case 6 - diabetes review Flashcards
what is the WHO diagnosis for diabetes in the fasting state
normal: fasting; less than 6.1mmol/L
Impaired fasting glycaemia: 6.1-6.9mmol/L
Diabetes: greater than 7mmol/L
what is the WHO diagnosis for diabetes 24 hours post prandial
impaired glucose tolerance: greater than 7.8-11mmol/L
Diabetes: greater than 11 mmol/L
what is the value of HbA1c that confirms type 2
HbA1c greater than 48mmol/mol
describe the physiology of the beta cells
islet: beta cells
pancreatic beta cells express GLUT2 glucose transporters, which permit rapid glucose uptake regardless of the extracellular sugar concentration
what happens in type 1 diabetes
beta cells get destroyed which leads to no or very little insulin produced
what are the effects of insulin on the liver
increased glucose uptake and glycogen synthesis
what are the effects of insulin on the muscle
increased glucose uptake and glycogen synthesis
what are the effects of insulin on adipose tissue
increased glucose uptake and storage as fat
decreased breakdown to fatty acids
what are the effects of insulin on blood
glucose levels fall
what are the effects of lack of insulin on the liver
decreased glucose uptake
Increased glycogen breakdown and gluconeogenesis
Conversion of fatty acids to ketone bodies
what are the effects of lack of insulin on the muscle
decreased glucose uptake via GLUT4
what are the effects of lack of insulin on adipose
decreased glucose uptake and storage
increased breakdown of fat and release of fatty acids
what are the effects of lack of insulin in the blood
glucose levels rise
what are the pathophysiology steps of diabetes;
low utilisation of glucose and increased endogenous production of glucose by the liver
hyperglycaemia
loss of glucose in the urine
increased urination - polyuria, nocturia
dehydration - increased thirst-polydipsia
what happens when there is loss of glucose in the urine
osmotic drag of glucose on water
water and glucose lost in urine
electrolytes lost along with water
what are the specific tests used to diagnose type 1 diabetes - there are 5
GAD65 antibodies - around 80% at diagnosis
Islet cell antibodies - around 69-90% at diagnosis
ZnT8 antibodies
Insulin antibodies (IAA)
C-peptide/insulin/glucose levels
what are markers of beta cell autoimmunity in type 1 diabetes
autoantibodies
islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell), antibodies to glutamic acid decarboxylase (GAD-65), insulin autoantibodies (IAA), and IA-2A, to protein tyrosine phosphatase
Autoantibodies against GAD 65 are found in 80% of patients with type 1 diabetes at clinical presentation
Presence of ICA and IA-2A at diagnosis for type 1 diabetes range from 69-90% and 54-75%, respectively
what does IAA prevalence correlate with
correlates inversely with age at onset of diabetes; it is usually the first marker in young children at risk for diabetes and found in approximately 70% of young children at the time of diagnosis
what are the features of type 2 diabetes
due to insulin resistance
less acute onset compared to type one
progressive decline in beta cell function
describe in more detail, the progressive decline in beta cell functionn
may have up to 50% beta cell loss at the time of diagnosis
4-6% decline per year thereafter
what does the progressive decline in beta cell function in type 2 diabetes lead to
a gradual loss of effectiveness for anti hyperglycaemic therapies that lower blood glucose levels via the action of endogenous insulin
what are the modifiable risk factors for type 2 diabetes
overweight and obesity
Sedentary lifestyle
Previously identified glucose intolerance
Metabolic syndrome
Hypertension
Decrease HDL cholesterol
Increased triglycerides
dietary factors
Intrauterine environment
Inflammation
what are the non modifiable risk factors for type 2 diabetes
ethnicity
Family history of type 2 diabetes
Age
History of gestational diabetes
Polycystic ovary syndrome
what is first line treatment for diabetes type 2
metformin
what is 2nd line for diabetes type 2
NICE - SU
what is 3rd line for type 2 diabetes
in obese overweight, if HbA1c is 64 (8%) e.g SGLT2i/DPP4 inhibtors/ GLP-1 receptor agonists
what happens in HbA1c is ober 80
need to add insulin
what is the dosage of metformin
start at 500mg, increase to max 2.5 - 3g/day
what is the BMI used for metformin
BMI greater than or equal to 18kg/m2
when do you avoid metformin
–eGFR <30; caution with eGFR 45
–Severe hepatic impairment
–Stop with intercurrent illness
what do you use if there is GI intolerance
metformin MR
what kind of onset is metformin
slow onset - for rapid control consider SU therapy
what are the advantages of metformin
safe and effective
Over 50 years of use
Weight neutral
Reduce CV morality
Can be used in pregnancy
what does metformin do to glucose
it decreases hepatic glucose production, decreases intestinal glucose absorption and improves insulin sensitivity in peripheral tissues
does metformin cause hypoglycaemia
not when used alone except in starvation, excessive exercise without food or use with alcohol intoxication
what are examples of GLP-1 receptor agonists
Exenatide, Exenatide Weekly, Lixisenatide, Liraglutide, Albiglutide & Dulaglutide
when are GLP-1 therapies used
as 3rd line
what does GLP-1 receptor agonists lead to
weight loss, reduction in SBP
what is a hypo episode
3.9mmol/L and below
what are the symptoms and signs of a hypo episode
Sympathetic:
*(Warning signs) Sweating, tremulousness, palpitations, blurring, hunger, pins & needles
–Neuroglycopenic
*Confusion, incoordination, drowsiness, seizures, coma,
what is the treatment of a hypo episode
glucose - rule of 15
what is DKA
diabetic ketoacidosis
when does DKA happen
in type 1 DM, new diagnosis, long standing type 2 rarely
what is hyperglycaemia
greater than 11mmol/L
what are the ketone measurements in DKA
*Ketones >=3 mmol/L , Urine >2+ ketones
what are the treatments for DKA
*IV Fluids
*Potassium replacement
*Insulin replacement
*Replacement of electolytes
LMWH, Antibiotics
what is the difference between HHS and HONK
HHS is a potentially life-threatening emergency
It does not usually lead to the presence of ketones in the urine, as occurs in diabetic ketoacidosis (DKA), which is why it was previously referred to as HONK (hyperglycaemic hyperosmolar non-ketotic coma).
what are the features of HHS and what are the treatments
*Poorly controlled Type 2
*Osmolality >320
*Treatment:
–IV Fluids, IV Fluids, IV Fluids
–Replace electrolytes
–IV insulin may be needed
–LMWH
