Type 2 diabetes usually develops in patients who are over 40 years old and who frequently are obese. The pathogenesis of type 2 diabetes involves insulin resistance and impairment of insulin secretion. It is unclear which of these mechanisms is primary, because they usually operate together. The response of the diabetic β-cell to the glucose stimulus in type 2 diabetes is suboptimal and, after glucose stimulation, there is no first phase of insulin secretion (see Fig. 20.2).
|
| There is no consistent inheritance pattern in type 2 diabetes. No doubt there is a strong hereditary component; monozygotic twins are 90-95% concordant for type 2 diabetes, and first-degree relatives of diabeteic persons have a 40% chance of developing the disease. By contrast, in people with no diabetic relatives such risk is only 10%.
|
| page 287 |  | | page 288 |
| TYPICAL PRESENTATION OF DIABETIC KETOACIDOSIS |
| A 15-year-old girl was admitted to the Accident and Emergency department. She was confused and her breath had a smell of acetone. She had signs of dehydration with reduced tissue turgor and dry tongue. She also had rapid pauseless respirations. Her blood glucose was 18.0 mmol/L (324 mg/dL) and ketones were present in the urine. Her serum potassium concentration was 4.9 mmol/L (normal = 3.5-5.0 mmol/L) and her arterial blood pH was 7.20 (normal = 7.37-7.44). |
| Comment. This is a typical presentation of diabetic ketoacidosis. Hyperventilation is a compensatory response to acidosis (see Chapter 22). A patient like this needs to be treated as a medical emergency. She received an intravenous infusion containing physiologic saline with potassium supplements to replace lost fluid and an infusion of insulin. |
| There is a genetic form of type 2 diabetes, the maturity onset diabetes of the young (MODY); however, it affects only a small minority of patients. MODY results from
mutations of at least six different genes: an enzyme glucokinase (MODY2), and several transcription factors (hepatocyte nuclear factor HNF-4α (MODY1), HNF-α1 (MODY3)), insulin promoter factor (IPF-1), HNF-1α and β-cell transcription factor (neuroD1). There is also a mitochondrial DNA mutation that leads to impaired oxidative phosphorylation and to the so-called 'mitochondrial diabetes'.
|
| In most patients the disease has a polygenic background
|
| A large research effort focuses presently on the identification susceptibility genes for type 2 diabetes. The recently discovered such gene is present in NIDDM1 locus on chromosome 2 and codes for calpain-10 (calcium-activated neutral protease). Other susceptibility genes could be coding for any of the components of fuel metabolism described above: the insulin receptor, IRS-1, GLUT4, or enzymes associated with carbohydrate and lipid pathways. Watch this space.
|
|
