This study was performed to test the hypothesis that inflammatory cytokines are produced in skeletal muscle in response to prolonged intense exercise. Muscle biopsies and blood samples were collected from runners before, immediately after, and 2 h after a marathon race. The concentration of interleukin (IL)‐6 protein in plasma increased from 1.5 ± 0.7 to 94.4 ± 12.6 pg ml−1 immediately post‐exercise and to 22.1 ± 3.8 pg ml−1 2 h post‐exercise. IL‐1 receptor antagonist (IL‐1ra) protein in plasma increased from 123 ± 23 to 2795 ± 551 pg ml−1, and increased further to 4119 ± 527 pg ml−1 2 h post‐exercise. The comparative polymerase chain reaction technique was used to evaluate mRNA for IL‐6, IL‐1ra, IL‐1β and tumour necrosis factor (TNF)‐α in skeletal muscle and blood mononuclear cells (BMNC) (n= 8). Before exercise, mRNA for IL‐6 could not be detected either in muscle or in BMNC, and was only detectable in muscle biopsies (5 out of 8) after exercise. Increased amounts of mRNA for IL‐1ra were found in two muscle biopsies and five BMNC samples, and increased amounts of IL‐1β mRNA were found in one muscle and four BMNC samples after exercise. TNF‐α mRNA was not detected in any samples. This study suggests that exercise‐induced destruction of muscle fibres in skeletal muscles may trigger local production of IL‐6, which stimulates the production of IL‐1ra from circulating BMNC.

Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arteriofemoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-␣/␤, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade. Diabetes 53: 294 -305, 2004 I t is an established finding that aerobic endurance training increases insulin action in patients with type 2 diabetes (1-9), and also that the effect of training is predominantly located to the skeletal muscle (10). Glycemic control also improves along with training (11). Furthermore, with the increased insulin action, the need for insulin to mediate the clearance of a given amount of glucose is lessened. Thus, the need for exogenous insulin or oral hypoglycemic agents is decreased (12). Apart from the beneficial effects on glucose metabolism, physical training also exerts marked improvement on most of the components of the metabolic syndrome (13).Despite the scientific evidence of the therapeutic effect of exercise training, it is a well-known clinical experience that it is often very difficult to engage the patients into taking exercise on a regular basis, and even if one succeeds, the adherence is disappointing. The majority of patients with type 2 diabetes are overweight and have usually been sedentary for the major part of their lives. For many reasons, both psychological and sociological, they are not likely to take up endurance training. Obesity may even be a physical problem in the performance of exercise, especially endurance-type exercises.For patients with type 2 diabetes, resistance training probably represents an attractive exercise modality, but little is known about the overall effect, and the effect in muscle has not been studied. Furthermore, dose-response studies on resistance training effects have not been carried out. To provide support for the recommendations about...

AimsTo confirm, in a 26‐week extension study, the sustained efficacy and safety of a fixed combination of insulin degludec and liraglutide (IDegLira) compared with either insulin degludec or liraglutide alone, in patients with type 2 diabetes.MethodsInsulin‐naïve adults with type 2 diabetes randomized to once‐daily IDegLira, insulin degludec or liraglutide, in addition to metformin ± pioglitazone, continued their allocated treatment in this preplanned 26‐week extension of the DUAL I trial.ResultsA total of 78.8% of patients (1311/1663) continued into the extension phase. The mean glycated haemoglobin (HbA1c) concentration at 52 weeks was reduced from baseline by 1.84% (20.2 mmol/mol) for the IDegLira group, 1.40% (15.3 mmol/mol) for the insulin degludec group and 1.21% (13.2 mmol/mol) for the liraglutide group. Of the patients on IDegLira, 78% achieved an HbA1c of <7% (53 mmol/mol) versus 63% of the patients on insulin degludec and 57% of those on liraglutide. The mean fasting plasma glucose concentration at the end of the trial was similar for IDegLira (5.7 mmol/l) and insulin degludec (6.0 mmol/l), but higher for liraglutide (7.3 mmol/l). At 52 weeks, the daily insulin dose was 37% lower with IDegLira (39 units) than with insulin degludec (62 units). IDegLira was associated with a significantly greater decrease in body weight (estimated treatment difference, −2.80 kg, p < 0.0001) and a 37% lower rate of hypoglycaemia compared with insulin degludec. Overall, all treatments were well tolerated and no new adverse events or tolerability issues were observed for IDegLira.ConclusionsThese 12‐month data, derived from a 26‐week extension of the DUAL I trial, confirm the initial 26‐week main phase results and the sustainability of the benefits of IDegLira compared with its components in glycaemic efficacy, safety and tolerability.

IMPORTANCEIt is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. OBJECTIVE To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non-insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34).INTERVENTIONS All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months.MAIN OUTCOMES AND MEASURES Primary outcome was change in hemoglobin A 1c (HbA 1c ) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication. RESULTS Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA 1c , 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA 1c level changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of −0.26% [95% CI, −0.52% to −0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group.CONCLUSIONS AND RELEVANCE Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings.