Type 2 diabetes Flashcards
What is type 2 diabetes?
The combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always
How can type 2 diabetes be managed?
The resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible
With time glucose lowering therapy e.g. insulin, is needed
What insulin deficiency do you get in T2DM?
Relative insulin deficiency as opposed to absolute
Why is diagnosing T2DM more difficult now?
T2DM may present in youth / young adults
Diabetic ketoacidosis can be a feature of T2DM
If you are diagnosed early what does this mean for prognosis?
On average die earlier a patient is diagnosed with T2DM
What are some epidemiological facts of T2DM?
Prevalence of T2DM varies enormously
Increasing prevalence
Occurring and being diagnosed younger
Greatest in ethnic groups that move from rural to urban lifestyle
What ethnic groups are more susceptible to T2DM?
Asian
Pacific Islanders
Afro-Caribbean’s
What are the stages of development of type 2 diabetes?
Normal
Intermediate state
T2DM
What glucose levels can define intermediate state via fasting glucose levels?
<6mmol/L (normal)
Impaired fasting glycaemia
>7 mmol/L (T2DM)
What glucose levels can define intermediate state via 2hr glucose (OGTT)?
<7.7 mmol/L
Impaired glucose tolerance
>11 mmol/L
What glucose levels can define intermediate state via HbA1c?
<42 mmol/L
Pre-diabetes or non-diabetic hyperglycaemia
>48 mmol/L
What is the relationship between insulin resistance and stage of development of T2DM?
Insulin resistance increases
Non-linear relationship
Curve that plateaus
So, if insulin resistance plateaus why does T2DM develop from the intermediate state?
Insulin production decreases
What are the 4 ways of diagnosing T2DM?
Fasting glucose
2-hour glucose tolerance test
HbA1c
Random blood glucose (only with symptoms)
What is beta-cell function at diagnosis of T2DM?
By the time someone presents with T2DM they have already lost some beta-cell function already
In order to present with hyperglycaemia
What are the main features of relative insulin deficiency?
Insulin is produced by beta-cells but not enough to overcome resistance
Relative deficiency of insulin
Why is the fact that the insulin deficiency is relative important?
This is important to understand as it explains why the hyperglycaemia encountered does not cause ketosis under ‘usual’ circumstances
Enough insulin to suppress the beta-oxidation forming ketones
What happens when T2DM is longterm?
beta-cell failure may progress to complete insulin deficiency
Usually on insulin at this point in any case, but important not to stop as at risk of ketoacidosis
What factors are associated with an increased risk of T2DM?
Genes Intrauterine environment (early foetal programming that modifies risk) Adult environment Insulin resistance Insulin secretion defects Fatty acids
What is a misconception of T2DM?
HETEROGENOUS
People develop T2DM at variable BMI, ages and progress differently
What does reduced insulin action cause?
less uptake of glucose into skeletal muscle
hepatic glucose production is also increased due to both a reduction in insulin action and increase in glucagon action
What is the relationship between insulin resistance and secretion?
Non-linear
Downward curve
What happens to the relationship between resistance and secretion in T2DM?
People developing type 2 diabetes have ‘fallen off the curve’
And for a given degree of insulin sensitivity secrete less insulin
What are the consequences of insulin resistance?
Excess hepatic glucose production
Decreased uptake of glucose by skeletal muscle
Why do beta cells stop functioning?
Beta cells become exhausted from overproduction of insulin
Creates toxic environment in pancreas
Beta cell apoptosis
Is inflammation involved in the pathophysiology of T2DM?
Adipokines have a huge variety of effects
What does polygenic mean?
Polymorphisms increasing risk of diabetes
‘Not born with it but high risk and may develop later depending on other factors’
What are the main features of monogenic diabetes?
Single gene mutation ==> Diabetes (MODY)
‘Born with it, always going to develop diabetes’
What is the spectrum of genetic/environment interactions?
Low genetic risk + strong environmental
High genetic risk + weak environmental
High genetic risk + strong environmental
Low genetic risk + weak environmental
What can you find from GWA studies?
400 SNPs have been found to increase risk of T2DM
TCF7L2 has the strongest effect (1.4%)
Summation of multiple SNPs can contribute majorly
What is the role of obesity in T2DM?
Major risk factor for T2DM Fatty acids and adipocytokines important Central vs visceral obesity 80% T2DM are obese Weight reduction useful treatment
How does T2DM present?
Hyperglycaemia Overweight Dyslipidaemia Fewer osmotic symptoms With complications Insulin resistance Later insulin deficiency
What are the risk factors for T2DM?
Age
PCOS
Increased BMI Family Hx
Ethnicity Inactivity
How do you diagnose T2DM?
HbA1c most commonly
Osmotic symptoms
Infections
Screening test: incidental finding
at presentation of complication
Acute; hyperosmolar hyperglycaemic state,
Chronic; ischaemic heart disease, retinopathy
What are the criteria for diagnosis of T2DM?
1x HbA1c >=48mmol/L with symptoms
Or
2x HbA1c >=48 mmol/mol if aysymptomatic
What are the main features of hyperosmolar hyperglycaemic state?
Presents commonly with renal failure.
Insufficient insulin (NOT ABSENT) for prevention of hyperglycemia but sufficient insulin for suppression of lipolysis and ketogenesis.
Absence of significant acidosis.
Often identifiable precipitating event (infection, MI).
How do you manage T2DM?
Diet Oral medication Structured education May need insulin later Remission / reversal
What are the categories of diabetes related complications?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular
What are the principles of a T2DM consultation?
Glycaemia: HbA1c, glucose monitoring if on insulin, medication review
Weight assessment
Blood pressure
Dyslipidaemia: cholesterol profile
Screening for complications: foot check, retinal screening
What are the dietary recommendations made for T2DM?
Total calories control Reduce calories as fat Reduce calories as refined carbohydrate Increase calories as complex carbohydrate Increase soluble fibre Decrease sodium
How do you manage excess hepatic glucose production?
Metfomin
How do you improve insulin sensitivity?
Metformin
Thiozolidinediones
How do you boost insulin secretion?
Sulphonylureas
DPP4-inhibitors
GLP-1 Agonists
How do you Inhibit carbohydrate gut absorption and
Inhibit renal glucose resorption?
Alpha glucosidase inhibitor
SGLT-2 inhibitor
What are the main features of metformin?
Biguanide, insulin sensitiser
First line if dietary / lifestyle adjustment has made no difference
Reduces insulin resistance
Reduced hepatic glucose output
Increases peripheral glucose disposal
GI side effects
Contraindicated in severe liver, severe cardiac or moderate renal failure
What are the main features of Sulphonylureas?
Normal insulin release requires closer of the
ATP-sensitive potassium channel
Sulphonylureas eg gliclazide, bind to the ATP-sensitive potassium channel and close it, independent of glucose / ATP
What are the main features of Pioglitazone?
Peroxisome proliferator-actived receptor agonists PPAR-γ
Insulin sensitizer, mainly peripheral
Adipocyte differentiation modified, weight gain but peripheral not central
Improvement in glycaemia and lipids
Evidence base on vascular outcomes
Side effects of older types hepatitis, heart failure
What is GLP-1?
Gut hormone
Secreted in response to nutrients in gut
Transcription product of pro-glucagon gene, mostly from L-cell
Stimulates insulin, suppresses glucagon
↑ satiety (feeling of ‘fullness’)
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPP4 inhibitor)
Used in treatment of diabetes mellitus
How do GLP-2 agonists work?
Liraglutide, Semaglutide Injectable –daily, weekly Decrease [glucagon] Decrease [glucose] Weight loss
How do Gliptins (DPPG-4 inhibitor) work?
Increase half life of exogenous GLP-1 Increase [GLP-1] Decrease [glucagon] Decrease [glucose] Neutral on weight
How do SGLT-2 inhibitors work?
Inhibits Na-Glu transporter, increases glycosuria
Empagliflozin, dapagliflozin, canagliflozin
HbA1c lower
32% lower all cause mortality
35% lower risk heart failure
Improve CKD
What can cause remission of T2DM?
Gastric bypass surgery
Low-calorie diet (800 kcal/day) for 3-6 months
What are other aspects of management?
Blood pressure
Lipid management, insulin normally inhibits lipolysis
- Atorvarstatin 20mg if q-risk > 10%
- Atorvarstatin 80mg if IHD/CVD/PVD
What skin conditions is seen in T2DM?
Acanthosis nigracans
Darkening of armpits
When can you not use HbA1c?
Pregnancy
Sickle cell
What is the
Step 1: Metformin
Step 2: Another drug e.g. DPP-4 inhibitor, pioglitazone, SU, SGLT-2i
Step 3: Further drug or insulin
What is the difference between HTN in diabetics?
Type II
Everyone gets ACEi or ARBs not CCB
What can cause hypoglycaemia?
Missed meals Alcohol Exercise Inapprop insulin Some drugs e.g SU or SGLT-2i
What is the treatment for a hypo?
Conscious: Oral glucose and complex CHO
Impaired conscious:
Parenteral: 1mg Glucagon IM
10% IV Dextrose
