Diabetes Mellitus: Symptoms and Mechanisms

• Diabetes Mellitus is a chronic multi-system disease

Definition

• Diabetes Mellitus is related to abnormal insulin production, impaired insulin utilization, or both
• It is the leading cause of end-stage renal disease, adult blindness, and non-traumatic lower limb amputation
• Is a major contributing factor to heart disease and stroke

Types of Diabetes

• Type 1 and Type 2 are the most common types
• Other types include gestational diabetes, prediabetes, and secondary diabetes

Etiology and Pathophysiology of Diabetes

• Theories suggest its cause is linked to a single or combination of genetic, autoimmune, viral, and environmental factors
• Normal insulin metabolism involves insulin being produced by the β cells in the Islets of Langerhans
• Insulin is released continuously into the bloodstream in small increments, with larger amounts released after food intake
• Insulin stabilizes glucose range to 70 to 120 mg/dL

Insulin Function

• Insulin promotes glucose transport from the bloodstream across the cell membrane to the cytoplasm of the cell
• Insulin decreases glucose in the bloodstream
• Insulin stimulates storage of glucose as glycogen in the liver and muscle
• Insulin inhibits gluconeogenesis
• Insulin enhances fat deposition
• Insulin increases protein synthesis

Counterregulatory Hormones

• Counterregulatory hormones oppose the effects of Insulin
• Increase blood glucose levels
• Provide regulated release of glucose for energy
• Help maintain normal blood glucose levels
• Examples are glucagon, epinephrine, growth hormone, and cortisol

Type 1 Diabetes Mellitus

• Type 1 Diabetes Mellitus was formerly known as “juvenile-onset” or “insulin-dependent” diabetes
• Most often occurs in people younger than 40 years of age
• Occurs more frequently in younger children
• There is a progressive destruction of pancreatic β cells by the body's own T cells
• Autoantibodies cause a reduction of 80% to 90% in normal β-cell function before manifestations occur

Type 1 Diabetes Mellitus Onset

• There is a long pre-clinical period
• Antibodies are present for months to years before symptoms occur
• Manifestations develop when the pancreas can no longer produce insulin
• There is rapid onset of symptoms
• Patients usually present at ED with ketoacidosis
• Will require exogenous insulin to sustain life
• Diabetic ketoacidosis (DKA) occurs in absence of exogenous insulin
• Is a life-threatening condition
• Results in metabolic acidosis

Type 1 Diabetes diagnostic symptoms

• Classic symptoms include polyuria (frequent urination), polydipsia (excessive thirst), and polyphagia (excessive hunger).
• Other symptoms include weight loss, weakness, and fatigue

Prediabetes

• Individuals are already at risk for diabetes
• Blood glucose is high but not high enough to be diagnosed as having diabetes
• IFG: Fasting Glucose Levels are 100 to 125 mg/dL
• IGT: 2-hour plasma glucose levels are between 140 and 199 mg/dL
• AIC is in range of 5.7 - 6.4%
• Long-term damage is already occurring to heart and blood vessels
• Usually presents with no symptoms
• Must watch for diabetes symptoms like polyuria, polyphagia, and polydipsia

Type 2 Diabetes Mellitus

• Most prevalent type of diabetes
• Occurs in more than 90% of patients with diabetes
• Usually occurs in people over 35 years of age
• 80% to 90% of patients are overweight
• Prevalence increases with age
• Genetic basis
• Greater in some ethnic populations

Type 2 Diabetes Mellitus Etiology and Pathophysiology

• The pancreas continues to produce some endogenous insulin
• Insulin produced is insufficient or is poorly utilized by tissues
• Obesity (abdominal/visceral) is the most powerful risk factor
• Genetic mutations can lead to insulin resistance

Type 2 Diabetes Metabolic Abnormalities

• There are four major metabolic abnormalities that lead to this disorder
• First: Insulin resistance; where body tissues do not respond to insulin due to insulin receptors are either unresponsive or insufficient in number
• Second: pancreas' ability to produce insulin will decrease; B cells get fatigued from compensating and B-cell mass gets lost
• Third: inappropriate glucose production from the liver where livers response of regulating release of glucose is haphazard
• Fourth: Alteration in production of hormones and adipokines; the play a role in glucose and fat metabolism; the two main types are adiponectin and leptin.

Type 2 Diabetes diagnostic symptoms

• Symptoms include nonspecific symptoms
• May have classic symptoms of type 1
• Gradual onset
• Person may go many years with undetected hyperglycemia.
• Osmotic fluid/electrolyte loss from hyperglycemia may become severe.
• Leading to hyperosmolar coma
• Other symptoms include fatigue, recurrent infection, recurrent vaginal yeast or monilia infect prolonged wound healing, and visual changes

Diagnosing Diabetes

• Four methods of diagnosis include:
  • AIC ≥ 6.5%
  • Fasting Plasma Glucose Level >126 mg/dL
  • Random or Casual Plasma Glucose Measurement ≥200 mg/dL plus symptoms
  • Two-hour OGTT Level ≥200 mg/dL when a glucose load of 75 g is used

Diagnostic studies

• Hemoglobin A1C test is used for determining glycemic levels over time
• Shows the amount of glucose attached to hemoglobin molecules over RBC life span
• Approximately 120 days
• Ideal goal: ADA ≤7.0%
• American College of Endocrinology <6.5%
• Normal A1C reduces risks of Retinopathy, Nephropathy, and Neuropathy

Goals of Diabetes Management

• Decrease symptoms
• Prevent acute complications
• Delay onset and progression of long-term complications
• Patient education like self monitoring
• Other treatments include nutritional therapy, drug therapy, and exercise

Diabetes Drug Therapy - Insulin

• Exogenous insulin comes from an outside source
• Required for Type 1 diabetes
• Prescribed for patients with Type 2 diabetes who cannot control blood glucose by other means
• Insulin cannot be taken orally
• Administered via a subcutaneous injection for self-administration, or IV administration
• Rapid-acting insulin lispro, aspart or glulisine are often prescribed for injection 0 to 15 minutes before a meal and have an onset of action of 15 mins
• Short Acting regular insulins are injected 30 to 45 mins before meal and have an onset of 30 to 60 mins
• Long acting is injected once a day at bedtime or in the morning and are released steadily with no peak action
• Long acting insulin cannot be mixed with any others
• Insulin pens should not be injected into site about to be exercised and do not require an alcohol swab
• Insulin pumps are continuous subcutaneous infusion, that are battery-operated devices
• Potential for tight glucose control

Problems with Insulin Therapy

• Hypoglycemia
• Allergic reaction
• Lipodystrophy
• Somogyi effect
• Dawn phenomenon

Somogyi Effect

• Rebound effect in which an overdose of insulin causes hypoglycemia
• Usually during hours of sleep
• Counterregulatory hormones released
• Rebound hyperglycemia and ketosis may occur.

Dawn Phenomenon

• Characterized by hyperglycemia present on awakening in the morning
• Due to release of counterregulatory hormones in predawn hours

Oral Diabetes Medications

• Oral agents work on three defects of type 2 diabetes, which are:
  • Insulin resistance
  • Decreased insulin production
  • Increased hepatic glucose production
• Common oral medications include:
  • Sulfonylureas
  • Meglitinides
  • Biguanides -A-glucosidase inhibitors -Thiazolidinediones
• DDP-4 is also used to inhibit the hormone

Oral agents

• Sulfonylureas increase insulin production from the pancreas, but there is a chance of prolonged hypoglycemia
• Examples include Glipizide (Glucotrol), Glimepiride (Amaryl)
• Meglitinides increase insulin production from pancreas, and should be taken 30 minutes before each meal up to time of meal
  • Examples include Repaglinide (Prandin), Nateglinide (Starlix)
• Biguanides reduce glucose production by the liver, enhance insulin sensitivity at tissues, improve glucose transport into cells, and do not promote weight gain
  • Example includeMetformin(Glucophage)
  • A-Glucosidase Inhibitors can be referred as "starch blockers", which slow down absorption of carbohydrate in the small intestine
  • Example, Acarbose (Precose)
• Thiazolidinediones are effective in those with insulin resistance, improving insulin sensitivity, transport, and utilization at target tissues
  • Examples: Pioglitazone (Actos), Rosiglitazone (Avand

Diabetes Nutritional Therapy

• Type 1 Diabetes Mellitus
  • Meal plan is based on individual's usual food intake and is balanced with insulin and exercise patterns
  • Insulin regimen is managed day to day
• Type 2 Diabetes Mellitus
  • Emphasis is based on achieving glucose, lipid, and blood pressure goals, also requires calorie reduction -Other management includes Glycemic Index (GI) diet teaching with the plate method, alcohol restrictions -Patients should also exercise, several small carbohydrate snacks can be taken every 30 minutes during exercise to prevent hypoglycemia and should be done after meals Self-monitoring of blood glucose (SMBG), will enable the patient to make self-management decisions regarding diet, exercise, and medication

Acute Complications

• Diabetic Ketoacidosis (DKA)
  • Hyperosmolar Hyperglycemic Syndrome (HHS)
  • Hypoglycemia

Diabetic Ketoacidosis (DKA)

• Caused by profound deficiency of Insulin
• Body breaks down fat stores and Ketones are by-products of fat metabolism.
• Alter ph balance, causing metabolic acidosis
• Ketone bodies are then excreted in urine
• Electrolytes become depleted
• Is characterized by Hyperglycemia, Ketosis, Acidosis, and Dehydration
• Most likely occurs in Type 1

DKA Diagnostic symptoms

• Early symptoms include lethargy and weakness
• Dehydration shown by poor skin turgor and dry mucous membranes
• Includes Tachycardia and Orthostatic hypotension
• Leading to Abdominal pain and Anorexia with Vomiting
• Leads to Kussmaul respirations, which is rapid deep breathing in an attempt to reverse metabolic acidosis
• and sweet fruity odor

DKA - MANGEMENT

• Requires airway management
• Oxygen administration
• Correct fluid/electrolyte imbalance
• IV infusion 0.45% or 0.9% NaCL, to restore urine output and raise blood pressure
• When blood glucose levels approach 250 mg/dL, 5% dextrose added to regimen to prevent hypoglycemia
• Includes Potassium replacement and Sodium bicarbonate
• Insulin Therapy: withheld until fluid resuscitation has initianted and followed by insulin drip

HHS

• Hyperosmolar Hyperglycemic Syndrome (HHS) is a life-threatening syndrome Less common than DKA
• Often occurs in patients older than 60 years with type 2
• Patient has enough circulating insulin that ketoacidosis does not occur
• Produces fewer symptoms in earlier stages
• Neurologic manifestations occur because of ↑ serum osmolality

HHS- LABS/MANAGEMENT

• Blood glucose >400 mg/dL with Increase in serum osmolality Absent/minimal ketone bodies
• Is a Medical emergency that leads to a high mortality rate
• Therapy similar to DKA requires great fluid replacement
• HHS diagnostic findings include Tachycardia, Fever, Positive orthostatic tilt test, Dehydration, Thirst, Dizziness and poor skin turgor
• Other symptoms include altered mental status, Confusion, Weakness, Dry oral mucosa, Dry warm skin, Polyuria or oliguria and Nausea with vomiting

HYPOGLYCEMIA

• Low blood glucose that occurs when too much insulin in proportion to glucose in the blood
• Blood glucose level less than 70 mg/dL
• Common manifestations include confusion, irritability, diaphoresis, tremors, hunger, weakness, and visual disturbances
• Untreated can progress to loss of consciousness, seizures, coma, and death

HYPOGLYCEMIA MANGEMENT

• Check blood glucose at the first sign If ,70 mg/dL, begin treatment But If /70 mg/dL investigate further for the symptoms
• Treatment for conscious patients is to give 15 to 20 G of a simple carbohydrate
• Recheck blood sugar 15 minutes after treatment
• Repeat until blood sugar ,70 mg/dL.
• unconscious patients are to be Administer 1 mg of glucagon IM or subcutaneously and in acute care settings 20-50 ml of 50% dextrose IV push

When blood glucose ,70 mg/dl, give 15 - 20g of a simple carbohydrate, recheck blood sugar in 15 minutes; repeat until blood sugar,70 mg/dl, patient should eat regularly scheduled meal/snack to prevent rebound hypoglycemia

Medical Awareness

• Patients should carry a card and wear a bracelet or necklace indicates diabetes that will to ensure prompt attention

Chronic Complications

• Angiopathy is the main macro & microvascular complication
• Macrovascular Diseases:
  • Occur to large and medium sized blood vessels
  • tight glucose control may delay atherosclerotic process -Risk factors: obesity,smoking, hypertension, and sedantry lifestyle

Microvascular Complications

• Angiopathy results from thickening of vessel membranes in capillaries and arterioles
• In response to chronic hyperglycemia
• Is specific to Diabetes, unlike Macrovascular Diseases

Microvascular Diseases effects these areas: Eyes (Retinopathy) Kidneys (Nephropathy) Skin (Dermopathy) Clinical manifestations usually appear after 10-20 years of diabetes

Diabetic Retinopathy

Micro Vascular damages to the retina result of chronic hyperglycemia

• Most common cuase fo new cases of blindness in people 20-74 tears
• Earliest and Most Treatable stages often produces no vision changing effects
• Must have dilation eye examinations for type-1 diabetes Diabeteic Nephropathy is associated with damage to the kidney
• Is the leading cause of end stage renal disease Critical factors for delay, tight glucose control of the kidney
• Has two main components, blood pressure with angiotensin Yearly screenings, microalbuminuria in urine and serum creatinine is important

Diabetic Neuropathy

• Diabetic neuropathy is nerve damage related to metabolic derangements of diabetes
• 60-70% of the diabetes patients have some degree of that
• Nerve damage due to metabolic derangement of diabete
• sensory versus autonomic neuropathy with its complications are described now
• There are is sensory neuropathy which exhibits distal symmetric
• is the most common form that affects hands and/or feet laterally
• It consists characteristics include the loss of sensation , abnormal sensations, the potential for foot ulcers, and pain with paresthesia

Sensory Neuropathy Treatment

• Is to do tight blood glucose control and topical creams with possible DRUG treatments.

• these DRUGS include tricyclic antidepressants, a selective serotonin Norepinephrine reuptake inhibitor ,and anti-sea medication

• Autonomic Neuropathy which involves CAN affect nearly ALL the BODY system and COMPLICATIONS

• Foot Complications with it's Lower Extremity

• It’s the MOST Common CASE OF HOSPITALIZATION in Diabeteses

• Is a RESULT from COMBINATION of MICROVASCULARR DISEASE and MacroVASCULAR DISEASE

Foot Complications with Diabetetes- RIISK factors

• Sensory NEUROPATHY and Peripheral ARTERIAL Disease

Foot Complications with Diabetetes- Other contributors

• SMOKING and CLOTTING Abnormalities
• Additionally: Impaired IMMUNE Function and AUTONOMIC Neuropath

Explore key aspects of diabetes mellitus, including associated symptoms, insulin function, and counterregulatory hormones. Understand the mechanisms behind hyperglycemia in type 1 diabetes and the progression of the disease. Discover screening measures for complications like diabetic nephropathy and retinopathy.