Diabetes Flashcards
Which hormones lead to decrease of glucose? Increase?
There are several hormones that lead to an increase in blood glucose (glucagon, epinephrin, cortisol, GH)
There is only one that decreased blood glucose- insulin
Which cells produce insulin? Glucagon?
Insulin- b-cells
Glucagon: a-cells
What is the biggest producer and user of glucose in fasted state? What are other sources and users
Producer: liver
User: brain (has GLUT1 transporter that doesn’t require insulin to be activated)
Other source: reabsorption by kidneys
Other users: Liver, Muscle + fat, Kidney
Predominant hormone basal vs post-prandial states
Basal: glucagon
Post-prandial: insulin
What is the biggest source and user of glucose in postprandial state?
Source: gut
User: liver, muscle and CNS consume roughly equal amounts
Concentration of insulin and glucagon: Diabetic and healthy subjects
Glucose:
Healthy- Increase after meals and then decrease
Diabetes: higher increase, slower decrease
Insulin:
Healthy- rapid and large spike
Diabetes- almost to increase + delayed
Glucagon:
Healthy- drop after a meal due to insulin presence
Diabetes- excessive glucagon level, non-inhibited by insulin
Is only insulin response varied in diabetes>
both insulin and glucagon levels are affected
Insulin action on Glucose metabolism
Increases anabolism as insulin stimulates
▪ Glucose transport (GLUT: muscle and adipose tissue)
▪ Glycogenesis
Decreases catabolism as insulin inhibits:
▪ Gluconeogenesis (liver)
▪ Glycogenolysis (liver and muscle)
Insulin action on Lipid metabolism
↑ Anabolism as Insulin stimulates
▪ Lipogenesis
▪ Synthesis of triglycerides (Adipose tissue)
▪ Synthesis of free fatty acid (Liver)
↓ Anti-Catabolic as insulin inhibits:
▪ Lipolysis
Insulin action
Protein metabolism and electrolytes
↑ Anabolism as Insulin stimulates
▪ Transport of amino acid
▪ Protein synthesis
▪ Electrolytes: Potassium enter into the cell
↓ Anti-Catabolic as Insulin inhibits
▪ Proteins
▪ Protein catabolism
What is first phase insulin?
● The initial burst of insulin; 5-10 minutes after
β-cell is exposed to a rapid increase in Glucose
● Important for decreasing hepatic glucose production, decreasing lipolysis, and to prepare target cells for the action of insulin
what is second phase insulin
after first phase aka acute response, insulin secretion rises more gradually and is directly related to the degree and duration of stimulus
What is the effect on insulin response of administering glucose oraly vs IV
Oral administration results in much bigger insulin response
What are incretins
Incretins are a group of metabolic hormones that trigger insulin release
The main ones are GLP-1 and GIP
What are the initial symptoms of diabetes?
• Increased thirst (polydipsia) • Increased urination (polyuria) • Increased hunger (polyphagia) • Weight loss (type I) or obesity (II) in later stages of T2 there will also be some weight loss
T1DM Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
- Most <25 by can occur at any age (but not before the age of 6 months)
Weight: Usually thin, but with obesity epidemic, can have overweight or obesity
Islet auto- antibodies: Usually present
C-peptide: Undetectable/low
Insulin production- Absent
First line treatment- insulin
Family history of diabetes- Infrequent (5-10%)
DKA- common
T2DM Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
Age of onset: Usually >24 but incidence increasing in adolescents, paralleling increasing rate of obesity in children & adolescents
Weight- >90% at least overweight
Islet auto- antibodies- absent
C-peptide- normal/high
Insulin production- present
First line treatment- Non-insulin antihyperglycemic agents, gradual dependence on insulin may occur
Family history of diabetes- Frequent (75-90%)
DKA- rare
Monogenic diabetes Age of onset Weight Islet auto- antibodies C-peptide Insulin production First line treatment Family history of diabetes DKA
Age of onset- Usually <25 Neonatal diabetes <6 months*
Weight- Similar to general population
Islet auto- antibodies- absent
C-peptide- normal
Insulin production- usually present
First line treatment- Depends on subtype of MODY
Family history of diabetes- Multigenerational, autosomal pattern of inheritance
DKA- Rare (except for neonatal diabetes*)
Is genetics a big factor in T1 and T2
genetics is not that important in T1
much more important in T2
Is T1 a children’s disease?
Not a children disease
42% of people with type 1 diabetes = diagnosis between the ages of 31 and 60
What is DKA? Symptoms?
Diabetic Ketoacidosis (DKA): Complication of severe insulin deficiency leading to hyperglycemia, causing glucosuria, dehydration and ketogenesis to the eventual acidosis. Common symptoms: • Vomiting • Abdominal Pain • Hyperventilation • Lethargy • Confusion • Dehydration • Fruity Breath
What decreases with insulin resitance?
Decrease in:
• Ability of insulin to suppress endogenous glucose production in the liver
• Uptake of glucose in tissues with insulin-dependent glucose transporters (mainly in skeletal muscle)
• Inhibition of lipolysis-> thus more FA gets produced
Pathogenic features of hyperglycaemia in type 2 diabetes
- Increased lypolysis
- Increased glucose reabsorption by kidneys
- Decreased muscle tissue glucose uptake
- Increased hepatic glucose production
- Increased glucagon secretion
- Impaired insulin secretion
Lab values to diagnose diabetes
1) FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or
2) A1C ≥6.5% (in adults)
Using a standardized, validated assay in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes
or
3) 2hPG in a 75 g OGTT ≥11.1 mmol/L
or
4) Random PG ≥11.1 mmol/L
Random = any time of the day, without regard to the interval since the last meal
Postprandial glycemia (or post load) values in normal, pre-diabetic and diabetic individuals
Postprandial
<7.8 - normal
7.8- 11.1- pre-diabetes
>11.1- diabetes
Fasted glucose levels in normal, pre-diabetic and diabetic individuals
Fasted:
<5.6 -normal
5.6-6- pre-diabetes
>7- diabetes
What are the AMDR for diabetic people?
CHO: 45-60%
Protein: 15-20% (or 1-1.5g /kg BW*)
Fat: 20-35%
Fibre recommendations
↑Total fibre to 30-50 g per day
>1/3 (10-20 g per day) from viscous soluble fibre*
Sat fat recommendations
↓Saturated fatty acids to <9% of energy intake to decrease CVD risk
Why is weight loss recommended?
Weight loss of 5-10% of initial body weight->
Improved insulin sensitivity, glycemic control, blood pressure control, lipid levels
Flowchart for Nutritional management of hyperglycemia in type 2 diabetes
- Clinical assessment: Healthy behaviour interventions by Registered Dietitian
behaviour interventions by Registered Dietitian - Initiate intensive healthy behaviour interventions or energy restriction and increased physical activity to achieve/maintain a healthy body weight
- Provide counselling on a diet best suited to the individual based on values, preferences, and treatment goals using the advantages/disadvantages listed in Table 1
If not at target - Continue healthy behaviour interventions and add pharmacotherapy
- Timely adjustments to healthy behaviour interventions and/or pharmacotherapy should be made to attain A1C within 2 to 3 months for healthy behaviour interventions alone or 3 to 6 months for any combination with pharmacotherapy
Pre-diabetes management targets and strategies
• Weight loss or maintenance* • Portion control • Guidance to include low GI CHO and reduce refined CHO • Physical activity
Early T2 management targets and strategies
• Weight loss or maintenance* • Portion control • Low GI CHO • High fibre • CHO distribution • Dietary pattern of choice ** • Physical activity
Nutritional therapy recommendations that ar related to CVD
To reduce the risk of CVD, adults with diabetes should avoid trans fatty acids (TFA) and consume less than 9% of total daily energy from saturated fatty acids (SFA) replacing these fatty acids with polyunsaturated fatty acids (PUFA) particularly mixed n-3/n-6 sources, monounsaturated fatty acids (MUFA) from plant sources, whole grains or low GI carbohydrates
Fixed insulin dose vs insulin to carb ratio
Fixed insulin dose: The amount of carbs and the insulin dose taken are always the same for a given meal (e.g., 6 insulin units for 45 g of carbs at breakfast).
Insulin to carb ratio: 1 un : XX g or XX un: 10g
Before you begin carbohydrate counting education:
Determine the person’s base knowledge:
- Knowledge of the goals for healthy eating in general
- Knowledge of the goals for healthy eating in diabetes
- Preconceived notions (e.g., what a person with diabetes should or should not eat)
- Understanding of basic nutrition concepts: Macronutrients and the the foods that provide them
- Understanding of blood glucose lowering medication Onset, action, duration and mechanism of action
Carb counting: concepts to teach
- Identify foods that contain carbs
- Identify foods that do not contain carbs
- Understand that many foods containing carbs are healthy
- Healthy foods containing carbs should not be significantly limited • How much carb to eat per day
- How much carb to eat at meals and snacks
- Define a serving of a variety of common foods
Concept to teach about polyols
Foods that contain polyols (sugar alcohol) : subtract half of them Examples of sugar alchohol: erythritol glycerol (also known as glycerin or glycerine) isomalt lactitol maltitol mannitol sorbitol xylitol
Tips: How do we plan the meals for the day?
- Meals: distribute Carb servings relatively evenly.
- All meals should have a protein source.
- Can use range (example 3 to 4 Carb servings per meal) for flexibility.
- Breakfast could be lower # Carbs than other meals if client has high blood glucose in am. • Consider need for snacks.
- Consider exercise, may need extra snack(s) particularly for aerobic exercises.
- Evening snack should have protein + carbohydrate.
- Snacks should be minimum 3 hours from a meal.
- Meals can be 4 – 5 hours apart without a snack, or further apart with a snack.
- Encourage vegetables as desired.
Artificial Sweetener: Benefits
- More variety in food→
- It enables people that are carb sugar or calorie conscious to take in a wider range of foods that they would either not be allowed to eat or could only eat in such tiny amounts that they were not satisfying
- Does not raise blood glucose
- Does not contain calories
- Can help avoid dental caries, while still enhancing flavor
Artificial Sweetener: Health Concerns
- Can be associated with cancer
- Can cause cell damage
- Can cause bloating
- Can be associated to hypertriglyceridemia and gastrointestinal symptoms
- Can be associated with increase incidence of Type 2 Diabetes
- Can be associated with increase weight and obesity
- Provide no nutritional value
Who needs to snack? Appropriate Snacking
- Bedtime snack is most common. (If time between supper and bed is > 3 hours.)
• Include protein to slow digestion.
The bedtime snack may reduce the chance of having a low blood sugar during
the night, and/or may improve morning blood sugars - If client has a gap of 5 hours (on insulin) or 6 or more (without insulin) between their meals, then a snack should be planned.
- Clients who regularly have low blood glucose at a certain time of day will need a snack at that time.
- If client is starting a new exercise program, exercising for a longer period than usual, or has a fairly low blood sugar reading prior to starting an intensive exercise.
- Whenever a delay to the next meal is possible
(stuck in traffic driving, waiting at airport for a flight,…)
Examples of Appropriate Snacks
Healthy source of CHO • High in fiber • Avoid juice • Lean protein • Here's a list of examples of snacks for diabetes : • Whole grain toast + peanut butter • Whole grain crackers + cheese • Oatmeal + nuts/raisins + Milk
Using your 24h recall:
- Did you eat 3 balanced meals?
- Were your meals at the usual time that you eat those meals?
- Were meals 4 to 6 hours apart (not more than 6 hours)?
- Did you have any sugar, sweets, candy, dessert, fruit juice or sweetened beverages?
- Did you have any high fat items?
- Did you choose foods of low glycemic index?
- Did you have a source of protein at every meal?
- Did you have 3 to 5 Carb servings of about 15 g each, at each meal?
Advantages of A1C measuring
Provides a glycemic history of the previous 120 days - most accurately reflects
the previous 2-3 months of glycemic control. Predicts risk for complications
Why dont we just measure A1C?
A1c doesn’t reflect in fluctuations on blood sugar levels
thus daily measurements with blood sugar monitors should be done
How often should A1C be measured
every 3-6 months
Other Glycated Proteins: GSA & GSP
Glycosylated serum albumin (GSA) and glycosylated total serum proteins (GSP)
Used when A1C cannot be measured or during hemolytic anemia
Not yet shown to be an indicator of risk for complications
Needs to be measured more often
A1C levels for pregnancy recommendations
women should target <6.5 before pregnancy to limit the risk of gestational diabetes and for better pregnancy outcomes
A1C targets recommendations
≤ 6.5 : Adults with type 2 diabetes to reduce the risk of CKD and retinopathy if at low risk of hypoglycemia
≤ 7.0: MOST ADULTS WITH TYPE 1 OR TYPE 2 DIABETES
7.1 -8.5:
• Recurrent severe hypoglycemia and/or hypoglycemia
unawareness
• Limited life expectancy
• Frail elderly and/or with dementia**
What should Preprandial PG and 2 hour Postprandial PG (mmol/L) be to achieve A1C ≤ 7.0%
For most patients:
Preprandial PG (mmol/L): 4.0-7.0
2 hour Postprandial PG (mmol/L): 5.0-10.0
If A1C ≤7.0% not achieved despite the above PG targets
Preprandial PG (mmol/L): 4.0-5.5
2 hour Postprandial PG (mmol/L): 5.0-8.0
What should you remember about Correlation between A1C and estimated mean glucose values
A1C values (%) will be lower than estimated mean glucose values THEY ARE NOT EQUAL
Targets for A1C (%),
FPG / premeal PG (mmol/L) and
2-hour pc PG (mmol/L) for <18 yo
A1C (%): ≤ 7.5%
FPG / premeal PG (mmol/L): 4.0-8.0
2-hour pc PG (mmol/L): 5.0 – 10.0
Hygiene and blood glucose
make sure that fingers are clean, otherwise it can pick up glucose from fingers
blood glucose meters can make errors
How often should BG be measured in T1 and T2?
t1- measure blood 4-5x/day
t2- very individual, but glucose levels are more stable generally
Blood Glucose meter vs Continuous glucose monitor
Blood Glucose meter measures sugar in blood.
CGM measures glucose in interstitial fluid
there is a 5-10 min gap between the sugar level in your blood and in your interstitial fluid
Blood glucose measurement and adjusting insulin
before adjusting insulin levels, measure your blood sugar for several days
if your glucose levels have been out of target for several days and there are specific trends (e.g. constantly lower sugar before breakfast)-> adjust
reduce insulin at that time of there:s a trend of hypoglycemia
Increase insulin at that time is theres a trend of hyperglycemia
Make sure that these trends aren”t caused by changes in your regular routine e.g.. inaccurate carb counting, increased/decreased physical activity
Blood glucose measuremnt variability
if glucose levels are stable CGM and blood glucose meter will show similar results
BSM will reflect changes in blood sugar levels first
meds can also distort the values on CGM
validate CGM measurements with BGM
Uncontrolled diabetes and adolescence
between adolescence and young adulthood, there is a peak of uncontrolled diabetes : due to hormones, change of the person who takes care of diabetes
Initial choice of therapy for
A1C < 1.5% over target and A1C ≥ 1.5% over target
A1C < 1.5% over target
- Initiate healthy behavior interventions and start metformin if not at target in 3 months
OR
- Start metformin with healthy behavior interventions
A1C ≥ 1.5% over target
Start metformin with healthy behavior interventions
AND
Consider second concurrent agent
Pharmacotherapy in Type 2 Diabetes Checklist
CHOOSE initial therapy based on glycemia
START with metformin +/- others
INDIVIDUALIZE your therapy choice based on characteristics of the person with diabetes and the agent
REACH TARGET within 3-6 months of diagnosis
What is active insulin?
• Portion of rapid-acting insulin still in circulation
• Important to understand this concept to avoid insulin stacking
when injection new dose of insulin to lower hyperglycemia it is important to know if there is still some insulin left in the circulation
1st line of treatment for t2
(nutritional therapy, weight management, physical activity) +/- metformin
DPP4-inhibitors and GLP-1 receptor agonist mechanism
act on pancreas
Stimulate insulin secretion Inhibit glucagon secretion
Thiazolidinedione (TZD) mechanism
act on liver, muscle and adipose tissue
Decrease insulin resistance
Alpha-glucosidase inhibitors meachnism
act on the gut
decrease glucose absorption
Biguanides (Metformin) mechanism
act on the liver
decrease gluconeogenesis
Insulin secretagogue examples + mechanism
act on pancreas
Sulfonylurea
Meglitinide
Stimulate insulin secretion
What class of drugs is metformin BEnefits and risks
Biguanide BENEFITS A1C 1 to 1.5% reduction Negligible risk as monotherapy (low risk of hypoglycemia) No weight gain pH VERY SAFE
Risks
• GI side effects
• Creatinine clearance:
• Caution if < 60 mL/min
• Contraindicated if < 30 mL/min (or hepatic failure)
• Lactic acidosis: rarely occurs if contraindications are taken into account
• B12 deficiency
Insulin secretagogues
benefis + risk
Benefits
A1C; 0.7 to 0.8% reduction – Rapid onset of response
Risks
All associated with risk of hypoglycemia
Weight gain
Blood sugar control is lost earlier than with Metformin (ADOPT)
Alpha-glucosidase inhibitors (AGIs)
benefis + risk
act upon the gut to delay glucose absorption
Benefits
– A1C Reduction of postprandial glycemia
Negligible risk as monotherapy (low risk of hypoglycemia)
Risks
Not recommended as initial therapy in people with A1C ≥8.5%
Contraindications:
– Diabetic ketoacidosis
– Inflammatory boweld isease
0.6% reduction
GI side effects: glucose will remain in GI-> bloating, discomfort
Thiazolidinediones (TZDs) method of action, benefits and risks
Benefits A1C 0.8% reduction Negligible risk as monotherapy Cardiovascular benefits – ↑HDL-C – ↓Triglycerides(pioglitazone) – ?↓CVDevents(ProACTIVE, pioglitazone)
Risks
Weight gain
Cardiovascular risks
DPP-4 inhibitors are usually take with
metformin
DPP-4 inhibitors benefits and risks
Benefits A1C 0.7% reduction Negligible risk as monotherapy Weight neutral Well tolerated
Risks
Rare cases of pancreatitis
Long-term safety is unclear
Which diabetic med is injectable?
GLP-1 receptor agonists
GLP-1 action pricniple
GLP-1 is released during meals
will increase insulin production and decrease glucagon secretion
DPP-4 function and why do diabetics use DPP-4 inhibitors
DPP-4 will reduce the amount of GLP-1-> less insulin
Additional effects are observed at pharmacologic levels of GLP-1
Decreased Gastric emptying Increased Satiety Decreased Energy intake Increased Nausea Decreased Weight V increased Insulin secretion V decreased Glucagon
GLP-1 receptor agonists benefits and risks
Benefits
A1C 1.0% reduction
Negligible risk as monotherapy
Significant weight loss
Risks
• GI side effects:
• Long-term safety is unclear
GLP-1 receptors agonist: Patient Education
- Gastro-intestinal symptoms
- if on insulin monitor for hypoglycemias and adjust accordingly
- Delivered via pen ( like insulin)
• refrigeration of the pen prior to first use (exenatide and liraglutide multiuse pens can be kept at room temperature after first use),
• hand washing and inspection of the medication for cloudiness or particulate matter before use
Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors additional benefits
- weight loss
- decreased BP
- slower progression of kidney disease
- decreased risk of CVD
Both __ and __ are excreted when SGLT2 is blocked
Both sodium and glucose are excreted when SGLT2 is blocked
Benefits of SGLt2
- Weight loss
- A1C reduction
- Reduction in blood pressure
- possibly also slow down kidney disease progression
- Positive impact on CV health
- Negligible risk as monotherapy
risks of SGLt2
Mycotic genital infection and UPI risks
• Euglycemic ketoacidosis: insulin + SGLT2-> risk of ketoacedosis without high blood glucose levels
SGLT2-inhibitors: Educate patients
Use like Metformin – stop before surgery and acute illness
• Given that the half-life of the SGLT2 inhibitors ranges from 11 to 13 hours, and the SGLT2 inhibitor effect can persist for at least a few days after discontinuation, these agents should be discontinued ~3 days before major surgical procedures.
Recognize Signs & Symptoms:
• Nausea, vomiting, malaise, urine ketones
• Encourage adequate fluid/Carbohydrate intake
Do not STOP insulin
Summary – SGLT2-i / GLP1-RA
the good and the bad
The good Lower A1c 3-5mmHg decrease systolic blood pressure (SGLT2-i) Weight loss (~2-3 kg) Renal protection CVD protection
The bad (what we have to look out for) Genital mycotic infection (SGLT2- i) Diuretic-like side effects (SGLT2- i) DKA (SGLT2-i) GI side effects (GLP1-RA) Expensive (GLP1-RA >SGLT2-i), thus not frontline Hypoglycemia if using with insulin
Does having pre-diabetes mean that u will develop diabetes?
Not all individuals with prediabetes will necessarily progress to develop diabetes. A lot of people diagnosed with IFG or IGT will go back to normoglycemia.
WHat is monogenic diabetes?
Monogenic diabetes is a rare disorder caused by genetic defects of beta cell function that typically presents in young people
Obesity and physical signs of insulin resistance (e.g. acanthosis nigricans) are more common in children and adolescents with type_ diabetes than type _ diabetes.
Obesity and physical signs of insulin resistance (e.g. acanthosis nigricans) are more common in children and adolescents with type 2 diabetes than type 1 diabetes.
What are the markers for diagnosis of T1?
The presence of autoimmune markers, such as anti-glutamic acid decarboxylase (GAD) or anti-islet cell (ICA) autoantibodies, may be helpful in identifying type 1 diabetes and rapid progression to insulin requirement, but levels wane over time and they do not have sufficient diagnostic accuracy to be used routinely
the absence of autoantibodies does not rule out type 1 diabetes.
