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.RESEARCH DESIGN AND METHODS-We analyzed fasting plasma ceramide subspecies by quantitative tandem mass spectrometry in 13 obese type 2 diabetic patients and 14 lean healthy control subjects. Results were related to insulin sensitivity measured with the hyperinsulinemic-euglycemic clamp technique and with plasma tumor necrosis factor-␣ (TNF-␣) levels, a marker of inflammation. Ceramide species (C18:1, 18:0, 20:0, 24:1, and 24:0) were quantified using electrospray ionization tandem mass spectrometry after separation with high-performance liquid chromatography.
RESULTS-Insulin sensitivity (mg ⅐ kgϪ1 ⅐ min Ϫ1 ) was lower in type 2 diabetic patients (4.90 Ϯ 0.3) versus control subjects (9.6 Ϯ 0.4) (P Ͻ 0.0001). Type 2 diabetic subjects had higher (P Ͻ 0.05) concentrations of C18:0, C20:0, C24:1, and total ceramide. Insulin sensitivity was inversely correlated with C18:0, C20:0, C24:1, C24:0, and total ceramide (all P Ͻ 0.01). Plasma TNF-␣ concentration was increased (P Ͻ 0.05) in type 2 diabetic subjects and correlated with increased C18:1 and C18:0 ceramide subspecies.CONCLUSIONS-Plasma ceramide levels are elevated in type 2 diabetic subjects and may contribute to insulin resistance through activation of inflammatory mediators, such as TNF-␣.
Context: Hyperglycemia resolves quickly after bariatric surgery, but the underlying mechanism and the most effective type of surgery remains unclear. Objective: To examine glucose metabolism and b-cell function in patients with type 2 diabetes mellitus (T2DM) after two types of bariatric intervention; Roux-en-Y gastric bypass (RYGB) and gastric restrictive (GR) surgery. Design: Prospective, nonrandomized, repeated-measures, 4-week, longitudinal clinical trial. Patients: In all, 16 T2DM patients (9 males and 7 females, 52±14 years, 47±9 kg m À2 , HbA1c 7.2±1.1%) undergoing either RYGB (N ¼ 9) or GR (N ¼ 7) surgery. Outcome measures: Glucose, insulin secretion, insulin sensitivity at baseline, and 1 and 4 weeks post-surgery, using hyperglycemic clamps and C-peptide modeling kinetics; glucose, insulin secretion and gut-peptide responses to mixed meal tolerance test (MMTT) at baseline and 4 weeks post-surgery. Results: At 1 week post-surgery, both groups experienced a similar weight loss and reduction in fasting glucose (Po0.01). However, insulin sensitivity increased only after RYGB, (Po0.05). At 4 weeks post-surgery, weight loss remained similar for both groups, but fasting glucose was normalized only after RYGB (95 ± 3 mg 100 ml À1 ). Insulin sensitivity improved after RYGB (Po0.01) and did not change with GR, whereas the disposition index remained unchanged after RYGB and increased 30% after GR (P ¼ 0.10). The MMTT elicited a robust increase in insulin secretion, glucagon-like peptide-1 (GLP-1) levels and b-cell sensitivity to glucose only after RYGB (Po0.05). Conclusion: RYGB provides a more rapid improvement in glucose regulation compared with GR. This improvement is accompanied by enhanced insulin sensitivity and b-cell responsiveness to glucose, in part because of an incretin effect.
Although lifestyle-induced weight loss improves insulin resistance in prediabetic individuals, postprandial hyperinsulinemia is reduced only when a low-GI diet is consumed. In contrast, a high-GI diet impairs pancreatic β cell and intestinal K cell function despite significant weight loss. These findings highlight the important role of the gut in mediating the effects of a low-GI diet on type 2 diabetes risk reduction.
OBJECTIVERestoration of insulin secretion is critical for the treatment of type 2 diabetes. Exercise and diet can alter glucose-induced insulin responses, but whether this is due to changes in β-cell function per se is not clear. The mechanisms by which lifestyle intervention may modify insulin secretion in type 2 diabetes have also not been examined but may involve the incretin axis.RESEARCH DESIGN AND METHODSTwenty-nine older, obese (aged 65 ± 1 years; BMI 33.6 ± 1.0 kg/m2) subjects, including individuals with newly diagnosed type 2 diabetes (obese-type 2 diabetic) and individuals with normal glucose tolerance (obese-NGT), underwent 3 months of nutritional counseling and exercise training. β-Cell function (oral glucose–induced insulin secretion corrected for insulin resistance assessed by hyperinsulinemic-euglycemic clamps) and the role of glucose-dependent insulinotropic polypeptide (GIP) were examined.RESULTSAfter exercise and diet-induced weight loss (−5.0 ± 0.7 kg), oral glucose–induced insulin secretion was increased in the obese-type 2 diabetic group and decreased in the obese-NGT group (both P < 0.05). When corrected for alterations in insulin resistance, the change in insulin secretion remained significant only in the obese-type 2 diabetic group (1.23 ± 0.26 vs. 2.04 ± 0.46 arbitrary units; P < 0.01). Changes in insulin secretion were directly related to the GIP responses to oral glucose (r = 0.64, P = 0.005), which were augmented in the obese-type 2 diabetic group and only moderately suppressed in the obese-NGT group.CONCLUSIONSAfter lifestyle-induced weight loss, improvements in oral glucose–induced insulin secretion in older, obese, nondiabetic subjects seem to be largely dependent on improved insulin sensitivity. However, in older obese diabetic patients, improved insulin secretion is a consequence of elevated β-cell function. We demonstrate for the first time that changes in insulin secretion after lifestyle intervention may be mediated via alterations in GIP secretion from intestinal K-cells.
This article summarizes presentations from a 2014 United States Department of Defense (DoD) Health Affairs Women in Combat symposium addressing physiological, musculoskeletal injury, and optimized physical training considerations from the operational physical performance section. The symposium was held to provide a state-of-the-science meeting on the U.S. DoD's rescinding of the ground combat exclusion policy opening up combat-centric occupations to women. Physiological, metabolic, body composition, bone density, cardiorespiratory fitness, and thermoregulation differences between men and women were briefly reviewed. Injury epidemiological data are presented within military training and operational environments demonstrating women to be at a higher risk for musculoskeletal injuries than men. Physical training considerations for improved muscle strength and power, occupational task performance, load carriage were also reviewed. Particular focus of this article was given to translating physiological and epidemiological findings from the literature on these topics toward actionable guidance and policy recommendations for military leaders responsible for military physical training doctrine: (1) inclusion of resistance training with special emphasis on strength and power development (i.e., activation of high-threshold motor units and recruitment of type II high-force muscle fibers), upper-body strength development, and heavy load carriage, (2) moving away from "field expediency" as the major criteria for determining military physical training policy and training implementation, (3) improvement of load carriage ability with emphasis placed on specific load carriage task performance, combined with both resistance and endurance training, and (4) providing greater equipment resources, coaching assets, and increased training time dedicated to physical readiness training.
Low-glycemic index diets and exercise independently improve glucose tolerance and reduce diabetes risk. However, the combined effect of a low-glycemic index diet and exercise on inflammation and glucose metabolism is not known. Therefore, we randomized 28 insulin-resistant adults (age: 66 ± 1 y; BMI: 34.2 ± 0.7 kg · m(-2)) to a 12-wk, low (LGI = 40) or high- (HGI = 80) glycemic index diet plus aerobic exercise (5 d · wk(-1), 60 min · d(-1), 80-85% heart rate(max)) intervention. All food and fluids were provided during the study. Inflammation was assessed from cytokine (TNFα and IL-6) secretion using peripheral blood mononuclear cells (MNC) stimulated overnight with LPS. Glycemic response was determined following ingestion of a 75-g glucose solution. Fasting blood samples were collected for additional cytokine [TNFα, IL-6, and monocyte chemoattractant protein 1 (MCP-1)] analysis. Both interventions decreased BMI (P < 0.001), fasting plasma glucose (P = 0.01), and insulin (P = 0.02). The glycemic response was reduced only in the LGI group (P = 0.04). Plasma and MNC-derived TNFα secretion were reduced in the LGI group (P = 0.02) but increased in the HGI group (P = 0.02). Secretion of IL-6 from MNC and plasma IL-6 and MCP-1 concentrations were reduced in the LGI group. The change in MNC-derived TNFα (r = 0.43; P = 0.04) and plasma MCP-1 (r = 0.44; P = 0.04) correlated with decreases in the glycemic response. These data highlight the importance of diet composition in the treatment and prevention of inflammation and hyperglycemia. A low-glycemic index diet has antiinflammatory and antidiabetogenic effects when combined with exercise in older, obese prediabetics.
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