What are the 3 different types of diabetes you can have?
- Type I
- Type II
- Monogenic diabetes (e.g. MODY “maturity onset diabetes of the young”, mitochondrial diabetes)
What is type I diabetes mellitus?
- An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
-Can have predisposed genetic risks, and contributed by environmental triggers - The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
- The resultant hyperglycaemia requires life-long insulin treatment (still responds to insulin)
What are the stages of development of type I diabetes?
a. Genetic predisposition
b. Potential enviornmental precipitating event/ trigger
c. Immunological response
- Destruction of the beta cells (progresses with time):
- Development of at least 1 autoantibody
Stage 1. Development of 2 or more autoantibodies but blood sugar still normal- glucose normal, no symptoms
Stage 2. Overt diabetes, abnormal blood sugar, but still no symptoms (C peptide still detectable)
Stage 3. Clinical diagnosis: significant beta cell loss + Symptoms of T1D
(no C-peptide detectable)
What causes the destruction of the beta cells?
- Usually in the body if there are auto-antigens: (attempting to suppress autoimmunity) T reg cells inhibit T cell proliferation and cytokine production
However, in Type I diabetes there are defects in regulatory T-cells that fail to suppress autoimmunity, so instead:
- 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
Some people with type I diabetes still have some undestroyed beta cells, why do they still require insulin therapy?
-Continue to produce small amounts of insulin but it is not enough to negate the need for insulin therapy
What increases the genetic susceptibility of having type I diabetes mellitus?
- HLA-DR allele increases the risk (how significant the risk is, depends on where the allele is found/ the locus)
- NOTE: this just increases susceptibility- still need a trigger
What are potential environmental triggers of type I diabetes mellitus?
(Multiple factors implicated, but causality has not been established)
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What are the symptoms of Type I diabetes mellitus?
Excessive urination (polyuria)
Nocturian (getting up in the night to pee)
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
What are some signs of Type I diabetes mellitus?
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
What effect does insulin deficiency have on the organs of the body?
- Increased proteinolysis (breakdown of muscle) to gain amino acids- used for fuel
- Increased hepatic glucose output (HGO)- Counterintuitive- blood glucose is high but it is not being used, so the body gets confused and increases production
- Increased lipolysis (breakdown of fat/ adipose tissue) to gain non-esterified fatty acids/ NEFA’s for fuel
-Formation of ketone bodies
Why are ketone bodies formed as a result of insulin definicency?
-Breakdown of fat:
- Fatty Acyl-Co A into the ketone bodies
- Used as fuel during starvation
- Acidic: accumulation= acidosis
What are the aims with Type 1 Diabetes Mellitus treatment?
People with type 1 diabetes, require insulin FOR LIFE
Aims:
Maintain glucose levels without excessive hypoglycemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation (e.g. ketoacidosis or severe hypoglycemia)
Prevent microvascular and macrovascular complications
What are the complications of hyperglycaemia?
- Acute:
Diabetic ketoacidosis - Chronic:
Microvascular (Retinopathy, Neuropathy, Nephropathy- damage to kidney)
Macrovascular (Ischaemic heart disease, Cerebrovascular disease, Peripheral vascular disease)
What is the management of Type I diabetes mellitus?
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
(Type 1 diabetes is a condition that is ‘self-managed’)
What are 3 facts about plasma insulin levels?
- Insulin is never completely suppressed (levels on a profile never at 0)
- Insulin has a 1st phase release (estimate for how much you’ll eat) and 2nd phase release (more accurate to meet the amount of food)= 2 peaks
What are the 2 types of insulin?
- Short/ quick acting insulin
(Human insulin – exact molecular replicate of human insulin (actrapid)
Insulin analogue (Lispro, Aspart, Glulisine))
GIVEN THREE TIMES A DAY - Long-acting/ basal
(Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
Insulin analogue (Glargine, Determir, Degludec))
GIVEN ONCE A DAY
What is 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
pros:
Variable basal rates (replicates the true response more accurately)
Extended boluses
Greater flexibility
How is dietary advice given for Type I diabetes mellitus?
- Dose adjustment for carbohydrate content of food
- All people with type 1 diabetes should receive training for carbohydrate counting (known as a Structured Education Programme- 5 day course on skills and traning in self-management
- Where possible, substitute refined carbohydrate containing foods (sugary / high glycaemic index) with complex carbohydrates (starchy / low glycaemic index
How does a closed loop/ artificial pancreas work?
- Change in glucose
- Real-time continuous glucose sensor
- Algorithm to use glucose value to calculate insulin requirement
- Insulin pump delivers calculated insulin
How would a transplantation treat Type I diabetes mellitus?
- 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
Even if incomplete, often results in better control
Limitations: availability of donors, complications of life-long immunosuppression
How are glucose levels monitored?
- Capillary (finger prick) blood glucose monitoring
- Continuous glucose monitoring (restricted availability, NICE guidelines)
- Glycated haemoglobin (HbA1c)
What are pros and cons of using HbA1c to monitor glucose levels?
Pros:
- Reflect last 3 months (red blood cell lifespan) of glycaemia
cons:
- Biased to the 30 days preceding measurement
- Anything that affects the haemolglobin in the body will affects HbA1c (e.g. anaemia, haemolysis)
What are some acute complications from type 1 diabetes
Diabetic ketoacidosis
Uncontrolled hyperglycaemia
Hypoglycaemia
What can cause diabetic ketoacidosis to occur as a complication of treatment/ management?
Acute illness
Missed insulin doses
Inadequate insulin doses
-
Hypopituitarism27
-
Cortical organisation and function38
-
Cerebral vasculature23
-
Hyperthyroidism25
-
Pituitary tumours22
-
Calcium dysregulation23
-
Adrenal disorders47
-
Infertility34
-
Reproductive treatments26
-
Type 1 Diabetes Mellitus31
-
Type 2 Diabetes Mellitus34
-
Microvascular & Macrovascular complications of diabetes mellitus40
-
Disorders of vasopressin30
-
Obesity18
