34 Diabetes Types Quiz

Pharmacology of Diabetes Mellitus

• This lecture covers the pharmacology of diabetes, specifically focusing on insulin and other glucose-lowering medications.
• The course is Endocrine and Breast module, year 2.
• The lecturer is Professor Steve Safrany 341.
• The date of the lecture is January 2024.

Learning Outcomes

• Students will learn the mechanism of action of insulin and understand its therapeutic and adverse effects.
• Compare and contrast different types of insulin preparations and regimens, including their advantages and disadvantages.
• Explore potential future directions in insulin therapy, including new formulations, devices, and technologies.
• Understand the principles of pharmacotherapy for type 2 diabetes, including different drug classes, their mechanisms of action, and potential adverse effects.
• Students will evaluate the clinical efficacy of antidiabetic drugs regarding their impact on glycemic control, weight, blood pressure, lipid profiles, and other outcomes.

Diagnosis

• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or two-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) after an oral glucose tolerance test (OGTT).
• HbA1c ≥48 mmol/mol (equivalent to 6.5%) or random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of symptoms of hyperglycemia.

Type 2 vs Type 1 Diabetes

• Type 2 diabetes is characterized by insulin resistance with relative insulin deficiency, with hyperglycemia developing gradually. It can often be treated with oral medications and is associated with increasing age and obesity.
• Type 1 diabetes is characterized by absolute insulin deficiency, with an abrupt onset of hyperglycemia and a propensity for diabetic ketoacidosis (DKA). Insulin therapy is required, and it is associated with autoantibodies and predominantly diagnosed in individuals under 30 years old.

Management of Diabetes Mellitus

• Type 2 diabetes management involves a multidisciplinary approach, including patient education and support; lifestyle modifications (diet, exercise, weight loss); pharmacologic therapies (e.g., oral medications, GLP-1 agonists, and insulin); and consideration of bariatric surgery.
• Type 1 diabetes management primarily involves a multidisciplinary approach, including patient education and support; dietary advice (including carb counting, glycemic index diets and dietary advice, and physical activity advice; insulin therapy (injections or insulin pump); and newer treatments on the horizon (e.g., islet cell and stem cell therapies).

Indications for Insulin

• Insulin is indicated for treatment of type 1 diabetes.
• It's also used in cases of inadequately controlled type 2 diabetes.
• Other indications include temporary use during hospitalization or surgery, during pregnancy, for patients with renal disease when oral medications are not appropriate, or for initially controlling severe new-onset type 2 diabetes.

A Century of Insulin Therapy

• Timeline of insulin therapy innovation, from the first human treatment, the development of NPH insulin, pump therapy, human insulin, and insulin analogs.

Insulin Therapy in Type 1 Diabetes

• Includes insulin replacement therapy with adjustments based on carbohydrate intake, exercise, and blood glucose profiles.
• Regular monitoring of blood glucose levels and adjustment of insulin doses as appropriate is necessary.
• Monitoring for complications related to diabetes is crucial.

Bolus Insulin

• Used for mealtime or post-meal coverage of needed insulin.
• Includes short-acting, regular, rapid-acting (aspart, lispro, and glulisine) insulin preparations, including inhalation powder.
• Used before meals, or to correct hyperglycemia.

Basal Insulin

• Mimics the body's basal insulin secretion to maintain euglycemia (normal blood glucose) between meals.
• Includes intermediate-acting insulin (NPH, available in multiple brands like Humulin N and Novolin N) as well as long-acting options for ongoing, constant blood sugar regulation.
• Includes glargine, detemir, and degludec.

NPH Insulin (Intermediate-acting)

• Neutral protamine Hagedorn insulin, a suspension of zinc insulin combined with protamine.
• Developed in 1936, it was among the first basal insulins.
• Action duration: 10-20 hours, but has a peak in action that increases risk of hypoglycemia.
• Can be combined with other insulins.

Insulin Glargine

• Peakless 24-hour basal insulin delivered as a subcutaneous injection.
• Modifications to the insulin structure (substitution of glycine at A21 and addition of two arginines at B30) allow for a unique release pattern and a steady, sustained rate.
• Administered once per day.

Insulin Pharmacodynamics

• Table showing the onset, peak, and duration of action for various insulin preparations.
• This aids in understanding how different insulins work in the body.

Summary of Insulin Activity

• Graph demonstrating the activity profiles of various insulin preparations.
• The graph shows how different types of insulin affect blood sugar over time and their duration of action.

Insulin Administration Regimens

• Conventional regimen: Basal insulin only; twice daily mixed split (intermediate and short or rapid-acting insulin).
• Basal-bolus: Long-acting insulin combined with rapid-acting insulin before meals.
• Insulin pump (Continuous Subcutaneous Insulin Infusion): Continuous delivery of insulin throughout the day to match fluctuating blood sugar needs.

Pitfalls of Conventional Twice-daily Split-Mixed Regimen

• Shows the potential challenges of using a twice-daily mixed insulin regimen.
• Features areas of potential high and low blood sugar swings.

Mimicking Nature: The Basal-Bolus Insulin Concept

• Graphical illustration of how basal-bolus insulin therapy mimics normal physiological insulin patterns throughout a day.
• This helps clinicians to understand how to match insulin delivery with normal body rhythms, leading to better glucose regulation.

Insulin Pump Therapy

• Mechanism of insulin pump delivery of insulin.
• Description of the insulin pump use, and how it continuously delivers insulin to match blood sugar fluctuations.

Pharmacokinetic Advantages of Insulin Pump (CSII)

• Uses only rapid-acting insulin.
• Single injection site for insulin delivery.
• Basal insulin requirements delivered as mini-boluses every 5 minutes, allowing for precise blood sugar control.

Automated Insulin Delivery Systems (Hybrid Closed Loop Device)

• Combination of insulin pump and continuous glucose monitor (CGM) that enables automatic insulin delivery adjustments.
• Algorithms to automatically adjust basal insulin rates based on incoming CGM glucose data.
• Patients still need to manually give pre-meal boluses.
• Benefits: better glycemic control, less severe hypoglycemia.
• Drawbacks: High cost.

Inhaled Insulin

• Rapid-acting insulin delivered via inhalation, a newer form of insulin administration.
• Quick onset (median time to peak effect about 53 minutes).
• For non-smokers without pulmonary disease; rarely used.
• It is less effective than subcutaneous insulin delivery.
• Potential pulmonary toxicity.

Advances in Insulin Delivery

• Pictures demonstrating various insulin delivery technologies, from older to newer approaches, including inhaled insulin, insulin pens, insulin pumps, and CGM devices.

Insulin Side Effects

• Common: hypoglycemia.
• Less common: Lipodystrophy, including localized loss of subcutaneous fat (lipoatrophy) and localized fat buildup (lipohypertrophy) at injection sites.
• Allergic reactions (local or systemic) can also happen at the injection site and even throughout the body.

Summary of Insulin Use

• Insulin's use in treating both type 1 and type 2 diabetes.
• Basal-bolus insulin regimens as the most common method of administration.
• Importance of patient education on potential side effects like hypoglycemia.

Principles of Glucose Lowering Agents in Type 2 Diabetes

• Describes various types of drugs used in treatment of Type 2 diabetes.
• Includes multiple drugs, each with tissue-specific actions.
• Points out contraindications in pregnancy, highlighting which drugs are safe and those that should not be used together.
• Metformin is a preferred first-line choice though there may be other appropriate starting choices.

Insulin Resistance Associated Clinical Conditions

• Visual diagram showing conditions related to insulin resistance, such as hypertension, prediabetes, atherosclerosis, dyslipidemia (low HDL, high LDL, high triglycerides), obesity, polycystic ovary syndrome, and acanthosis nigricans.

Pathogenesis of Hyperglycemia in T2D

• Illustrates how insulin resistance leads to hyperglycemia in type 2 diabetes (T2D).
• Shows the relationship between liver glucose production, peripheral tissue glucose uptake, the pancreas, and the overall increase of blood glucose levels.

Organs Regulating Plasma Glucose

• Visual depiction of the interaction between various organs in regulating plasma glucose levels, highlighting the target actions of different drug classes.
• The diagram includes organs like the liver, pancreas, muscles, intestines, and kidneys.

Metformin (Glucophage)

• Mechanism of action on the liver (influencing AMPK) and potentially on intestinal glucose absorption and peripheral tissue utilization.
• Associated with mild weight loss, not inducing hypoglycemia.
• High efficacy, commonly prescribed for type 2 diabetes (T2D) and first-line treatment due to general safety profile.

Side Effects and Contraindications of Metformin

• Commonly encountered side effects, such as gastrointestinal issues (nausea, diarrhea).
• Serious but rare side effect: Lactic acidosis.
• Points out vitamin B12 deficiency as a potential side effect.
• Contraindications: T1D, severe renal dysfunction (low GFR).

Insulin Secretagogues: Sulfonylureas

• Mechanism of action: stimulating pancreatic insulin secretion for 12-24 hours.
• Drugs: Glipizide, glimepiride, and glyburide.
• Mechanism of action: Binds to K+ channels, increasing Ca2+ and stimulating insulin release.
• Adverse effects: hypoglycemia, weight gain.
• Contraindications: Type 1 diabetes, diabetic ketoacidosis (DKA), sulfa allergy.
• Metabolism: hepatic. Active metabolites excreted via the kidneys. Use caution in patients with renal impairment.
• Efficacy: Low to moderate A1c lowering.

Meglitinides/Glinides

• Mechanism: same as sulfonylureas, but faster onset and shorter duration of action (3-4 hours).
• Drugs: Repaglinide.
• Faster onset of action.
• Generally used to manage mealtime blood sugar spikes.
• Side effects: hypoglycemia, weight gain.
• Contraindications: Type 1 diabetes, liver failure, DKA, sulfa allergy.
• Metabolism: hepatic via CYP450 enzyme system
• Efficacy: Modest A1c lowering.

Alpha-glucosidase Inhibitors

• Mechanism: slows the breakdown of carbohydrates in the intestines, thereby decreasing the rise in blood glucose after meals.
• Drug: Acarbose,
• Administration: Oral, taken with meals.
• Side effects: flatulence, bloating.
• Contraindications: gastrointestinal disorders like inflammatory bowel disease.
• Metabolism: excreted unchanged in the urine
• Efficacy: A1c lowering is somewhat lower (typically under 0.5%).

Incretin Hormones

• Released from the intestine after a meal, stimulating insulin release from the pancreas and reducing glucagon secretion. This improves blood glucose control.
• GLP-1 and GIP are primarily responsible.
• Often diminished release of incretins in T2DM.

The Incretin System

• Diagram illustrating the process of incretin hormones impacting insulin secretion, blood glucose homeostasis, and glucagon regulation.
• Gut hormones influence pancreatic function to improve blood glucose control after eating.

GLP-1 Receptor Agonists (GLP-1 RA)

• Mechanism of action: enhance glucose-dependent insulin secretion, slow gastric emptying, reduce glucagon secretion to affect blood sugar levels and help with satiety.
• Administration: subcutaneous injection or some oral options.
• These drugs mimic and enhance the function of GLP-1.
• Drugs: Semaglutide, liraglutide, and dulaglutide.
• Side effects: GI issues; pancreatitis.
• Contraindications: Pre-existing pancreatitis

GIP/GLP-1 Receptor Agonists

• Mechanism: combined GIP and GLP-1 receptor agonist for enhanced insulin secretion and reduced glucagon secretion.
• Drug: Tirzepatide
• Administration: Subcutaneous injection.
• Side effects: GI issues; pancreatitis
• A1c lowering and weight loss

DPP IV Inhibitors

• Mechanism: inhibits the enzyme DPP-IV, increasing the activity of incretins GLP-1 and GIP, increasing insulin secretion.
• Drugs: Sitagliptin, linagliptin, vildagliptin, saxagliptin.
• Metabolism: variable (some excreted unchanged in urine).
• Contraindications: pre-existing pancreatitis.
• Side effects: mostly gastrointestinal.
• No/minimal hypoglycemia and weight neutral.
• Efficacy: lowers A1c ~ 0.7%.

Normal Renal Glucose Handling

• Diagram showing the kidneys' role in filtering and reabsorbing glucose.
• SGLTs (sodium-glucose co-transporters) predominantly SGLT2 responsible, reabsorbing approximately 90% filtered glucose.

SGLT2 Inhibitors

• Mechanism: Block reabsorption of glucose in the kidney, increasing glucose excretion in the urine (which carries some calories with it.) .
• Drugs: Empagliflozin, canagliflozin, dapagliflozin.
• Side effects: genital yeast infections, urinary tract infections, osmotic diuresis, sometimes euglycemic diabetic ketoacidosis (euglycemic DKA).
• Contraindications: severe kidney impairment and end-stage kidney disease (ESRD).
• Weight loss.

Summary of Adverse Effects and Contraindications

• Summarizes the adverse effects (negative side effects), effect on weight, and contraindications (situations when a drug should not be given or used).

Test your knowledge on the differences between Type 1 and Type 2 diabetes with this quiz. Explore questions about hyperglycemia onset, clinical features, treatment approaches, and associated characteristics. It's an essential assessment for students and professionals alike.