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1.
H. Kahles 《Der Diabetologe》2016,12(4):232-239
Objective
Vitamin D is not only essential for bone metabolism, but also has an additional immune-modulating effect on the immune system, which may play a role in the pathogenesis of several endocrine diseases.Aim
In this review, we debate the effects and recommendations of vitamin D supplementation, especially in the context of the nonclassical effects.Results
Evidence from animal model and epidemiological studies supports a role for vitamin D in many endocrine conditions. Vitamin D supplementation may play a role in the prevention of type 1 diabetes mellitus.Conclusions
Although observational studies support a potential role of vitamin D in endocrine disease, high-quality evidence from clinical trials to establish a place for vitamin D supplementation in optimizing endocrine health are lacking. Based on observational studies, vitamin D deficiency should probably be avoided in individuals at high risk of developing type 1 diabetes, specifically in early life.2.
Background
The intestinal microbiome plays an essential role in the development of chronic inflammatory diseases, such as inflammatory bowel disease (IBD) or metabolic disorders.Objectives
What is the pathophysiological role of the intestine as an interface between bacterial and host functions?Methods
Recent findings related to intestinal function and microbe–host interactions in the context of inflammatory and metabolic disorders are reviewed.Results and conclusions
Changes in gut microbiota composition and function (dysbiosis) are associated with a variety of different pathologies. Dysbiosis in combination with the loss of gut barrier and immune functions are shared in inflammatory and metabolic disorders. Causal mechanisms for the interaction of dysbiotic microbial communities in the gut and disease onset require additional clinical and experimental validation including prospective cohort and gnotobiotic animal studies. Fecal microbiota transplantation and targeted microbial therapies are promising strategies for clinical intervention; however many questions need to be addressed including disease-specific selection of donor microbiota or synthetic bacterial consortia, application strategies and risk evaluation.3.
A. F. H. Pfeiffer 《Der Diabetologe》2016,12(7):468-472
Background
Disturbances of glucose metabolism are common in chronic liver disease and about 30–40?% of patients with liver cirrhosis develop type 2 diabetes. The diabetes may be a direct consequence of the hepatic disease due to excessive insulin resistance or may be caused by classical type 2 diabetes.Blood glucose determination
Patients with chronic liver disease frequently have a normal fasting glucose despite manifest type 2 diabetes with postprandial excessive increases in glucose. Therefore, oral glucose tolerance tests should be performed after diagnosis of hepatic cirrhosis.Prognosis
Diabetes mellitus is associated with increased mortality and an increased risk of complications of liver cirrhosis including premature death, hepatocellular carcinoma, hepatic encephalopathy, and spontaneous bacterial peritonitis. Therapy of diabetes should include metformin and α?glucosidase inhibitors which can reduce the risk of these complications. Therefore, the diagnosis of diabetes has important consequences in chronic liver disease.4.
Background
Diabetes is associated with a two- to three-fold increased risk of cardiovascular events, and cardiovascular disease is the leading cause of death in patients with diabetes. The association with cardiovascular disease is particularly strong in patients with type 2 diabetes who, in addition to hyperglycemia, exhibit other atherogenic stigmata of insulin resistance such as abdominal obesity, dyslipidemia, and arterial hypertension. However, patients with type 1 diabetes are also at an increased risk of cardiovascular events over the long term, which is partly explained by direct glucotoxic damage to the endothelium.Prophylaxis
Lowering glucose both in type 2 and type 1 diabetes over long observational periods has been found to be associated with a decreased risk of cardiovascular events; however, at least in the short term glucose lowering is less efficacious in decreasing cardiovascular risk than lowering LDL (low density lipoprotein) cholesterol or normalizing blood pressure. Overly aggressive glucose lowering at the price of frequent hypoglycemia can even negatively affect cardiovascular outcomes because hypoglycemia is associated with an increased cardiovascular event risk.Important cardiovascular diseases in diabetes
In addition to coronary diseases, the increased heart failure risk of patients with diabetes has attracted increasing interest.5.
Background
A paradigm shift in therapeutic management of sigmoid diverticulitis has occurred with increasing reluctance regarding surgical treatment. While there is still a clear surgical indication in cases of complications such as strictures, fistulas, perforations or persistent bleeding, an elective indication for sigmoid resection is not clearly defined, especially in chronic-recurrent courses.Objectives
The main aspects of elective surgery for sigmoid diverticulitis are discussed.Materials and methods
Relevant studies were selected and the reference lists from those studies were also searched.Results
An uncomplicated form of acute diverticulitis (Classification of Diverticular Disease [CDD] type 1a/b) is not an indication for surgery (exception: immunosuppressed patients). In acute complicated diverticulitis (except free perforation), elective surgery should only be recommended in case of a macroabscess (CDD type 2b). In chronic recurrent, uncomplicated diverticulitis (CDD typ 3a/b), indication for surgery should be individualized. However, indications for elective surgery are complications such as strictures or fistulas (CDD type 3c). Recent data show that patients with type 2b and 3 diverticulitis benefit from elective surgery, especially in terms of quality of life.Conclusions
Although the majority of patients with diverticulitis can be treated conservatively, elective surgery should also be considered in terms of better quality of life compared to conservative therapy.6.
C. Lebherz 《Der Diabetologe》2016,12(2):80-87
Background
Patients with type 2 diabetes are at increased risk of developing cardiovascular diseases and have been shown to greatly benefit from tight control not only of the blood glucose but also of LDL (low density lipoprotein) cholesterol levels.Cardiovascular risk reduction
So far an aggressive treatment regimen with potent statins has been recommended. The IMPROVE IT study caused a paradigm shift in that it showed additional cardiovascular risk reduction if LDL cholesterol was reduced below target levels independent of the pleiotropic statin actions. These effects were even more significant in patients with type 2 diabetes.Conclusions
Therefore even though statins are still first choice, a combination with ezetimibe or the novel PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors is warranted to further reduce cardiovascular risk. As secondary targets, non-HDL (high density lipoprotein) cholesterol or ApoB (apolipoprotein B) levels serve as surrogate markers for atherogenic lipid particles. Depending on the individual lipid levels, combination therapy with fibrates or ω?3 fatty acids might be of benefit.7.
Background
The prevalence of nonalcoholic fatty liver disease (NAFLD) continues to increase. An estimated 25?% of the adult population worldwide and more than 50?% of patients with type 2 diabetes or obesity have NAFLD.Objectives
An overview of the natural history and complications of NAFLD is provided.Materials and methods
Following an extensive literature research, the current guidelines, expert opinions and studies focusing on NAFLD were analyzed.Results
The term NAFLD includes the entities nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which are defined by histological parameters. Importantly, “benign” NAFL may progress towards more aggressive NASH with the development of liver fibrosis. The grade of fibrosis is the most important predictor for overall and liver-related mortality in NAFLD patients and patients suffering from type 2 diabetes mellitus have a higher risk for progressive fibrosis. Progressive NAFLD can develop into liver cirrhosis with the potential of fatal complications of portal hypertension and liver failure. Notably, hepatocellular carcinoma may also develop in noncirrhotic NAFLD. Furthermore, NAFLD is an independent risk factor for cardiovascular disease and extrahepatic malignancy, which represent the two most frequent causes of death in NAFLD patients. To date, a lifestyle intervention aiming at weight reduction and increased physical activity is the first-line therapy for NAFLD.Conclusions
NAFLD is one of the most common liver diseases and is associated with relevant hepatic and extrahepatic morbidity and mortality.8.
Thorsten Feige 《Der Diabetologe》2018,14(7):465-469
Background
Most type 1 diabetes mellitus patients are not capable of achieving close to normal glucose levels and thus face a constant risk of severe hypoglycemia and diabetic ketoacidosis.Objectives
Patients develop their own personal non-approved medical devices to compensate for gaps in the existing medical technology.Materials and methods
Current studies are assessed and basic work and challenges are discussed.Results
The authorization of such systems from patients themselves results in the development of medical devices suitable for use but approved only based on freely available algorithms. Legal framework conditions, lack of standards on the interoperability of medical devices and uncertainties about future technology trends are giving rise to ongoing controversies.Conclusions
There is a need to validate these new approaches, agree upon success criteria and provide solid evidence of their effectiveness.9.
J. H. Stupin 《Der Diabetologe》2016,12(1):13-21
Background
Exclusive breastfeeding provides optimal nutrition and health protection for mothers and their offspring.Health benefits of breastfeeding for diabetic women
Diabetic mothers who breastfeed in the first 4 months postpartum have improved metabolic parameters, e.g., lower blood lipids, lower blood glucose, and greater insulin sensitivity. Studies have reported that longer duration of breastfeeding in women with a history of gestational diabetes may reduce long-term risks of cardiometabolic disease, including type 2 diabetes.Health benefits of breastfeeding for children
Children of diabetic mothers may benefit from breastfeeding in that they have lower rates of hypoglycemia immediately after birth and lower rates of obesity in later life. It has been suggested that the latter benefits may only be observed if breastfeeding is continued beyond a certain period where breastmilk composition would have normalized over time.Conclusion
Due to several risk factors and pathophysiological mechanisms, diabetic women are less likely and for a shorter duration to breastfeed. Therefore, diabetic women should be encouraged to breastfeed exclusively for at least 4–6 months to improve maternal and child morbidity, to prevent noncommunicable diseases in later life, and to decrease health care costs.10.
D. F. Braus 《Der Diabetologe》2016,12(5):346-351
Background
One of four patients with type 2 diabetes mellitus (T2DM) has clinically relevant depression. On the other hand, depression increases the risk for T2DM as well as micro- and macrovascular complications.Objectives
This association may reflect a shared pathophysiology consisting of complex bidirectional interactions, which may influence therapy and prognosis.Materials and methods
Recent findings, reviews and basic literature are analysed and an update is presented and discussed.Results
Overall, accumulating evidence indicates a metabolic–mood syndrome with a linkage that includes stress sensitivity, insulin resistance (IR), neurohormonal dysregulation and inflammation. IR alters dopamine turnover and causes depression-like behaviour. Furthermore IR is associated with worse memory performance. Metabolic risk influences neurodevelopment. However, cross-sectional data do not support a genetic association between T2DM and depression.Conclusions
T2DM may promote depression and interact with neurodevelopment and neurodegeneration. Comorbidity seems to be particularly toxic. Both prevention of T2DM in depressed patients and treatment of depression in T2DM are of considerable significance. Serotonin reuptake inhibition (SSRI) and psychotherapy are effective in the treatment of depression.11.
Purpose of Review
The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple. The clinical implications from observations on the microbiome and disease are broad.Recent Findings
A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease. The microbiome has a marked effect on the immune system. Our understanding of immune pathways modulated by the microbiota such as the induction of T helper 17 (Th17) cells and secretory immunoglobulin A (IgA) responses to segmented filamentous bacteria continues to expand. In addition to the gut microbiome, bacterial communities of other sites such as the mouth, lung, and skin have also been associated with the pathogenesis of rheumatic diseases.Summary
Strategies to alter the microbiome or to alter the immune activation from the microbiome might play a role in the future therapy for rheumatic diseases.12.
M. Blaut 《Der Diabetologe》2016,12(6):386-393
Background
The human digestive tract is populated with a complex community of mostly anaerobic microorganisms referred to as the intestinal microbiome. The importance of the intestinal microbiome for the host only became apparent after methods for the growth of strict anaerobes and the culture-independent retrieval of metagenomic information had been established.Colonization of the intestinal tract and functions of the microbiome
Microbial colonization of the intestinal tract occurs via the oral route during and after birth. Intestinal bacteria gain energy by fermenting undigested food components and endogenous substances. The microbiome endows the host with a wide spectrum of enzymes that enable the degradation of nondigestible food components. Nutrition is a major factor influencing the composition and activity of the intestinal microbiome. Bacterial fermentation in the colon gives rise to short-chain fatty acids which—in addition to delivering energy to the host—possess regulatory functions.13.
Purpose of Review
Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.Recent findings
Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.Summary
While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.14.
J. de Heer 《Der Diabetologe》2016,12(7):461-467
The role of the liver in carbohydrate metabolism
The liver plays a central role in carbohydrate metabolism. After food ingestion, glucose is taken up into the liver to be stored as glycogen, to be subject to glycolysis or conversion to fatty acids. In the fasted state, endogenous glucose is produced by degradation of glycogen or gluconeogenesis to warrant the peripheral tissues with a continuous supply of energy substrates.Glucose homeostasis
Glucose homoeostasis is based on the complex interplay of numerous factors, of which the pancreatic hormones insulin and glucagon are of particular importance. By both modification of gene expression and direct posttranslational effects on enzyme activity, they influence glucose metabolism and preclude extreme glucose variation. The exact molecular mechanisms underlying this regulation are still not fully understood.Conclusion
Considering the increasing prevalence of type 2 diabetes mellitus and obesity, as well as nonalcoholic fatty liver disease, efforts to explore the molecular mechanisms underlying the regulation of glucose metabolism should be intensified in order to discover new pharmacological targets to optimize treatment.15.
Purpose of Review
The objective of this review is to critically assess the contributing role of the gut microbiota in human obesity and type 2 diabetes (T2D).Recent Findings
Experiments in animal and human studies have produced growing evidence for the causality of the gut microbiome in developing obesity and T2D. The introduction of high-throughput sequencing technologies has provided novel insight into the interpersonal differences in microbiome composition and function.Summary
The intestinal microbiota is known to be associated with metabolic syndrome and related comorbidities. Associated diseases including obesity, T2D, and fatty liver disease (NAFLD/NASH) all seem to be linked to altered microbial composition; however, causality has not been proven yet. Elucidating the potential causal and personalized role of the human gut microbiota in obesity and T2D is highly prioritized.16.
N. Junge J. Dingemann C. Petersen M. P. Manns N. Richter J. Klempnauer U. Baumann A. Schneider 《Der Internist》2018,59(11):1146-1156
Background
A growing number of patients with biliary atresia and congenital cholestatic syndromes are reaching adulthood. These patients often have a number of typical medical features, including specific characteristics of liver transplantation medicine.Objective
What are the special features in the care of adults suffering from liver diseases with manifestation in childhood and adolescence, both before and after liver transplantation (LTX). How does the progression of individual diseases differ depending on age at manifestation? What are specific aspects following pediatric LTX?Patients and methods
Evaluation and discussion of existing guidelines and recommendations of the individual disciplines and professional societies as well as the current literature. Joint discussion of the recommendations between disciplines (gastroenterology, pediatric gastroenterology, surgery). Inclusion of center-specific experiences with transition from existing transition outpatient departments and training.Results
The recommendations are presented specifically for each disease. Special features in individual diseases after LTX are also discussed. Diagnosis-independent general treatment concepts for cholestasis and chronic liver disease are presented.Conclusion
Patients with biliary atresia and congenital cholestatic syndromes have a life-long chronic liver disease with and without LTX and require specific medical care. The patients benefit from the pooling of expertise in the individual disciplines.17.
Background
Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.Objectives
The psychosocial support given by self-help associations in different phases is evaluated.Materials and methods
Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.Results
On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.Conclusions
The removal of barriers and development of effective structures are overdue.18.
Background
Despite widespread use of antiviral cytomegalovirus (CMV) prophylaxis, active CMV infections with progression to CMV disease remain of paramount importance after renal transplantation, which can lead to severe complications particularly in CMV seronegative recipients of a CMV seropositive donor kidney.Objective
Risk stratification of active CMV infections and CMV disease, immune reactivity, clinical challenges, and development of approaches to disease management.Methods
Discussion of recent developments and expert recommendations.Results
There is a particularly high risk for the development of active CMV infections and CMV disease in CMV seronegative recipients of a CMV seropositive donor kidney. In this case CMV prophylaxis followed by preemptive therapy is recommended. The focus of this combined strategy is to prevent severe tissue-invasive CMV disease and to reduce the indirect effects of active CMV infections with inferior patient and transplant survival. Patients at increased risk who do not generate adequate CMV-specific cellular immunity after transplantation, nevertheless develop severe and occasionally recurrent active CMV infections after termination of prophylactic measures. In the case of life-threatening therapy-resistant CMV disease, adoptive transfer of CMV-specific T?cells has been proven to be a safe and effective therapy option.Conclusion
Clinically problematic courses of active CMV infections are limited to those patients with severely impaired CMV-specific immunity. The quantification of CMV-specific cellular immunity represents an appropriate instrument to achieve a better stratification of the risk of active CMV infections in patients at increased risk and is the subject of current research studies.19.
Background
Tumor budding in colorectal cancer has been identified as a robust biomarker. This morphological phenomenon, namely single tumor cells and small clusters of tumor cells that detach from the main tumor body, can also be used in certain clinical scenarios to guide patient management; however, tumor budding has hardly been integrated in colorectal cancer reporting protocols, mainly due to the lack of a standardized scoring method. The International Tumor Budding Consensus Conference (ITBCC), held in 2016 in Bern, Switzerland, has established evidence-based guidelines for assessing and reporting tumor budding in colorectal cancer.Objective
Presentation of the current understanding of tumor budding in colorectal cancer with emphasis on clinically relevant applications.Material and methods
Evaluation and overview of the relevant literature and level of evidence as a basis for the ITBCC guidelines.Results
Current findings support tumor budding as a morphological correlate of epithelial-mesenchymal transition. Strong associations with nodal metastases, poorer survival and higher recurrence rates mean tumor budding can be used to identify at-risk patients with endoscopically resected pT1 colorectal cancer and stage II colorectal cancer who may require segmental resection or be offered adjuvant chemotherapy, respectively. According to the ITBCC tumor budding should be reported in both of these scenarios.Conclusion
The ITBCC provides a basis for tumor budding to be integrated into standard colorectal cancer protocols; therefore, it can be expected that this marker will be increasingly reported. The ITBCC recommends that tumor budding be considered as an additional risk factor in a multidisciplinary setting.20.
T. Luedde C. Roderburg M. Binnebösel U. P. Neumann C. Trautwein 《Der Gastroenterologe》2016,11(6):479-488