pathogenesis of Type 1 diabetes
b-cell failure = absolute insulin deficiency
pathogenesis of Type 2 diabetes
Hyperinsulinaemia + insulin resistance
Beta Cell dysfunction
T1DM presentation
pre-school/pre-puberty severe weight loss ketonuria ± metabolic acidosis Tired polydipsia + polyuria i.e. very thirsty + peeing a lot
T2DM presentation
middle-aged/elderly
usually obese
insidious onset over weeks to years
risk factors for T2DM
central obesity
FH
Age
Phx of MI/stroke
symptoms of DM
Thirst Polyuria Thrush Weakness Fatigue Blurred Vision Infections Weight Loss T2DM- Signs of complications- neuropathy, retinopathy
useful discriminatory tests for type 1 and type 2
GAD/ Anti-Islet Cell antibodies
Ketones
C-peptide (plasma)
what is LADA
late-onset type 1 diabetes
what causes Type 3 diabetes
Pancreatic disease
Endocrine disease
Drug-induced
Abnormalities of insulin and its receptor i.e. Genetic diseases
what pancreatic diseases can cause diabetes
Chronic or recurrent pancreatitis
Haemochromatosis
Cystic Fibrosis
what endocrine diseases can cause diabetes
Cushing’s syndrome
Acromegaly
Phaechromocytoma
glucagonoma
what drugs can cause diabetes
Glucocorticoids
Diuretics
B-blockers
what genetic diseases are related to diabetes
Cystic fibrosis
Myotonic dystrophy
Turner’s syndrome
what is Type 4 diabetes
Gestational diabetes:
i.e. Any degree of glucose intolerance arising or diagnosed during pregnancy
what is HbA1c and why do we measure it
glycated hemoglobin
provides a measure of glucose control over past 2-3 months
what are complications of diabetes
Micro-vascular: Retinopathy, Nephropathy, Neuropathy
Macro-vascular: Heart disease and stroke
what Ix findings are suggestive of diabetes
Diagnose diabetes
Fasting glucose ≥ 7.0mmol/l
Random ≥ 11.1mmol/l
and symptoms, OR repeat test
how can the type of diabetes be differentiated
Often Type 1 diabetes is diagnosed on the history and presentation (e.g. DKA) alone
GAD/IA2 antibodies [and C-peptide] may help
what antibodies are related to Type 1 DM
GAD
IA2 antibodies
IAA
ZnT8Ab
what can be seen on a histology slide of type 1 diabetes
lymphocytes attacking the islet
what gene is associated with T1DM
HLA genes
why can C-peptide be a diagnostic test
C-peptide is produced when insulin is made
if there is a low volume of C-peptide suggests that insulin is not being made
what is the classic triad of DM
Polyuria
- Enuresis in children
Polydipsia
Weight loss
what is enuresis
involuntary urination, especially by children at night.
Mx of newly diagnosed Type 1 DM
Blood glucose and ketone monitoring
Insulin: usually basal [once daily] bolus [with meals] regimen
Carbohydrate estimation
Regular check of prevailing glycaemic control
what is the ideal range of glucose control in T1DM
HbA1c 48 to 58 mmol/mol
insulin therapy in Type 1; for adults
either regular human or rapid-acting insulin analogues
insulin therapy in Type 1; for children/teens
either insulin analogues (rapid-acting or basal), regular human insulin and NPH preparations or an appropriate combination
where is insulin secreted to
portal vein
neonatal diabetes - Children diagnosed under the age of six months are more likely to have what
Monogenic
rather than T1DM
when should LADA be suspected
age 25-40 male more often non-obese auto-antibody positive associated auto-immune conditions
CF and diabetes relationship
found in ‘severe’ mutations, i.e. ∆508
prone to complications
insulin therapy preferred
what is Wolfram syndrome also known as and why
DIDMOAD
Diabetes Insipidus Diabetes Mellitus Optic Atrophy Deafness Neurological anomalies
presentation of Bardet-Biedl Syndrome
Often very obese Polydactyly Hypogonadal Visual impairment Hearing impairment Mental retardation Diabetes
what are the associated auto-immune conditions of diabetes
Thyroid disease Coeliac disease Pernicious Anaemia Addison’s disease IgA deficiency Auto-immune polyglandular syndromes [Type 1 and Type 2]
what is Pernicious Anaemia
a deficiency in the production of red blood cells through a lack of vitamin B12
which type of Polyglandular Endocrinopathy is associated w/ T1DM
Type 2
what else is type 2 Polyglandular Endocrinopathy associated with
T1DM Addison’s disease Vitiligo Primary hypogonadism Primary hypothyroidism Coeliac disease
what is type 1 Polyglandular Endocrinopathy associated with
Primary hypoparathyroidism/Pernicious anaemia/alopecia
what is insulin resistance
receptor is not as responsive to the insulin molecule and therefore less glucose enters the cell. This results in a build up of glucose in the blood
what causes Insulin Resistance
Ectopic Fat Accumulation and increase FFA circulation
+ increase inflammatory mediators
> > > Inhibition of insulin via serine kinases responsible for phosphorylation of Insulin Receptor Substrate-1 (IRS-1)
> > > Reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport
what is insulin resistance a pre-cursor for
Type 2 diabetes
how does the beta cells initially compensate for increasing insulin resistance
body tries to compensate by producing more insulin as insulin resistance increases
when do blood glucose levels increase
when the beta cells burn out
what cause declining beta cell function
Glucotoxicity - hyperglycaemia
Lipotoxicity - elevated FFA, TG
what is the Metabolic Syndrome
at least three of five of the following:
- abdominal (central) obesity,
- elevated blood pressure,
- insulin resistance
- high serum triglycerides
- low HDL levels.
what is the therapy staircase for Type 2 diabetes
1 - diet and exercise
2 - oral mono therapy
3 - oral combination
4 - injectable and oral therapy
what are the risks with alcohol consumption in diabetes
Hypoglycaemia, esp. if no food (alcohol activity of insulin) - more prone if using insulin or sulphonylureas
‘Confusing’ hypo symptoms
what is MODY
Maturity onset diabetes of the young
Autosomal dominant inheritance
Non-insulin dependent diabetes
Age of onset usually before age 25
what are the 2 phenotypes of MODY
transcription factor (HNF-1alpha) glucokinase (GCK)
what are HNF1A sensitive to
SU
what is the treatment of GCK MODY
does not require treatment
what can cause neonatal diabetes
potassium channel mutation
what are the two types of neonatal diabetes
Transient neonatal diabetes (TNDM)
Permanent neonatal diabetes (PNDM)
what is PNDM treated with
SU’s
what are symptoms of hypoglycaemia
shaking sweating anxious, irritable dizziness tachycardia blurred vision weakness fatigue headache hunger
what can hypoglycaemia cause
seizures, unconsciousness
Tx of mild hypoglycaemia
Consume 15-20 grams of glucose or simple carbohydrates
Recheck your blood glucose after 15 minutes
examples of 15grams of simple carbohydrates
glucose tablets
gel tube
coke/lucazade
Tx of severe hypoglycaemia
Glucagon 1 mg
- Inject into buttock / arm or thigh
- May cause nausea + vomiting
what is impaired hypoglycemia awareness
When hypoglycaemia occurs (4.0-3.5 mmol/l) and individuals feel no or a change symptoms.
what are common precipitant of DKA
infection - Gastroenteritis
illicit drugs and alcohol
non-adherence w/ treatment
newly diagnosed diabetes
symptoms/signs of DKA
Thirst/Polyuria/Dehydration Flushed Vomiting Abdo pain and tenderness Breathless - Kussmaul's respiration
classic biochemistry of DKA at presentation
Glucose: Median level around 40 mmol/L [Normal 5
Complications of DKA
Cerebral oedema
ARDS
Hypokalemia»_space; Cardiac dysrhythmia
Mx of DKA
IV fluids
- Potassium replace
- IV insulin
Supportive care
what do urine ketone testing machines measure
acetoacetate levels
when should a T1DM be admitted into hospital
Unable to tolerate oral fluids Persistent vomiting Persistent hyperglycaemia Persistent positive/increasing levels of ketones Abdominal pain / breathlessness
what is Hyperglycaemic Hypersomolar Syndrome (HHS)
complication of T2DM - severe hyperglycaemia, hyperosmolality, and volume depletion, in the absence of severe ketoacidosis.
features of HHS
Diabetes may be known, often not
If known, then often treatment is ‘diet alone’
Usually older individuals
Associated risks - MI, stroke, sepsis, Glucocorticoids and thiazides
symptoms/signs of HHS
altered mental state
thirsty/polyuria/weight loss
weakness
poor skin turgor
Tx of HHS
IV fluids
Supportive
Insulin
Treat underlying cause
what is lactic acidosis
when lactic acid builds up in the bloodstream faster than it can be removed
clinical features of lactic acidosis
Hyperventilation
Mental confusion
Stupor or coma if severe
lab findings of lactic acidosis
reduced bicarbonate
raised anion gap
raised phosphate
absent of ketonaemia
what is the target of type 2 diabetics glucose control
HbA1c 48mmol/mol
complications of diabetes
Macrovascular:
IHD
Stroke
Microvascular:
Neuropathy
Nephropathy
Retinopathy
Erectile Dysfunction
how does diabetes cause microvascular problems
reduced blood flow
precipitating factors of neuropathy
poor glycemic control
T1DM > T2DM
Smoking + Alcohol
increased length of diabetes
what are symptoms of Peripheral nerve damage (PND)
Numbness/ insensitivity Tingling/ burning Sharp pains or cramps Sensitivity to touch Loss of balance and coordination
complications of PND
infections/ulcers
deformities (hammertoes)
amputations
Tx of PND
Analgesia
Stronger opiods
symptoms of Autonomic neuropathy
Constipation/Diarrhoea
Gastroparesis - nausea, vomiting, bloating
Oesophagus nerve damage - swallowing difficulty
what is Charcot foot
Fractures and dislocations of bones and joints that occur with minimal or no known trauma. Occurs in patients with neuropathy.
what is diabetic nephropathy
damage of capillaries in glomeruli
consequences of diabetic nephropathy
Development of hypertension
Relentless decline in renal function - can lead to Kidney failure
Accelerated vascular disease
what can be a sign of impending trouble
microalbuminuria
risk factors of nephropathy profession
hypertension
high cholesterol
smoking
albuminuria
what can be very useful in Tx of diabetic nephropathy
ACE inhibitors
what pathology of the eyes do diabetics get
diabetic retinopathy
cataract
glaucoma
visual blurring due to acute hyperglycamia
what are the stages of retinopathy
Mild non-proliferative
Moderate non-proliferative
Severe non-proliferative
Proliferative
what is seen in pre-proliferative retinopathy
Micro aneurysms, hard exudates, haemorrages
what is seen in Severe Non-proliferative Retinopathy
(IRMA, venous beading, haemorrages)
what is seen in severe proliferative retinopathy
new vessel formation
complications of diabetic retinopathy
bleeding - sudden change in vision
floaters
secondary glaucoma
retinal detachment
Tx of diabetic retinopathy
Laser
Vitrectomy
Anti-VEGF injections
what are guidelines in place to reduce chance of CHD in diabetics
Lipid lowering therapy in diabetes over age 40 regardless of baseline cholesterol
BP
what are psychiatric complications
Depression
Eating Disorders
Bi-polar
Schizophrenia