What is Insulin Resistance

The fundamental role of insulin is to facilitate cellular uptake of glucose in skeletal muscle and to limit hepatic gluconeogenesis, the other key determinant of steady-state plasma glucose levels. In the steady (or fasted) state the quantity of insulin required to maintain a plasma glucose level depends on muscle mass and hepatic glucose output. However, there is more than a twofold variation in the plasma insulin levels required to maintain identical plasma glucose levels in normal subjects (Hollenbeck and Reaven, 1987). This variation in insulin requirement for glucose disposal has been termed

Time

Figure 2.2 As insulin resistance worsens with age, the pancreas is often able to secrete increasing amounts of insulin over many years to maintain glucose homeostasis. In susceptible individuals, the pancreas eventually becomes 'exhausted' and subsequently glucose concentrations rise into the diabetic range. However, an array of other risk factor abnormalities such as elevations in triglyceride (Trig) or blood pressure (BP), and many novel parameters demonstrated in Figure 2.1 and detailed in the text, frequently accompany worsening insulin resistance. Since many of these are also CVD risk factors, this explains why CVD risk is already high at diagnosis of type 2 diabetes (b). It also explains why the hyperglycaemic element in type 2 diabetes is perhaps a late element in the excess risk of vascular disease in this condition. Of course, risk is further accelerated should individuals with diabetes subsequently develop renal disease. This simplified but conceptual model also illustrates why hyperglycaemia only modestly increases the already high established vascular risk in type 2 diabetes and why treating high glucose levels in isolation will only minimally attenuate vascular risk.

Time

Figure 2.2 As insulin resistance worsens with age, the pancreas is often able to secrete increasing amounts of insulin over many years to maintain glucose homeostasis. In susceptible individuals, the pancreas eventually becomes 'exhausted' and subsequently glucose concentrations rise into the diabetic range. However, an array of other risk factor abnormalities such as elevations in triglyceride (Trig) or blood pressure (BP), and many novel parameters demonstrated in Figure 2.1 and detailed in the text, frequently accompany worsening insulin resistance. Since many of these are also CVD risk factors, this explains why CVD risk is already high at diagnosis of type 2 diabetes (b). It also explains why the hyperglycaemic element in type 2 diabetes is perhaps a late element in the excess risk of vascular disease in this condition. Of course, risk is further accelerated should individuals with diabetes subsequently develop renal disease. This simplified but conceptual model also illustrates why hyperglycaemia only modestly increases the already high established vascular risk in type 2 diabetes and why treating high glucose levels in isolation will only minimally attenuate vascular risk.

insulin resistance, whereby subjects needing higher amounts of insulin are 'insulin resistant' compared to those who need lesser amounts of insulin. Insulin response is a linear variable across populations; insulin resistance (or insulin sensitivity) is a relative concept in normal glucose-tolerant subjects, and there are no absolute cut-off values.

In pathogenic terms insulin resistance is a principal feature of type 2 diabetes and precedes the clinical development of the disease by 10-20 years (Warram etal., 1990). Insulin resistance is caused by the decreased ability of peripheral target tissues (muscle and liver) to respond properly to normal insulin levels. Initially, increasing pancreatic insulin secretion is able to counteract insulin resistance and thus normal glucose homoeostasis can be maintained. However, pancreatic reserve eventually diminishes in the face of increasing peripheral demands and thus glucose concentrations rise, heralding a diagnosis of type 2 diabetes once plasma glucose concentrations go beyond universally agreed diagnostic cut-offs, whether fasting or post-glucose loading.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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