Lalita Khaodhiar

Obesity and its comorbid conditions.

Obese patients are at an increased risk for developing many medical problems, including insulin resistance and type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, stroke, sleep apnea, gallbladder disease, hyperuricemia and gout, and osteoarthritis. Certain cancers are also associated with obesity, including colorectal and prostate cancer in men and endometrial, breast, and gallbladder cancer in women (1-6). Excess body weight is also associated with substantial increases in mortality from all causes, in particular, cardiovascular disease. More than 5% of the national health expenditure in the United States is directed at medical costs associated with obesity (7). In addition, certain psychologic problems, including binge-eating disorder and depression, are more common among obese persons than they are in the general population (8.9). Finally, obese individuals may suffer from social stigmatization and discrimination, and severely obese people may experience greater risk of impaired psychosocial and physical functioning, causing a negative impact on their quality of life (10).

Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity.

BACKGROUND 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. METHODS A total of 9 nonobese, including normal and overweight (body mass index [BMI] <30 kg/m2) and 41 obese (BMI > or =30 kg/m2) adults were included in this study. Among obese subjects, 11 subjects were grade I or II obese (BMI > or =30 and <40 kg/m2), and 30 subjects were morbidly obese (grade III obese, BMI > or =40 kg/m2). Serum levels of glucose, insulin, TNF, sTNF-RII, IL-6, and CRP were measured. RESULTS Obese subjects (BMI > or =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. CONCLUSIONS 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.

Metabolic syndrome with the atypical antipsychotics.

PURPOSE OF REVIEW 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. RECENT FINDINGS 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. SUMMARY 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.

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND 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. METHODS 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). FINDINGS 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 (p<0.0001). 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]; p<0.0001). INTERPRETATION 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.

Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women.

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.

Perioperative hyperglycemia, infection or risk?

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.

THE ENDOCRINOPATHIES OF ANOREXIA NERVOSA

OBJECTIVE To describe the hormonal adaptations and alterations in anorexia nervosa. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Obesity Surgery: Evidence for Diabetes Prevention/Management

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.

Diet and breast cancer.

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.

Iron deficiency anemia in patients receiving home total parenteral nutrition

BACKGROUND 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. METHODS The records of 55 patients treated with HPN for >6 months between January 1, 1994 and December 31, 1999 were examined. RESULTS 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. CONCLUSIONS 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.