Diabetes mellitus - pathogenesis, clinical features
All diabetes has one thing in common, a degree of insulin deficiency. This may be absolute, and due to reduced production as in the case in type 1, or it may be relative, with coexisting insulin resistance, as in type 2.
All diabetes can be largely divided into type 1 or type 2, although there are various phenotypes within these two categories.
Type 1 has childhood or early adulthood manifestation generally, with a genetic risk defined but most cases are sporadic. All patients require insulin, and these cases make up about 10% of all diabetic patients. Type 1 is in effect an autoimmune disease (more on this later), so is often found with other autoimmune diseases, especially those affecting the thyroid and other endocrine disorders.
Type 2 on the other hand generally manifests later, although can be found in obese childrne. There is a strong genetic component, with various genes identified as conferring risk. Obesity and a sedentary lifestyle confer a great risk to the patients, and these cases make up 90% of all diabetes cases. Requirement for insulin is variable, and the disease often comes with comorbidities that we would expect in metabolic syndrome.
Diabetes can also be found as part of several inherited syndromes including:
- Turner
- Klinefelter
- Prader-Willi
- Down syndrome
- And Wolfram syndrome
Diagnosis
Diabetes is diagnosed using the following criteria:
- 1. Diabetes symptom (e.g. polyuria, polydipsia, polyphagia) plus
- a. A random venous plasma glucose concentration >11.1 mmmol/l or
- b. A fasting plasma glucose concentration >7 mmol/l or
- c. Two hour plasma glucose concentration >11.1 mmol/l two hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT)
- 2. With no symptoms diagnosis should be based on two abnormal blood glucose values (either fasting or random)
- 3. HbA1c (glycated haemoglobin) value>48mmol/mol (6.5%) can also be used for diagnosis
- a. Note - a patient whose HbA1c is under 48 mmol/mol may still be diagnosed as diabetic if they meet the criterias above
It is worth noting that HbA1c can be erroneous as a result of other conditions, some examples have been provided below:
- Diseases which reduce RBC lifespan (hemolytic anemia, acute blood loss etc) will put HbA1c falsely low
- Increased RBC lifespan (iron deficiency anemia) - falsely high
- Altered glycation (high dose vitamin supplementation) - falsely low
- Chronic renal disease - falsely high
- Chronic liver disease - falsely low