TYPE 2 DIABETES MELLITUS

What is it?
Insulin resistance (insulin usually facilitates glucose uptake in muscles and fat, and suppresses glucose production in the liver)
There is no immune disturbance, unlike in Type I
NOTE: The normal blood glucose level is 3.5-8.0 mmol/L

It can also cluster with other conditions that increase cardiovascular risk (Insulin resistance syndrome):

• Hypertension
  
• Obesity
  
• Hypertriglyceridaemia
  
• Decreased HDL-cholesterol
  
• Acanthosis Nigricans (skin condition – dark, hyperpigmented patches of skin, which can appear velvety or warty when advanced)

Four major determinants

• Increasing age
• Obesity (due to reduced exercise rather than increased food intake)
  
• Ethnicity (Asian, African, Polynesian, and American-Indian)
  
• Family History

Onset can be accelerated by:

• Pregnancy
  
• Drug treatment
  
• Intercurrent illness

Causes
Abnormalities of insulin secretion and action

Insulin can still bind normally to the insulin receptors. However, there is a problem with the insulin signalling within the cell. It is this that produces the insulin resistance (it is thought that intracellular triglyceride in muscle and liver cells contributes to this). When the individual is unable to secrete enough insulin to overcome this resistance is when Type II diabetes develops.

Beta-cells are in a state of high output failure; thus, there is an increased glucose production by the liver and inadequate uptake of glucose peripherally. The gradual loss of beta cells (not to the extent of Type I) means that there is reduced insulin secretion, which is unable to control the glucose concentration in the individual.

Genetics

Type II is a polygenetic disorder, but many of the genes have yet to be identified.

NOTE: Whether an individual develops Type II diabetes is due to genetics. When an individual develops it is due to lifestyle (diet, exercise, drugs which control glucose levels)

Environmental factors
There is an association between low birth weight/weight at 12 months, and glucose intolerance later in life (especially if there is excess weight gain when in adulthood). Poor nutrition when young leads to impaired beta cell development and function, which can then predispose the individual to diabetes.

Immunology and inflammation

There is no evidence of immune involvement in Type II diabetes. Where patients have antibodies against GAD (glutamic acid decarboxylase, an enzyme found in the pancreas which secretes GABA), it can be possible that the Type I diabetes is masquerading as Type II.

The clinical inflammatory changes that occur in Type II also occur in obesity. These include high levels of C-reactive proteins (inflammatory globulins which can reflect the presence and intensity of inflammation), raised fibrinogen, increased plasminogen-activatior-inhibitor-1 (PAL-1) and elevated levels of the proinflammatory cytokines TNF-α and IL-6. These all contribute to cardiovascular risk (the risk can be reduced by the use of anti-inflammatory agents).

Presentation
In older patients:

• Thirst (osmotic diuresis due to increased glucose levels)
• Polyuria (loss of fluid and electrolytes - osmotic diuresis)
• Weight loss (fluid depletion and the breakdown of fat and muscle due to insulin deficiency)
• Fatigue
• Visual blurring (glucose interferes with refraction)
• Candida infection
  

Other complications:

• Arterial disease (can lead to MI or gangrene)
• Macrovascular disease – can cause coronary artery disease, peripheral vascular disease and stroke
• Microvascular damage – diabetic retinopathy (diagnostic) and nephopathy
• Staphylococcal skin infection
• Polyneuropathy (tingling and numbness in feet)
• Erectile dysfunction

Diagnosis

• Impaired fasting glucose (fasting plasma glucose between 6.1 and 6.7 mmol/L)
• Glucose tolerance test (test body’s ability to metabolise carbohydrates)
  

Treatment
Diet

• Low in sugar (not sugar-free)
• High in starchy carbohydrate (Low glycaemic index – thus, they are absorbed at a slower rate, and do not have a sudden impact on blood glucose levels)
• High in fibre
• Low in fat (especially saturated fat)

If diet and life style changes don’t work - use drugs

• Sulphonylureas – promote insulin secretion in response to glucose
• Meglitinides – promote insulin secretion in response to meals
• Biguanides – reduces gluconeogenesis (suppresses glucose release by liver) and increases insulin sensitivity
• Thiazolidinediones – reduce insulin resistance and reduce glucose production by the liver
  Intestinal enzyme inhibitors – inhibit enzymes involves in carbohydrate digestion, and thus reduce post-prandial (post-meal) blood glucose increases
• Insulin treatment

Sources: Kumar and Clarke

~ Rushmi