Thirty-Day Morbidity and Mortality of the Laparoscopic Ileal Interposition Associated with Sleeve Gastrectomy for the Treatment of Type 2 Diabetic Patients with BMI < 35: An Analysis of 454 Consecutive Patients

Background The objective of this study was to evaluate the early results of the laparoscopic interposition of a segment of ileum associated with a sleeve gastrectomy (LII-SG) in order to treat patients with type 2 diabetes mellitus (T2DM) and BMI <35. Data regarding morbidly obese diabetic patients subjected to surgery has consistently been validated. To date, there is scarce information about morbidity and mortality related to the surgical treatment of a ""true"" typical diabetic population with BMI <35. Methods The procedures were performed in 454 patients (322 male, 132 female). Mean age was 53.6 +/- 8 years (range = 27-75). Mean BMI was 29.7 +/- 3.6 kg/m(2) (range = 19-34.8). All patients had the diagnosis of T2DM for at least 3 years. Insulin therapy was used by 45.6% of patients. Mean duration of T2DM was 10.8 +/- 5.9 years (range = 3-35). Mean hemoglobin A(1c) was 8.8 +/- 1.9%. Dyslipidemia was observed in 78.4%, hypertension in 64.8%, nephropathy in 28.6%, retinopathy in 32.6%, neuropathy in 34.6%, and coronary heart disease in 13%. Results There was no conversion to open surgery. All patients were evaluated postoperatively. Mortality was 0.4%. There were 29 major complications (6.4%) in 22 patients (4.8%) and 51 minor complications (11.2%). Reoperations were performed on 8 patients (1.7%). Twenty patients (4.4%) were readmitted to the hospital. Mean postoperative BMI was 25.8 +/- 3.5 kg/m(2). Mean fasting plasma glucose decreased from 198 +/- 69 to 128 +/- 67 mg/dl and mean postprandial plasma glucose decreased from 262 +/- 101 to 136 +/- 43 mg/dl. Conclusions The laparoscopic ileal interposition associated with a sleeve gastrectomy was considered a safe operation with low rates of morbidity and mortality in a diabetic population with BMI < 35. An early control of postprandial glycemia was observed.

Conversion to Sirolimus in Kidney-Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21.%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%). Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 +/- 0.5 vs 1.6 +/- 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 +/- 1.1.1 vs 3.1 +/- 1.3 nmol/L; P = .01.8). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion. We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.

Dietary salt restriction increases plasma lipoprotein and inflammatory marker concentrations in hypertensive patients

Background: Dietary salt restriction has been reported to adversely modify the plasma lipoprotein profile in hypertensive and in normotensive subjects. We investigated the effects of the low sodium intake (LSI) on the plasma lipoprotein profile and on inflammation and thrombosis biomarkers during the fasting and postprandial periods. Methods: Non-obese, non-treated hypertensive adults (n=41) were fed strictly controlled diets. An initial week on a control diet (CID, Na=160 mmol/day) was followed by 3 weeks on LSI (Na=60mmol/day). At admission and on the last day of each period, the 24-h ambulatory blood pressure was monitored and blood was drawn after an overnight fasting period and after a fat-rich test meal. Results: The dietary adherence was confirmed by 24-h urinary sodium excretion. Fasting triglyceride (TG), chylomicron-cholesterol, hsC-reactive protein (CRP), tumor necrosis factor-a (TNF-alpha). interleukin-6 (IL-6) concentrations, renin activity, aldosterone, insulin, and homeostasis model assessment insulin resistance (HOMA-IR) Values were higher, but non-esterified fatty acids (NEFA) were lower on LSI than on CD. For LSI, areas under the curve (AUC) of TG, chylomicron-cholesterol, apoB and the cholesterol/apoB ratio were increased, whereas AUC-NEFA was lowered. LSI did not modify body weight, hematocrit, fasting plasma cholesterol, glucose, adiponectin, leptin, fibrinogen and factor VII (FVII), and AUC of lipoprotein lipase and of lipoprotein remnants. Conclusion: LSI induced alterations in the plasma lipoproteins and in inflammatory markers that are common features of the metabolic syndrome. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

The impact of diabetes on survival among patients with first myocardial infarction

OBJECTIVE - The purpose of this paper is to estimate the impact of diabetes on survival among patients with first acute myocardial infarction, using data from the World Health Organization (WHO) Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) Project in Newcastle, New South Wales, Australia. RESEARCH DESIGN AND METHODS - The WHO MONICA Project is a community-based surveillance system that monitors coronary heart disease morbidity and mortality. All patients with suspected coronary events were observed for 28 days after the onset of symptoms. RESULTS - Of 5,322 patients with acute myocardial infarction and no previous history of ischemic heart disease (3,643 men and 1,679 women), 333 men (9%) and 224 women (13%) had a history of diabetes. The age-adjusted 28-day case fatality for women with diabetes (25%) was significantly higher than for women without diabetes (16%); relative risk 1.56 (95% CI: 1.19-2.04). The difference for men was also significant (25% with diabetes and 20% without diabetes); relative risk 1.25 (95% CI: 1.02-1.53). Age-specific case fatality increased significantly with age in both men and women without diabetes, but systematic age effects were not so apparent in patients with diabetes. Case fatality significantly decreased over the study period in patients without diabetes, but not among the diabetic patients. CONCLUSIONS - The increased risk of death in the diabetic patients remained after accounting for their poorer risk factor profiles; even if they reached the hospital alive, diabetic patients were also less likely to survive than nondiabetic patients. The relative impact of diabetes on survival is greater in women than in men.

Clinical Approaches to Preserve beta-Cell Function in Diabetes

In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.

Glycemia and prognosis of patients with chronic heart failure-Subanalysis of the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial

Background Heart failure and diabetes often occur simultaneously in patients, but the prognostic value of glycemia in chronic heart failure is debatable. We evaluated the role of glycemia on prognosis of heart failure. Methods Outpatients with chronic heart failure from the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial were grouped according to the presence of diabetes and level of glycemia. All-cause mortality/heart transplantation and unplanned hospital admission were evaluated. Results Four hundred fifty-six patients were included (135 [29.5%] female, 124 [27.2%] with diabetes mellitus, age of w50.2 +/- 11.4 years, and left-ventricle ejection fraction of 34.7% +/- 10.5%). During follow-up (3.6 +/- 2.2 years), 27 (5.9%) patients were submitted to heart transplantation and 202 (44.2%) died; survival was similar in patients with and without diabetes mellitus. When patients with and without diabetes were categorized according to glucose range (glycemia <= 100 mg/dL [5.5 mmol/L]), as well as when distributed in quintiles of glucose, the survival was significantly worse among patients with lower levels of glycemia. This finding persisted in Cox proportional hazards regression model that included gender, etiology, left ventricle ejection fraction, left ventricle diastolic diameter, creatinine level and beta-blocker therapy, and functional status (hazard ratio 1.45, 95% CI 1.09-1.69, P = .039). No difference regarding unplanned hospital admission was found. Conclusion We report on an inverse association between glycemia and mortality in outpatients with chronic heart failure. These results point to a new pathophysiologic understanding of the interactions between diabetes mellitus, hyperglycemia, and heart disease. (Am Heart J 2010; 159: 90-7.)

Metabolic syndrome determinants in an urban population from Brazil: Social class and gender-specific interaction

Introduction: The metabolic syndrome (MS) is characterized by multiple cardiovascular risk factors such as central obesity, arterial hypertension, dislipidemia and hyperinsulinemia and is associated with a higher incidence of cardiovascular events and mortality. The aim of the present work is to describe the prevalence of MS in an urban population from a highly admixed developing country and to characterize the different correlations between this diagnosis, cardiovascular risk factors and demographic variables distributed in this population. Materials and methods: A cross-sectional study of risk factors for cardiovascular diseases was performed in the urban population of Vitoria, Brazil (n= 1507). Major cardiovascular risk factors such as smoking habits, alcohol intake, amount of physical activity, diabetes and hypertension were inquired. Blood biochemical assays were performed by standard techniques in 12 h fasting blood sample and Metabolic Syndrome (MS) was characterizes following the ATP III criteria. Results: The analysis of 1507 individuals showed a 25.43% general prevalence of MS without any significant difference between sexes, but a clear relation of the prevalence with progressing age (p=<0.0001). Even though both sexes showed similar prevalence rates, distribution of risk factors that defined MS was different between men and women, with the prevalence of hypertension, fasting hyperglycemia and hypertriglyceridemia being higher in men. Race was not an important risk factor for MS in this population as opposed to social economic class that was highly associated with the risk of MS in women as their social class was lower, but not in men. Conclusion: This cross-sectional study from a large urban population in Brazil showed a high general prevalence of MS (25.4%), which is increased as the population becomes older (especially in women) and poorer. Although prevalence was very similar in both genders, the frequency of components defining the syndrome varied greatly amongst them. In particular, a significant interaction between gender and social class was observed and may shed light in our understanding of the complex interplay between demographic and biological risk factors for metabolic syndrome. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose: The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients. Methods: This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement +/- 150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment-subcutaneous insulin if glucose > 150 mg/dL. The main efficacy outcome was the mean of patients` median BG, and the safety outcome was the incidence of hypoglycemia (<= 40 mg/dL). Results: The mean of patients` median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional). Conclusions: The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols. (C) 2009 Elsevier Inc. All rights reserved.

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19). The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.

Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit

Purpose: The aim of this study was to characterize the first 48-hour evolution of metabolic acidosis of adult patients with diabetic ketoacidosis admitted to the intensive care unit. Materials and Methods: We studied 9 patients retrieved from our prospective collected database, using the physicochemical approach to acid-base disturbances. Results: Mean (SD) age was 34 (13) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score was 16 (10); mean (SD) blood glucose level on admission was 480 (144) mg/dL; mean (SD) pH was 7.17 (0.18); and mean (SD) standard base excess was -16.8 (7.7) mEq/L. On admission, a great part of metabolic acidosis was attributed to unmeasured anions (strong ion gap [SIG], 20 +/- 10 mEq/L), with a wide range of strong ion difference (41 +/- 10 mEq/L). During the first 48 hours of treatment, 297 +/- 180 IU of insulin and 9240 +/- 6505 mL of fluids were used. Metabolic improvement was marked by the normalization of pH, partial correction of standard base excess, and a reduction of hyperglycemia. There was a significant improvement of SIG (7.6 +/- 6.2 mEq/L) and a worsening of strong ion difference acidosis (36 +/- 5 mEq/L) in the first 24 hours, with a trend toward recuperation between 24 and 48 hours (38 +/- 6 mEq/L). Conclusion: Initial metabolic acidosis was due to SIG, and the treatment was associated with a significant decrease of SIG with an elevation of serum chloride above the normal range. (C) 2011 Elsevier Inc. All rights reserved.

HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus

Purpose: In this study we analyzed the role played by aerobic exercise training in the plasma lipoprotein profile, prebeta 1-HDL concentration, and in the in vitro HDL3 ability to remove cholesterol from macrophages and inhibit LDL oxidation in type 2 diabetes mellitus (DM) patients and control subjects, in the fasting and postprandial states. Methods: Healthy controls (HTC, N = 11; 1 M/10 F) and subjects with type 2 diabetes mellitus (DMT, N = 11; 3M/ 8F) were engaged in a 4-month aerobic training program, and compared with a group of sedentary subjects with type 2 diabetes mellitus (DMS, N = 10; 4 M/6 F). All groups were submitted to an oral fat load test to analyze all parameters, both at the beginning of the investigation protocol (basal) and at the end of the study period (final). Results: Exercising did not modify body weight, BMI, plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (TG), glucose, insulin, or HOMA-IR, but it reduced the waist circumference. The HDL3 Composition did not change, and its ability to remove cell cholesterol was unaltered by aerobic training. In DMT but not in HTC, aerobic training improved 15% the HDL3 protective effect against LDL maximal oxidation rate in the fasting state, and reduced 24% the plasma prebeta 1-HDL concentration in the postprandial state, suggesting an enhanced prebeta 1-HDL conversion into larger, more mature HDL particles. In this regard, regular aerobic exercise enriched HDL2 with TG in the fasting and postprandial states in HTC and in the fasting phase in DMT. Conclusion: Our results show that aerobic exercise training in diabetes mellitus improves the HDL efficiency against LDL oxidation and favors HDL maturation. These findings were independent of changes in insulin resistance and of the rise of plasma HDL cholesterol concentration.

Enterohormonal changes after digestive adaptation: Five-year results of a surgical proposal to treat obesity and associated diseases

Background Recent physiological knowledge allows the design of bariatric procedures that aim at neuroendocrine changes instead of at restriction and malabsorption. Digestive adaptation is a surgical technique for obesity based in this rationale. Methods The technique includes a sleeve gastrectomy, an omentectomy and a jejunectomy that leaves initial jejunum and small bowel totaling at least 3 m (still within normal variation of adult human bowel length). Fasting ghrelin and resistin and fasting and postprandial GLP-1 and PYY were measured pre- and postoperatively. Results Patients: 228 patients with initial body mass index (BMI) varying from 35 to 51 kg/m(2); follow-up: I to 5 years; average EBMIL% was 79.7% in the first year; 77.7% in the second year; 71.6% in the third year; 68.9% in the fourth year. Patients present early satiety and major improvement in presurgical comorbidities, especially diabetes. Fasting ghrelin and resistin were significantly reduced (P<0.05); GLP-1 and PYY response to food ingestion was enhanced (P<0.05). Surgical complications (4.4%) were resolved without sequela and without mortality. There was neither diarrhea nor detected malabsorption. Conclusions Based on physiological and supported by evolutionary data, this procedure creates a proportionally reduced gastrointestinal (GI) tract that amplifies postprandial neuroendocrine responses. It leaves basic GI functions unharmed. It reduces production of ghrelin and resistin and takes more nutrients to be absorbed distally enhancing GLP-1 and PYY secretion. Diabetes was improved significantly without duodenal exclusion. The patients do not present symptoms nor need nutritional support or drug medication because of the procedure, which is safe to perform.

Regression of glomerular injury by losartan in experimental diabetic nephropathy

Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman`s capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blocker, losartan, is dose-dependent. Here we determined if moderate and advanced glomerular lesions, associated with streptozotocin-induced diabetes, regress with conventional or high-dose losartan treatment. Using daily insulin injection for 10 months, we maintained diabetic adult male Munich-Wistar rats in a state of moderate hyperglycemia. Following this period, some rats continued to receive insulin with or without conventional or high-dose losartan for an additional 2 months. Diabetic rats pretreated with insulin for 10 months and age-matched non-diabetic rats served as controls. Mesangial expansion was found in the control diabetic rats and was exacerbated in those rats maintained on only insulin for an additional 2 months. Conventional and high-dose losartan treatments reduced this mesangial expansion and the severity of synechiae lesions below that found prior to treatment; however, the frequency of the latter was unchanged. There was no dose-response effect of losartan. Our results show that regression of mesangial expansion and contraction of sclerotic lesions is feasible in the treatment of diabetes, but complete resolution of advanced glomerulosclerosis may be hard to achieve.

Low protein diet changes the energetic balance and sympathetic activity in brown adipose tissue of growing rats

Objective: The aim of this study was to assess the effects of protein restriction in growing rats. Methods: Rats (approximate weight, 100 g) were maintained with low-protein (LP; 6%) or normo-proteic (control; 17%) diets, and at the end of the 15th day, hormonal and biochemistry parameters and energetic balance were evaluated. Data were analyzed using Student`s t test (with statistical significance set at P <= .05). Results: LP animals were hyperphagic and showed increased energetic gain (24%) and energy expenditure (EE) compared with controls. The increase in EE was followed by increased sympathetic activity in brown adipose tissue, evidenced by increased norepinephrine turnover, suggesting increased thermogenesis. In spite of hyperphagia, protein ingestion in LP animals was lower than that of controls (P < 0.01). The LP diet impaired body growth and caused deep alterations in body chemical composition, with an increase in carcass lipid content (64%) and reductions of protein and water. In LP animals, postprandial glycemia was unchanged, and insulinemia was lower than in controls (P <= .01). Reduction in fasting glycemia without changes in insulinemia also was detected (P < .01), suggesting increased insulin sensitivity. The LP diet caused a 100% increase in serum leptin (P < .01). Conclusions: Protein restriction led to an increase in EE, with probable activation of thermogenesis in brown adipose tissue, evidenced by an increase in catecholamines levels. Despite the higher EE, energetic gain and lipids increased. The high level of leptin associated with hyperphagia led to the supposition that these animals are leptin resistant, and the increase in insulin sensitivity, suggested by the relation between insulin and glycemia in fasting and fed animals, might contribute to lipid accumulation. (C) 2009 Elsevier Inc. All rights reserved.

Gastrointestinal transit, appetite, and energy balance in gastrectomized patients

Background: Alterations in gastrointestinal tract physiology after gastrectomy may affect appetite and energy balance. Objective: The objective of this study was to examine energy balance, appetite, and gastrointestinal transit in subjects with gastrectomy. Design: Seven subjects with total gastrectomy (TG) and 14 subjects with partial gastrectomy (PG), who were free from signs of recurrent disease, and 10 healthy control subjects were studied. Resting energy expenditure (REE) was measured by indirect calorimetry and compared with REE predicted by the Harris-Benedict equation (mREE/pREE%). Gastrointestinal transit was measured by scintigraphy. Habitual food intake was assessed, and appetite was measured during scintigraphy after ingestion of a test meal (361 kcal). Results: Body mass index was not different among the groups. mREE/pREE% was higher in patients with PG (P < 0.01) than in control subjects. The TG group showed higher energy intake (P < 0.05) than the PG group and control subjects. Gastric emptying was faster in the PG group than in control subjects, and gastrointestinal transit was accelerated in both PG and TG groups. An intense, precocious postprandial fullness and a relatively early recovery of hunger and prospective consumption sensations were seen in these patients. Conclusions: Patients with PG or TG have higher than predicted energy expenditure, which in TG seems to be compensated for by increased energy intake. These patients have preserved postprandial appetite responses and precocious postprandial fullness, which seem to be associated with disturbances in gastrointestinal transit of the ingested meal and are likely to be independent of vagal fiber integrity or stomach-released ghrelin. Am J Clin Nutr 2009; 89: 231-9.