[Investigation of glycaemic and nutritional status of patients suffering from cancer.] / Daganatos betegek glykaemiás és tápláltsági állapotának vizsgálata.

INTRODUCTION: Obesity, type 2 diabetes mellitus and cancers are equally endemic in our country. Their partially common metabolism may constitute the base of their similar epidemiology. OBJECTIVE: Proving metabolic relation between glycaemic and nutritional status and progression of cancers, as well as confirming the antitumor effect of non-insulin antidiabetics, primarily metformin. METHOD: We processed the data of 1224 patients treated at the Oncology Center in county Békés. We examined the progression of cancers depending on body mass index, blood glucose levels, the presence and therapy of type 2 diabetes, over and above analyzed changes in glycemic and nutritional status in relation to tumor stage, further more prevalence of diabetes mellitus. RESULTS: Despite of malignant cachexy, we found obesity or corresponding body mass index in relatively high rate (23.28%) more often associated with metastatic stage. We detected higher rate of type 2 diabetes (20.34%) compared to average population. We found even larger scale of diabetes among patients suffering from primary hepatocellular (60%, p<0.001), pancreatic (50%, p<0.001), urinary bladder (50%, p<0.001), prostate (50%, p<0.002), endometrial (50%, p<0.02) and postmenopausal breast cancer (30%, p<0.006), compared to other part of the studied population. Patients treated by non-insulin antidiabetics, taking metformin was accompanied by the lowest incidence of metastatic stage, the highest body mass index and blood glucose level. DISCUSSION: In our study, the order of malignant diseases most frequently associated with type-2 diabetes correspond to previously published literature data. Development of insulin resistance accompanied by tumor progression can be effectively delayed by antimetabolic medicines. The combined antimetastatic effect of metformin could achieve glucose and weight control independently. CONCLUSION: Based on our results, targeted screening for cancer among diabetic patients, and seeking and adequately treating glycometabolic disorders with concomitant malignant conditions, respectively , are suggested, mainly using metformin and new non-insulin antidiabetic medicines. Through these efforts, the fight against cancer can be more effective. Orv Hetil. 2023; 164(23) 900-910.

Oncodiabetology II. Antidiabetics and cancer prevention / Onkodiabetológia II. Antidiabetikumok és rákmegelozés

The number of patients with type 2 diabetes is increasing worldwide. In Hungary, the prevalence of known diabetic adults exceeds 9.1%, causing increased economical and medical burden to the society. It is obvious that there is a considerable urge to develop novel, safer and more efficient antidiabetic drugs. Therefore, studies have been focusing on the beneficial or detrimental side effects of antidiabetic drugs besides their general metabolic effects. Every anti-diabetic agent has an indirect anti-tumor effect as a consequence of lowering blood glucose levels and controlling carbohydrate, protein and lipid metabolism. In addition, most agents have their own direct antitumor effects, on the other hand, some may play a negligible role in cancer promotion. While the latter possibility is based mainly on pre-clinical, experimental data or on short-duration clinical studies, the informations about the safety of antidiabetic drugs are verified by large-scale, randomized, multicenter, placebo-controlled trials. Nowadays, metformin is the only drug that has been shown to reduce cancer risk in a variety of tumor localizations in monotherapy or in combination with other antidiabetic agents and insulins, and even in combination with certain cytostatics and biological therapies. The available data about the role of other antidiabetics in tumor prevention are less clear or insufficient. Here, we review the available ­ sometimes contradictory ­ literature about the relationship of tumor and antidiabet ics, verifying the safety of antidiabetics. Here, we propose that in the future tumor-specifically optimized antidiabetic treatment may play a role in tumor prevention or even in specific oncotherapy in patients with or without diabetes.

Oncodiabetology III. The relationship of antineoplastic therapies and carbohydrate metabolism / Onkodiabetológia III. Az antineoplasztikus terápiák és a szénhidrát-anyagcsere viszonya

The epidemiological indicators of malignant diseases and diabetes are changing similarly, as lately both have been dynamically increasing worldwide. They occur usually in the same patient synchronously or metachronously, because of their common metabolic and molecular background. Consequently, in more and more cases they require common treatment. That has led to a new science, called oncodiabetology, the main purpose of which is to optimize the combination of antineoplastic and antidiabetic therapies. Regarding the antineoplastic agents, their complex influence on metabolism has to be considered, especially diabetogenic side effects inducing insulin-resistance and decreasing insulin production. According to antidiabetic agents' role in preventing tumors, diminishing toxicity of cytostatic drugs, and promoting the breakthrough of chemoresistance should be considered. In this study, we investigate the contexts of antineoplastic agents' efficiency and the glucometabolism of the organization, the characteristics of oncotherapy in patients suffering from malignant disease and diabetes, and review those cytostatic agents, having massive diabetogenic adverse effects. We describe the properties and subtypes of secondary diabetes, thoroughly discuss the specific characteristics of hyperglycaemia and diabetes caused by malignant diseases and antineoplastic treatments, especially pancreatic diabetes. In the end, we attempt to determine the proper place and role of oncodiabetology in the treatment of patients suffering from malignancies. During our investigation, we assessed the effects on glucometabolism of the recently used classic cytostatics, molecularly targeted therapies and different endocrine manipulations treating malignancies. We reviewed the schedules and scientific background of almost 300 medicines for this aim. We established that every third antineoplastic agent influenced glucometabolism adversely. We report our further observations in our next reviews.

Oncodiabetology I. Metabolic and molecular relationships between cancer and diabetes / Onkodiabetológia I. Metabolikus és molekuláris összefüggések a rosszindulatú daganatok és a cukorbetegség között

In the recent decades, numerous studies have investigated the metabolic and molecular links between carbohydrate metabolic disorders and cancer, raising potential anti-tumor therapies. Based on epidemiological, preclinical, and clinical studies, now we know that advanced diabetes is a distinct risk factor of the development of many tumors, and even prediabetes may lead to the increased risk of developing cancer. Nowadays we can also state that the relationship is also present vice versa. It is a well-known fact that malignancies cause metabolic and molecular changes in the host over time resulting in an insulin-resistant state, characteristic of early diabetes. The tumor-induced insulin resistance may lead to the development of secondary diabetes in some patients with cancer. Furthermore, the diabetogenic ef-fect of the present anticancer therapies may worsen the metabolic condition. In recent years, research exploring the molecular causes of the correlation between malignancies and type 2 diabetes mellitus has highlighted the central role of RAS and PI3K signaling pathways. The altered function of these pathways significantly effects cell cycle, cellular metabolism, cell growth and proliferation, thus modifying cell survival, leading to tumorigenesis and tumor progres-sion and to insulin resistance as well. Without understanding the correlations between IGF receptors, RAS and PI3K signaling pathways the underlying molecular mechanism cannot be understood. Therefore, here we focus on these molecular mechanisms after a brief description of the most important metabolic connections between cancer and diabetes.

[Gastrointestinal locations of primary melanoma]. / A primer melanoma malignum ritka gastrointestinalis lokalizációi.

Primary gastrointestinal melanomas, part of the mucosal melanoma group, are uncommon. They constitute about five percent of all melanomas and most of them are located in the rectum (3 percent of all melanomas). The prognosis is poor, overall 5-year survival in rectal melanoma is 10-20 percent. We present three of our cases. The first case - a 68-year-old male patient - was operated on for histologically proved rectal melanoma. Three years after radical excision and oncological treatment a metastasis of the primary tumor was diagnosed in the stomach. Total gastrectomy was performed, followed by oncological treatment. In the second case of a 59-year-old male patient an appendectomy was performed for symptoms of appendicitis. The histopathological examination revealed melanoma of the appendix. Further investigations revealed the primary tumor in the stomach and metastases in the lungs as well. The third case - an 82-year-old female patient - was investigated for frequent defecations, mucus in stool and fecal incontinence. Primary melanoma was proved in the lower third of the rectum with multiple hepatic metastases. These three cases in our practice are remarkable for the rarity of the disease, and in two cases the presence of both the primary tumor and the metastasis were located in the gastrointestinal tract.

[Antidiabetic therapy--a new possibility in the complex therapy of cancer?]. / Antidiabetikus kezelés, mint újabb lehetoség a daganatok komplex terápiájában.

Nowadays the lack of exercise and improper eating habits are main characteristics of modern life style. This favors not only formation of type 2 diabetes or cardiovascular diseases, but also increaseas the incidence and prevalence of malignant tumors. Today there are many epidemiologic trials that demonstrate the connection between type 2 diabetes and formation of several malignomas. Its cause should be searched in common paths of pathologic processes. One of this is the birth of hyperinsulinsulinemia, which accompanies insulin resistance. Hyperinsulinemia of the host leads to increased glucose uptake in the highly insuline sensitive tumor cells which supports tumor growth. This makes type 2 diabetes a metabolic state favoring tumor formation, suggesting a potential application of oral insulin sensitizers in cancer therapy. Currently several international trials are testing the anti-tumor activity of metformin and thiazolidinedions (TZD). Besides this, encouraging results were obtained with the use of anti-IGFR antibodies in the treatment of tumors. A common therapy of diabetes and tumor may lead to new possibilities in the treatment of malignant tumor diseases. By doing this we could be able to weaken the tumor and strengthen the body, enabling it to fight against cancer. Bánhegyi RJ, Rus-Gal PO, Nagy AK, Martyin T, Varga R, Pikó B. Correlation between type 2 diabetes and malignant tumors - new possibilities in the complex therapy of cancers?