Diabetes Flashcards
Diagnosis of Diabetes
HbA1c ≥ 6.5% //
FPG ≥ 7.0 mmol/L (no caloric intake for at least 8 hours) //
2-h PG ≥ 11.1 mmol/L during OGTT (75g glucose in water) //
random plasma glucose ≥ 11.1 mmol/L + symptoms of hyperglycaemia or hyperglycemic crisis
Type 1 Diabetes
Autoimmune T-cell mediated disease that causes Beta cell destruction, usually leading to absolute insulin deficiency
Type 2 Diabetes
Progressive insulin secretory defect on the background of insulin resistance
Gestational diabetes mellitus
Diabetes diagnosed in the 2nd or 3rd trimester that is clearly not overt diabetes
Other causes of diabetes
MODY
Neonatal diabetes
Disease of exocrine pancreas - CF
drug/chemical induced diabetes - treatment of HIV/organt transplantation
T1DM association
Thyroid, Coeliac (1:20), Addison/s, pernicious anaemia, vitiligo
Eisenbarth 1996
Genetic susceptibility
Environmental trigger
Prolonged prodrome (months-years)
80-90% loss of beta cell function before marked hyperglycaemia
What is LADA
Latent Autoimmune Diabetes of Adulthood 20% of T2DM slowly-progressive non-obese, no FHx T2DM, >35y, mild IR, low c-peptide, HLA positive insulin independence in 6y
Polyglandular endocrinopathy type 2
Type 1 diabetes may be associated with any/all of: Addison/s disease, Hypothyroidism, Hypogonadism, Vitiligo, Coeliac
Type 1 endocrinopathy
mild immune deficiancy (mucocutaneous candidiasis) + T1DM associated with Addisons/ Hypothyroidism/ Hypogonadism/ Vitiligo/ Coeliac/ + Alopecia/ Pernicious Anaemia/ Hypoparathyroidism
T1DM in Scotland
>228,000 1:25 Many undiagnosed 12% of diabetic population other diabetes types account for 0.6%
Islet antibodies
IA-2
IA-2β
GAD
Zn-T8
Autoantibodies typically present in 70-80% of newly diagnosed
5y risk of T1D if antibody positive
1 Ab: 20-25%
2 Ab: 50-60%
3 Ab: 70%
(IA2,GAD, Znt8)
What is GAD
Glutamate Decarboxylase Antibody
- converts glutamate to GABA
- 75-84% of recent onset T1DM
- F>M
- 10-15% of T2DM
Genetics of T1DM
HLA-DR3 and HLA-DR4 genes
Chromosome 6
what does c-peptide tell you
insulin in the blood
Insulin actions
stimulate glucose uptake in the skeletal muscle
inhibit gluconeogenesis
inhibit lipolysis
Glucagon actions
stimulate gluconeogenesis
stimulate lipolysis
Accelerated starvation in insulin deficiency
Decreased glucose uptake -hyperglycaemia -glycosuria Increased protein catabolism -increased plasma AAs -urinary nitrogen loss Increased lipolysis -increased plasma FFA -ketogenesis -ketonuria
Counter-regulatory failure in T1DM
glucagon not really increased in hypoglycaemia
Type 1 Diabetes Clinical Presentation
Polyuria
Polydipsia
Weight loss
General Malaise
Diabetic Ketoacidosis
Vomiting, Abdominal pain Altered consciousness, Acidotic breathing Kussmaul's breathing pH < 7.3 urine ketones +++ dehydrated severe or untreated leads to coma and death
T1DM presentation - textbook scenario
Acute onset DKA / severe symptoms peak: pre-school and peri-puberty non-obese insulin dependent FHx uncommon
T2DM presentation -textbook scenario
Slow onset - 6-10y before presentation middle-aged / elderly obese & sedentary non-insulin dependent FHx common
T1DM diagnosis
GAD, IA2, ZnT8 used in diagnosis - make sure you don’t misdiagnose
<30 years in 60%
short acting insulin
lispro - 15 minutes before meal
long acting insulin
glargine - single bedtime dose
% of insulin granules are in RRP
5
KATP channel consists of
SUR1 Kir6
sulphonylureas & mechanisms of action
inhibits KATP (SUR1) tolbutamide, glibenclamide
diazoxide
stimulates KATP
helps congenital hyperinsulinism
