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1.
From classical dualistic antagonism to hormone synergy: potential of overlapping action of glucagon, insulin and GLP-1 for the treatment of diabesity.
Kistkins, S, Moser, O, Ankudovičs, V, Bliznuks, D, Mihailovs, T, Lobanovs, S, Sourij, H, Pfeiffer, AFH, Pirags, V
Endocrine connections. 2024
Abstract
The increasing prevalence of "diabesity," a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behavior, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of "anti-diabesity" treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.
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2.
Efficacy of Fasting in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review.
Herz, D, Haupt, S, Zimmer, RT, Wachsmuth, NB, Schierbauer, J, Zimmermann, P, Voit, T, Thurm, U, Khoramipour, K, Rilstone, S, et al
Nutrients. 2023;(16)
Abstract
Over the last decade, studies suggested that dietary behavior modification, including fasting, can improve metabolic and cardiovascular markers as well as body composition. Given the increasing prevalence of people with type 1 (T1DM) and type 2 diabetes mellitus (T2DM) and the increasing obesity (also in combination with diabetes), nutritional therapies are gaining importance, besides pharmaceutical interventions. Fasting has demonstrated beneficial effects for both healthy individuals and those with metabolic diseases, leading to increased research interest in its impact on glycemia and associated short- and long-term complications. Therefore, this review aimed to investigate whether fasting can be used safely and effectively in addition to medications to support the therapy in T1DM and T2DM. A literature search on fasting and its interaction with diabetes was conducted via PubMed in September 2022. Fasting has the potential to minimize the risk of hypoglycemia in T1DM, lower glycaemic variability, and improve fat metabolism in T1DM and T2DM. It also increases insulin sensitivity, reduces endogenous glucose production in diabetes, lowers body weight, and improves body composition. To conclude, fasting is efficient for therapy management for both people with T1DM and T2DM and can be safely performed, when necessary, with the support of health care professionals.
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3.
SGLT2 Inhibitors in Long COVID Syndrome: Is There a Potential Role?
Zimmermann, P, Sourij, H, Aberer, F, Rilstone, S, Schierbauer, J, Moser, O
Journal of cardiovascular development and disease. 2023;(12)
Abstract
The coronavirus disease (COVID)-19 has turned into a pandemic causing a global public health crisis. While acute COVID-19 mainly affects the respiratory system and can cause acute respiratory distress syndrome, an association with persistent inflammatory stress affecting different organ systems has been elucidated in long COVID syndrome (LCS). Increased severity and mortality rates have been reported due to cardiophysiological and metabolic systemic disorders as well as multiorgan failure in COVID-19, additionally accompanied by chronic dyspnea and fatigue in LCS. Hence, novel therapies have been tested to improve the outcomes of LCS of which one potential candidate might be sodium-glucose cotransporter 2 (SGLT2) inhibitors. The aim of this narrative review was to discuss rationales for investigating SGLT2 inhibitor therapy in people suffering from LCS. In this regard, we discuss their potential positive effects-next to the well described "cardio-renal-metabolic" conditions-with a focus on potential anti-inflammatory and beneficial systemic effects in LCS. However, potential beneficial as well as potential disadvantageous effects of SGLT2 inhibitors on the prevalence and long-term outcomes of COVID-19 will need to be established in ongoing research.
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4.
Acute Fluid Intake Impacts Assessment of Body Composition via Bioelectrical Impedance Analysis. A Randomized, Controlled Crossover Pilot Trial.
Schierbauer, J, Günther, S, Haupt, S, Zimmer, RT, Herz, D, Voit, T, Zimmermann, P, Wachsmuth, NB, Aberer, F, Moser, O
Metabolites. 2023;(4)
Abstract
Bioelectrical impedance analysis (BIA) has proven to be particularly useful due to its inexpensive and rapid assessment of total body water and body density. However, recent fluid intake may confound BIA results since equilibration of fluid between intra- and extracellular spaces may take several hours and furthermore, ingested fluids may not be fully absorbed. Therefore, we aimed to evaluate the impact of different fluid compositions on the BIA. A total of eighteen healthy individuals (10 females, mean ± SD age of 23.1 ± 1.8 years) performed a baseline measurement of body composition before they consumed isotonic 0.9% sodium-chloride (ISO), 5% glucose (GLU) or Ringer (RIN) solutions. During the visit of the control arm (CON), no fluid was consumed. Further impedance analyses were conducted every 10 min after the fluid consumption for 120 min. We found statistically significant interactions between the effects of solution ingestion and time for intra- (ICW, p < 0.01) and extracellular water (ECW, p < 0.0001), skeletal muscle mass (SMM, p < 0.001) and body fat mass (FM, p < 0.01), respectively. Simple main effects analysis showed that time had a statistically significant effect on changes in ICW (p < 0.01), ECW (p < 0.01), SMM (p < 0.01) and FM (p < 0.01), while fluid intake did not have a significant effect. Our results highlight the importance of a standardized pre-measurement nutrition, with particular attention to hydration status when using a BIA for the evaluation of body composition.
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5.
The Arrhythmogenic Face of COVID-19: Brugada ECG Pattern in SARS-CoV-2 Infection.
Zimmermann, P, Aberer, F, Braun, M, Sourij, H, Moser, O
Journal of cardiovascular development and disease. 2022;(4)
Abstract
In 1992, Brugada syndrome (BS) was first described; an often unrecognized cardiac conduction disorder mainly associated with unexplained sudden cardiac arrest and consecutive syncope. Nevertheless, the pathomechanism of BS and sudden cardiac death remains mainly explained. Mutations in the cardiac sodium channels, which cause a reduction or functional loss of these channels, are associated with characteristic electrocardiographic (ECG) abnormalities and malignant arrhythmia. The majority of affected people are previously healthy and unaware of their genetic predisposition for BS and might experience ventricular tachyarrhythmias and cardiac arrest potentially triggered by several factors (e.g., alcohol, sodium channel blockers, psychotropic drugs, and fever). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was firstly identified in Wuhan in early December 2019 and rapidly spread worldwide as coronavirus disease (COVID-19). COVID-19 is typically characterized by a severe inflammatory response, activation of the immune system, and high febrile illness. Due to this condition, symptomatic COVID-19 infection or vaccination might serve as inciting factor for unmasking the Brugada pattern and represents a risk factor for developing proarrhythmic complications. The aim of this narrative review was to detail the association between virus-related issues such as fever, electrolyte disturbance, and inflammatory stress of COVID-19 infection with transient Brugada-like symptoms and ECG-pattern and its susceptibility to proarrhythmogenic episodes.
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6.
Glucose and Fructose Supplementation and Their Acute Effects on Anaerobic Endurance and Resistance Exercise Performance in Healthy Individuals: A Double-Blind Randomized Placebo-Controlled Crossover Trial.
Eckstein, ML, Erlmann, MP, Aberer, F, Haupt, S, Zimmermann, P, Wachsmuth, NB, Schierbauer, J, Zimmer, RT, Herz, D, Obermayer-Pietsch, B, et al
Nutrients. 2022;(23)
Abstract
BACKGROUND The effects of glucose, fructose and a combination of these on physical performance have been subject of investigation, resulting in diverse findings. OBJECTIVE The aim of this study was to investigate how an individualized amount of glucose, fructose, and a combination of these compared to placebo (sucralose) alter endurance performance on a cycle ergometer, lower and upper body resistance exercise performance at individualized thresholds in healthy young individuals. METHODS A total of 16 healthy adults (9 females) with an age of 23.8 ± 1.6 years and a BMI of 22.6 ± 1.8 kg/m2 (body mass (BM) 70.9 ± 10.8 kg, height 1.76 ± 0.08 m) participated in this study. During the screening visit, the lactate turn point 2 (LTP2) was defined and the weights for chest-press and leg-press were determined. Furthermore, 30 min prior to each exercise session, participants received either 1 g/kg BM of glucose (Glu), 1 g/kg BM of fructose (Fru), 0.5 g/kg BM of glucose/fructose (GluFru) (each), or 0.2 g sucralose (placebo), respectively, which were dissolved in 300 mL of water. All exercises were performed until volitional exhaustion. Time until exhaustion (TTE) and cardio-pulmonary variables were determined for all cycling visits; during resistance exercise, repetitions until muscular failure were counted and time was measured. During all visits, capillary blood glucose and blood lactate concentrations as well as venous insulin levels were measured. RESULTS TTE in cycling was 449 ± 163 s (s) (Glu), 443 ± 156 s (Fru), 429 ± 160 s (GluFru) and 466 ± 162 s (Pla) (p = 0.48). TTE during chest-press sessions was 180 ± 95 s (Glu), 180 ± 92 s (Fru), 172 ± 78 s (GluFru) and 162 ± 66 s (Pla) (p = 0.25), respectively. CONCLUSIONS Pre-exercise supplementation of Glu, Fru and a combination of these did not have an ergogenic effect on high-intensity anaerobic endurance performance and on upper and lower body moderate resistance exercise in comparison to placebo.
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7.
Accuracy of Real Time Continuous Glucose Monitoring during Different Liquid Solution Challenges in Healthy Adults: A Randomized Controlled Cross-Over Trial.
Schierbauer, JR, Günther, S, Haupt, S, Zimmer, RT, Zunner, BEM, Zimmermann, P, Wachsmuth, NB, Eckstein, ML, Aberer, F, Sourij, H, et al
Sensors (Basel, Switzerland). 2022;(9)
Abstract
Continuous glucose monitoring (CGM) represents an integral of modern diabetes management, however, there is still a lack of sensor performance data when rapidly consuming different liquids and thus changing total body water. 18 healthy adults (ten females, age: 23.1 ± 1.8 years, BMI 22.2 ± 2.1 kg·m−2) performed four trial visits consisting of oral ingestion (12 mL per kg body mass) of either a 0.9% sodium chloride, 5% glucose or Ringer’s solution and a control visit, in which no liquid was administered (control). Sensor glucose levels (Dexcom G6, Dexcom Inc., San Diego, CA, USA) were obtained at rest and in 10-min intervals for a period of 120 min after solution consumption and compared against reference capillary blood glucose measurements. The overall MedARD [IQR] was 7.1% [3.3−10.8]; during control 5.9% [2.7−10.8], sodium chloride 5.0% [2.7−10.2], 5% glucose 11.0% [5.3−21.6] and Ringer’s 7.5% [3.1−13.2] (p < 0.0001). The overall bias [95% LoA] was 4.3 mg·dL−1 [−19 to 28]; during control 3.9 mg·dL−1 [−11 to 18], sodium chloride 4.8 mg·dL−1 [−9 to 19], 5% glucose 3.6 mg·dL−1 [−33 to 41] and Ringer’s solution 4.9 mg·dL−1 [−13 to 23]. The Dexcom G6 CGM system detects glucose with very good accuracy during liquid solution challenges in normoglycemic individuals, however, our data suggest that in people without diabetes, sensor performance is influenced by different solutions.
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8.
Glucose and Fructose Supplementation and Their Acute Effects on Electrocardiographic Time Intervals during Anaerobic Cycling Exercise in Healthy Individuals: A Secondary Outcome Analysis of a Double-Blind Randomized Crossover-Controlled Trial.
Eckstein, ML, Zimmermann, P, Erlmann, MP, Wachsmuth, NB, Haupt, S, Zimmer, RT, Schierbauer, J, Herz, D, Aberer, F, Sourij, H, et al
Nutrients. 2022;(16)
Abstract
The impact of glucose and fructose supplementation on acute cardiac effects during cardiopulmonary exercise testing (CPET) is a topic that is rarely investigated. The aim of the presented secondary outcome analysis of a double-blind, randomized crossover-controlled trial was to investigate the impact of glucose (Glu), fructose (Fru), glucose and fructose (GluFru), and sucralose on electrocardiogram (ECG), heart rate variability (HRV), premature ventricular complexes (PVCs), and heart rate turn points (HRTP) during CPET. Fourteen healthy individuals (age 25.4 ± 2.5 years, body mass index (BMI) 23.7 ± 1.7 kg/m2, body mass (BM) of 76.3 ± 12.3 kg) participated in this study, of which 12 were included for analysis. Participants received 1 g/kg BM of Glu, 1 g/kg BM of Fru, 0.5 g/kg BM of GluFru (each), and 0.2 g sucralose dissolved in 300 mL 30 min prior to each exercise session. No relevant clinical pathology or significant inter-individual differences between our participants could be revealed for baseline ECG parameters, such as heart rate (HR) (mean HR 70 ± 16 bpm), PQ interval (146 ± 20 ms), QRS interval (87 ± 16 ms) and the QT (405 ± 39 ms), and QTc interval (431 ± 15 ms). We found preserved cardiac autonomic function by analyzing the acute effects of different Glu, Fru, GluFru, or sucralose supplementation on cardiac autonomic function by Schellong-1 testing. SDNN and RMSSD revealed normal sympathetic and parasympathetic activities displaying a balanced system of cardiac autonomic regulation across our participating subjects with no impact on the metabolism. During CPET performance analyses, HRV values did not indicate significant changes between the ingested drinks within the different time points. Comparing the HRTP of the CPET with endurance testing by variable metabolic conditions, no significant differences were found between the HRTP of the CPET data (170 ± 12 bpm), Glu (171 ± 10 bpm), Fru (171 ± 9 bpm), GluFru (172 ± 9 bpm), and sucralose (170 ± 8 bpm) (p = 0.83). Additionally, the obtained time to reach HRTP did not significantly differ between Glu (202 ± 75 s), Fru (190 ± 88 s), GluFru (210 ± 89 s), and sucralose (190 ± 34 s) (p = 0.59). The significance of this study lies in evaluating the varying metabolic conditions on cardiac autonomic modulation in young healthy individuals. In contrast, our participants showed comparable cardiac autonomic responses determined by ECG and CPET.
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9.
The Impact of a High-Carbohydrate/Low Fat vs. Low-Carbohydrate Diet on Performance and Body Composition in Physically Active Adults: A Cross-Over Controlled Trial.
Wachsmuth, NB, Aberer, F, Haupt, S, Schierbauer, JR, Zimmer, RT, Eckstein, ML, Zunner, B, Schmidt, W, Niedrist, T, Sourij, H, et al
Nutrients. 2022;(3)
Abstract
Background: Recently, high-carbohydrate or low-carbohydrate (HC/LC) diets have gained substantial popularity, speculated to improve physical performance in athletes; however, the effects of short-term changes of the aforementioned nutritional interventions remain largely unclear. Methods: The present study investigated the impact of a three-week period of HC/low-fat (HC) diet followed by a three-week wash-out-phase and subsequent LC diet on the parameters of physical capacity assessed via cardiopulmonary exercise testing, body composition via bioimpedance analysis and blood profiles, which were assessed after each of the respective diet periods. Twenty-four physically active adults (14 females, age 25.8 ± 3.7 years, body mass index 22.1 ± 2.2 kg/m2), of which six participants served as a control group, were enrolled in the study. Results: After three weeks of each diet, VO2peak was comparable following both interventions (46.8 ± 6.7 (HC) vs. 47.2 ± 6.7 mL/kg/min (LC; p = 0.58)) while a significantly higher peak performance (251 ± 43 W (HC) vs. 240 ± 45 W (LC); (p = 0.0001), longer time to exhaustion (14.5 ± 2.4 min (HC) vs. 14.1 ± 2.4 min (LC); p = 0.002) and greater Watt/kg performance (4.1 ± 0.5 W/kg (HC) vs. 3.9 ± 0.5 W/kg (LC); p = 0.003) was demonstrated after the HC diet. In both trial arms, a significant reduction in body mass (65.2 ± 11.2 to 63.8 ± 11.8 kg (HC) vs. 64.8 ± 11.6 to 63.5 ± 11.3 kg (LC); both p < 0.0001) and fat mass (22.7% to 21.2%; (HC) vs. 22.3% to 20.6% (LC); both p < 0.0001) but not in lean body mass or skeletal muscle mass was shown when compared to baseline. Resting metabolic rate was not different within both groups (p > 0.05). Total cholesterol and LDL-cholesterol significantly decreased after the HC diet (97.9 ± 33.6 mg/dL at baseline to 78.2 ± 23.5 mg/dL; p = 0.02) while triglycerides significantly increased (76 ± 38 mg/dL at baseline to 104 ± 44 mg/dL; p = 0.005). Conclusion: A short-term HC and LC diet showed improvements in various performance parameters in favor of the HC diet. Some parameters of body composition significantly changed during both diets. The HC diet led to a significant reduction in total and LDL-cholesterol while triglycerides significantly increased.
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10.
Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis.
Eckstein, ML, Farinha, JB, McCarthy, O, West, DJ, Yardley, JE, Bally, L, Zueger, T, Stettler, C, Boff, W, Reischak-Oliveira, A, et al
Diabetes care. 2021;(1):240-247
Abstract
OBJECTIVE To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes. RESEARCH DESIGN AND METHODS We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO2, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions (P < 0.05). RESULTS Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m2, HbA1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO2peak (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all P < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [-0.75; 1.09] vs. 0.66 [-0.28; 1.45]; P < 0.001). None of the exercise physiological responses were associated with HbA1c in individuals with type 1 diabetes. CONCLUSIONS Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing.