Introduction Flashcards
What’s Diabetes
A clinical syndrome is characterized by chronic hyperglycemia as a result of relative absolute deficiency of insulin
Predisposed diabetes is
TYPE 1
Predetermined diabetes
Type 2
Diabetes can be a result of an absolute deficiency of insulin; here,
the pancreatic β-cells are not producing insulin due to the destruction of the β-cells (Type 1).
In relative deficiency of insulin
there is an amount of insulin being produced by the
β-cells
Type 1 diabetes is NOT strongly linked to
genetics
In type 1 there is exposure to toxins like
NITROSAMINES causing beta cell destruction
A global pandemic of diabetes what are some of the causes of type 2
- Lack of exercise
2.Obesity - SEDENTARY LIFESTYLE
4.URBANIZATION - Time of meals
Lack of insulin in the system will affect the metabolism of
carbohydrates,
fats,
amino acids
The number 1 structure affected in Diabetes is
BLOOD VESSELS
Why is wound healing difficult diabetes?
The hyperglycemia in diabetic patients provides a good medium for microbes to thrive,
Proteolysis also leads to reduced immunity since
proteins are the foundation of immunity.
Peripheral vascular disease OCCURS IN DM BECAUSE
insulin is low, there will be a breakdown of TG leading to more free fatty acids in the system that can lead to peripheral vascular disease which blocks the perfusion of blood to the extremities.
diabetic nephropathy due to
accumulation of sugar in the nephrons.
the body is able to maintain sugar level from
3.5 – 8mmol/L.
The body is able to maintain sugar levels by two simple methods;
• Intake of glucose and
• Utilization of glucose
Liver impairment will need
Glucose
Intake of glucose involves
1.From diet
2. GLUCONEOGENSIS when bodybis not getting glucose from food
In the adipose tissues, free fatty acids and glycerol
are produced from
breakdown of triglycerides (TG).
The substrates that move to the liver for hepatic Gluconeogensis are
GLYCEROL, PYRUVATE, LACTATE , and AMINO ACID
Free fatty acids move into the liver to initiate
Ketogenesis to produce ketone bodies.
In diabetes, there is no insulin to
push the glucose into the cells which leads to hyperglycemia
What will availability of insulin do?
pushes glucose from blood into the cells hence reducing
** hyperglycemia and gluconeogenesis **
Insulin inhibits
PROTEOLYSIS ie it is ANTIPROTEOLYTIC
Insulin is Anabolic meaning
helps in the buildup of muscles rather than their breakdown.
Insulin leads to the formation of
TRIGLYCERIDES
Since insulin leads to TG formation it causes
WEIGHT GAIN
β-cells do not produce direct insulin.
True They produce Proinsulin
The pro-insulin gets into the blood and is cleaved to produce
insulin and a C-peptide.
Significance of C-peptide
shows how much insulin is produced by the body.
Phase 2 insulin is
Plateau ie basal insulin
Phase 1 is characteristic of
soluble insulin.
Type 2 diabetes causes WHAT COMPLICATION
HHS (Hyperosmolar Hyperglycemic State) just as type 1 cases DKA.
CLINICAL IMPORTANCE OF C-PEPTIDE
- HELPS determine the amount of insulin produced since its in equimolar amounts
- Determine the secretory power of beta cells
3.To differentiate between type 1 and type 2
Causes of Type 2 diabetes
1.Genetic factors
2. Environmental factors
• Lifestyle
• Age
NB: Old age leads to reduction of β-cells.
Intake of fast foods causes the buildup of fat which opposes insulin action
Narrate the Pathophysiology of Insulin resistance 1
- Abdominal fats oppose insulin action at the periphery. Fats in the abdomen are stored in adipocytes.
- When the adipocytes get full, there is a spillage of fats into the blood which is deposited in the muscles and liver. These fats oppose the antilipolytic action of insulin.
- Also, when the adipocytes are full, the walls of the cells stretch.
This triggers the release of cytokines (Bad cytokines).
Narrate the Pathophysiology of Insulin resistance 2
1.Resistin: This opposes the action of insulin in the periphery.
- Tumor necrosis factor alpha (TNF-α) or interleukin 6 (IL-6): Causes inflammation (pro-inflammatory agent)
- Plasminogen activator inhibitor I: Causes thrombosis (pro-thrombotic agent)
Metformin is cardioprotective because
it inhibits plasminogen activator inhibitor I to prevent thrombosis.
Preventing occlusion
What therapy prevents the overstretched cytokinesADIPOCYTES?
Statins
Microvascular complications of diabetes
Retinopathy
• Nephropathy
• Neuropathy
Macrovascular complications
Coronary heart disease
• Stroke
• Peripheral vascular disease (PVD)
MOA of Metformin
-increases the sensitivity of insulin at the periphery.
- It inhibits gluconeogenesis in the liver.
-Metformin reduces the GI absorption of glucose.
- It also blocks the action of glucagon.
Is metformin metabolised?
NO, it is excreted via the Kidneys unchanged.
elimination half-life of metformin
1.3 – 4.5 hours
Metformin does not cause hypoglycaemia because
it does not stimulate insulin secretion. does not cause weight gain but rather causes a reduction in weight.
SE of Metformin
• GI disturbances – Diarrhea, abdominal cramping, nausea, etc. Hence, it is
advisable to take metformin with food.
• Lactic acidosis (rare) - because it reduces oxygen levels
• Vitamin B12 Deficiency
• Appetite decreased
• Diarrhoea (usually transient)
• Nausea and vomiting
• Taste altered
What is the purpose of combining metformin and insulin in the treatment of diabetes?
This is done to preserve the β-cells. It reduces the burden on β-cells to produce insulin hence preventing their downregulation
Contraindications of Metformin
-ACute MI
• Severe heart failure
• Liver disease
• Impaired renal function (eGFR < 30 mL/minute/1.73 m2)
• Acute metabolic acidosis (including lactic acidosis and diabetic ketoacidosis)
