12.3 Disorders Of Glucose Metabolism Flashcards
Define Diabetes Mellitus
- Clinical condition characterised by a chronically ELEVATED BLOOD SUGAR LEVEL
- Caused by absolute or relative insulin deficiency
- Disease which affects the metabolism of carbohydrates, protein and fat
- Results in complications in every tissue and organ of the body
Absolute vs Relative insulin deficiency
Absolute
- insulin not produced by pancreas
Relative
- insufficient insulin or insulin actions for body’s requirements
Insulin overview
- Hormone - synthesised in the Beta-cells of the islets of Langerhans in the pancreas
- Preproinsulin ➡️ Proinsulin ➡️ Insulin & C-peptide (cleaved within secretory granules)
- Secreted by Beta-cells in response to elevated blood glucose levels e.g. mealtimes
- Pancreas secretes 30u/day, basal and related to meals
What is the significance of C-peptide related to DM?
C-peptide is a peptide that is produced when proinsulin (a precursor to insulin) is cleaved during the process of insulin synthesis in the pancreas.
**Significance:*
Marker of Insulin Production:
- useful marker for assessing endogenous insulin production by the pancreas
- Type 1 diabetes = little to no C-peptide is produced (immune system destroys the insulin-producing beta cells in the pancreas)
- Type 2 diabetes = higher C-peptide levels (pancreas is still producing insulin, even if it is not used effectively)
Diagnostic criteria of DM
- Symptoms of diabetes (polyuria, polydipsia and unexplained weight loss) and random glucose >11.1mmol/I
OR - Fasting plasma glucose of >7.0mmol/I
OR - Two hour plasma glucose >11.1mmol/I in standard 75g oral glucose tolerance test
- HbAlc ≥ 6.5% (blood test that shows what your average blood sugar (glucose) level was over the past two to three months)
Impaired fasting gluocse
- Normal fasting glucose < 5.6mmol/I
- Impaired fasting glucose > 5.6mmol/1 - 7.0mmol/I
NB:macrovascular complications can occur prior to onset of diabetes
Classification of DM
Type 1 diabetes mellitus
- autoimmune
- idiopathic
Type 2 diabetes mellitus
Gestational diabetes mellitus
Other:
- endocrinopathies
- exocrine pancreatic problems
- genetic defects of beta cell function
- drug-induced diabetes
- genetic syndromes associated with diabetes
Type 1 DM
Definition
Pathogenesis
Presentation
Def
- State of absolute insulin deficiency
- Secondary to pancreatic-cell destruction
- Dependent on insulin (treatment) for survival
- Altered fat metabolism results in ketone production
Pathogenesis
- Genetic susceptibility
- Environmental insult
Leads to:
➡️Insulitis
➡️Activation of autoimmunity
➡️B-cell destruction
➡️Diabetes mellitus
Presentation:
10 - 20% of all diabetics
- Usually presents in childhood/ adolescence
- Marked loss of weight
- Polyuria
- Polydipsia
- Blurred vision
- Diabetic ketoacidosis
Type 2 DM
Def
Clinical RF
Pathogenesis
Def:
- Insulin resistance ➡️ hyperinsulinemia
- Varying degree of beta-cell dysfunction
Classic type 2 diabetic:
- Obese > 80 %
- insulin resistance
Non-obese < 20 %:
- Beta-cell dysfunction
Clinical RF:
- Age
- Obesity
- Lack of physical activity
- Family history of diabetes
- Previous gestational diabetes
- Secondary causes: drugs, endocrinopathies
- Race / geography
Pathogenesis:
- western lifestyle (decreased exercise; high fat diet; smoking)
⬇️
- Central obesity
⬇️
- increased FFA
⬇️
- increased insulin resistance (genetic predisposition; aging)
Define + Clinical sign of insulin resistance
Def:
- A state where a given concentration of insulin is associated with a subnormal glucose response as a result of insensitivity of the peripheral tissue to the effect of insulin.
- gives rise to hyperinsulinemia
Clinical sign indicating insulin resistance: Acanthosis nigricans
Metabolic syndrome
Def
Predisposition of
Combination of:
- Obesity/ central adiposity
- Hyperglycaemia
- Hyperinsulinaemia
- Dyslipidaemia
- Hypertension
➡️Predisposed to macrovascular disease - heart attacks and strokes
Insulin resistance and atherosclerosis
- Hypertension
- Obesity
- Hyperinsulinemia
- Diabetes
- Hypertriglyceridemia
- Small, dense LDL
- Low HDL
- Hypercoagulability
Type 2 DM
Presentation
Usually incidental finding (NB: consider to screen if high risk!)
Subacute and may present with:
- Chronic tiredness
- Pruritis - balanitis or vaginitis secondary to candidiasis
- Recurrent skin infections, muscle cramps in legs
- Blurred vision secondary to osmotic changes in the lens
- Complications as the initial presentation e.g. neuropathy, heart attacks, strokes
- Presentation may be precipitated by pregnancy, intercurrent illness, drugs
DM type 1 and type 2 comparison
Type 1
- Younger, thinner
- Symptoms: weeks
- Weight loss: +++
- HLA DR3/DR4
- Autoimmunity, association with other autoimmune diseases
- Insulin deficient, DKA, insulin essential
- Eventual disappearance of C- peptide
- 30 - 40% concordance twins
Type 2
- Older, often obese
- Symptoms: months to years
- Weight loss: +/-
- No HLA links
- No evidence of immune disturbance
- Partial insulin deficiency, may require insulin late in disease
- C-peptide persists
- 90% concordance in identical twins
Endocrinopathies related to DM
Excess production of certain hormones
- GH (acromegaly)
- Cortisol (Cushing’s)
- Catecholamines (phaechromocytoma)
- Thyroid hormone (thyrotoxicosis)
Decreased peripheral responsiveness to insulin - associated with dysglycaemia
