Diabetes

• Islet of Langerhans

  Makes up 2%, A cells secrete glucagon and B cells secrete insulin
• Islet of Langerhans


  • Contains hormones insulin and glucagon which are secreted into the liver to maintain 4 to 6 mmol/L
• Insulin


  • Continuously released into the body with increased amount after eating
  • Required for glucose uptake in skeletal, fat, and heart muscle
  • Suppress liver production of glucose
  • Converts excess glucose to free fatty acids through a process called glycogenesis
• Glucagon


  • Raises blood glucose
  • Released in response to low levels of blood glucose and releases it to the liver
  • Counter to insulin and stimulates glycogenolysis (Breakdown of glycogen to glucose)
• Diabetes

  • Multisystem disease related to abnormal insulin or impaired use of insulin
  • Metabolism disorder affecting carbs, fats and proteins
• Reasons for diabetes

  • Inadequate production of insulin due to destruction of B cells
  • Insulin resistance due the cells are less able to metabolize the glucose available to them
  • Enhanced stress which is a proinflammatory state stimulates glycogenolysis and gluconeogenesis
• Type 1 diabetes

  • Insulin dependent or juvenile onset
  • Autoimmune destruction of B cells with 90% of them destroyed
  • Long preclinical period where the patient becomes symptomatic until they can no longer produce insulin
  • Treatment requires insulin
• Type 1 diabetes manifestations

  • Glucosuria, polyuria, polydipsia, polyphagia, weight loss
• Type 2 diabetes


  • Most prevalent with 90% of patients
  • Pancreas can still produce insulin but the cells are not able to metabolize it efficiently
  • Hyperinsulinemia leads to increased glucagon release from pancreas which leads to increased glucose production by the liver
  • Impaired insulin secretion - Insulin is no longer tightly coupled to plasma glucose content and gradual loss of Langerhans function
• Symptoms of type 2 diabetes


  • Gradual onset with increasing fatigue
  • Chronic complications of hyperglycemia
  • Fatigue, chronic infections, visual acuity, peripheral neuropathy on the feet
• Methods of diabetes diagnosis

  • Hemoglobin A1C of greater than 6.5%
  • Fasting blood glucose over 7 mmol/L
  • Random plasma blood glucose reading of 11.1
  • 2 hour oral glucose tolerance test less than 11.1 mmol at 30 and 60
• Screening every four years if over 40 years of age or if you have high risk
• Diabetic ketoacidosis

  • In the absence of insulin fats are metabolized instead of glucose, common with TYPE 1
  • Characterized by Hyperglycemia
  • Ketones are an acidic byproduct of fat metabolism
  • Clinical manifestations: hypovolemia, hypokalemia, Kussmaul's respirations, fruity breath
• Ketonuria

  Ketones are secreted in the urine
• Precipitating factors of diabetic ketoacidosis

  • Illness, infection, inadequate insulin dosage, insulin omission, undiagnosed Type 1 DM, poor self-management
• Hyperosmolar hyperglycemic state (HHS)

  • Seen in people with type 2 that can produce insulin
  • Hyperglycemia can be two times higher than in ketoacidosis
  • Decreased mental status and can go into a coma
  • Treatment: fluid replacement of 0.9 or 0.45 NS
• Hypoglycemia


  • Caused by too much insulin available in relation to glucose
  • Triggers release with endocrine hormones which causes neurogenic manifestations
  • Untreated can lead to loss of consciousness, seizures, coma, and death
• Hypoglycemia Manifestations

  • Shaky, nauseated, confused, hungry, HR increase, Weak, drowsy, numbness or tingling
• Complications of diabetes

  • Eye: Glaucoma, cataracts, and blindness
  • Kidney: Nephropathy
  • Neuropathy: Loss of sensation with burning and tingling
  • Brain: Increased risk of stroke, cardiovascular disease, and cognitive impairment
  • Heart: High blood pressure and insulin resistance increases risk of heart disease
  • Extremities: Peripheral vascular disease
• Metabolic syndrome


  Caused by high blood pressure, high cholesterol, and obesity
• Care with diabetes

  • Pharmacotherapy of insulin and oral antiglycemics
  • Blood sugar monitoring
• Non modifiable risk factors for diabetes

  • Men are more likely to get type 2 diabetes
  • African, Asian, Arab, Hispanic are at a increased risk of type 2 diabetes
  • Indigenous are also at a high risk for diabetes
• Modifiable diabetes risk factors

  • Physically active
  • Eating healthy food and enough fruits and vegetables
  • Cessation of tobacco
  • Losing weight
• Age related pancreas changes

  • Increase in fibrosis and fatty deposits in pancreas
  • Increases glucose intolerance
  • Insulin sensitivity
• Diet for diabetes

  Low sugar, high fiber, limiting high fat food, drinking water
• Exogenous (injected) Insulin


  • Required when a patient has inadequate insulin to meet specific metabolic needs
  • Always required for Type 1 DM
  • May be used in combination with oral antihyperglycemic agents (OHAs) to treat Type 2 DM
  • Various types of insulin that differ in onset, peak action, and duration
  • Insulin regimens are tailored to an individual patients needs and lifestyle
  • Goal is to maintain near normal blood sugar levels by replicating the bodies basal-bolus insulin regimen
• Oral Antihyperglycemics (OAHs)

  • Once diagnosed with Type 2 DM, standard of care is to start a patient on an OAH and support them to make lifestyle modifications
  • Patients can be on multiple different OAHs, each with different MOAs, to maintain target blood sugar levels
  • If OAHs and lifestyle modifications are not successful in maintaining stable blood sugars, a patient with type 2 DM can be prescribed injected insulin
• Metformin


  • Can delay the development of Type 2 DM in high-risk individuals
  • Inhibits glucose production in the liver
  • Sensitizes insulin receptors in target tissues (fat and skeletal muscle), increasing glucose uptake and slightly reduces glucose absorption in the gut.
  • Slightly reduces glucose absorption in the gut
• Gliclazide

  • Stimulates the release of insulin from pancreatic beta cells, and may increase target cell sensitivity to insulin
  • Adverse effects: can cause hypoglycemia - dose-dependent reduction in blood glucose
  • Patients should take right before or with meals
  • Eliminated by hepatic metabolism and renal excretion
• Gabapentin


  • May enhance GABA release, thereby increasing GABA-mediated inhibition of neuronal firing
  • Increase in GABA block the neurotransmission of pain signals
  • Decrease awareness/sensation of pain
  • Side effects: drowsiness, confusion, dizziness
• Semaglutide Injection (Ozempic)


  • To reduce the risk of major cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes with known heart disease
  • Reduce A1C
  • Reduce risk of CVD
  • Weight loss
• Metformin is not metabolized but excreted unchanged by the kidneys, in the event of kidney impairment, metformin can accumulate to toxic levels.
• Side effects of Metformin: GI disturbance

  
  

  Adverse effect of Metformin: lactic acidosis – avoid giving to patients who have liver disease, severe infection, or history of lactic acidosis. Does not cause weight gain. Does not cause hypoglycemia

  • Well suited for patients who tend to skip meals
• Semaglutide injections (Ozempic) Side effects: Thyroid Cancer, inflammation of pancreas, changes in vision, hypoglycemia, kidney failure, gallbladder problems, allergic reactions, nausea, vomiting, diarrhea, stomach pain, constipation
• Side effects of gliclazide: diarrhea, spots/redness on skin, nausea and vomiting, may make skin more sensitive to UV rays, may cause low blood sugar (hypoglycemia)