Diabetes Management and Insulin Types Quiz

Diabetes Mellitus (DM)

• DM is a group of metabolic disorders characterized by chronically elevated blood glucose (BG), abnormal carbohydrate, fat, and protein metabolism
• It affects the body's ability to produce and/or utilize insulin.
• DM has categories including Type 1 and Type 2.
• Without treatment DM can cause acute complications such as Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)
• Chronic hyperglycemia can lead to microvascular, macrovascular and neuropathic complications.

Type 1 DM

• (5%-10% of cases) Characterized by the pancreas not producing insulin
• Usually due to autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.
• Occurs in children and adolescents but can occur at any age.
• Amylin (a hormone co-secreted from beta cells with insulin), is deficient in patients with Type 1 DM

Type 2 DM

• (90%-95% of cases)
• The age of onset is ≥45 years
• Insulin resistance:
  • Excess hepatic glucose production -↓ skeletal muscle uptake of glucose -↑ lipolysis and F.A production.
  • Impairment in insulin secretion, Beta cell mass and function are reduced.
• Incretin effects: GLP-1 & GIP are released, to stimulate insulin secretion and suppress glucagon release.
• The condition is progressive.

Clinical Presentation Type 1

• Patients often exhibit symptoms in the days or weeks preceding the diagnosis.
• Common initial symptoms include polyuria, polydipsia, polyphagia, weight loss, fatigue, and lethargy.
• Individuals are often thin and are prone to develop DKA in the absence of an adequate insulin supply.
• Symptom onset can sometimes be triggered by infection, trauma, or psychological stress.

Clinical Presentation Type 2

• Many patients are asymptomatic or have only mild fatigue at the time of diagnosis.
• Patients with Type 2 DM are often found incidentally during routine lab. testing.
• Complications such as myocardial infarction and stroke, may be present at the time of diagnosis.
• Hemoglobin A1c (HbA1c) is an important blood test that provides an average blood glucose over the past 2-3 months.
• Most patients are overweight or obese with an elevated waist-to-hip ratio

Diagnosis

• Diagnostic criteria vary but involve a combination of parameters testing fasting blood glucose (FPG), a two-hour post-load plasma glucose (oral glucose tolerance test) and glycosylated hemoglobin A1C (A1C).
• Prediabetes is a condition of abnormal BG but does not meet thresholds to define DM.

Goals of Treatment

• The primary goal is preventing or delaying the progression of long-term microvascular and macrovascular complications of hyperglycemia.
• Additional goals involve alleviating symptoms, minimizing hypoglycemia, minimizing treatment burden, and maintaining quality of life.
• Appropriate glycemic targets for non-pregnant adults with diabetes are detailed in a table.

Insulin

• Endogenous insulin moves glucose out of the bloodstream into the cells, lowering serum glucose levels.
• Two main groups of exogenous insulin are human insulins and insulin analogues.
• Insulin's main advantage is achieving a wide range of glucose targets.
• Disadvantages include an increased risk of hypoglycemia, a need for injections, weight gain, and treatment burden.

Insulin Administration

• Most insulin products are administered subcutaneously (SC).
• An exception is inhaled human insulin, a dry powder of regular insulin absorbed through the lungs.
• Various methods for insulin administration exist (syringe, pen, pump, inhaler)

Insulin Concentration & Pharmacokinetics

• The most common insulin concentration is 100 units/mL (U-100).
• More concentrated insulins (e.g., U-200, U-300, U-500) may be required in patients needing larger doses
• Insulin products are characterized by their onset, peak, and duration of action.

Types of Insulin

• Insulin can be broadly classified by the rate of onset and duration for achieving the desired effect.
• Rapid-acting, regular/short-acting, intermediate-acting, and long-acting are distinct types of insulin based on its differing onset and duration.
• Acarbose is an inhibitor of alpha-glucosidase enzymes, used to slow glucose absorption, reducing postprandial glucose levels.

Basal Insulin

• This type of insulin is also background insulin.
• It helps regulate blood glucose levels between meals and during the night.
• Common forms of basal insulin include NPH and glargine.

Bolus Insulin

• Bolus insulin, or prandial insulin, is given to cover meals and is short or rapid-acting.
• The insulin dose is taken to control and address elevated blood glucose levels.
• Types of bolus insulins include Insulin Aspart, Lispro, and Glulisine.

Rapid-acting Insulins

• Rapid-acting insulins offer a faster onset and shorter duration of action compared to regular insulins;
• Ultra-rapid acting insulins provide an even faster onset.

Adverse Effects

• Hypoglycemia is the most common adverse effect, Insulin also causes a dose-dependent weight gain, predominantly truncal fat.
• Injection site reactions, such as redness, pain, itching, urticaria, edema, and inflammation can occur.
• Lipoatrophy or lipo-hypertrophy (a lump of fatty tissue) can develop under the skin with improper injection site rotation.
• Inhaled human insulin is contraindicated in patients with COPD and asthma.
• The risk of hypoglycemia is reduced when GLP1RAs are administered with Metformin, or a TZD.

Biguanides (Metformin)

• Oral medication for type 2 diabetes.
• Reduces hepatic glucose production and enhances insulin sensitivity in peripheral tissues (muscle).
• Enables glucose uptake into muscle cells.
• 1st-line pharmacotherapy for type 2 DM (unless CI or intolerability)
• Initial therapy is at a low dose (typically 500 mg) with meals.
• Dosage is progressively increased (in 500-mg increments) over several weeks.

Advantages of Metformin

• Reduces A1C levels by 1.5%–2% and FPG levels by 60–80 mg/dL in drug-naïve patients.
• Reduces plasma triglycerides (TG) and LDL-C by 8%–15% and may moderately increase HDL-C levels.
• Does not cause weight gain, may lead to a modest weight loss
• Relatively low risk of hypoglycemia.

Disadvantages of Metformin

• Frequently causes GI side effects (diarrhea, abdominal discomfort).
• Metallic taste and may decrease vitamin B12 levels.
• Contraindicated in renal insufficiency (eGFR <30 mL/min/1.73 m2).

Thiazolidinediones (TZDs) (Pioglitazone, Rosiglitazone)

• Agents for reducing insulin resistance.
• Enhance insulin sensitivity in muscle, liver, and fat tissues
• Improve glycemic control in patients with type 2 diabetes.
• Both can achieve an A1C reduction of 1%–1.5% and a FPG reduction of 60–70 mg/dL (3.3–3.9 mmol/L)
• The maximum effect may not appear until 4–6 weeks of treatment.
• Taken orally once daily with or without food.
• TZDs can be used in combination with metformin and other commonly prescribed medications for type 2 DM.

Disadvantages of TZDs

• Fluid retention (peripheral edema), heart failure, and osteoporosis are common side effects .
• Pioglitazone is linked to reduced plasma triglycerides (TG and LDL-C) while Rosiglitazone may increase LDL-C
• Weight gain (4 kg or more) is frequently reported
• TZDs are associated with an increased risk of fractures, especially in postmenopausal women.

Alpha-glucosidase Inhibitors

• Acarbose and Miglitol are used to slow glucose absorption from the intestines.
• Reducing postprandial glucose (PPG) levels.
• A1C lowering is modest.
• Commonly reported side effects include flatulence, abdominal pain, and diarrhea.
• Contraindicated in patients with cirrhosis, colonic ulcers, intestinal disease, or diabetic ketoacidosis.

Amylin Analogs (Pramlintide)

• Synthetic amylin analog that reduces glucagon secretion
• Slows gastric emptying
• Increases satiety
• Decreases postprandial glucose (PPG)
• First non-insulin agent approved for type 1 DM.
• Lowering both PPG levels and A1C levels, with reductions of 0.6% in type 2 and 0.4%–0.5% in type 1.
• Often used as adjunctive therapy for patients with type 1 and 2 who are not adequately controlling postprandial blood glucose.

Glucagon-like Peptide 1 Receptor Agonists

• Class of incretins (GLP-1RAs).
• Stimulate insulin secretion, suppress glucagon secretion
• Decrease hepatic glucose output.
• Decrease gastric emptying and promote satiety.
• Weight loss (1–3 kg) is a common side effect.
• Available as both short-acting (exenatide, lixisenatide) and long-acting (dulaglutide, exenatide XR, liraglutide, semaglutide)
• The most common side effects include nausea, vomiting, and diarrhea, injection site reactions, hypersensitivity reactions (including anaphylaxis).

GLP-1 RAs Precautions

• GLP-1RAs are not frequently recommended as first-line therapy.
• Used as second-line therapy in patients with established atherosclerotic disease, CKD and require careful monitoring if using with other diabetes medications such as, sulfonylureas, or insulin.