Abnormal blood sugar presentation Flashcards
(48 cards)
1
Q
Define abnormal blood sugar
A
Blood sugar measurement outside of the normal range 3.5 to 5.5 mmol/L
In reality hypo or hyper glycaemia are defined by large deviations from the above range (i.e 6 mmol/L is not considered hyperglycaemic)
2
Q
Define hyperglycaemia
A
Venous or capillary blood blood glucose levels > 7mmol/L when fasting OR 11mmol/L 2 hours post prandial
3
Q
define hypoglycaemia
A
venous of capillary blood glucose levesl < 3.3 mmol/L
4
Q
What is whipple’s triad?
A
- Whipple’s triad –> present in cases of true hypoglycaemia:
- hypoglycaemic symptoms
- low blood glucose concentration
- resolution of symptoms after raising blood glucose concentration to normal
5
Q
What are the key diagnostic factors for hypoglycaemia in history?
A
-
Sympathoadrenal symptoms: sympathoadrenal sx result as a decrease glucose causes sympathetic activation of adrenal glands and catecholamine release.
- Diaphoresis
- anxiety/ irritability
- hunger/ nausea
- tremor
- palpitations
- dizziness
-
Neuroglypenic symptoms:
- confusion
- drowsy
- visual disturbance/ blurred vision
- seizure
- coma
- generalised tingling
6
Q
What is the pathophysiology underlying hypoglycaemia?
A
- Glucose = obligate fuel for the brain, to maintain proper brain function plasma glucose must be maintained within narrow range
- counterregulatory mechanisms exist to prevent/ correct hypoglycaemia:
- decreased insulin secretion
- increase in glucagon secretion
- increase in epinephrine secretion
- increase cortisol and growth hormone
- symptoms prompting food ingestion - develop after drop below 3mmol/L
7
Q
What are the red flags for hypoglycaemia?
What are the risk factors/causes for/of hypoglycaemia?
A
Red flags –> hypoglycaemia = medical emergency, all symptoms are potentially red flags.
Risk factors:
- Middle age
- female
- insulinoma - neuroendocrine tumour that secretes insulin unregulated
- exogenous poisoning or insulin - e.g. incorrect dose, intentional overdose, correct dose but decreased food intake
- liver failure/ ethanol –> depleted glycogen stores, impaired gluconeogenesis
- intense exercise (leads to glucose uptake independent of insulin)
- adrenal insufficiency –> lack of cortisol response to low blood glucose levels, fail to counteract hypoglycaemia (significant cause in paediatric cases)
- growth hormone deficiency –> again lack of counteractive response, common in paediatric cases
- hypopituitarism –> failure of HPA, deficient growth hormone or adrenocorticotropic hormone secretion
- fibromas/sarcomas/fibrosarcomas –> large tumours that secrete insulin like growth factor unregulated
- anorexia nervosa –> chronic malnourishment leads to lack glycogen stores needed to counteract hypoglycaemia
8
Q
PMH: what conditions can cause hypoglycaemia?
A
- adrenal insufficiency
- growth hormone insufficiency
- hypopituitarism
- fibromas/sarcoma/fibrosarcomas
- glycogen storage diseases - lack of stored glycogen hinders production of glucose to counteract hypoglycaemia
- anorexia
- malnutrition
- liver failure
- renal failure –> may impair gluconeogenesis
- ethanol consumption –> heavy alcohol consumption decreases hepatic production of glucose
- bariatric surgery –> may cause abnormalities in stomach emptying )rapid transit of carbs) can lead to hypoglycaemia
9
Q
Drug history: what drugs can cause hypoglycaemia?
A
- Quinine and quinolones
- sulfonylurea (stimulates insulin secretion therefore increasing insulin production, also increases insulin binding to receptors so stimualtes glucose uptake)
- haloperidol (alpha adrenergic block)
- tramadol (increase risk hypoglycaemia)
- salicylates (increase in insulin response)
- beta blockers - adrenergic blockade, sustains hypoglycaemia
10
Q
What examination features for hypoglycaemia?
A
- Diaphoresis
- tremor
- tachycardia
- unexplained weight gain –> w hypoglyaemic symptoms may suggest insulinoma
- unexplained weight loss –> may suggest adrenal insufficiency
- hyperpigmentation –> typically in folds/ scars notexposed to sun, may suggest adrenal insufficiency –> lack of cortisol response to low serum glucose fails to counteract hypoglycaemia (common in paediatric)
- hypotension –> adrenal insufficiency
- short stature –> growth hormone deficiency (typically in paediatrics)
11
Q
What is the cause of hypoglycaemia in a known diabetic?
A
- Most common cause in diabetic = insulin or sulfonylurea use (accidental or non accidental oversode, or non adjustment of dose depending on activity level and/or food intake)
- T2DM –> post prandial (reactive) hypoglycaemia can occur within 4 hours of eating a high carbohydrate meal
12
Q
What are the causes of hypoglycaemia in non diabetics?
A
EXPLAIN causes
EX –> exogenous drugs –> insulin or hypoglycaemics (alcohol, aspirin, beta blockers, quinine, sulfonlyureas (increase release insulin from pancreas))
P –> Pituitary insufficiency
L –> Liver failure, rare inherited enzyme diseases
A –> Addison’s disease
I –> Islet cell tumour (insulinoma) and immune hypoglycaemia (Anti-insulin receptor Ig in Hogkin’s disease)
N = non pancreatic neoplasma e.g. fibrosarcomas that produce insulin like growth factor 2 or tumours with high metabolic demand utilising free glucose
13
Q
What is the pathophysiology behind:
exogenous drugs causing hypoglycaemia?
A
1) Insulin overdose/ incorrect dosing for food intake –> insulin binds insulin receptor on cells leading to expression of GLUT4 in the outer membrane of skeletal and liver cells, activation of glycogenesis and lipogenesis in adipose tissue, inhibition proteolysis/gluconeogenesis —> leads to increase uptake of glucose from the blood.
Excess insulin or IGF-2 from tumours act via the same mechanism
Sulphoylureas –> close the ATP sensitive K+ channels in beta ells, causing constant depolarisation and insulin release unregulated
14
Q
Pathophysiology: HPA axis problems?
A
- Normally the hypothalamus detects hypoglycaemia and secretes corticotrophin releasing hormone (CRH) –> stimulates the pituitary gland to secrete adrenocorticotrophic hormone which in turn stimulates the adrenal gland to secrete cortisol and other molecules
- Cortisol stimulates gluconeogeneis (pyruvate –> glucose) in order to increase blood glucose levvels
- Tissues at any point in this axis can lead to hypoglycaemia, as the body cannot respond to dropping glucose levels e..g pituitary insufficiency and addison’s disease (adrenal insufficiency, lack of adrenal hormones/ glucocorticoids).
15
Q
Pathophysiology: liver failure
A
Liver = major site of gluconeogenesis, thus damage = inability to correct hypoglycaemic state
overall result –> blood glucose levels drop such that the HPA axis is stimulated –> leads to cortisol and adrenaline secretion –> leads to sympathoadrenal symptoms of hypoglycaemia (diaphoresis, tachycardia, anxiety, tremor) at levels usually around 3.6 mmol/L and below
At levels below 2.8 mmol/L, neuroglycopenic symptoms (blurred vision, dizziness, confusion, coma) result due to an inability of the brain to function in abscence of sufficient glucose (glucose = primary energy source for brain, unable to store therefore needs constant supply via vasculature).
16
Q
Diagnosis: Hypoglycaemia
What bedside/ lab investigations need to be done and why?
A
- Do a capillary blood sugar on all patients with any suggestion of hypoglycaemia
- Further investigations are needed is presentation of Whipples triad (symptoms of hypoglycaemia, low blood sugar, reversed by raising serum glucose).
-
1) Serum Glucose:
- When symptoms present OR during 72 hour fast = < 2.8 mmol/L. If fasting, if glucagon administration at conclusion shows >1.4 mmol/L glucose increase = Insulinoma or IGFII secretion
- 2) LFT’s to rule out hepatic cause
- 3) Renal function testing - to rule out renal cause e.g congestive HF, chronic renal failure or hepatorenal syndrome.
-
4) Serum insulin
- should be undetectable when <3.3 mmol/L glucose. If high (>21pmol/L) = exogenous insulin, sulphonylurea or insulinoma
- 5) C - peptide (from cleavage of proinsulin into mature insulin and C peptide) : to distinguish between endogenous and exogenous insulin. If high (> 200pmol/L) insulin is endogenous e.g. insulinoma or sulphonylurea induced hypoglycaemia.
- 6) serum beta hydroxybutyrate –> measured at time of symptoms or end of 72 hour fast, excessive insulin or insulin like growth factor ii inhibits ketogenesis –> lowers beta hydroxybutryrate (supports diagnosis of tumour). Need Beta hydroxybutryrate < 2.7 mmol/L
- 7) Serum sulfonylurea –> presence indicates iatrogenic hypoglycaemia, usually done in urine or serum. If positive know medication induced
- 8) Thyroid stimulating hormones –> to rule out thyroid dysfunction
- 9) serum cortisol –> low level to indicate adrenal glands or hypopituitarism as source of adrenal insufficiency.
17
Q
What is the purpose of testing serum C peptide in hypoglycaemia?
A
C - peptide (from cleavage of proinsulin into mature insulin and C peptide) :
to distinguish between endogenous and exogenous insulin.
C peptide is a useful marker of insulin production.
High concentrations indicate high insulin (insulinoma, excessive insulin production e.g. reactive hypoglycaemia which indicates insulin resistance early), hypokalaemia, pregnancy, cushing’s, kidney disease.
Low conc of C peptide when insuffient insulin is produced by beta cells or production is suppressed by injected insulin.
18
Q
What two further tests could be considered in the hypoglycaemic patient?
A
- 48-72 observed fast –> indicated in adults if presence of hypoglycaemic symptoms but blood glucose > 2.8 mmol/L. Blood glucose levels checked every 6 hours, once below 3.3 mmol/L then checked every hour w serum proinsulin, c peptide and insulin. Test ends with sympathoadrenal or neuroglypenic symptoms/ 72 hours passes or blood glucose drops below 2.8 mmol/L
- Oral glucose tolerance test –> performed to rule of diabetes mellitus, late reactive hypoglycaemia occuring within 3/5 hours after meal can occur in patients with prediabetes or impaired glucose tolerance/ pregnancy.
19
Q
What is the treatment/ management of hypoglycaemia?
A
- If consious and orientated, give 15-20 g fast acting carbohydrate e.g. 200ml orange juice and repeat blood sugar monitoring every 15 minutes. Repeat snack up to 3 times.
- If conscious and non-cooperative, squirt glucose gel between teeth and gums
- If unconcious or above measures do not work:
- 10% or 50% dextrose IV
- Glucagon IV or IM (not appropriate in malnourshed patients)
- Once patient’s symptoms have recovered and glucose =. 4 mmol/L give long acting carbohydrate orally e.g. toast/ sandwich
- If overdose, consider psychiatric referral
- If insulinoma, or IGF2 secreting tumour, surgically excise and give glucaogn injections/ IV glucose.
- for renal failure/liver failure/ sepsis or other endocrinopathy treatment should focuse on management of underlying organ dysfunction. Support with glucose infusion may be necessary until condition resolves.
20
Q
Define type 1 diabetes mellitus and its underlying pathophysiology
A
- Metabolic disorder defined by hyperglycaemia due to an absolute insulin deficiency which, if untreated leads to microvascular and macrovascular pathology.
- 5-10% of all diabetes worldwide, more common in europeans, less common in asians.
- Typically presents in younger lean patients caused by autoimmune destruction of beta cells in islets of langerhans, loss of insulin secretion leading to hyperglycaemia.
- Can only be treated with insulin injections
- often associated with otehr autoimmune diseases
21
Q
What are the key features of Type 1 diabetes in the history?
A
-
PC/HPC/:
- Typically presents in younger, lean patients (average age 14 yrs). Often presents as acute development of illness over 6 weeks.
Hyperglycaemic symptoms:
- Polyuria –> due to elevated blood glucsoe, overwhelming glucose transported in nephron, leads to glycosuria, draws water increasing urine volume
- polydipsia –> physiological response to polyuria, along with direct stimulation of thirst receptors by hyperglycaemic increase in plasma osmolarity
- weight loss –> loss of insulin release, inability to store glycogen in the liver, loss of suppression of glucagon release –> gluconeogenesis and production of alternative fuels for energy (proteolysis and lipolysis, ketogenesis)
- Fatigue –> loss of glucose stores
- blurred vision
- recurrent infections
- abdominal pain/ nausea/ vomiting
22
Q
What are the key symptoms of diabetic ketoacidosis?
What is the underlying pathophysiology?
Key to look out for in history?
A
- Nausea and vomiting (decreased appetite and anorexia)
- abdominal pain –> severe
- tachypnoea –> increased RR to blow off excess acid
- lethargy/ general weakness
- altered conciousness or coma (coma uncommon but can occur in severe cases)
- shock symptoms from severe dehydration
Pathophysiology:
- Acute life threatening complication of diabetes characterised by hyperglycaemia, keotacidosis and ketonuria
- Raised levels of ketoacids produced for alternative energy source –> Acetoacetate, acetate, betahydroxybutyrate
- Insulin deficiency inhibits ability of glucose to enter cells for utilization as metabolic fuel
- results in liver rapidly breaking down fat into ketone to employ as alt fuel source
- overproduction of ketones leads to accumulation in blood and urine, and causes acidosis.
Key in HX:
- failure to comply with insulin therapy or missed insulin injections (could be due to vomiting/ physiological reasons, mechanical failure of insulin infusion pump)>
23
Q
What are risk factors for type 1 diabetes?
key aspects of PMH?
A
- family hx
- geographical region –> varies between countries, certain HLA risk profile may reflect increased environmental influence on suscpetible genotypes.
- genetic predisposition –> concordance between monozygotic twins 27%, HLA on chromosome 6 thought to contribute to half of familial basis, insulin gene on chromosome 11 involved too.
- human enterovirus infection
PMH: diabetes, pancreas disease, congenital rubella/ enteroviruses.
24
Q
Describe glucose homeostasis:
Hyperglycaemic/ post prandial state –> how is insulin released?
What happens intracellularly?
what pattern of release is there?
A
- Rise in blood glucose levels
- glucose transport into beta cell in iL via GLUT2
- rise in glucose concentration within the cell –> increase in ATP:ADP ratio
- closure of ATP dependent K+ channel
- depolarisation from resting membrane potential –> opening VG ca2+ cahnnels –> Ca2+ influx promotes exocytosis of vesicles containing insulin
- Biphasic pattern of release –> 1st phase = rapid, 10 mins, release of docked and primed vesicles
- 2nd phase –> plateau phase lasting as long as hyperglycaemia persists -> release is slower due to time it takes to dock/prime
- not all stored insulin is released during hyperglycaemic periods –> blood glucose mainly controlled via release rather than synthesis
25
Glucose homeostasis: what are the actions of insulin?
* **Insulin acts on insulin receptors on adipocytes/muscle cells** to activate insulin receptor substrate 1 --\> activates PI3K (phosphatidyly kinase) --\> PIP2 converted to PIP3 --\> activates AKT **--\> leads to transportation of GLUT4 vesicles to PM and activates glycogen synthase**
* **increase in glycogen synthesis**
* **increase in lipogenesis**
* **increase protein synthesis**
* **inhibit ketogenesis**
* **ultimately leads to lowering of blood glucose levels.**
26
What is the counterregulatory hormone to insulin?
What are its actions?
* Glucagon: synthesised and released from alpha cells in islets of langerhans
* main stimulation for release is HYPOglycaemia, also stimulated by loss of suppression of insulin (when glucose low, no insulin release, no inhibition of glucagon release)
* ACTIONS:
* promotes gluconeogenesis
* glyogenolysis in muscle and liver
* inhibits lipogenesis and glucose uptake in adipose tissue
* promotes lipolysis and release of free fatty acids
* promotes ketogenesis and proteolysis (production of alternative energy substrates)
27
Compare post absorpative state (fasted) vs post prandial state (fed)
**Post absorptive state: catabolic**
* 14-16 hours glucose levels remain stable by balance of utilisation and release
* primarily by the LIVER which releases glucose by glycogenoysis and gluconeogenesis (50:50)
* 48 hours --\> liver used most of glycogen store, switches primarily to gluconeogenesis (90%)
* kidneys also able to release glucose by gluconeogenesis similar output to the liver
* blood glucose falls, insulin release falls, loss of suppresion of glucagon release, glucagon is released
* Glucagon action --\> glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, proteolysis.
**Post prandial (fed) : Anabolic:**
* Blood glucose rise --\> release insulin --\> promote glycogen synthesis, inhibit gluconeogenesis, promote lipogenesis and protein synthesis
28
What additional hormones are involved in glucose homeostasis?
* **_Mimic insulin actions:_**
* **Incretins** (**GLP1 (Glucagon like peptide)** and **GIP (gastric inhibitory peptide)).**
* stimulated for release by ***L cells of small intestine by ORAL glucose load*** (same response does not occur by IV glucose load)
* **Actions :** increase insulin release, inhibit glucagon/somatostatin release, delay gastric emptying, maintain beta cell mass.
* **_Mimic glucagon:_**
* ***catecholamines (adrenaline, NA***) and ***cortisol*** = increase blood glucose when sympathetic NS is active (fight or flight)
* ***Cortisol directly** **inhibits insulin release*** (be aware steroids can cause hyperglycaemia)
* **cortisol and *growth hormone--\>*** promote gluconeogenesis and inhibit glucose transport.
29
What is the pathophysiology of type 1 diabetes?
* autoimmunue destruction occurs subclinically for months/ years until 80-90% of beta cells are lost
* at this point hyperglycaemia develops due to absolute deficiency of insulin
* leads to decreased upatke and utilisation of glucose in muscel and adipose tissues leading to glucagon release --\> increased proteolysis, lipolysis, glycogenolysis and gluconeogenesis
* patients often present with diabetic ketoacidosis: acidosis, ketosis and hyperglycaemia
30
Diagnosis of T1DM
* Diagnosis made on basis of any of the following:
* symptomatic patient --\> random plasma glucose \> 11mmol
* fasting plasma glucose \>6.9 mmol/L
* plasma glucose \>or equal to 11 mmol 2 hours after 75mg oral glucose
* HbA1c --\> \> or equal to 48 mmol/mol (remember avoid in pregnant, children, T1DM and Hb-opathies)
* Diagnosis often obvious from clinical presentation but can be confirmed with additional tests:
* low C peptide levels
* prescence of one or more autoimmune markers --\> autoantibodies to glutamic acid decarboxylase GAD, insulin, islet cells, islet antigens (IA2/IA2-beta), zinc transported ZnT8.
* Consider monogenic diabetes (Genetic cause mutation in one gene) --\> suspicion higher if antibody negative, ketone negative paediatric diabetes w family hx of diabetes in multiple generations.
* MODY = maturity onset diabetes of the young, neonatal diabetes
31
Management of T1DM
* basal bolus regime:
* one half given as basal (long acting) and one half as bolus (short or rapid acting)
* bolus dossing divided and given before meals
* patient self monitors blood glucose
* insulin dose adjusted according to target
* simple method = 1 unit insulin per 15 g carbohydrate in meal
32
What complications may arise from diabetes?
* long term hyperglycaemia leads to ***_vascular disease:_***
* **Microvascular** --\> nephropathy, retinpathy, neuropathy
* **Macrovascular** --\> IHD, cerebrovascular disease, peripheral vascular disease
33
Explain the underlying pathophysiology of diabetic complications:
Toxicity of glucose?
* **Hyperglycaemia** leads to **increased glucose intracellularly,** especially in cells with ***insulin- independent glucose uptake mechanisms***
* *cells which take up glucose independently of insulin = **endothelial, renal, retinal, peripheral neurones.***
* High glucose leads to increase in ROS, and activation of 4 main pathways: hexosamine, PKC/DAG, Polyol, and AGE p/w
* increase in DAG/hexosamine p/w leads to increase in vascular permeability and thrombogenesis
* polyol p/w leads to endothelial damage and AGE p/w leads to vascular inflammation & endothelial damage.
* this leads to vascular damage, and atheroma formation --\> micro and macrovascular damage
34
LO: explain underlying pathophysiology of diabetic complications:
Nephropathy
* Nephropathy/chronic kidney disease:
* Chronic kidney damaged due to ***chronic hyperglycaemia***
* defined by ***micro or macroalbuminuria***
* Process:
* **Hyperfiltration** --\> glycation of efferent arteriole basement membrane leads to narrowing (hyaline arteriosclerosis); hyperglycaemia also activates RAAS leading to further efferent arteriole constriction, both leading to increased glomerular pressure and GFR
* **Mesangial expansion** --\> increased glomerular pressure leads to increased deposition of collagen and matrix proteins by mesangial cells causing expansion of the size of the glomerulus. Leads to decreased surface area for filtration (uniform matrix deposition and discrete foci of matrix proteins called Kimmelstiel Wilson nodules).
* **Basement membrane thickening** --\> counterintuitivel allows leakage of proteins, process aided by mesangial expansion which stretches podocyte foot processes leading to larger gaps in the filtration barrier
* All process lead to ***increased excretion of protein in the urine, decreased GFR, HTN and ultimately renal failure.***
35
How do you diagnose diabetic nephropathy?
* urinanalysis: proteinuria
* macroalbuminuria (ACR \> 34 mg/mmol) OR microalbuminuria (ACR 3.4-34mg/mol) AND retinopathy OR \>10 yrs duration of T1DM
* creatinine elevated
* GFR : raised initialyl due to hyperfiltration, then normalises and eventually decreases
* may present with nephrotic syndrome (proteinuria, hypoalbuminaemia, oedema)
36
LO: explain pathophysiology of diabetic complications
Retinopathy
* retinal damage due to chronic microvascular leakage and occlusion.
* can be non proliferative or proliferative
* ultimately leads to visual disturbance or loss
* Process:
* increased glucose uptake in retinal endothelial cells leading to increased ROS formation and activation of glucose pathways --\> increased vascular permeability, inflammation, thrombogenesis and vascular damage
* increased vascular permeability --\> leads to aneurysms, haemorrhage, oedema and cholesterol deposition
* Thrombogenesis --\> leads to vessel occlusion and ischaemia/ infarction
* ischaemia --\> can lead to angiogenesis (becomes proliferative retinopathy), fibrosis and retinal detachment
* Signs on examination:
* Cotton wool spots (nerve damage, accumualation of nerve cytoplasm- ischaemia )
* microaneurysms - discrete red spots
* macular thickening
* new vessel formation
* haemorrhages (red with less definable edges)
*
37
LO: explain pathophysiology of diabetic complications:
Neuropathy
Signs of this complication?
Neuropathy = peripheral nerve dysfunction with or without autonomic dysfunction
Process:
* Hyperglycaemia causes increase in ROS and AGE's in peripheral nerve fibres
* Ultimately leads to damage and loss of schwann cells and peripheral neurones, particularly those which transmit PAIN and Temp input.
Presentation:
* Loss of sensation described as "glove and stocking" distribution.
* sensation loss is often patchy therefore examine multiple sites
* Presence if neuropathic deformity --\> Charcot joint, pes cavus (high arch deformity), claw toes (fixed flexion), loss of transverse arch (flat arch at metatarsals).
* Ulceration --\> usually painless
38
Explain pathophysiology of diabetic complications:
Macrovascular disease
* Due to atherosclerosis and other risk factors e.g. hypertension, dyslipidaemia
* Hyperglycaemia contributes to atheroma formation due to increased endothelial inflammtion, permeability, damage and thrombogenesis
* **Cardiovascular** --\> occlusion = angina pectoris, rupture =MI
* **Cerebrovascular** --\> occlusion = TIA, rupture = Stroke
* **Peripheral vascular** --\> occlusion = claudication; rupture = gangrene/infarction
39
What examinations should be done to monitor diabetic complications?
1. Ankle-brachial pressure index: ratio of ankle to brachial BP: low in leg suggests PAD (ratio less than 0.9 indicates mild claudication).
2. Albumin to creatinine ratio: macroalbuminuria (ACR\> 34 mg/mmol) OR micoalbuminuria (ACR 3.4-34 mg/mol) AND retinopathy OR \>10 yrs duration diabetes
3. ECG: may indicate ischaemia
4. Dilated retinal examination --\> retinopathy
5. foot examination : sensation, ulceration, neuropathic deformities
40
Define Type II DM:
* Progressive metabolic disorder defined by **defects** in ***insulin secretion and action*** which lead to abnormal glucose metabolism.
* 90% of all DM cases. 80-90% associated w overweight/obesity \>90% with lipid disorders, 70% HTN
* 80% concordance between identical twins
41
What are key factors in the history of T2DM?
pc/hpc/SR --\> polyuria, polydipsia (less common than in T1DM), blurred vision, genital thrush, skin infections/abscesses, UTI's, asymptoatic (screening), fatigue, paraesthesia
RF's: signs of DKA
Risk: family hx, overweight, black/hispanic/native america, hx of gestational DM, PCOS, physical inactivity, HTN, dyslipidaemia, CVD, male, \>40 yrs
PMH: prediabetes, HTN, obesity, dyslipidaemia, CVD, PCOS
Fx: type 2 diabetes
sx: poverty and diet
42
Key signs of T2DM on examination?
dyslipidaemia --\> corneal arcus, xanthalasmata
obesity
sings/ sx of PCOS, CVD, HTN
43
Aetiology of T2DM?
* background of genetic predispostion; characterised by insulin resistance and relative insulin deficiency
* insulin resistance is aggravated by aging, physical inactivity, overweight (BMI 25-29.9) or obesity (BMI\> 30 kg/m2)
* insulin resistnace primarily affects liver, muscle and adipocytes, and is characterised by complex derangements in cellular receptors/intracellular glucose kinase function and other IC metabolic processes.
44
What is the pathophsiology of insulin resistance?
* high levels of fatty acids in blood leads to interference with insulin signalling pathway
* fatty acids in blood enter adipocytes/muscle cells and convert to ceramide which inhibits AKT2 (serine/threonine kinase). Also activates PKC which inhibits IRS1 (insulin receptor substrate 1), prevents GSK activation and GLUT4 translocation
* Hyperglycaemia persists
45
Diagnosis of T2DM?
* Random plasma glucose \> 11 mmol/L AND sx present
* Fasting plasma glucose \>equal to 7 mmol/L
* plasma glucose \>equal to 11 mmol/L 2 hrs post 75 g glucose oral intake
* HbA1c \>equal to 48 mmol/mol (6.5%) suggests DM (avoid in pregnancy/children, T1DM and Hb opathies)
* fasting lipid profile --\> may have high LDL, low HDL, high triglycerides
* urine/plasma ketones --\> exclude T1DM
46
describe values for diabetes continuum
1. normal FG or OGTT in normal range, non diabetic
2. impaired fastng glycaemia (pre diabetes) 6.1-6.9 mmol/L
3. impaired oral glucose tolerance test (pre diabetes) 7.8 to 11 mmol
4. diabetes --\> fasting glucose \> 7 mmol, OGTT \>11 mmol/L
47
Management of T2DM?
1. Lifestyle --\> decreased saturated fats, sugar, inactivity, increased exercise, complex carbohydrates, moderate protein intake, avoid alcohol, lose weight. 80% T2DM is preventable by aggressive obesity prevention in all age groups
2. Metformin --\> 1st line for glycaemic control, decreases hepatic gluconeogenesis and glycogenolysis, increases sensitivity to insulin, increases glucose uptake and glycogenolysis in muscle, decreases beta oxidation in muscles
3. if HbA1C rises to 58 mmol/mol try dual therapy: ADD ONE OF:
1. DPP4 inhibitor --\> DPP4 degrades GLP1; GLP1 augments insulin secretion
2. Pioglitazone: thiazolidinedione class, increases insulin sensitivity of cells
3. sulphonylurea: gliclazide class; blocks ATP sensitive K+ channels in beta cells causing continuous depol and insulin secretion
4. SGLT2 inhibitor: blocks glucose reabsorption in kidneys
5. If HbA1C remains higher than 58mmol/mol try triple therapy, insulin therapy, GLP analogues
48
Medical prevention of diabetic risk factors?
1. Beta blockers, Ca channel blockers, ACE inhibitors to protect from atherosclerosis, vascular disease, renal disease
2. antiplatelet therapy (clopidorgrel and aspirin) to prevent thromboses
3. statins for lipid control
