Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance

Aim: The aetiology of the development of type 2 diabetes remains unresolved. In the present study, we assessed whether an impairment of insulin-mediated microvascular perfusion occurs early in the onset of insulin resistance. Materials and methods: Hooded Wistar rats were fed either a normal diet (ND) or a high-fat diet (HFD) for 4 weeks. Anaesthetized animals were subjected to an isoglycaemic hyperinsulinaemic clamp (3 or 10 mU/min/kg × 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2-deoxy-d-glucose (R′g), glucose appearance (Ra), glucose disappearance (Rd), femoral blood flow (FBF) and hindleg 1-methylxanthine disappearance (1-MXD, an index of microvascular perfusion). Results: Compared with ND-fed animal, HFD feeding led to a mild increase in fasting plasma glucose and plasma insulin, without an increase in total body weight. During the clamps, HFD rats showed an impairment of insulin-mediated action on GIR, hindleg glucose uptake, R′g, Ra, Rd and FBF, with a greater loss of insulin responsiveness at 3 mU/min/kg than at 10 mU/min/kg. The HFD also impaired insulin-mediated microvascular perfusion as assessed by 1-MXD. Interestingly, 1-MXD was the only measurement that remained unresponsive to the higher dose of 10 mU/min/kg insulin. Conclusions: We conclude that the early stage of insulin resistance is characterized by an impairment of the insulin-mediated microvascular responses in skeletal muscle. This is likely to cause greater whole body insulin resistance by limiting the delivery of hormones and nutrients to muscle.

Physical Education can improve insulin resistance: The LOOK randomized cluster trial

Purpose
As impaired glucose metabolism may arise progressively during childhood, we sought to determine whether the introduction of specialist-taught school physical education (PE) based on sound educational principles could improve insulin resistance (IR) in elementary school children.

Methods
In this 4-yr cluster-randomized intervention study, participants were 367 boys and 341 girls (mean age = 8.1 yr, SD = 0.35) initially in grade 2 in 29 elementary schools situated in suburbs of similar socioeconomic status. In 13 schools, 100 min·wk−1 of PE, usually conducted by general classroom teachers, was replaced with two classes per week taught by visiting specialist PE teachers; the remaining schools formed the control group. Teacher and pupil behavior were recorded, and measurements in grades 2, 4, and 6 included fasting blood glucose and insulin to calculate the homeostatic model of IR, percent body fat, physical activity, fitness, and pubertal development.

Results
On average, the intervention PE classes included more fitness work than the control PE classes (7 vs 1 min, P < 0.001) and more moderate physical activity (17 vs 10 min, P < 0.001). With no differences at baseline, by grade 6, the intervention had lowered IR by 14% (95% confidence interval = 1%–31%) in the boys and by 9% (95% confidence interval = 5%–26%) in the girls, and the percentage of children with IR greater than 3, a cutoff point for metabolic risk, was lower in the intervention than the control group (combined, 22% vs 31%, P = 0.03; boys, 12% vs 21%, P = 0.06; girls, 32% vs 40%, P = 0.05).

Conclusions
Specialist-taught primary school PE improved IR in community-based children, thereby offering a primordial preventative strategy that could be coordinated widely although a school-based approach.