GDF-15 Is Associated with Cancer Incidence in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer. METHODS: We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period. RESULTS: During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53-2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22-2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28-2.28, P < 0.001) and 1.68 (95% CI 1.02-2.76, P = 0.042), respectively. CONCLUSIONS: Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.

Cardiovascular safety of metformin and sulfonylureas in patients with different cardiac risk profiles.

OBJECTIVES/BACKGROUND: Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. METHODS: 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis. RESULTS: During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP. CONCLUSIONS: Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.

[Type 2 Diabetes mellitus-screening and prevention: Update 2016]. / Typ 2 Diabetes mellitus - Screening und Prävention : Update 2016.

The prevalence of diabetes is increasing in westernized countries. In addition, about half of all patients suffering from diabetes are not diagnosed. The current article represents the recommendations of the Austrian Diabetes Association for the screening and prevention of type 2 diabetes, based on currently available evidence.

Effects of smoking cessation on ß-cell function, insulin sensitivity, body weight, and appetite.

OBJECTIVE: To stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, ß-cell function, and appetite. SUBJECTS AND METHODS: Twenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m(2)) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B; n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and ß-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured. RESULTS: AFTER 3 MONTHS' SMOKING ABSTINENCE, BODY WEIGHT, AND FAT MASS WERE INCREASED (+4 AND +22% RESPECTIVELY, P0.05) AND FASTING INSULIN SENSITIVITY DETERIORATED (QUICKI: post, 0.37±0.02 vs baseline, 0.41±0.2; P<0.05), while OGIS remained unchanged throughout. IGI40 increased by 31% after >3 months' smoking abstinence (P<0.01). Carbohydrate ingestion increased after stopping smoking (P<0.05). NPY fasting levels were increased after >3 months (P<0.05), PYY, GLP1, leptin, ghrelin, and visfatin were unchanged. CONCLUSION: Smoking cessation is associated with transient metabolic changes including increased ß-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.

Estimated glomerular filtration rate and albuminuria: true predictors of cardiovascular events in obese patients with type 2 diabetes?

BACKGROUND: The widely used MDRD formula underestimates kidney function in obese patients with diabetes mellitus. Therefore we aimed to evaluate the predictive value of estimated glomerular filtration rate (eGFR) for cardiovascular events in a typical cohort of patients with diabetes mellitus. METHODS: A total of 988 patients were analyzed. Cox regression models including the variables HbA1c, age, duration of diabetes, eGFR and urinary albumin to creatinine ratio (UACR) were run. First the whole collective was analyzed, in a second step the cohort was split into four different groups according to body mass index (BMI) and eGFR (Group 1, 475 Pts: eGFR > 60 ml/min; BMI < 30 kg/m(2), Group 2, 274 Pts: eGFR > 60 ml/min;BMI > 30 kg/m(2), Group 3, 110 Pts,: eGFR < 60 ml/min; BMI > 30 kg/m(2) and Group 4, 129 Pts.: eGFR < 60 ml/min;BMI < 30 kg/m(2)). eGFR was calculated using MDRD, Cockroft-Gault, and CKD-EPI formula. The endpoint was defined as unplanned cardiovascular hospitalization. RESULTS: Patients (571 male, 417 female) were 61 ± 22 years of age, mean duration of diabetes was 14.3 ± 12.3 years. After a median follow-up of 29 months 95 (9.6 %) patients reached the defined endpoint. The first model, including all patients showed that UACR (HR 1.001, p < 0.001) and eGFR (HR 0.957, p < 0.001) were significant predictors of the composite endpoint. In obese patients eGFR completely lost its predictive value for cardiovascular events. The prevalence of normoalbuminuria in patients with an eGFR below 60 ml/min was 59.4 %. CONCLUSION: In obese patients eGFR is not predictive for cardiovascular events.

[Type 2 diabetes mellitus-screening and prevention]. / Typ 2 Diabetes Mellitus - Screening und Prävention.

The prevalence of diabetes is increasing in westernized countries. In addition, about half of all patients suffering from diabetes are not diagnosed. The current article represents the recommendations of the Austrian Diabetes Association for the screening and prevention of type 2 diabetes, based on currently available evidence.

Non-conventional markers of atherosclerosis before and after gastric banding surgery.

AIMS: Obesity and type 2 diabetes are associated with increased cardiovascular risk and elevation of traditional and non-traditional risk markers. As bariatric surgery reduces overweight and improves metabolic derangement, we examined a cluster of established and emerging cardiovascular risk factors, such as soluble CD40 ligand (sCD40L) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), which might improve prediction of future cardiovascular events because of their more direct involvement in plaque destabilization. METHODS AND RESULTS: Obese patients [n = 32, body mass index (BMI) 46.1 +/- 5.9 kg/m(2)] underwent clinical examinations and blood sampling for measurement of glucose and lipid parameters as well as non-traditional cardiovascular risk markers, i.e. high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 (PAI-1), soluble cellular adhesion molecules (CAM), MMP-2, MMP-9, CD40L, and Lp-PLA(2) before and after 1 year following laparoscopic adjustable gastric banding (LAGB), respectively. In patients undergoing LAGB, blood pressure (P < 0.0001) and blood glucose (P = 0.02) were significantly lowered by approximately 16% as well as triglyceride levels by approximately 29% (P = 0.002). In addition to a decrease of the inflammatory and pro-thrombotic marker PAI-1 (P = 0.001), CAMs, and MMP-9 (P = 0.004) were reduced, whereas no change was observed for plasma levels of MMP-2, sCD40L, and Lp-PLA(2) after LAGB, respectively. Individual changes in (ICAM-1) intercellular adhesion molecule-1 (DeltaICAM-1) were related to changes in insulin (Deltafasting insulin) before and after LAGB (r = 0.36 and r = 0.38; both P = 0.04). E-selectin correlated positively with changes in BMI (r = 0.38; P = 0.04 and r = 0.36; P = 0.05), while Lp-PLA(2) concentration was negatively correlated with BMI (r =-0.41; P = 0.02) after 1 year. Changes were comparable in both overweight diabetic and non-diabetic subjects. CONCLUSION: LAGB not only induced weight loss but also an improvement in the subclinical pro-inflammatory state. However, concentrations of most of the non-traditional risk factors for plaque instability, i.e. MMP-9, sCD40L, and Lp-PLA(2) remained unchanged.

NT-proBNP has a high negative predictive value to rule-out short-term cardiovascular events in patients with diabetes mellitus.

AIMS: This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events. METHODS AND RESULTS: A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. Of all variables analysed (age, gender, history of hypertension, ischaemic heart disease/any cardiac disease, smoking, duration of diabetes, body mass index, blood pressure, New York Heart Association-class, Dyspnoea score, Minnesota Living with Heart Failure Questionnaire, LDL-cholesterol, HbA(1c), creatinine, glomerular filtration rate), the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis (P < 0.0001). Bootstrapping with 500 samples supports this result in 95% samples. The negative predictive value of a normal value (<125 pg/mL) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98%. CONCLUSION: We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus. With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events. NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers, in this unselected cohort.

Relation of fasting plasma peptide YY to glucose metabolism and cardiovascular risk factors after restrictive bariatric surgery.

INTRODUCTION: Surgically induced weight loss results in reduction of comorbidities in severely obese humans. Reversal of abnormal secretion of appetite-regulating gut hormones such as peptide YY (PYY) could be contributing to the improvement of cardiovascular risk factors. METHODS: Severely obese patients (n = 42, BMI = 45.7 +/- 5.3 kg/m(2)) underwent clinical examination and blood sampling for measurement of PYY, plasma lipids, oral glucose tolerance testing and assessment of insulin secretion (HOMA-%B) and action (HOMA-R, QUICKI) before and during 12 months following gastric banding. Comparisons were made at each time point of the study as well as across the total study period. RESULTS: Weight loss after bariatric surgery resulted in improvement of insulin resistance by 54% (p < 0.03) and plasma triglycerides by 26% (p < 0.01) without changes in fasting PYY (16.2 +/- 8.7 pmol/l at baseline, 15.1 +/- 6.3 pmol/l at 12 months). Fasting PYY correlated negatively with plasma total cholesterol at baseline (p = 0.02) but was not associated with body weight, body mass or abdominal diameter. Individual changes in PYY (DeltaPYY) related to changes in insulin (Deltafasting insulin) at 12 months (r = -0.582, p = 0.02) and HOMA-B at 6 months (r = -0.677, p = 0.006) and 12 months (r = -0.660, p = 0.007). Diabetic status had no impact on these correlations. DISCUSSION: PYY correlates with a major cardiovascular risk factor and surrogate parameters of insulin secretion but not to weight loss or body mass in severe obesity.

Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?

OBJECTIVE: In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones. RESEARCH DESIGN AND METHODS: Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT). RESULTS: PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004). CONCLUSIONS: After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.

[The metabolic syndrome: effects of a pronounced weight loss induced by bariatric surgery]. / Das Metabolische Syndrom: Auswirkungen einer ausgeprägten Gewichtsabnahme mittels chirurgischer Intervention.

The prevalence of obesity is rising worldwide dramatically, affecting up to 50 percent of the population. The epidemic of obesity leads to a marked increase in the metabolic syndrome, a cluster of cardiovascular risk factors characterized by visceral obesity, insulin resistance, low HDL-Cholesterol, hypertriglyceridemia, and a subclinical proinflammatory state. In the last years, the NCEP and the WHO highlighted and defined the key features of the metabolic syndrome to facilitate the clinical diagnosis and preventive interventions. The conservative therapy of obesity and the metabolic syndrome by life style intervention and pharmacological interventions leads only to moderate weight loss with inconstant long-term success. Intervention by bariatric surgery can serve as a model for the metabolic effects of permanent weight loss. In several studies the pronounced weight loss induced a reduction of almost all components of the metabolic syndrome, including glucose and lipid status and is followed by an improvement in the quality of life. Recent research suggested a decrease in mortality rate in addition to cost effectiveness of bariatric surgery.

[Peritoneal dialysis in patients with diabetic nephropathy]. / Peritonealdialyse bei Patienten mit diabetischer Nephropathie.

Since the introduction of peritoneal dialysis (PD) into clinical nephrology at the end of the 1970s, many improvements have led to acceptance of this method as renal replacement therapy equivalent to hemodialysis. It is unclear whether the diabetic patient is the ideal candidate for PD and if this procedure should be the preferred method of treatment of renal failure in these patients, especially when kidney transplantation cannot be performed. PD may provide several advantages for diabetic patients with end-stage renal failure; for example, better hemodynamic stability is achieved during peritoneal ultrafiltration and vascular access surgery becomes unnecessary. On the other hand, the continuous glucose absorption may lead to increased insulin requirements, obesity and hyperlipidemia. Furthermore, peritoneal protein loss may aggravate malnutrition, which is frequently present in these patients. However, for a differentiated assessment of outcome in PD, the individual history (diabetes type 1 or type 2) and accompanying comorbidity of diabetic patients have to be considered. Nowadays nephrologists have to be aware of the concept of individualized therapy, which is integrated into an overall plan and takes into account the different conditions of diabetic patients and their treatment options. By improving removal of sodium and water, as well as improving quality of metabolic control, new dialysis solutions (icodextrin, neutral-pH solutions) and automated PD could have a positive impact on outcome in diabetic patients. In contrast, from retrospective studies on PD there is evidence of higher long-term mortality rates in elderly women with diabetes and in patients with cardiac insufficiency than in those on hemodialysis. Further research is necessary in order to optimize individualized therapy for diabetic patients with end-stage renal disease in the future.

PAI-1 4G/5G insertion/deletion promoter polymorphism and microvascular complications in type 2 diabetes mellitus.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the regulation of fibrinolysis and extracellular matrix turnover. PAI-1 4G/5G insertion/deletion polymorphism in the PAI-1 promoter region has been shown to modulate PAI-1 plasma levels. We investigated the relationship between this polymorphism and the prevalence of diabetic nephropathy and retinopathy in patients with type 2 diabetes in the Austrian population. PATIENTS AND METHODS: 147 consecutive patients with type 2 diabetes mellitus (96 men, 51 women; median age, 65 years; IQR, 59-71) were analyzed for the PAI-1 4G/5G genotype. RESULTS: The genotype distribution in the individuals tested was as follows: 17% (n = 25) 5G/5G, 54% (n = 80) 4G/5G, and 29% (n = 42) 4G/4G. Patients homozygous for allele 4G had a significantly higher risk of diabetic proliferative retinopathy than patients without signs of diabetic retinopathy or nonproliferative retinopathy (OR, 7.3; 95% CI, 1.4-38.8; P = 0.02). No significant associations were observed between the PAI-1 genotype and the presence of albuminuria. CONCLUSION: According to our results, diabetic proliferative retinopathy might be associated with the prevalence of PAI-1 genotype 4G/4G.

Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding.

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/- 5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53 pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action. In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.

The prevalence of symptoms of sensorimotor and autonomic neuropathy in Type 1 and Type 2 diabetic subjects.

The aim of this study was to analyze the prevalence and severity of sensorimotor and autonomic neuropathic symptoms within an outpatients diabetic population. A total of 350 consecutive Type 1 (26.9%) and Type 2 diabetic subjects were investigated using the Michigan Neuropathy Screening Instrument (MNSI). The original questionnaire was extended with questions on autonomic neuropathy and to include a six-point scale to rate the severity of symptoms, which were recorded accurately in order to avoid overrating. More than one half of Type 2 and nearly a third of Type 1 diabetic subjects suffer from at least one neuropathic symptom; the former suffered significantly more often from paresthesia (P<.05) and burning pain (P=.05). Less than 10% of the study population had autonomic symptoms. The prevalence of symptomatic polyneuropathy (PNP), diagnosed by an abnormal MNSI together with the presence of any symptom, was 16.0% in Type 1 and 37.5% (P<.001) in Type 2 diabetic subjects. Subjects with an abnormal ankle reflex (54.6%) had in 48.2% any sensorimotor, in 35.1% any autonomic, and in 25.7% any sensorimotor plus autonomic symptoms. The corresponding percentages for subjects with an abnormal vibration perception threshold (VPT; 28.9%) were 59.4%, 46.5%, and 34.7%, respectively. An abnormal ankle reflex was significantly correlated to numbness, and to the the sum of sensorimotor and autonomic symptoms. An abnormal vibration perception was significantly correlated to numbness, to paresthesia pain, and to the sum of sensorimotor and autonomic symptoms. A higher percentage of Type 2 diabetic subjects had symptoms of neuropathy and the most frequent symptoms were numbness, muscle cramps and postural hypotension.

Improvement of insulin resistance and early atherosclerosis in patients after gastric banding.

OBJECTIVE: To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS). RESEARCH METHODS AND PROCEDURES: Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured. RESULTS: BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels. DISCUSSION: Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

[Type 2 diabetes mellitus--screening and prevention]. / Typ 2 Diabetes mellitus--Screening und Prävention.

The prevalence of diabetes is increasing in westernized countries. In addition, about half of all patients suffering from diabetes are not diagnosed. The current article represents the recommendations of the Austrian Diabetes Association for the screening and prevention of type 2 diabetes, based on currently available evidence.

[Indication for bariatric surgery]. / Indikation zur operativen Adipositastherapie.

Morbid obesity is defined as obesity with body mass index (BMI) > or = 40 kg/m2 with secondary serious diseases. Conservative treatment generally fails to produce long-term weight loss in these patients, since several bariatric surgical techniques have been developed which are based on gastric restriction and/or gastric malabsorption resulting in permanent weight loss over years. Preoperative evaluation might detect suitable patients and reduce both non-surgical and surgical complications. Postoperative follow-up in a multidisciplinary program, including specialists in various fields of medicine, e.g. surgery, internal medicine, radiology, paediatrics and nutritional surveillance are mandatory in the treatment of patients after obesity surgery. Bariatric surgery results in a major weight loss, with amelioration of most obesity-associated conditions. The most serious side effect of some surgical procedere is malnutrition.

Effect of gastric banding on aminoterminal pro-brain natriuretic peptide in the morbidly obese.

OBJECTIVE: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT-proBNP and the effect of weight reduction on this parameter. RESEARCH METHODS AND PROCEDURES: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT-proBNP levels were measured before and 12 months after the surgery. RESULTS: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p < 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normal-weight control subjects (341.15 +/- 127.78 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p < 0.00001). After bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 +/- 127.78 fmol/mL to 204.87 +/- 59.84 fmol/mL (p < 0.00001) and remained statistically significantly elevated (204.88 +/- 59.84 fmol/mL vs. 161.68 +/- 75.78 fmol/mL; p = 0.04) compared with normal-weight subjects. DISCUSSION: This investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT-proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction.

Basal and dynamic proinsulin-insulin relationship to assess beta-cell function during OGTT in metabolic disorders.

The fasting proinsulin-to-insulin ratio is a currently used marker of beta-cell dysfunction. This ratio is calculated at the basal condition, but its behavior in dynamic conditions, i.e., during glucose stimulation, could be more informative. Given the different kinetics of the peptides, a mathematical model was necessary to analyze the oral glucose tolerance test (OGTT) data of insulin, C-peptide, and proinsulin in 55 healthy (NGT), 30 impaired glucose-tolerant (IGT), and 31 type 2 diabetic (T2DM) subjects. The model provided for secretion and disappearance of the peptides and an index of beta-cell function under dynamic conditions. Total proinsulin secretion during the OGTT was not different (P > 0.053) among NGT (0.17 +/- 0.01 mmol/l in 3 h), IGT (0.22 +/- 0.02), and T2DM (0.21 +/- 0.02) subjects. The proinsulin-to-insulin molar ratio measured from basal samples was higher (P < 0.0001) in T2DM (0.39 +/- 0.05) than in NGT (0.14 +/- 0.01) and IGT (0.13 +/- 0.02) subjects, and similar results (P < 0.003) were found by the dynamic index (0.27 +/- 0.04, 0.14 +/- 0.01, 0.15 +/- 0.01 in T2DM, NGT, IGT subjects, respectively). The basal ratio significantly correlated with the dynamic index, and the regression line slope was lower than 1 (0.43 +/- 0.08, 0.61 +/- 0.10, and 0.56 +/- 0.03 in NGT, IGT, and T2DM subjects, respectively, P < 0.0001). Impaired beta-cell function in T2DM could then be indicated by proinsulin-to-insulin indexes at both basal and dynamic phases.