Diabetes Mellitus Flashcards
What’s DM?
DM is a group of metabolic diseases characterized by hyperglycemia resulting from impaired secretion of insulin, impaired action of insulin or both
The chronic hyperglycemics of diabetes is associated with long-term damage,dysfunction failure of various organs, eye, kidney, heart, blood vessels, nerves
Physiology of DM and action of insulin
Betacells from pancreas secrete insulin,
Insulin acts on target tissues (e.g., muscle, liver, and adipose tissue
Insulin connect/ bind with specific receptors( insulin receptors) on cell surface to transport glucose to or in the cell.
Insulin Regulates/ maintains the normal glucose levels (3.3-5-5
M/mol/L)
Insulin also takes part in protein synthesis and lipid synthesis
Levels that regulate glucose
For insulin
Glycogen synthesis+
Gluconogenesis-
Glycolysis+
For Glucagon/ glucocorticoids
Glycogen synthesis-
Gluconogenesis+
Glycolysis-
More info on the levels that regulate glucose
Glycogen Synthesis (Glycogenesis)
Glycogen synthesis, also known as glycogenesis, is the process by which glucose molecules are converted into glycogen, a storage form of glucose in the body. Glycogenesis primarily takes place in the liver and muscle cells. It is stimulated by insulin and facilitated by the enzymes glycogen synthase and branching enzyme. Glycogen is an important energy reserve that can be broken down into glucose during periods of fasting or increased energy demand, such as during exercise.
Gluconeogenesis
Gluconeogenesis is the process of generating glucose from non-carbohydrate sources, such as lactic acid, glycerol, and certain amino acids. This process occurs primarily in the liver and, to a lesser extent, in the kidneys. Gluconeogenesis is essential during periods of fasting, intense exercise, or low carbohydrate diets, as it helps to maintain a stable blood glucose level and provide energy to glucose-dependent tissues like the brain and red blood cells. Key enzymes involved in gluconeogenesis include pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase.
Glycolysis
Glycolysis is a metabolic pathway that breaks down glucose (a six-carbon molecule) into two molecules of pyruvate (a three-carbon molecule). This process occurs in the cytoplasm of cells and generates ATP (adenosine triphosphate), NADH (nicotinamide adenine dinucleotide), and other intermediate metabolites. Glycolysis is an anaerobic process (does not require oxygen) and serves as a primary energy source for cells, especially under anaerobic conditions or during periods of high energy demand. Key enzymes involved in glycolysis include hexokinase, phosphofructokinase-1, and pyruvate kinase.
In summary, glycogenesis and gluconeogenesis are two opposing metabolic pathways responsible for the synthesis and degradation of glycogen, respectively. Glycogen acts as an energy storage molecule. Glycolysis, on the other hand, is the breakdown of glucose to produce energy in the form of ATP, which fuels various cellular processes.
More info on the levels that regulate glucose
Glycogen Synthesis (Glycogenesis)
Glycogen synthesis, also known as glycogenesis, is the process by which glucose molecules are converted into glycogen, a storage form of glucose in the body. Glycogenesis primarily takes place in the liver and muscle cells. It is stimulated by insulin and facilitated by the enzymes glycogen synthase and branching enzyme. Glycogen is an important energy reserve that can be broken down into glucose during periods of fasting or increased energy demand, such as during exercise.
Gluconeogenesis
Gluconeogenesis is the process of generating glucose from non-carbohydrate sources, such as lactic acid, glycerol, and certain amino acids. This process occurs primarily in the liver and, to a lesser extent, in the kidneys. Gluconeogenesis is essential during periods of fasting, intense exercise, or low carbohydrate diets, as it helps to maintain a stable blood glucose level and provide energy to glucose-dependent tissues like the brain and red blood cells. Key enzymes involved in gluconeogenesis include pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase.
Glycolysis
Glycolysis is a metabolic pathway that breaks down glucose (a six-carbon molecule) into two molecules of pyruvate (a three-carbon molecule). This process occurs in the cytoplasm of cells and generates ATP (adenosine triphosphate), NADH (nicotinamide adenine dinucleotide), and other intermediate metabolites. Glycolysis is an anaerobic process (does not require oxygen) and serves as a primary energy source for cells, especially under anaerobic conditions or during periods of high energy demand. Key enzymes involved in glycolysis include hexokinase, phosphofructokinase-1, and pyruvate kinase.
In summary, glycogenesis and gluconeogenesis are two opposing metabolic pathways responsible for the synthesis and degradation of glycogen, respectively. Glycogen acts as an energy storage molecule. Glycolysis, on the other hand, is the breakdown of glucose to produce energy in the form of ATP, which fuels various cellular processes.
Classifications of DM
Type I - idiopathic and autoimmune( immune mediated)
Type 2 - insulin resistance and insulin secretory deficiency
Others specify-
a)Monogenic DM(MODY)- typical for young people basically like type one with mild symptoms of type 2 caused by mutation of genes responsible for insulin secretion. usually develops before the age of 25
b)Secondary DM- i) by endocrine disorders normally with hyper production of hormones example Pheochromocytoma(that produces an excessive amount of adrenaline and noradrenaline). Cushing’s Syndrome ( caused by the overproduction of cortisol, a stress hormone produced by the adrenal gland)
ii) by pancreas disease- Pancreatic Trauma (Traumatic injuries to the pancreas), chronic pancreatitis,cystic fibrosis,
c)Drug induced DM- glucocorticoids drugs
Gestation Diabetes-leaves after pregnancy
Diabetes in pregnancy
Type one DM
Type 1 Diabetes
Type 1 diabetes, also known as insulin-dependent, is an autoimmune disorder where the body’s immune system attacks and destroys insulin-producing beta cells in the pancreas.
It usually develops in childhood or adolescence but can occur at any age.
Fast process, severe leads to absolute insulin
Insufficiency
Type one symptoms
Thirst, weight loss, hunger, polyuria,
Excessive thirst and increased fluid intake (polydipsia).
Frequent urination (polyuria), particularly at night (nocturia).
Unexplained weight loss, despite increased appetite and food intake (polyphagia).
Fatigue and weakness due to the body’s inability to properly use glucose for energy.
Blurred vision as a result of high blood glucose levels causing fluid shifts in the eye.
Slow-healing wounds and frequent infections, as high blood glucose can impair the immune system and hinder wound healing.
Nausea, vomiting, or stomach pain, which can occur as a result of diabetic ketoacidosis (DKA), a life-threatening complication of Type 1 diabetes.
Type two DM
Type 2 diabetes, also known as non-insulin-dependent or adult-onset diabetes, is the most common form of diabetes.
It occurs when the body becomes resistant to the effects of insulin or does not produce enough insulin to meet its needs.
Type 2 diabetes typically develops in adulthood, but is increasingly seen in children and adolescents due to rising obesity rates.
Gradual, mild clinical symptoms, problem with receptors
Symptoms of type two
Obesity,
Increased thirst and frequent urination: Just like in Type 1 diabetes, the body tries to rid itself of excess glucose through urine, leading to increased thirst and urination.
Fatigue: High blood glucose levels can cause fatigue, as the body is unable to use glucose for energy effectively.
Blurred vision: High blood glucose levels can cause fluid shifts in the eye, leading to blurred vision.
Slow healing wounds: High blood glucose levels can impair the immune system and delay wound healing.
Numbness or tingling in the hands or feet: Over time, high blood glucose levels can cause nerve damage, resulting in numbness or tingling sensations in the extremities.
Dark patches of skin: Diabetes can cause dark patches of skin, especially in the armpits and neck.
DM diagnostics
Blood glucose test( capillary/ venous)
Oral glucose tolerance
Glycated hemoglobin BT( HBAIc)
DM Insulin therapy- absolute indication for insulin
DM type 1
DM + diabetes ketoacidosis , diabetic coma
DM+ pregnancy
DM type2 + therapeutic failure of oral antidiabetic agents
Normal secretion of Insulin in thebody
A) basal secretion- insulin is secreted in Bits (long and intermediate)
B) prandial secretion -meal secretion here insulin increases after eating ( short acting and rapid)
Mixed
Prandial secretion rapid acting drugs and short acting drugs
Prandial secretion refers to the release of certain hormones or enzymes in response to food intake.
Rapid-acting insulin: These drugs are designed to be absorbed quickly and start working within 15 minutes, with a peak action time of about 1 hour
Rapid-acting insulin:
NovoLog (insulin aspart)
Humalog (insulin lispro)
Apidra (insulin glulisine)
Short-acting insulin: These drugs take longer to start working compared in to rapid-acting insulin, usually beginning to act within 30 minutes and peaking after 2-3 hours
Short-acting insulin:
Regular insulin (Humulin R)
Actrapid
basal secretion interme acting drugs and long acting drugs Examples
Basal secretion refers to the continuous release of insulin by the pancreas to meet the body’s needs between meals and during periods of fasting
Intermediate-acting insulin:
Humulin N (NPH insulin)
Novolin N (NPH insulin)
Long-acting insulin:
Lantus (insulin glargine)
Levemir (insulin detemir)
Tresiba (insulin degludec)
DM insulin therapy
Insulin regimen
Intensive insulin Therapy
Conventional insulin therapy
Difference between intensive and conventional insulin therapy
A.Intensive insulin therapy involves multiple daily injections or or the use of an insulin pump to deliver insulin throughout the day while conventional therapy usually requires one or two injections per day
B. Due to its focus on tight glycemic control, intensive insulin therapy may increase the risk of hypoglycemic events compared to conventional therapy.
C. Intensive therapy has been shown to reduce the risk of long-term diabetes-related complications, such as retinopathy, nephropathy, and neuropathy, compared to conventional therapy
C.
Intensive insulin therapy and conventional insulin therapy
Intensive involves combination of basal insulin (long-acting) and bolus/prandial insulin (rapid-acting)
Usually for type 1DM
One drug is normally used
conventional involves use of insulin twice. before breakfast and dinner
Type 2DM
Simpler
DM
Insulin therapy
Devices for injection
And technique
Insulin syringe- subcutaneously 90
Pen-injector
Insulin pump
Injection Aids
Insulin Inhalers
Area
Arms (triceps)
Abdomen (umbilical region)
Upper outer quadrant of Glutes
Upper anterior lateral of area of hip
Indication for oral anti diabetic drugs treatment
And
Contraindications
Indications
DM type 2
Prediabetes ( metformin
Contraindications
Diabetic ketacidosis
Diabetic coma
Renal, hepatic failure
The pathophysiology of type 2 diabetes mellitus (T2DM) involves a complex interplay of genetic, environmental, and lifestyle factors that contribute to the development of insulin resistance and impaired insulin secretion.
Insulin Resistance: Insulin resistance is a decreased ability of target tissues (such as muscle, fat, and liver) to respond to insulin, leading to reduced glucose uptake and utilization. This is one of the earliest detectable abnormalities in T2DM.
Beta Cell Dysfunction: Pancreatic beta cells, responsible for insulin production, initially compensate for insulin resistance by increasing insulin secretion. However, over time, beta cell function declines, leading to insufficient insulin production to overcome insulin resistance.
Increased Glucagon Secretion: In T2DM, there is often increased secretion of glucagon, a hormone that stimulates glucose release from the liver. This contributes to elevated blood glucose levels.
Impaired Incretin Effect: Incretins are gut hormones that stimulate insulin secretion in response to meals. In T2DM, the incretin effect is reduced, leading to decreased insulin secretion and increased postprandial glucose levels.
Altered Fat Metabolism: Insulin resistance affects fat metabolism, leading to increased lipolysis and elevated levels of free fatty acids in the blood. This can cause ectopic fat deposition in the liver and muscle, contributing to insulin resistance.
Inflammation: Chronic low-grade inflammation is observed in T2DM, which may contribute to insulin resistance and beta cell dysfunction. Adipose tissue inflammation and activation of immune cells play a role in this process.
Genetic Factors: Genetic susceptibility plays a role in the development of T2DM, with multiple genes identified as contributing factors. These genes influence various aspects of insulin action, secretion, and metabolism.
Lifestyle Factors: Sedentary lifestyle, unhealthy diet, and obesity are significant risk factors for developing T2DM. They exacerbate insulin resistance and beta cell dysfunction, leading to disease progression.
The pathophysiology of type 2 diabetes involves a combination of these factors, leading to hyperglycemia, dyslipidemia, and increased risk of cardiovascular complications. Treatment strategies for T2DM aim to address these underlying abnormalities, focusing on lifestyle modifications, improving insulin sensitivity, and enhancing insulin secretion.
Oralantidiabeticdrugs
Oral forms and subcutaneous forms
Oral forms
A. Drugs that reduce insulin resistance-biguanides(metformin)
B. Drugs the enhance insulin secretion-sulfonylurea(Glimepiride,Glibenclamide)
C. Drugs which enhance glucose urinary excretion-SGLT-2inhibitors (gliflozins)
Sodium-Glucose Cotransporter 2inhibitor (Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
D.incretins - DPP-4 inhibitors (gliptins)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Subcutaneous form
Incretin- glp-1 analogues
GLP-1 receptor agonists are a class of injectable medications that mimic the actions of GLP-1, leading to improved glucose control in people with type 2 diabetes. Examples include:
Exenatide (Byetta, Bydureon)
Liraglutide (Victoza, Saxenda)
Dulaglutide (Trulicity)
Semaglutide (Ozempic)
Insulin
