Type-1 Diabetes
Key Hormones
Pancreatic islets are tiny clusters of pancreatic cells.
The pancreatic islets receive good, oxygenated blood supply from major arteries, allowing rapid release of insulin and glucagon into the portal vein.
Insulin is secreted by the β-cells of the pancreatic islets.
Glucagon is secreted by α-cells of pancreatic islets.
Insulin and glucagon are antagonistic hormones - insulin is secreted in response to elevated blood glucose, glucagon in repose to low glucose.
Insulin stimulation the utilization of biomolecules (glucose, FFAs, amino acids) for storage or energy usage
Insulin and C-peptide
Insulin is a 53 amino acids polypeptide synthesized as a prohormone: proinsulin
Causes and Development of T1D
Proinsulin undergoes cleavage by protests to release insulin and C-peptide.
C-peptide is a marker of endogenous insulin production and this the function of β-cells.
Diabetes mellitus is a group of illnesses characterized by chronic hyperglucaemia.
Genetic risk
Indential twins - 40% chance of both developing T1D
Genetic polymorphisms in the HLA region of chromosome 6 are known to be a risk factor for T1D (>50% compared to other loci). This collection of genes encodes proteins that regulate immune function and might trigger autoimmunity.
These genetic risk factors offer no clinical utility
Environmental Risk
Viruses
Pollution
Immunotherapy drugs
Antibiotic use.
Incidence of T1D
The global incidence of T1D has been increasing worldwide for several decades - 39 million worldwide; 300,000 in the UK, highest for younger teenagers.
In Finland, Germany, and Norway, annual increases in incidence of 2.4%, 2.6%, and 3.3%, respectively.
The incidence of T1D in India and China are conversely very low.
The explanation for these marked differences in geographic incidence is unknown but have largely been attributed to environmental influences.
Meal stimulated C-peptide responses in T1D
Fasting and AUC C-peptidde (i.e., production following a glucose-based meal diminish progressively following diagnosis with T1D).
There is limited endogenous insulin production after 2 years of diagnosis.
Preserved C-peptide Secretion (Gibb et al.)
Preserved C-peptide secretion is associated with fewer low-glucose events and lower glucose variability on flash glucose monitoring in adults with type-1 diabetes
Less time with glucose - <3.9 mmol/L (3% vs. 5%
Fewer low glucose events over fortnight (7 vs. 10)
Lower glucose variation (SD, 3.8 vs. 4.8 mmol/L)
Hyperglycemic Complications: Keroacidosis
Clinical Signs
High blood glucose
High levels of ketones/glucose in urine.
Main Cause
Mismanagement of insulin levels - inadequate dose.
Warning signs
Thirst, dry mouth, tired, flushed, frequent urination, confusion, nausea, fruity odor to breath.
Why?
A decrease usage of insulin and clearance of blood glucose.
This decrease glucose availability for tissues for energy.
The body promotes gluconeogensis to increase glucose.
Ketone acids compromise protein function and cause major issue for the pH balance of the blood.