a randomized controlled trial

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism

Diurnal distribution of carbohydrates and fat affects substrate oxidation and adipokine secretion in humans.

BACKGROUND: A diet in which fat is mainly eaten in the morning and carbohydrates mainly in the evening (compared with the reverse order) was recently shown to worsen glycemic control in people with prediabetes. OBJECTIVE: We investigated the effects of these dietary patterns on energy metabolism, and on the daily profiles of circulating lipids, adipokines, and inflammatory markers. DESIGN: In a randomized controlled crossover trial, 29 nonobese men (with normal glucose tolerance, n = 18; or impaired fasting glucose/glucose tolerance, n = 11) underwent 2 isocaloric 4-wk diets: 1) carbohydrate-rich meals until 1330 and fat-rich meals between 1630 and 2200 (HC/HF); or 2) the inverse sequence of meals (HF/HC). During a 12-h clinical investigation day after each intervention period, 2 meal tolerance tests were performed, at 0900 and 1540, respectively. Substrate oxidation and concentrations of circulating lipids, adipokines, and cytokines were assessed pre- and postprandially. The postprandial inflammatory response in leukocytes was analyzed ex vivo. RESULTS: Fasting carbohydrate oxidation decreased (P = 0.004) and lipid oxidation increased (P = 0.012) after the HC/HF diet. Fasting concentrations of blood markers did not differ between diets. The diets modulated the daily profiles of carbohydrate oxidation, lipid oxidation, and β-hydroxybutyrate, although the average daily values of these parameters showed no difference between the diets, and no interaction between diet and glucose tolerance status. Diurnal patterns of triglycerides, low-density lipoprotein cholesterol, leptin, visfatin, and of LPS-induced cytokine secretion in blood leukocytes were also modulated by the diets. Average daily concentrations of leptin (P = 0.017) and visfatin (P = 0.041) were lower on the HF/HC diet than on the HC/HF diet. CONCLUSIONS: Diurnal distribution of carbohydrates and fat affects the daily profiles of substrate oxidation, circulating lipids, and cytokine secretion, and alters the average daily concentrations of adipokine secretion in nonobese nondiabetic humans. The study was registered at clinicaltrials.gov as NCT02487576

The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism

Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.

CONTEXT: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. OBJECTIVE: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. DESIGN: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. RESULTS: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. CONCLUSIONS: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity

Application of hyperglycemic clamp with three different secretagogues for a phenotyping of early metabolic alterations in first degree relatives of patients with type 2 diabetes mellitus

Titelblatt, Inhaltsverzeichnis 1 Einleitung 9 1.1 Typ 2 Diabetes mellitus 9 1.2 Probleme der Phänotypisierung der frühen ß-Zellfunktionsstörungen 9 1.3 Methoden zur Untersuchung der ß-Zellfunktion in vivo 11 1.3.1 Hyperglykämischer Glukoseklemmtest 11 1.3.2 Inkretine und ß-Zellfunktionsstörungen 13 1.3.3 Arginin und Insulinsekretion 14 1.4 Probleme der Methodik der Insulinkonzentrationsbestimmungen 14 1.4.1 Physiologie und Messung der Insulinsekretion 14 1.4.2 Physiologie und Messung der Insulinclearance 15 1.4.3 Physiologie und Messung der Proinsulinprozessing 16 2 Ziel der Studie 17 3 Methodik 18 3.1 Studienprotokoll 18 3.2 Patientencharakteristika 18 3.3 Versuchsprotokoll 18 3.4 Infusionslösungen 20 3.5 Blutentnahmen 22 3.6 Laborbestimmungen 23 3.6.1 Kapilläre Blutglukose 23 3.6.2 Hormone 23 3.7 Auswertung 25 3.7.1 HOMA-Analyse 25 3.7.2 Pankreatische Insulinsekretionsrate 25 3.7.3 Metabolische Clearancerate von endogenem Insulin 27 3.7.4 Proinsulin zu Insulin und Proinsulin zu C-Peptid Ratio 28 3.7.5 Insulin Sensitivität Index 28 3.7.6 Dispositionsindex 28 3.7.7 Phasen der Insulinsekretion 28 3.7.8 Statistische Auswertung 29 4 Ergebnisse 30 4.1 Charakterisierung der Probanden 30 4.2 Blutglukose 30 4.3 Glukose Infusionsrate 33 4.4 HOMA-Analyse 33 4.4.1 Insulinresistenz Index 33 4.4.2 ß-Zell-Sekretionskapazität 33 4.5 Periphere Insulinkonzentrationen 33 4.6 C-Peptid 36 4.7 Pankreatische Insulinsekretionsrate 40 4.8 Endogene Insulinclearance 43 4.9 Proinsulin 48 4.10 Insulin Sensitivität Index 50 4.11 Dispositionsindex 53 5 Diskussion 55 5.1 Korrelationen zwischen den verschiedenen Phasen der Insulinsekretion 55 5.2 Einfluß der Insulin Resistenz auf die Phasen der Insulinsekretion 56 5.3 Einschätzung der maximalen Insulinsekretionskapazität 57 5.4 ISR in verschiedenen Phasen des hyperglykämischen Glukoseklemmtests 57 5.5 Insulinotrope Wirkung des GIP bei erstgradigen Verwandten von T2DM 58 5.6 Veränderungen des endogenen Insulinclearance 59 5.7 Absolute und relative Hyperproinsulinämie 60 6 Zusammenfassung 62 7 Literaturverzeichnis 64 8 Danksagungen 73Der Typ 2 Diabetes mellitus (T2DM) ist eng mit erblichen Defekten der Insulinwirkung und Insulinsekretion verknüpft. In dieser Arbeit wurde ein neuer 3-Stufen kumulativer Infusionstest mit Glukose, Gastric Inhibitory Polypeptide (GIP) und Arginin bei gesunden Probanden und gesunden Kindern von Patienten mit T2DM zur differenzierten Untersuchung früher Insulinsekretionsdefekte entworfen und eingesetzt. Methodisch wurde in hyperglykämischen Glukoseklemmtest zusätzlich nach 60 min GIP und nach weiteren 30 min Arginin als Bolus und Infusion zugegeben. Insulin-, C-Peptid- und Proinsulinkonzentrationen wurden durch spezifische ELISAs bestimmt und zur Berechnung der pankreatischen Insulinsekretionsrate, der Insulinclearance und des Insulinprozessierens verwendet. Nach jedem Stimulus wurde eine akute, erste Phase und eine zweite langsamere Phase der Insulinsekretion beobachtet. Die Effekte des Sekretagogen waren additiv und bedingten eine etwa 80-fache Steigerung der Insulinsekretion. In beiden Gruppen der Probanden wurde eine hohe Korrelation zwischen einzelnen Phasen der Insulinsekretion nachgewiesen. Der Insulinresistenz Index war bei der Kinder von Patienten mit T2DM signifikant höher als in der Kontrollgruppe. Die Kinder von Patienten mit T2DM wiesen eine erhöhte basale Insulinsekretion, reduzierte Insulinantwort auf GIP und eine eingeschränkte maximale Insulinsekretionskapazität in hyperglykämischen Glukoseklemmtest auf. Wegen einer reduzierten hepatischen Insulinextraktion bei Kinder von Patienten mit T2DM waren diese Befunde nicht durch eine Abnahme der peripheren Insulinkonzentrationen festzustellen, sondern durch die verminderte, mittels C-Peptidkonzentrationen berechnete, Insulinsekretionsrate zu identifizieren. Ein Vergleich des Insulin Resistenz Index und der endogenen Insulinclearance Rate ergab in der Korrelationsanalyse einen signifikanten negativen Zusammenhang für die endogene Insulinclearance Rate unter GIP-Infusionen und unter Infusion von 3 Sekretagogen zusammen. Somit zeigten die Kinder von Typ 2 Diabetiker eine Insulinresistenz, die durch unterschiedliche Mechanismen kompensiert wurde: Eine Zunahme der basalen Insulinsekretionsrate und eine damit verbundene basale Hyperinsulinämie bei unveränderter basalen Insulinclearance. Eine verminderte Insulinclearance unter ß-Zellstimulation und die peripheren Insulinkonzentrationen, welche trotz reduziertem Anstieg der Insulinsekretionsrate vergleichbar mit peripheren Insulinkonzentrationen in der Kontrollgruppe waren. Ein weiteres wichtiges Ergebnis dieser Studie ist, dass GIP einen doppelten Effekt zur Überwindung der Insulinresistenz ausübt: eine Zunahme der ß-Zellsekretion unter Hyperglykämie und eine Abnahme der Insulinclearance. Bei jüngeren, glukosetoleranten, erstgradigen Verwandten von Typ 2 Diabetikern scheint nur die ß-zellstimulierende Wirkung des GIP eingeschränkt zu sein. Dafür spricht auch bei Kinder von Typ 2 Diabetiker beobachtete absolute und relative Hyperproinsulinämie in Antwort auf GIP- und Arginin- Stimulation. Schlußfolgerung: Die neue Modifikation des hyperglykämischen Glukoseklemmtests ist für die metabolische Phänotypisierung gut geeignet. Insulinresistente Kinder von T2DM weisen unter hyperglykämischen Bedingungen mehrere Defekte der Insulinantwort auf. Defekte der Insulinsekretion werden durch eine veränderte Insulinclearance kompensiert.Background: Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder with varying degrees of impaired insulin sensitivity and insulin secretion resulting from interaction of genetic and environmental factors. To study early metabolic abnormality by healthy first degree relatives of patients with T2DM we designed a modified hyperglycaemic clamp which permitted determination of both insulin secretion and insulin action. Methods: We studied 8 (2w/6m) healthy, normal glucose-tolerant volunteers (age 32.6± 8.9 years, BMI 23.9±2.9 kg m ?2) and 8 (3w/5m) healthy, normal glucose-tolerant first degree relatives of patients with T2DM (age 26.4± 5.3 years, BMI 24.5±4.7 kg m ?2). We designed a intravenous test that during a single session evaluates: first- and second- phases of glucose-induced insulin secretion (120 min hyperglycemia of 11.1 mmol/l); insulin secretion during an incretin stimulus (hyperglycemia plus 1 h infusion of gastric inhibitory polipeptide (GIP)); and first and second phases of an arginine induced insulin secretion (hyperglycemia plus GIP-infusion plus 30 min arginine bolus and infusion). Insulin, C-peptide and proinsulin concentrations were defined with specific ELISAs that were used for calculation of a pancreatic insulin secretion rate, an insulin clearance, a proinsulin to insulin ratio and a proinsulin to C-peptide ratio. Results: An insulin resistance index was significant higher in the group of first degree relatives of patients with T2DM (p<0.001).The effect of three secretagogues were additiv and caused a 80-times raising of insulin concentration at 120 min of the clamp. A high grad of correlation between different phases of insulin secretion were proved in the both groups. First degree relatives of patients with T2DM demonstrated a complex pattern of the abnormality in the insulin secretion: increased basal insulin secretion rate (p<0.05); increased basal insulin concentrations (p<0.05); reduced GIP-stimulated insulin secretion rate (p<0.05) and reduced insulin secretion capacity (p<0.05). The insulin clearance was significant reduced in the group of first degree relatives of patients with T2DM in the lest 60 min of the hyperglycemic clamp. A significant negative correlation between insulin resistance index and insulin clearance under GIP infusion was detected. The proinsulin to C-peptide ratio was increased in first degree relatives of patients with T2DM in the lest 60 min of the clamp, with no difference between the groups for the proinsulin to insulin ratio. Conclusions: We have identified multiple metabolic abnormalities in normal glucose tolerant relatives of T2DM families. We propose that the decreased insulin secretion and decreased insulin sensitivity is limited by compensatory mechanisms, one of which includes a GIP-dependent reduction of the hepatic insulin clearance that will increase peripheral insulin levels to maintain normoglycemia

Bedeutung der gastrointestinalen Hormone in der metabolischen Dysfunktion bei der Adipositas und adipositas-assoziierten Erkrankungen

The worldwide obesity pandemia leads to persistent increase of type 2 diabetes mellitus and associated diseases. The gastrointestinal tract is the body´s largest endocrine organ and releases different peptide hormones that have important role in the nutritional sensing and regulation of appetite and energy expenditure. The work of the applicant focused on two topics: the role of gastrointestinal hormones GIP and ghrelin in obesity and the regulation of insulin degradation in obesity and T2DM. With respect to pathogenesis of obesity, the fat depot specifically expression and weight reduction dependent regulation of Glucose-dependent insulinotropic peptide (GIP) Receptor were analysed in two cohort of postmenopausal women. Decreased expression of the GIPR gene in subcutaneous fat tissue is associated with signs of insulin resistance in this cohort. Moreover, weight reduction in a moderate range, did not significantly change gene expression levels of GIP receptors in subcutaneous adipose tissue. Additionally we tested hypothesis, that GIP may influences all components of insulin handling: insulin secretion, insulin sensitivity and insulin degradation. In this second study, GIP infusion lead to significant reduction of hepatic insulin degradation in the healthy first degree relatives of diabetic subjects, but there was no general defect in insulin clearance in response to glucose and arginine in the hyperglycemic clamp. Thus, we propose that impairment in insulin secretion capacity and decreased insulin sensitivity is compensated for several mechanisms, one of which includes a GIP-dependent reduction of the insulin clearance that will increase peripheral insulin levels to maintain normoglycemia. Based on the growing evidence that GIP is involved in the control of fuel metabolism beyond its role as an incretin, we tested hypothesis that GIP may influences appetite and safety regulation via interactions with other gastro-intestinal hormones. We used extended 4-hours GIP-infusion protocol and hypothesized that GIP and/or insulin and their metabolites may affect ghrelin. Apart from analysis of plasma ghrelin and insulin levels, metabolic profiling with use of the GC- TOF/MS analysis was applied to decipher relevant metabolomic patterns from the same plasma samples. We created a hormone-metabolite network for each experiment and analysed the GIP and insulin effects on circulating ghrelin levels within the framework of those networks. GIP decreases circulating levels of the only hormone promoting food intake and may affect the ghrelin system via modification of circulating long-chain fatty acids pool. These observations were independent from insulin and offer potential mechanistic underpinnings for the involvement of GIP in systemic control of energy metabolism. The second focus of the applicant was the role of impaired insulin metabolism in the pathogenesis of obesity and type 2 diabetes mellitus. Decreased hepatic insulin degradation is the earliest phenotypical marker of disturbances in the insulin metabolism in obesity and may intensify the insulin resistance via chronically elevated circulating fasting and postprandial insulin levels. Insulin degrading enzyme (IDE) is a major enzyme responsible to insulin degradation in vivo. We performed the detailed analysis of the regulation of IDE functions by different concentrations of insulin and glucose in human hepatoma cells. In this liver cell model, IDE regulation was analysed at three levels: IDE transcription, IDE translation and IDE protein activity. Moreover, we proofed the regulation of IDE by different clamped glucose and insulin concentrations in vivo in man. Our data provide the first evidence of increase of IDE activity in hepatoma cells after insulin treatment in normal glucose conditions. Moreover, hyperglycemia suppress the insulin- induced change of IDE activity in vitro. The observed effects of the insulin and high glucose on the IDE activity may contribute to the regulation of insulin degradation in liver and to reduced hepatic extraction of insulin in T2DM. In the next step we validated and confirmed the association of IDE polymorphisms with T2DM risk in the prospective German cohort and provided novel evidence of influences of IDE genetic variants on insulin metabolism in the second cross-sectional German cohort of Berlin-Brandenburg region.Die weltweite Pandemie der Adipositas führt zu drastische Zunahme des Typs 2 mellitus und diabetes- assoziierten Erkrankungen. Der Gastrointestinaltrakt ist das größte endokrine Organ des Körpers und ein Sekretionsort von verschiedenen Peptidhormonen, welche eine wichtige Rolle in der Regulierung des Appetits und Energieverbrauchs spielen. Die vorgelegte Arbeit konzentriert sich auf zwei Themen: die Rolle der gastrointestinalen Hormonen Glucose- dependent Insulinotropic Peptide (GIP) und Ghrelin in der Pathogenese der Adipositas und die Regulation der Insulinabbau in Adipositas und Typ 2 Diabetes mellitus (T2DM). In der ersten Studie wurde das fettdepotspezifische Expression des GIP Rezeptors Gene (GIPR) in zwei Kohorten der postmenopausalen Frauen analysiert. Die verminderte GIPR Genexpression im subkutanen und viszeralen Fettgewebe war mit allen Zeichen der Insulinresistenz verbunden. Außerdem führte die Gewichtsreduktion in dieser Gruppe zu nicht signifikanten Anstieg der GIPR Genexpression in dem subkutanen Fettgewebe. In nächstem Schritt prüften wir Hypothese, dass GIP die Einflüsse auf verschiedenen Komponenten des Insulinmetabolismus wie Insulinsekretion, Insulinempfindlichkeit und Insulindegradation ausüben konnte: In dieser Studie führte akute 1 sündige GIP-Infusion zur bedeutenden Verminderung der hepatischen Insulinabbau in den gesunden erstgrädigen Verwandten von Patienten mit T2DM. Zudem wiesen diese Personen keinen allgemeinen Defekt in der Insulinantwort während dreistufigen Glukoseklemmtests auf. Auf diesem Weg kann die GIP- abhängige Verminderung der Insulinabbau bei T2DM prädisponierten Personen die periphere Insulinresistenz überbrücken und somit zu Aufrechterhaltung der Normoglykämie führen. Gestützt auf die wachsenden Hinweise, dass GIP an der Kontrolle des Energie Metabolismus außer seiner Rolle als einer Inkretin beteiligt ist, prüften wir die Hypothese, dass GIP die Wechselwirkungen mit dem Ghrelin, einem appetitförderndes Hormon aus dem GIT, haben kann. Wir verwendeten erweitertes 4-Stunden GIP-Infusionsprotokoll und setzten voraus, dass GIP und/oder Insulin und ihre Metaboliten die zirkulierende Ghrelinspiegel bei übergewichtigen Personen beeinflussen können. Abgesondert von der Analyse der Ghrelin- und Insulin-Konzentrationen in Plasma, der GC-TOF/MS-basierte Bestimmung der Plasmametaboliten wurde angewandt, um relevante Metabolitenmustern von der unterschiedlichen Experimenten mit und ohne GIP zu entziffern. Wir verwendeten so genanntes „Hormon-Metabolite-Netzwerk“ für jedes Experiment und analysierten den GIP und Insulin-Wirkungen auf die Ghrelinspiegel innerhalb des Fachwerks jedes Netzwerkes. Akute GIP-infusion führte zur signifikanten Senkung der Ghrelinspiegel, warscheinlich über die Modifizierung der zirkulierenden Fettsäuremuster. Diese Beobachtungen waren vom Insulin unabhängig und bieten potenzielle Erklärung des bekannten Phänomens der postprandiale Absenkung der Ghrelinspiegel. Somit ist GIP indirekt in der Regulation des Energie Metabolismus beteiligt. Der zweite Fokus der vorliegenden Arbeit befand sich in der Erforschung die Bedeutung der verminderten Insulinabbau in der Entstehung und Progression der Adipositas und T2DM. Verminderte hepatische Insulinabbau ist der frühste phenotypische Marker der Adipositas und kann die Insulinresistenz über das chronische Hyperinsulinämia verstärken. Wir führten die ausführliche Analyse der Funktionsregulierungen des Insulin Degrading Enzyms (IDE), welches eine zentrale Rolle bei Insulindegradation spielt, durch verschiedene Konzentrationen des Insulins und Glukose in vitro und in vivo Experimenten. Unsere Daten stellen die ersten Beweise dass Insulin die Aktivität der IDE in der Normoglykämie erhöht. Die Hypoglykämie führt zu Verminderung der IDE Aktivität und kann über diesen Weg zur chronischen Hyperinsulinämie und periphere Insulinresistenz in T2DM führen. In unsere nächste Studie konnten wir die Assoziationen der IDE Genpolymorphismen und Risiko für T2DM in dem prospektiven EPIC-Potsdam Studie beweisen. Zudem beeinflussen die Genpolymorphismen im Bereich des IDE-Gene das Insulinabbau in den Personen mit normale Glukosetoleranz in unserem cross-sektionalem MESYBEPO-Kohort

Subacute Thyroiditis Complicating COVID-19 Infection

Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood, it is generally associated to viral infections. Current evidence highlights that SAT may be a potentially uncommon manifestation of ongoing Coronavirus disease 2019 (COVID-19) infection or a post-viral complication of the disease. Despite that SAT is a rare manifestation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease both in ongoing and resolved COVID-19 infection, the ever-increasing numbers of COVID-19 patients strengthens the possibility that this particular disease entity will be of more immediate concern in the future. The current work aims to summarize the approach of SARS-CoV-2-associated SAT, present its pathophysiology, outline current research evidence found in the literature, and discuss potential differential diagnoses and diagnostic dilemmas through an illustrative case

Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity

Background Diets high in cereal-fiber (HCF) have been shown to improve whole-body insulin sensitivity. In search for potential mechanisms we hypothesized that a supplemented HCF-diet influences the composition of the human gut microbiota and/or biomarkers of colonic carbohydrate fermentation. Methods We performed a randomized controlled 18-week intervention in group-matched overweight participants. Fecal samples of 69 participants receiving isoenergetic HCF (cereal-fiber 43 g/day), or control (cereal-fiber 14 g/day), or high-protein (HP, 28% of energy-intake, cereal-fiber 14 g/day), or moderately high cereal fiber/protein diets (MIX; protein 23% of energy-intake, cereal-fiber 26 g/day) with comparable fat contents were investigated for diet-induced changes of dominant groups of the gut microbiota, and of fecal short-chain fatty-acids (SCFA) including several of their proposed targets, after 0, 6, and 18-weeks of dietary intervention. In vitro fermentation of the cereal fiber extracts as used in the HCF and MIX diets was analyzed using gas chromatography. Diet-induced effects on whole-body insulin-sensitivity were measured using euglycaemic-hyperinsulinemic clamps and re-calculated in the here investigated subset of n = 69 participants that provided sufficient fecal samples on all study days. Results Gut microbiota groups and biomarkers of colonic fermentation were comparable between groups at baseline (week 0). No diet-induced differences were detected between groups during this isoenergetic intervention, neither in the full model nor in uncorrected subgroup-analyses. The cereal-fiber extract as used for preparation of the supplements in the HCF and MIX groups did not support in vitro fermentation. Fecal acetate, propionate, and butyrate concentrations remained unchanged, as well as potential targets of increased SCFA, whereas valerate increased after 6-weeks in the HP-group only (p = 0.037). Insulin-sensitivity significantly increased in the HCF-group from week-6 (baseline M-value 3.8 ± 0.4 vs 4.3 ± 0.4 mg·kg-1·min-1, p = 0.015; full model 0-18-weeks, treatment-x-time interaction, p = 0.046). Conclusions Changes in the composition of the gut microbiota and/or markers of colonic carbohydrate fermentation did not contribute explaining the observed early onset and significant improvement of whole-body insulin sensitivity with the here investigated HCF-diet

Effects of acarbose treatment on markers of insulin sensitivity and systemic inflammation

Background: This study assessed the effect of postprandial glucose reduction by acarbose on insulin sensitivity and biomarkers of systemic inflammation. Methods: This was a single-center, double-blind, randomized, placebo-controlled, crossover study <40 weeks in duration, involving 66 subjects with varying degrees of glucose tolerance. Eligible patients completed a 3-week run-in period and were randomized to receive either 100 mg of acarbose three times daily followed by placebo, or vice versa, lasting 12 weeks each with a 12-week washout between interventions. Liquid meal challenges and hyperinsulinemic-euglycemic glucose clamp were performed at weeks 0, 12, 24, and 36. Results: Fasting proinsulin levels and proinsulin-to-adiponectin ratios but not fasting adiponectin levels were significantly lower during acarbose versus placebo treatment. Clamp-derived insulin sensitivity index and body weight were unchanged by the intervention. Levels of fasting insulin, fasting glucose, monocyte chemoattractant protein-1, interleukin-6, and interleukin-1 beta were comparable between treatments. In the liquid meal challenge tests, postprandial glucose and insulin responses were significantly lower during acarbose versus placebo treatment. The effects of acarbose on the reduction of fasting proinsulin was most pronounced in subjects with impaired fasting glucose/impaired glucose tolerance (n = 24). Conclusions: Reduction of the glycemic load by acarbose decreased fasting levels of proinsulin but had no effect on adiponectin and whole-body insulin sensitivity as well as biomarkers reflecting inflammation. The preventive effects of acarbose on type 2 diabetes mellitus and cardiovascular risk need further investigation and cannot be explained by changes of insulin resistance and inflammatory biomarkers