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.

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.

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.

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).

Effect of a 1-week, eucaloric, moderately high-fat diet on peripheral insulin sensitivity in healthy premenopausal women.

OBJECTIVES: To determine whether a weight-maintaining, moderate (50%) high-fat diet is deleterious to insulin sensitivity in healthy premenopausal women. DESIGN/SETTING/PARTICIPANTS: 23 African-American and non-Hispanic white, healthy, overweight, and obese premenopausal women recruited in New York City, USA, fed either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a randomized crossover design. MAIN OUTCOME MEASURES: Peripheral insulin sensitivity and metabolic flexibility during a euglycemic hyperinsulinemic (80 mU/m(2)/min) clamp measured during the follicular phase of the menstrual cycle, at the end of each diet period. RESULTS: Peripheral insulin sensitivity (mg kg/fat-free mass/min (µU/mL)×10(-1)) was not decreased after the high-fat diet vs the low-fat diet (0.09±0.01 vs 0.08±0.01, p=0.09, respectively) in the combined group of African-American and white women, with no significant diet by race interaction (p=0.6). Metabolic flexibility (change in substrate utilization, ΔNPRQ, in response to insulin during the clamp) was similarly unaltered by the diet (0.12±0.01 vs 0.11, p=0.48, for the high-fat diet vs the low-fat diet, respectively) in the combined group of women, with no significant diet by race interaction (p=0.9). African-American women had a lower insulin clearance compared with the white women, regardless of the diet (p<0.05). CONCLUSIONS: We conclude that a short term (1 week), moderate (50%), eucaloric high-fat diet does not lower peripheral insulin sensitivity in healthy, overweight and obese premenopausal women.

High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.

Receipt of Glucose Testing and Performance of Two US Diabetes Screening Guidelines, 2007-2012.

BACKGROUND: Screening guidelines are used to help identify prediabetes and diabetes before implementing evidence-based prevention and treatment interventions. We examined screening practices benchmarking against two US guidelines, and the capacity of each guideline to identify dysglycemia. METHODS: Using 2007-2012 National Health and Nutrition Examination Surveys, we analyzed nationally-representative, cross-sectional data from 5,813 fasting non-pregnant adults aged ≥20 years without self-reported diabetes. We examined proportions of adults eligible for diagnostic glucose testing and those who self-reported receiving testing in the past three years, as recommended by the American Diabetes Association (ADA) and the US Preventive Services Task Force (USPSTF-2008) guidelines. For each screening guideline, we also assessed sensitivity, specificity, and positive (PPV) and negative predictive values in identifying dysglycemia (defined as fasting plasma glucose ≥100 mg/dl or hemoglobin A1c ≥5.7%). RESULTS: In 2007-2012, 73.0% and 23.7% of US adults without diagnosed diabetes met ADA and USPSTF-2008 criteria for screening, respectively; and 91.5% had at least one major risk factor for diabetes. Of those ADA- or USPSTF-eligible adults, about 51% reported being tested within the past three years. Eligible individuals not tested were more likely to be lower educated, poorer, uninsured, or have no usual place of care compared to tested eligible adults. Among adults with ≥1 major risk factor, 45.7% reported being tested, and dysglycemia yields (i.e., PPV) ranged from 45.8% (high-risk ethnicity) to 72.6% (self-reported prediabetes). ADA criteria and having any risk factor were more sensitive than the USPSTF-2008 guideline (88.8-97.7% vs. 31.0%) but less specific (13.5-39.7% vs. 82.1%) in recommending glucose testing, resulting in lower PPVs (47.7-54.4% vs. 58.4%). CONCLUSION: Diverging recommendations and variable performance of different guidelines may be impeding national diabetes prevention and treatment efforts. Efforts to align screening recommendations may result in earlier identification of adults at high risk for prediabetes and diabetes.

Evaluating diabetes health policies using natural experiments: the natural experiments for translation in diabetes study.

The high prevalence and costs of type 2 diabetes makes it a rapidly evolving focus of policy action. Health systems, employers, community organizations, and public agencies have increasingly looked to translate the benefits of promising research interventions into innovative policies intended to prevent or control diabetes. Though guided by research, these health policies provide no guarantee of effectiveness and may have opportunity costs or unintended consequences. Natural experiments use pragmatic and available data sources to compare specific policies to other policy alternatives or predictions of what would likely have happened in the absence of any intervention. The Natural Experiments for Translation in Diabetes (NEXT-D) Study is a network of academic, community, industry, and policy partners, collaborating to advance the methods and practice of natural experimental research, with a shared aim of identifying and prioritizing the best policies to prevent and control diabetes. This manuscript describes the NEXT-D Study group's multi-sector natural experiments in areas of diabetes prevention or control as case examples to illustrate the selection, design, analysis, and challenges inherent to natural experimental study approaches to inform development or evaluation of health policies.

Experimental sleep curtailment causes wake-dependent increases in 24-h energy expenditure as measured by whole-room indirect calorimetry.

BACKGROUND: Epidemiologic evidence has shown a link between short sleep and obesity. Clinical studies suggest a role of increased energy intake in this relation, whereas the contributions of energy expenditure (EE) and substrate utilization are less clearly defined. OBJECTIVE: Our aim was to investigate the effects of sleep curtailment on 24-h EE and respiratory quotient (RQ) by using whole-room indirect calorimetry under fixed-meal conditions. DESIGN: Ten females aged 22-43 y with a BMI (in kg/m²) of 23.4-27.5 completed a randomized, crossover study. Participants were studied under short- (4 h/night) and habitual- (8 h/night) sleep conditions for 3 d, with a 4-wk washout period between visits. Standardized weight-maintenance meals were served at 0800, 1200, and 1900 with a snack at 1600. Measures included EE and RQ during the sleep episode on day 2 and continuously over 23 h on day 3. RESULTS: Short compared with habitual sleep resulted in significantly higher (± SEM) 24-h EE (1914.0 ± 62.4 compared with 1822.1 ± 43.8 kcal; P = 0.012). EE during the scheduled sleep episode (0100-0500 and 2300-0700 in short- and habitual-sleep conditions, respectively) and across the waking episode (0800-2300) were unaffected by sleep restriction. RQ was unaffected by sleep restriction. CONCLUSIONS: Short compared with habitual sleep is associated with an increased 24-h EE of ~92 kcal (~5%)--lower than the increased energy intake observed in prior sleep-curtailment studies. This finding supports the hypothesis that short sleep may predispose to weight gain as a result of an increase in energy intake that is beyond the modest energy costs associated with prolonged nocturnal wakefulness.

Adipose tissue expression of adipose (WDTC1) gene is associated with lower fat mass and enhanced insulin sensitivity in humans.

OBJECTIVE: The overexpression of the adipose gene (adp/WDTC1) in mice inhibits lipid accumulation and improves the metabolic profile. Subcutaneous fat adp expression in humans and its relation to metabolic parameters was evaluated. DESIGN AND METHODS: Abdominal subcutaneous fat adp expression, insulin sensitivity (clamp), and respiratory quotient (RQ; indirect calorimetry) were assessed in: 36 obese and 56 BMI-, race-, and sex-matched type 2 diabetic volunteers (Look AHEAD Adipose Ancillary Study); 37 nondiabetic Pima Indians including obese (n = 18) and nonobese (n = 19) subjects and; 62 nonobese nondiabetic subjects at the Pennington Center in the ADAPT study. RESULTS: In the Look AHEAD Study, adp expression normalized for cyclophilin B was higher in males versus females (1.27 ± 0.06 vs. 1.11 ± 0.04; P < 0.01) but not after controlling for body fat. Adp expression was not influenced by the presence of diabetes but was related to body fat (r = -0.23; P = 0.03), insulin sensitivity (r = 0.23; P = 0.03) and fasting/insulin-stimulated RQ (r = 0.31 and 0.33; P < 0.01). In Pima Indians, adp expression was also higher in males versus females (1.00 ± 0.05 vs. 0.77 ± 0.05; P = 0.02) and higher in nonobese versus obese (1.02 ± 0.05 vs. 0.80 ± 0.06; P = 0.03). In the ADAPT study, there was no difference in adp expression between males and females. CONCLUSION: Consistent with animal studies, our results suggest that high adp expression in human adipose tissue is associated with lower adiposity and enhanced glucose utilization.

Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose.

AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic ß-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic ß-cell function.

The bariatric surgery patient: lost to follow-up; from morbid obesity to severe malnutrition.

OBJECTIVE: To describe the potential long-term risk of malnutrition after Roux-en-Y gastric bypass (GBP) through an uncommon occurrence of inflammatory bowel disease (IBD) postoperatively, which posed a serious threat to the nutritional status and the life of the patient. METHODS: We present a case report of a 44-year-old woman in whom Crohn disease developed 4 years after she had undergone GBP. The double insult of IBD and GBP resulted in severe malnutrition, with a serum albumin concentration of 0.9 g/dL (reference range, 3.5 to 5.0), weight loss, and watery diarrhea necessitating 6 hospital admissions during a period of 7 months. RESULTS: Ultimately, the administration of total parenteral nutrition with aggressive macronutrient, vitamin, and mineral repletion resulted in substantial improvement in the patient's strength, function, and quality of life, in parallel with diminished symptoms of IBD. CONCLUSION: Rarely, IBD develops after GBP, but the relationship between the 2 conditions remains unclear. Regardless, in addition to the altered anatomy after bariatric surgery, the further insult of IBD poses a severe threat to the nutritional status of affected patients. Malnutrition needs to be recognized and aggressively treated. Nutritional markers should be followed closely in this population of bariatric patients in an effort to avert the onset of severe malnutrition.

Body mass index and all-cause mortality in a large Chinese cohort.

BACKGROUND: Obesity is known to be associated with an increased risk of death, but current definitions of obesity are based on data from white populations. We examined the association between body mass index (BMI) and the risk of death in a large population of adult Chinese people. METHODS: We examined the association between body mass index (BMI) and all-cause mortality prospectively among 58,738 men and 65,718 women aged 20 years and older enrolled in 1998-1999 from four national health screening centres in Taiwan. We used Cox proportional hazards regression analyses to estimate the relative risks of all-cause mortality for different BMI categories during a maximum follow-up of 10 years. RESULTS: A total of 3947 participants died during the follow-up period. The lowest risk of death was observed among men and women who had a BMI of 24.0-25.9 (mean 24.9). After adjustment for age, smoking status, alcohol intake, betel-nut chewing, level of physical activity, income level and education level, we observed a U-shaped association between BMI and all-cause mortality. Similar U-shaped associations were observed when we analyzed data by age (20-64 or ≥ 65 years), smoking (never, < 10 pack-years or ≥ 10 pack-years) and presence of a pre-existing chronic disease, and after we excluded deaths that occurred in the first three years of follow-up. INTERPRETATION: BMI and all-cause mortality had a U-shaped association among adult Chinese people in our study. The lowest risk of death was among adults who had a BMI of 24.0-25.9 (mean 24.9). Our findings do not support the use of a lower cutoff value for overweight and obesity in the adult Chinese population.

Improved diabetic control in advanced heart failure patients treated with left ventricular assist devices.

AIMS: Left ventricular assist devices (LVADs) are increasingly used as therapeutic options for patients with advanced congestive heart failure (CHF), many of whom suffer from diabetes mellitus (DM). The aim of this study was to evaluate the effect of restoration of normal cardiac output using LVAD support on diabetes control in patients with advanced CHF. METHODS AND RESULTS: A retrospective chart review of all clinic patients supported with long-term LVADs between July 2008 and July 2009 at Columbia University Medical Center was performed. Patients with DM diagnosed prior to device implantation were included in this analysis. Clinical and laboratory data within 1 month preceding and 6 months following LVAD implantation were collected. Of 43 LVAD patients followed in our clinic during the study period, 15 had a diagnosis of DM. Thirteen of the 15 patients were male, mean age was 63 ± 11 years, and the pre-LVAD left ventricular ejection fraction (LVEF) was 16.5 ± 5.7%. Fasting glucose levels, HbA1c, and daily insulin requirement within 1 month before and an average of 4.0 ± 2.3 months after LVAD placement were 157.7 ± 50.6 vs. 104.1 ± 21.4 mg/dL, 7.7 ± 0.9 vs. 6.0 ± 0.8.%, and 53.3 ± 51.7 vs. 24.2 ± 27.2 IU, respectively (P < 0.05 for all comparisons). Six of the 15 patients were completely free of antidiabetic medications and had blood glucose < 126 mg/dL as well as HbA1c < 6% after LVAD. Body mass index (BMI) was slightly increased after LVAD (28.7 ± 5.3 vs. 30.2 ± 4.1 kg/m², P NS). CONCLUSION: Restoration of normal cardiac output after LVAD implantation improves diabetic control in patients with advanced CHF. Additional studies are warranted to determine the mechanisms that worsen or possibly induce DM in patients with advanced CHF.

Lifestyle, anthropometric, and obesity-related physiologic determinants of insulin-like growth factor-1 in the Third National Health and Nutrition Examination Survey (1988-1994).

PURPOSE: Epidemiologic studies suggest that insulin-like growth factor-1 (IGF-1) is associated with obesity and, more recently, cancer. This study investigates multiple lifestyle, physiologic, and anthropometric determinants of circulating IGF-1 concentrations. METHODS: Nationally representative data were used from the cross-sectional Third National Health and Nutrition Examination (NHANES III, 1988-1994) survey, which measured IGF-1 concentrations in blood, from a subsample of participants who were examined in the morning. After exclusion of persons with missing data, 6,058 men and women 20 years of age or older were included in the study. RESULTS: The mean IGF-1 concentrations were 260 ng/mL in the entire population and were higher among men as compared with women (278.8 vs. 241.3 ng/mL; p<0.0001). IGF-1 decreased with increasing age (p<0.0001), body mass index (p<0.0001), and waist circumference (p<0.0001). Individuals with metabolic syndrome had lower IGF-1 concentrations after adjustment for covariates (p=0.0008). IGF-1 was inversely associated with increasing number of metabolic syndrome abnormalities (p=0.0008). All associations were stronger among women compared with men except across concentrations of glucose. IGF-1 concentrations did not vary by any other lifestyle or physiologic factors. CONCLUSIONS: Age, adiposity, hyperglycemia, and metabolic syndrome influenced circulating IGF-1 concentrations. Diet and physical activity had no impact on IGF-1 in this nationally representative population.

Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey.

Insulin and glucose may influence cancer mortality via their proliferative and anti-apoptotic properties. Using longitudinal data from the nationally representative Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994), with an average follow-up of 8.5 years to death, we evaluated markers of glucose and insulin metabolism, with cancer mortality, ascertained using death certificates or the National Death Index. Plasma glucose, insulin, C-peptide, and lipid concentrations were measured. Anthropometrics, lifestyle, medical, and demographic information was obtained during in-person interviews. After adjusting for age, race, sex, smoking status, physical activity, and body mass index, for every 50 mg/dl increase in plasma glucose, there was a 22% increased risk of overall cancer mortality. Insulin resistance was associated with a 41% (95% confidence interval (CI) (1.07-1.87; p = 0.01) increased risk of overall cancer mortality. These associations were stronger after excluding lung cancer deaths for insulin-resistant individuals (HR: 1.67; 95% CI: 1.15-2.42; p = 0.01), specifically among those with lower levels of physical activity (HR: 2.06; 95% CI: 1.4-3.0; p = 0.0001). Similar associations were observed for other blood markers of glucose and insulin, albeit not statistically significant. In conclusion, hyperglycemia and insulin resistance may be 'high-risk' conditions for cancer mortality. Managing these conditions may be effective cancer control tools.