Showing papers by "Andreas L. Birkenfeld published in 2018"

Incidence of Hypoglycemia After Gastric Bypass vs Sleeve Gastrectomy: A Randomized Trial.

Abstract: Context We compared the incidence of hypoglycemia after Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG). Design, Setting, and Main Outcome Measures Randomized, open-label trial conducted at the outpatient obesity clinic in a university hospital in Rome, Italy. The primary aim was the incidence of reactive hypoglycemia (<3.1 mmol/L after 75-g oral glucose load) at 1 year after surgery. Secondary aims were hypoglycemia under everyday life conditions, insulin sensitivity, insulin secretion, and lipid profile. Results Of 175 eligible patients, 120 were randomized 1:1 to RYGB or SG; 117 (93%) completed the 12-month follow-up. Reactive hypoglycemia was detected in 14% and 29% of SG and RYGB patients (P = 0.079), respectively, with the effect of treatment in multivariate analysis significant at P = 0.018. Daily hypoglycemic episodes during continuous glucose monitoring did not differ between groups (P = 0.75). Four of 59 RYGB subjects (6.8%) had 1 to 3 hospitalizations for symptomatic hypoglycemia vs 0 in SG. The static β-cell glucose sensitivity index increased after both treatments (P < 0.001), but the dynamic β-cell glucose sensitivity index increased significantly in SG (P = 0.008) and decreased in RYGB (P = 0.004 for time × treatment interaction). Whole-body insulin sensitivity increased about 10-fold in both groups. Conclusions We show that reactive hypoglycemia is no less common after SG and is not a safer option than RYGB, but RYGB is associated with more severe hypoglycemic episodes. This is likely due to the lack of improvement of β-cell sensitivity to changes in circulating glucose after RYGB, which determines an inappropriately high insulin secretion.

Natriuretic Peptides in Cardiovascular and Metabolic Crosstalk: Implications for Hypertension Management.

Abstract: Natriuretic peptides are commonly considered cardiovascular and renal hormones. Indeed, genetic natriuretic peptide deletion promotes arterial hypertension and associated organ damage.1 Conversely, pharmacological natriuretic peptide augmentation lowers blood pressure. Less recognized is the fact that natriuretic peptides potently affect lipid and glucose metabolism. Through these metabolic actions, natriuretic peptides may provide a pathophysiological link between cardiovascular and metabolic disease. Indeed, arterial hypertension and insulin resistance or overt type 2 diabetes mellitus commonly occur in the same patients. Similarly, heart failure is associated with impaired skeletal, muscular oxidative function and insulin resistance.2,3 The review focusses on recent epidemiological, genetic, physiological, and pharmacological evidence linking the natriuretic peptide system with metabolic disease. Moreover, we discuss clinical trials evidence suggesting that natriuretic peptide modulation could be pursued further in metabolic disease prevention and treatment. ANP (atrial natriuretic peptide) and BNP (B-type natriuretic peptide) are released from cardiac atria and ventricles, respectively. Both peptides are produced as preprohormones and are stored as prohormones in intracellular granules. The native peptides are released in equimolar amounts with N-terminal peptide fragments, which are more stable than the native hormones and can serve as natriuretic peptide release markers. Stretch of atrial or ventricular cardiomyocytes which can be secondary to increased sodium intake, physical exercise, or diseases associated with volume overload triggers natriuretic peptide release. Both natriuretic peptide and their N-terminal peptide fragments are clinically established heart failure biomarkers. Once released, natriuretic peptides raise renal sodium excretion, elicit vasodilation, and are the physiological antagonists of the renin-angiotensin system.4 Natriuretic peptides also attenuate sympathetic nervous system activity at least in part through interaction with central vasopressin pathways.5 ANP and BNP responses are primarily mediated by the GCA (guanylyl cyclase-coupled natriuretic peptide receptor; also known as NPR-A [natriuretic peptide receptor A]). NPR-C, which is sometimes …

Analysis of naturally occurring mutations in the human uptake transporter NaCT important for bone and brain development and energy metabolism

Abstract: The human uptake transporter NaCT is important for human brain development, brain function and energy metabolism and mediates the uptake of citrate and other intermediates of the tricarboxylic acid cycle from blood into neurons and hepatocytes. Mutations in the SLC13A5 gene encoding NaCT are associated with epileptic encephalopathy. To gain more insights into the transport mechanisms we analyzed the functional consequences of mutations in the SLC13A5 gene on NaCT-mediated transport function. Using HEK293 cells expressing wild-type and eight mutated NaCT proteins, we investigated the mRNA and protein amount as well as the protein localization of all NaCT variants. Furthermore, the impact on NaCT-mediated citrate uptake was measured. In addition, a structural model of the transport pore was generated to rationalize the consequences of the mutations on a structural basis. We demonstrated that all proteins were synthesized with an identical molecular weight as the wild-type transporter but several mutations (NaCTp.G219R, -p.G219E, -p.T227M, -p.L420P and -p.L488P) lead to a complete loss of NaCT-mediated citrate transport. This loss of transport activity can be explained on the basis of the developed structural model. This model may help in the further elucidation of the transport mechanism of this important uptake transporter.

The anorexigenic peptide neurotensin relates to insulin sensitivity in obese patients after BPD or RYGB metabolic surgery.

Abstract: Neurotensin is a peptide with effects on appetite and intestinal lipid absorption. Experimental data suggest a role in glucose homeostasis, while human data is missing. Here, 20 morbidly obese subjects either underwent biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB) in a randomized fashion. Before and 1 year after surgery, anthropometric data, body composition, clinical biochemistry, insulin sensitivity by means of euglycemic hyperinsulinemic clamps (HEC) and fasting plasma proneurotensin 1–117 were analyzed. Plasma proneurotensin increased significantly more 1 year after BDP than RYGB (P = 0.028), while weight loss was comparable. After metabolic surgery, proneurotensin correlated positively with insulin sensitivity (M-value) (r = 0.55, P < 0.001), while an inverse relationship with fasting glucose, HOMA-IR and HbA1c was observed (P < 0.05 for all components). After adjustment for age and gender, proneurotensin and BMI remained independently related with delta of M-value (β = 0.46 and β = 0.51, P < 0.05, resp.). From these data we conclude that proneurotensin positively correlates with insulin sensitivity uniquely after weight loss induced by metabolic surgery in humans. BDP leads to a stronger increase in the anorexigenic peptide compared to RYGB.

Intravenous Ferric Carboxymaltose in Patients with Type 2 Diabetes Mellitus and Iron Deficiency: CLEVER Trial Study Design and Protocol

Abstract: In the original publication, the text in Table 2 stated 'Hypersensitivity to the active substance, to Ferinject, or to any of its excipients'.

Urinary Lipidomics: evidence for multiple sources and sexual dimorphism in healthy individuals.

Abstract: Urinary lipidomics may add new valuable biomarkers to the diagnostic armamentarium for early detection of metabolic and kidney diseases. Sources and composition of urinary lipids in healthy individuals, however, have not been investigated in detail. Shotgun lipidomics was used to quantify lipidomic profiles in native urine samples from 16 individuals (eight men, eight women) collected in five fractions over 24 h. All probands were comprehensively characterized by urinary and clinical indices. The mean total urinary lipid concentration per sample was 0.84 μM in men and 1.03 μM in women. We observed significant intra- and interindividual variations of lipid concentrations over time, but failed to detect a clear circadian pattern. Based on quantity and subclass composition it seems very unlikely that plasma serves as major source for the urinary lipidome. Considering lipid metabolites occurring in at least 20% of all samples 38 lipid species from 7 lipid classes were identified. Four phosphatidylserine and one phosphatidylethanolamine ether species (PE-O 36:5) were detectable in almost all urine samples. Sexual dimorphism has been found mainly for phosphatidylcholines and phosphatidylethanolamines. In men and in women urinary lipid species were highly correlated with urinary creatinine and albumin excretion, reflecting glomerular filtration and tubular transport processes. In women, however, lipid species deriving from urinary cells and cellular constituents of the lower genitourinary tract considerably contributed to the urinary lipidome. In conclusion, our study revealed the potential of urinary lipidomics but also the complexity of methodological challenges which have to be overcome for its implementation as a routine diagnostic tool for renal, urological and metabolic diseases.