Fecal incontinence among morbid obese women seeking for weight loss surgery: an underappreciated association with adverse impact on quality of life

Purpose Morbid obesity is associated with urinary incontinence (UI). The study purpose was to determine the prevalence of fecal incontinence (FI), its associated risk factors, and its impact on quality of life (QOL) in morbidly obese women. Materials and methods A questionnaire-based study on morbidly obese women [body mass index (BMI) ≥ 35 m/kg²], attending a bariatric surgery seminar, was conducted. Data included demographics, past medical, surgical and obstetric history, and obesity-related co-morbidities. Patients who reported of FI, completed the Cleveland Clinic Foundation Fecal Incontinence scale (CCF-FI) and the Fecal Incontinence Quality of Life scale (FIQL). Results Participants included 256 women [median age 45 years (19–70)] and mean BMI of 49.3 ± 9.4 m/kg². FI was reported in 63%. History of obstetric injury (OR: 2.4, 95% CI: 1.33–4.3; p < 0.001) and UI (OR: 1.2, 95% CI: 1.1–1.4; p < 0.001) were significantly associated with FI. There was no association with age, BMI, parity, and presence of diabetes or hypertension. Median CCF-FI score was 7 (1–20); 34.5% scored ≥10. Incontinence for gas was the most frequent type (87%) of FI, followed by incontinence for liquids (80%), which also had the highest impact on QOL (p < 0.01). Mean FIQL scores were >3 for all four domains studied. CCF-FI scores were significantly correlated with FIQL scores in all domains (p = 0.02). Comment The prevalence of FI among morbidly obese women may be much higher than the rates reported in the general population. FI has adverse effects on QOL. Its correlation with UI suggests that morbid obesity may pose a risk of global pelvic floor dysfunction.     

BMI is an independent risk factor for snoring in Chinese women aged over 30?years

Objective  The study was designed to analyze body mass index (BMI) as one of risk factors for snoring in Chinese women. Materials and methods  Totally, 2,938 women (2,423 available for evaluation of menstrual status) aged over 30 years from a population-based epidemiologic study were enrolled. Results and discussions  For those with regular menstrual status, BMI was the main risk factor with OR 3.906 (BMI ≥25 kg/m²) and 8.467 (BMI ≥30 kg/m²), respectively, compared with those of BMI 20–25 kg/m² (p < 0.001). For postmenopausal women, BMI was also indicated as a risk factor with OR 2.041 (BMI ≥25 kg/m²) and 2.884 (BMI ≥30 kg/m²) compared with those of BMI 20–25 kg/m² (p < 0.01). As for different BMI, menopause was the only risk factor for women with BMI < 20 kg/m² (OR = 10.568, p < 0.05). Whereas for those with BMI between 20 and 25 kg/m², the risk factors included post-menopause, family history, drinking, etc. Conclusion  In conclusion, the prevalence of snoring was correlated with BMI independent of menstrual status, and lower BMI is a protective factor against snoring in premenopausal women.     

Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in obese insulin-resistant subjects

Aims/hypothesis This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects.Methods A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 ± 2 years; BMI, 32.6 ± 0.8 kg/m²; homeostasis model assessment of insulin resistance, 5.6 ± 0.5; systolic blood pressure [SBP], 140.8 ± 3.2; diastolic blood pressure [DBP], 88.8 ± 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content.Results Ramipril treatment decreased ACE activity compared with placebo (−22.0 ± 1.7 vs 0.2 ± 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, −10.8 ± 2.1 vs −2.7 ± 2.0 mmHg, respectively, p = 0.01; DBP, −10.1 ± 1.3 vs −4.2 ± 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 ± 2.0, after: 19.1 ± 2.4 μmol kg body weight⁻¹ min⁻¹, p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 ± 0.39, after: 1.92 ± 0.29 μmol 100 ml forearm tissue⁻¹ min⁻¹, p = 0.81) and IMTG content (before: 45.4 ± 18.8, after: 48.8 ± 27.5 μmol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments.Conclusions/interpretation Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.     

Effect of beta-adrenergic stimulation on whole-body and abdominal subcutaneous adipose tissue lipolysis in lean and obese men

Aims/hypothesis Obesity is characterised by increased triacylglycerol storage in adipose tissue. There is in vitro evidence for a blunted beta-adrenergically mediated lipolytic response in abdominal subcutaneous adipose tissue (SAT) of obese individuals and evidence for this at the whole-body level in vivo. We hypothesised that the beta-adrenergically mediated effect on lipolysis in abdominal SAT is also impaired in vivo in obese humans. Methods We investigated whole-body and abdominal SAT glycerol metabolism in vivo during 3 h and 6 h [²H₅]glycerol infusions. Arterio–venous concentration differences were measured in 13 lean and ten obese men after an overnight fast and during intravenous infusion of the non-selective beta-adrenergic agonist isoprenaline [20 ng (kg fat free mass)⁻¹ min⁻¹]. Results Lean and obese participants showed comparable fasting glycerol uptake by SAT (9.7 ± 3.4 vs 9.3 ± 2.5% of total release, p = 0.92). Furthermore, obese participants showed an increased whole-body beta-adrenergically mediated lipolytic response versus lean participants. However, their fasting lipolysis was blunted [glycerol rate of appearance: 7.3 ± 0.6 vs 13.1 ± 0.9 μmol (kg fat mass)⁻¹ min⁻¹, p < 0.01], as was the beta-adrenergically mediated lipolytic response per unit SAT [Δ total glycerol release: 140 ± 71 vs 394 ± 112 nmol (100 g tissue)⁻¹ min⁻¹, p < 0.05] compared with lean participants. Net triacylglycerol flux tended to increase in obese compared with lean participants during beta-adrenergic stimulation [Δ net triacylglycerol flux: 75 ± 32 vs 16 ± 11 nmol (100 g tissue)⁻¹ min⁻¹, p = 0.06]. Conclusions/interpretation We demonstrated in vivo that beta-adrenergically mediated lipolytic response is impaired systematically and in abdominal SAT of obese versus lean men. This may be important in the development or maintenance of increased triacylglycerol stores and obesity.     

Influence of gestational diabetes on the long-term control of glucose tolerance

Aims/hypothesis Gestational diabetes (GDM) carries a high risk of subsequent diabetes. We asked what impact prior GDM has on beta cell function and insulin action in women who maintain normal glucose tolerance (NGT) for a long time. Methods Ninety-one women with NGT (aged 41 ± 8 years, mean±SD) were studied (by mathematical modelling of the C-peptide response to an OGTT) 7 [6] years (median [interquartile range]) after the index pregnancy, during which 52 had GDM (pGDM) and 39 had NGT (pNGT). In all women an OGTT had also been performed at 29 ± 3 weeks of the index pregnancy. Results Women with pGDM were matched with women with pNGT for age, familial diabetes, time and weight gain since index pregnancy, parity, BMI (25.4 ± 3.9 vs 26.8 ± 6.4 kg/m²), and fasting (4.64 ± 0.56 vs 4.97 ± 0.46 mmol/l) and 2 h plasma glucose levels (5.91 ± 1.14 vs 5.91 ± 1.21 mmol/l). Nonetheless, fasting (49 [29] vs 70 [45] pmol min⁻¹ m⁻², p < 0.001) and total insulin secretion (32 [17] vs 48 [21] nmol m⁻², p < 0.0001) and beta cell glucose sensitivity (slope of the insulin secretion/plasma glucose concentration–response function) (95 [71] vs 115 [79] pmol min⁻¹ m⁻² (mmol/l)⁻¹, p = 0.025) were reduced in the pGDM group compared with the pNGT group, while insulin sensitivity was preserved (424 [98] vs 398 [77] ml min⁻¹ m⁻²). At index pregnancy, women with pGDM and those with pNGT had similar age and BMI. However, both insulin sensitivity (359 [93] vs 417 [92] ml min⁻¹ m⁻², p = 0.0012) and the insulin/glucose incremental area ratio (an empirical index of beta cell function; 98 [74] vs 138 [122] pmol/mmol, p = 0.028) were reduced in women with pGDM. Conclusions Even in women who maintain normal insulin sensitivity, impaired beta cell function is carried over into the NGT status several years after a GDM pregnancy.     

Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

Aims/hypothesis Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. Methods We compared the effects of a normal (NPD; 1.38 ± 0.08 g kg⁻¹ day⁻¹) or low (LPD; 0.81 ± 0.04 g kg⁻¹ day⁻¹) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (l-[5,5,5,-²H₃]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. Results In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 ± 1.1 vs 42 ± 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 ± 0.6 vs 7.2 ± 0.5 μmol/l (3.64 ± 0.22 vs 2.45 ± 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 ± 1.17 vs 6.0 ± 1.8 μmol 1.73 m⁻² day⁻¹ (3.7 ± 0.4 vs 1.9 ± 0.3 g 1.73 m⁻² day⁻¹); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 ± 0.4 vs 4.51 ± 0.8 g/day; p < 0.05), ELF (1.93 ± 0.08 vs 2.11 ± 0.08 μmol kg⁻¹ min⁻¹; p < 0.05) and total fibrinogen pool; increased serum albumin (42 ± 1 vs 38 ± 1 g/l; p < 0.01) and albumin ASR (14.1 ± 1 vs 9.9 ± 1 g 1.73 m⁻² day⁻¹; p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = −0.749; p < 0.05). Conclusions/interpretation LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration. ISRCTN ID no: CCT-NAPN-16911     

Body Mass Index is Inversely Related to Mortality in Elderly Subjects

Purpose To study the long-term effect of being overweight on mortality in very elderly subjects. Methods The medical records of 470 inpatients (226 males) with a mean age of 81.5 ± 7 years and hospitalized in an acute geriatric ward between 1999 and 2000 were reviewed for this study. Body mass index (BMI) at admission day was subdivided into quartiles: <22, 22–25, 25.01–28, and ≥28 kg/m². Patients were followed-up until August 31, 2004. Mortality data were taken from death certificates. Results During a mean follow-up of 3.46 ± 1.87 years (median 4.2 years [range 1.6 to 5.34 years]), 248 patients died. Those who died had lower baseline BMI than those who survived (24.1 ± 4.2 vs 26.3 ± 4.6 kg/m²; p < .0001). The age-adjusted mortality rate decreased from 24 to 9.6 per 100 patient-years from the highest to lowest BMI quartile (p < .001). BMI was associated with all-cause and cause-specific mortality even after controlling for sex. A multivariate Cox proportional hazards model identified that even after controlling for male gender, age, renal failure, and diabetes mellitus, which increased the risk of all-cause mortality, elevated BMI decreased the all-cause mortality risk. Conclusions In very elderly subjects, elevated BMI was associated with reduced mortality risk.     

Effect of type 2 diabetes mellitus on exercise intolerance and the physiological responses to exercise in peripheral arterial disease

Aims/hypothesis There are conflicting data about the effect of type 2 diabetes mellitus on exercise tolerance in peripheral arterial disease. To elucidate this problem, we compared the tolerance and physiological responses to treadmill and cycle exercise in 31 patients with peripheral arterial disease and intermittent claudication. Materials and methods One group of these patients had type 2 diabetes (n = 12) and its members were matched for sex and age with a group of patients who did not have diabetes (n = 12). Since BMI and body weight were greater in the diabetic group (28.4 ± 3.7 vs 25.2 ± 2.4 kg/m²; 84.0 ± 14.6 vs 73.8 ± 8.0 kg), we also studied a third, ‘heavy’ group of non-diabetic patients with claudication of similar age (n = 7; BMI = 30.9 ± 5.3 kg/m²; body weight = 85.2 ± 8.2 kg). Results Compared with the ‘light’ non-diabetic group, maximum treadmill times were shorter for the diabetic and heavy non-diabetic groups (1,448 vs 845 and 915 s; ANOVA p = 0.01); maximum cycle time also tended to be shorter (ANOVA, p = 0.08) in the diabetic and heavy non-diabetic groups (median = 1,231 vs 730 and 797 s). The majority of physiological responses assessed were not different between the groups, although the time constant of oxygen uptake during submaximal treadmill and cycle exercise was significantly larger (ANOVA p < 0.05) for the diabetic group. Conclusions/interpretation These data demonstrate that exercise tolerance is lower in diabetic than non-diabetic patients with claudication, but that this difference is due to obesity rather than diabetes itself.     

Hyperinsulinaemia during exercise does not suppress hepatic glycogen concentrations in patients with type 1 diabetes: a magnetic resonance spectroscopy study

Aims/hypothesis We compared in vivo changes in liver glycogen concentration during exercise between patients with type 1 diabetes and healthy volunteers. Methods We studied seven men with type 1 diabetes (mean ± SEM diabetes duration 10 ± 2 years, age 33 ± 3 years, BMI 24 ± 1 kg/m², HbA_1c 8.1 ± 0.2% and VO₂ peak 43 ± 2 ml [kg lean body mass]⁻¹ min⁻¹) and five non-diabetic controls (mean ± SEM age 30 ± 3 years, BMI 22 ± 1 kg/m², HbA_1c 5.4 ± 0.1% and VO₂ peak 52 ± 4 ml [kg lean body mass]⁻¹ min⁻¹, before and after a standardised breakfast and after three bouts (EX1, EX2, EX3) of 40 min of cycling at 60% VO₂ peak. ¹³C Magnetic resonance spectroscopy of liver glycogen was acquired in a 3.0 T magnet using a surface coil. Whole-body substrate oxidation was determined using indirect calorimetry. Results Blood glucose and serum insulin concentrations were significantly higher (p < 0.05) in the fasting state, during the postprandial period and during EX1 and EX2 in subjects with type 1 diabetes compared with controls. Serum insulin concentration was still different between groups during EX3 (p < 0.05), but blood glucose concentration was similar. There was no difference between groups in liver glycogen concentration before or after the three bouts of exercise, despite the relative hyperinsulinaemia in type 1 diabetes. There were also no differences in substrate oxidation rates between groups. Conclusions/interpretation In patients with type 1 diabetes, hyperinsulinaemic and hyperglycaemic conditions during moderate exercise did not suppress hepatic glycogen concentrations. These findings do not support the hypothesis that exercise-induced hypoglycaemia in patients with type 1 diabetes is due to suppression of hepatic glycogen mobilisation. K. Chokkalingam and K. Tsintzas contributed equally to this study.     

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

Aims/hypothesis  We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. Methods  Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic–hyperinsulinaemic clamp. Results  Basal GLP1 relative amplitude (amplitude/mesor × 100) was 25.82–4.06% in NGT; it increased to 41.38–4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 ± 94 to 846 ± 161 pmol l⁻¹ min in NGT, whereas GIP AUC decreased significantly from 1,373 ± 565 to 513 ± 186 pmol l⁻¹ min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD × diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 ± 3.63 to 36.04 ± 8.55 μmol [kg fat-free mass]⁻¹ min⁻¹) and diabetic patients (from 9.49 ± 3.56 to 38.57 ± 4.62 μmol [kg fat-free mass]⁻¹ min⁻¹). Conclusions/interpretation  An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.     

Gender influence on ocular manifestations and their outcome in Behcet’s Disease. A long-term follow-up of up to 20 years

It is of general belief that males are prone to more frequent, more severe manifestations, and less favorable outcome. We evaluated this hypothesis in ophthalmological manifestations (OM) of Behcet's Disease (BD). Visual acuity (VA), anterior uveitis, posterior uveitis (PU), and retinal vasculitis (RV) were checked, according to Ben Ezra, in 1,515 patients with eye lesions. The data at baseline and last visit were compared. Male/female ratio was 1.2 in the BD registry (6,500 patients) and 1.51 for OM patients (Chi² = 98.962, p < 0.0001). The patients-year-follow-up was 4,987. All parameters improved significantly from the baseline. Mean VA improved from 4.87 to 5.35 for males (p < 0.0001) and from 5.20 to 5.74 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.60). The mean improvement for males/females was statistically non-significant (p = 0.58). Percent improvement of eyes for males/females was 47.1%/48.8% (p = 0.41). Mean PU improved from 1.83 to 0.71 for males (p < 0.0001) and from 1.66 to 0.49 for females (p < 0.0001). Difference between males/females at baseline was significant (p = 0.01). The mean improvement for males/females was statistically non-significant (p = 0.45). Percent improvement of eyes for males/females was 75.4%/81.0% (p = 0.004). Mean RV improved from 2.05 to 1.16 for males (p < 0.0001) and from 1.97 to 0.99 for females (p < 0.0001). Difference between males/females at baseline was not significant (p = 0.42). The mean improvement for males/females was statistically non-significant (p = 0.47). Percent improvement of eyes for males/females was 62%/64.4% (p = 0.33). Male gender is more prone to ocular manifestations. The severity of lesions at baseline was the same for VA and RV. For PU, the difference was statistically significant, but was not clinically relevant. The therapeutic outcome (mean improvement and percent of improved eyes) was the same for all parameters.     

Electrical Stimulation and Pelvic Floor Muscle Training With Biofeedback in Patients With Fecal Incontinence: A Cohort Study of 281 Patients

Purpose Pelvic floor rehabilitation is an appealing treatment for patients with fecal incontinence but reported results vary. This study was designed to assess the outcome of pelvic floor rehabilitation in a large series of consecutive patients with fecal incontinence caused by different etiologies. Methods A total of 281 patients (252 females) were included. Data about medical history, anal manometry, rectal capacity measurement, and endoanal sonography were collected. Subgroups of patients were defined by anal sphincter complex integrity, and nature and possible underlying causes of fecal incontinence. Subsequently patients were referred for pelvic floor rehabilitation, comprising nine sessions of electric stimulation and pelvic floor muscle training with biofeedback. Pelvic floor rehabilitation outcome was documented with Vaizey score, anal manometry, and rectal capacity measurement findings. Results Vaizey score improved from baseline in 143 of 239 patients (60 percent), remained unchanged in 56 patients (23 percent), and deteriorated in 40 patients (17 percent). Mean Vaizey score reduced with 3.2 points (P < 0.001). A Vaizey score reduction of ≥ 50 percent was observed in 32 patients (13 percent). Mean squeeze pressure (+5.1 mmHg; P = 0.04) and maximal tolerated volume (+11 ml; P = 0.01) improved from baseline. Resting pressure (P = 0.22), sensory threshold (P = 0.52), and urge sensation (P = 0.06) remained unchanged. Subgroup analyses did not show substantial differences in effects of pelvic floor rehabilitation between subgroups. Conclusions Pelvic floor rehabilitation leads overall to a modest improvement in severity of fecal incontinence, squeeze pressure, and maximal tolerated volume. Only in a few patients, a substantial improvement of the baseline Vaizey score was observed. Further studies are needed to identify patients who most likely will benefit from pelvic floor rehabilitation. Supported by grant 945-01-013 of the Netherlands Organization for Health Research and Development. Presented at the United European Gastroenterology Week, Copenhagen, Denmark, October 15 to October 19, 2005. Reprints are not available.     

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

Aims/hypothesis The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing bilio-pancreatic diversion (BPD).Subjects and methods We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic–hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52±7 kg/m², mean±SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery.Results BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341±79 ml min⁻¹ m⁻², post-BPD 511±57 ml min⁻¹ m⁻², lean 478±49 ml min⁻¹ m⁻²). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min⁻¹ m⁻² l mmol⁻¹, median [interquartile range]) compared with lean subjects (82 [98]; p≤0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r ²=0.67, partial r=−0.76 and −0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement.Conclusions/interpretation Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity.     

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects

Aims/hypothesis Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls. Methods In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4 ± 1 and 29.3 ± 0.9 kg/m² respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic–euglycaemic clamp. Results The PCr half-time was 45% longer in diabetic patients compared with controls (27.3 ± 3.5 vs 18.7 ± 0.9 s, p < 0.05), whereas IMCL content was similar (1.37 ± 0.30 vs 1.25 ± 0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0 ± 2.2 vs 18.9 ± 2.3 μmol min⁻¹ kg⁻¹, p < 0.05 [all mean ± SEM]). PCr half-time correlated positively with fasting plasma glucose (r ² = 0.42, p < 0.01) and HbA_1c (r ² = 0.48, p < 0.05) in diabetic patients. Conclusions/interpretation The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.     

Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle

Aims/hypothesis Insulin resistance and type 2 diabetes are associated with mitochondrial dysfunction. The aim of the present study was to test the hypothesis that oxidative phosphorylation and electron transport capacity are diminished in the skeletal muscle of type 2 diabetic subjects, as a result of a reduction in the mitochondrial content. Materials and methods The O₂ flux capacity of permeabilised muscle fibres from biopsies of the quadriceps in healthy subjects (n = 8; age 58 ± 2 years [mean±SEM]; BMI 28 ± 1 kg/m²; fasting plasma glucose 5.4 ± 0.2 mmol/l) and patients with type 2 diabetes (n = 11; age 62 ± 2 years; BMI 32 ± 2 kg/m²; fasting plasma glucose 9.0 ± 0.8 mmol/l) was measured by high-resolution respirometry. Results O₂ flux expressed per mg of muscle (fresh weight) during ADP-stimulated state 3 respiration was lower (p < 0.05) in patients with type 2 diabetes in the presence of complex I substrate (glutamate) (31 ± 2 vs 43 ± 3 pmol O₂ s⁻¹ mg⁻¹) and in response to glutamate + succinate (parallel electron input from complexes I and II) (63 ± 3 vs 85 ± 6 pmol s⁻¹ mg⁻¹). Further increases in O₂ flux capacity were observed in response to uncoupling by FCCP, but were again lower (p < 0.05) in type 2 diabetic patients than in healthy control subjects (86 ± 4 vs 109 ± 8 pmol s⁻¹ mg⁻¹). However, when O₂ flux was normalised for mitochondrial DNA content or citrate synthase activity, there were no differences in oxidative phosphorylation or electron transport capacity between patients with type 2 diabetes and healthy control subjects. Conclusions/interpretation Mitochondrial function is normal in type 2 diabetes. Blunting of coupled and uncoupled respiration in type 2 diabetic patients can be attributed to lower mitochondrial content.     

Upper Gastrointestinal Symptoms and Associated Disorders in Morbidly Obese Patients: A Prospective Study

Objective To prospectively evaluate the frequency of upper gastrointestinal symptoms and associated disorders in morbidly obese patients with endoscopy and histology prior to their gastric bypass surgery in comparison with age- and sex-matched nonobese control subjects. Methods All patients who were scheduled to undergo laparoscopic gastric bypass for treatment of morbid obesity (body mass index, BMI > 40 kg/m²) during a 1-year period (n = 101) were included in the study. Age- and sex-matched nonobese patients who were seen in the medical clinics during the study period were enrolled as control subjects. The demographic data, total body weight, body mass index, and gastrointestinal symptoms were recorded, and the results of upper endoscopy and histology were tabulated. Endoscopic documentation of hiatal hernia, esophagitis, gastritis, gastric polyps, and peptic ulcer disease was also noted along with the histologic findings of the mucosal biopsies from the upper gastrointestinal tract. Results The prevalence of heartburn as a symptom was significantly higher (P < 0.05) in the morbidly obese patients (32.6%) compared with in the control group (18.8%). Endoscopically, the prevalence of hiatal hernia was also significantly higher (P < 0.05) in the morbidly obese group (38.6%) compared with in the control group (13.8%). Similarly the frequency of endoscopically and histologically identified gastritis was significantly higher (P < 0.01) in the morbidly obese patient group. However, the frequency of histologically identified Helicobacter pylori was not statistically different in the two groups. Conclusion These observations suggest a significant increase in the frequency of heartburn, hiatal hernia, and histologically identified gastritis in morbidly obese patients.     

A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans

Aims/hypothesis  It has recently been suggested that the rs738409 G allele in PNPLA3, which encodes adiponutrin, is strongly associated with increased liver fat content in three different ethnic groups. The aims of the present study were as follows: (1) to try to replicate these findings in European individuals with quantitative measures of hepatic fat content; (2) to study whether the polymorphism influences hepatic and adipose tissue insulin sensitivity; and (3) to investigate whether PNPLA3 expression is altered in the human fatty liver. Methods  We genotyped 291 Finnish individuals in whom liver fat had been measured using proton magnetic resonance spectroscopy. Hepatic PNPLA3 expression was measured in 32 participants. Hepatic and adipose tissue insulin sensitivities were measured using a euglycaemic–hyperinsulinaemic (insulin infusion 0.3 mU kg⁻¹ min⁻¹) clamp technique combined with infusion of [3-³H]glucose in 109 participants. Results  The rs738409 G allele in PNPLA3 was associated with increased quantitative measures of liver fat content (p = 0.011) and serum aspartate aminotransferase concentrations (p = 0.002) independently of age, sex and BMI. Fasting serum insulin and hepatic and adipose tissue insulin sensitivity were related to liver fat content independently of genotype status. PNPLA3 mRNA expression in the liver was positively related to obesity (r = 0.62, p < 0.0001) and to liver fat content (r = 0.58, p = 0.025) in participants who were not morbidly obese (BMI < 40 kg/m²). Conclusions/interpretation  A common variant in PNPLA3 increases the risk of hepatic steatosis in humans. A. Kotronen and L. E. Johansson contributed equally to this study.     

Age Effects on Internal Anal Sphincter Thickness and Diameter in Nulliparous Females

Purpose Age can affect the delicate physiologic balance of the internal anal sphincter diameters and pressure governed by Laplace’s law. This study compares the effect of aging on the internal anal sphincter thickness and diameter in younger and older nulliparous females without symptoms of fecal incontinence undisturbed by an endoanal probe. Methods Magnetic resonance images were selected from a large database of nulliparous females to form two groups: “younger” females, aged 30 years and younger (n = 32), and “older” females, aged 50 years and older (n = 32). All patients were scanned without endoanal coils to allow undistorted measurement of the internal anal sphincter diameters. Inner and outer diameters were measured from axial magnetic resonance images and used to calculate sphincter thickness and mean radius by two independent investigators blinded to patient age. Results The mean age in the younger group was 26 ± 2.8 years, whereas that of the older group was 61.8 ± 7.6 years. Older females had a 33 percent thicker internal anal sphincter (younger vs. older: 4.5 ± 0.7 vs. 5.9 ± 1 mm; P < 0.001), a 20 percent larger inner diameter (7.1 ± 1.3 vs. 8.5 ± 1.8 mm; P = 0.001), and a 27 percent larger outer diameter (16 ± 2.1 vs. 20.3 ± 3.3 mm; P < 0.001) than younger females. Neither sphincter thickness nor inner or outer diameter correlated with body mass index. Conclusions There is an increase in internal anal sphincter thickness, inner diameter, and outer diameter, which correlates with age in asymptomatic nulliparous females. Supported by the National Institutes of Health, ORWH & NICHD Sex & Gender Factors Affecting Women’s Health SCOR: P50, and NICHD R01 HD 044406: NICHD R01 DK 051405, R01 HD 038665; German Research Foundation (DFG, HU1502/1–1). Presented as a poster at the annual meeting of the American Urogynecologic Society, October 19 to 21, 2006, Palm Springs, Florida. Presented as an oral poster at the annual meeting of the International Urogynecological Association, September 6 to 9, 2006, Athens, Greece. Presented as an oral poster and oral presentation at the annual meeting of the German Association of Gynecology and Obstetrics, September 19 to 22, 2006, Berlin, Germany.     

Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes

Aims/hypothesis Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. The aim of our study was to assess parameters of the skeletal muscle sphingomyelin signalling pathway in men at risk of developing type 2 diabetes. Methods We studied 12 lean (BMI < 25 kg/m²) men without a family history of diabetes (control group), 12 lean male offspring of type 2 diabetic patients, and 21 men with overweight or obesity comprising 12 with NGT (obese-NGT) and nine with IGT (obese-IGT). A euglycaemic-hyperinsulinaemic clamp and a biopsy of vastus lateralis muscle were performed. Ceramide, sphingomyelin, sphinganine and sphingosine levels and sphingomyelinase and ceramidase activities were measured in muscle. Muscle diacylglycerol and triacylglycerol levels were estimated in a subgroup of 27 men (comprising men from all the above groups). Results Compared with the control group, the lean offspring of diabetic patients and the men with overweight or obesity showed lower insulin sensitivity (all p < 0.005) and a greater muscle ceramide level (all p < 0.01). The obese-IGT group had lower insulin sensitivity (p = 0.0018) and higher muscle ceramide (p = 0.0022) than the obese-NGT group. There was lower muscle sphingosine level and alkaline ceramidase activity in offspring of diabetic patients (p = 0.038 and p = 0.031, respectively) and higher sphinganine level in the obese-NGT (p = 0.049) and obese-IGT (p = 0.002) groups than in the control group. Muscle sphingomyelin was lower (p = 0.0028) and neutral sphingomyelinase activity was higher (p = 0.00079) in the obese-IGT than in the obese-NGT group. Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions. Conclusions/interpretations Ceramide accumulates in muscle of men at risk of developing type 2 diabetes.     

Results, Outcome Predictors, and Complications after Stapled Transanal Rectal Resection for Obstructed Defecation

Purpose Obstructed defecation may be treated by stapled transanal rectal resection, but different complications and recurrence rates have been reported. The present study was designed to evaluate stapled transanal rectal resection results, outcome predictive factors, and nature of complications. Methods Clinical and functional data of 123 patients were retrospectively analyzed. All patients had symptoms of obstructed defecation before surgery and had rectocele and/or intussusception. Of them, 85 were operated on by the authors and 38 were referred after stapled transanal rectal resection had been performed elsewhere. Results At a median follow-up of 17 (range, 3–44) months, 65 percent of the patients operated on by the authors had subjective improvement. Recurrent rectocele was present in 29 percent and recurrent intussusception was present in 28 percent of patients. At univariate analysis, results were worse in those with preoperative digitation (P < 0.01), puborectalis dyssynergia (P < 0.05), enterocele (P < 0.05), larger size rectocele (P < 0.05), lower bowel frequency (P < 0.05), and sense of incomplete evacuation (P < 0.05). Bleeding was the most common perioperative complication occurring in 12 percent of cases. Reoperations were needed in 16 patients (19 percent): 9 for recurrent disease. In the 38 patients referred after stapled transanal rectal resection, the most common problems were perineal pain (53 percent), constipation with recurrent rectocele and/or intussusception (50 percent), and incontinence (28 percent). Of these patients, 14 (37 percent) underwent reoperations: 7 for recurrence. Three patients presented with a rectovaginal fistula. One other patient died for necrotizing pelvic fasciitis. Conclusions Stapled transanal rectal resection achieved acceptable results at the cost of a high reoperation rate. Patients with puborectalis dyssynergia and lower bowel frequency may do worse because surgery does not address the causes of their constipation. Patients with large rectoceles, enteroceles, digitation, and a sense of incomplete evacuation may have more advanced pelvic floor disease for which stapled transanal rectal resection, which simply removes redundant tissue, may not be adequate. This, together with the complications observed in patients referred after stapled transanal rectal resection, suggests that this procedure should be performed by colorectal surgeons and in carefully selected patients. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7 2006. Reprints are not available.