Topic 2 - Diabetes Flashcards
What occurs to Carbs, Fat, and Protein during the Absorptive State?
Carbohydrates –> Converted into glucose and fat as major energy source
Fat –> Triglyceride synthesis and storage
Protein –> Protein synthesis, Excess converted and stored as triglyceride fat
What happens to the three main metabolic fuels during the Postabsorptive state?
Carbohydrates –> Glycogen degradation
Fat –> Triglyceride catabolism, Fatty acids provide major energy source for non glucose-dependent tissues
AAs –> gluconeogenesis
What do Beta cells secrete?
Secretory granules containing inactive C-peptide, insulin, and Amylin
How is proinsulin converted into insulin?
Cleaved by C-peptide
What do Alpha cells secrete?
Glucagon
What is the anabolic hormone?
Insulin
Why do elevated amino acid levels trigger the release of insulin?
Insulin is involved in the removal of amino acids and free fatty acids.
Why is it so important to maintain BGL?
Glucose is the brain’s only energy source, and it does not store glycogen.
How does adipose tissue affect metabolism?
Adipose tissue is the main energy storage site, it regulates fatty acid levels in the blood.
How does the liver affect metabolism?
The liver’s primary role is to maintain normal BGL. Promotes interconversions such as gluconeogenesis.
How does muscle affect metabolism?
Skeletal muscle is the primary site of AA storage as well as a major energy user
What is the role of incretins in regulating blood sugar? When are they released?
Incretins, such as GIP and GLP-1 are released after eating food. They exacerbate insulin secretion.
Why do elevated AA levels trigger glucagon secretion?
Protein rich meals require energy to be digested and for their energy to be used. Release of glucagon primes the body to metabolize AAs.
What are some examples of insulin’s counter-regulatory hormones?
–> Growth hormone
–> Glucocorticoids (Cortisol)
–> Adrenaline
What is Stress Induced Hyperglycaemia?
Stress hormones increase glucose production in the liver and decrease glucose use. E/NE increase FFAs in blood and inhibit peripheral glucose uptake.
How does exercise affect insulin levels?
Insulin levels decrease and glucagon levels increase. Additionally, muscle contractions increase insulin sensitivity, which maintains normal BGL in the presence of lower insulin levels.
What is Amylin?
A hormone secreted with insulin by Beta Islets. It inhibits gastric emptying and suppresses glucagon release.
Describe the process of how Beta Cells secrete insulin
- Glucose binds to GLUT 1
- Glucose is converted to ATP
- ATP activates K+ channel
- Cell depolarizes
- Ca2+ Channel opens
- Increased Ca2+ triggers exocytosis of insulin + amylin + C-peptide granule
Describe both phases of insulin secretion
1st Phase - Incretin hormones (GIP + GLP) trigger spike in insulin levels 3-5 minutes after eating. Release of preformed insulin
— Small drop in levels —
2nd Phase - At around 15 minutes the insulin secretion rises again and reach a new plateau in 2-3 hours. Most of this insulin is newly produced.
Describe the three kinds of insulin independent Glucose Transporters.
GLUT 1 - Makes blood brain barrier + B cells
GLUT 2 - Small amount in B cells
GLUT 3 - Pancreatic B cells + predominantly neurons
What kind of Glucose transporter is insulin dependent? Where are they found?
GLUT 4 - Muscle and Adipose Tissue
Where is GLUT 4 located? What is the advantage of this?
Located in the cells cytoplasm and packaged into vesicles. This way, transporters do not need to be manufactured, just implemented into their correct location.
What happens to an insulin receptor after it binds with insulin?
Insulin-receptor complex enters the cell via endocytosis.
–> Receptors are recycled to the cell surface
–> Insulin is degraded in lysosomes
What is the definition of diabetes? What is this condition characterized by?
Diabetes Mellitus is a glucose tolerance disorder characterized by hyperglycemia.
What kind of situations can cause secondary diabetes mellitus?
–> Pancreatic diseases
–> Diseases of the endocrine glands
–> Drug induced
What kinds of medication might cause secondary diabetes?
Corticosteroids used to treat severe asthma
What is acromegaly? Why might it cause secondary diabetes?
Excessive HGH, which inhibits insulin secretion
What is Cushing’s syndrome? Why might is cause secondary diabetes?
Excessive cortisol production, which increases gluconeogenesis and decreased peripheral glucose utilization.
What might cause glucose oversecretion?
Tumors of the A cells which increases glucagon secretion and gluconeogenesis.
What is a FPG? What are normal values for this test?
A fasting plasma glucose test. Patient is not allowed to eat for 8 hours, after which glucose levels are taken. Any measurement below 5.6 mmol/L indicates normoglycemic levels. Measurements between 5.6-6.9 indicate impaired fasting glucose (IFG) and any measurement of 7.0 or higher indicates DM.
What is a 2-OGTT? What are normal values for this test?
Patient is given oral glucose dose of 75 grams and their GBL is taken after two hours. Any measurement lower than 7.8 mmol/L indicates normoglycemic levels. 7.8-11.0 indicates high levels, and any measurement of 11.1< indicates DM
What is an HbA1C test?
A test to determine the amount of Glycosylated hemoglobin (A1c, or the amount of Hb with glucose attatched in bloodstream). High levels (>6.5%) indicate chronically high BGL.
Why is more insulin secreted after an oral dose vs an IV push?
Incretins, which exacerbate insulin secretion, are released only when food is eaten.
DM1 is characterized by hyperglycemia due to _____
Insulin deficiency
What is Type 1B DM?
Idiopathic DM, or degeneration of the B cells without a know autoimmune cause.
What is Type 1A DM?
Autoimmune destruction of B cells.
What are the three kinds of type 1A DM?
–> Polygenic (80-90%)
–> Monogenic (Rare)
–> LADA, Latent autoimmune diabetes in adults. Typically diagnosed after 35. (2-12%)
Describe the process of the onset of DM1 that leads to hyperglycemia.
- Genetic predisposition couples with environmental factors to trigger the production of autoantigens of B cells.
- Autoantigens activate cellular and humoral immunity toward B cells.
- B cell destruction leads to decreased insulin secretion and therefore, hyperglycemia and related metabolic disturbances.
What are diabetogenic viruses?
Viruses that increase might increase the risk of DM1 developing in a genetically predisposed individual. Such as infections of the immune B-cells (CMV), or systemic infections with cross-reacting immune responses (MMR, Cocsackie B, VZV)
Which dietary factors might contribute to the development of DM1 in a genetically predisposed individual?
–> Certain cow’s milk proteins may cause molecular mimicry
–> Decreased Vit D
What environmental factors might contribute to the development of DM1?
Diabetogenic viruses, Dietary factors, microbiome.
(See slide 28 or slides above)
It might take awhile for a person experiencing a progressive loss of Beta cells to exhibit hyperglycemia. Why is this?
Because the remaining beta cells will compensate for the lost insulin until they become overwhelmed.
In a person with DM1, the pancreas is still releasing glucagon despite high BGL. Why is this?
Insulin inhibits lipolysis, or the breaking down of triglycerides by adipose tissue, which releases FFAs into the bloodstream. The presence of increased FFAs triggers the secretion of glucagon.
What is the honeymoon period of a DM1 diagnosis?
The period of time shortly after diagnosis and restabilizing that the failing Beta cells become hyper productive and compensate for the failing insulin response. During this time symptoms might disappear and insulin injections are reduced or not needed.
Type 2 Diabetes Mellitus is characterized by ______
Insulin resistance
The development of Type 2 DM is a gradual process that usually begins with ____
Weight gain and obesity
What are the five characteristics are metabolic syndrome?
- Insulin resistance
- Visceral obesity
- Fasting hyperglycemia
- Dyslipidemia (high TG/ low HDL)
- Hypertension
What are some risk factors for type 2 DM?
–> Age 40+
–> Family history
–> Hypertension
–> Obesity
–> Low physical activity
–> Stress + socioeconomic factors
–> gestational diabetes, prediabetes, or giving birth to a baby that weighed over 9lb at birth
–> Heart disease
Dm2 is often characterized by hyperinsulinism, and yet it can progress into hypoinsulinemia. Why is this?
Increased demand for insulin, decreased activity of incretins and amylin lead to a degeneration of Beta cell mass and function.
What is diagnostic of DM2?
A loss of the first phase of insulin secretion. Second phase also decreases with time.
With time, eventually type 2 begins to resemble type 1.
Name four acute complications of DM.
- Acute hyperglycemia
- Diabetic ketoacidosis
- Nonketotic hyperglycemic hyperosmolar syndrome
- Acute hypoglycemia
What are symptoms are acute hypergylcemia?
Polyuria, polydipsia, polyphagia, nausea, fatigue, and blurred vision.
What is diabetic ketoacidosis (DKA)? Describe the process that causes it, the symptoms an how it can be managed.
Acidic blood due to presence of ketone bodies.
- Insulin deficiency –> lipolysis
- FFAs in blood are converted into ketone bodies and acetoacetic acids
- DKA –> metabolic acidosis.
--- Symptoms --- Kussmal Respirations --> labored hyperventilation
— Management —
–> Monitor fluids + electrolytes, carefully supplement with K+
–> Insulin for hyperglycemia
–> Manage hypothermia
What is hyperglycemic hyperosmolar nonketotic syndrome (HHNKS)? Describe the process that causes it, the symptoms, and how to manage it.
Striking dehydration due to severe hyperglycemia
- Hyperglycemia causes solute diuresis –> polyurea
- Dehydration causes hyperosmolarity and CNS depression
--- Symptoms --- Intense dehydration and thirst in a conscious patient
— Management —
–> Slow rehydration
–> 0.45% saline until osmolarity approaches normal, then 0.9% saline
–> insulin for hyperglycemia. Start slowly, as a person with HHNKS can be highly insulin sensitive.
DKA is more common in those with which kind of DM?
DM1
HHNKS is more common in those that have which kind of DM?
DM2
What are Kussmal Respirations?
Deep labored breathing often seen in those compensating for metabolism acidosis.
What is the Dawn Phenomenon? What causes it?
A BGL spike seen in the morning due to normal release of GH, cortisol, glucagon and NE.
Spikes in these hormones are normal but dysregulate BGL in those with insulin deficiencies.
What is the Somogyi effect? What causes it?
A spike of BGL in the morning following insulin induced hypoglycemia during the night. Caused by overcompensation counterregulatory hormones. Often caused by taking too much insulin the preceding evening.
What are symptoms of hypoglycemia?
Weakness, confusion, sweating, tremors, tachycardia.
low BGL stimulates sympathetic NS.
What are some risk factors for long-term complications of DM?
–> Degree on control is major factor
–> Duration of diabetes
–> Age of onset
–> Glycated hemoglobin
What are the three categories of long term complications of DM?
- Vascular - Macro or Micro
- Nephopathic
- Neuropathic
What is Oxidative Stress? Describe how chronic hyperglycemia might trigger it as well as how it effects the body.
Chronic hyperglycemia caused increased production of free radicals. This leads into an increased activation in metabolic pathways associated with atherogenesis, which damages blood vessels.
How to Advanced Glycation end Proteins affect blood vessels?
A build up of these proteins causes damage and thickening of the basement membrane, leading to structural defects in BVs.
Levels of activation in which pathway are elevated in those with chronic hyperglycemia? What does this lead to?
Protein Kinase C pathway –> vascular damage
How does the shunting of glucose into the polyol pathway affect other systems?
Sorbitol, a secondary product of this conversion, is osmotically active. Causes swelling and damage in blood vessels, nerves, and the lens of the eye.
Damage to large blood vessels can lead to what? What kinds of complication of DM are these?
Macrovascular complications.
CAD, peripheral vascular disease, and stroke.
How can we prevent macrovascular complications in those with DM?
Controlling dyslipidemia and hypertension; both of which improve with BGL control.
What causes retinopathy and nephropathy in those with DM?
Thickening of basement membrane due to the accumulation of Advanced Glycation End Products
What is the leading cause of blindness in adults? How does it do this?
DM associated retinopathy causes micro aneurysmal dilations, microinfarctions with hemorrhage, and reactive proliferation of vascular sprouts. Glaucoma and cataracts also occur.
What is the leading cause of renal disease and kidney failure?
Nephropathy due to DM
How does diabetic neuropathy affect the autonomic system?
Autonomic dysfunction can lead to GI disturbances, bladder dysfunction, tachycardia, postural hypotension, and sexual dysfunction.
How does diabetic neuropathy affect the sensory system?
May cause carpal tunnel or paresthesia in extremities.
Which summation of events can lead to a neuropathic ulcer?
Loss of sensory information caused increased likelihood of developing injuries and not feeling them.
Decreased vascularity leads to slower healing and higher glucose levels increase risk of infection.
For these reasons, diabetes is the leading cause of non-traumatic amputation of the legs, feet, and toes.
What are the main goals of treating someone with any kind of diabetes?
Normalize BGL and therefore keep HbA1c below 6.5%.
This will avoid acute and chronic complications
What are special consideration when treating a child with DM?
Achieving normal growth and development, addressing psychosocial issues, and educating children regarding self-care is crucial.
The child and family need ongoing education and support. Insulin dosage and BGL regulation needs will change as the child ages.
What are the special considerations for treating a geriatric patient with DM?
Attention to psychosocial issues and education of patient and family members are important. Education should be altered for visual or cognitive impairment. Oral agents should be chosen carefully with consideration for renal and hepatic function.
Exercise and meal planning is advised.
What might a treatment plan look like for someone with type 1 DM?
Glucose monitoring and insulin replacement therapy is necessary.
Stress management is also advised to control counterregulatory mechanisms related to cortisol.
When would long acting insulin be administered?
usually taken one daily to maintain overall BGL
When is intermediate-acting insulin administered?
Used to regulate BGL between meals. Might be combined with short-acting insulin.
What is short acting insulin used for?
Usually injected just before a meal to regulate.
What is the purpose of rapid acting insulin?
Used at the start of a meal or in emergency situations.
What is a closed loop system?
A system that self monitors BGL and administers insulin accordingly. Implant replaced once a month.
What are some examples of experimental new therapies for Type 1 DM?
–> Pancreas transplant
–> Islet transplant
–> Liver targeted insulin
–> Stem cell experiments
What are some examples of secretagogues?
Sulfonylureas
–> Enhances insulin secretion and reduces hepatic insulin clearance
Incretin Mimetics
–> stimulate insulin secretion and delay gastric emptying
What might a treatment plan for Type 2 DM look like?
- Weight loss and decrease in waist circumference
- Dietary changes
- Aerobic and resistance exercise
- Healthy sleep patterns
- Smoking cessation
- Treat hypertension and hyperlipidemia
- Treat with drugs like insulin and oral hypoglycemic agents
What are examples of sensitizers?
Biguanides
–> decrease hepatic glucose production
Thiazolidindediones
–> Increase peripheral insulin sensitivity and inihibit hepatic gluconeogenesis
What do Alpha glucosidase inhibitors do?
Decrease carb absorption small intestine
What do Sodium glucose cotransporter (SGLT2) inhibitors do?
Block glucose reuptake in proximal tubule
What are some risk factors for developing gestational diabetes?
–> Obesity
–> History of gestational diabetes
–> previously giving birth to child weighing over 9 lb
–> glucosuria
–> family history is type 2 DM
What are some adverse maternal affects of gestational diabetes?
–> preeclampsia
–> Birth trauma
–> Increased risk of developing T2DM
What are some adverse fetal effects of gestational diabetes?
–> Macrosomia
–> RDS
–> Neonatal hypoglycemia/jaundice
–> polycythemia
–> Hypocalcemia
