Expansion of Electronic Health Record-Based Screening, Prevention, and Management of Diabetes in New York City

To address the increasing burden of diabetes in New York City, we designed 2 electronic health records (EHRs)-facilitated diabetes management systems to be implemented in 6 primary care practices on the West Side of Manhattan, a standard system and an enhanced system. The standard system includes screening for diabetes. The enhanced system includes screening and ensures close patient follow-up; it applies principles of the chronic care model, including community–clinic linkages, to the management of patients newly diagnosed with diabetes and prediabetes through screening. We will stagger implementation of the enhanced system across the 6 clinics allowing comparison, through a quasi-experimental design (pre–post difference with a control group), of patients treated in the enhanced system with similar patients treated in the standard system. The findings could inform health system practices at multiple levels and influence the integration of community resources into routine diabetes care

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 β-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 β-cell function

Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes

WSTĘP. Celem pracy było określenie związku między długotrwałą poprawą wskaźników obwodowej wrażliwości na insulinę [wskaźnik zużycia glukozy (GDR, glucose disposal rate)], stężenia glukozy na czczo i wolnych kwasów tłuszczowych (FFA, free fatty acids) a towarzyszącymi zmianami wagi, masy i dystrybucji tkanki tłuszczowej w wyniku wprowadzenia modyfikacji stylu życia u otyłych chorych na cukrzycę typu 2. MATERIAŁ I METODY. Zmierzono GDR, stężenie glukozy na czczo i FFA metodą klamry normoglikemicznej, a także masę i dystrybucję tkanki tłuszczowej, tłuszcz narządowy, rozmiar adipocytów za pomocą absorpcjometrii podwójnej energii promieniowania rentgenowskiego, tomografii komputerowej i biopsji tkanki tłuszczowej u 26 mężczyzn i 32 kobiet w próbie Look-AHEAD przed stosowaniem rocznej diety i ćwiczeń fizycznych, ukierunkowanych na utratę masy ciała, oraz po ich stosowaniu. WYNIKI. Masa ciała i stężenie glukozy na czczo znacznie się zmniejszyły (p < 0,0001), bardziej znamiennie u mężczyzn niż u kobiet (odpowiednio: -12% do -8% i -16% do -7%; p < 0,05), podczas gdy FFA zredukowano w czasie hiperinsulinemii, a GDR znamiennie wzrósł (p < 0,00001) u osób obojga płci (odpowiednio: -53% do -41% i 63% do 43%; p = NS). U mężczyzn stwierdzono korzystniejszą zmianę rozkładu tkanki tłuszczowej poprzez redukcję w większym stopniu górnych niż dolnych i głębszych niż płytszych magazynów tkanki tłuszczowej (p < 0,01). Spadki masy ciała i masy tkanki tłuszczowej poprzedzały poprawę GDR, ale nie stężenia glukozy na czczo lub FFA na czczo; jednak zmniejszenie FFA podczas hiperinsulinemii znacząco wpłynęło na polepszenie GDR. Tłuszcz wątrobowy był jedyną lokalizacją narządową, której zmiana wpływała niezależnie na zmianę wskaźników metabolicznych. WNIOSKI. U chorych na cukrzycę typu 2 poddanych rocznej zmianie stylu życia stwierdzono znaczącą poprawę GDR, stężenia glukozy na czczo, FFA i dystrybucji tkanki tłuszczowej. Natomiast najważniejszymi determinantami poprawy metabolizmu były ogólne zmiany masy ciała (masy tkanki tłuszczowej) i tłuszczu wątrobowego. (Diabet. Prakt. 2011; 11, 4: 142-152)OBJECTIVE. To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate, GDR), fasting glucose, and free fatty acids (FFA) and concomitant changes in weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS. We measured GDR, fasting glucose, and FFAs during a euglycemic clamp and adipose tissue mass and distribution, organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and after 1 year of diet and exercise aimed at weight loss. RESULTS. Weight and fasting glucose decreased significantly (p < 0.0001) and significantly more in men than in women (-12 vs. -8% and -16 vs. -7%, respectively; p < 0.05), while FFAs during hyperinsulinemia decreased and GDR increased significantly (p < 0.00001) and similarly in both sexes (-53 vs. -41% and 63 vs. 43%; p = NS). Men achieved a more favorable fat distribution by losing more from upper compared with lower and from deeper compared with superficial adipose tissue depots (p < 0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR but not in fasting glucose or fasting FFAs; however, decreases in FFAs during hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the only regional fat measure whose change contributed independently to changes in metabolic variables. CONCLUSIONS. Patients with type 2 diabetes undergoing a 1-year lifestyle intervention had significant improvements in GDR, fasting glucose, FFAs and adipose tissue distribution. However, changes in overall weight (adipose tissue mass) and hepatic fat were the most important determinants of metabolic improvements. (Diabet. Prakt. 2011; 11, 4: 142-152

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

ObjectiveExtrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises &lt;1% of prostate cancers and has been implicated in castration resistance.MethodsClinical, laboratory, imaging, and pathology data are presented.ResultsA 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 (&gt;30 ng/mL), and PTH-related peptide (PTHrP) 63.4 pmol/L (&lt;2.3 pmol/L). Workup for hypokalemia yielded aldosterone 5.3 ng/dL (&lt;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.ConclusionExtensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes

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

Energy expenditure, sex, and endogenous fuel availability in humans

Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because “normal” FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean and obese adults (25 women). Resting energy expenditure (REE), but not body composition, predicted most of the interindividual variation in FFA release. There was a significant, positive linear relationship between palmitate release and REE; however, women released approximately 40% more FFA than men relative to REE. Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women. Glucose release rates were not different in men and women whether related to REE or fat free mass. These findings indicate that nonoxidative FFA clearance is greater in women than in men. This could be an advantage at times of increased fuel needs. We conclude that “normal” adipose tissue lipolysis is different in men and women and that the fuel export role of adipose tissue in obesity will need to be reassessed

Composition of Weight Loss In Severely Obese Women: A New Look At Old Methods

Seven severely obese, outpatient dieters lost weight (mean ± SEM, 14 ± 1 kg), and the composition of weight lost was determined by six different models. Total body water (TBW), total body potassium (TBK), and body density, bone mineral content, and fat as determined by dual photon absorptiometry (DPA) were measured while subjects were weight-stable, before and after weight loss. Fat loss was calculated by three two-compartment models (2C-TBW, 2C-TBK, and hydrodensitometry [2C-HD]), one three-compartment model (HD with correction for water content of fat-free mass (FFM], 3C), and one four-compartment model (HD with correction for water and mineral content of FFM, 4C), and was measured directly by DPA. Mean composition of weight loss was similar for all models (mean weight lost as fat: 89% for DPA, 91.5% for 4C, 89% for 3C, 88.6% for 2C-HD, and 87% for 2C-TBW) except 2C-TBK (weight lost as fat, 66%). There was a much wider range of individual values for the 2C-TBW and 2C-TBK models (17% to 138% and 18% to 93%, respectively) than for the multicompartment models (63% to 112%) and DPA (76% to 107%). Almost opposite results were obtained for the same individual when using the 2C-TBK and 2C-TBW models. The discrepancy between these models was due to the inverse relationship between changes in TBW and TBK in the group as a whole (r = - .34, NS). In addition, TBK loss was found to be dependent on the initial level of hyperinsulinemia, calculated as the area under the 2-hour oral glucose tolerance curve. In conclusion, in severely obese patients, fat-loss measurements by presently available methods are not very consistent for individuals, although group averages are similar. Individual differences are due to variable changes in body fluid and potassium compartments, and multicompartment models are recommended to correct for this

Body composition and metabolic effects of a diet and exercise weight loss regimen on obese, HIV-infected women

HIV has classically been a wasting disease. However, in the United States, obesity is increasingly common among HIV-infected individuals receiving effective antiviral treatment. The risks of obesity are unclear in HIV, although the increased prevalence of diabetes and cardiovascular disease in the presence or absence of obesity causes growing concern. This study aimed to assess the effects of weight loss (through energy restriction combined with aerobic and resistance exercise) on body composition, body fat distribution, resting energy expenditure, quality of life (QOL), strength and fitness, and metabolic risk factors in obese, HIV-infected women. Eighteen HIV-infected women with a body mass index of 30 or more completed a 12-week weight loss program. Before and after the intervention, body composition and fat distribution by dual energy x-ray absorptiometry and whole-body magnetic resonance imaging, resting energy expenditure by indirect calorimetry, QOL, strength, and fitness were measured. Insulin sensitivity by intravenous glucose tolerance test and circulating cardiovascular risk factors (including lipids, tissue plasminogen activator, and plasminogen activator inhibitor 1) were measured in a subset (n = 9). Daily food intake and total body weight decreased (mean ± SD) by 3195 ± 477 kJ and 6.7 ± 4.2 kg, respectively. Weight lost was 95.5% fat by dual energy x-ray absorptiometry or 6.2 L of subcutaneous adipose tissue, 0.7 L visceral adipose tissue, and 0.8 L skeletal muscle by magnetic resonance imaging. Resting energy expenditure fell approximately 419 kJ, strength and fitness increased by 28.9% ± 18.5% and 36.8% ± 41.6%, respectively, and QOL improved in 11 of 13 dimensions. There was significant insulin resistance in the subset with metabolic measurements at baseline, and at follow-up there was no improvement in fasting glucose, insulin, or insulin sensitivity, nor was there any change in fasting lipids, tissue plasminogen activator, or plasminogen activator inhibitor 1. There was no significant change in CD4 count or HIV viral load. In conclusion, moderate weight loss achieved by a short-term program of diet and exercise in obese HIV-positive women appears safe and induces loss of adiposity in both the subcutaneous adipose tissue and visceral adipose tissue regions. Despite reduced food intake, weight and fat loss, as well as improvements in strength, fitness, and QOL, the lack of improvement in metabolic parameters suggests that additional interventions may be necessary to reduce the risk of diabetes and cardiovascular disease in this population