Von Willebrand factor propeptide makes it easy to identify the shorter Von Willebrand factor survival in patients with type 1 and type Vicenza von Willebrand disease

Reduced von Willebrand factor (VWF) half-life has been suggested as a new pathogenic mechanism in von Willebrand disease (VWD). The usefulness of VWF propeptide (VWFpp) in exploring VWF half-life was assessed in 22 type 1 and 14 type Vicenza VWD patients, and in 30 normal subjects, by comparing the findings on post-Desmopressin (DDAVP) VWF t(1/2) elimination (t(1/2el)). The VWFpp/VWF antigen ratio (VWFpp ratio) was dramatically increased in type Vicenza VWD (13.02 +/- 0.49) when compared to normal subjects (1.45 +/- 0.06), whereas it appeared to be normal in all type 1 VWD patients (1.56 +/- 0.7), except for the four carrying the C1130F mutation (4.69 +/- 0.67). A very short VWF t(1/2el) was found in type Vicenza VWD (1.3 +/- 0.2 h), while all type 1 VWD patients had a t(1/2el) similar to that of the controls (11.6 +/- 1.4 and 15.4 +/- 2.5 h respectively), except for the four patients carrying the C1130F mutation, who had a significantly shorter VWF survival (4.1 +/- 0.2 h). A significant inverse correlation emerged between VWFpp ratio and VWF t(1/2el) in both VWD patients and normal subjects. The VWFpp ratio thus seemed very useful for distinguishing between type 1 VWD cases with a normal and a reduced VWF survival, as well as for identifying type Vicenza VWD.     

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.     

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/m²) 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.Type 2 diabetes is associated with serious complications, including cardiovascular disease, premature death, blindness, renal failure, amputations, and cognitive decline (1). Recently, the efficacy of the stringent glycemic control by medical therapy was found to be ineffective in reducing major macrovascular complications, suggesting the presence of other causative factors. In fact, intensive treatment, targeted at attaining normal glycated hemoglobin levels, i.e., <6.0%, not only was found to be ineffective in reducing cardiovascular events but also was found to be associated with significantly higher mortality, leading to the decision to terminate the intensive regimen after 3.5 years of follow-up in the Action to Control Cardiovacular Risk in Diabetes (ACCORD) trial (2). Also, the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) (3), where pioglitazone was added to ongoing glucose-lowering therapy in type 2 diabetic patients at high cardiovascular risk, did not show significant reduction of cardiovascular events, in spite of a significant improvement of HbA_1c. As shown in the Veterans Affairs Diabetes Trial (VADT) (4), although a comparison of intensive versus standard therapy did not reveal significant effects on either death rate or microvascular complications, strict glycemic control seems to be relevant in decreasing the conversion from normo- to micro- or macroalbuminuria. Similar results, i.e., a decreased incidence of albuminuria, were also obtained in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (5).Importantly, when intensive glucose control strategy was started at the time of diagnosis, a significantly decreased risk of myocardial infarction and death from any cause, in addition to a large reduction in the risk of microvascular disease, was observed, suggesting that it is crucial to start adequate medical treatment and lifestyle modification as soon as possible (6). Unfortunately, obese diabetic patients have a limited compliance to the diet, which is essential to obtain a reasonable metabolic control. There is evidence in the literature that type 2 diabetes is controlled in fewer than 50% of patients in the U.S. (7). Even with the most recent therapy, liraglutide in monotherapy, the American Diabetes Association’s HbA_1c goal of <7% was reached only in the 51% of patients with the highest daily dose of 1.8 mg (8). Therefore, bariatric surgery can represent a valid option to the medical treatment failure, at least in morbidly obese subjects.A recent systematic review and meta-analysis of the literature (9) showed that the clinical and laboratory manifestations of type 2 diabetes are resolved in 78.1% and are improved in 86.6% of patients after bariatric surgery. However, a gradation of effectiveness exists among the different bariatric procedures, with bilio-pancreatic diversion (BPD) and duodenal switch providing the greatest effect (9).The Swedish Obese Subjects (SOS) study (10), in which gastric bypass, vertical banded gastroplasty, and banding bariatric surgery were performed in obese subjects, was associated with significant reduction in overall mortality after 10 years of follow-up compared with conventional treatment. These data were so impressive that diabetologists have proposed the surgical option in type 2 diabetes as soon as possible (11).In previous studies, we have shown that, similarly to what has been observed after Roux-en-Y gastric bypass (12), after BPD, type 2 diabetes also rapidly reverses to normal glucose tolerance independently of weight loss (13,14). To our knowledge, no study is available in the literature about the long-term effect of bariatric surgery on diabetic complications. In the current study, we report 10-year follow-up effects of BPD on micro- and macrovascular outcomes in newly diagnosed type 2 diabetic patients with severe obesity.     

Menopause, insulin resistance, and risk factors for cardiovascular disease

OBJECTIVE: In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance. DESIGN: Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age (cutoff 50 y). RESULTS: M/kg(FFM)/I significantly decreased after menopause (12.41 +/- 3.40 vs 10.96 +/- 3.68; P < 0.01) and in men 50 years and older (11.39 +/- 3.47 vs 10.32 +/- 3.77 micromol x min(-1) x kg(-1) x microUI/mL; P < 0.02). CVS was lowest in fertile women (-0.414 +/- 0.57 vs 0.107 +/- 0.43; P < 0.0001) and highest in men 50 years and older (0.045 +/- 0.455 vs 0.257 +/- 0.51; P < 0.001). CVS significantly correlated with M/kg(FFM)/I in men 49 years and younger (r(o) = -0.27, P < 0.0001) and 50 years and older (r(o) = -0.38, P < 0.0001) and with fasting insulin in fertile women (r(o) = -0.29, P < 0.01) and in the other groups (r(o) ranging from 0.37 to 0.45, P < 0.0001). CONCLUSIONS: Menopause does not seem to strictly relate to a decrease in insulin sensitivity as postmenopausal women had the same insulin sensitivity as age-matched men. In the population studied, the best predictor of CVS was fasting insulin rather than insulin sensitivity.     

Oxidation and oxidation potential in contemporary packaging for polyethylene total joint replacement components

The packaging and chemical stability of both conventional and highly crosslinked polyethylene (PE) components available for clinical use in Italy were analyzed. A total of 100 sterilized PE components were entered by 18 orthopedic manufacturers into the study. Six of the manufacturers were Italian and the remaining were based in Europe or America. Hydroperoxide, oxidation, and trans-vinylene levels within the PE components were characterized using Fourier-transform infrared spectroscopy (FTIR). None of the 31 gas-sterilized components had detectable free radicals, hydroperoxide content, or oxidation. Among radiation-sterilized inserts, the highest oxidation and hydroperoxide levels were associated with gas-permeable and polymer-barrier packaging. To the authors' knowledge, this is the first study that relates elevated oxidation and hydroperoxide content in gamma-sterilized PE components to certain types of contemporary, polymeric barrier packaging.