Diabetes Intro Flashcards
What characterizes Type 1 DM?
Insulin-dependent (IDDM) → autoimmune/idiopathic destruction of pancreatic B-cells which results in absolute deficiency of insulin production
Juvenile or growth onset
Ketosis prone
What characterizes Type 2 DM?
Non-insulin dependent (mostly) → insulin resistance of cells, causing hyperglycemia/hyperinsulinemia (pancreas compensates with insulin production → may lead to damage)
Maturity onset (mostly) → also now in younger people because of high prevalence of obesity
Not prone to ketosis
What treatment is proposed for Type 2 diabetics that are ketosis prone?
Insulin
What treatment options are proposed for T2D patients who are ketosis resistant?
Diet, Oral meds and Insulin for both Obese and normal weight patients
Which provinces have the highest prevalence of diabetes?
Newfoundland (6.5%), Nova Scotia (6.1%), and Ontario (6.0%)
What are general causes of T1DM?
Environmental factors, genetic predisposition that results in the production of islet cell autoantibodies (ICA) that results in B cell injury → decreased or no insulin production. B cell injury can also be caused by other random factors.
What are the symptoms of diabetes?
- Initial Observations:
Increased thirst(polydipsia)
increased urination(polyuria)
increased hunger(polyphagia)
weight loss (T1DM) or obesity (T2DM) - What do clinical laboratory tests reveal?
Glycosuria, hyperglycemia, and an abnormal glucose tolerance (GTT)
What are insulin’s actions?
Increased glucose uptake and storage, lipogenesis, and protein synthesis
Decreased glycogenolysis, gluconeogenesis (= decreased endogenous glucose prod.), lipolysis and proteolysis.
Describe the pathophysiology of diabetes and insulin deficiency?
Insulin deficiency causes hyperglycemia in T1DM patients. This is directly due to an increase in hepatic glucose output, a decrease in glucose uptake by cells and increased gluconeogenesis (with amino acids coming from an increase in protein degradation).
As for fats, insulin deficiency causes a decrease in TG synthesis and increased lipolysis, therefore increasing blood F.A.s, which is an alternative energy source for cells. This process is called ketosis, which can lead to metabolic acidosis, increased ventilation and a diabetic coma → DEATH :)
Describe the fuel flux in diabetics in fasted state.
The liver produces endogenous glucose from gluconeogenesis using amino acids from muscle protein. Fatty acids from adipose tissue (hydrolyzed TGs) also contribute to metabolic fuel and are converted to ketones.
Describe the fuel flux in diabetics in fed state.
In fed state, there will be extra input from dietary sources in addition to contributions of amino acids from muscles and fatty acids to gluconeogenesis in the liver. There will still be muscle wasting occuring due to decreased protein synthesis as a result of insulin deficiency
Why is the fed state worse than the fasting state in diabetics from a metabolic point of view?
Because there is no insulin to stimulate protein synthesis, the ingested amino acids contribute to gluconeogenesis in the liver as well as the ones provided from muscle. This means that even if a person is ingesting protein, he/she’s muscles are still wasting to contribute to glucose production.
Describe the overall causes/pathophysiology of T2DM
In general, excessive food intake, a lack of exercise and to an extent, genetic predisposition contributes to a state of obesity. As a result of obesity, there is inflammation which along with genetic predisposition results in insulin resistance. Insulin resistance leads to hyperglycemia which leads to B-cell decompensation which is what characterizes T2DM. Hyperglycemia also results in compensatory hyperinsulinemia which further contributes to obesity. There is also lipotoxicity inflammation from excess free FA that can lead to damaging cells in the pancreas further reducing B-cell function. (for diagram reference slide 27 Lecture 18)
Define insulin resistance
A lower sensitivity of insulin’s action which will decrease the cells ability to suppress hepatic glucose production and increase glucose uptake, caused by defective insulin signaling within cells
Receptors may be defected leading to decreased number and affinity of binding
Most common cause of insulin resistance is due to post-receptor second messenger signaling
in the body, insulin resistance will increase gluconeogenesis in the liver, increase lipolysis in adipocytes and decrease glucose uptake, GLUT4 expression, glucose oxidation and glycogenesis in the muscle which ultimately will increase blood glucose levels and FFA in circulation
How does insulin-induced glucose uptake work?
Insulin release from the pancreas is stimulated by a rise in blood glucose. Insulin stimulates a membrane-bound receptor, which signals glucose transporters (GLUT4) to move from the cytoplasm to the cell membrane. These GLUT4 enable glucose to move from the extracellular space into the cytoplasm.
Insulin signaling thus increases glucose transport (GLUT4) in muscle and adipose cells, increases glycogen synthesis in muscle and liver cells, increases lipogenesis in liver and adipose cells, decreases gluconeogenesis in liver cells and decreases lipolysis in adipose cells.
What are risk factors for type 2 diabetes?
Age, obesity, sedentary lifestyle, ethnicity (aboriginal, african, south asian, hispanic), prediabetes (impaired fasting glucose or impaired glucose tolerance), family Hx, Hx of GDM, child of a woman with poorly controlled diabetes during pregnancy, low birth weight (< 2.5kg) and high birth weight (> 4kg), PCOS.
What are some other conditions related to insulin resistance?
- Obstructive sleep apnea
- Infection
- Steroid-induced
- cushing’s syndrome - rare condition that is the result of too much of the hormone cortisol in the body (most common in women over men age 20-40)
- Hemochromatosis (iron build up)
How does T2DM develop?
Obesity is at the source of either causing insulin resistance or impaired glucose tolerance/impaired fasting glucose. These in turn cause early diabetes, which is decreased insulin secretion, leading to beta-cell failure and late diabetes. Another pathway that leads to early diabetes is hyperinsulinemia/hyperglycemia that causes beta-cell defect, causing the decreased insulin secretion. Anything before early diabetes can be reversible by weight loss, exercise, and medication.
Compare T1DM vs T2DM by their onset
Onset: Type 1 is
Sudden; <25 y.o.; usually lean; minor family history
Type 2:
Gradually; 90% obese; marked family history
Compare T1DM vs T2DM by their symptoms
Type 1:
Very pronounced; wasted appearance; polyphagia, polydypsia, polyuria, HLA and islet cell Ab present
Type 2:
Often not evident; usually obese; fatigue, vision changes, recent weight loss, HLA and islet cell Ab absent
Comapre T1DM vs T2DM by their control
Type 1:
Difficult; small changes in insulin, exercise, diet greatly affect glucos
Type 2:
Easier; rapid changes in blood glucose not observed
Compare T1DM vs T2DM by their stability
Type 1:
Unstable; regulation of food and insulin crucial
Type 2:
Easily stabilized
Compare T1DM vs T2DM based on ketoacidosis
Type 1: Frequent, develops if insufficient insulin
Type 2: Rare
Compare T1DM vs T2DM based on oral anti-HTG agents
Type 1: Not effective
Type 2: Effective
Compare T1DM vs T2DM based on insulin treatment
Type 1: necessary - islet cell loss
Type 2: 20-30% need insulin
Compare T1DM vs T2DM by their diets
Type 1: very important but control may be difficult
Type 2: important, possibly only treatment necessary
Compare T1DM vs T2DM by their complications
Type 1:
Vascular complications evident after 5 yrs from Dx
Type 2:
May occur if poorly controlled, e.g. atherosclerosi
What are the short term complications related to diabetes?
- Hypoglycemia
- Diabetic ketoacidosis which can be life threatening and more common in T1DM, will increase during illness, infections and stress
- Hyperglycemic hyperosmolar syndrome seen in T2DM with excessive blood glucose levels >33mmol/L often infection and dehydration are contributing factors
What characterizes hypoglycemia?
- Blood glucose < 3.9 mmol/L
- Neurogenic (adrenergic) symptoms such as sweating, shakiness, tachycardia, anxiety, sensation of hunger. These symptoms appear early on.
- Neuroglycopenic symptoms such as weakness, dizziness (occur early). Confusion, poor coordination, blurred vision, loss of consciousness and coma. These last symptoms appear later on, usually happen after an overnight fast.
- Etiology: skipped/delayed meals, reduced CHO intake without med compensation, misdosage of insulin, unplanned exercise
- Tx: 15-15 rule - give 15 g of fast absorbed CHO, check BG 15 min later, repeat is BG is low.
- Severe hypoglycemia: treatment is to inject glucagon or glucose
What are the long term complications of diabetes?
- Damage of the vascular walls
- Microvascular
Retinopathy: cataracts, glaucoma, macular edema leading to blindness
Nephropathy: 20-40% of patients with chronic kidney disease/failure
Neuropathy: ~50% of patients, impaired sensation of pain in extremities, gastroparesis lowering bowel movements which will affect appetite and digestion - Macrovascular
CVD, CHD, stroke - Patients may also have poor wound healing, erectile dysfunction ,increased susceptibility to infections
Describe the pathophysiology of DM complications
Glucotoxicity leads to the production of glycated proteins which along with lipotoxicity result in endothelial damage. This results in the acceleration of plaque formation, atherosclerosis which in turn leads to HTN, thrombosis and ischemic end organ damage.
What is hemoglobin A1C and what does it indicate?
Hemoglobin A1C is glycated hemoglobin and is measure as a % of Hb. It is an indicator of long-term glycemic control (½ life of Hb = about 3 months). A high A1C can indicate poor glycemic control, and is used as one of the indicators for T2DM.
What type of dyslipidemia can occur in T1DM patients?
HyperTG can occur in T1DM patients due impaired LPL activity (depends on insulin), which causes a defective removal of chylomicrons and VLDL. HDL and LDL-C may appear as normal.
What type of dyslipidemia can occur in T2DM patients?
HyperTG because of the high rates of de novo synthesis of TGs from glucose (increased lipogenesis), low HDL-C (due to obesity) and LDL-C is often elevated but can be normal (depending on obesity and excess energy intake).
What is the link between diabetes and heart disease?
Diabetic patients have a 2-4 times risk of developing CVD - there is a greater independent risk than smoking, hypertension, hypercholesterolemia and obesity
What are the recommendations for diabetes screening? (who and with what?)
- Screen every 3yrs in indv >=40y/age and in indv at high risk using risk calc
- Screen earlier/more frequently in people with additional risk factors or diabetes or for those at v high risk using a risk calc
- Screen using CANRISK
What are the 4 diagnosis tests for prediabetes and diabetes and there ranges?
- FPG (Fasting Plasma Glucose) test (mmol/L): no caloric intake for at least 8 hours.
Results: 6.1-6.9 mmol/L → Impaired Fasting Glucose (IFG), > or equal to 7 mmol/L → diabetes - 2hPG in a 75g OGTT (oral glucose tolerance test) (mmol/L)
Results: 7.8-11 mmol/L → Impaired Glucose Tolerance (IGT), > or equal to 11.1 → diabetes - A1C(%): Standardized, validated assay, in the absence of factors that affect the accuracy of A1C and not for suspected type 1 diabetes.
Results: 6-6.4% → prediabetes, > or equal to 6.5% → diabetes - Random PG (mmol/L)
Results: > or equal to 11.1 → diabetes
If asymptomatic, repeat confirmatory test (FPG, A1C or 2hrPH in a 75g OGTT). If symptomatic → diagnosis made and begin Tx.
Describe the OGTT Blood Glucose Curve
Normal blood glucose stays below 8mmol/L, IGT blood glucose goes up to 11 mmol/L and T2DM goes up to 14 mmol/L. Has you go from normal to IGT to T2DM, the fasting glucose levels are higher (before and 3h after the 75g glucose drink)
What method used in the diabetes prevention program (DPP) was shown to be most effective on the cumulative incidence of diabetes?
Lifestyle alone (diet and exercise) reduced the incidence of diabetes by 58% compared to the drug (metformin) alone.
What are the recommendations of vascular protection for all patients with diabetes?(ABCDES)
- A1c - optimal glycemic control <=7%
- BP - optimal blood pressure control (<130/80 mmHg)
- Cholesterol - LDL-C <=2.0 mmol/L if decision made to treat
- Drugs - to protect the heart
A- ACEi or ARB
S - statin
A - ASA if indicated - Exercise/Eating - regular physical activity, healthy diet,achievement, maintenance of healthy BW
- Smoking cessation
How is the target of A1C determined and what is the range?
Range for diabetic patients: 6 - 8.5%
Typically the target is at 7%
For some T2DM patients may need to consider aiming for 6.5% to lower the risk of microvascular complications such as nephropathy and retinopathy which will need to be balanced against the risk of hypoglycemia
A1C levels above 7% are only considered if patients are experiencing complications such as limited life expectancy, high level of functional dependency, history of recurrent severe hypoglycemia, extensive coronary artery disease, multiple co-morbidities
What are the Canadian glycemic control guidelines?
A1C: 4.3-6% is ideal (non DM), <7% is optimal (DM target), 7.1-8.5% is suboptimal (consider action) and >8.5% is inadequate (action required).
Fasting glucose: 3.9-5.6 mmol/L is ideal (non DM), 4.0-7.0 mmol/L is optimal (DM target), 7.1-10.0 mmol/L is suboptimal (consider action) and >10.0mmol/L is inadequate (action required).
Glucose 2hrs PC: 4.4-7.0 mmol/L is ideal (non DM), 5.0-11 mmol/L is optimal (DM target), 11.1-14.0 mmol/L is suboptimal (consider action) and >14.0 mmol/L is inadequate (action required).
What tools are used to monitor glycemic control in diabetics?
SMBG* (self-monitoring blood glucose), blood glucose, urine glucose, urine ketones, blood ketones, and glycated proteins are measured to avoid complications.
*SMBGs are used as daily monitors for T1DM and some T2DM cases. It is important to use if people are on antihyperglycemic agents or insulin to prevent hypoglycemia, may not be necessary for those only on diet Tx.
