Diabetes Intro Flashcards
Define Diabetes mellitus
A metabolic disorder characterized by elevated blood glucose concentrations and disturbances of carbohydrates, lipids and protein due to defective insulin secretion and/or action.
What are different types of diabetes?
- Type 1 DM
- Type 2 DM
- Gestational diabetes
- Other types
- Pre-diabetes
What are the major differences between T1DM and T2DM?
Type 1 DM
- Insulin-dependent (IDDM)
- Juvenile or growth onset
- Ketosis prone
Type 2 DM
- Non-insulin dependent (mostly)
- Maturity onset (mostly)
- Not prone to ketosis
What is T1DM?
Autoimmune or idiopathic destruction of pancreatic ß-cells
→ absolute deficiency in insulin production
What is T2DM?
- Cells do not respond normally to insulin (resistance)
- Cells do not take up and utilize glucose efficiently →
hyperglycemia - Pancreas may compensate or not with insulin production → hyperinsulinemia or normal levels
What is the prevalence of diabetes in Canada?
6.7% (2.0 million) of Canadians >12 yrs reported diagnosed diabetes (type 1, 2 and GDM)
How did the prevalence of diabetes changed in Canada from 2011 to 2013?
Increase from 2011 (but not from 2013)
- 7.5% in males
- 5.8% in females
Which provinces of Canada have the highest and the lowest amount of people with diabetes?
NL, NS and ON had the highest prevalence, while NU, AB and QC had the lowest.
What is the pattern of obesity and diabetes in the U.S?
diabetes follows the prevalence of obesity
increasing since 1994
Which part of the world has the highest prevalence of diabetes in the world?
western pacific - Australia
What is the prevalence of diabetes in the world?
387 Million
46.3% undiagnosed
What is the expected number of increase in people with diabetes by 2035?
+ 205 million people
so 592 million people will be living with diabetes (53% increase)
What are the causes of T1DM?
environmental causes: virus, toxins and genetic predisposition lead to Islet cell auto- antibodies (ICA) and β cell Injury. Therefore, decrease in insulin production.
What are the symptoms/initial observations of T1DM?
- Increased thirst (polydipsia)
- Increased urination (polyuria)
- Increased hunger (polyphagia)
- Weight loss (T1DM) or obesity (T2DM)
What are the symptoms/lab tests of T1DM?
- Glycosuria
- Hyperglycemia
- Abnormal glucose tolerance (GTT)
What are the functions of insulin? (6)
- ↑ glucose uptake and storage
- ↓ glycogenolysis and gluconeogenesis = ↓endogenous glucose production
- ↑lipogenesis
- ↓ lipolysis
- ↑ protein synthesis
- ↓ proteolysis
What are the causes of T2DM?
- Excessive food intake + lack of exercise + genetic predisposition –> obesity
- obesity –> inflammation + insulin resistance
- insulin resistance –> hyperglycemia + Lipotoxicity + ß cell decompensation
What is insulin resistance?
Defined as a lesser sensitivity to insulin’s action in suppressing hepatic glucose production and stimulating glucose uptake
Mostly due to defective insulin signalling within cells
What are the normal steps of insulin-induced glucose uptake?
- In response to rising blood glucose, the pancreas releases more insulin into the blood
- Insulin bind to a membrane-bound receptor
- The binding of insulin to its receptor signals glucose transporters to move from the cytoplasm to the cell membrane
- Glucose transporters enable glucose to move from the extracellular space into the cytoplasm
What are the two types of insulin resistance in terms cellular mechanisms?
Receptor defects: decreased number and affinity
- Rare cases of genetic mutations of INSR gene
Post-receptor second messenger signalling
- Most cases of IR
What are the two types of regulation by insulin action?
long term regulation
- cell growth and differentiation
short term regulation of actions of insulin between fasted and fed state through P of proteins rapidly
- muscle: increased glucose transport and glycogen synthesis
- liver: increased glycogen synthesis, lipogenesis and decreased gluconeogenesis
- adipose: increased glucose transport, lipogenesis and decreased lipolysis
What are the effects of insulin resistance on blood, muscle, liver and adipose tissue?
liver: increased gluconeogenesis
muscle: decreased glucose uptake, glut 4 expression translocation, glucose oxidation, glycogenesis
adipose: increased lipolysis
blood: increased blood glucose and non essential fatty acids (NEFA)
List some of the risk factors for T2DM
o Age
o Obesity
o Sedentary lifestyle
o Ethnicity (e.g. Aboriginal, African, South Asian, Hispanic)
o Prediabetes: impaired fasting glucose or impaired glucose tolerance
o Family history
o History of GDM
o Child of a woman with poorly controlled diabetes during pregnancy
o Low birth weight (<2.5 kg) and high birth weight (>4.0 kg) o Polycystic ovary syndrome (PCOS)
** NOTE: sex is not included
What are other related conditions to insulin resistance?
¢ Obstructive sleep apnea ¢ Infection ¢ Steroid-induced ¢ Cushing’s syndrome ¢ Hemochromatosis ¢ Lipodystrophic diabetes ¢ Acanthosis nigricans ¢ Werner’s syndrome (adult form of progeria) ¢ Idiopathic
Explain the metabolic staging of type 2 diabetes
obesity –> insulin resistance –> impaired glucose tolerance + impaired fasting glucose –> hyperinsulinemia + hyperglycemia –> beta-cell defect –> decreased insulin secretion –> early diabetes –> beta-cell failure –> late diabetes
Can early diabetes be reversed?
Yes! Reversible by weight loss, exercise, medication
Compare T1DM and T2DM in terms of onset
T1DM - Sudden; <25 y.o.; usually lean; minor family history
T2DM - Gradually; 90% obese; marked family history
What are the symptoms of T1DM?
Very pronounced; wasted appearance; polyphagia, polydypsia, polyuria, HLA and islet cell Ab present
What are the symptoms of T2DM?
Often not evident; usually obese; fatigue, vision changes, recent weight loss, HLA and islet cell Ab absent
Compare T1DM and T2DM in terms of control
T1DM - Difficult; small changes in insulin, exercise, diet greatly affect glucose
T2DM - Easier; rapid changes in blood glucose not observed
Compare T1DM and T2DM in terms of stability
T1DM - Unstable; regulation of food and insulin crucial
T2DM - Easily stabilized
Compare T1DM and T2DM in terms of ketoacidosis
T1DM - Frequent; develops if insufficient insulin
T2DM - rare
Compare T1DM and T2DM in terms of oral anti- hyperglycemic agents
T1DM - Not effective
T2DM - Effective and increase insulin sensitivity
Compare T1DM and T2DM in terms of diet
T1DM - Very important but control may be difficult
T2DM - Important, possibly the only treatment necessary
What are the complications that can be faced in T1DM?
Vascular complications evident after 5 yrs from Dx
What are the complications that can be faced in T2DM?
May occur if poorly controlled, e.g. atherosclerosis
What are short-term complications of diabetes?
- Hypoglycemic episodes
- Diabetic ketoacidosis: life-threatening
- Hyperglycemic hyperosmolar syndrome
What are the symptoms of diabetic ketoacidosis?
Symptoms: N/V, stomach pain, acetone breath, rapid respirations, cognitive changes
↑risk during illness, infection, stress
What is the type of diabetes that diabetic ketoacidosis is associated with?
more in T1DM
What is the type of diabetes that hyperglycemic hyperosmolar syndrome is associated with?
more in T2DM
What are the indications of hyperglycemic hyperosmolar syndrome?
Seen with blood glucose >33 mmol/L
Infection and dehydration are precipitating factors
What is hypoglycemia?
BG < 3.9 mmo/L
What are the symptoms of hypoglycemia?
Neurogenic (adrenergic) - early:
- Sweating, shakiness, tachycardia, anxiety, sensation of hunger
Neuroglycopenic - late:
- Weakness, dizziness, confusion, poor coordination, blurred vision, loss of consciousness, coma
What is the common etiology of hypoglycemia?
- skipping or delaying meals,
- reduced CHO intake without med compensation,
- mis-dosage of insulin,
- unplanned exercise
What is the treatment of hypoglycemia?
15-15 rule
- Give 15 g of fast absorbed CHO, check BG 15 min later,
repeat if BG still low
Severe hypoglycemia: treatment (from care provider): injection of glucagon or glucose
What are long term complications of diabetes?
Microvascular
- Retinopathy: cataracts, glaucoma, macular edema
→ blindness
- Nephropathy: 20-40% of persons with DM chronic
kidney disease/failure → dialysis, transplantation
- Neuropathy: ~ 50% of persons with DM
impaired sensation or pain in extremities →
amputations
gastroparesis: ↓peristaltis
Macrovascular: CVD, CHD, stroke
Other common complications: poor wound healing, erectile dysfunction, increased susceptibility to infections
What are microvascular complications of diabetes?
Retinopathy: cataracts, glaucoma, macular edema → blindness
Nephropathy: 20-40% of persons with DM chronic
- kidney disease/failure → dialysis, transplantation
Neuropathy: ~ 50% of persons with DM
- impaired sensation or pain in extremities → amputations
- gastroparesis: ↓peristaltis
What are macrovascular complications of diabetes?
CVD, CHD, stroke
Explain the pathophysiology of DM Complications?
Lipotoxicity + Glucotoxicity + Glycated proteins (eg. A1C, others) –> Endothelial damage (stiffening & oxidative) –> Acceleration of plaque formation & atherosclerosis –> Hypertension, thrombosis, Ischemic end-organ damage
What is A1C?
- Glycated hemoglobin
- Measured as a % of Hb
- A1C is an indicator of long-term glycemic control because Hb half-life is about 3 months
What are the features of T1DM in terms of dyslipidemia?
- HyperTG due to defective removal of chylomicrons and VLDL resulting from impaired LPL activity (insulin dependent)
- HDL and LDL-C may be normal
What are the features of T2DM in terms of dyslipidemia?
- HyperTG due to elevated de novo synthesis from glucose
- Low HDL-C (due to obesity)
- LDL-C often elevated but may be normal
What is the link between diabetes and heart disease?
¢ Diabetic patients have 2-4 X risk of developing CVD: greater independent risk than smoking, hypertension, hypercholesterolemia, obesity
¢ Heart disease is the major cause of death in DM: 65%
¢ Recommendations for cardiovascular protection: the ABCDEs
Who do we screen for diabetes and what do we screen with?
- Screen every 3 years in individuals >40 years of age or in individuals at high risk using a risk calculator
- Screen earlier or/and more frequently in people with additional risk factors for diabetes or for those are at very high risk using a risk calculator
What is the level of FPG ( mmol/L) in diabetes?
> 7 mmol/L
What is the level of 2hPG in a 75g OGTT ( mmol/L) in diabetes?
> 11.1 mmol/L
What is the level of A1C (%) in PRE-diabetes?
6.0-6.4 %
What is the level of A1C (%) in diabetes?
> 6.5%
What is the level of random PG ( mmol/L) in diabetes?
> 11.1 mmol/L
What is the DPP Study?
Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients
Further decrease in life-style changes
What are the ABCDEs?
A - A1C (<7%) B - BP (<130/80) C - Cholesterol (LDL-C < 2.0 mmol/L D - Drugs (A - ACEi; S - Statin; A - ASA if indicated) E - Exercise/Eating S - Smoking cessation
What is the optimal target for A1C in Non DM vs DM
4.3-6.0 % in Non DM
< 7.0% DM
What is the optimal target for fasting glucose in Non DM vs DM
- 9-5.6 mmol/L in Non DM
4. 0-7.0 mmol/L in DM
What is the optimal target for 2hPC in Non DM vs DM
- 4-7.0 mmol/L Non DM
5. 0-11.0 mmol/L DM
How is blood glucose monitored?
- SMBG: self-monitoring blood glucose
- Blood glucose
- Urine glucose
- Urine ketones
- Blood ketones
- Glycated proteins
What are the recommendations of SMBG in T1DM?
TID for type 1 (conventional Tx), more with intensive Tx
