Longitudinal Effects of Glucose-Lowering Medications on ß-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

OBJECTIVE: To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and ß-cell function. RESEARCH DESIGN AND METHODS: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting ß-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test ß-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of ß-cell function. RESULTS: HOMA2-%S increased from baseline to year 1 with glargine and remained stable thereafter, while it did not change from baseline in the other treatment groups. HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time. At year 5, CPI was similar between liraglutide and sitagliptin, and higher for both than for glargine and glimepiride [0.80, 0.87, 0.74, and 0.64 (nmol/L)/(mg/dL) * 100, respectively; P < 0.001], while the total C-peptide response was greatest with liraglutide, followed in descending order by sitagliptin, glargine, and glimepiride [1.54, 1.25, 1.02, and 0.87 (nmol/L)/(mg/dL) * 100, respectively, P < 0.001]. After adjustment for HOMA2-%S to obtain an estimate of ß-cell function, the nature of the change in ß-cell responses reflected those in ß-cell function. CONCLUSIONS: The differential long-term effects on insulin sensitivity and ß-cell function of four different glucose-lowering medications when added to metformin highlight the importance of the loss of ß-cell function in the progression of type 2 diabetes.

Discrepancy between predicted and measured exercise intensity for eliciting the maximal rate of lipid oxidation.

BACKGROUND AND AIMS: Ectopic lipid storage is implicated in type 2 diabetes pathogenesis; hence, exercise to deplete stores (i.e., at the intensity that allows for maximal rate of lipid oxidation; MLO) might be optimal for restoring metabolic health. This intensity ("Fatmax") is estimated during incremental exercise ("Fatmax test"). However, in "the field" general recommendations exist regarding a range of percentages of maximal heart rate (HR) to elicit MLO. The degree to which this range is aligned with measured Fatmax has not been investigated. We compared measured HR at Fatmax, with maximal HR percentages within the typically recommended range in a sample of 26 individuals (Female: n = 11, European ancestry: n = 17). METHODS AND RESULTS: Subjects completed a modified Fatmax test with a 5-min warmup, followed by incremental stages starting at 15 W with work rate increased by 15 W every 5 min until termination criteria were reached. Pulmonary gas exchange was recorded and average values for V˙ o2 and V˙ co2 for the final minute of each stage were used to estimate substrate-oxidation rates. We modeled lipid-oxidation kinetics using a sinusoidal model and expressed MLO relative to peak V˙ o2 and HR. Bland-Altman analysis demonstrated lack of concordance between HR at Fatmax and at 50%, 70%, and 80% of age-predicted maximum with a mean difference of 23 b·min-1. CONCLUSION: Our results indicate that estimated "fat-burning" heart rate zones are inappropriate for prescribing exercise to elicit MLO and we recommend direct individual exercise lipid oxidation measurements to elicit these values.

Whole body lipid oxidation during exercise is impaired with poor insulin sensitivity but not with obesity per se.

Equivocal findings regarding the influence of overweight/obesity on exercise lipid-oxidizing capacity (EX-LIPOX) might reflect inadequate control of 1) acute energy balance/macronutrient composition of diet; 2) intensity/duration of exercise; and/or 3) insulin sensitivity (IS) of participant. To assess independent/combined influences of IS and overweight/obesity with other factors controlled, we recruited sedentary adults with normal weight (NW; n = 15) or overweight/obesity (O; n = 15) subdivided into metabolically healthy (MH; n = 8) and unhealthy (MU; n = 7) groups (IS; MH > MU). Participants completed a 9-day, weight-stabilizing, controlled-feeding protocol comprising measurements of resting metabolism, body composition, oral glucose tolerance, and maximal exercise capacity. We measured EX-LIPOX during the initial 45 min of "steady state" during constant-work-rate cycling at 70% and 100% of participant gas-exchange threshold (GET). At 70%, average EX-LIPOX in absolute (0.11 ± 0.02 g·min-1) and relative (2.4 ± 0.3 mg·kgFFM-1·min-1) terms was lower for NW-MU than MH regardless of body composition (NW-MH, 0.19 ± 0.02 g·min-1/3.9 ± 0.3 mg·kgFFM-1·min-1; O-MH, 0.19 ± 0.02 g·min-1/3.7 ± 0.3 mg·kgFFM-1·min-1), whereas no difference was present for NW-MU and O-MU (0.15 ± 0.02 g·min-1/2.8 ± 0.3 mg·kgFFM-1·min-1). Multiple regression confirmed that with IS-controlled, overweight/obesity was not associated with decreased EX-LIPOX, whereas decreased EX-LIPOX was associated with decreased IS independent of overweight/obesity. Overweight/obesity also did not influence EX-LIPOX across MH groups or with cohort divided by body-composition classification alone (P > 0.05). Exercise lipid-oxidizing capacity is impaired with poor IS regardless of body composition, but not with overweight/obesity per se.NEW & NOTEWORTHY In this study, we have shown that the capacity to oxidize lipid during exercise is influenced by metabolic health of the exerciser regardless of body composition, but not by body composition per se. This observation refutes the belief that a reduced capacity to oxidize lipid is an obligatory characteristic of the overweight/obese condition while supporting the contention that exercise should be prescribed with specificity based on both absence/presence of overweight/obesity and compromise/lack thereof in metabolic health.

Feasibility of a progressive protocol of high-intensity interval training for overweight/obese, sedentary African American women: a retrospective analysis.

BACKGROUND: African American (AA) women have a higher prevalence of obesity and related metabolic dysfunction and lower level of physical activity compared to white counterparts. Determining feasible exercise alternatives for AA women is, therefore, paramount. Time-efficient high-intensity interval training (HIIT) might be particularly suited for AA women who cite time constraints as a frequent barrier to exercise adherence. The purpose of this study was to assess the feasibility of a 14-week progressive HIIT protocol for previously-sedentary overweight/obese AA women. METHODS: Twenty-eight healthy, premenopausal (age, 20-40 yr), sedentary, nondiabetic, overweight/obese AA women volunteered to participate in the randomized controlled clinical trial from which these data were retrospectively analysed. After assessment, participants were randomly allocated to a HIIT group (n = 14) or a no-exercise control group. The HIIT intervention consisted of 24-min sessions performed three times per week for 14 weeks during which work-interval intensity (75 to 90% of heart rate reserve; HRR) and duration (30 to 60 s) and work/recovery ratio (1:7 to 1:3) were progressed in four stages. Feasibility was assessed based on adherence (attrition rate), perceptual response (RPE) and success rate, which was calculated based on the degree to which target intensities for work intervals were achieved/maintained. RESULTS: Five of 14 participants (35%) in the HIIT group dropped out during the intervention. One-way repeated-measures ANOVA revealed a significant difference across stages for success rate (p = 0.018) with post-hoc analysis indicating a significant difference between stage 1 and the other stages and stage 4 and the other stages. There was no significant difference in RPE across stages (p = 0.057). CONCLUSION: Albeit based on a limited number of participants, we found an attrition rate that was higher than what has been reported previously for HIIT (~ 17.6%) when previously-sedentary overweight/obese AA women performed a protocol with work-interval intensity progressed from 75 to 90% HRR during a 14-week intervention. With respect to intensity, the precipitous drop for achievement of the target HR during the fourth stage (weeks 8-14) for those who did complete the protocol implies that it might be advisable to restrict work-interval intensity to < 90% HRR. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT04293367). Registered 03 March 2020 - Retrospectively registered.

Severe-intensity constant-work-rate cycling indicates that ramp incremental cycling underestimates ⩒o2max in a heterogeneous cohort of sedentary individuals.

In the absence of a ⩒o2-work-rate plateau, debate continues regarding the best way to verify that the peak ⩒o2 achieved during incremental exercise (⩒o2peak) is the "true ⩒o2max." Oft-used "secondary criteria" have been questioned in conjunction with the contention that a severe-intensity constant-work-rate "verification bout" should be considered the "gold standard." The purpose of this study was to compare the ⩒o2peak during ramp incremental cycling (RAMP-INC) by a heterogeneous (with respect to body composition and sex) cohort of sedentary individuals with the ⩒o2peak during severe-intensity constant-work-rate cycling (CWR) performed after RAMP-INC at the highest work rate achieved. A secondary purpose was to determine the degree to which traditional and newly-proposed age-dependent secondary criteria (RER, HR) identified RAMP-INC which CWR confirmed were characterized by a submaximal ⩒o2peak. Thirty-five healthy male (n = 19: 33.4 ± 6.3 yrs) and female (26.8 ± 3.6 yrs) sedentary participants performed RAMP-INC followed by CWR. The ⩒o2peak values from the two tests were correlated (r = 0.96; p < 0.01; mean CV = 24%); however, ⩒o2peak for CWR was significantly greater (29.6 ± 7.2 v. 28.6 ± 6.8 mL∙min-1∙kg-1; p < 0.01) with a mean bias of 0.98 mL∙min-1∙kg-1 (z = -2.9, p < 0.01). Both traditional and newly-proposed criterion values for RER were achieved during RAMP-INC by 33 of 35 participants (including 21 of 23 who registered a higher ⩒o2peak on CWR). The traditional HR criterion value was achieved on only seven tests (three of which were confirmed to be characterized by a submaximal ⩒o2peak) while use of less stringent newly-proposed criteria resulted in acceptance of an additional seven tests of which five were confirmed to be submaximal. Severe-intensity CWR to limit of tolerance indicates that RAMP-INC underestimates ⩒o2max in sedentary individuals and both traditional and newly-proposed secondary criteria are ineffective for identifying such tests.

Reliability and responsiveness of virtual portion size creation tasks: Influences of context, foods, and a bariatric surgical procedure.

Food portion size influences energy intake and sustained high-energy intake often leads to obesity. Virtual portion creation tasks (VPCTs), in which a participant creates portions of food on a computer screen, predict intake in healthy individuals. The objective of this study was to determine whether portions created in VPCTs are stable over time (test-retest reliability) and responsive to factors known to influence food intake, such as eating contexts and food types, and to determine if virtual portions can predict weight loss. Patients with obesity scheduled for bariatric surgery (n = 29), and individuals with a normal BMI (18.5-24.9 kg/m2, controls, n = 29), were instructed to create virtual portions of eight snack foods, which varied in energy density (low and high) and taste (sweet and salty). Portions were created in response to the following eating situations, or "contexts": What they would a) eat to stay healthy (healthy), b) typically eat (typical), c) eat to feel comfortably satisfied (satisfied), d) consider the most that they could tolerate eating (maximum), and e) eat if nothing was limiting them (desired). Tasks were completed before, and 3 months after, surgery in patients, and at two visits, 3 months apart, in controls. Body weight (kg) was recorded at both visits. Virtual portions differed significantly across groups, visits, eating contexts, energy densities (low vs. high), and tastes (sweet vs. salty). Portions created by controls did not change over time, while portions created by patients decreased significantly after surgery, for all contexts except healthy. For patients, desired and healthy portions predicted 3-month weight loss. VPCTs are replicable, responsive to foods and eating contexts, and predict surgical weight loss. These tasks could be useful for individual assessment of expectations of amounts that are eaten in health and disease and for prediction of weight loss.

No Influence of Overweight/Obesity on Exercise Lipid Oxidation: A Systematic Review.

Compared to lean counterparts, overweight/obese individuals rely less on lipid during fasting. This deficiency has been implicated in the association between overweight/obesity and blunted insulin signaling via elevated intramuscular triglycerides. However, the capacity for overweight/obese individuals to use lipid during exercise is unclear. This review was conducted to formulate a consensus regarding the influence of overweight/obesity on exercise lipid use. PubMed, ProQuest, ISI Web of Science, and Cochrane Library databases were searched. Articles were included if they presented original research on the influence of overweight/obesity on exercise fuel use in generally healthy sedentary adults. Articles were excluded if they assessed older adults, individuals with chronic disease, and/or exercise limitations or physically-active individuals. The search identified 1205 articles with 729 considered for inclusion after duplicate removal. Once titles, abstracts, and/or manuscripts were assessed, 24 articles were included. The preponderance of evidence from these articles indicates that overweight/obese individuals rely on lipid to a similar extent during exercise. However, conflicting findings were found in eight articles due to the outcome measure cited, participant characteristics other than overweight/obesity and characteristics of the exercise bout(s). We also identified factors other than body fatness which can influence exercise lipid oxidation that should be controlled in future research.

Preoperative liking and wanting for sweet beverages as predictors of body weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Patients who receive Roux-en-Y gastric bypass (RYGB) lose more weight than those who receive vertical sleeve gastrectomy (VSG). RYGB and VSG alter hedonic responses to sweet flavor, but whether baseline differences in hedonic responses modulate weight loss after RYGB or VSG remains untested. PARTICIPANTS/METHODS: Male and female candidates (n = 66) for RYGB or VSG were recruited and tested for their subjective liking and wanting ratings of sucrose solutions and flavored beverages sweetened with aspartame. Participants were classified by unsupervised hierarchical clustering for their liking and wanting ratings of sucrose and aspartame. Participant liking ratings were also used in a supervised classification using pre-established categories of liking ratings (liker, disliker, and inverted u-shape). Effects of categories obtained from unsupervised or supervised classification on body weight loss and their interaction with surgery type were analyzed separately at 3 and 12 months after surgery using linear models corrected for sex and age. RESULTS: RYGB participants lost more body weight compared with VSG participants at 3 and 12 months after surgery (P < 0.001 for both time points). Unsupervised clustering analysis identified clusters corresponding to high and low wanting or liking ratings for sucrose or aspartame. RYGB participants in high-wanting clusters based on sucrose, but not aspartame, lost more weight than VSG at both 3 (P = 0.01) and 12 months (P = 0.03), yielding a significant cluster by surgery interaction. Categories based on supervised classification using liking ratings for sucrose or aspartame showed no significant effects on body weight loss between RYGB and VSG participants. CONCLUSIONS: Classification of patients into high/low-wanting ratings for sucrose before surgery can predict differential body weight loss after RYGB or VSG in adults and could be used to advise on surgery type.

Combined effects of cholecystokinin-8 and gastric distension on food intake in humans.

In a previous study (Kissileff HR, Carretta JC, Geliebter A, Pi-Sunyer FX. Am J Physiol Regul Integr Comp Physiol 285: R992-R998, 2003), when subthreshold gastric distension (300 ml) and a low dose of cholecystokinin octapeptide (CCK-8) (112 ng/min for 21 min) were concurrently administered to human participants, intake of a test meal was significantly reduced. However, the supra-additive interaction of CCK-8 and gastric distension was not significant. The purpose of the present study was to determine whether a significant interaction would be obtained when CCK-8 and gastric distension were each increased by 50% above levels used in the previous study. Twelve normal-weight, healthy participants were tested four times each with either CCK-8 (168 ng/min for 30 min) or saline infusion crossed with gastric distension (450 ml) or no distension. The combination of CCK-8 and gastric distension reduced food intake by a mean of 405 ± 86 g (SE) in comparison with the saline nondistension condition (P < 0.001), which is a 51% reduction. Although there were some differences in the protocols, the combined effect was double that seen in the previous study. Although the interactive effect was larger [118 ± 109 g (SE)] than it was previously [73 ± 86 (SE)], it was not significant (P = 0.29). There were also reports of a short-lived sick feeling after CCK-8, with and without distension, that was not observed in the previous study. Thus the combination of CCK-8 at 1.5 times threshold and gastric distension at 450 ml (increased from 300 ml) resulted in a combined effect to reduce food intake, which was also 1.5 times its previous value, and thus appears linear.

Advancing Health Policy and Program Research in Diabetes: Findings from the Natural Experiments for Translation in Diabetes (NEXT-D) Network.

PURPOSE OF REVIEW: To advance our understanding of the impacts of policies and programs aimed at improving detection, engagement, prevention, and clinical diabetes management in the USA, we synthesized findings from a network of studies that used natural experiments to evaluate diabetes health policies and programs. FINDINGS: Studies from the Natural EXperiments for Translation in Diabetes (NEXT-D) network used rigorous longitudinal quasi-experimental study designs (e.g., interrupted time series) and analytical methods (e.g., difference-in-differences) to augment causal inference. Investigators partnered with health system stakeholders to evaluate whether glucose testing rates changed from before-to-after clinic interventions (e.g., integrating electronic screening decision prompts in New York City) or employer programs (e.g., targeted messaging and waiving copayments for at-risk employees). Other studies examined participation and behavior change in low- (e.g., wellness coaching) or high-intensity lifestyle modification programs (e.g., diabetes prevention program-like interventions) offered by payers or employers. Lastly, studies assessed how employer health insurance benefits impacted healthcare utilization, adherence, and outcomes among people with diabetes. NEXT-D demonstrated that low-intensity interventions to facilitate glucose testing and enhance engagement in lifestyle modification were associated with small improvements in weight but large improvements in screening and testing when supported by electronic health record-based decision-support. Regarding high-intensity diabetes prevention program-like lifestyle programs offered by payers or employers, enrollment was modest and led to weight loss and marginally lower short-term health expenditures. Health plans that incentivize patient behaviors were associated with increases in medication adherence. Meanwhile, shifting patients to high-deductible health plans was associated with no change in medication use and preventive screenings, but patients with diabetes delayed accessing healthcare for acute complications (e.g., cellulitis). Findings were more pronounced among lower-income patients, who experienced increased rates and acuity of emergency department visits for diabetes complications and other high-severity conditions. Findings from NEXT-D studies provide informative data that can guide programs and policies to facilitate detection, prevention, and treatment of diabetes in practice.

Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review.

OBJECTIVE: Extrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance. METHODS: Clinical, laboratory, imaging, and pathology data are presented. RESULTS: A 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5-10.5 mg/dL), albumin 3.6 g/dL (3.5-5 mg/dL), and potassium 2.8 mmol/L (3.5-5.2 mmol/L). Hypercalcemia investigation revealed intact PTH 19 pg/mL (16-87 pg/mL), 25-OH vitamin D 15.7 ng/mL (>30 ng/mL), and PTH-related peptide (PTHrP) 63.4 pmol/L (<2.3 pmol/L). Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL), renin 0.6 ng/mL/h (0.5-4 ng/mL/h), and 6:00 a.m. cortisol 82 µg/dL (6.7-22.6 µg/dL) with ACTH 147 pg/mL (no ref. range). High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement. CONCLUSION: Extensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes.

Validation of whole room indirect calorimeters: refinement of current methodologies.

Whole room indirect calorimeter (WRIC) validation techniques consist of propane combustion (PC) or infusion of mixed carbon dioxide (CO2) and nitrogen (N2) by a precision blender (PB). To determine the best method, PC of 6, 10, 22-h and PB infusions of 6, 10, and 14-h, were conducted. The 14-h infusion consisted of two metabolic settings. Energy expenditure (EE; kJ), ventilation (V; liters/min) of oxygen (VO2), VCO2, and respiratory quotient (VCO2/VO2) obtained from the WRIC were extrapolated to the respective test durations and compared to similarly calculated values. Moreover, accurate equations (AE) were derived to correct infusions for additional N2 As a final evaluation of a PC validated WRIC, weight maintenance (WM), energy balance (EB), respiratory quotient (RQ), and food quotients (FQ) were determined in 22 subjects who had repeat 24-h EE measurements. Statistical analyses (P < 0.05) were conducted (SPSS, version 23). Significant differences in RQ existed between PC and stoichiometry after 6-h. Errors for the rest of the PC tests ranged from -1.5 ± 2.4 (VCO2) to 2.8 ± 4.6% (EE). When compared with the WRIC, all uncorrected metabolic parameters for six and 10-h PB infusions were significantly different with errors from -12.8 ± 1.6 (VO2) to 6.0 ± 2.8% (RQ). The AE reduced the magnitude of errors to -12.4 ± 1.5 (RQ) to 2.2 ± 3.0% (RQ). The PB infusion with two settings showed similar performance. No differences in WM, EB, RQ, or FQ existed in the subjects. In conclusion, 10-h PC tests are sufficient for validating WRICs.

Pathway for the Management of Hyperglycemia in the Cardiac Care Unit.

Inpatient hyperglycemia has been associated with increased morbidity and mortality in critically ill patients. Optimal control of blood glucose (BG) levels using insulin infusion protocols has been shown to improve clinical outcomes. Protocols have been developed to prescribe a safe and effective rate of insulin infusion for optimal control of BG levels; however, a major obstacle in their implementation is their complexity. We have revised and updated our previously published pathway for the management of hyperglycemia, which introduces the "wheel" concept for insulin dosing. The "wheel" serves as a treatment guide. It is made up of 6 concentric circles. The core circle represents the goal of BG in critically ill patients, with inner circle showing the actual BG range of the patient. The 4 outer circles correspond to increasing rates of insulin infusion from tier 1 to tier 4. Simple guidelines are provided to facilitate conversion from insulin infusion to a subcutaneous insulin-delivery regimen in preparation for transfer from the cardiac care unit (CCU) setting. Our protocols also provide guidelines for management of diabetic ketoacidosis and hyperosmolar hyperglycemic states while at the same time creates a flowchart for activation of diabetes care team and their involvement in the multidisciplinary care of a patient in CCU with hyperglycemia and/or diabetes mellitus. This pathway provides a comprehensive and detailed, yet simple and practical algorithm for management of hyperglycemia in the CCU.

An Interrupted Time Series Analysis to Determine the Effect of an Electronic Health Record-Based Intervention on Appropriate Screening for Type 2 Diabetes in Urban Primary Care Clinics in New York City.

OBJECTIVE: To determine the impact of a health system-wide primary care diabetes management system, which included targeted guidelines for type 2 diabetes (T2DM) and prediabetes (dysglycemia) screening, on detection of previously undiagnosed dysglycemia cases. RESEARCH DESIGN AND METHODS: Intervention included electronic health record (EHR)-based decision support and standardized providers and staff training for using the American Diabetes Association guidelines for dysglycemia screening. Using EHR data, we identified 40,456 adults without T2DM or recent screening with a face-to-face visit (March 2011-December 2013) in five urban clinics. Interrupted time series analyses examined the impact of the intervention on trends in three outcomes: 1) monthly proportion of eligible patients receiving dysglycemia testing, 2) two negative comparison conditions (dysglycemia testing among ineligible patients and cholesterol screening), and 3) yield of undiagnosed dysglycemia among those tested. RESULTS: Baseline monthly proportion of eligible patients receiving testing was 7.4-10.4%. After the intervention, screening doubled (mean increase + 11.0% [95% CI 9.0, 13.0], proportion range 18.6-25.3%). The proportion of ineligible patients tested also increased (+5.0% [95% CI 3.0, 8.0]) with no concurrent change in cholesterol testing (+0% [95% CI -0.02, 0.05]). About 59% of test results in eligible patients showed dysglycemia both before and after the intervention. CONCLUSIONS: Implementation of a policy for systematic dysglycemia screening including formal training and EHR templates in urban academic primary care clinics resulted in a doubling of appropriate testing and the number of patients who could be targeted for treatment to prevent or delay T2DM.

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation.

BACKGROUND/OBJECTIVE: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. METHODS: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n=63) and 12 (n=46-48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen. RESULTS: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups. DISCUSSION: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

A New Whole Room Indirect Calorimeter for Measurement of the Energetics of Exercise.

The purpose of this study was to compare the accuracy of exercise energy expenditure (EXEE) measurements from a metabolic cart (HG_MC) to that obtained with a new exercise whole room indirect calorimeter (EX_WRIC). First, the HG_MC and the EX_WRIC were subjected to 10, 30-min ethanol (99.8% purity) and propane (99.5% purity) combustion validations, respectively, for EE, ventilation rates (liters) of oxygen (VO2), carbon dioxide (VCO2), and the respiratory quotient (RQ; VCO2/VO2). Then, 15 healthy adults (13 men and 2 women) cycled at 65% age predicted heart rate max for random determination of their EXEE, VO2, VCO2 and RQ after a 12-hr fast with both the HG-MC and EX_WRIC. Comparing stoichiometry to combustion, the HG_MC underestimated EE (P<0.05), VO2 (P<0.05), VCO2 (P<0.05), and RQ (P<0.05) while no differences were found for the EX_WRIC. The EXEE and VO2 were lower (P<0.05) while RQ was greater (P<0.05) when measured with the HG_MC versus the EX_WRIC. The EX_WRIC was more accurate than the HG_MC without the related tethered connections.

OPPORTUNISTIC SCREENING FOR DIABETES AND PREDIABETES USING HEMOGLOBIN A1C IN AN URBAN PRIMARY CARE SETTING.

OBJECTIVE: In 2010, the American Diabetes Association (ADA) endorsed hemoglobin A1c (HbA1c) as 1 of 3 tests for diabetes and prediabetes screening. We describe the use of HbA1c testing for screening during routine visits in primary care clinics of an urban health care system in the U.S. METHODS: In 2013 to 2014, retrospective analyses of deidentified electronic health records over a 2-year period, January 2010 to December 2011, for academic private practices (clinic group 1) and federally-qualified Community Health Centers (clinic group 2) identified 11,885 adults without prior diabetes or recent HbA1c testing. We estimated the proportion of patients eligible for screening according to ADA and U.S. Preventative Services Task Force (USPSTF) guidelines and calculated the potential yield of previously undiagnosed diabetes or prediabetes among those who received at least 1 HbA1c test. RESULTS: Overall, 3,316 and 5,613 patients of clinic groups 1 and 2 (75.2% of each) were eligible for screening by ADA guidelines, while only 1,764 (39.9%) of clinic group 1 and 3,799 (50.9%) of clinic group 2 were eligible by USPSTF guidelines. In those eligible by either guideline, 731 (21.4%) patients of clinic group 1 and 1,293 (21.5%) of clinic group 2 received HbA1c testing; among these, in 71 (9.7%) and 121 (9.4%) patients from clinic groups 1 and 2, respectively, HbA1c results were in the diabetes range, and in 330 (45.2%) and 733 (56.7%), results were in the prediabetes range. CONCLUSION: In urban primary care settings, appropriate HbA1c testing could result in the detection of a substantial number of previously undiagnosed diabetes and prediabetes cases needing treatment.

The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial.

BACKGROUND: Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. METHODS: HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12. RESULTS: 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09). CONCLUSIONS: Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).

Evaluation of a new whole room indirect calorimeter specific for measurement of resting metabolic rate.

BACKGROUND: The most common methods for obtaining human resting metabolic rate (RMR) use either a ventilated hood connected to a metabolic cart (VH_MC) or calculation by many prediction equations utilizing the person's height and weight. These methods may be inherently inaccurate. The objective of this study is to compare the accuracy for the measurement of RMR by three methods: a new whole room indirect calorimeter specific for this purpose (RMR_WRIC), VH_MC and calculation by the Mifflin equation (ME). First, the VH_MC (Vmax Encore 2900, Carefusion Inc, San Diego, CA) and RMR_WRIC (Promethion GA-6/FG-1, Sable Systems Intl, Las Vegas, NV) were subjected to 10, one-hour ethanol (99.8 % purity) and propane (99.5 % purity) combustion tests, respectively, for simulated metabolic measurements. Thereafter, 40 healthy adults (22 M/18 F, 78.0 ± 24.5 kg, BMI = 25.6 ± 4.8, age 36.6 ± 13.4 years) had one-hour RMR (kcal), ventilation (liters) rates of oxygen (VO2), carbon dioxide (VCO2) and RQ (VCO2/VO2) measured after a 12-h fast with both the VH_ MC and the RMR_WRIC in a randomized fashion. The resting state was documented by heart rate. The RMR was also calculated using the ME, which was compared to both the RMR_WRIC and the VH_MC. All simulated and human metabolic data were extrapolated to 24-h and analyzed (SPSS, Ver. 22). RESULTS: Comparing stoichiometry to actual combustion, the VH_MC underestimated simulated RMR (p < 0.05), VO2 (p < 0.05), VCO2 (p < 0.05) and the RQ. Similarly the RMR_WRIC underestimated simulated RMR (p < 0.05) and VO2 while overestimating VCO2 and the RQ. There was much greater variability in the simulated metabolic data between combustion and the VH_MC as compared to that of the RMR_WRIC. With regards to the volunteers, the RMR, RQ, VO2 and VCO2 determined by the VH_MC tended to be lower in comparison to these measurements determined by the RMR_WRIC. Finally, RMR calculated utilizing the ME was significantly (p < 0.05) less than the RMR_WRIC but similar to that obtained by the VH_MC. CONCLUSION: The RMR_WRIC was more accurate and precise than either the VH_MC or ME, which has implications for determining energy requirements for individuals participating in weight loss or nutrition rehabilitation programs.

The State of Evaluation Research on Food Policies to Reduce Obesity and Diabetes Among Adults in the United States, 2000-2011.

INTRODUCTION: Improvements in diet can prevent obesity and type 2 diabetes. Although policy changes provide a foundation for improvement at the population level, evidence for the effectiveness of such changes is slim. This study summarizes the literature on recent efforts in the United States to change food-related policies to prevent obesity and diabetes among adults. METHODS: We conducted a systematic review of evidence of the impact of food policies. Websites of government, academic, and nonprofit organizations were scanned to generate a typology of food-related policies, which we classified into 18 categories. A key-word search and a search of policy reports identified empirical evaluation studies of these categories. Analyses were limited to strategies with 10 or more reports. Of 422 articles identified, 94 met these criteria. Using publication date, study design, study quality, and dietary outcomes assessed, we evaluated the strength of evidence for each strategy in 3 assessment categories: time period, quality, and study design. RESULTS: Five strategies yielded 10 or more reports. Only 2 of the 5 strategies, menu labeling and taxes on unhealthy foods, had 50% or more studies with positive findings in at least 2 of 3 assessment categories. Most studies used methods that were rated medium quality. Although the number of published studies increased over 11 years, study quality did not show any clear trend nor did it vary by strategy. CONCLUSION: Researchers and policy makers can improve the quality and rigor of policy evaluations to synthesize existing evidence and develop better methods for gleaning policy guidance from the ample but imperfect data available.