Week 3 & 4: Diabetes Type 1 & 2 Flashcards
Discuss the etiology, pathophysiology, and manifestations of Type 1 Diabetes
Type 1 diabetes involved cellular-mediated autoimmune destruction of pancreatic beta cells that leads to absolute insulin deficiency. These individuals are insulin dependent and prone to ketoacidosis, usually not obese. 75% of individuals develop this condition before 30 years of age. Insulin resistance at diagnosis is unusual, but insulin resistance may occur as the individual ages and gains weight.
Etiology is thought to be from a unique interaction between genetics and environment. Usually a first degree relative (parent or sibling) with type 1 diabetes. Environmental factors include viral infection, H.pylori, exposure to cow’s milk proteins, and relative lack of vitamin D.
In auto-immune mediated diabetes, environmental-genetic factors are thought to trigger cell-mediated destruction of pancreatic beta cells.
Pathophysiology involves lymphocyte and macrophages infiltrating the islets, resulting in inflammation and islet beta cell death. Both alpha and beta cell functions are abnormal, and both lack insulin and amylin and have a relative excess of glucagon, contributing to hyperglycemia.
Manifestation is typically a long pre-clinical period with gradual beta-cell destruction, leading to insulin deficiency and hyperglycemia, which will present with polydipsia, polyuria, polyphagia, weight loss, and fatigue.
Discuss the etiology, pathophysiology, and manifestations of Type 2 Diabetes
Type 2 diabetes is more common than Type 1 and ranges from insulin resistance with relative insulin deficiency to predominately an insulin secretory defect with insulin resistance. Risk factors include age, obesity, HTN, physical inactivity, and family history, as well as metabolic syndrome. Can impact both children and adults but individual must be genetically predisposed. Usually not insulin dependent but may be insulin requiring. Individual is not in ketosis, but can form ketones under stress. Obesity is common in the abdominal region and is associated with hypertension and dyslipidemia. Strong genetic disposition.
Pathophysiology involves 3 core mechanisms:
1. Insulin resistance: response of insulin sensitive tissues to insulin is suboptimal; obesity makes a person prone to insulin resistance.
2. Beta cell dysfunction: beta cell mass is decreased due to inflammation resulting from adipokines.
3. Glucagon: pancreatic alpha cells are less responsive to glucose inhibition; resulting in hyperglycemia. Abnormally high levels of glucagon increase hepatic production of glucose.
Manifestations will include recurrent infections and prolonged wound healing, genital pruritus, visual changes, paresthesia, fatigue, and acanthosis nigricans.
Discuss evaluation and diagnostics of prediabetes
FPG(mmol/L): 6.1-6.9: IFG (Impaired fasting glucose)
2h PG in a 75 OGTT(mmol/L) 7.8-11.0: IGT (Impaired glucose tolerance)
A1C(%): 6.0-6.4: Prediabetes
Discuss evaluation and diagnostics of diabetes
We do not need to screen for type 1 diabetes; there is insufficient evidence for interventions to prevent or delay type 1 diabetes.
Type 2 Diabetes: screen every 3 years in individuals >40 years of age or in individuals at high risk using a risk calculator.
- FPG <5.6mmol/L and/or A1C <5.5%: Normal, rescreen as recommended
- FPG 5.6-6.0mmol/L and/or A1C 5.5-5.9%: At risk, rescreen more frequently
- FPG 6.1-6.9mmol/L and/or A1C 6.0-6.4%: Prediabetes, rescreen more frequently
- FPG >7.0 mmol/L and/or A1C >6.5%: Diabetes
Glycosylated hemoglobin (HgA1C) levels: permanent attachment of glucose to hemoglobin molecules; reflects average glucose exposure over life of a red blood cell (approximately 90-120 days)
FPG: Fasting plasma glucose levels
Two-hour plasma glucose during oral glucose tolerance testing using a 75g oral glucose load: >11.1 mmol/L
Random glucose levels in an individual with symptoms: >11.1 mmol/L
Discuss dietary and exercise requirements for diabetes
Type 1: goal is restoration of near normal BG levels and correction of related metabolic disorders through a combination on insulin, meal planning, exercising, and self-monitoring of BG. In extreme cases, a transplant of islet cells or whole pancreas.
Type 2: prevention, especially in those with prediabetes, hinges on diet and exercise. However, as with type 1, the goal of treatment is the restoration of near normal BG levels and correction of related metabolic disorders.
Describe the diagnostics and management of obesity and metabolic syndrome
Diagnostic criteria for metabolic syndrome include an elevated waste circumference, elevated TG, reduced HDL-C, elevated BP, and elevated FPG. A BMI greater than 30 is also considered. Management includes correction of metabolic abnormalities, weight reduction and exercise, self-motivation and support systems, bariatric surgical procedures, anti-obesity medications, and psycho/behavioral therapy
Explain the relationships between obesity, metabolic syndrome and type 1 and 2 diabetes
Obesity is characterized by abnormal or excessive body fat, known as adiposity. Excessive adiposity is a source of adipokines and inflammatory mediators that alter glucose and fat metabolism leading to increased risk of CV disease, type 2 diabetes, and many other health complications. The degree of obesity directly affects the degree of insulin resistance; obesity acts through several important mechanisms:
* alteration in production of adipokines by adipose tissue
* elevated serum free fatty acids and intracellular lipid deposits
* release of inflammatory cytokines from adipose tissue
* reduced insulin-stimulated mitochondrial activity
* obesity-associated insulin resistance
* increase in adipocyte size leads to dysregulation of adipokines, macrophage infiltration, insulin resistance, chronic proinflammatory state, and altered lipid metabolism
* Excess free fatty acids are distributed to non-adipose cells, when their utilization capacity is exceeded, cellular dysfunction or death occurs (lipotoxicity)
Metabolic syndrome: Is a cluster of disorders that include central/visceral obesity, dyslipidemia, increased blood pressure, and increased fasting blood glucose that predispose an individual to developing diabetes.
Explain the role of the gut microbiome dysfunction in the pathogenesis of obesity and type 2 diabetes
Gut microbiota may have a causal role in the development of obesity and insulin resistance.
Discuss hypoglycemia
Hypoglycemia is considered a lowered plasma glucose level in children and adults of less than 4mmol/L (3.9 or less) and can result in insulin shock or insulin reaction. It results in Type 1 and Type 2 diabetes when unexpected changes in caloric intake without modification of insulin or non-insulin treatments occur; taking too much insulin or non-insulin treatments, not timing treatment appropriately with food intake, and drug interactions with insulin.
Clinical manifestations include:
* tachycardia
* palpations
* diaphoresis
* tremors
* pallor
* arousal anxiety (not impending doom)
Treatment:
* oral or IV glucose
* D50W
* Glucagon prescribed for emergency use - will stimulate the pancreas to turn on glucose
Neuroglycopenic symptoms are considered late signs and involve abrupt cessation of glucose delivery to the brain!
Discuss the Dawn phenomenon
Different from the Somogyi effect, the Dawn Phenomenon involves an early morning rise in blood glucose WITHOUT nocturnal hypoglycemia. It is related to nocturnal growth hormone elevation which decreases the metabolism of glucose by muscle and fat. The nocturnal growth hormone elevation may be fine for the non-diabetic individual, but might be too much for those with diabetes. Treatment involves altering the timing and dose of insulin or increasing the evening dose.
Discuss diabetic ketoacidosis
Absolute or relative deficiency of insulin and increase in counter-regulatory hormones results in increased fat mobilization with release of fatty acids that leads to the production of keto acids. This condition is typically caused by poor adherence to insulin treatment or interruption of administration, infection, trauma, surgery or myocardial infarction. It is most commonly found in individuals with type 1 diabetes because there is an absolute insulin deficiency. With some insulin on board, DKA is unlikely to occur.
In DKA we see extreme hyperglycemia, as the body tries to compensate for glucose not reaching the cells (no insulin) by breaking down fats for energy. As a result, osmotic diuresis will occur where glucose will be filtered through the kidneys and eliminated in the urine. The ketone bodies created through the metabolization of lipids reduce pH causing metabolic acidosis.
Signs & Symptoms:
* ketonuria
* polyuria
* dehydration
* thirst
* kussmaul respirations
* acetone breath
Treatment:
* Give insulin
* Decrease BG
* fluids
* replace lost fluid volume (osmotic diuresis d/t hyperglycemia)
* electrolytes (potassium!)
Discuss hyperosmolar hyperglycemic state (HHNKS/HHS)
HHNKS is a life-threatening complication of uncontrolled diabetes mellitus. This syndrome is characterized by severe hyperglycemia, a marked increase in serum osmolality, and clinical evidence of dehydration without significant accumulation of keto-acids. Typically occurs in type 2 diabetes because they do not have absolute insulin deficiency and is precipitated by infections, meds, non-adherence, and co-morbidity. Insulin levels are sufficient to prevent excessive lipolysis but not to use glucose properly.
Manifestations:
* glycosuria
* polyuria
* dehydration
* neurologic changes
* BG >33 mmol/L
* absent or low urine ketones
Treatment:
* insulin infusion combined with fluid & electrolyte replacement
Discuss diabetic neuropathy
The most common complication of diabetes, consists of sensory and motor deficits resulting in peripheral neuropathy where the distal portions of neurons are impacted by the degeneration of axonal and Schwann cells. With small nerve damage you will see neuropathic pain and loss of sensation and with large nerve damage you will see sensory loss of proprioception.
Discuss diabetic nephropathy
The most common cause of end-stage kidney disease, involves progressive changes resulting in glomerular enlargement and basement membrane thickening. Filtration is impacted and kidneys become damaged leading to the dysregulation of RAAS, resulting in more vessel damage. Microalbuminuria is the first manifestation and develops within 5-10 years of disease. Screening for CKD occurs 5 years after diagnosis and repeated yearly for Type 1; and at diagnosis and yearly for Type 2.
Discuss Diabetic retinopathy
The leading cause of blindness worldwide, involves:
Maculopathy: progressive process that accompanies retinal capillary permeability, vessel occlusion, and ischemia
Macular edema: fluid accumulation and retinal thickening
Treatment: if caught early, can involve laser treatment, vitrectomy, intravitreal steroids, anti-vascular endothelial growth factor, and renin-angiotensin system inhibitors if there is elevated systemic blood pressure, can increase pressure in the eye
There are 3 stages of retinopathy that lead to loss of vision:
1. Nonproliferative stage: characterized by an increase in retinal capillary permeability, vein dilation, micro aneurysm formation, and superficial and deep hemorrhages, no proliferation yet
2. Preproliferative: a progression of retinal ischemia, with areas of poor perfusion that culminate in infarcts; just before things start to proliferate
3. Proliferative stage: the result of angiogenesis and fibrous tissue formation with the retina or optic disc. Can lead to retinal detachment or hemorrhage, with severe blurring or loss of vision. Overgrowth of vessels, too much fibrous tissues being formed.
Discuss chronic complications of Diabetes
Chronic complications include micro & macrovascular disease damaging the eyes, brain, heart, kidneys, and nerves, and impacting circulation.
Microvascular:
* damage to capillaries
* diabetic retinopathy
* diabetic nephropathy
* diabetic neuropathy
Macrovascular:
* damage to medium and larger arteries
* coronary artery disease
* MI
*cerebral vascular disease
* peripheral vascular disease
Infection from high glucose in the blood and urine!
Explain the effect of counter-regulatory hormones on the management of diabetes
Infection, illness, injury/trauma, surgery, and/or physical and/or emotional stress cause hyperglycemia to occur as a counter-regulatory hormone response (body needs energy, stat!) In addition, epinephrine, GH, and cortisol are also increased. Glucose uptake is inhibited, as it may be needed in emergency (the body is telling certain cells to ignore insulin for now). As a result, blood sugar is further elevated through glycogenolysis and gluconeogenesis. Hyperglycemia and ketoacidosis can occur. Drug regime may change in anticipation of this effect.
