Biomedical subjects

Geltrude Mingrone

Publications and source records attributed to Geltrude Mingrone.

At least 19 recordsLinked to original sources

PubMed2006

Effect of massive weight loss on inflammatory adipocytokines and the innate immune system in morbidly obese women.

CONTEXT: Obesity may be regarded as a low-grade inflammatory state. OBJECTIVE: The aim of this study was to evaluate changes in pro-inflammatory adipocytokines and the innate immune system, cardiovascular risk, and insulin sensitivity after massive weight loss. DESIGN: This was a longitudinal study. SETTING: The study was conducted at Catholic University, Rome. SUBJECTS AND METHODS: There were 10 normoglucose-tolerant obese women evaluated before and 36 months after bilio-pancreatic diversion (BPD). Glucose sensitivity (M value) was estimated using the euglycemic-hyperinsulinemic clamp. Mannan-binding lectin (MBL), bactericidal/permeability increasing protein (BPI), alpha-defensins, soluble CD14 receptor (sCD14), C-reactive protein, adiponectin, leptin, visfatin, IL-6, and TNF-alpha were assayed. RESULTS: After massive weight loss (53% of excess body weight), leptin (P <or= 0.0001), IL-6 (P <or= 0.0001), alpha-defensins (P <or= 0.001), and C-reactive protein (P <or= 0.0001) decreased significantly. Adiponectin increased significantly (P <or= 0.001). Of the nine subjects who lost more than 20% of body mass index, sCD14 (2.87 +/- 0.5 to 2.55 +/- 0.5; P = 0.016) and visfatin levels (12.20 +/- 0.93 to 10.63 +/- 1.93 ng/ml; P = 0.045) decreased significantly. No significant changes were observed in TNF-alpha, BPI, or MBL. Insulin sensitivity more than doubled after BPD (P <or= 0.0001). sCD14 changes were significantly associated with body mass index (r0 = 0.80; P = 0.003) and M changes (r0 = -0.59; P = 0.03). MBL correlated with insulin sensitivity in obese (r0 = 0.93; P = 0.0001) and post-BPD women (r(0) = 0.66; P = 0.038). Adiponectin correlated negatively with cardiovascular risk (r0 = -0.709; P = 0.02) and IL-6 (r0 = -0.634; P = 0.05). Multiple linear regression analysis showed that changes in sCD14 were also significantly related to changes in insulin sensitivity. CONCLUSIONS: Surgically induced weight loss is capable of reversing low-grade inflammation, at least partially. The relationships between sCD14, MBL, BPI, and glucose sensitivity, and the role of TNF-alpha in obesity warrant further investigation.

Acute-Phase Reaction↗

PubMed2006

Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects.

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal (P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise ( approximately 60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.

Administration, Oral↗

PubMed2006

Ultradian ghrelin pulsatility is disrupted in morbidly obese subjects after weight loss induced by malabsorptive bariatric surgery.

BACKGROUND: Suppression of ghrelin production after Roux-en-Y gastric bypass that suggested its contribution to appetite reduction has been reported. OBJECTIVE: Because biliopancreatic diversion (BPD) does not affect appetite, we compared ghrelin production and 24-h pulsatility between healthy control subjects and obese subjects before and after BPD. DESIGN: A computerized algorithm identified peak heights, clearance rate, and peak frequency of ghrelin over 24 h. Twenty-four-hour energy expenditure was measured in the calorimetric chamber, and energy intakes were computed. Insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp. RESULTS: Mean (+/-SD) 24-h plasma ghrelin concentrations were significantly (P < 0.0001) higher in control than in obese subjects (338.17 +/- 22.09 and 164.47 +/- 29.19 microg/L, respectively), but they increased to 204.64 +/- 28.51 microg/L in the obese subjects after BPD (P < 0.01). The pulsatility index was 0.098 +/- 0.016 and 0.041 +/- 0.014 microg . L(-1) . min(-1) in control and obese subjects, respectively (P < 0.01), and decreased to 0.025 +/- 0.007 microg . l(-1) . min(-1) after BPD (P < 0.05). Energy intakes before and after BFP did not differ significantly. Although metabolizable energy after BPD was 40% of the energy intake, that (per kg fat-free mass) after BPD did not different significantly from that before BPD. CONCLUSIONS: Weight loss induced by malabsorptive bariatric surgery is associated with greater ghrelin concentrations, which, however, remain consistently lower than those in control subjects, whereas ghrelin pulsatility is subverted. Higher ghrelin concentrations may contribute to the high calorie intakes observed in post-BPD subjects. The lack of normal pulsatility may explain the new impulse of these subjects to eat very frequently.

Activity Cycles↗

PubMed2006

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

SUMMARY BACKGROUND DATA: Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. METHODS: Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. RESULTS: There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. CONCLUSIONS: This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

Animals↗

PubMed2006

Medium-chain, even-numbered dicarboxylic acids as novel energy substrates: an update.

Medium-chain dicarboxylic acids are produced by higher plants and animals via fatty acid omega-oxidation or by beta-oxidation of longer-chain dicarboxylic acids. In plants, dicarboxylic acids are components of the natural protective polymers cutin and suberin; in animals, dicarboxylic acids are mainly oxidized in mitochondria, where they are transported through four different pathways. Their energy density is intermediate between glucose and fatty acids. Dicarboxylic acid administration does not require insulin or stimulate insulin secretion, and the beta-oxidation of dicarboxylic acids produces succinic acid, a gluconeogenic substrate. Therefore, dicarboxylic acids might be a suitable fuel substrate, particularly in clinical conditions in which marked insulin resistance and/or impairment of aerobic glycolysis occur.

Animals↗

PubMed2006

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.

Adiponectin↗

PubMed2005

A mathematical model of the euglycemic hyperinsulinemic clamp.

BACKGROUND: The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity, and in its usual form the patient is followed under insulinization for two hours. In the present study, sixteen subjects with BMI between 18.5 and 63.6 kg/m(2) were studied by long-duration (five hours) EHC. RESULTS: From the results of this series and from similar reports in the literature it is clear that, in obese subjects, glucose uptake rates continue to increase if the clamp procedure is prolonged beyond the customary 2 hours. A mathematical model of the EHC, incorporating delays, was fitted to the recorded data, and the insulin resistance behaviour of obese subjects was assessed analytically. Obese subjects had significantly less effective suppression of hepatic glucose output and higher pancreatic insulin secretion than lean subjects. Tissue insulin resistance appeared to be higher in the obese group, but this difference did not reach statistical significance. CONCLUSION: The use of a mathematical model allows a greater amount of information to be recovered from clamp data, making it easier to understand the components of insulin resistance in obese vs. normal subjects.

Blood Glucose↗

PubMed2005

Approximate linear confidence and curvature of a kinetic model of dodecanedioic acid in humans.

Dicarboxylic acids with an even number of carbon atoms have been proposed as an alternate energy substrate for enteral or parenteral nutrition in the acutely ill patient, due to their water solubility and their yielding TCA cycle intermediates upon beta-oxidation. In the present work, a nonlinear compartmental model of the kinetics of dodecanedioic acid is developed, and its parameters are estimated from time concentration experimental observations obtained from six healthy volunteers undergoing a per os administration of 3 g of the substance. Although the model is linear in the transfer of the free substance from plasma to the tissues, the exchange between gut and plasma compartments is represented as a saturable function. Albumin binding is then incorporated to obtain the final model in terms of the measured total concentrations. Estimates of the model's structural parameters were computed for each experimental subject, and the usual single-subject approximate confidence regions for the parameters were derived by inversion of the Hessian at the optimum. To verify the applicability of this approximation, the nonlinearity of the expectation surface at the optimum was measured by computing the normal (intrinsic) component of curvature. Because the model curvature was excessive in all subjects, the usual approximation could not be trusted to provide acceptable approximations to the parameter confidence regions. A suitable Monte Carlo simulation yielded empirical joint parameter distributions from which the approximate parameter variances could finally be obtained.

Computer Simulation↗

PubMed2005

Leptin pulsatility in formerly obese women.

Plasma leptin and growth hormone (GH) profile and pulsatility have been studied in morbidly obese subjects before and 14 months after bilio-pancreatic diversion (BPD), a bariatric technique producing massive lipid malabsorption. The maximum leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs. 1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1) after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1); P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after the bariatric operation, while it was 69.2+/-8.5% before. After the operation, skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/-40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/-0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in 24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In conclusion, the reversion of insulin resistance after BPD might allow reversal of leptin resistance, restoration of leptin pulsatility, and consequent inhibition of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA, which, in turn, results in increased fatty acid oxidation. Finally, since leptin inhibits GH secretion, a reduction of circulating leptin levels might have produced an increase in GH secretion, as observed in our series.

Acetyl-CoA Carboxylase↗

PubMed2005

Low 25-hydroxyvitamin D does not affect insulin sensitivity in obesity after bariatric surgery.

OBJECTIVE: A positive correlation between levels of 25-hydroxyvitamin D [25(OH)D] and insulin sensitivity has been shown in healthy subjects. We aimed to test the hypothesis that concentration of 25(OH)D influences insulin sensitivity in obesity before and after weight loss. RESEARCH METHODS AND PROCEDURES: We investigated the relation between serum 25(OH)D and insulin sensitivity (estimated by euglycemic-hyperinsulinemic clamp) in 116 obese women (BMI > or = 40 kg/m2) evaluated before and 5 and 10 years after biliopancreatic diversion (BPD). Body composition was estimated by the isotope dilution method. RESULTS: Prevalence of hypovitaminosis D was 76% in the obese status and 91% and 89% at 5 and 10 years after BPD, respectively, despite ergocalciferol supplementation. 25(OH)D concentration decreased from 39.2 +/- 22.3 in obesity (p = 0.0001) to 27.4 +/- 16.4 and 25.1 +/- 13.9 nM 5 and 10 years after BPD, respectively. Whole-body glucose uptake increased from 24.27 +/- 4.44 at the baseline to 57.29 +/- 11.56 and 57.71 +/- 8.41 mumol/kg(fat free mass) per minute 5 and 10 years after BPD, respectively (p = 0.0001). Predictor of 25(OH)D was fat mass (R2 = 0.26, p = 0.0001 in obesity; R2 = 0.20, p = 0.02 after BPD). Parathormone correlated with fat mass (R2 = 0.19; p = 0.0001) and BMI (R2 = 0.053; p = 0.01) and inversely with M value (R2 = 0.16; p = 0.0001), but only in obese subjects. DISCUSSION: A high prevalence of hypovitaminosis D was observed in morbid obesity both before and after BPD. Low 25(OH)D did not necessarily imply increased insulin resistance after BPD, a condition where, probably, more powerful determinants of insulin sensitivity overcome the low circulating 25(OH)D levels. However, the present data cannot exclude some kind of influence of vitamin D status on glucose and insulin metabolism.

Adult↗

PubMed2005

Changes in fat mass influence SREBP-1c and UCP-2 gene expression in formerly obese subjects.

OBJECTIVE: To investigate the effect of fat mass (FM) reduction on adipose tissue gene expression in terms of lipid synthesis [sterol regulatory binding protein 1c (SREBP-1c)] and lipid oxidation [uncoupling protein 2 (UCP-2)] 2 years after lipid malabsorption and to assess the influence of lipid malabsorption on fat-free mass (FFM) maintenance evaluating the expression of genes related to glycolysis [hexokinase (HKII)] and glucose storage [glycogen synthase (GS)]. RESEARCH METHOD AND PROCEDURES: SREBP-1c, UCP-2, HKII, and GS mRNA expression were studied by reverse transcriptase-competitive polymerase chain reaction in 10 massively obese subjects before and 2 years after bilio-pancreatic diversion (BPD). Body composition was assessed by isotopic dilution method and insulin sensitivity by euglycemic-hyperinsulinemic clamp. RESULTS: FM decrease was approximately 60%, whereas FFM remained at normal physiological levels. In adipose tissue, SREBP-1c mRNA reduction (-39%, p < 0.005) was related only to FM changes after BPD, and UCP-2 decrease (-37%, p < 0.05) was dependent on free fatty acid (FFA) changes. No significant variations were observed in HKII and GS gene expression in skeletal muscle. DISCUSSION: Lipid malabsorption induced by BPD altered the expression of genes involved in glucose and lipid metabolism, with different consequences on FM and FFM. The degree of FM loss seems to interfere with SREBP-1c gene suppression to preserve an adequate amount of fat storage, in accordance with the thrifty genotype hypothesis. The reduction of FFAs induced by BPD acts in inhibiting FFA transportation to the mitochondria (UCP-2), contributing to the decreased lipid oxidation inside the adipose tissue.

Adipose Tissue↗

PubMed2005

Ghrelin does not influence gastric emptying in obese subjects.

OBJECTIVE: To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects. RESEARCH METHODS AND PROCEDURES: We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m2) and 16 nonobese control subjects (7 men and 9 women, BMI < or = 25 kg/m2). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc-single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively. RESULTS: The gastric half-emptying time was similar in obese men and women (67.8 +/- 14.79 vs. 66.6 +/- 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 +/- 11.72 minutes; women: 97.25 +/- 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 +/- 47.67 vs. 306.3 +/- 45.52 pg/mL; p < 0.0001 in men and 162.13 +/- 32.95 vs. 272.8 +/- 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = -0.2391x + 157.9; R2 = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R2) in a multiple regression analysis. DISCUSSION: This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity.

Adult↗

PubMed2005

Reduced plasma ghrelin concentration in celiac disease after gluten-free diet treatment.

OBJECTIVE: Celiac disease (CD) is characterized by malabsorption, weight loss and increased energy expenditure. The aim of this study was to investigate the relationship between circulating ghrelin and leptin, which are produced at gastrointestinal level and are involved in energy balance regulation, and changes in body composition and energy metabolism in CD patients before and after gluten-free diet (GFD)-induced restoration of the intestinal mucosa. MATERIAL AND METHODS: Body composition (by dual-energy X-ray absorptiometry), resting metabolic rate and substrate oxidation rates (by indirect calorimetry) were assessed in 18 adult women with the classic form of CD (age 31.4 +/- 7.8 years, body mass index (BMI) 20.6 +/- 2.1 kg/m2) before and at least 2 years after GFD treatment and in 22 age-matched healthy women (age 33.1 +/- 7.2 years, BMI 22.9 +/- 2.1 kg/m2). Plasma leptin and ghrelin concentrations were assessed by the ELISA and RIA procedures, respectively. RESULTS: Fat-free mass was reduced before and after GFD compared to control subjects (p < 0.01), while fat mass increased after treatment (p < 0.01). Plasma leptin concentration was similar between groups and correlated only with BMI (r = 0.84; p < 0.0001) and percentage body fat (r = 0.86; p < 0.0001). Circulating ghrelin levels (pg/ml) were similar between untreated patients and control subjects, but decreased after GFD treatment (untreated CD: 282.6 +/- 55.5 versus treated 109.2 +/- 49.9; p < 0.0001 and versus control subjects 262.2 +/- 30.0; p < 0.0001) and were negatively correlated with BMI in CD patients (r = -0.32; p < 0.01). CONCLUSIONS: The low plasma ghrelin concentration found in CD patients after GFD treatment could only be partially explained by the slight increase in body-weight and fat mass. Further studies are needed to better ascertain the role played by an incomplete functional or quantitative recovery of ghrelin-producing cells in CD.

Adult↗

PubMed2005

Effects of binge eating behavior on fuel oxidation and body composition.

OBJECTIVE: To investigate energy expenditure and glucose metabolism after a standard oral glucose load (75 g) in 8 normal weight bulimic women and 8 normal weight control women and to evaluate the relative endocrine implication. DESIGN: Serum glucose and insulin were measured both in basal conditions and after the glucose load; a basal endocrine assessment and body composition was evaluated and glucose induced thermogenesis (GIT) was calculated during 300 min following the glucose load. RESULTS: Serum glucose levels were significantly lower in bulimics both in fasting and in post-prandial state. Insulin levels were similar in bulimic and control women before and after the glucose load. FSH, leptin and free urinary cortisol (FUC) were all within the normal ranges, but significantly lower in bulimic patients compared with controls (p < 0.001). Fat mass (FM) and Fat-free mass (FFM) were reduced in bulimic patients, even if they normalized after correction per body weight. Resting energy expenditure (REE) was similar in the two groups even after FFM normalization, while GIT was lower in bulimic patients and it was strongly related to free urinary chortisol. Glucose oxidation was higher in fasting state and post glucose load, while lipid oxidation was strongly reduced. CONCLUSION: An energy preservation mechanism seems to be the key element for normal-weight bulimic patients' metabolism, consisting in leptin levels and GIT reduction, and lipid oxidation inhibition.

Absorptiometry, Photon↗

PubMed2005

Predictors of weight loss and reversal of comorbidities in malabsorptive bariatric surgery.

BACKGROUND: Cardiovascular and metabolic comorbidities are dramatically increased in severe obesity, a condition highly resistant to nonsurgical therapy. OBJECTIVE: The objective was to identify predictors of weight loss and reversal of comorbidity in obese patients undergoing malabsorptive bariatric surgery. DESIGN: Morbidly obese men and women (n = 107) were studied before and 2 y after biliopancreatic diversion (BPD). Body composition, serum lipid profile, oral glucose tolerance, and blood pressure were measured. Insulin sensitivity was determined by use of a euglycemic clamp. The length of the small intestine was measured during surgery. RESULTS: Intestinal length was 671 +/- 99 cm, and the residual absorbing intestine after BPD ranged from 54% to 24% of initial length. Patients lost an average of 36% of their initial weight, with approximately 50% of them reaching a body mass index (in kg/m(2)) < 30. Serum cholesterol decreased (from 4.58 +/- 1.11 to 3.34 +/- 0.73 mmol/L; P < 0.0001), as did serum triacylglycerols (from 1.52 +/- 0.59 to 0.88 +/- 0.35 mmol/L; P < 0.0001), whereas insulin sensitivity rose 150% (from 26 +/- 4 to 64 +/- 11 micromol . min(-1) . kg fat-free mass(-1); P < 0.0001). Diabetes (in 23% of patients before surgery) and hypertension (in 83%) were reduced (by 88% and 96%, respectively) after surgery. In a multivariate model (including sex, age, intestinal length, presence of diabetes, insulin sensitivity, and initial fat mass), age and diabetes were independent, negative predictors of weight loss, whereas initial fat mass was a strong positive predictor (r(2) = 0.51). CONCLUSIONS: Two years after BPD in morbidly obese patients, comorbidities are largely corrected and insulin resistance is fully reversed despite persistent obesity. Initial fat mass, but not residual intestinal length, is the strongest predictor of weight loss after BPD.

Adipose Tissue↗

PubMed2005

Effects of weight loss and calorie restriction on carbohydrate metabolism.

PURPOSE OF REVIEW: This article provides an overview of the most recent molecular and clinical outcomes of studies that investigate the effect of weight loss and calorie restriction on carbohydrate metabolism, obtained either by dieting or bariatric surgery. It will focus on aspects of carbohydrate metabolism related to insulin action. The discussion begins by describing attempts to restrain calories by shifting the macronutrient balance from carbohydrates to a higher protein and fat content. The topics covered include insulin secretion and resistance, glucose homeostasis and allostasis, changes in the secretive patterns of adipose tissue and the entero-insular axis. RECENT FINDINGS: Any improvement in glucose homeostasis, insulin sensitivity and secretion after a low-carbohydrate high-fat diet is still unproved. However, the restriction of dietary carbohydrate seems to reduce glycogenolysis and endogenous glucose production in type 2 diabetes mellitus, thus inducing the amelioration of plasma glucose levels, ultimately resulting in a reduction in the glycated haemoglobin concentration. The increased endogenous glucose production caused by enhanced gluconeogenesis and glycogenolysis, reduced insulin sensitivity, mainly caused by acquired defects of glucose transport and phosphorylation, and the impairment of insulin secretion all together contribute to maintain a chronic status of hyperglycaemia. Weight loss and calorie restriction restore glucose homeostasis and produce changes in the secretive activities of adipose tissue and the entero-insular axis. SUMMARY: Weight loss and calorie restriction partly explain the positive changes of glucose disposal. The multistep interaction of several factors at sites of insulin action, insulin secretion, adipose tissue and the entero-insular axis needs further investigation.

Adipose Tissue↗

PubMed2005

Biliopancreatic diversion as a novel approach to the HAIR-AN syndrome.

BACKGROUND: The HAIR-AN syndrome is a rare multisystem disorder in women, that consists of hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). The IR is likely due to a primary defect of the insulin receptor. METHODS: We report the case of a 42-year-old Caucasian woman with HAIR-AN syndrome, impaired glucose tolerance (IGT), mild hyperlipemia, and hypertension, who underwent biliopancreatic diversion (BPD). RESULTS: Within 24 months follow-up after BPD, impaired glucose tolerance, mild hyperlipemia, and hypertension completely reversed. Although insulin sensitivity, estimated by the euglycemic hyperinsulinemic clamp, did not improve, signs and symptoms of hyperandrogenism and acanthosis nigricans resolved fully. CONCLUSION: In HAIR-AN syndrome, malabsorptive bariatric surgery is effective in improving hyperandrogenism and acanthosis nigricans, with noteworthy esthetic consequences. BPD was followed by disappearance of co-morbidities of the syndrome, such as IGT, hypertension and hyperlipemia.

Acanthosis Nigricans↗

PubMed2005

Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6.

The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)alpha or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFalpha or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFalpha and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.

Charcot-Marie-Tooth Disease↗