Type 2 Diabetes Flashcards by Abi S

What is type 2 diabetes

A condition in which the combination of insulin resistance and beta-cell failure result in hyperglycaemia
Associated with obesity but not always
The resultant chronic hyperglycaemia may initially be managed by changes to diet / weight loss and may even be reversible
With time glucose lowering therapy including insulin, is needed

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What does fasting glucose show?

≤ 6 mmol/L

Impaired fasting glycaemia

≥7 mmol/L

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What does 2-hr glucose (OGTT)

< 7.7 mmol/L

Impaired glucose tolerance

≥11 mmol/L

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What does HbA1c show

< 42 mmol/mol

Pre-diabetes or non-diabetic hyperglycaemia

≥ 48 mmol/mol

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What does random glucose show?

> 11.1 with symptoms is diabetic

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How is the beta cell function diagnosis of T2DM different from T1

The start of treatment is at a higher level of beta cell function

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Why type of insulin deficiency is present in type 2 diabetes and why is this important

Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance
There is therefore a relative deficiency of insulin
This is important to understand as it explains why the hyperglycaemia encountered does not cause ketosis under ‘usual’ circumstances

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What are factors that affect insulin secretion and action

Body weight
Physical activity
Smoking
Heavy alcohol consumption
Genetic predisposition
Gene-environment interaction
Epigenetics

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What does insulin resistance and beta cell dysfunction lead to

Increase in hepatic glucose production (also due to increase in glucagon action)

Decrease in glucose uptake in adipose tissue and skeletal muscle

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What happens to the first phase inulin release in type 2 diabetes?

There is no sharp first phase insulin release

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Describe the relationship between insulin resistance and insulin secretion

The more sensitive, the less is needed to be secreted

People developing type 2 diabetes have ‘fallen off the curve’
And for a given degree of insulin sensitivity secrete less insulin

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Where are the consequences of insulin resistance seen

Liver
Adipocytes
Muscle

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What happens in terms of inflammatory adipokines?

There is an excess

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What is monogenic

Single gene mutation ==> Diabetes (MODY)
‘Born with it, always going to develop diabetes’

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What is polygenic

Polymorphisms increasing risk of diabetes
‘Not born with it but high risk and may develop later depending on other factors

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What is the role of obesity in type 2 diabetes

Major risk factor for T2DM
Fatty acids and adipocytokines important
Central vs visceral obesity
80% T2DM are obese
Weight reduction useful treatment

What else plays a role in type 2 diabetes

Perturbations in gut microbiota
Intra-uterine growth retardation

What are the presentations of T2DM

Hyperglycaemia
Overweight
Dyslipidaemia
Fewer osmotic symptoms
With complications
Insulin resistance
Later insulin deficiency

What are the risk factors for T2DM

Age
PCOS
Inc BMI
Family Hx
Ethnicity
Inactivity

How to diagnose type 2 diabetes

First line test for diagnosis is HbA1c. – more practical

1x HbA1c >=48mmol/L with symptoms

2x HbA1c >=48 mmol/mol if aysymptomatic

Osmotic symptoms
Infections
Screening test: incidental finding
at presentation of complication
Acute; hyperosmolar hyperglycaemic state,
Chronic; ischaemic heart disease, retinopathy

What is 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).

Dehydration -

What is the management difference between type 1 and type 2 diabetes

Exogenous insulin (basal-bolus regime)
Self-monitoring of glucose
Structured education
Technology

Diet
Oral medication
Structured education
May need insulin later
Remission / reversal

What diabetes-related complications and their risk factors are we trying to prevent

Retinopathy
Neuropathy
Nephropathy
Cardiovascular

What are the principles of a diabetes 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 to do when there is excess hepatic glucose production

Reduce hepatic glucose production Meformin

What to do when there is resistance to action of circulating insulin

Improve insulin sensitivity Metformin Thiozolidinediones

What to do when there is an inadequate insulin production for extent of insulin resistance

Boost insulin secretion Sulphonylureas DPP4-inhibitors GLP-1 Agonists

What to do when there is excess glucose in circulation

Inhibit carbohydrate gut absorption Inhibit renal glucose resorption Alpha glucosidase inhibitor SGLT-2 inhibitor

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

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

Pioglitazone

Peroxisome proliferator-actived receptor agonists PPAR-γ Pioglitazone 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

Glucagon like (GLP-1) peptide-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

Incretin effect?

Orally ingested glucose elicits a much greater insulin response than that obtained when glucose is infused intravenously to give identical blood glucose levels

GLP-1 agonist

Liraglutide, Semaglutide Injectable –daily, weekly Decrease [glucagon] Decrease [glucose] Weight loss

Gliptins (DPPG-4 inhibitor)

Increase half life of exogenous GLP-1 Increase [GLP-1] Decrease [glucagon] Decrease [glucose] Neutral on weight

SGLT-2 inhibitors

Inhibits Na-Glu transporter, increases glycosuria Empagliflozin, dapagliflozin, canagliflozin HbA1c lower 32% lower all cause mortality 35% lower risk heart failure Improve CKD

Remission of T2DM?

Gastric bypass surgery has the potential to induce remission of type 2 diabetes Very low-calorie diet (800 kcal/day) for 3-6 months has the potential to induce remission, which appears to be sustained at 2 years

What are the other aspects of management for T2DM?

Blood Pressure management Hypertension very common in T2DM Clear benefits for reduction esp with use of ACE-inhibitors Lipid management Total cholesterol raised Triglycerides raised HDL cholesterol reduced Clear benefit to lipid-lowering therapy