Type 1 Diabetes Mellitus Flashcards
Type 1 diabetes
An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
The resultant hyperglycaemia requires life-long insulin treatment
Overlaps between diabetes
Autoimmune diabetes leading to insulin deficiency can present later in life = latent autoimmune diabetes in adults (LADA)
T2DM may present in childhood
Diabetic ketoacidosis can be a feature of T2DM
Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
Diabetes may present following pancreatic damage or other endocrine disease
Type 1 diabetes can develop in adults
Stages of development of type 1 diabetes
Genetic predisposition
Potential precipitating event
Overt immunological abnormalities - normal insulin release
Progressive loss of insulin release - glucose normal
Overt diabetes, C peptide present (cleavage product of pro-insulin)
No C peptide present
From proinsulin to C peptide and insulin - C peptide measured over insulin as people are usually on insulin injection - not used for those not diagnosed
Immune response in type 1 diabetes
Increased risk of T1D for genetically susceptible
Immune activation - beta cells attacked
Immune response - development of single autoantibodies
Generate antibodies
Why is the immune basis important ?
Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically
Immune modulation offers the possibility of novel treatments - Not there yet
Immunology
Defect in innate and adaptive immune system
Primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
Exacerbated by release of pro-inflammatory cytokines
Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity
Some people with type 1 diabetes continue to produce small amounts of insulin
Not enough to negate the need for insulin therapy
Genetic susceptibility related to HLA
Environmental factors
Multiple factors implicated, but causality has not been established
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
Pancreatic auto-antibodies
Detectable in the sera of people with Type 1 diabetes at diagnosis.
Not generally needed for diagnosis in most cases
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
Presentation of type 1 diabetes
Excessive urination (polyuria) Nocturia Excessive thirst (polydipsia) Blurring of vision Recurrent infections eg thrush Weight loss Fatigue
dehydration cachexia hyperventilation smell of ketones glycosuria ketonuria
Effects of insulin deficiency
Proteinolysis - amino acids
Hepatic glucose output (HGO) - glucose
Lipolysis - non esterified fatty acids and triglyceride
Ketone bodies
NEFA go into liver to undergo oxidation
Generate Acetyl CoA, Acetoacetate, Acetone + 3 OH-B (ketone bodies) - acidic, so accumulate to turn blood acidic - diabetic ketoacidosis
Aims of treatment in type 1 diabetes
People with type 1 diabetes, require insulin FOR LIFE
Aims:
Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications
Complications
Acute
Diabetic ketoacidosis
Chronic Microvascular Retinopathy Neuropathy Nephropathy Macrovascular Ischaemic heart disease Cerebrovascular disease Peripheral vascular disease
Hypoglycaemia
Management of type 1 diabetes
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
Type 1 diabetes is a condition that is ‘self-managed’
Physiological insulin profile
Insulin is never completely suppressed
Basal insulin has a flat profile
Prandial peak has two phases
Types of insulin
With meals (short / quick-acting insulin): Human insulin – exact molecular replicate of human insulin (actrapid) Insulin analogue (Lispro, Aspart, Glulisine)
Background (long-acting / basal): Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH) Insulin analogue (Glargine, Determir, Degludec)
Three times short acting with once or twice daily long acting
Insulin pump therapy
Continuous delivery of short-acting insulin analogue e.g. novorapid via pump
Delivery of insulin into subcutaneous space
Programme the device to deliver fixed units / hour throughout the day (basal)
Actively bolus for meals
Variable basal rates
Extended boluses
Greater flexibility
Dietary advice integral
Dose adjustment for carbohydrate content of food.
All people with type 1 diabetes should receive training for carbohydrate counting
Where possible, substitute refined carbohydrate containing foods (sugary / high glycaemic index) with complex carbohydrates (starchy / low glycaemic index)
Artificial pancreas
Real-time continuous glucose sensor
Change in glucose
Algorithm to use glucose value to calculate insulin requirement
Insulin pump delivers calculated insulin
Transplantation
Islet cell transplants:
Isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein
Requires life-long immunosuppression
Simultaneous pancreas and kidney transplants:
Better survival of pancreas graft when transplanted with kidneys
Requires life-long immunosuppression
How do we monitor glucose levels?
Capillary (finger prick) blood glucose monitoring
Continuous glucose monitoring (restricted availability, NICE guidelines)
Glycated haemoglobin (HbA1c)
Reflect last 3 months (red blood cell lifespan) of glycaemia
Biased to the 30 days preceding measurement
Glycated NOT glycosylated (enzymatic)
Therefore linear relationship
Irreversible reaction
Acute complications from type 1 diabetes
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
Diabetic ketoacidosis
Can be a presenting feature of new-onset type 1 diabetes
Occurs in those with established type 1 diabetes
Acute illness
Missed insulin doses
Inadequate insulin doses
Life-threatening complication
Can occur in any type of diabetes
Diabetic ketoacidosis diagnosis
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
Hypoglycaemia
To some extent an inevitable feature of the self-management of type 1 diabetes
‘Lost normal physiology and homeostasis’
May become debilitating with increased frequency
Numerical definition (variable) <3.6 mmol/L
Severe hypoglycaemia: any event requiring 3rd party assistance
Problematic hypoglycaemia
When does hypoglycaemia become a problem?
Excessive frequency
Impaired awareness (unable to detect low blood glucose)
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia
Risks of hypoglycaemia Seizure / coma/ death (dead in bed) Impacts on emotional well-being Impacts on driving Impacts on day to day function Impacts on cognition
Who is at risk of hypoglycaemia
All people with type 1 diabetes
Risk factors: Exercise Missed meals Inappropriate insulin regime Alcohol intake Lower HbA1c Lack of training around dose-adjustment for meals
Strategies to support problematic hypoglycaemia
Indication for insulin-pump therapy (CSII)
May try different insulin analogues
Revisit carbohydrate counting / structured education
Behavioral psychology support
Transplantation
Acute management of hypoglycaemia
Alert & Orientated - Oral Carbohydrates (juice/sweets or sandwich)
Drowsy / confused but swallow intact - Buccal glucose (glucogel)
Unconscious or concerned about swallow - IV access
