Dapagliflozin or Saxagliptin in Pediatric Type 2 Diabetes.

BACKGROUND: Incidence of type 2 diabetes (T2D) in children and adolescents is increasing, but treatment options are limited. METHODS: This was a 26-week, phase 3 trial with a 26-week extension among patients (10 to 17 years of age) with uncontrolled T2D (A1C 6.5 to 10.5%) receiving metformin, insulin, or both. Participants were randomly assigned 1:1:1 to 5 mg of dapagliflozin (N=81), 2.5 mg of saxagliptin (N=88), or placebo (N=76). Patients in active treatment groups with A1C ≥7% at week 12 were further randomly assigned 1:1 at week 14 to continue the dose or up-titrate to a higher dose (10 mg of dapagliflozin or 5 mg of saxagliptin). The primary end point was change in A1C at week 26. Safety was assessed over 52 weeks. RESULTS: At week 26, the difference versus placebo in adjusted mean change in A1C was −1.03 percentage points (95% confidence interval [CI], −1.57 to −0.49; P<0.001) for dapagliflozin and −0.44 percentage points (95% CI, −0.93 to 0.05; P=0.078) for saxagliptin. Adverse events (AEs) and serious AEs occurred in 72.8% and 8.6% of patients receiving dapagliflozin, 69.3% and 8.0% of patients receiving saxagliptin, and 71.1% and 6.6% of patients receiving placebo. Severe hypoglycemia occurred in 4.9%, 4.5%, and 7.9% of patients in each group, respectively. Over 52 weeks, the most common AE was headache (dapagliflozin 14.8%; placebo 5.3%). Most events were mild and none was considered serious or resulted in discontinuation. CONCLUSIONS: Dapagliflozin, but not saxagliptin, showed significant improvement in A1C compared with placebo. Nonserious headaches were more common in participants treated with dapagliflozin than in those receiving placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03199053.)

Obesity Affects Submaximal Oxygen Uptake-Heart Rate Relationship and Exercise Economy Differently in Pre- and Post-pubescent Boys and Girls.

The purpose of this study was to develop regression equations for estimating the intensity of the exercise work rate (relative peak oxygen uptake-heart rate [%VO2-HR]) and the metabolic energy expenditure (MEE) for exercise prescription and rehabilitation medicine that are specific to children. This study took into account that the specific data in terms of obesity, sex, and pubertal status are currently unavailable. Our hypothesis was that obesity would affect the submaximal exercise the oxygen uptake (VO2), heart rate (HR), and metabolic energy expenditure (MEE), and exercise economy (ExEco). In this retrospective study, the regression analysis was performed on 126 children, matching groups for Tanner pubertal status (prepubertal: 1.8±0.7; postpubertal: 4.1±0.7), BMI-for-age percentile (lean: 50±26; obese: 96±4), and sex (girls: 48%; boys: 52%). Percent peakVO2 was regressed against HR, MEE against work rate (watt), and exercise economy (ExEco, mLO2·kg lean body mass-1·min-1) against work rate. Additionally, stepwise linear regression was used to identify predictors for exercise peak work rate. Prepubertal and postpubertal boys exercise at lower work rates than obese (%peakVO2-HR slope; P=0.01). The reverse was true in girls, lean prepubertal work at lower compared lean postpubertal (%peakVO2-HR slope; P=0.03). Boys expend more calories during exercise compared to girls (MEE-slope; P=0.01), with no effect of puberty or obesity. Obese prepubertal children have poor ExEco compared to lean prepubertal children (ExEco-work rate slopes; P<0.01) but not in postpubertal children. Strong correlations (r=0.92-0.94) for %peakVO2-HR and MEE regressions for boys and girls accounted for 85-92% variation. Height, lean leg, and leg fat mass accounted for 83% of the variance for predicting peak work rate. Obesity, sex, and puberty affect exercise characteristics in children and should be considered for an individualized approach to exercise prescription in children.

Exercise management in type 1 diabetes: a consensus statement.

Type 1 diabetes is a challenging condition to manage for various physiological and behavioural reasons. Regular exercise is important, but management of different forms of physical activity is particularly difficult for both the individual with type 1 diabetes and the health-care provider. People with type 1 diabetes tend to be at least as inactive as the general population, with a large percentage of individuals not maintaining a healthy body mass nor achieving the minimum amount of moderate to vigorous aerobic activity per week. Regular exercise can improve health and wellbeing, and can help individuals to achieve their target lipid profile, body composition, and fitness and glycaemic goals. However, several additional barriers to exercise can exist for a person with diabetes, including fear of hypoglycaemia, loss of glycaemic control, and inadequate knowledge around exercise management. This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions.

Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome.

Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is a lipid mediator involved in the control of feeding, body weight and energy metabolism. OEA produced by small-intestinal enterocytes during dietary fat digestion activates type-α peroxisome proliferator-activated receptors (PPAR-α) to trigger an afferent signal that causes satiety. Emerging evidence from genetic and human laboratory studies suggests that deficits in OEA-mediated signaling might be implicated in human obesity. In the present study, we investigated whether OEA contributes to feeding dysregulation in Magel2m+/p- (Magel2 KO) mice, an animal model of PWS. Fasted/refed male Magel2 KO mice eat more than do their wild-type littermates and become overweight with age. Meal pattern analyses show that hyperphagia in Magel2 KO is due to increased meal size and meal duration rather than to lengthening of the intermeal interval, which is suggestive of a defect in mechanisms underlying satiation. Food-dependent OEA accumulation in jejunum and fasting OEA levels in plasma are significantly greater in Magel2 KO mice than in wild-type controls. Together, these findings indicate that deletion of the Magel2 gene is accompanied by marked changes in OEA signaling. Importantly, intraperitoneal administration of OEA (10mg/kg) significantly reduces food intake in fasted/refed Magel2 KO mice, pointing to a possible use of this natural compound to control hunger in PWS.

Exercise and Repeated Testing Improves Accuracy of Laser Doppler Assessment of Microvascular Function Following Shortened (1-minute) Blood Flow Occlusion.

OBJECTIVES: To determine whether stability/accuracy of post-occlusive LDF following shortened, one-minute blood flow occlusion, increases in the post-exercise state or by averaging multiple measurements. METHODS: Six healthy adults (3F) underwent LDF eight times at rest and following exercise, assessing post-occlusive (one-minute occlusion) reactive hyperemia in the cutaneous microcirculation of the forefinger. Measured variables included: pre- and post-occlusion steady-state perfusion (Plat1, Plat2), maximum post-occlusive perfusion (Max), PkT, and the ratio Max/Plat1. RESULTS: Stability/accuracy of all variables improved performing measurements after exercise (p < 0.05 Plat 1, Plat 2, Max and Max/Plat1). PkT and Max/Plat 1 displayed the greatest accuracy at rest (26.6 ± 5.1% and 26.6 ± 4.4% average difference, %Diff, of single measurements from individual "true" means, respectively); for these variables, %Diff improved to 19.5 ± 5.3 and 17.6 ± 2.1, respectively, following exercise. Overall, averaging multiple measurements performed at rest also improved stability/accuracy in all variables. This improvement was comparable to that obtained with a single measurement following exercise. CONCLUSIONS: A standardized exercise stimulus prior to testing significantly improves stability/accuracy of LDF following shortened, one-minute blood flow occlusion. Our results suggest the possibilities of broader applications of exercise to optimize measurements from a variety of skin perfusion methodologies.

Cardiopulmonary Exercise Testing in Children and Adolescents with High Body Mass Index.

Consensus has yet to be achieved on whether obesity is inexorably tied to poor fitness. We tested the hypothesis that appropriate reference of cardiopulmonary exercise testing (CPET) variables to lean body mass (LBM) would eliminate differences in fitness between high-BMI (≥ 95th percentile, n = 72, 50% female) and normal-BMI (< 85th percentile, n = 142, 49% female), otherwise-healthy children and adolescents typically seen when referencing body weight. We measured body composition with dual x-ray absorptiometry (DXA) and CPET variables from cycle ergometry using both peak values and submaximal exercise slopes (peak VO2, ΔVO2/ΔHR, ΔWR/ΔHR, ΔVO2/ΔWR, and ΔVE/ΔVCO2). In contrast to our hypothesis, referencing to LBM tended to lessen, but did not eliminate, the differences (peak VO2 [p < .004] and ΔVO2/ΔHR [p < .02]) in males and females; ΔWR/ΔHR differed between the two groups in females (p = .041) but not males (p = .1). The mean percent predicted values for all CPET variables were below 100% in the high-BMI group. The pattern of CPET abnormalities suggested a pervasive impairment of O2 delivery in the high-BMI group (ΔVO2/ΔWR was in fact highest in normal-BMI males). Tailoring lifestyle interventions to the specific fitness capabilities of each child (personalized exercise medicine) may be one of the ways to stem what has been an intractable epidemic.

Cerebral and Muscle Tissue Oxygenation During Incremental Cycling in Male Adolescents Measured by Time-Resolved Near-Infrared Spectroscopy.

Near-infrared spectroscopy has long been used to measure tissue-specific O2 dynamics in exercise, but most published data have used continuous wave devices incapable of quantifying absolute Hemoglobin (Hb) concentrations. We used time-resolved near-infrared spectroscopy to study exercising muscle (Vastus Lateralis, VL) and prefrontal cortex (PFC) Hb oxygenation in 11 young males (15.3 ± 2.1 yrs) performing incremental cycling until exhaustion (peak VO2 = 42.7 ± 6.1 ml/min/kg, mean peak power = 181 ± 38 W). Time-resolved near-infrared spectroscopy measurements of reduced scattering (µs´) and absorption (µa) at three wavelengths (759, 796, and 833 nm) were used to calculate concentrations of oxyHb ([HbO2]), deoxy Hb ([HbR]), total Hb ([THb]), and O2 saturation (stO2). In PFC, significant increases were observed in both [HbO2] and [HbR] during intense exercise. PFC stO2% remained stable until 80% of total exercise time, then dropped (-2.95%, p = .0064). In VL, stO2% decreased until peak time (-6.8%, p = .01). Segmented linear regression identified thresholds for PFC [HbO2], [HbR], VL [THb]. There was a strong correlation between timing of second ventilatory threshold and decline in PFC [HbO2] (r = .84). These findings show that time-resolved near-infrared spectroscopy can be used to study physiological threshold phenomena in children during maximal exercise, providing insight into tissue specific hemodynamics and metabolism.

CTSA Consortium Consensus Scientific Review Committee (SRC) Working Group Report on the SRC Processes.

Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided.

Effects of intravenous glucose and lipids on innate immune cell activation in healthy, obese, and type 2 diabetic subjects.

Atherosclerosis/cardiovascular disease are major causes of morbidity/mortality in obesity and type 2 diabetes (T2D), and have been associated with activation of innate immune cells, their diapedesis to the arterial intima and formation of the atherosclerotic plaque. While in obesity/T2D immune cell activation likely depends on dysregulated metabolism, the interaction between individual metabolic factors typical of these conditions (hyperglycemia, hyperlipidemia), innate immune cell activation, and the progression of atherosclerosis remains unclear. We, therefore, measured by flow cytometry cell surface expression of CD11b, CD14, CD16, CD62L, and CD66b, known markers of granulocyte (Gc) and monocyte (Mc) activation, in five healthy, five obese, and five T2D subjects, during 4-h i.v. infusions of 20% dextrose (raising blood sugar levels to ~220 mg/dL), 20% Intralipid (raising trygliceride levels to ~6 mmol/L), or a combination of the two. We hypothesized that both glucose and lipids would increase Gc/Mc surface marker expression, and simultaneous infusion would have an additive or synergistic effect. Surprisingly, though, infusion of glucose alone had little effect, while lipids, alone or combined with glucose, significantly increased expression of several markers (such as CD11b in Gc and Mc, and CD66 b in GC) within 60-90 min. Less pronounced increases in systemic inflammatory cytokines also occurred in obese and T2D subject, with no acute changes in gene expression of the the proinflammatory genes NFκB and CCR2. Our results suggest that lipids may be stronger acute contributors to innate cell activation than acute hyperglycemia per se, possibly helping shape more effective preventive dietary guidelines in T2D.

Effect of blood flow restriction on tissue oxygenation during knee extension.

PURPOSE: Time-resolved near-infrared spectroscopy was used to quantify tissue oxy- and deoxyhemoglobin concentrations ([HbO2] and [HbR]) and O2 saturation (stO2) in the oblique fibers of the vastus medialis muscle and brain prefrontal cortex during knee extension with and without blood flow restriction (BFR). METHODS: Six young healthy males performed three sets of knee extensions on a dynamometer (50% one-repetition maximum) separated by 90-s rest periods in three conditions: 1) until fatigue without BFR (fatigue), 2) until fatigue with BFR (100 mm Hg cuff constriction around thigh (BFR)), 3) same number of repetitions from condition 2 without BFR (matched). Each condition was performed on a separate visit. RESULTS: BFR was associated with higher [HbR] at the oblique fibers of the vastus medialis muscle (rest 1: 57.8 (BFR) vs 35.0 µM (matched); P < 0.0001) and a significantly lower stO2 during recovery periods between sets (7.5%-11.2 % lower than non-BFR conditions for rest 1 and 2, P < 0.0001). Using a piecewise linear spline method, a spike in [HbR] was observed before the onset of HbR clearance during recovery, causing HbR clearance to begin at a higher concentration (81 (BFR) vs 62 µM (matched), P = 0.029). [HbO2] kinetics during recovery were also affected by BFR, with longer duration (BFR, 51 s; matched, 31 s; P = 0.047) but lower rate of increase (BFR, 58 µM·min; matched, 89 µM·min; P = 0.004) during recovery. In the prefrontal cortex, BFR was associated with increased [HbR], diminished increase in [HbO2], and higher subjective exertion. CONCLUSIONS: These findings yield insight into possible physiological mechanisms of BFR and suggest a role of time-resolved near-infrared spectroscopy in monitoring and optimization of BFR exercise on an individual basis.

Exercise in pediatric type 1 diabetes.

The beneficial effects of exercise, including reduction of cardiovascular risk, are especially important in children with type 1 diabetes (T1DM), in whom incidence of lifetime cardiovascular complications remains elevated despite good glycemic control. Being able to exercise safely is therefore a paramount concern. Dysregulated metabolism in T1DM however, causes frequent occurrence of both hypo- and hyperglycemia, the former typically associated with prolonged, moderate exercise, the latter with higher intensity, if shorter, challenges. While very few absolute contraindications to exercising exist in these children, exercise should not be started with glycemia outside the 80-250 mg/dl range. Within this glycemic range, careful adjustments in insulin administration (reduction or infusion rate via insulin pumps, or overall reduction of dosage of multiple injections) should be combined with carbohydrate ingestion before/during exercise, based on prior, individual experience with specific exercise formats. Unfamiliar exercise should always be tackled with exceeding caution, based on known responses to other exercise formats. Finally, gaining a deep understanding of other complex exercise responses, such as the modulation of inflammatory status, which is a major determinant of the cardio-protective effects of exercise, can help determine which exercise formats and which individual metabolic conditions can lead to maximally beneficial health effects.

Altered insulin response to an acute bout of exercise in pediatric obesity.

Pediatric obesity typically induces insulin resistance, often later evolving into type 2 diabetes. While exercise, enhancing insulin sensitivity, is broadly used to prevent this transition, it is unknown whether alterations in the exercise insulin response pattern occur in obese children. Therefore, we measured exercise insulin responses in 57 healthy weight (NW), 20 overweight (OW), and 56 obese (Ob) children. Blood samples were drawn before and after 30 min of intermittent (2 min on, 1 min off) cycling at ~80% VO2max. In a smaller group (14 NW, 6 OW, 15 Ob), a high-fat meal was ingested 45 min preexercise. Baseline glycemia was similar and increased slightly and similarly in all groups during exercise. Basal insulin (pmol/L) was significantly higher in Ob vs. other groups; postexercise, insulin increased in NW (+7± 3) and OW (+5 ± 8), but decreased in Ob (-15±5, p < .0167 vs. NW). This insulin drop in Ob was disproportionately more pronounced in the half of Ob children with higher basal insulin (Ob-H). In all groups, high-fat feeding caused a rapid rise in insulin, promptly corrected by exercise. In Ob, however, insulin rose again 30 min postexercise. Our data indicates a distinct pattern of exercise-induced insulin modulation in pediatric obesity, possibly modulated by basal insulin concentrations.

Effect of genetic subtypes and growth hormone treatment on bone mineral density in Prader-Willi syndrome.

UNLABELLED: Abstract Background: Currently, there is limited information on the effects of growth hormone and of the different genetic subtypes on bone mineral density (BMD) in Prader-Willi syndrome (PWS). METHODS: We evaluated BMD in 79 individuals with the common subtypes of PWS (48 with deletion and 27 with UPD) and the effect of growth hormone treatment (n=46) vs. no growth hormone treatment. RESULTS: Forty-four percent of the individuals studied had whole body, hip, or spine BMD <-1 standard deviation (SD) and 10% had a BMD <-2 SD. BMD Z-scores and total BMD (g/cm2) of the spine were significantly higher in the growth hormone group. With each year of growth hormone treatment, these values increased by a factor of 0.207 and 0.011 (p=0.006 and 0.032), respectively. Individuals with uniparental disomy revealed higher spine BMD compared with deletion subclass; however, the differences were not significant. CONCLUSION: This study emphasizes the importance of evaluating bone mineralization in individuals with PWS and the beneficial effects of prolonged treatment with growth hormone. There was a trend for a higher BMD in individuals with uniparental disomy.

Dynamic interactions of gas exchange, body mass, and progressive exercise in children.

PURPOSE: Cardiopulmonary exercise testing (CPET) is increasingly used as a biomarker of fitness in children. Maximal or peak values remain the most common variables obtained in CPET, but these physiologically challenging high-intensity work rates (WR) are often not achieved. We hypothesized that interactions of gas exchange, heart rate (HR), and WR CPET variables (slopes) could yield useful mechanistic and clinical insights that might enhance the clinical utility of CPET in children. We further hypothesized that the dependence of the slope on body mass could be predicted by the first-principle analysis of body size and physiological response. METHODS: One hundred and sixty-nine healthy participants (8-18 yr old, body mass index <95th percentile, 82 females) underwent dual x-ray absorptiometry scan to estimate lean body mass (LBM) and performed a ramp-type progressive cycle ergometry exercise protocol with a breath-by-breath measurement of gas exchange. Linear regression was used to calculate the slopes among VO2, VCO2, VE, HR, and WR. RESULTS: ΔWR/ΔHR (r = 0.87) and ΔVO2/ΔHR (r = 0.96) were strongly correlated with VO2peak, whereas ΔVO2/ΔWR (r = 0.42) and ΔVE/ΔVCO2 (r = -0.51) were mildly correlated with peak values. LBM was more highly correlated with those slopes predicted to be body size dependent (P < 0.0001) compared with total body mass. CONCLUSIONS: The data largely supported our original hypotheses. Unlike peak or maximal values, which are derived from no more than a few data points at the end of a progressive exercise test, the CPET slopes were calculated from a much larger data set obtained throughout the test. An analysis of these slopes might ultimately prove useful clinically and in research studies when peak values are not achieved.

Relations between isoprene and nitric oxide in exhaled breath and the potential influence of outdoor ozone: a pilot study.

The role of endogenous isoprene in the human body, if any, is unclear because previous research is inconsistent and mechanistic evidence for the biologic function of isoprene is lacking. Given previous evidence that exhaled isoprene is elevated in systemic inflammatory states, we hypothesized that exhaled isoprene would be positively associated with a breath biomarker of airway inflammation, the fractional concentration of exhaled nitric oxide (FENO). We examined relationships of exhaled breath isoprene with FENO and with outdoor ozone given that ozone chemically reacts with isoprene and has been positively associated with FENO in past studies. Sixteen elderly subjects were followed with ≤12 weekly exhaled hydrocarbon and FENO collections at the subjects' retirement community. Outdoor ozone concentrations were measured continuously on site. Mixed-effects regression analyses tested relations of FENO with isoprene, and FENO and isoprene with ozone, adjusted for temperature. We found FENO was inversely associated with isoprene, and this was not confounded by ozone. Isoprene was inversely related to ozone. FENO was positively related to ozone and this relation was not confounded by isoprene. In contrast to hypothesized relations, we conclude that exhaled isoprene is inversely associated with FENO as well as outdoor ozone, which suggests possible protective ozone-scavenging functions of endogenous isoprene. Findings may indicate chemical reactions of isoprene oxidation by ozone and by hydroxyl radicals in the presence of O2 that is dependent on NO concentration. These preliminary results need to be confirmed in additional studies of human subjects, particularly as they apply to FENO monitoring in asthma.

Pro-HEART - a randomized clinical trial to test the effectiveness of a high protein diet targeting obese individuals with heart failure: rationale, design and baseline characteristics.

There is ample research to support the potential benefits of a high protein diet on clinical outcomes in overweight/obese, diabetic subjects. However, nutritional management of overweight/obese individuals with heart failure (HF) and type 2 diabetes mellitus (DM) or metabolic syndrome (MS) is poorly understood and few clinical guidelines related to nutritional approaches exist for this subgroup. This article describes the design, methods, and baseline characteristics of study participants enrolled in Pro-HEART, a randomized clinical trial to determine the short term and long term effects of a high protein diet (30% protein [~110 g/day], 40% carbohydrates [150 g/day], 30% fat [~50 g/day]) versus a standard protein diet (15% protein [~55 g/day], 55% carbohydrates [~200 g/day], 30% fat [~50 g/day]) on body weight and adiposity, cardiac structure and function, functional status, lipid profile, glycemic control, and quality of life. Between August, 2009 and May, 2013, 61 individuals agreed to participate in the study; 52 (85%) - mean age 58.2 ± 9.8 years; 15.4% Blacks; 57.7% Whites; 19.2% Hispanics; 7.7% Asians; 73.1% male; weight 112.0 ± 22.6 kg - were randomized to a 3-month intensive weight management program of either a high protein or standard protein diet; data were collected at baseline, 3 months, and 15 months. This study has the potential to reveal significant details about the role of macronutrients in weight management of overweight/obese individuals with HF and DM or MS.

Exercise and type 1 diabetes (T1DM).

Physical exercise is firmly incorporated in the management of type 1 diabetes (T1DM), due to multiple recognized beneficial health effects (cardiovascular disease prevention being preeminent). When glycemic values are not excessively low or high at the time of exercise, few absolute contraindications exist; practical guidelines regarding amount, type, and duration of age-appropriate exercise are regularly updated by entities such as the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes. Practical implementation of exercise regimens, however, may at times be problematic. In the poorly controlled patient, specific structural changes may occur within skeletal muscle fiber, which is considered by some to be a disease-specific myopathy. Further, even in well-controlled patients, several homeostatic mechanisms regulating carbohydrate metabolism often become impaired, causing hypo- or hyperglycemia during and/or after exercise. Some altered responses may be related to inappropriate exogenous insulin administration, but are often also partly caused by the "metabolic memory" of prior glycemic events. In this context, prior hyperglycemia correlates with increased inflammatory and oxidative stress responses, possibly modulating key exercise-associated cardio-protective pathways. Similarly, prior hypoglycemia correlates with impaired glucose counterregulation, resulting in greater likelihood of further hypoglycemia to develop. Additional exercise responses that may be altered in T1DM include growth factor release, which may be especially important in children and adolescents. These multiple alterations in the exercise response should not discourage physical activity in patients with T1DM, but rather should stimulate the quest for the identification of the exercise formats that maximize beneficial health effects.

Monitoring states of altered carbohydrate metabolism via breath analysis: are times ripe for transition from potential to reality?

PURPOSE OF REVIEW: To introduce the potential of breath analysis as a diagnostic or monitoring tool in diabetes. RECENT FINDINGS: Blood testing for plasma glucose and other metabolic variables is the base for the diagnosis and management of diabetes, whose two main types (type 1 and type 2, T1DM, T2DM) are projected to affect 450 million by 2030. As blood testing is often uncomfortable, painful, costly, and in some situations unreliable, the quest for alternative, noninvasive methods has been ongoing for decades. Breath analysis has emerged as an ideal alternative as sample collection is easy, painless, flexible, noninvasive, practical, and inexpensive. No single exhaled gas can reflect systemic glucose concentrations. Multiple gases, however, have been linked to various aspects of glucose metabolism, and integrated analysis of their simultaneous profiles during prolonged glycemic fluctuations has yielded accurate predictions of plasma values, building expectation that a clinically usable breath-based glucometer may be developed within a few years. SUMMARY: While prototypes of hand-held breath testing glucometers may still be several years away, current research shows the imminent promise of this methodology and the widening support for its development.

Fasting glucose level modulates cell surface expression of CD11b and CD66b in granulocytes and monocytes of patients with type 2 diabetes.

INTRODUCTION: Cardiovascular complications are the leading cause of mortality in type 2 diabetes (T2DM), in which onset and progression of atherosclerosis is linked to chronic inflammation. Activation status of innate immune cells (granulocytes [Gc], monocytes [Mc]), as reflected by increased CD11b, CD66b, and other surface markers, increases their endothelial and cytokines/chemokines release. Whereas this inflammatory activation seems inversely related to poor glycemic control, the effect of acute spontaneous hyperglycemia on innate immune cell activation remains unclear. METHODS: Expression of key markers (CD11b, CD14, CD16, CD62L, and CD66b) was therefore determined by flow cytometry on whole blood of healthy subjects and patients with T2DM with spontaneous fasting euglycemia or hyperglycemia both at baseline and after 30, 90, and 240 minutes of incubation at room temperature. RESULTS: Hyperglycemic patients with T2DM had significantly higher Gc and Mc CD11b and Gc CD66b surface mean fluorescence intensity compared with the euglycemic patients with T2DM whose values were similar to those of the healthy controls. CD16 expression in CD14+CD16+ Mc was elevated in all patients with T2DM, regardless of glycemic levels. CONCLUSION: Our data suggest that whereas the presence of diabetes per se may have a proinflammatory effect, hyperglycemia seems to further acutely exacerbate innate cell inflammatory status and their consequent endothelial adhesion and vascular damage potential.