Hyperglycaemia ✅ Flashcards
What history is important in a child presenting with hyperglycaemia?
- Duration of symptoms
- Infection, particularly candidiasis
- Vomiting or abdominal pain
- Family history of diabetes or other autoimmune disease
What might vomiting and abdominal pain suggest with hyperglycaemia?
Ketoacidosis
What is often found on clinical examination in children with newly diagnosed diabetes?
No abnormal findings
What is critical in children with hyperglycaemia and presumed diabetes?
To distinguish between T1DM and T2DM
Why is it important to differentiate between T1DM and T2DM?
Treatment will be very different for each form
What suggests type 1 diabetes?
- Weight loss
- Dehydration
- Signs of acidosis such as Kussmaul breathing
- Sweet breath
- Depressed consciousness
- Signs of cerebral oedema
What is Kussmaul breathing?
Deep and tachypnoeic
What suggests type 2 diabetes?
- Overweight
- Hypertension
- Acanthosis nigrans
What investigations need to be considered in hyperglycaemic children?
- Glucose testing
- HbA1c
- GAD antibodies
- Screening for other autoimmune disease
What are the forms of glucose testing?
- Random
- Two hour glucose tolerance test
- Fasting
What is the diagnostic value for diabetes on random or GTT?
> 11.1mmol/L
What is the diagnostic value for diabetes on fasting blood glucose?
> 7mmol/L
What can HbA1c tell you in a newly presenting child with hyperglycaemia?
May indicate the length of the prodrome
What are GAD antibodies?
Glutamic acid decarboxylase antibodies
What does the presence of GAD antibodies suggest?
Autoimmune mediated T1DM
When is screening for other autoimmune diseases indicated?
When a diagnosis of T1DM seems likely
What testing can indicate T2DM when there is uncertainty?
Formal oral glucose tolerance test with measurement of high concentrations of insulin and c-peptide on baseline and 2 hour blood samples, along with suppressed sex hormone binding globulin concentrations
What is the most common form of childhood diabetes?
T1DM
What causes T1DM?
T-cell mediated autoimmune damage to pancreatic beta cells
What genes are implicated in T1DM?
Strong HLA associations with DQA, DQ8, and DRB
What kind of genes are DQA, DQ8, and DRB?
Major histocompatibility class II genes
How does the onset of T1DM compare between pre-school children and adolescents?
Has a more rapid onset in pre-school children
What does the rapidly increasing incidence of T1DM suggest?
An additional change in some unknown environmental precipitant, e.g. diet, viruses, hygiene, toxins
When do symptoms occur in T1DM, with regard to beta cells?
When approx 90% of beta cells are destroyed
What are children with T1DM at increased risk of?
Other autoimmune disease, e.g. coeliac, thyroid
What does treatment of T1DM require?
Insulin injections 2-4+ times a day, or delivered by pump in continuous subcutaneous injection
Give 2 examples of rapid acting insulins
- Insulin lispro
- Insulin aspart
Why are insulin lispro and insulin aspart rapid acting?
Due to a change in their molecular structure, which prevents polymerisation into inactive hexamers following SC injection
Give 2 examples of long acting insulins
- Insulin glargine
- Insulin detemir
Why is insulin glargine long acting?
Molecular changes shift it’s isoelectric point to result in precipitation and slow dissolution to release bioactive molecules
Why is insulin detemir long acting?
Molecular changes promote potent binding to albumin, which prolongs duration of active
What is current research evaluating, regarding T1DM management?
Autoimmune modulation at diagnosis to prolong residual beta-cell activity
What is required with any diagnosis of T1DM, with regards to support?
Considerable support and a detailed educational programme to help learn how to self manage diabetes
What should be included in the education programme teaching how to self-manage T1DM?
- Appropriate changes to insulin dose, guided by results of self blood glucose testing
- Estimation of carbohydrate content of food
- Estimation of known effects of exercise on their blood glucose measurements
Why is optimal blood glucose control aimed for in T1DM?
Minimises microvascular complications
How is blood glucose control judged in T1DM?
Repeated measurement of HbA1c (glycosylated haemoglobin)
What causes glycosylated haemoglobin to rise?
It is a consequence of non-enzymatic glycation of haemoglobin when exposed to plasma glucose
What causes glycosylated haemoglobin to rise?
It is a consequence of non-enzymatic glycation of haemoglobin when exposed to plasma glucose
What does measuring HbA1c provide?
An integrated measure of circulating blood glucose over the previous 2-3 months
When might HbA1c be unreliable?
In conditions which affect circulating red cell half life, e.g. haemoglobinopathies
What is required for diabetes monitoring in conditions that affect circulating red cell half life?
Other measures such as continuous blood glucose monitoring or fructosamine
What do patients and their carers need to be trained to do in T1DM, regarding hypoglycaemia?
Recognise and treat these episodes
What does inadequate insulin lead to in the short term?
Hyperglycaemia
What happens when hyperglycaemia exceeds the renal threshold for absorbing glucose?
Results in glycosuria and polyuria through concomitant osmotic effects
What does excessive urinary loss of glucose lead to?
Negative calorie balance, and over time weight loss
What does the cachexic state induced by chronic hyperglycaemia lead to in the long term?
Growth hormone resistance with impaired growth and suppressed gonadotrophin secretion, causing pubertal delay.
How does excessive insulin deficiency lead to ketosis?
Due to lipolysis
What does accumulation of ketones lead to?
Progressive acidosis with vomiting and impaired consciousness
What does persistent hyperglycaemia produce in the longer term?
Microvascular changes
What microvascular changes are caused by persistent hyperglycaemia?
The basement membrane of the epithelial cells becomes damaged through the presence of excess glycoproteins
What do the microvascular changes in hyperglycaemia lead to?
- Retinopathy
- Nephropathy
- Neuropathy
How does the presentation of T2DM compare to T1?
Similar, but ketoacidosis less common
Are genetics involved in the development of T2DM?
There is a clear genetic predisposition, but different genes involved compared to T1
What is the primary mechanism of development of T2DM?
Obesity-induced insulin resistance, with a secondary relative degree of insulin insufficiency, leading to excessive hepatic release of glucose
What does the management of T2DM involve?
Lifestyle changes to increase physical activity and reduce calorie intake to promote weight loss and increase insulin sensitivity
What do most children require in the management of T2DM?
Additional medical therapy using metformin
How does metformin primarily act?
By suppressing hepatic gluconeogenesis
What additional therapy (to metformin) may be required in the management of T2DM?
- Sulphonylureas
- Insulin
How do sulphonylureas act?
They bind to the potassium channel on the pancreatic beta cell, precipitating membrane depolarisation, calcium influx, and insulin release
What screening is required in T2DM?
Screening for the development of microvascular complications
What condition are teenage girls with T2DM at risk of?
PCOS
What causes maturity onset diabetes of the young (MODY)?
Genetic defects of genes, mostly transcription factors, expressed in the beta-cell, producing variable defects in insulin secretion (but not action)
What is MODY characterised by?
Mild asymptomatic hyperglycaemia in non-obese children
What family history is MODY often characterised by?
Strong autosomal dominant family history of ‘diabetes’
What is the risk of complications in MODY?
Low or non-existent
Does MODY require treatment?
Most cases don’t
What are some rare causes of diabetes mellitus?
- Mutations in mitochondrial DNA
- Insulin sensitivity impaired by genetic defects in insulin receptor signalling
Give 2 examples of conditions with mutations in mitochondrial DNA leading to diabetes
- Maternally inherited diabetes and deafness syndrome
- Kearns-Sayre syndrome
Give an example of a condition with genetic defecs in insulin receptor signalling
Leprechaunism
Why are children with cystic fibrosis at increased risk of developing diabetes?
Combination of pancreatic destruction and insulin resistance, particularly during pulmonary exacerbations
What treatment is requried with CF associated diabetes?
Insulin
Why is insulin required with CF associated diabetes?
To support an unrestricted diet
What care needs to be taken in CF associated diabetes?
To avoid hypoglycaemia
Why is it particularly important to avoid hypoglycaemia in CF associated diabetes?
Due to increased risks associated with co-existent alpha cell damage
What has neonatal diabetes recently been recognised to be due to?
Defects in genes expressed in the pancreatic beta cell
What is the result of neonatal diabetes being due to defects in genes expressed in the pancreatic beta cell on the management?
Has shown that in those with mutations in certain genes (encoding the Kir6.2 subunit of the ATP-sensitive potassium channel KCNJ11), treatment with sulphonylureas can be even more effective than insulin, allowing patients to be weaned off daily injections
