OBJECTIVE—To quantitate plasma ceramide subspecies concentrations in obese subjects with type 2 diabetes and relate these plasma levels to the severity of insulin resistance. Ceramides are a putative mediator of insulin resistance and lipotoxicity, and accumulation of ceramides within tissues in obese and diabetic subjects has been well described.

Exercise is typically one of the first management strategies advised for patients newly diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an essential component of all diabetes and obesity prevention and lifestyle intervention programs. Exercise training, whether aerobic or resistance training or a combination, facilitates improved glucose regulation. High-intensity interval training is also effective and has the added benefit of being very time-efficient. While the efficacy, scalability, and affordability of exercise for the prevention and management of type 2 diabetes are well established, sustainability of exercise recommendations for patients remains elusive.

Sarcopenic obesity, or the loss of muscle mass and function associated with excess adiposity, is a largely untreatable medical condition associated with diminished quality of life and increased risk of mortality. To date, it remains somewhat paradoxical and mechanistically undefined as to why a subset of adults with obesity develop muscular decline, an anabolic stimulus generally associated with retention of lean mass. Here, we review evidence surrounding the definition, etiology, and treatment of sarcopenic obesity with an emphasis on emerging regulatory nodes with therapeutic potential. We review the available clinical evidence largely focused on diet, lifestyle, and behavioral interventions to improve quality of life in patients with sarcopenic obesity. Based upon available evidence, relieving consequences of energy burden, such as oxidative stress, myosteatosis, and/or mitochondrial dysfunction, is a promising area for therapeutic development in the treatment and management of sarcopenic obesity.

The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin sensitivity and responsiveness and 2) short-term exercise training results in improved suppression of hepatic glucose production by insulin. Fourteen obese patients with type 2 diabetes, age 64 ± 2 yr, underwent a two-stage hyperinsulinemic euglycemic clamp procedure, first stage 40 mU·m⁻²·min⁻¹insulin infusion, second stage 1,000 mU·m⁻²·min⁻¹insulin infusion, together with a [3-³H]glucose infusion, before and after 7 days of exercise. The training consisted of 30 min of cycling and 30 min of treadmill walking at ∼70% of maximal aerobic capacity daily for 7 days. The exercise program resulted in improvements in insulin action in the absence of weight loss. Glucose disposal rates during the euglycemic clamp were significantly increased at both hyperinsulinemic stages after training (40 mU: 1.84 ± 0.32 to 2.67 ± 0.37 mg·kg⁻¹·min⁻¹, P < 0.0001; 1,000 mU: 7.57 ± 0.61 to 8.84 ± 0.56 mg·kg⁻¹·min⁻¹, P = 0.008). Hepatic glucose production, both in the basal state (3.17 ± 0.43 vs. 2.54 ± 0.26 mg·kg⁻¹·min⁻¹, P = 0.05) and during the 40-mU clamp stage (1.15 ± 0.41 vs. 0.46 ± 0.20 mg·kg⁻¹·min⁻¹, P = 0.03), was significantly reduced after training. One week of vigorous exercise training can induce significant improvements in insulin action in type 2 diabetes. These improvements include increased peripheral insulin sensitivity and responsiveness as well as enhanced suppression of hepatic glucose production.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 ± 1 yr, body mass index 33.2 ± 1.4 kg/m²) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (V̇o_2max)] with either normal caloric intake (eucaloric group, 1,901 ± 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 ± 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (V̇o_2max), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups ( P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL ( r = −0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after ( r = 0.65, P = 0.0007) but not before the intervention ( r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.