Pathophysiology and Pharmacological Treatment of Insulin Resistance*

Abstract

Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic beta-cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., a-glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease.

Tumor necrosis factor-alpha 308 G/A polymorphism and type 2 diabetes mellitus; a systematic review and meta-analysis

“…Decrease in insulin secretion and/or resistance to it are known to be involved in the development of DM (1). In general, DM refers to a heterogeneous group of metabolic disorders characterized by decreased insulin action or resistance to it, or both and is divided into two main categories; diabetes type 1, and type 2.…”

Pre-school children with diabetes: focus on UK dietary issues and challenges

“…For example, the National Diet and Nutritional Survey, Young People, 1997 1 states that 'Children in Britain eat on average only two portions of fruit and vegetables a day -with one in five eating no fruit at all,' and that 'The average amounts of saturated fat and added sugars eaten by 4 to 18 year olds are above recommended levels. ' The National Diet and Nutrition Survey 2002 1 reports that 'The consumption of fizzy drinks has almost doubled in the past 15 years. ' Promotion of a healthy diet among young children is a national public health concern in the UK, since dietary factors contribute substantially to the burden of preventable illness and death, especially cardiovascular disease.…”

Does insulin therapy lead to an increased risk of cancer in type 2 diabetes mellitus?

“…For example, the National Diet and Nutritional Survey, Young People, 1997 1 states that 'Children in Britain eat on average only two portions of fruit and vegetables a day -with one in five eating no fruit at all,' and that 'The average amounts of saturated fat and added sugars eaten by 4 to 18 year olds are above recommended levels.' The National Diet and Nutrition Survey 2002 1 reports that 'The consumption of fizzy drinks has almost doubled in the past 15 years.…”

“…The pathophysiological hallmarks of type 2 diabetes mellitus are insulin resistance, pancreatic beta-cell dysfunction and increased endogenous glucose production. 1 Resistance to insulin action is a primary defect in type 2 diabetes mellitus and predates the emergence of the clinical syndrome. 1 A sub-clinical inflammatory reaction has also been shown to precede the onset of type 2 diabetes.…”

“…1 Resistance to insulin action is a primary defect in type 2 diabetes mellitus and predates the emergence of the clinical syndrome. 1 A sub-clinical inflammatory reaction has also been shown to precede the onset of type 2 diabetes. Spranger et al demonstrated that patients with a combined elevation of interleukin-6 (IL-6) and interleukin-1 beta (IL-1-β) had a roughly three-fold increased risk of developing type 2 diabetes.…”