Lucio Cabrerizo

Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis

Despite the well-documented association between insulin resistance and cardiovascular disease, the key targets of insulin relevant to the development of cardiovascular disease are not known. Here, using non-biased profiling methods, we identify the enzyme flavin-containing monooxygenase 3 (Fmo3) to be a target of insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been suggested to promote atherosclerosis in mice and humans. We show that FMO3 is suppressed by insulin in vitro, increased in obese/insulin resistant male mice and increased in obese/insulin-resistant humans. Knockdown of FMO3 in insulin-resistant mice suppresses FoxO1, a central node for metabolic control, and entirely prevents the development of hyperglycaemia, hyperlipidemia and atherosclerosis. Taken together, these data indicate that FMO3 is required for FoxO1 expression and the development of metabolic dysfunction.

Effects of Weight Loss after Bariatric Surgery for Morbid Obesity on Vascular Endothelial Growth Factor-A, Adipocytokines, and Insulin

BACKGROUND Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development. OBJECTIVES Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes. METHODS A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12 months after surgery. RESULTS Obese patients showed significantly higher VEGF-A levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty. CONCLUSION Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.

Single-anastomosis duodenoileal bypass with sleeve gastrectomy: metabolic improvement and weight loss in first 100 patients

BACKGROUND Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a simplified 1-loop duodenal switch with a 200-250 common channel. Our objective was to analyze the weight loss and metabolic results of the technique on a series of 100 consecutively operated patients at a tertiary center university hospital. METHODS A total of 100 patients consecutively underwent surgery. The criteria of inclusion were morbid obesity or metabolic disease. In the first 50 cases, the common/efferent limb measured 200 cm. The length was changed to 250 cm to reduce the hypoproteinemia rate. RESULTS No mortality and no severe complications developed. The mean excess weight loss was >95% maintained during the follow-up period. More than 90% of the patients experimented complete remission of type 2 diabetes mellitus. Two conversions to a standard duodenal switch with a longer alimentary channel were required because of recurrent hypoproteinemia. Hypertension was controlled in 98% of the patients, with a 58% remission rate. The mean number of bowel movements was 2.5/d. CONCLUSION Single-anastomosis duodenoileal bypass with sleeve gastrectomy is a simplified duodenal switch procedure that is safe and quicker to perform and offers good results for the treatment of both morbid obesity and its metabolic complications.

Parenteral Nutrition–Associated Hyperglycemia in Non–Critically Ill Inpatients Increases the Risk of In-Hospital Mortality (Multicenter Study)

OBJECTIVE Hyperglycemia may increase mortality in patients who receive total parenteral nutrition (TPN). However, this has not been well studied in noncritically ill patients (i.e., patients in the nonintensive care unit setting). The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality. RESULTS The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47–21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA1c levels. CONCLUSIONS Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality.

Single-anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) for obese diabetic patients

BACKGROUND Bariatric operations achieve a high remission rate of type 2 diabetes in patients with morbid obesity. Malabsorptive operations usually are followed by a higher rate of metabolic improvement, though complications and secondary effects of these operations are usually higher. OBJECTIVES Analyze the results of a simplified duodenal switch, the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) on patients with obesity and type 2 diabetes mellitus (T2 DM). SETTING University Hospital, Madrid, Spain. METHODS Ninety-seven T2 DM patients with a mean body mass index (BMI) of 44.3 kg/m(2) were included. Mean preoperative glycated hemoglobin was 7.6%, and mean duration of the disease was 8.5 years. Forty patients were under insulin treatment. SADI-S was completed with a sleeve gastrectomy performed over a 54 French bougie and a 200 cm common limb in 28 cases and 250 cm in 69. RESULTS Follow up was possible for 86 patients (95.5%) in the first postoperative year, 74 (92.5%) in the second, 66 (91.6%) in the third, 46 (86.7%) in the fourth and 25 out of 32 (78%) in the fifht postoperative year. Mean glycemia and glycated hemoglobin decreased immediately. Control of the disease, with HbA1c below 6%, was obtained in 70 to 84% in the long term, depending on the initial antidiabetic therapy. Most patients abandoned antidiabetic therapy after the operation. Absolute remission rate was higher for patients under oral therapy than for those under initial insulin therapy, 92.5% versus 47% in the first postoperative year, 96.4% versus 56% in the third and 75% versus 38.4% in the fifth. A short diabetes history and no need for insulin were related to a higher remission rate. Three patients had to be reoperated for recurrent hypoproteinemia. CONCLUSION SADI-S is an effective therapeutic option for obese patients with diabetes mellitus.

The Subjective Global Assessment Predicts In-Hospital Mortality Better than Other Nutrition-Related Risk Indexes in Noncritically Ill Inpatients Who Receive Total Parenteral Nutrition in Spain (Prospective Multicenter Study)

Malnutrition in hospitalized patients is associated with an increased risk of death and complications. The purpose of this study was to determine which nutrition-related risk index predicts mortality better in patients receiving total parenteral nutrition. This prospective, multicenter study involved noncritically ill patients who were prescribed total parenteral nutrition. Data were collected on Subjective Global Assessment (SGA), Nutritional Risk Index, Geriatric Nutritional Risk Index, body mass index, albumin and prealbumin, as well as in-hospital mortality, length of stay, and infectious complications. Of the 605 patients included in the study, 18.8% developed infectious complications and 9.6% died in the hospital. SGA, albumin, Nutritional Risk Index and Geriatric Nutritional Risk Index were associated with longer hospital stay. Prealbumin levels were associated with infectious complications. Multiple logistic regression analysis showed (after adjustment for age, sex, C-reactive protein levels, mean blood glucose levels, use of corticoids, prior comorbidity, carbohydrates infused, diagnosis, and infectious complications) that the SGA, Geriatric Nutritional Risk Index, body mass index, albumin, and prealbumin were associated with an increased risk for in-hospital mortality. SGA was the tool that best predicted mortality and adequately discriminated the values of the other nutrition-related risk indexes studied. The SGA is a clinically effective and simple tool for nutrition assessment in noncritically ill patients receiving total parenteral nutrition and detects the risk of inpatient mortality better than others.

C-peptide levels predict type 2 diabetes remission after bariatric surgery

BACKGROUND C-peptide (Cp) serves as a surrogate of pancreatic beta-cell reserve. This study evaluates the clinical significance of basal Cp as a predictor of type 2 diabetes (T2D) remission after bariatric surgery (BS). RESEARCH DESIGN AND METHODS Retrospective study of 22 patients with BMI > 35 kg/m² and T2D who underwent BS. Evaluation of anthropometric and glucose metabolism parameters before BS and at one-year follow-up. Analysis of patients with T2D remission (HbA1c < 6%, fasting glucose (FG) < 100 mg/dl, absence of pharmacologic treatment) and preoperative characteristics associated (logistic binary regression model). ROC curve to estimate an optimal Cp value to predict T2D remission. RESULTS Preoperativeley (mean ± SD): age 53.3 ± 9.4 years, BMI 42.9 ± 6.8 kg/m², T2D duration 6.9 ± 5.2 years, FG 159.6 ± 56.6 mg/dL, HbA1c 7.5 ± 1.1%, Cp 4.0 ± 2.0 (median 3.8, range 0.1-8.9) ng/mL. At one year follow-up, remission of T2D in 12 cases (54.5%). Preoperative Cp correlated with 12-month HbA1c (r = -0.519, p = 0.013). Preoperative Cp was higher in those who achieved remission: 5.0 ± 1.7 vs 3.0 ± 1.7 ng/ml, p = 0,013. A Cp concentration > 3.75 ng/mL provided a clinically useful cut-off for prediction of T2D remission. T2D remission rates were different according to median preoperative Cp: 27.3% if Cp < 3.8 ng/mL and 81.7% if Cp > 3.8 ng/mL (p = 0.010). CONCLUSIONS Patients with elevated preoperative Cp levels achieve higher rates of T2D remission one year after BS. A Cp concentration > 3.75 ng/mL seems clinically useful.

Mucocele of the Gastric Tube after Conversion of Vertical Banded Gastroplasty to Duodenal Switch: Not just a Radiological Image

We present two patients who underwent a duodenal switch operation after a failed vertical banded gastroplasty. Both patients had a complicated postoperative course because of an abdominal infection, and both presented the radiological image of a gastric fundus mucocele in the part of the fundus excluded between two staple-lines. Although initially considered as a radiological image with no clinical significance, the presentation of the second case with the same abdominal complication led us to contemplate the possibility of a connection between the gastric mucocele and the postoperative infection.

Family physician and endocrinologist coordination as the basis for diabetes care in clinical practice.

BackgroundTo estimate the proportion of diabetic patients (DPts) with peripheral vascular disease treated at a primary health care site after an endocrinologist-based intervention, who meet ATP III and Steno targets of metabolic control, as well as to compare the outcome with the results of the patients treated by endocrinologists.MethodsA controlled, prospective over 30-months period study was conducted in area 7 of Madrid. One hundred twenty six eligible diabetic patients diagnosed as having peripheral vascular disease between January 2003 and June 2004 were included in the study. After a treatment period of three months by the Diabetes team at St Carlos Hospital, 63 patients were randomly assigned to continue their follow up by diabetes team (Group A) and other 63 to be treated by the family physicians (FP) at primary care level with continuous diabetes team coordination (Group B). 57 DPts from Group A and 59 from Group B, completed the 30 months follow-up period. At baseline both groups were similar in age, weight, time from diagnosis and metabolic control. The main outcomes of this study were the proportion of patients meeting ATP III and Steno goals for HbA1c (%), Cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, blood pressure, albumine-to-creatinine excretion ratio (ACR), body mass index (BMI), waist circumference (WC), anti-aggregation treatment and smoking status.ResultsAt the end of the follow up, no differences were found between the groups. More than 37% of diabetic patients assigned to be treated by FP achieved a HbA1c < 6.5%, more than 50% a ACR < 30 mg/g, and more than 80% reached low risk values for cholesterol, LDL cholesterol, triglycerides, diastolic blood pressure and were anti-aggregated, and 12% remained smokers. In contrast, less than 45% achieved a systolic blood pressure < 130 mm Hg, less than 12% had a BMI < 25 Kg.m-2 (versus 23% in group A; p < 0.05) and 49%/30% (men/women) had a waist circumference of low risk.ConclusionImprovements in metabolic control among diabetic patients with peripheral vascular disease treated at a primary health care setting is possible, reaching similar results to the patients treated at a specialized level. Despite such an improvement, body weight control remains more than poor in both levels, mainly at primary care level. General practitioner and endocrinologist coordination care may be important to enhance diabetes management in primary care settings.Trial registrationClinical Trial number ISRCTN75037597

Quality Aspects of Pork Meat and Its Nutritional Impact

Pork meat production in Europe has followed a steady increase over the last decade, with about 19,000,000 tons produced in 1,999, and is expected to remain fairly stable or even experiment a small increase over the next few years. Spain constitutes the second largest producer of pig meat in the European Union. The production has risen to about 2,900,000 tons in 1,999. Pork meat is recognised as an important part of the European diet. However, consumers perception in recent years is not so good because they believe pork meat contains a high amount of visible fat with a high content in saturated fatty acids and cholesterol.