Type 2 diabetes mellitus Flashcards
What is diabetes mellitus?
A state of chronic hyperglycaemia sufficient to cause long-term damage to specific tissues, notably the retina, kidney, nerves and arteries.
What is the normal fasting blood glucose level?
<6mmol/L.
What is the normal 2 hour blood glucose level in a 75g oral glucose tolerance test?
<7.8mmol/L.
What is the normal random blood glucose level?
<11.1mmol/L.
What are the parameters that define diabetes mellitus?
Fasting blood glucose >7mmol/L.
2 hour blood glucose >11.1mmol/L.
Random blood glucose >11.1mmol/L.
What are the numerical boundaries of impaired fasting glucose?
6.0-7.0mmol/L.
What are the numerical boundaries of impaired glucose tolerance?
7.8-11.1mmol/L.
What do impaired fasting glucose and/or impaired glucose tolerance show?
Greater risk of macrovascular risk- at risk of progressing to higher sugar, but doesn’t yet have diabetes or microvascular risk.
Discuss the pathophysiology of T2DM.
MODY relatively uncommon but gives useful metabolic insights.
Genes and intrauterine environment and adult environment.
Insulin resistance and insulin secretion defects.
Fatty acids important in pathogenesis and complications- contribute to damage to beta cells and insulin resistance.
What is MODY?
Maturity onset diabetes of the young.
Several hereditary forms (1-8).
Autosomal dominant.
Ineffective pancreatic B cell insulin production.
Mutations of transcription factor genes, glucokinase gene.
Positive family history, no obesity.
Specific treatment for type.
What are the mechanisms of T2DM?
Mostly genetic disorder, behaving as autosomal dominant- don’t know the genes, not a single gene disorder.
Genes contribute to insulin resistance through adult life and probably through childhood.
Adipocytokines are a mechanism of diabetes.
Genes for diabetes associated with IUGR.
Genes associated with obesity and handling of fatty acids- part of mechanism.
Insulin resistance associated with metabolic complications like dyslipidaemia.
Metabolic and mitogenic complications due to insulin resistance lead to macrovascular complications.
Patient slowly fails to make enough insulin- B cell failure leading to hyperglycaemia and metabolic dyslipidaemia.
Inflammatory effects of insulin resistance.
Hyperglycaemia leads to microvascular complications.
B cell failure may become absolute- insulin requirement.
How does T2DM present?
Heterogeneous. Obesity. Insulin resistance and insulin secretion deficit. Hyperglycaemia and dyslipidaemia. Acute and chronic complications.
What is the simplest clinical measurement that can be taken to predict risk of ischaemic heart disease?
Waist circumference.
What percentage of T2DM patients are obese?
80%.
How may perturbations in gut microbiota be linked to T2DM?
Obesity, insulin resistance T2DM.
Host signalling.
Bacterial lipopolysaccharides fermentation to short chain fatty acids, bacterial modulation bile acids.
Inflammation, signalling metabolic pathways.
Most studies correlative.
Which diabetes drug is not associated with weight gain?
Metformin.
How do patients present with T2DM?
Osmotic symptoms, e.g. polyuria, polydipsia.
Infections.
Screening test.
At presentation of complication: acute, e.g. hyperosmolar coma, or chronic, e.g. ischaemic heart disease, retinopathy.
What are the microvascular complications of T2DM?
Retinopathy.
Nephropathy.
Neuropathy.
What are the macrovascular complications of T2DM?
Ischaemic heart disease.
Cerebrovascular.
Renal artery stenosis.
Peripheral vascular disease.
What are the metabolic complications of T2DM?
Lactic acidosis.
Hyperosmolar.
What is a complication of treatment of diabetes mellitus?
Hypoglycaemia.
What are the basics of management of T2DM?
Education.
Diet.
Pharmacological treatment.
Complication screening.
Why treat T2DM patients?
Remove symptoms.
Reduce chance of acute metabolic complications.
Reduce chance of long term complications.
Education.
What is the recommended diet for patients with T2DM?
Control total calories/ increase exercise (weight).
Reduce refined carbohydrate (less sugar).
Increase complex carbohydrate (more rice, etc.).
Reduce fat as proportion of calories (less IR).
Increase unsaturated fat as proportion of fat (IHD).
Increase soluble fibre (longer to absorb CHO).
Address salt (BP risk).
How is T2DM treated and monitored?
Weight
Glycaemia
BP
Dyslipidaemia
How is weight treated in T2DM?
Orlistat- GI lipase inhibitor.
Gastric bypass.
How is glucose treated in T2DM?
Metformin. Insulin. Sulphonylureas. Metaglinides. Alpha-glucosidase inhibitors. Thiazolidinediones. Glucagon like peptide. DPP4 inhibitors. SGLT2 inhibitors.
What is metformin?
Biguanide, insulin sensitiser.
Overweight patient with T2DM where diet alone has not succeeded.
Reduces insulin resistance by reducing hepatic glucose output and increasing peripheral glucose disposal.
GI side effects.
Do not use if severe liver, severe cardiac or mild renal failure.
What are sulphonylureas?
Glibenclamide, insulin secretagogue.
Lean patients with T2DM where diet alone has not succeeded.
S/E: hypoglycaemia, weight gain.
What is acarbose?
Alpha glucosidase inhibitor. Prolongs absorption of oligosaccharides. Allows insulin secretion to cope, following defective first phase insulin. As effective as metformin. S/E: flatus.
What are thiazolidinediones?
Peroxisome proliferator-activated receptor agonists, PPAR-gamma.
Pioglitazone.
Insulin sensitiser, mainly peripheral.
Adipocyte differentiation modified, weight gain but peripheral not central.
Improvement in glycaemia and lipids.
Evidence base on vascular outcomes.
S/E: hepatitis, heart failure.
What is glucagon like peptide-1 (GLP-1)?
Secreted in response to nutrients in gut.
Transcription product of proglucagon gene, mostly from L cell.
Stimulates insulin, suppresses glucagon.
Increases satiety.
Restores B cell glucose sensitivity.
Short half-life, rapid degradation from enzyme dipeptidyl peptidase 4 (DPPG-4 inhibitor).
How can GLP-1 be used in diabetes treatment?
GLP-1 agonist, e.g. eventide, liraglutide: Injectable. Long acting GLP-1 agonist. Decreases glucagon concentration. Decreases glucose concentration. Weight loss.
Gliptins (DPPG-4 inhibitor): Increase half-life of exogenous GLP-1. Increase concentration of GLP-1. Decrease glucagon concentration. Decrease glucose concentration. Neutral on weight.
How do SGLT2 inhibitors work against diabetes?
Suppress the action of SGLT2.
Reduce glucose reabsorption.
Increase urinary glucose excretion.
What is empaglifozin?
Inhibits Na-Glu transporter, increases glycosuria.
Lower all cause mortality.
HbA1c lower.
Lower risk heart failure.
What is the prevalence of T1DM and T2DM?
Type 1: 0.25%.
Type 2: 4-7%.
What is the typical age of presentation of type 1 and 2 DM?
Type 1: child, adolescent.
Type 2: middle-aged +
What is the mode of onset of type 1 and 2 DM?
Type 1: acute
Type 2: gradual
What is the habitus of type 1 vs. type 2 DM?
Type 1: lean.
Type 2: often obese.
Is there a family history in type 1 and 2 DM?
Uncommon in type 1.
Common in type 2.
Compare the geography of T1DM and T2DM.
Type 1: europids.
Type 2: less euripides.
Is there weight loss in T1DM and T2DM?
Type 1: usual
Type 2: uncommon
Are T1DM and T2DM ketosis prone?
Type 1: yes.
Type 2: no.
Compare serum insulin levels in T1DM and T2DM.
Type 1: low or absent
Type 2: variable
Is there HLA association in T1DM and T2DM?
Type 1: DR3, DR4.
Type 2: none.
Compare the state of islet B cells in T1DM and T2DM.
Type 1: destroyed.
Type 2: function.
Are islet cell antibodies present in T1DM and T2DM?
Type 1: present.
Type 2: absent.
