Type 2 Diabetes Flashcards
What is type 2 diabetes?
A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
What condition is associated with type 2 diabetes a lot?
Obesity
How is type 2 diabetes initially managed?
Lifestyle measures: diet changes and weight loss
Who typically presents with T2DM?
Usually late adulthood but can present in youth
What type of diabetes are you most likely to see diabetic ketoacidosis in and why?
T1DM
In type 2 you still produce a small enough insulin which is enough to suppress formation of ketones through lipolysis
How much does T2DM reduce life expectancy?
A lot when you are younger but less as you get older
Where is T2DM most prevalent? Given an example country
Ethnic groups that move from rural to urban lifestyle- biggest change seen in India
What is the biggest contributory factor to developing T2DM?
Can be insulin resistance mainly, but beta cell failure contributes
What is fasting glucose for a diagnosis of diabetes?
> 7 mmol/L
What is HbA1c for a diagnosis of diabetes?
> 48 mmol/L
What is OGTT for a diagnosis of diabetes?
> 11 mmol/L
What is fasting glucose in the intermediate stage of diabetes development?
Greater than 6 but less than 7 mmol/L
What is OGTT in the intermediate stage of diabetes development?
Greater than 7.7 but less than 11 mmol/L
What is HbA1c in the intermediate stage of diabetes development?
Greater than 42 but less than 48 mmol/L
How does insulin resistance change as someone is developing diabetes?
It curves up and plateaus before diabetes has even been diagnosed
What are the 3 ways of diagnosing diabetes?
Fasting glucose
OGTT
Random glucose
What level do beta cells function at diagnosis of T2DM?
Around 50%
Does diabetic ketoacidosis occur in T2DM? Explain your answer
Not usually, there is a small amount of circulating insulin (not enough to overcome resistance), which is enough to suppress the synthesis of ketone bodies from the breakdown of fat- this is relative insulin deficiency
What happens in long duration type 2 diabetes? What feature of diabetes becomes more prominent once this develops?
Beta cell failure may progress to complete insulin deficiency (this is where diabetic ketoacidosis may occur)
Does T2DM have a genetic risk?
Yes.
It’s influenced by genes, intrauterine environment and adult environment
How can risk of T2DM be increased in utero?
Foetal growth retardation
How is beta cell function assessed?
Hyperglycaemic clamp
What is hyperglycaemic clamp?
Glucose levels are elevated, in normal people insulin will shoot up, fall rapidly and then steadily fall, with T2 diabetics there will be hardly any rise in insulin
When is hyperglycaemic clamp used?
To assess beta cell function
What happens to glucose uptake in skeletal muscles in T2DM?
Reduced uptake of glucose due to reduced insulin
What happens to hepatic glucose output in T2DM? How?
Increased due to reduced insulin action and increased glucagon action
What happens to insulin sensitivity when we put on weight (in normal people)?
Insulin becomes less sensitive so more is secreted
What happens in the liver, adipocytes and muscle when theres insulin resistance?
Liver: less glycogen synthesis and greater hepatic glucose output
Adipocytes: less glucose uptake, less triglyceride synthesis
Muscle: less glucose uptake
What happens to inflammatory adipokines in T2DM?
Levels are high
Is T2DM monogenic or polygenic?
Polygenic- polymorphisms (Small changes to genes) inc. risk of diabetes
You’re not born with polygenic traits
Is MODY monogenic or polygenic?
Monogenic
What type of adiposity increases T2DM risk most?
Visceral adiposity increases risk a lot more than central
How does T2DM present?
Hyperglycaemia Overweight Dyslipidemia (high cholesterol) Fewer osmotic symptoms With complications Insulin resistance Later insulin deficiency
What are risk factors for T2DM?
Age High BMI Ethnicity PCOS Family history Inactivity
What is the first line test for the diagnosis of type 2 diabetes?
HbA1c
When will random glucose work as a diagnostic test?
If there are symptoms
How is HbA1c used as a diagnostic test?
If symptomatic 1 test can confirm diagnosis
If asymptomatic, 2 positive tests confirm diagnosis
What is hyperosmolar hyperglycaemic state? What does it commonly present with?
An acute compication of T2DM
Presents commonly with renal failure.
Insufficient insulin (NOT ABSENT) for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis. Glucose is >30 mmol/L
How is type 2 managed?
Diet Oral medication Structured education May need insulin later Remission / reversal Prevention of complications
How does a T2DM consultation go?
Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
Weight assessment
Blood pressure
Dyslipidaemia: cholesterol profile
Screening for complications: foot check, retinal screening
What dietary changes are recommended in T2DM?
Total calories control Reduce calories as fat Reduce calories as refined carbohydrate Increase calories as complex carbohydrate Increase soluble fibre Decrease sodium
If lifestyle changes don’t work for a diabetic patient, what do we give them?
Metformin
Aka. Biguanide
It’s first line if lifestyle changes aren’t working
Reduces insulin resistance through reduced HGO and inc. peripheral glucose disposal
What drug is given to improve insulin sensitivity?
Metformin
Thiozolidinediones
What drug is given to boost insulin secretion?
Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists
What drug is given to inhibit carb absorption in gut and inhibit renal glucose absorption?
Alpha glucosidase inhibitor
SGLT-2 inhibitor (renal)
What is the first line drug is lifestayle changes have no effect?
Metformin
How do sulphonyureas work?
Bind to ATP sensitive K+ channel and close it independant to glucose so insulin production is boosted
Normal insulin release requires closure of ATP sensitive K+ channel
What is pioglitazone?
S/Es?
It’s a peroxisome proliferator-activated receptor agonist PPAR-y
Insulin sensitizers, mainly peripheral
Adipocyte differentiation modified so you can get weight gain- peripheral however, not central
Side effects (of older types): hepatitis, heart failure
How does metformin effect weight?
Lowers it
What is GLP-1?
Gut hormone which stimulates insulin and suppresses glucagon
Increases satiety
Secreted in response to nutrients in gut from L cells
Transcripted from pro-glucagon gene
What is the incretin effect?
Oral glucose increases insulin almost double as much as intravenous glucose
How do DPP-4 inhibitors work?
Inhibits DPP-4 enzyme which metabolises GLP-1
How do SGLT-2 inhibitors work? Examples?
Inhibit Na-Glu transporter so encourages glycosuria
Lower HBA1C
e.g. dapagliflozin, empagliflozin, canagliflozin
Do drugs work for diabetes?
Yes but eventually insulin will be needed and beta cell function will always decline
What surgery can remit diabetes? (not cure)
Gastric bypass surgery
What lifestyle change can remit diabetes?
Very low calorie diet (800-900 cals a day) for 3-6 months
How does diabetic ketoacidosis compare to hyperosmolar hyperglycaemic syndrome?
Volume: In DK you’re dehydrated wheras is HHS you’re hypovolemic
Glucose: In DK, >11mmol/L. In HHS, >30mmol/L
Capillary blood ketones: DK, >3mmol/L. HSS <3mmol/L
Osmolarity: DK its variable. HHS >320mmol/l
Treatment: IV fluids for both immediately. In DK insulin given immediately at rate infusion of 0.1 units/kg/h. In HHS insulin only given immediately if capillary ketones >1mmol/L (urine >2), otherwise hold insulin until fluid resuscitation
What are the different inflammatory adipokines?
TNF-a & IL-6: stimulate lipolysis and VLDL secretion- inc. insulin resistance, dec. adiponectin expression
Endocannabinoids: As fat IR inc. circulation EC inc.
Glucocorticoids: Inc. 11B HSD-1 in fat. Inc. IR. Inc. glucose, BP and lipids
Adiponectin: dec. insulin sensitivity. Predictive of diabetes
Leptin: Elevated in obesity. Inc. IR, dec. appetite, inc. metabolic rate
Fatty acids: Elevated in obesity and T2DM. Inc. IR, Dec b cell function, increased liver TG secretion, inc. organ fat
Visfatin: Visceral fat. Dec IR
Resistin: Inc. in obesity and T2DM. Inc. IR, Inc. liver TG secretion
Apelin: Insulin stimulated its expression in fat. Elevated in hyperinsulin. CV affects
How do genetic risks and environmental risks vary for the development of T2DM?
If you have a low genetic risk, you’ll need a strong environmental risk
If you have a high genetic risk you will need a weak environmental risk
What is the imact of SNPs on diabetes?
Each individual SNP only has a small effect of risk but cumulative SNPs have a big risk of developing T2DM
Apart from obesity, what else can influence diabetes risk?
Stability of gut microbiota. Instability caused by:
Obesity and IR
Bacterial lipopolysaccharide fermentation to short hain FA
Inflammation
What are side effects and contraindications of metformin?
GI side effects
Contraindicated in severe liver, cardiac or moderate renal failure
What is the effect of GLP-1 agonists and give examples
Decrease glucagon con and glucose conc
Injected daily
Lead to weight loss
E.g. Liraglutide, semaglutide
What is the effect of DPPG-4 inhibitors?
Aka. Gliptins
Inc. half life of exogenous GLP-1
Increase conc. of GLP-1
Dec. glucagon and glucose conc.
No weight change
What are pros of SGLT-2 inhibitors?
Improve CKD
Lower HbA1C
Lower mortality
Lower risk of hrt failure
What is the most effective medication in increasing beta cell function?
Sulfonylureas
Then metformin, the diet
What other aspects of management do we have to consider with T2DM?
Blood pressure management (maybe give ACEi)
Lipid management: Cholesterol, triglycerides, HDLs
What are examples of empowering language for a diabetic patient?
Person living with diabetes
What are your thoughts on your glucose levels?
Lets talk through options and see what suits you?
