Skeletal muscle mitochondrial dysfunction & diabetes.

Skeletal muscle insulin resistance is a key contributor to the pathophysiology of type 2 diabetes. Recent studies have shown that insulin resistance in a variety of conditions including type 2 diabetes, ageing and in offspring of type 2 diabetes is associated with muscle mitochondrial dysfunction. The important question is whether insulin resistance results from muscle mitochondrial dysfunction or vise versa. Gene array studies from muscle biopsy samples showed that transcript levels of several genes, especially OXPHOS genes are altered in type 2 diabetic patients during poor glycaemic control but many of these alterations are normalized by insulin treatment suggesting that reduced insulin action is a factor involved in muscle mitochondrial dysfunction. Moreover, insulin infusion while maintaining glucose and amino acid levels results in increase in muscle mitochondrial gene transcript levels and ATP production indicating that insulin is a key regulator of muscle mitochondrial biogenesis. At a similar post-absorptive insulin levels both type 2 diabetic patients and non diabetic controls have similar muscle mitochondrial ATP production but increasing insulin from low to high levels stimulate ATP production only in non diabetic people but not in the diabetic people. The lack of muscle mitochondrial response to insulin in type 2 diabetic patients is likely to be related to insulin resistance and reduced substrate utilization.

Diabetes in old age: an emerging epidemic.

Diabetes in the elderly is emerging as one of the most important public health problems of the 21st century. In developing countries, the majority of people with diabetes are in the age range of 45-64 years. A better understanding on the pathogenesis of diabetes in the aging population is required to successfully treat and prevent its devastating complications. Changes in body composition with accumulation of fat in the abdomen is a key factor in the causation of diabetes in the aging population. The size and strength of skeletal muscle, a major tissue involved in glucose metabolism, also declines leading to muscle weakness and a reduction in physical activity. These changes lead to marked reduction in energy expenditure and abdominal fat accumulation causing insulin resistance. Recent evidence suggests that four months of aerobic exercise can improve muscle oxidative capacity similarly in younger and older people, but that insulin sensitivity is less likely to improve in older people. It appears that older people need to exercise more frequently to improve their insulin sensitivity. Diagnosis and management of diabetes in the elderly requires special attention since age, genetics, body composition and lifestyle factors all interact. Increasing evidence suggests that postprandial hyperglycemia is more sensitive to diagnose diabetes in elderly people than in the young. Age related changes in body function and cognition demand special caution in the selection of hypoglycemic drugs in the elderly. Targets of diabetes therapy in the elderly have to be individualized, considering the age of the patient, remaining life-expectancy and severity of co-morbid conditions. Short acting insulin secretogogues are preferred to avoid prolonged and frequent hypoglycemia. Judicious choice of insulin sensitizers, timely introduction of insulin, meticulous control of hypertension and hyperlipidemia are critical to prevent complications.