Diabetes

Question 1

Define Diabetes Mellitus.

Answer 1

Metabolic disorder affecting the metabolism of carbohydrates, fats and proteins.

Characterized by hyperglycemia.

Result of decreased insulin secretion or action or both.

Typically a chronic, progressive disease but some cases of DMII have gone into remission.

Question 2

Epidemiology in Canada.

Answer 2

In 2023, 10% of the Canadian population diagnosed with DMI or DMII.

Estimated prevalence including undiagnosed and pre-diabetes is approx 30%.

Question 3

What is the leading cause of death for individuals with diabetes?

Answer 3

Cardiovascular disease.

Question 4

Define type 1 diabetes including prevalence.

Answer 4

Previously known as juvenile or insulin-dependent diabetes.

Hyperglycemia caused by pancreatic beta cell destruction usually resulting a complete insulin deficiency. Accounts for 10% of people diagnosed with diabetes.
1. immune-mediated (90%)
2. idopathic (10%)

Diagnosed between 6 months to 25 years.

Equal diagnosis in males and females.

Prone to diabetic ketoacidosis.

Requires insulin.

Question 5

Define type 2 diabetes including prevelance.

Answer 5

Previously known as non-insulin dependent diabetes.

Hyperglycemia resulting from progressive destruction of pancreatic beta cells along with insulin resistance resulting in relative insulin deficiency.

Accounts for 90% of diabetes.

Usually manifests after age 40 but rising incidence amongst overweight and obese children and adolescents.

Treated with lifestyle modifications (diet, exercise, medication - some require insulin).

Question 6

Describe gestational diabetes.

Answer 6

Glucose intolerance with first onset or detection during pregnancy.

Occurs in 3-20% of pregnancies

Hormonal changes and weight gain increase insulin resistance.

All pregnant people are screened at 24-28 weeks.

Increased risks include advanced maternal age, obesity, history of GDM, first degree relative with type 2 diabetes etc.

Question 7

Other then DMI, DMII and gestational diabetes, what other types of diabetes exist?

Answer 7

Genetic defects in beta cell function or insulin action.

Diabetes secondary to other diseases or medications.

Question 8

How does glyburide (sulfonylurea) work to increase insulin secretion?

Answer 8

Directly triggers the closure of ATP-sensitive K+ channels in pancreatic beta cells - triggering the process to release insulin.

(ordinarily, glucose is required to enter pancreatic beta cells via GLUT-2 transporters, convert to C-6-P with glucokinase, which is metabolized to make ATP which then triggers the closure of the ATP sensitive K+ channels).

Question 9

Describe the etiology of type 1 diabetes.

Answer 9

1. Genetic predisposition:
   - varient in HLA-DQ or HLA-DR alleles
2. Environmental factors:
   Initiate attack on pancreatic beta cells in those predisposed.
   Proposed that triggers could be:
   - disease (coxsackie virus, H. Pylori)
   - diet (early exposure to cows milk and gluten)
   - gut microbiome dysbiosis (less diversity)
   - Vit D deficiency

Question 10

What are some risk factors for type 1 diabetes?

Answer 10

Family history

Age

Geography (further away from the equator)

Genetic factors

Environmental factors

Question 11

Describe the pathogenesis of type 1 diabetes.

Answer 11

1. Individual is genetically predisposed.
2. Precipitating event - triggers the destruction of pancreatic beta cells by autoantibodies. At this point the autoantibodies would be detectable in blood but not generally screed for as individual would not be symptomatic.
3. As beta cell destruction continues, with the decrease in insulin and rise in blood sugar you have increasing glucose intolerance.
4. When beta cells are 80-90% destroyed, individual becomes symptomatic.

Question 12

Describe how the autoantibodies of pancreatic islet cells contributes to type 1 diabetes.

Answer 12

Autoantibodies are produced through molecular mimicry against various proteins in the islet cells.

e.g. Glutamic acid has a protein that is structurally similar to the coxsackie virus. An individual infected with coxsackie and with the genetic predisposition, will also inappropriately produce autoantibodies against glutamic acid.

Molecular mimicry also thought to contribute to cow’s milk and gluten reaction.

These autoantibodies do not themselves cause b cell destruction but signal there is an inappropriate reaction occurring.

Question 13

What is responsible for the destruction of beta cells in type 1 diabetes.

Answer 13

An autoimmune reaction involving cytotoxic T cells.

Question 14

What tests can identify type 1 diabetes?

Answer 14

1. presence of islet cell autoantibodies (70-80% of cases).
2. measuring c-protein (low in type 1 diabetes)
3. elevated ketones

Question 15

Why are low glycemic index foods recommended in diabetes.

Answer 15

Insulin response is biphasic but with diabetes the initial phase is missing (type 1 and type 2) so important to select foods that don’t immediately spike blood sugar.

Question 16

Describe insulin resistance.

Answer 16

Decrease in the number or function of insulin receptors on the plasma membrane of target cells (cells requiring insulin to move glucose = liver, muscle and adipose).

Disrupted function could be post-receptor defect = problem with signalling pathways.

Question 17

Describe type 2 diabetes etiology.

Answer 17

1. Genetic predisposition.
   - Having a first degree family members increases chances 5-10 fold.
   - polygenic (multiple genes involved). Genes involved in insulin resistance and beta cell function.
2. Environmental factors:
   - factors that cause insulin resistance
   - obesity, sedentary lifestyle, diet, gut microbiome

Question 18

What role does obesity play in type 2 diabetes.

Answer 18

80% of people with type 2 diabetes are overweight.

Central obesity (excess abdominal fat) vs. peripheral obesity (subcutaneous fat on thighs and buttocks) is more of a risk factor. Adipose tissue releases adipokines, inflammatory cytokines and FFA’s that cause hormonal changes and insulin resistance. So even mild weight loss lessens insulin resistance.

waist:hip ratio indicates level of risk - so someone that is not overweight may still be at risk depending on fat distribution.

Question 19

How does exercise impact insulin sensitivity?

Answer 19

Active muscle cells require glucose and so become more sensitive to the smaller amounts of insulin available. This effect can last up to 16 hours after exercise.

In particular, exercises that increase muscle mass are recommended as more muscle is present to take up glucose, better controlling blood glucose levels.

Question 20

What are risk factors for type 2 diabetes?

Answer 20

• age (40 or over)
• first degree relevant
• excess body weight
• history of pre-diabetes
• history of gestational diabetes or delivering a baby over 4kg birth weight (macrosomic) baby
• metabolic syndrome

Question 21

What is metabolic syndrome?

Answer 21

Having 3 or more of the following increases risk for type 2 diabetes and CVD:
- visceral obesity
- hypertension
- insulin resistance
- elevated trigrylcerides
- low HDL-cholesterol

Question 22

What are risk factors for insulin resistance?

Answer 22

1. acanthosis nigricans = dark, velvety areas of skin in creases (neck and armpit)
2. polycystic ovarian syndrome
3. sleep apnea

Question 23

Describe the pathogenesis of type 2 diabetes.

Answer 23

1. Predisposition + lifestyle factors = insulin resistance.
2. pancreatic beta cell hyperplasia to compensate = normoglycemic and hyperinsulienmia.
3. Beta cell failure early (exhaustion, desensitization to high glucose, when insulin becomes deficient you get a rise in FFA’s which inhibit release of insulin from pancreas, 40% of people have an accumulation of amyloid protein in the pancreas which is a sign of pancreatic injury and contributes to beta cell dysfunction) = increasing glucose intolerance
4. Beta cell failure late = diabetes and symptom onset

Question 24

Can insulin resistance alone develop into type 2 diabetes?

Answer 24

No. Requires genetic predisposition and beta cell failure.

Question 25

What is latent autoimmune diabetes in adults (LADA)?

Answer 25

The precipitating factor leading to type 1 diabetes occurs after age 25.

Question 26

What are the effects of GDM on a baby?

Answer 26

• increased birth weight
• hypoglycemia at birth (increased insulin levels to combat high glucose as glucose not insulin crosses the placenta)
• premature birth
• risk for obesity and type 2 diabetes

Question 27

What are the effects of GDM on the mother?

Answer 27

• c-section due to increased size of baby
• maternal glucose tolerance usually returns to normal in 97% of mums
• increased risk for GDM in future
• increased risk for type 2 diabetes. 50% of GDM develop type 2 diabetes within 5 years.

Question 28

Describe insulin deficiency relative to glucagon excess.

Answer 28

1. decreased glucose uptake by muscle, adipose tissue and liver.
2. Glyconeogenesis and glycogenolysis.

(1+2 = hyperglycemia)

3. increased lipolysis = increased release of glycerol (contributes to glyconeogenesis) and increased FFA’s which increase ketones and lipoproteins which cause increased VLDL and LDL in blood.
4. decreased aa intake and increased protein breakdown in muscles (prevented by having some insulin present).

Question 29

What is polyuria in relation to diabetes?

Answer 29

Normally 100% of glucose is reabsorbed in the tubules. Excess glucose creates an osmotic gradient, drawing water with it, resulting in increased loss of glucose and water in urine.
= polyuria
= nocturia
= glucosuria

Question 30

What is polydypsia?

Answer 30

Increased thirst:
1. dehydration d/t polyuria (also risk for electrolyte imbalance).

2. hyperosmolality of blood (blood glucose pulls fluid from tissues - detected by osmoreceptors which stimulate thirst)

Question 31

What are manifestations of type 1 diabetes?

Answer 31

1. polyphagia = increased appetite as cells are starved for glucose and disruption in brain of satiety signal.
2. unexplained weight loss:
   - lack of inhibitory effects of insulin on muscle and fat catabolism
   - dependency on fat and protein for energy
   - causes muscle wasting
3. hyperketonemia and ketonuria due to increased lipolysis.

Question 32

What are some non-specific manifestations of type 1 and 2 but not specific to diabetes?

Answer 32

1. fatigue
2. blurry vision (diabetic retinopathy occurs later)
3. slow wound healing (peripheral vascular disease occurs later)
4. numbness or tingling of extremities d/t poor circulation (diabetic neuropathy develops later)
5. increased infections d/t increased glucose (bacteria loves sugar), poor circulation and impaired macrophage function d/t hyperglycemia.

Question 33

What is hemoglobin A1C (HbA1C or glycated hemoglobin)

Answer 33

Hemoglobin permanently binds glucose for the duration of the RBC’s life.

Measures glucose and therapy over three months so during initial therapy is recorded every three months then 6.

Question 34

Describe the screening process for type 2 diabetes.

Answer 34

Annual risk factor review.

If no risk factors and over 40 screen every 3 years.

If risk factors screen every 6-12 months.

Screening = FPG or A1C

Question 35

What is prediabetes?

Answer 35

When glucose levels are higher then normal but not high enough to diagnose diabetes. It is a risk factor for developing type 2 diabetes. Macrovascular complications begin with prediabetes.

Question 36

Why do we not screen for type 1 diabetes?

Answer 36

Insufficient evidence for interventions to prevent or delay type 1 diabetes.

Question 37

What are glycemic goals in the management of diabetes?

Answer 37

Optimal A1C levels (based on individual factors) and minimizing episodes of hyper and hypoglycemia.

Management of diabetes is aimed at preventing acute and chronic complications of diabetes.