Diabetes Flashcards
How many people diagnosed with diabetes in UK
3 million
4.9% of population
How much does DM lower life expectancy by
7 years
Insulin effect on liver
Inhibits gluconeogenesis
Promotes glycogen storage
Insulin effect on muscle
Glucose uptake
Promotes glycogen storage
Insulin effect on adipose tissue
Inhibits lipolysis
Increases fat synthesis
Type 1 onset
Usually juvenile onset (before 35)
Type 2 onset
Mainly after 35
More common in males
Which diabetes is prone to ketosis
Type 1
Which diabetes is prone to weight loss
Type 1
Type 1 Insulin
Insulin deficiency
Ketoacidosis
ALWAYS need insulin
Type 2 insulin
Insulin resistance - may have deficiency
Partial insulin deficiency initially and hyperosmolar state
Need insulin when Beta cells fail over time
Type 1 + autoimmune
GAD and ICA antibodies
Attack B cells
Type 2 + autoimmune
Non autoimmune
Associated with metabolic syndrome
Type 1 + HLA
HLA-DR3 and HLA-DR4 in more than 90%
Islet cell antibodies
Type 2 + HLA
No HLA relation
MZ Twins + Diabetes
50% concordance Type 1
100% concordance Type 2
Symptom duration
Type 1- weeks
Type 2- months/years
Ethnicity Type 1
Higher risk Northern European
Ethnicity Type 2
Higher risk Asian, African, poylnesian, native american
C peptide
Disappears in Type 1
Persists in Type 2
LADA
Latent autoimmune diabetes of adults
Type 1B DM
MODY
Maturity onset diabetes of the young
Rare autosomal form of T2DM
Secondary Diabetes- Pancreatic disease (diseases of exocrine pancreas)
Acute + chronic pancreatitis Trauma Pancreatectomy Neoplasia Cystic Fibrosis Haemochromatosis Thalassaemia Fibrocalculous pancreatopathy
Secondary Diabetes- Endocrine disease (diseases of endocrine pancreas)
Acromegaly Cushing's Glucagonoma Phaeochromocytoma Hyperthyroidism Conn's disease Aldosteronoma Somatostatinoma
Drug-induced Diabetes
Immunosuppressive agents- glucocorticoids, cyclosporin, tacrolimus, sirolimus Beta blockers Beta adrenergic agonists Atypical antipsychotics (clozapine, olanzapine) Thiazide diuretics Phenytoin Levothyroxine Interferon alpha HIV treatment Niacin (B3) Pentamidine
Secondary diabetes- Genetic defects of:
Beta cell function Insulin action (receptor mutations) Genetic syndromes- Down's, Friedreich's ataxia, Huntington's chorea Klinefelter syndrome Prader- Willi Turner
Secondary diabetes- Infections
Congenital rubella
CMV
Secondary diabetes- uncommon forms f immune mediated diabetes
Stiff person syndrome
Anti-insulin receptor antibodies
Diabetes Investigations
Fasting plasma glucose (FPG)
Random plasma glucose (RPG)
75g oral glucose tolerance test (OGTT)
HbA1c
75g Oral glucose tolerance test
Fast for 9 hours
Check fasting plasma glucose
Give 75g of glucose
Check 2 hour plasma glucose
HbA1c
Measure for average glucose control over 3 month period
Normal- below 42 mmol/mol
Generally below 53 indicates well controlled diabetes
Investigating with symptoms
1 diagnostic test
Investigating without symptoms
2 diagnostic tests OR 1 abnormal OGTT
Type 1 Aetiology
Polygenic
Autoantibodies against pancreatic islets
Pancreatic beta cell destruction –> absolute insulin deficiency
LADA
diagnosed in adulthood
Usually non-acute –> can be diagnosed as T2DM
ICA or GAD +ve
Require insulin
T1DM environmental influences
Peak age onset 5-7 years
Puberty
Seasonal variation
Predominantly European population
T1DM Genetic susceptibility
HLA genes on chromosome 6q (MHC)-HLA DR3/4
Genes on chromosomes 2q, 15q and 11q
Pathogenic sequence of T1DM
Genetic susceptibility
Environmental insult (virus)
Development of insulitis (infiltration of activated T lymphocytes)
Activation of autoimmunity
Immune attack on Beta vells
Development of DM (when more than 90% of Beta cells are destroyed)
When do you develop T1DM
When more than 90% of Beta cells are destroyed
Glucose toxicity
Beta cells have decreased functionality when exposed to high levels of glucose
–> lowering glucose may increase beta cell function and promote greater insulin secretion
Alpha cells in T2DM
Increased
Leads to increased glucagon/insulin ratio
Classic Osmotic Symptoms
Polyuria Polydipsia Weight loss Nocturia Fatigue Pruritis Blurred Vision Recurrent UTI or GU infections DKA
HHS
Hyperosmolar Hyperglycaemic Syndrome
Diabetes complications
Skin infections Foot problems Retinopathy Erectile dysfunction Arterial disease
Factors in obesity contributing to insulin resistance
Adipokines
Inflammation
Lipids
Insulin resistance
Diminution in the response of the body’s tissues to insulin, so that higher concentrations of serum insulin are required to maintain normal circulating glucose levels; eventually the islet cells can no longer produce adequate amounts of insulin for effective glucose lowering, resulting in hyperglycaemia
Metabolic syndrome
Cluster of conditions that together increase risk of heart disease, stroke + T2DM Central obesity Dyslipidaemia Hypertension Impaired fasting glucose
Metabolic syndrome: Central obesity
BMI > 30 or Waist circumference of: Caucasian men- >94 Caucasian women- >80 South Asian men- >90 South Asian women- >80
Metabolic syndrome: Dyslipidaemia
Increased Triglycerides >150mg/dL
Decreased HDL-cholesterol: <40mg/dL women, <50mg/dL men
Metabolic syndrome: Hypertension
Systolic >130
Diastolic>85
Metabolic syndrome: Impaired fasting glucose
Fasting glucose >6.1mmol/L
Self monitoring blood glucose aims
Pre-prandial: 4-7mmol/L
Post-prandial (2hrs): 5-9mmol/L
Fructosamine
Another glycated protein- lasts around 2 weeks
Can be used if HbA1c invalid e.g. haemoglobinopathy, increased RBC turnover
Useful in glucose control in pregnancy
First line T2DM
Diet
Physical activity- 3x30mins
3-5% weight reduction
Smoking cessation
Smoking in diabetes
1 cigarette is equal to 5 cigarettes for non-diabetic
Diabetic BP control
Aim 140/80
If CVD or renal disease too, 130/80
Diabetic cholesterol control
Diabetic>40 or Diabetic<40 + 1 risk factor= statin
Aim total cholesterol <4, LDL <2
Biguanides
Metformin
Biguanides function
1st line T2DM
Decreases hepatic glucose production (gluconeogenesis and glycogenolysis)
Improve insulin sensitivity in liver + muscle
Doesn’t affect insulin secretion, doesn’t induce hypoglycaemia and doesn’t predispose to weight gain
Biguanides SEs
Nausea Diarrhoea Abdominal pain Anorexia Hypoglycaemia
Biguanides STOP IF
Tissue hypoxia e.g. sepsis or MI
General anaesthesia
Before contrast medium containing iodine –> renal failure + subsequent lactic acidosis
Restart no earlier than 48hr after test of renal function shows no deterioration
Insulin Secretagogues
Sulfonylureas
Meglitinides
Biguanides Contraindictions
Severe hepatic disease
Severe renal disease (CKD stage 4 or eGFR<36ml/min)
–> can cause lactic acidosis
Sulfonylureas examples
Gliclazide Tolbutamide Glibenclamide Glipizide Glimepiride Chlorpropamide
Sulfonylureas function
Oral hypoglycaemic
Increases insulin release from pancreas
Opens K+ channels in beta cells
Sulfonylureas side effects
Hypoglycaemia
Weight gain
Meglitinides examples
Repaglinide
Nateglinide
Meglitinide function
Opens K+ channels in Beta cells to increase insulin release
Short acting agents that promote postprandial release of insulin- Prandial Glucose Regulators (PGRs)
Thiazolidinediones (TZDs)/Glitazones example
Pioglitazone
TZDs MOA
PPAR-gamma agonist
Modulates gene transcription of regions controlling lipid metabolism in the muscle, adipose tissue and liver –> decreases insulin resistance peripherally + increases insulin sensitivity
TZDs SEs
Hypoglycaemia Weight gain Fluid retention Heart failure Liver impairment Bladder cancer Mild anaemia Osteoporosis/fractures
TZDs contraindications
Past/present HF
Osteoporosis
Glucagon like peptide - 1 (GLP-1)
Incretin
Gut peptide that augments insulin release when glucose is detected + decreases glucagon secretion
Slows gastric emptying + induces satiety
Stimulate + preserve Beta cells
GLP 1 receptor analogues examples
Exenatide
Liraglutide
Lixisenatide
GLP1 receptor analogues
Injected not oral
Only used in overweight patients (BMI > 35) with poor glucose control