Andreas L Birkenfeld

Universitätsklinikum Tübingen and Helmholtz Munich · Diabetolgy Endocrinology and Nephrology

Background: Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. Methods: We did a randomised, double-blind, placebo and ac...

Background Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. Methods We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomiz...

Background The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus. Methods GFR was measured in 93 patients with diabetes mellitus using iohexol clearance a...

OBJECTIVE Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of...

Biological sex has a strong impact on skeletal muscle metabolism and performance. By a comprehensive investigation of epigenetic, transcriptomic and proteomic differences between female and male skeletal muscle of untrained subjects we provide a molecular basis for the sexual dimorphism of glucose and lipid metabolism. The sex-specific multi-OMICs...

Background Reduced inhibitory control is associated with obesity and neuroimaging studies indicate that diminished prefrontal cortex activity influence eating behavior and metabolism. The hypothalamus regulates energy homeostasis and is functionally connected to cortical and subcortical regions especially the frontal areas. Objectives We tested net...

Aims Central insulin has been shown to regulate eating behavior and cognitive processes in a sex-specific manner. Besides memory, the hippocampus is pivotal in the control of appetite. However, how insulin interacts with the hippocampal food cue response and the role of sex hormones in this context remain unclear. Methods Using fMRI, we evaluated...

Background The potential impact of specific food additives, common in Western diets, on the risk of developing type 2 diabetes is not well understood. This study focuses on carrageenan, a widely used food additive known to induce insulin resistance and gut inflammation in animal models, and its effects on human health. Methods In a randomised, dou...

There is an unmet need for a biomarker of liver fat. We identified dimethylguanidino valeric acid (DMGV) as a circulating biomarker of liver fat. Here, we assess its two isoforms—symmetric (SDGV) and asymmetric (ADGV)—as biomarkers of steatosis. We determined plasma ADGV, SDGV, related metabolites, alanine aminotransferase (ALT), and the fatty live...

Objective Infiltration of adipocytes into the pancreatic parenchyma has been linked to impaired insulin secretion in individuals with increased genetic risk of T2D and prediabetic conditions. However, the study of this ectopic fat depot has been limited by the lack of suitable in vitro models. Methods Here, we developed a novel 3D model of functio...

Type 2 diabetes (T2D) is a chronic disease currently affecting around 500 million people worldwide with often severe health consequences. Yet, histopathological analyses are still inadequate to infer the glycaemic state of a person based on morphological alterations linked to impaired insulin secretion and β-cell failure in T2D. Giga-pixel microsco...

The German Center for Diabetes Research (DZD) established a core data set (CDS) of clinical parameters relevant for diabetes research in 2021. The CDS is central to the design of current and future DZD studies. Here, we describe the process and outcomes of FAIRifying the initial version of the CDS. We first did a baseline evaluation of the FAIRness...

Measures of neural complexity have been shown to evolve with age during the earliest weeks of infancy and to differentiate between typical and atypical development, suggesting that they may be promising surrogate markers of brain maturation. In our current work, we explored developmental trends in neural complexity with the goals of better understa...

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to add...

Aim: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). Patients-methods: In the present...

Objectives Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affect...

Background: Adenosine triphosphate-citrate lyase (ACLY) inhibition has proven clinically efficacious for low-density lipoprotein cholesterol (LDL-c) lowering and cardiovascular disease (CVD) risk reduction. Clinical and genetic evidence suggests that some LDL-c lowering strategies, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inh...

The root cause of type 2 diabetes (T2D) is insulin resistance (IR), defined by the failure of cells to respond to circulating insulin to maintain lipid and glucose homeostasis. While the causes of whole-body insulin resistance are multifactorial, a major contributing factor is dysregulation of liver and adipose tissue function. Adipose dysfunction,...

Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (ma...

We have previously shown that weight loss-induced remission of prediabetes is mediated by improved insulin sensitivity (IS) and characterized by reduced visceral adipose tissue mass (VAT). Remission markedly reduces the risk for type 2 diabetes. We hypothesized that patients from specific high-risk Tübingen Prediabetes Clusters show a reduced remis...

In type 2 diabetes, relapse after remission is characterized by a loss of recovered beta cell function and re-accumulation of ectopic lipids. Mechanistic insights on relapse and maintenance after prediabetes remission are lacking.In the multicenter Prediabetes Lifestyle Intervention Study (n=1105), people with prediabetes underwent 12 months of lif...

Exercise is a potent skeletal muscle stimulus and one of the most effective strategies to prevent muscle loss and type 2 diabetes. Biological sex-based differences are reported for aerobic capacity, muscle mass, and exercise performance. We aimed to provide a yet missing comprehensive picture of molecular differences between female and male skeleta...

Introduction & Objective: Insulin resistance is a central pathophysiologic feature of type 2 diabetes (T2D), and to varying degrees also present in type 1 diabetes (T1D) and prediabetes. This study aims to discern patterns of tissue-specific insulin resistance to understand its contribution to metabolic heterogeneity. Methods: This study used k-mea...

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in...

In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtrat...

Aim In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS. Methods The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amilo...

Alterations in the function of K ⁺ channels such as the voltage- and Ca ²⁺ -activated K ⁺ channel of large conductance (BK Ca ) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK Ca splice variant localized to the inner...

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targe...

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifes...

Alterations in the function of K + channels such as the voltage- and Ca 2+ activated K + channel of large conductance (BK Ca ) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK Ca splice variant localized to the inner m...

Methods We studied acute exercise- and training-induced changes in plasma metabolites in sedentary subjects with overweight (8 male, 14 female) participating in an eight-week supervised training program flanked by two acute endurance exercise sessions. Plasma metabolites were quantified using LC- and CE-MS. In a separate study (n=9 lean males), we...

In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/d, max. 15 mg/d) in nephrotic patients in comparison to standard therapy with the loop...

Aims/hypothesis: For individuals with prediabetes, the current American Diabetes Association (ADA) guidelines recommend a body weight loss >7% to prevent the development of type 2 diabetes (T2D) without any glycemic target goals. However, we have recently shown that weight loss induced prediabetes remission reduces relative T2D risk by 73% within t...

Objective Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases. Since the underlying mechanisms are still poorly understood, we here examined the impact of breastfeeding on the plasmatic coagulation system in women with and without history of gestational diabetes mellitus (GDM). Methods 76 participants of the German...

Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current human skeletal muscle models in vitro are incapable of fully recapitulating its physiological functions especially muscle contractility. By supplementation of insulin-like growth factor 1 (IGF1), a gr...

Objectives Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affect...

Objective Insulin resistance during childhood is a risk factor for developing type 2 diabetes and other health problems later in life. Studies in adults have shown that insulin resistance affects regional and network activity in the brain which are vital for behavior, e.g. ingestion and metabolic control. To date, no study has investigated whether...

Introduction: SGLT2 inhibitors are used to reduce the risk of progression of chronic kidney disease (CKD). In patients with type 2 diabetes, they have been found to reduce extracellular volume. Given the high prevalence of extracellular volume expansion and overhydration in CKD, we investigated whether SGLT2 inhibitors might correct these disturban...

OBJECTIVE To explore whether insulin resistance, assessed by estimated glucose disposal rate (eGDR), is associated with cardiorenal risk and whether it modifies finerenone efficacy. RESEARCH DESIGN AND METHODS In FIDELITY (N = 13,026), patients with type 2 diabetes, either 1) urine albumin-to-creatinine ratio (UACR) of ≥30 to <300 mg/g and estimat...

Background Solute carrier family 13 member 5 (SLC13A5) is a Na⁺-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the...

Alterations in the function of K+ channels such as the voltage- and Ca2+ activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitocho...

Alterations in the function of K+ channels such as the voltage- and Ca2+ activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitocho...

Reduced expression of the plasma membrane citrate transporter SLC13A5, also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1–5% of bone weight, binding to mineral apatite surfaces. Our previous research hig...

Context Exercise training is known to improve glucose tolerance and reverse insulin resistance in people with obesity. However, some individuals fail to improve or even decline in their clinical traits following exercise intervention. Objective This study focused on gene expression and DNA methylation signatures in skeletal muscle of low (LRE) and...

Introduction Type 2 diabetes (T2D) is associated with severe complications, including chronic kidney disease (CKD), cardiovascular disease, heart failure and premature death. By the time T2D is diagnosed, many patients already have emerging complications. Therefore, early treatment has the potential for prevention or even early reversal of serious...

Purpose Insulinoma is a rare tumor of the pancreas that can lead to hypoglycemia. To date, the standard therapy is surgical resection. After the first case report of successful endoscopic ultrasound-guided (EUS) ethanol injection 16 years ago, the need for establishing an alternative treatment method remains unchanged given the high morbidity rates...

MicroRNAs (miRNAs) recently emerged as means of communication between insulin-sensitive tissues to mediate diabetes development and progression, and as such they present a valuable proxy for epigenetic alterations associated with type 2 diabetes. In order to identify miRNA markers for the precursor of diabetes called prediabetes, we applied a trans...