Type 1 Diabetes Flashcards
How would diabetes be diagnosed?
Symptoms: Thirsty, passing lots of urine, blurred vision, fatigue, thrush.
Fasting blood glucose: >7
OGTT: >11
HbA1c: >48 (not used in glasgow yet).
2 abnormal tests or 1 test + symptoms.
List the types of diabetes?
Type 1 (insulin deficient)
Type 2 (insulin resistant)
MODY (maturity onset diabetes of the young - autosomal dominant).
Gestational
Secondary (pancreatits, cystic fibrosis, haemachromatosis, steroid induced, acromegaly).
What auto-antibodies are usually found in Type 1 DM?
ICA (islet cell antibody) I-A2 (Insulinoma-associated antigen-2). IAA (insulin auto-antibody) GAD65 (Glutamic acid decarboxylase 65) ZnT8 (zinc transporter).
What ways are there to predict type 1 diabetes?
HLA Auto-antibodies First-phase insulin response to glucose Tcell function Elevated lysophosphatidylchloine Reduced B-cell mass by PET scan.
What other autoimmune diseases is Type 1 DM usually associated with?
Thyroid disease (hypo/hyper) Coeliac Addisons disease Pernicious anaemia Inflammatory bowel disease Premature ovarian failure.
How do pancreatic B cells release insulin?
GLUT2 receptors sense blood glucose levels.
Glucose is taken up and converted to G6P (glucokinase) then pyruvate which is turned into ATP in mitochondria.
B-cells have a K+ channel and K+ moves out of the cell.
The cell depolarises and Ca2+ enters via a voltage-gated calcium channel.
This determines how many secretory granules of insulin are released.
Lots of glucose = lots of ATP = lots of K+ going out = lots of calcium going in = lots of insulin released.
What causes MODY in B-cells?
Islet transcription factors modulate processes in the cell. If a transcription factor is wiped out then a ‘breaking mechanism’ is put on the cell giving insufficient insulin release.
What are the 2 most common types of MODY and their prevalence?
HNF-1alpha: 60%
Glucokinase: 20%
List the main hypoglycaemic drugs?
Sulphonylureas Biguanides Thiazolidinediones Incretin minics & DPP-4 inhibitors SGLT2 inhibitors.
How do sulphonylureas work?
Inhibit ATP-sensitve K+ channels.
therefor cell doesnt depolarise, no insulin released
How do Biguanides (metformin) work?
Mimicsinsulin by inhibiting hepatic gluconeogenesis.
Thought to be by inhibiting mitochondrial ATP synthesis - gluconeogenesis stops at it is very energy consuming.
How do Thiazolidinediones work?
Stops inappropriate deposition of lipid in non-adipose tissue (which leads to insulin resistance) - therefore improves insulin sensitivity.
Pioglitazone still used.
How do Incretins work?
GI hormones that potentiate insulin secretion.
Glucogon-like peptide-1 (GLP-1).
Gastric Inhibitory peptide (GIP).
Which drug degrades Incretins?
DPP-4 Inhibitors.
How do SGLT2 Inhibitors work?
Give examples of drugs.
Inhibit renal re-uptake of glucose from filtrate by SGLT2.
Produce lots of sweet urine - also have an effect on BP as water is lost.
Canagliflozin, Dapagliflozin.
Why are SGLT1 inhibitors not used?
As these receptors are found in the gut for uptake of glucose transport after a meal, so would cause you to by hypoglycaemic.
