Search

Bariatric surgery is the most effective treatment for obesity; however, some patients experience significant weight regain. Weight loss medications (WLM) are being increasingly used in surgery patients with limited evidence. We examine weight loss outcomes in patients using WLM after bariatric surgery. In a retrospective study, 197 bariatric surgery patients who started WLM between 2016 and 2019 at a single center were analyzed. Patients were categorized into 3 groups based on outcomes of the initial surgery: (1) Weight regainers (WR) = achieved goal weight loss after surgery (15% total body weight loss (TBWL) for sleeve gastrectomy (SG) and 25% TBWL for Roux-en-Y gastric bypass (RYGB)) with subsequent regain of > 20% of weight lost; (2) Adequate weight loss (AWL) = achieved goal weight loss without > 20% weight regain; (3) Non-responders (NR) = never achieved goal weight loss. Weight loss and medication use patterns were analyzed. Among the three categories, there was no significant difference in duration of medical therapy or %TBWL with medications. RYGB patients lost more weight than SG patients using WLM (p = 0.03). Of the medications used, patients treated with phentermine + topiramate had the highest likelihood of achieving 5%, 10%, and 15% weight loss. Compared to other 2 groups, AWL group initiated WLM earlier and experienced more weight loss when compared to their pre-operative weight or post-operative nadir. RYGB patients respond better to WLM than SG patients. Those who had started WLM before regaining weight (AWL) experienced greater overall weight loss, suggesting that proactive medical therapy at the time of weight plateau can help with greater total weight loss. Phentermine + topiramate is the most effective WLM in post-bariatric surgery patients.

Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with severe mental illnesses. Atypical or second-generation antipsychotics (SGAs) are associated with obesity and other components of metabolic syndrome, particularly abnormal glucose and lipid metabolism. This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available.Studies have identified younger, antipsychotic-naive patients with first-episode psychosis as a population vulnerable to adverse metabolic effects from SGAs. These patients gained more weight and developed evident lipid and glucose abnormalities as soon as 8-12 weeks after treatment initiation. Findings are more striking among children and adolescents. The differential effects of various SGAs are well described, with clozapine and olanzapine associated with the highest metabolic risk. In addition to behavioral therapy, emerging data suggest that pharmacological therapy, most notably metformin, is efficacious in the treatment and possibly prevention of SGA-associated metabolic derangements.More data have become available on the burden from metabolic complications associated with SGAs. New and effective treatment options are required in the near future to improve cardiovascular health in this susceptible population.

Objective The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women. Design This was a randomized, double-blind, placebo-controlled trial of menopausal women, aged 38 to 60 years, who experienced 4 to 14 hot flashes per day. After a 1-week run-in period, a total of 190 menopausal women were randomized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks. The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary. The secondary outcomes included changes in quality of life and hormonal profiles. Results A total of 147 women (77%) completed the study. It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally. At 8 weeks hot flash frequency was reduced by 43% in the 40-mg DRI group and by 41% in the 60-mg DRI group, compared with 32% in the placebo group (P = not significant vs placebo). The corresponding numbers for 12 weeks were 52%, 51%, and 39%, respectively (P = 0.07 and 0.09 vs placebo). When comparing the two treatment groups with the placebo group, there were significant reductions in mean daily hot flash frequency. The supplement (either 40 or 60 mg) reduced hot flash frequency by 43% at 8 weeks (P = 0.1) and 52% at 12 weeks (P = 0.048) but did not cause any significant changes in endogenous sex hormones or thyroid hormones. Menopausal quality of life improved in all three groups, although there were no statistically significant differences between groups. Conclusions DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes.

OBJECTIVE—Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy- and deoxyhemoglobin to predict diabetic foot ulcer healing. RESEARCH DESIGN AND METHODS—Ten type 1 diabetic patients with 21 foot ulcer sites, 13 type 1 diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values. RESULTS—Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P < 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P < 0.05) and the palm (P < 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P < 0.05 and P < 0.01, respectively). CONCLUSIONS—HT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. HT can assist in the management of foot ulceration.

Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient’s access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.

ObjectiveTo examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects.MethodsThis was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial.ResultsTreatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (−22% to 27%) during placebo treatment (P < .05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P < .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor α, C-reactive protein, adiponectin, and plasma activator inhibitor 1.ConclusionsValsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.

Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease.We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr).The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p0.0001).Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

OBJECTIVE—To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 (31P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS—We studied 12 control subjects, 9 nonneuropathic diabetic patients, and 12 neuropathic diabetic patients using 31P RARE and proton (1H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial 1H and 31P images. The average 31P concentration across the metatarsal head region was measured from the 31P images. RESULTS—The muscle area−to−total area ratio differed among all three groups (means ± SD): 0.55 ± 0.04 vs. 0.44 ± 0.05 vs. 0.06 ± 0.06 for control, nonneuropathic, and neuropathic subjects, respectively (P < 0.0001). The average 31P concentration also differed among all groups: 27.7 ± 3.8 vs. 21.7 ± 4.8 vs. 7.9 ± 8.8 mmol/l for control, nonneuropathic, and neuropathic subjects (P < 0.0001). The muscle area−to−total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = −0.83, P < 0.0001; vibration perception threshold, r = −0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = −0.87, P < 0.0001. CONCLUSIONS—Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The 31P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.

We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E–treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended.

It has been noted that elevated inflammatory markers, such as tumor necrosis factor-alpha (TNF), soluble TNF receptor II (sTNF-RII), interleukin 6 (IL-6) and C-reactive protein (CRP), are characteristically found in the serum in obese patients. In this study, we examined the correlation of these markers with BMI in nonobese, obese, and morbidly obese individuals to explore this relationship across the broad range of obesity.A total of 9 nonobese, including normal and overweight (body mass index [BMI]30 kg/m2) and 41 obese (BMIor =30 kg/m2) adults were included in this study. Among obese subjects, 11 subjects were grade I or II obese (BMIor =30 and40 kg/m2), and 30 subjects were morbidly obese (grade III obese, BMIor =40 kg/m2). Serum levels of glucose, insulin, TNF, sTNF-RII, IL-6, and CRP were measured.Obese subjects (BMIor =30 kg/m2) had significantly higher serum levels of TNF, sTNF-RII, IL-6, and CRP compared with nonobese subjects. Serum levels of sTNF-RII, IL-6, and CRP, but not TNF, were positively correlated with BMI in obese subjects. However, in morbidly obese subjects, only the serum concentrations of IL-6 and CRP remained correlated with BMI, primarily because of this relationship in men.The present results support evidence that obesity represents an inflammatory state. In morbid obesity, the correlation of only IL-6 and CRP with BMI, particularly in males, suggests that IL-6 may be secreted in an endocrine manner in proportion to the expansion of fat mass particularly in the abdominal region, with a corresponding increase in hepatic production of CRP.

OBJECTIVE—Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS—A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject’s mechanical noise threshold of perception. RESULTS—The baseline values (mean ± SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 ± 2.5, Neuropathy Disability Score (NDS) 5.0 ± 2.1, VPT 24 ± 11 V, and SWF threshold 5.6 ± 0.8 at the plantar surface of the foot and 5.3 ± 0.9 at the big toe. The VPT improved significantly from 24 ± 11 under null condition to 19 ± 10 V with mechanical noise (P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 ± 11 vs. 59 ± 15%, P < 0.02) but not at the big toe (63 ± 10 vs. 61 ± 16%, P = NS). CONCLUSIONS—Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function.

To evaluate the effect of local anesthesia on the skin vasodilation induced by the iontophoresis of sodium nitroprusside and heating.Skin vascular reactivity, in response to iontophoresis of sodium nitroprusside (SNP), was evaluated at the forearm and foot in 13 neuropathic diabetic (DN) and 11 nonneuropathic diabetic (D) patients and 9 healthy, nondiabetic subjects who served as controls (C). The direct (DI) and nerve axon reflex-related (N-V) vasodilation were measured by using two single-point laser Doppler probes. The vasodilation in response to local warming was also assessed. A topical anesthetic was applied on the contralateral forearm and foot and all the measurements were repeated.Dermal anesthesia resulted in a reduction of the direct vasodilation to SNP at the forearm [C: 58.1 +/- 16, D: 60.6 +/- 11%, and DN: 48.3 +/- 37% (postanesthesia percentage of reduction; mean +/- SEM), P0.01] and at the foot in all three groups (D: 38.5 +/- 12%, P0.01; C: 27.2 +/- 14% and DN: 11.3 +/- 17.5%, P=NS). The N-V related vasodilation was very low before and did not change after local anesthesia. The postanesthesia hyperemic response to warming was significantly reduced at low temperatures but did not change at 44 degrees C.The sodium nitroprusside-related vasodilation is reduced after local anesthesia in a similar way in healthy subjects and diabetic patients with and without neuropathy. The response to heating is also reduced at low temperatures. This indicates a stabilizing effect of local anesthesia on the smooth muscle cell.

Obesity, overweight, and a sedentary lifestyle-all common conditions in breast cancer patients-are likely to be associated with poor survival and poor quality of life in women with breast cancer. Diet-related factors are thought to account for about 30% of cancers in developed countries. Most studies of diet and healthcare have focused on the role of single nutrients, foods, or food groups in disease prevention or promotion. Recent cancer guidelines on nutrition and physical activity emphasize diets that promote maintenance of a healthy body weight and a prudent dietary pattern that is low in red and processed meats and high in a variety of vegetables, fruits, and whole grains. Except for dietary fat, few nutritional factors in adult life have been associated with breast cancer. Extensive data from animal model research, international correlations linking fat intake and breast cancer rates, and case-control studies support the hypothesis that a high-fat diet is conducive to the development of breast cancer in postmenopausal women. Conflicting findings from cohort studies, however, have created uncertainty over the role of dietary fat in breast cancer growth and recurrence. Results from large-scale nutritional intervention trials are expected to resolve such issues. As new and improved data on dietary factors and patterns accumulate, dietary guidelines for cancer risk reduction will become more focused.

Patients receiving home total parenteral nutrition (HTPN) are at risk for the development of essential fatty acid deficiency (EFAD). This study examined the essential fatty acid status of patients on long-term HTPN for gut failure. Serum phospholipid and triglyceride fatty acids were measured in 11 patients and 10 healthy volunteers. Patients had similar levels of linoleic acid (18:2w6) in serum triglyceride fatty acids but significantly lower levels of 18:2w6 in serum phospholipids compared to controls. Although there was accumulation of Mead acid (20:3w9) in both fatty acid fractions, the ratio of 20:3w9 to arachidonic acid (20:4w6) remained less than 0.2, reflecting an adequate essential fatty acid status in these patients. There were, however, substantial increases in 20:4w6 content in both triglyceride and phospholipid fractions in serum despite the lower levels of 18:2w6 in serum phospholipids, suggesting that an accelerated hepatic conversion of 18:2w6 to 20:4w6 occurs in HTPN patients, as well as the 20-carbon members of w3 (20:3w3) and w9 (20:3w9) families. The determination of optimal parenteral fat intakes should be investigated further as important priority in patients receiving long term HTPN.

This study was designed to examine circulating and urine cytokine levels in patients receiving long-term home total parenteral nutrition (TPN) support. Twelve patients who had been receiving home TPN for more than 1 year (range, 1.3-19.5 years) were enrolled for study. To avoid the potential confounding effects of intercurrent infection, patients were studied during periods of clinical stability without clinical evidence of infection. Ten normal healthy volunteers served as controls. Serum levels of albumin and C-reactive protein, temperature, body weight, and blood white cell counts were determined. The levels of soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin 6 (IL-6) were measured in serum and 24-hr urine. The results showed that the concentrations of sTNF-RII and IL-6 in 24-hr urine and serum were significantly higher in patients, indicating that long-term home TPN may be associated with a persistent low-grade inflammatory state.

In most chronic disease conditions, the systemic inflammatory response and its mediators play an essential pathogenic role. Protein calorie malnutrition, a prominent feature of end-stage renal disease (ESRD), also develops, largely as a consequence of the systemic inflammatory response. ESRD (uremia), dialysis, systemic metabolic acidosis, and infections activate the systemic inflammatory response. Elevations in C-reactive protein and depressions of serum albumin below 4 g/dL are found in more than 50% of ESRD patients undergoing dialysis. In many patients receiving dialysis, the impact of this acute-phase response on measures of iron metabolism limits the ability to diagnose iron deficiency. Furthermore, there are risks to iron administration, although data linking iron overload to risk of infection in dialysis patients is suggestive, not definitive. It seems reasonable to hypothesize that the greatest risk of iron administration is in patents who are already infected, and the greater risk would be to raise the serum iron level and transferrin saturation precipitously. The total-dose infusion method, which provides all iron required to correct deficiency in 1 dose, is more likely to produce side effects and rapidly raise serum iron levels and transferrin saturation. The use of low-dose intravenous iron supplementation (10 to 20 mg per dialysis treatment or 100 mg every second week) avoids iron overtreatment and should reduce adverse events. In ESRD patients receiving dialysis, the importance of the systemic inflammatory response in the development of protein calorie malnutrition, the impact of the acute-phase response on iron nutriture, and the response to erythropoietin therapy must be considered to achieve an understanding of the altered responses to nutritional therapy in this setting.

Total parenteral nutrition therapy can be life-saving for specific groups of patients, but is not without risks. Complications that may occur are divided into three groups: mechanical, infectious, and metabolic. While mechanical complications related to central venous catheter placement can be minimized by the skill and experience of the operator, infectious and metabolic complications, such as hyperglycemia and electrolyte abnormalities, are more likely to be decreased by careful observation and monitoring of the patient. Certain guidelines, which are presented here, should be followed to prevent such complications, while problems that may occur should be recognized and treated promptly.

While it is well known that interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) play a role in the regulation of thyroid growth and differentiated functions, the cellular and molecular mechanisms involved in mediating the effects of IFN gamma and TNF alpha on thyroid function are unknown. In the present study, we used FRTL-5 rat thyroid cells to examine the effects of IFN gamma and TNF alpha on gene expression of transcription factor interferon regulatory factor-1 (IRF-1), which is involved in mediating the effects of these cytokines in a number of cell types. Northern blot analysis of FRTL-5 mRNA showed a single IRF-1 mRNA at 2.2 Kb. In quiescent FRTL-5 cells, IRF-1 mRNA levels were low but detectable by Northern analysis. Incubation of FRTL-5 cells with IFN gamma or TNF alpha resulted in a dose- and time-dependent increase in IRF-1 mRNA levels. We have shown that TNF-alpha and IFN-gamma act synergistically to block the TSH-induced increase in type I 5'-deiodinase(5'D-I) activity and 5'D-I gene expression in FRTL-5 rat thyroid cells. Incubation of FRTL-5 cells with IFN gamma and TNF alpha in combination, however, did not synergistically increase IRF-1 mRNA levels. Electrophoretic mobility shift assay (EMSA) revealed that IFN gamma induced the formation of a single complex to a IFN gamma activation site (GAS) probe in a dose dependent manner. Several lines of evidence suggest that TNF alpha activates transcription factor nuclear factor-kappa B (NF kappa B) through activation of protein kinase C (PKC) or the hydrolysis of sphingomyelin to ceramide in a number of cell types. Here we demonstrate that hydrolysis of sphingomyelin to ceramide by sphingomyelinase (SMase), but not activation of PKC by 12-O-tetradecanoylphorbol 13-acetate (TPA), was involved in the activation of NF kappa B in FRTL-5 cells. Similarly, hydrolysis of sphingomyelin to ceramide, but not activation of PKC, resulted in an increased in IRF-1 mRNA levels in FRTL-5 cells. The present data demonstrate that IFN gamma and TNF alpha increase IRF-1 mRNA levels in FRTL-5 cells through activation of GAS and NF kappa B binding proteins, respectively. Thus, our results suggest that upregulation of IRF-1 may play a role in mediating the effects of IFN gamma and TNF alpha on thyroid function. Our results also suggest that the induction of IRF-1 mRNA by IFN gamma and TNF alpha is not the cellular mechanism involved in the synergistic effect of these cytokines on thyroid function.

This review covers the recent studies that have served to further our understanding of the nature of the relationship between perioperative hyperglycemia and nosocomial infection. On the one hand hyperglycemia can be a consequence of the systemic inflammatory response, and can serve as a marker of the severity of stress and the degree of immunocompetence resulting from infection or injury. Strong evidence is, however, emerging that hyperglycemia in the perioperative period can also be a significant risk factor for the development of nosocomial infection.

Purpose. Assess whether a convenient care clinic (CCC) medical weight-loss program can promote weight loss. Design. Prospective cohort study with follow-up at 10 weeks. Setting. A CCC (Lindora Health Clinic) weight-loss program (Lean for Life) based in a retail pharmacy (Rite Aid Pharmacy) in Costa Mesa, California. Subjects. The first 100 people to purchase the weight-loss program. Intervention. A 10-week, $465 medical weight-loss program with individual counseling sessions; a hypocaloric diet of 900 to 1200 kcal/day (25%–30% carbohydrates, 40% protein, 25% fat); and adjunctive pharmacologic treatment, if necessary. Measures. We collected data on age, height, weight, visits per week, medication use, comorbid conditions, and weight change. Analysis. Data were analyzed based on length of enrollment and mean percent weight loss. Statistical tests used were t-test and Spearman rank correlation test. Results. Eighty-six subjects had valid data entries for weight change over the 10-week period. Average age was 51.6 years; mean starting body mass index was 30.3. Thirty patients participated for 0 to 4 weeks, 30 for 4 to 9 weeks, and 26 for 10 weeks. Mean percent weight changes for the 0 to 4, 5 to 9, and 10-week groups were −1.6, −6.0, and −8.1, respectively. Forty-five (45%) of the patients achieved medically significant weight loss (≥ 5%). Conclusion. The study shows that a medical weight-loss program offered at a CCC in a retail pharmacy can produce medically significant weight loss of ≥5%. Further research of collaborations between the retail and medical weight-loss industries is warranted. Study design limitations included selection bias and confounding variables other than the weight-loss program.

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In obesity, the adipose cell releases nonesterified free fatty acids, hormones, adipocytokines, and other substances that are involved in insulin resistance. Under normal conditions, the pancreatic islet beta cells increase production of insulin sufficiently to maintain normal blood glucose concentrations despite insulin resistance. However, in genetically predisposed patients, the beta cells eventually become dysfunctional and T2DM develops. The development of T2DM can be delayed or sometimes prevented in individuals with obesity who are able to lose weight. Weight loss can be achieved medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. In this article, we summarize the evidence of obesity management in treating T2DM and prediabetes.

To describe the hormonal adaptations and alterations in anorexia nervosa.We performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.Anorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.The effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously.

The objective of the study was to examine the effect of a 6-month daily treatment with 160 mg valsartan, an angiotensin II receptor blocker, on the left ventricular systolic function and aortic elasticity of patients with type 2 diabetes mellitus (T2DM) and healthy subjects. This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen healthy control subjects and 11 patients with T2DM were enrolled in the study. Eight control subjects and 4 T2DM patients completed the study. Cardiovascular magnetic resonance was used to evaluate the effect of valsartan on the left ventricular function and aortic elasticity. At baseline, T2DM patients had increased left ventricular mass (P = .006) when compared with the healthy controls. In the T2DM patients, treatment with valsartan, in comparison with receiving placebo, resulted in a reduction of aortic radius (P = .026) and wall thickness (P = .032) of the ascending aorta. In the abdominal aorta, valsartan treatment, when compared with placebo treatment, reduced the arterial compliance (P = .014) in the T2DM patients. Valsartan treatment for 6 months decreased the diameter and wall thickness of the ascending aorta in patients with T2DM, but may decrease AC of the abdominal aorta.

The aim of this study was to determine the effect of DRIs on hot flash symptoms in menopausal women.This was a randomized, double-blind, placebo-controlled trial of menopausal women, aged 38 to 60 years, who experienced 4 to 14 hot flashes per day. After a 1-week run-in period, a total of 190 menopausal women were randomized to receive a placebo or 40 or 60 mg/day of a DRI for 12 weeks. The primary outcome was the mean changes from baseline to week 12 in the frequency of hot flashes recorded in the participant diary. The secondary outcomes included changes in quality of life and hormonal profiles.A total of 147 women (77%) completed the study. It was found that 40 and 60 mg of DRI improved hot flash frequency and severity equally. At 8 weeks hot flash frequency was reduced by 43% in the 40-mg DRI group and by 41% in the 60-mg DRI group, compared with 32% in the placebo group (P = not significant vs placebo). The corresponding numbers for 12 weeks were 52%, 51%, and 39%, respectively (P = 0.07 and 0.09 vs placebo). When comparing the two treatment groups with the placebo group, there were significant reductions in mean daily hot flash frequency. The supplement (either 40 or 60 mg) reduced hot flash frequency by 43% at 8 weeks (P = 0.1) and 52% at 12 weeks (P = 0.048) but did not cause any significant changes in endogenous sex hormones or thyroid hormones. Menopausal quality of life improved in all three groups, although there were no statistically significant differences between groups.DRI supplementation may be an effective and acceptable alternative to hormone treatment for menopausal hot flashes.

Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. Development of type 2 diabetes can be delayed or sometimes prevented from manifestation in individuals with obesity that are able to lose weight. Weight loss can be achieved either medically with behavioral therapies that combine diet and exercise treatment or with behavioral therapies combined with weight-loss medications or weight-loss surgery. There is strong evidence of an amelioration or resolution of type 2 diabetes in patients undergoing gastric bypass surgery. A recently published retrospective cohort study indicated that long-term total mortality from diabetes, heart disease, and cancer after gastric bypass surgery was substantially reduced. In this review, we summarize the evidence of surgical interventions in the treatment of type 2 diabetes.

The prevalence of obesity and overweight is rising among adults and children. Ample evidence indicates that weight loss, even if moderate, can improve health status and lessen the incidence of obesity-related disease. A variety of treatments are available to deal with the condition. However, no matter what therapy is chosen, the patient must be aware that success may depend on adherence and follow-up with a health care practitioner.

The necessity for measuring the skin blood flows occurs in many areas of physiology, pharmacology, and clinical medicine. Although the measurement of blood flow in the large blood vessels in the human body has been performed for centuries, the use of techniques to explore microcirculation have just evolved over the past 30 years. Available tests for assessing the skin microcirculation include tissue pH measurement, radioactive isotope clearance, capillary microscopy, plethysmography, transcutaneous oxygen tension, ultrasonic Doppler flowmetry, and laser Doppler flowmetry. Keywords: doppler flowmetry; doppler principle; doppler frequency; laser probe; atherosclerosis

Obesity is a chronic condition that has become prevalent worldwide. In the United States, N50% of adults are currently overweight or obese. Traditionally, overweight has been defined as a body mass index (BMI) of 25 to 29.9 kg/m and obesity as a BMI z30 kg/m. Obese individuals are at increased risk for developing a myriad of medical, psychological, and behavioral problems. Medical conditions associated with obesity include insulin resistance and type 2 diabetes mellitus (non–insulin-dependent diabetes mellitus [NIDDM]), hypertension, hyperlipidemia, cardiovascular disease, stroke, pulmonary hypertension, sleep apnea, nonalcoholic fatty liver disease, gallbladder disease, hyperuricemia and gout, osteoarthritis, and certain types of cancer. 6 The total cost of obesity in the United States is estimated at US$100 billion per year, of which approximately US$50 billion relates to direct medical costs associated with diseases attributable to obesity. Although our understanding of the etiology of obesity is still incomplete, we know that the disorder involves a complex interaction between genetic, environmental, and psychosocial factors. The genetic component of obesity is very important; however, the recent substantial increase in the prevalence of this condition is best explained by behavioral and environmental changes. The rationale for treating persons with obesity is predicated on the increased risk mortality in this population and on the abundance of evidence, suggesting that reducing weight by as little as 5% to 10% can reduce the risk of cardiovascular disease and associated comorbidities. Treatment of overweight and obesity consists of 2 principal processes: assessment and management. Assessment requires determining the degree of obesity and the absolute risk status; management involves weight loss, maintenance of lower weight, and implementation of measures to control other risk factors. Persons at increased risk for obesity-related morbidity and mortality include those with a BMI N30 kg/m, those with upper-body fat

Endothelial dysfunction often marks an early stage in the development atherosclerosis and can be observed in coronary and peripheral arterial beds (1,2). Endothelial dysfunction has been documented in patients with type 2 diabetes (3, 4, 5) and also type 1 diabetes particularly those who have microalbuminuria (6). Recent data also showed its existence in individuals at high risk for developing diabetes (7) (e.g., impaired glucose tolerance [IGT], first-degree relatives of patients with type 2 diabetes and metabolic syndrome) and in women with pervious gestational diabetes (8).

Overweight and obesity have become epidemic in the United States and worldwide (1). Data from the National Center for Health Statistics indicate that the prevalence of obesity, defined as a body mass index (BMI) of 30 kg/m2 or more, increased from 12.8%in the years from 1976 to 1980, to 22.5% in the 1988 to1994 interval, to 30% in the 1999 and 2000 interval. Approximately 31% of US adults, about 59 million people, are considered obese, and more than 64% meet the criterion for overweight (BMI ≥25 kg/m2) (2).

The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation, endothelial function, and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes. Thirty-eight subjects with type 2 diabetes (D: age, 54 ± 10 years, mean ± SD, 24 men) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance (IGT) (relatives [R]: age 46 ± 11 years, 4 men) were included. Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach) and 1% sodium nitroprusside (SNP), and ultrasound was used to measure the flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) in the brachial artery. Renal oxygenation was assessed by magnetic resonance imaging (MRI) before and during water diuresis. A decrease in the magnetic parameter R2∗ implies an increase in oxygenation. Renal medullary oxygenation did not improve with diuresis in either group (D: −0.5 ± 1.9, R: −0.4 ± 2.1, P = not significant [NS]). The renal cortical oxygenation showed a small, but statistically significant, improvement after diuresis in the 2 groups (D: −0.6 ± 1.1, R: −0.5 ± 0.5, P < .05). There were no correlations between the change in cortical R2∗ (R2∗ post-minus R2∗ prewater diuresis) and the micro- and macrovascular reactivity. The postdiuresis renal cortical R2∗ was negatively correlated with both the Ach- and SNP-induced skin vasodilation (% change over baseline)(r = −.40, P < .01 and r = − .39, P < .05, respectively), while no correlation existed with the FMD and NID. The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation (r = −.36, P < .05) and positively correlated with the fasting plasma glucose, total cholesterol, and vascular cell adhesion molecule (VCAM) concentrations (r = .34, P < .05, r = .31, P < .05 and r = .37, P < .05, respectively). These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity, glycemia, and lipidemia. Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes.

We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk, prospective, randomized, placebo-controlled, double-blind clinical trial. The flow- mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (endothelium independent) in the brachial artery and the vascular reactivity at the forearm skin were measured. FMD improved in the atorvastatin-treated, at-risk subjects [median (25-75 percentile), 7.2% (2.9-9.6%) at exit visit vs. 6.6% (2.9-9.5%) at baseline; P < 0.05]. A similar improvement of FMD was found in atorvastatin-treated diabetic patients [median (25-75 percentile), 5.6 (3.9-7.9) at exit visit vs. 4.2 (3.2-7.2) at baseline; P = 0.07]. No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group. In the at-risk group, there was a decrease in the C-reactive protein [median (25-75 percentile), 0.12 mg/dl (0.07-0.27 mg/dl) at exit visit vs. 0.24 mg/dl (0.07-0.35 mg/dl) at baseline; P < 0.05] and TNF alpha [median (25-75 percentile), 2.6 pg/ml (1.8-4.1 pg/ml) at exit visit vs. 4.4 pg/ml (3.6-6.0 pg/ml) at baseline; P < 0.05] in the atorvastatin-treated patients, whereas in the diabetes group, a decrease in endothelin-1 (mean +/- SD, 0.97 +/- 0.29 pg/ml at exit visit vs. 1.19 +/- 0.42 pg/ml at baseline; P < 0.05) and plasminogen activator inhibitor-1 [median (25-75 percentile), 18 ng/ml (9-24 ng/ml) at exit visit vs. 27 ng/ml (7-41 ng/ml) at baseline; P < 0.05] were observed. We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation.

Patients receiving home total parenteral nutrition (HTPN) are at risk for the development of essential fatty acid deficiency (EFAD). This study examined the essential fatty acid status of patients on long-term HTPN for gut failure. Serum phospholipid and triglyceride fatty acids were measured in 11 patients and 10 healthy volunteers. Patients had similar levels of linoleic acid (18:2w6) in serum triglyceride fatty acids but significantly lower levels of 18:2w6 in serum phospholipids compared to controls. Although there was accumulation of Mead acid (20:3w9) in both fatty acid fractions, the ratio of 20:3w9 to arachidonic acid (20:4w6) remained less than 0.2, reflecting an adequate essential fatty acid status in these patients. There were, however, substantial increases in 20:4w6 content in both triglyceride and phospholipid fractions in serum despite the lower levels of 18:2w6 in serum phospholipids, suggesting that an accelerated hepatic conversion of 18:2w6 to 20:4w6 occurs in HTPN patients, as well as the 20-carbon members of w3 (20:3w3) and w9 (20:3w9) families. The determination of optimal parenteral fat intakes should be investigated further as important priority in patients receiving long term HTPN.

Certain patients receiving home total parenteral nutrition (HPN) are likely to develop iron-deficiency anemia because of inadequate absorption or chronic iron loss from gastrointestinal lesions. The objective of this study was to examine the incidence and prevalence of iron deficiency anemia in patients on long-term HPN (6 months) and to investigate both the efficacy of and rate of adverse reactions to parenteral iron dextran therapy.The records of 55 patients treated with HPN for6 months between January 1, 1994 and December 31, 1999 were examined.Thirty patients (55%) had evidence of iron-deficiency anemia. Ten patients were diagnosed at the initiation of HPN, and in 20 patients, iron deficiency developed after receiving HPN. The time between initiation of HPN and development of anemia ranged from 2 to 97 months (mean 28.8+/-26.2 months). Mild iron loss from the gastrointestinal tract seemed to be the predominant reason for iron deficiency. Regular treatment with small amounts of iron in HPN appeared to be safe and efficacious, with no reported side effects. Total dose infusion of iron was associated with adverse reactions in as many as 25% of these patients, although all reactions were mild and self-limited.Iron-deficiency anemia is common in patients receiving chronic HPN. Regular small doses of iron in HPN formula, rather than total dose infusion, is the preferred treatment.

The nature of the relationship between‘critical illness hyperglycemia’ and nosocomial infection is confounded by a dearth of randomized controlled trials examining the impact of good versus poor glycemic control on infection rates. It has long been clear that hyperglycemia may be a consequence of the systemic inflammatory response syndrome (SIRS) and thereby serve as a marker of severity of stress. However, evidence is emerging that hyperglycemia early in the postoperative period can be a significant risk factor for the subsequent development of nosocomial infection. Many patients with uncontrolled hyperglycemia in the intensive care unit (ICU) have underlying diabetes mellitus, either on the basis of insulin deficiency (type 1) or insulin resistance in combination with insulin deficiency (type 2) [1]. However, catabolic illness alone may produce sufficient insulin resistance that temporary hyperglycemia (‘stress diabetes’) can develop [2]. The major risk factors for insulin resistance in critical illness are

In a recent article by Desouza et al. (1), an improvement of brachial artery flow-mediated vasodilatation, a measurement indicating endothelium-dependent vasodilation, was reported with both acute and prolonged sildenafil treatment. No measurements of endothelium-independent vasodilation were performed. As the administration of sublingual nitroglycerin is mainly used to evaluate endothelium-independent vasodilation, it is understandable that possible side effects related to the concomitant use of sildenafil and nitroglycerine were the main reason for omitting this measurement. However, we believe that although the presented data are very interesting, they …