Bariatric surgery versus conventional medical therapy for type 2 diabetes.

BACKGROUND: Roux-en-Y gastric bypass and biliopancreatic diversion can markedly ameliorate diabetes in morbidly obese patients, often resulting in disease remission. Prospective, randomized trials comparing these procedures with medical therapy for the treatment of diabetes are needed. METHODS: In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy). RESULTS: At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group). CONCLUSIONS: In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; ClinicalTrials.gov number, NCT00888836.).

Medical and surgical treatment of haemorrhoids and anal fissure in Crohn's disease: a critical appraisal.

BACKGROUND: The principle to avoid surgery for haemorrhoids and/or anal fissure in Crohn's disease (CD) patients is still currently valid despite advances in medical and surgical treatments. In this study we report our prospectively recorded data on medical and surgical treatment of haemorrhoids and anal fissures in CD patients over a period of 8 years. METHODS: Clinical data of patients affected by perianal disease were routinely and prospectively inserted in a database between October 2003 and October 2011 at the Department of Surgery, Tor Vergata University Hospital, Rome. We reviewed and divided in two groups records on CD patients treated either medically or surgically according to the diagnosis of haemorrhoids or anal fissures. Moreover, we compared in each group the outcome in patients with prior diagnosis of CD and in patients diagnosed with CD only after perianal main treatment. RESULTS: Eighty-six CD patients were included in the study; 45 were treated for haemorrhoids and 41 presented with anal fissure. Conservative approach was initially adopted for all patients; in case of medical treatment failure, the presence of stable intestinal disease made them eligible for surgery. Fifteen patients underwent haemorrhoidectomy (open 11; closed 3; stapled 1), and two rubber band ligation. Fourteen patients required surgery for anal fissure (Botox ± fissurectomy 8; LIS 6). In both groups we observed high complication rate, 41.2% for haemorrhoids and 57.1% for anal fissure. Patients who underwent haemorrhoidectomy without certain diagnosis of CD had significantly higher risk of complications. CONCLUSIONS: Conservative treatment of proctologic diseases in CD patients has been advocated given the high risk of complications and the evidence that spontaneous healing may also occur. From these preliminary results a role of surgery is conceivable in high selected patients, but definitve conclusions can't be made. Further randomized trials are needed to establish the efficacy of the surgical approach, giving therapeutic recommendations and guidelines.

Social phobia and quality of life in morbidly obese patients before and after bariatric surgery.

BACKGROUND: Morbidly obesity is characterized by physical and psychological comorbidities which are associated with reduced quality of life. Bariatric surgery has been linked to a reduction of psychopathology other than to a reduction of weight and improvement in physical functioning. Aim of the present study was to compare psychological features of two groups of morbidly obese patients, before and after bariatric surgery, assessing social phobia and quality of life. METHODS: A total of 46 morbidly obese patients were enrolled in the study. Of them, 20 were waiting for bilio-pancreatic diversion (group A), while 26 had already undergone surgical procedure (group B). Psychometric evaluation assessed social phobia, fear for the body-shape and quality of life, using appropriate psychometric tests. RESULTS: The percentage of patients showing social phobia was significantly higher compared to a sample of healthy controls (p=0.004), both in group A (p=0.003) and in group B (p=0.029). No differences in percentage of patients affected by social phobia were found between groups. A significantly higher percentage of patients affected by distress about the body (p<0.0001) was found in group A with respect to group B. A reduction of quality of life was found in both groups. CONCLUSIONS: The present study shows a high prevalence of social phobia in a population of morbidly obese patients, both before and after surgery. A general reduction of quality of life was also observed, with a partial improvement after surgery. Future studies are needed to clarify the relationship between social phobia and quality of life in surgically-treated morbidly obese patients.

Effects of transoral gastroplasty on glucose homeostasis in obese subjects.

CONTEXT AND OBJECTIVE: Transoral gastroplasty (TOGA) is a safe and less invasive procedure than traditional bariatric surgery. We studied the effects of TOGA on the risk of progression from prediabetes to overt type 2 diabetes mellitus (T2DM) or on regression from diabetes or prediabetes to a lower risk category. DESIGN AND SETTING: Prospective, observational study (October 2008 to October 2010) performed at Catholic University, Rome, Italy. Fifty consecutive subjects 18-60 years old, 35 ≥ body mass index < 55 kg/m², were enrolled. Glucose tolerance, insulin sensitivity, and secretion were studied at baseline and 1 week and 1, 6, and 12 months after TOGA. Plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and ghrelin levels were measured. RESULTS: Forty-three patients (86%) completed the 1-year postoperative follow-up. Patients lost 16.90% of baseline weight (P level × factor time <0.001). Body mass index decreased from 42.24 ± 3.43 to 34.65 ± 4.58 kg/m² (P < .001). Twenty-three patients (53.5%) were diagnosed as normal glucose tolerance (NGT) before treatment, 2 (4.6%) were impaired fasting glucose (IFG), 12 (27.9%) were impaired glucose tolerance (IGT), 1 (2.3%) had both IFG and IGT, and 5 (11.6%) had T2DM. At 1-year posttreatment, the percentages changed to 86.0% NGT, 2.3% IFG, 11.6% IGT, 0% IFG plus IGT, and 0% T2DM, respectively. Peripheral insulin resistance and homeostasis model of assessment-insulin resistance improved significantly. Fasting glucose-dependent insulinotropic peptide and ghrelin decreased from 316.9 ± 143.1 to 156.2 ± 68.2 pg/mL (P < .001) and from 630.6 ± 52.1 to 456.7 ± 73.1 pg/mL (P < .001), respectively, whereas GLP-1 increased from 16.2 ± 4.9 to 23.7 ± 9.5 pg/mL (P < .001). CONCLUSIONS: TOGA induced glucose disposal improvement with regression of diabetes to NGT or IGT and regression of IGT and IFG to NGT in half of the cases. Regressors showed a much larger increase of GLP-1 levels than progressors.

Underestimation of urinary albumin to creatinine ratio in morbidly obese subjects due to high urinary creatinine excretion.

BACKGROUND & AIMS: Albuminuria, a chronic kidney and/or cardiovascular disease biomarker, is currently measured as albumin-to-creatinine ratio (ACR). We hypothesize that in severely obese individuals ACR might be abnormally low in spite of relatively high levels of urinary albumin due to increased creatininuria. METHODS: One-hundred-eighty-four subjects were divided into tertiles based on their BMI. Fat-free mass (FFM) and fat-mass were assessed by DEXA; 24-h creatinine and albumin excretion, ACR, lipid profile and blood pressure were measured. RESULTS: Twenty-four-hour creatinine highly correlated (R = 0.75) with FFM. Since both creatininuria and albuminuria increased with the BMI, being the increase in creatininuria preponderant in subjects with BMI>35, their ratio (AC-ratio) did not change significantly from that of subjects in the lower BMI tertile. ACR only correlated with the systolic blood pressure, while both albuminuria and cretininuria correlated (P = 0.01) with the absolute 10-year CHD risk. In subjects with BMI>35, 100 mg of albumin excreted with urine increased the CHD risk of 2%. CONCLUSIONS: Albumin-to-creatinine ratio is underestimated in severely obese individuals as a consequence of the large creatininuria, which is proportional to the increased FFM. Therefore, at least in this population 24-h albuminuria should be more reliable than ACR.

Effectiveness of the Transoral Endoscopic Vertical Gastroplasty (TOGa®): a good balance between weight loss and complications, if compared with gastric bypass and biliopancreatic diversion.

BACKGROUND: The effectiveness of restrictive procedures has been inferior to that of malabsorbitive ones. Recent variants of restrictive procedures, i.e., gastric banding and sleeve gastrectomy, confirm the strive for more efficacious solutions with less complications. We investigated the balance between effectiveness and complications for a new restrictive procedure, a Transoral Endoscopic Vertical Gastroplasty (TOGa®) METHODS: Seventy-nine morbidly obese patients were submitted to one out of three surgical procedures: TOGa® (29 patients), laparoscopic gastric bypass (LRYGBP; 20 patients), and biliopancreatic diversion (BPD; 30 patients). Mean BMI were 41.7 (35.4-46.6), 44.8 (36.4-54), and 47.5 (41-60.3), respectively. All the patients reached a 2-year follow-up. RESULTS: In TOGa® group BMI, respectively at 12 and 24 months, was 34.5 and 35.5, with 44 and 48.3% of patients with BMI lower than 35. In LRYGBP group, BMI was 30.7 and 29.2 kg/m(2), with 80 and 85% of patients with BMI < 35. In BPD group, BMI was 30 and 29.6 kg/m(2), with 100 and 93.3% of patients with BMI < 35. In TOGa® group, 59% of patients with an initial BMI < 45 reached a BMI < 35, in comparison to 48% recorded in the whole group and to 14.3% in patients with initial BMI ≥ 45. CONCLUSIONS: In selected patients, TOGa®, was associated with good results after two years in terms of weight loss, even in comparison with LRYGBP and BPD. Minimal trauma, absence of complications, and short hospital stay justify this procedure for patients with low BMI.

Effects of bilio-pancreatic diversion on diabetic complications: a 10-year follow-up.

OBJECTIVE: The surgical option could represent a valid alternative to medical therapy in some diabetic patients. However, no data are available on long-term effects of metabolic surgery on diabetic complications. We aimed to determine whether patients with newly diagnosed type 2 diabetes who underwent bilio-pancreatic diversion (BPD) had less micro- and macrovascular complications than those who received conventional therapy. RESEARCH DESIGN AND METHODS: This was an unblinded, case-controlled trial with 10-years' follow-up, conducted from July 1998 through October 2009 at the Day Hospital of Metabolic Diseases, Catholic University, Rome, Italy. A consecutive sample of 110 obese patients (BMI >35 kg/m(2)) with newly diagnosed type 2 diabetes was enrolled. The study was completed by 50 subjects. The main outcome measure was long-term effects (10 years) of BPD versus those associated with conventional therapy on microvascular outcome, micro- and macroalbuminuria, and glomerular filtration rate (GFR). Secondary measures included macrovascular outcomes, type 2 diabetes remission, glycated hemoglobin, and hyperlipidemia. RESULTS: Ten-year GFR variation was -45.7 ± 18.8% in the medical arm and 13.6 ± 24.5% in the surgical arm (P < 0.001). Ten-year hypercreatininemia prevalence was 39.3% in control subjects and 9% in BPD subjects (P = 0.001). After 10 years, all BPD subjects recovered from microalbuminuria, whereas microalbuminuria appeared or progressed to macroalbuminuria in control subjects. Three myocardial infarctions, determined by electrocardiogram, and one stroke occurred in control subjects. After the 10-year follow-up, coronary heart disease (CHD) probability was 0.22 ± 0.10 and 0.05 ± 0.04 in the medical and surgical groups, respectively (P < 0.001). Remission from type 2 diabetes was observed in all patients within 1 year of surgery. Surgical and medical subjects had lost 34.60 ± 10.25 and 0.38 ± 6.10% of initial weight at the 10-year follow-up (P < 0.001). CONCLUSIONS: Renal and cardiovascular complications were dramatically reduced in the surgical arm, indicating long-term benefits of BPD on diabetic complications, at least in the case of morbid obesity with decompensated type 2 diabetes.

Cardiovascular risk in obesity: different activation of inflammation and immune system between obese and morbidly obese subjects.

BACKGROUND: Both inflammation and immunity are involved in the development and progression of atherosclerosis. Obesity is considered a major modifiable cardiovascular risk factor, however, the correlation between increasing degrees of obesity and cardiovascular risk is not clear yet. Aim of our study was to investigate how different degrees of obesity are associated with inflammation and immune system responses. METHODS: One-hundred healthy individuals were divided into 3 groups according to body mass index (BMI): 22 overweight (OW), 26 obese (O) and 52 morbidly obese (MO). High-sensitivity C-Reactive Protein (hs-CRP, immunonephelometry), leptin (radio-immunoassay) and CD4+CD28nullT-lymphocytes (flow-cytometry), a particular subset of T-lymphocytes with pro-atherogenic and plaque-destabilizing properties, were assessed. RESULTS: hs-CRP levels were significantly higher in O vs OW (p=0.036), in MO vs OW (p<0.001) and in MO vs O (p=0.012). Similarly, leptin levels were higher in O vs OW (p=0.02), in MO vs OW (p<0.001) and in MO vs O (p<0.001). CD4+CD28nullT-lymphocytes were higher in O vs OW (p<0.001), in O vs MO (p=0.03) and in MO vs OW (p=0.01). hs-CRP and leptin levels significantly correlated each other (r=0.39; p<0.001) and with waist circumference (r=0.52; p<0.001; r=0.64; p<0.001) and BMI (r=0.60; p<0.001; r=0.74; p<0.001). CONCLUSIONS: Our study demonstrates that, notwithstanding higher levels of inflammation, MO are characterized by less detrimental immune activation, as shown by the reduced CD4+CD28nullT-cells expansion as compared to OW and O, which might translate in less immune vascular injury. These findings suggest that MO might represent a particular population, in which different pathophysiological mechanisms take part if compared with "classic" obesity.

Thyroid function and insulin sensitivity before and after bilio-pancreatic diversion.

BACKGROUND: Bilio-pancreatic diversion (BPD) induces permanent weight loss in previously severe obese patients through a malabsorptive mechanism. The aim of the study was to evaluate the modifications of circulating thyroid hormones after BPD, a surgical procedure which interferes with the entero-hepatic circulation of biliary metabolites. METHODS: Forty-five patients were studied before and 2 years after BPD. Thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), anti-thyroid antibodies, iodine urinary excretion, lipid profile, insulin and glucose plasma levels were assessed. The insulin-resistance HOMA IR index was calculated, and colour Doppler ultrasonography of the neck was performed. RESULTS: The subjects (23%) had subclinical hypothyroidism prior to BPD (TSH levels above the normal range with normal fT3 and fT4 levels). After 2 years 40.42% of the population showed subclinical hypothyroidism, while 6.3% became frankly hypothyroid, all of them with no evidence of auto-immune thyroiditis. Most of the patients, who became sub-clinically hypothyroid only following BPD, had already thyroid alterations at the sonogram (multi-nodular euthyroid goiter and thyroidal cysts) prior to surgery. CONCLUSIONS: BPD increases the prevalence of subclinical or even frank hypothyroidism, without causing a defect in thyroid function itself, through several integrated mechanisms. (1) It induces iodine malabsorption, which is partially compensated by iodine excretion contraction. (2) The entero-hepatic open circulation determines fT3 loss, which induces subclinical or frank hypothyroidism in patients with pre-existing thyroid alterations, interfering also with the weight loss progress. Iodine supplementation should be recommended in those patients reporting thyroid alterations at the sonogram prior to BPD, LT4 therapy should be strictly monitored in patients suffering of subclinical hypopthiroidism and T3 therapy should eventually be considered for patients diagnosed with frank hypothyroidism prior to BPD.

Influence of maternal obesity on insulin sensitivity and secretion in offspring.

OBJECTIVE: The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring. RESEARCH DESIGN AND METHODS: Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and beta-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry. RESULTS: No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 +/- 79.32 vs. 513.81 +/- 70.70 ml(-1) x min(-1) x m(-2) in women, P < 0.0001; 416.42 +/- 76.17 vs. 484.242 +/- 45.76 ml(-1) x min(-1) x m(-2) in men, P < 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 +/- 21.20 vs. 35.71 +/- 10.02 nmol x m(-2), P < 0.01) but did not differ significantly in women. beta-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and beta-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring. CONCLUSIONS: Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring.

Prolactin and insulin ultradian secretion and adipose tissue lipoprotein lipase expression in severely obese women after bariatric surgery.

BACKGROUND: Hyperprolactinemia is associated with obesity. Furthermore, in human adipose tissue cultured in vitro, prolactin (PRL) inhibited lipoprotein lipase (LPL) activity via functional PRL receptors. OBJECTIVE: To study PRL and insulin ultradian rhythm and subcutaneous adipose tissue LPL mRNA and protein expressions in severely obese women before and after malabsorptive bariatric surgery. METHODS AND PROCEDURES: Seven severely obese, fertile women were studied twice, once before and the second time 1 year after bilio-pancreatic diversion (BPD), when the weight was stable for at least 3 months. Metabolizable energy intake and 24-h energy expenditure (EE) were measured. Fourier and PULSEFIT analyses were applied to 24-h hormonal time-series to study daily fluctuations and hormonal clearance. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Quantitative-competitive reverse transcriptase-PCR and western blot analysis were used to measure LPL gene expression. RESULTS: Spontaneous 24-h PRL secretion was significantly reduced after BPD (mean-daily release, 128.4 +/- 28.1 microg/l vs. 67.2 +/- 9.2 microg/l distribution volume (Vd/l.24 h), P = 0.02); insulin secretion also was significantly reduced (499.9 +/- 204.0 microg/Vd/l.24 h vs. 85.6 +/- 21.0 microg/Vd/l.24 h, P = 0.0001). Metabolizable energy/kg(FFM) did not change significantly after BPD. Twenty-four-hour EE, but not 24-h EE/FFM, was significantly decreased after BPD (P < 0.05). Insulin sensitivity significantly (P < 0.0001) increased after BPD from 21.41 +/- 1.92 to 68.62 +/- 5.03 micromol/kg(FFM)/min. LPL mRNA concentration (from 42.63 +/- 4.21% to 19.00 +/- 2.74% of cyclophilin mRNA, P = 0.001) as well as LPL protein level (from 8.94 +/- 2.73 to 3.16 +/- 1.05 as ratios of protein of interest vs. housekeeping protein, P = 0.038) significantly decreased after BPD. The major determinant of PRL secretion was insulin secretion, whereas the best predictors of LPL expression were insulin and PRL secretion rates. DISCUSSION: The restriction of lipid metabolizable energy rather than weight loss seems to be responsible for both reduction in PRL circulating levels and normalization of its secretion rhythm after bariatric surgery. Furthermore, the reduced adipose tissue LPL expression, being significantly correlated with the decrease in insulin and PRL, suggests a role of hyperinsulinemia and hyperprolactinemia in inducing and sustaining obesity.