulated release of glucose for energy during food intake and fasting periods Insulins first form is proinsulin, which is routed through the liver, cleaved by enzymes to form insulin and C-peptides.

Type 1 Diabetes Mellitus Accounts for 5%-10% of all people with diabetes o Generally affects people under 40 Etiology and Pathophysiology o Type 1 diabetes is an immune-mediated disease. The bodys own T cells attack pancreatic beta cells (the source of insulin) o Autoantibodies to islet cells cause a reduction of 80%-90% of normal beta cell function prior to manifestations such as hyperglycemia. Onset Of Disease o Islet cell autoantibodies responsible for beta-cell destruction are present for months to years before the onset of symptoms. o Manifestations occur when the pancreas can no longer produce enough insulin to maintain glucose levels.

 Prediabetes

Manifestations include: polydipsia (excessive thirst), polyuria (frequent urination) and polyphagia(excessive hunger)

A condition where individuals are at increased risk of developing diabetes o Blood glucose levels are high, but not high enough to be diagnosed as diabetic Impaired Fasting Glucose and Impaired Glucose Tolerance are present o Fasting Levels are 100mg/dL-125mg/dL Prediabetics may have damage to heart and blood vessels

Type 2 Diabetes Mellitus Accounts for 90% of all diabetics - Etiology and Pathophysiology o The body is still producing its own insulin, but it is either not enough, poorly utilized by the body, or both. o Four Major Metabolic Abnormalities Insulin Resistance a condition in which body tissues ad not respond to the action of insulin Insulin Receptors are unresponsive to the insulin or there is an insufficient amount of insulin Decrease in the ability of the pancreas to produce insulin This is because Beta-cells are fatigued Inappropriate glucose production by the liver Altered production of hormones and cytokines by adipose tissue (adipokines). o Patients with metabolic syndrome are at a greater risk of developing diabetes - Onset Of Disease o Onset is usually gradual

Gestational Diabetes Develops during pregnancy (7% of pregnancy is US) o Women at high risk are: Severely obese History of gestational diabetes Presence of glycosuria Family History of type 2 Diabetes o Women with Gestational Diabetes have higher risk of C-section

Perinatal death Neonatal complications

Clinical Manifestations
Type 1 Diabetes Mellitus Classical Symptoms are o Polyuria o Polydipsia o Polyphagia Weight loss occurs when the body cant get glucose and turns to other energy sources (fat and protein)

Type 2 Diabetes Mellitus Patients may experience class symptoms More common manifestations include: o Fatigue o Recurring infections o Recurrent vaginal yeast or candida infections o Prolonged wound healing o Visual changes

Diagnostic Studies
Diagnosis of Diabetes can be confirmed through 1 of 4 methods o A1C > 6.5% o Fasting Plasma Glucose (FPG) level > 126mg/dL Fasting is define as no caloric intake for 8 hours o Two-hour plasma glucose level > 200 mg/dL during Oral Glucose Tolerance Test o A random plasma glucose of >200mg/dL in patients with classic symptoms of hyperglycemia or hyperglycemic crisis A1C is preferred to FPG because fasting is not required and less day-to-day alterations

Drug Therapy Insulin

Types of Insulin Rapid Acting Short Acting Intermediate Acting Long Acting

Duration times can be manipulated by adding zinc, acetate buffers and protamine

Insulin Regimens Single Dose, once a day Twice a day, Split-mixed dose Three Times a day Combination of mixed and single dose Basal-Bolus multiple doses (Intensive insulin therapy)

Mealtime Insulin (Bolus) The timing of rapid and short acting insulin in relation to meals is crucial in controlling postmeal blood glucose levels.

Long or Intermediate-Acting (Basal) Background Insulin People with type 1 diabetes need to use lone-acting basal or intermediate-acting insulin to control blood glucose between meals and overnight People with type 2 diabetes who take insulin with meals also require basal insulin to control glucose levels. Long acting insulin o Glargine and determir Used for once a day injections Intermediate acting insulin lasts 10-16 hours and peaks between 4-10 hours

Combination Therapy Insulins can be combined into one injection a day o May not be as effective at controlling blood glucose

Storage of Insulin Can be left at room temperature for up to 4 weeks (between 86-32 degrees F) o Insulin should avoid direct sunlight o It can be kept in a cooler (above 32degrees) in warmer climates Prefilled syringes are stable for up to 1 week when stored in refrigerator o Cloudy prefilled syringes should be stored with the needle up to avoid clumping of insulin binders

Administration of Insulin Can be administer subq or IV

Injection Steps to perform an insulin injection o Wash Hands o Inspect insulin Bottle (proper insulin, not expired, bottle top in perfect condition) o Gently roll bottle between palms if solution is cloudy o Select proper injection site o Clean skin with soap and water or alcohol o Pinch skin, insert 90 degrees o Push plunger o Destroy and dispose of single use syringe

Alternative Delivery Methods Insulin Pump

Problems With Insulin Therapy Allergic Reactions Itching Erythema Burning

Lipodystrophy Definition: atrophy of subcutaneous tissue Can occur if injection site is frequently used. Hypertrophy may occur if site is continually used o Thickening of subq tissue

Somogyi Effect and Dawn Phenomenon A rebound effect in which an overdose of insulin induces hypoglycemia, o Usually occurs while sleeping o Patient may report headaches or may recall nightsweats or nightmares The Dawn Phenomenon o Characterized by hyperglycemia that is present on awakening in the morning due to the release of counterregulatory hormones in predawn hours Treatment for Somogyi Effect is less insulin

Drug Therapy Oral Agents

Sulfonylureas The primary action of sulfonylureas are to increase insulin production from the pancreas

Meglitinides Nearly the same as sulfonylureas Encourage pancreas to produce more insulin o They are absorbed and excreted more quickly than sulfonylureas, so there is a lower chance of hypoglycemia

Biguanides The primary action of metformin is to reduce glucose production by the liver o Do not give to patients with kidney disease, liver disease, or heart failure o Do not use in people who drink excessive amounts of alcohol

Alpha-glucoidase Inhibitors These drugs work by slowing down the absorption of carbohydrates in the small intestines

Thiazolidinediones They improve insulin sensitivity, transport, and utilization at target tissues

DPP-4 Inhibitor These medication inhibit DPP-4, slowing the inactivation of incretin hormones

Combination Therapy Combining two drugs to treat diabetes

Incretin Mimetic Stimulate the incretin hormone GLP-1 found in people with type 2 diabetes o Acute pancreatitis and kidney problems have been associated with its use

Amylin Analog When taken concurrently with insulin, it provides for better glucose control

Diabetic Ketoacidosis
Etiology and Pathophysiology

Diabetic Ketoacidosis is caused by a profound deficiency of insulin and is characterized by hyperglycemia, ketosis, acidosis, and dehydration. o Most likely to occur in people with type 1 diabetes. o Percipitating factors include: Illness and infection inadequate insulin dosage undiagnoses type 1 diabetes poor self-management and neglect When there is not enough insulin in the blood to breakdown the glucose, the body starts breaking down fat as a secondary source Insulin deficiency impairs protein synthesis and causes excessive protein degradation o Results in nitrogen loss from tissue o Causes Insulin deficiency stimulates glucose production in the liver, further hyperglycemia Leads to osmotic diuresis Vomiting caused by the acidosis leads to hypovolemic shock shock caused by the decrease in the volume of circulating blood o This can lead to renal failure and eventually death

Clinical Manifestation Signs and symptoms of diabetes ketoacidosis o poor skin turgor o dry mucous membranes o tachycardia o orthostatic hypotension o Lethargy and Weakness o Kussmaul Respirations The bodys attempt to reverse the metabolic acidosis through the exhalation of excess carbon dioxide o Sweet, fruity breath caused by acetone o Blood Glucose levels >250 mg/dL

Neuropathy
Diabetic neuropathy is nerve damage that occurs because of the metabolic derangements o Occurs in 60-70% of patients o Most common form is sensory neuropathy Loss of protective sensation in the lower extremities.

Etiology and Pathophysiology The prevailing theory of the cause of diabetic neuropathy is that persistent hyperglycemia leads to an accumulation of sorbitol and fructose in the nerves that cause damage by an unknown process o Results in reduced blood circulation and demyelization

Sensory Neuropathy Most common form of sensory neuropathy is distal symmetric polyneuropathy o Affects hands and feet bilaterally o Characteristics include: Loss of sensation Numb hands and feet Loss of sensitivity to touch and temp Abnormal sensations Pain burning, cramping, crushing, tearing Paresthesias Controlling Blood Glucose is the only way to control neuropathy o Drugs can be given for the effects ofnearupathy

Autonomic Neuropathy Can Affect all bod systems Can Lead to: o Hypoglycemic unawareness o Bowel Incontinence and diarrhea o Urinary retention Caused by decreases in sensations in the inner walls of the bladder o Delayed gastric emptying which leads to Anorexia Nausea Vomiting Reflux Persistant feeling of fullness Cardiovascular abnormalities include: o Postural hypotension o Resting tachycardia o Painless myocardial function Can affect sexual Function o ED in men

o Candidal and nonspecific vaginitis as well as low libido are common

Complications of Feet and Lower Extremities

Diabetes greatly increases the risk of foot ulcerations and lower extremity amputations Micro and Macrovascular disease place patients at risk for injury and serious infection can lead to amputation Factors include: o Sensory neuropathy o Peripheral artery disease o Clotting abnormalities o Impaired immune function o Autonomic neuropathy Smoking greatly increases risk of lower extremity problems by damaging blood vessels Sensory neuropathy is a huge risk factor because of the loss of protective sensations prevent patients from becoming aware of pain or infections

Integumentary Complications
Acanthosis nigricans dark course, thickened skin predominantly seen in flexures on the neck Diabetic Dermatopathy - red-brown flat-topped papules Necrobiosis lipoidica diabeticorum appears as red-yellow lesions with atrophic skin that becomes shiny and transparent revealing tiny blood vessel o Associated with type 1 diabetes Granuloma annulare partial rings of papules, often on the dorsal surface of hands and feet o Associated with type 1 diabetes o Probably autoimmune in nature

Infections and Mental Health

People with diabetes are more susceptible to infection Patients with diabetes have high rates of psychiatric disorders o Depression o Eating Disorders Anorexia and bulimia