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.

Wound healing process in post-bariatric patients: an experimental evaluation.

Bariatric surgery is the most effective treatment for morbid obesity. Despite this, side effects are recorded. One of them is redundant skin hanging from the patients' body causing both aesthetical and functional deformities. They can only be corrected with body contouring surgery, whose wound complication rate is very high in previously obese population. Despite several hypotheses, an adequate explanation is still awaited. The aim of our study was to evaluate the wound healing process in post-bariatric patients. Seven patients, six women and one man, were enrolled. They all were nonsmokers and nondiabetic. They all underwent biliopancreatic diversion (BPD). After 36 months, abdominoplasty was performed. Biochemical parameters before and after bariatric surgery were evaluated. The content of total protein and hydroxyproline was assessed in multiple scar biopsies before and after BPD. Abdominoplasty horizontal scar skin samples were subjected to histological evaluation with Weigert-Van Gieson stain for elastic fibers and connectivum. All biochemical parameters analyzed were reduced post-BPD compared to the preoperative period. Tissue proteins were significantly reduced after BPD both in their totality and as hydroxyproline and hydroxyproline/total tissue protein. Histological evaluation revealed abnormal dermal elastic and collagen fibers. The cause of aberrant healing in massive weight loss body contouring is likely multifactorial. A relationship between nutritional state, wound collagen accumulation, and elastic fiber content seems to be only partially involved. The high mechanical stress of tissues before BPD probably influences the wound healing process after BPD.

Early effects of gastric banding (LGB) and of biliopancreatic diversion (BPD) on insulin sensitivity and on glucose and insulin response after OGTT.

BACKGROUND: Bariatric surgery improves glucose metabolism. METHODS: To assess the direct role of surgery (i.e., independently of significant weight loss) on insulin sensitivity (homeostasis model assessment (HOMA) insulin resistance (IR) and oral glucose insulin sensitivity (OGIS)), on glucose and insulin response (area under the curve (AUC) blood glucose (BG) and AUC insulin (Ins)) to oral glucose tolerance test (OGTT), and on glucose tolerance, 11 subjects underwent OGTT (75 g, p.o.) before and 5 days after laparoscopic gastric banding (LGB; no change of initial body mass index (BMI), 46.7 +/- 2.21 kg/m(2)), and ten subjects underwent OGTT before and 7 days after biliopancreatic diversion (BPD; BMI decreased from 54.5 +/- 3.75 to 52.1 +/- 4.03 kg/m(2)). As controls, we considered OGTT performed twice over a 30-45-day period in two groups of subjects [BMI 43.0 +/- 0.41 (n = 13, matched with LGB subjects for BMI) and 48.2 +/- 0.49 kg/m(2) (n = 14, matched with BPD subjects for BMI), respectively] with stable weight (+/-1.5 kg); a further control group was made of 11 subjects with a spontaneous weight loss similar to BPD subjects (BMI from 55.5 +/- 1.27 to 52.2 +/- 1.35 kg/m(2)). RESULTS: Fasting BG and OGIS improved in BPD subjects and in subjects with spontaneous weight loss, not in LGB subjects or in weight-stable controls; HOMA-IR, AUC BG, and AUC Ins only decreased in BPD subjects. Glucose tolerance was not affected in a different way in the various groups of subjects. CONCLUSIONS: These data indicate an early effect of BPD different from LGB on insulin sensitivity and on glucose and on insulin response to OGTT, mostly independent of weight loss.

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.

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.

Growth hormone and ghrelin secretion in severely obese women before and after bariatric surgery.

OBJECTIVE: The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone-releasing hormone (GHRH)/arginine test in severe obesity before and after surgically-induced weight loss. RESEARCH METHODS AND PROCEDURES: Our study population included 11 severely obese women 39 +/- 12 years of age, with a mean BMI of 48.6 +/- 2.4 kg/m2, re-studied in a phase of stabilized body weight, with a BMI of 33.4 +/- 1.2 kg/m2, 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test. RESULTS: Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 +/- 0.05 ng/mL to 1 +/- 0.3 ng/mL (p < 0.05) and from 514.76 +/- 98.7 ng/mL for 120 minutes to 1957.3 +/- 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 +/- 77.9 before BPD vs. 574.1 +/- 32.7 after BPD), ghrelin AUC significantly increased from -3253.9 +/- 2180.9 pg/mL for 120 minutes to 1142.3 +/- 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin-like growth factor (IGF)-1 concentration did not change significantly (133.6 +/- 9.9 ng/mL before vs. 153.3 +/- 25.2 ng/mL after BPD). DISCUSSION: Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.

Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery.

Currently, there are no data in the literature regarding the pathophysiological mechanisms involved in the rapid resolution of type 2 diabetes after bariatric surgery, which was reported as an additional benefit of the surgical treatment for morbid obesity. With this question in mind, insulin sensitivity, using euglycemic-hyperinsulinemic clamp, and insulin secretion, by the C-peptide deconvolution method after an oral glucose load, together with the circulating levels of intestinal incretins and adipocytokines, have been studied in 10 diabetic morbidly obese subjects before and shortly after biliopancreatic diversion (BPD) to avoid the weight loss interference. Diabetes disappeared 1 week after BPD, while insulin sensitivity (32.96 +/- 4.3 to 65.73 +/- 3.22 mumol . kg fat-free mass(-1) . min(-1) at 1 week and to 64.73 +/- 3.42 mumol . kg fat-free mass(-1) . min(-1) at 4 weeks; P < 0.0001) was fully normalized. Fasting insulin secretion rate (148.16 +/- 20.07 to 70.0.2 +/- 8.14 and 83.24 +/- 8.28 pmol/min per m(2); P < 0.01) and total insulin output (43.76 +/- 4.07 to 25.48 +/- 1.69 and 30.50 +/- 4.71 nmol/m(2); P < 0.05) dramatically decreased, while a significant improvement in beta-cell glucose sensitivity was observed. Both fasting and glucose-stimulated gastrointestinal polypeptide (13.40 +/- 1.99 to 6.58 +/- 1.72 pmol/l at 1 week and 5.83 +/- 0.80 pmol/l at 4 weeks) significantly (P < 0.001) decreased, while glucagon-like peptide 1 significantly increased (1.75 +/- 0.16 to 3.42 +/- 0.41 pmol/l at 1 week and 3.62 +/- 0.21 pmol/l at 4 weeks; P < 0.001). BPD determines a prompt reversibility of type 2 diabetes by normalizing peripheral insulin sensitivity and enhancing beta-cell sensitivity to glucose, these changes occurring very early after the operation. This operation may affect the enteroinsular axis function by diverting nutrients away from the proximal gastrointestinal tract and by delivering incompletely digested nutrients to the ileum.