Diabetes Flashcards
PRAMLINTIDE - mechanism of action in diabetes
This is amylin which has been changed by two peptides to resemble rat amylin that cannot form fibrils. When injected with amylin, helps to normalise fluctuating glucose levels to a greater degree than insulin alone. Helps with weight loss. Normal beta cells produce amylin (IAPP= islet amyloid polypeptide) along with insulin- may help to smooth control
somatostatin released from…
delta cells
Somatostatin effect
reduces insulin and glucagon secretion
stimulated by meal ingestion and gastric acid secretion
GLP-1 released from…
L cells in jej and ileum
stimulates insulin release and inhibit glucagon release
What is alpha cell anarchy
Where blunting of hyperglycaemia/postprandial suppression of glugagon
How does DPP4 inhib work?
Inhibits DPP4 which usually breaks down GLP1–>higher GLP 1 levels
Side effects/limitations of SGLT2 inhibitors
Inhibits glucose reuptake in high capacity SSGLT2 transporters in tubule- beyond capacity of later SGLT1 reabsorption in distal tubule.
NO increase risk UTI
polyuria
genital infection
cannot use in renal impairment as not enough filtration of glucose and not working properly anyway
Impaired Glucose tolerance define
asting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
Define diabetes
If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus, but less than 6.5 does not exclude
What is Impaired fasting glucose
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)
Where is glucose resorbed in the kidney?
SGLT1
- 10% load
- S2/S3 segment of proximal tubule
SGLT2
- 90% load
- S1 segment of proximal tubule
Secondary causes of hyperlipidaemia- cholesterol predominant and TAG predominant?
Cholesterol- hypothyroidism, cholestasis, nephrotic syndrome
TAG- diabetes, obesity, alcohol, chronic renal failure, liver disease, unopposed oestrogen, thiazides, nonselective beta blockers
Incretins actions
(GLP-1 and GIP)-
increase insulin reduce glucagon slow gastric emptying improve insulin sensitivity reduce food intake increase beta cell mass and maintain beta cell function
What is exenatide?
GLP-1 receptor agonist
BD sub cut injection
Results in modest weight loss
GI side effects, acute pancreatitis
What is sitagliptin and linagliptin?
DPP-4 inhibitors Reduce break down of GLP1 oral agents main side effect nasal stuffiness, allergy, headache Hypos with sulfonylureas weight neutral
Linagliptin NO dose reduction in CKD
Sigagliptin dose reduce.
What is Dapagliflozen? Empagliflozen?
SGLT2 inhibitor- blocks resorption of filtered glucose -90%- in proximal convoluted tubule
weight loss
cannot give if GFR under 60- not filtering, won’t work
cannot give with diuretics as precipitate hypotension
side effect genital infection, no actual proof of UTI, orthostatic hypotension, hypos with S/U or insulin
An add on therapy for metformin.
Recent empagliflozen study showed reduced weight, HbA1c, CV death, heart failure hospitalisation, all cause mortality. Slight cholesterol increase.
What did UKPDS show?
Reduced HbA1c by 1% gives improved microvascular complication risk , diabetes related death, and trend towards reduce MI
Also observationally in the long term follow up, there was a legacy of good glycaemic control
List the four antibodies against islet cells
IA-2
GAD
Pro(insulin)
ZnT8
ZnT8 and anti insulin are the only beta cell specific
ZnT8 positive in up to 5% patients who are negative in the others.
What is LADA?
Latent autoimmune diabetes of adulthood
Adults who present with diabetes and have a period of insulin independence but go on to need insulin quite fast.
Anti GAD positive.
Suspect if Age under 50 BMI under 25 History or FH autoimmunity Acute symptoms
Anti GAD positivity predicts needing to use insulin within 6 years.
How does clomiphene work in PCOS?
Sits on hypothalamic oestrogen receptor in hypothalamus
HbA1C lower than expected
Sickle cell
G6PD def
Blood transfusion
Spherocytosis
HbA1c of 7–>average BSL of 9.5
How does orlistat work?
Pancreatic lipase inhibitor that reduces absorption of lipids from intestine
Gestational diabetes effects
Fetal macrosomia Still birth Pre-eclampsia Difficult delivery and C section Fetal hypocalcaemia, hypoglycaemia, jaundice Resp compromise Prematurity increased risk of childhood obesity
Effects of gestational diabetes on mother
type 2 diabetes
