Risk of bladder cancer in patients with type 2 diabetes mellitus: a retrospective population-based cohort study in Lithuania.

PURPOSE: The objective of our study was to evaluate bladder cancer risk among Lithuanian type 2 diabetes mellitus (T2DM) patients and the effect of antihyperglycemic therapy on bladder cancer risk. METHODS: We analyzed bladder cancer risk in a cohort of patients who were diagnosed with T2DM between 2001 and 2012 in Lithuania. Bladder cancer risk in four groups of antihyperglycemic medication users (insulin-only, metformin-only, sulfonylurea-only, and pioglitazone ± any other drug) was also assessed. Standardized incidence ratios for bladder cancer were calculated. RESULTS: A total of 76,818 patients (28,762 males and 48,056 females) with T2DM were included in the final cohort. In the whole cohort of diabetic patients, 277 bladder cancer cases were observed, compared to 232.75 expected cases, according to bladder cancer rates in the general population (Standardized Incidence Ratio 1.19; 95% Confidence Interval: 1.06-1.34). Higher risk of bladder cancer was found in both men and women; however, in women the risk increase was not statistically significant. We found higher risk of bladder cancer in patients of both sexes diagnosed with T2DM at the age of 50-79 years and also in all groups of different antihyperglycemic medication users. CONCLUSION: T2DM was associated with increased risk of bladder cancer.

Metformin in Chemoprevention of Lung Cancer: A Retrospective Population-Based Cohort Study in Lithuania.

Background and Objectives: This study aimed to evaluate the potential chemopreventive effect of antidiabetic medications, specifically metformin and pioglitazone, on lung cancer in patients with type 2 diabetes mellitus (T2DM). Additionally, the potential dose-response relationship for metformin use was analyzed. Methods: We conducted a retrospective cohort study utilizing comprehensive national health insurance and cancer registry databases to gather a large cohort of T2DM patients. Cox proportional hazards regression models were used to assess the risk of lung cancer across different antidiabetic medication groups, adjusting for potential confounders such as age and gender. A dose-response analysis was conducted for metformin users. Results: Our results indicated that metformin users had a significantly lower lung cancer risk than the reference group (HR = 0.69, 95% CI [0.55-0.86], p = 0.001). The risk reduction increased with higher cumulative metformin doses: a metformin cumulative dose between 1,370,000 and 2,976,000 had an HR of 0.61 (95% CI [0.49-0.75], p < 0.001) vs. cumulative metformin dose >2,976,000 which had an HR of 0.35 (95% CI [0.21-0.59], p < 0.001). No significant association between pioglitazone use and the risk of lung cancer was found (HR = 1.00, 95% CI [0.25-4.02]). Conclusions: This study shows that metformin may have a dose-dependent chemopreventive effect against lung cancer in T2DM, while the impact of pioglitazone remains unclear and requires further investigation.

Does Iodine Influence the Metabolism of Glucose?

Thyroid function and glucose status are linked; experimental, clinical, and epidemiological studies have shown this. Iodine is a vital trace element that is inextricably linked to thyroid hormone synthesis. The latter is also associated with glucose metabolism and diabetes. Recently, some-but not all-studies have shown that iodine is linked to glucose metabolism, glucose intolerance, impaired fasting glucose, prediabetes, diabetes mellitus, or gestational diabetes. In this concise review, we review these studies, focusing on iodine and glucose metabolism and prediabetic conditions or type 2 diabetes mellitus. The potential beneficial effect of iodine on glucose metabolism may be attributed to its antioxidant properties.

Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review.

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

Reduced risk of prostate cancer in a cohort of Lithuanian diabetes mellitus patients.

BACKGROUND: During the past decade, a huge interest was devoted to the type-2 diabetes mellitus and their associations with prostate cancer development. OBJECTIVES: The aim of this study was to determine whether type 2 diabetes mellitus and treatment with metformin is associated with prostate cancer risk. MATERIALS AND METHODS: The cohort was composed of diabetic male patients identified in the National Health Insurance Fund database during 2000-2016 and cancer cases in national Cancer Registry. We calculated standardized incidence ratios (SIR) for prostate cancers as a ratio of observed number of cancer case in people with diagnosis of diabetes to the expected number of cancer cases in the underlying general population. RESULTS: 2754 prostate cancers were observed versus 3111.26 expected within the period of observation entailing an SIR of 0.89 (95% CI: 0.85-0.92). Significantly lower risk of prostate cancer was found in diabetes patients in all age groups, also was in metformin-users and never-users' groups, with higher risk reduction in metformin-users (SIR 0.71, 95% CI: 0.68-0.75) than in diabetes patients never-users (SIR 0.88, 95% CI: 0.80-0.96). CONCLUSION: In this large population-based study, we found a significantly decreased risk of prostate cancer among men with diabetes and metformin-users.

Increased kidney cancer risk in diabetes mellitus patients: a population-based cohort study in Lithuania.

BACKGROUND: Diabetes is associated with increased risk of various cancers but its association with kidney cancer is unclear. The objective of this study was to evaluate the association between T2DM with or without metformin use and the risk of kidney cancer in a population-based national cohort in Lithuania. METHODS: The cohort was composed of diabetic patients identified in the NHIF database during 2000-2012. Cancer cases were identified by record linkage with the national Cancer Registry. Standardized incidence ratios (SIRs) for kidney cancer as a ratio of observed number of cancer cases in diabetic patients to the expected number of cancer cases in the underlying general population were calculated. RESULTS: T2DM patients (11,592) between 2000 and 2012 were identified. Overall, 598 cases of primary kidney cancer were identified versus 393.95 expected yielding an overall SIR of 1.52 (95% CI: 1.40-1.64). Significantly higher risk was found in males and females. Significantly higher risk of kidney cancer was also found in both metformin users and never-users' groups (SIRs 1.45, 95% CI: 1.33-1.60 and 1.78 95% CI: 1.50-2.12, respectively). CONCLUSIONS: The patients with T2DM have higher risk for kidney cancer compared with the general Lithuanian population.

Epinephrine also acts on beta cells and insulin secretion.

In a recent review examining neurotransmitter modulation of insulin secretion, the significant impact of epinephrine was not addressed. Its primary action involves inhibiting insulin release via alpha-adrenergic receptors, thereby reducing the response to insulin secretion stimulators, through the activation of K+ channels and resulting in membrane hyperpolarization in beta cells.

Artificial night light and thyroid cancer.

BACKGROUND: The occurrence of thyroid cancer (TC) has increased in recent decades. Exposure to outdoor artificial light at night (ALN) is associated with an increased risk of cancer. AIM: To investigated the impact of ALN, as a significant environmental pollutant, on TC incidence worldwide. METHODS: The assessment involved analyzing satellite ALN data in conjunction with TC incidence data [adjusted standardized rate (ASR)], while considering the quality of cancer registries (QCR), gross domestic product (GDP) per person, and health expenditure per person (HEP) for each country. RESULTS: Results indicated a correlation between higher ASR and ALN exposure percentages, particularly in countries with higher GDP or HEP quartiles (all P< 0.05). Significant differences in ASR were observed across QCR levels, both high and low quality (all P < 0.05), but not in countries without registry activity. However, when evaluating ASR against ALN exposure percentages while considering GDP/HEP quartiles or QCR levels, no significant associations were found (all P > 0.10). CONCLUSION: The findings suggest a potential link between higher GDP and adverse health conditions, serving as possible risk factors for TC, rather than a direct association with ALN. Limitations include the use of cross-sectional data, temporal misalignment, and reliance on ALN as a socioeconomic proxy. It is proposed that light pollution might be connected to a lifestyle conducive to carcinogenesis. Additionally, the presence of higher GDP/HEP could enhance access to diagnostic resources, potentially facilitating TC diagnosis and inclusion in cancer registries.

The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study.

Objectives: The aim of this study was to determine the association between insulin glargine usage and the potential increase in cancer risk among the Lithuanian population diagnosed with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study was conducted. The cohort of insulin users was established by identifying all male and female patients diagnosed with T2DM, as recorded in the National Health Insurance Fund database between 1 January 2000 and 31 December 2012. The risk of cancer among insulin glargine users was compared with the risk in non-glargine insulin users. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Results: The overall cancer risk for all sites combined showed no significant difference (HR 0.84, 95% CI 0.67-1.05). Although a general decrease in the risk of cancers was observed at most sites for glargine users, the use of insulin glargine was associated with a non-significant increase in the risk of mouth and pharynx, stomach, non-melanoma skin, breast, cervical, ovarian, and central nervous system cancers. There was a tendency for a lower risk of colon, rectum, rectosigmoid, and anus cancer among glargine users (HR 0.45, 95% CI 0.18-1.12, p = 0.09). Conclusions: Our research contributes to the growing body of evidence showing that insulin glargine is not associated with an increased risk of all cancers or specific types of cancer.

Association of Urinary Sodium, Potassium, and the Sodium-to-Potassium Ratio with Impaired Kidney Function Assessed with 24-H Urine Analysis.

Background: Albuminuria and albumin excretion rate (AER) are important risk factors for chronic kidney disease (CKD) development. Despite the extensive evidence of the influence of sodium and potassium on cardiovascular health, the existing evidence regarding their impact on albuminuria and kidney disease is limited and inconsistent. Our study aimed to assess the correlation between urinary sodium and potassium excretion, and the sodium-to-potassium ratio (Na/K ratio) with impaired kidney function, particularly the AER and albuminuria. Materials and Methods: Data were collected from the Lithuanian NATRIJOD study. A total of 826 single 24-h urine samples from individuals aged 18 to 69 were collected and analyzed for their sodium and potassium levels, Na/K ratio, and AER. Albuminuria was defined as an AER exceeding 30 mg/24 h. Results: The participant mean age was 47.2 ± 12.1 years; 48.5% of the participants were male. The prevalence of albuminuria was 3%. Correlation analysis revealed a positive correlation between AER and urinary sodium excretion (rs = 0.21; p < 0.001) and urinary potassium excretion (rs = 0.28; p < 0.001). In univariate linear regression analysis, sodium and potassium excretion and the Na/K ratio were significant AER predictors with ß coefficients of 0.028 (95% CI: 0.015; 0.041; p < 0.001), 0.040 (95% CI: 0.003; 0.077; p = 0.035), and 1.234 (95% CI: 0.210; 2.259; p = 0.018), respectively. In the multivariable model, only urinary sodium excretion remained significant, with a ß coefficient of 0.028 (95% CI: 0.016; 0.041). Potential albuminuria predictive factors identified via univariate logistic regression included urinary sodium excretion (OR 1.00; 95% CI: 1:00; 1.01) and the Na/K ratio (OR 1.53; 95% CI: 1.11; 2.05). However, these factors became statistically insignificant in the multivariate model. Conclusions: Urinary sodium and potassium excretion and the Na/K ratio are significantly associated with kidney damage, considering the assessed 24-h albumin excretion rate and presence of albuminuria content.

Pandemic and precocious puberty - a Google trends study.

BACKGROUND: Recent publications from several countries have reported that more young people (mainly girls) are experiencing precocious puberty (PP)/menarche during the coronavirus disease 2019 pandemic compared to the past. This variation is attributed to the stress of confinement, lack of exercise, obesity and disturbed sleep patterns. A common feature of the relevant papers, however, is the small number of reported cases of PP. Studies have shown that searches for diseases on the internet also reflect to some extent the epidemiology of these diseases. AIM: To estimate, through internet searches for PP, any changes in the epidemiology of PP. METHODS: We assessed in Google Trends searches for 21 PP-related terms in English internationally (which practically dwarf searches in other languages), in the years 2017-2021. Additionally, we assessed local searches for selected terms, in English and local languages, in countries where a rise in PP has been reported. Searches were collected in Relative Search Volumes format and analyzed using Kendall's Tau test, with a statistical significance threshold of P < 0.05. RESULTS: Internationally, searches for three PP-related terms showed no noticeable change over the study period, while searches for eight terms showed a decrease. An increase was found over time in searches for nine PP-related terms. Of the 17 searches in English and local languages, in countries where a rise in PP has been reported, 5 showed a significant increase over time. CONCLUSION: Over the study period, more than half of the search terms showed little change or declined. The discrepancy between internet searches for PP and the reported increase in the literature is striking. It would be expected that a true increase in the incidence of PP would also be aptly reflected in Google trends. If our findings are valid, the literature may have been biased. The known secular trend of decreasing age of puberty may also have played a role.

Hyperglycaemia and Its Prognostic Value in Patients with COVID-19 Admitted to the Hospital in Lithuania.

BACKGROUND AND OBJECTIVES: Increased blood glucose levels atadmission are frequently observed in COVID-19 patients, even in those without pre-existing diabetes. Hyperglycaemia is associated with an increased incidence of severe COVID-19 infection. The aim of this study was to evaluate the association between hyperglycaemia at admission with the need for invasive mechanical ventilation (IMV) and in-hospital mortality in patients without diabetes who were hospitalized for COVID-19 infection. MATERIALS AND METHODS: This retrospective observational study was conducted at Vilnius University Hospital Santaros Clinics, Lithuania with adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 and were hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. Based on blood glucose levels on the day of admission, patients without diabetes were divided into 4 groups: patients with hypoglycaemia (blood glucose below 4.0 mmol/L), patients with normoglycaemia (blood glucose between ≥4.0 mmol/L and <6.1 mmol/L), patients with mild hyperglycaemia (blood glucose between ≥6.1 mmol/L and <7.8 mmol/L), and patients with intermittent hyperglycaemia (blood glucose levels ≥7.8 mmol/L and <11.1 mmol/L). A multivariable binary logistic regression model was created to determine the association between hyperglycaemia and the need for IMV. Survival analysis was performed to assess the effect of hyperglycaemia on outcome within 30 days of hospitalization. RESULTS: Among 1945 patients without diabetes at admission, 1078 (55.4%) had normal glucose levels, 651 (33.5%) had mild hyperglycaemia, 196 (10.1%) had intermittent hyperglycaemia, and 20 (1.0%) had hypoglycaemia. The oddsratio (OR) for IMV in patients with intermittent hyperglycaemia was 4.82 (95% CI 2.70-8.61, p < 0.001), and the OR was 2.00 (95% CI 1.21-3.31, p = 0.007) in those with mild hyperglycaemia compared to patients presenting normal glucose levels. The hazardratio (HR) for 30-day in-hospital mortality in patients with mild hyperglycaemia was 1.62 (95% CI 1.10-2.39, p = 0.015), while the HR was 3.04 (95% CI 2.01-4.60, p < 0.001) in patients with intermittent hyperglycaemia compared to those with normoglycaemia at admission. CONCLUSIONS: In COVID-19 patients without pre-existing diabetes, the presence of hyperglycaemia at admission is indicative of COVID-19-induced alterations in glucose metabolism and stress hyperglycaemia. Hyperglycaemia at admission in COVID-19 patients without diabetes is associated with an increased risk of invasive mechanical ventilation and in-hospital mortality. This finding highlights the importance for clinicians to carefully consider and select optimal support and treatment strategies for these patients. Further studies on the long-term consequences of hyperglycaemia in this specific population are warranted.

Sodium, Potassium and Iodine Intake in an Adult Population of Lithuania.

Hypertension is a leading risk factor for cardiovascular events and death. A reduction in salt intake is among the most cost-effective strategies to reduce blood pressure and the risk of cardiovascular diseases. Increasing potassium lowers blood pressure and is associated with lower cardiovascular risk. Adequate iodine intake is important to prevent iodine deficiency disorders. Salt iodization is a key strategy to prevent such deficiency. In Lithuania, no surveys have been performed to directly assess sodium, potassium and iodine consumption. The aim of the present study was to measure sodium, potassium and iodine intake in a randomly selected adult Lithuanian adult population using 24 h urine collections, and to assess knowledge, attitudes and behavior towards salt consumption. Salt and potassium intakes were estimated in 888 randomly selected participants by 24 h urine sodium and potassium excretion and 679 individuals provided suitable 24 h urine samples for the analysis of iodine excretion. Average salt intake was 10.0 (SD 5.3) g/24 h and average potassium intake was 3.3 (SD 1.3) g/24 h. Only 12.5% of participants consumed less than 5 g/24 h of salt. The median value of urinary iodine concentration (UIC) was 95.5 µg/L. Our study showed that average salt intake is twice as high as the maximum level recommended by the World Health Organization while potassium and iodine intakes in Lithuania are below the recommended levels.

Polycystic ovary syndrome: Pathways and mechanisms for possible increased susceptibility to COVID-19.

In 75% of women with polycystic ovary syndrome (PCOS), insulin action is impaired. In obesity, visceral adipose tissue becomes dysfunctional: Chronic inflammation is favored over storage, contributing to the development of metabolic complications. PCOS, metabolic syndrome (MetSy) and non-alcoholic fatty liver disease (NAFLD) apparently share common pathogenic factors; these include abdominal adiposity, excess body weight and insulin resistance. Alterations in the gut microbiome have been noted in women with PCOS compared to controls; these may lead to deterioration of the intestinal barrier, increased gut mucosal permeability and immune system activation, hyperinsulinemia and glucose intolerance, which hamper normal ovarian function and follicular development (all being hallmarks of PCOS). It has been proposed that PCOS may entail higher susceptibility to coronavirus disease 2019 (COVID-19) via its associated comorbidities (NAFLD, obesity, MetSy and alterations in the gut microbiome). Studies have found an association between acute respiratory distress syndrome (seen in severe cases of COVID-19) and the intestinal microbiome. Furthermore, apparently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can gain entry to the gastrointestinal tract via locally-expressed angiotensin converting enzyme type 2 receptors. Excess body weight is associated with more severe COVID-19 and increased mortality. Although robust links between SARS-CoV-2 infection and PCOS/NAFLD/gut microbiome/metabolic consequences are yet to be confirmed, it seems that strategies for adapting the intestinal microbiome could help reduce the severity of COVID-19 in women with PCOS with or without NAFLD, MetSy or obesity.

Risk of Endometrial Cancer in Women with Diabetes: A Population-Based Retrospective Cohort Study.

The aim of this study was to examine the association between type 2 diabetes (T2DM), use of glucose-lowering medications and endometrial cancer (EC) risk. METHODS: The risk of EC incidence among women with T2DM in Lithuania was assessed using a retrospective cohort study design. Female patients who were registered with T2DM between 1 January 2000 and 31 December 2012 were identified in the National Health Insurance Fund database. EC cases (ICD-10 code C54) were identified from the Lithuanian Cancer Registry. Standardized incidence ratios (SIRs) were calculated by dividing the observed numbers of EC among patients with T2DM by the expected number of EC, calculated using national rates. RESULTS: A total of 77,708 diabetic women were included in the analysis, and 995 cases of EC were identified. A significantly increased EC risk in diabetic women was found as compared to the general population (SIR = 1.69, 95% CI 1.59-1.80). The greatest EC risk was found among younger patients at T2DM diagnosis, and the risk declined gradually with increasing age but persisted in being significantly increased among all age groups. The risk for EC increased with increasing duration of diabetes, and the highest EC risk was observed more than 10 years after T2DM diagnosis. A significantly higher EC risk than expected from the general population was found in all patient groups by glucose-lowering medication combinations. The lowest EC risk was observed in diabetic women who were users of "oral only" (without metformin) (SIR = 1.42, 95% CI 1.10-1.83) and "metformin only" (SIR = 1.69, 95% CI 1.49-1.92) medications. A two times greater EC risk was observed among the remaining glucose-lowering medication categories. In contrast, use of insulin only was not related to a higher EC incidence risk (SIR = 0.45, 95% CI 0.23-0.86); however, the risk estimation was based on nine cases. CONCLUSIONS: Our study shows a significantly increased EC risk in diabetic women as compared to the general population. In this study, a significantly higher EC risk was found in all patient groups by glucose-lowering medication combinations, except for insulin only users.

[Body composition and polycystic ovary syndrome]. / Kuno sandara ir policistiniu kiausidziu sindromas.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders of reproductive age women. The main signs of PCOS are as follows: androgen excess, menstrual dysfunction, infertility, obesity, and other numerous health problems. By different authors, the disorder affects 2-28% of reproductive age women. Polycystic ovary syndrome is characterized by presence of hyperandrogenism, anovulation, menstrual cycle disturbances, also by the other metabolic changes. The lack of well-defined and universally accepted diagnostic criteria makes identification of this syndrome confusing to many clinicians. There are only few studies concerning the correlations between phenotypic expression, body composition and PCOS, and relationship with the processes of growth and sexual maturation and various environmental factors (nutrition, physical activity, stress, and other factors). There is a lack of knowledge about further PCOS development and prognosis, considering the individual and environmental factors. Variation in human body composition and shape ranges considerably: many body size and shape indices (height, weight, body composition, and proportions) are the result of long evolution process and adaptation to environment. Obviously, the morphological body parameters, physiological and biochemical indices are complex and compound the interdependent system. By current literature, more than 50% of women are overweight or obese. If waist circumference and waist-to-hip ratio of women with PCOS increase, reproductive function and metabolic state of a woman is altered more than in cases when there are no changes in these parameters. The investigations of the strongest sexual dimorphism sign--the subcutaneous and visceral fat topography--showed that women with PCOS have greater adipose tissue mass in the areas of the abdomen, waist, and upper arms than control women. It is known that some indices of sexual dimorphism may be considered as the morphological signs of hyperandrogenism, for example handgrip, waist-to-hip ratio, hand and foot length, 2nd-to-4th digit (finger length) ratio (2D:4D), certain facial characteristics. Only 2D:4D ratio was investigated for the women with PCOS. The early changes of certain morphological and other indices of physical status could help to predict some metabolic characteristics, development of PCOS, and outcome of this syndrome.

Positive effect of metformin treatment in colorectal cancer patients with type 2 diabetes: national cohort study.

We aimed to estimate colorectal cancer risk in patients with type 2 diabetes mellitus (T2DM) using metformin. Patients with colorectal cancer and diabetes from 2000 to 2012 were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Standardized incidence ratios (SIRs) for colorectal cancers as a ratio of observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population was calculated. We analysed 111 109 patients with diabetes. Overall, 1213 colorectal cancers were observed versus 954.91 expected within a period of observation entailing an SIR of 1.27 [95% confidence interval (CI): 1.20-1.34]. Significantly higher risk of colorectal cancer was found both in male and female patients with diabetes in all age groups. Higher risk was found for both colon and rectum cancers 1.36 (95% CI: 1.27-1.46) and 1.11 (95% CI: 1.01-1.22), respectively. There were no differences in risk over time since initial diabetes diagnosis. Never-users of metformin had twice higher risk of colorectal cancer compared to general population (SIR: 2.14, 95% CI: 1.95-2.35). Among metformin users, risk was lover (SIR: 1.47, 95% CI: 1.36-1.58) and colorectal cancer risk decreased with increasing cumulative dose of metformin (P < 0.001). Patients with T2DM had increased risk of colorectal cancer compared with the general Lithuanian population. Decreasing colorectal cancer risk with increasing cumulative dose of metformin indicates that metformin may be a protective agent for colorectal cancer development.

Cohort Study of Antihyperglycemic Medication and Pancreatic Cancer Patients Survival.

BACKGROUND: We assessed the association between the use of metformin and other antihyperglycemic medications on overall survival in diabetic patients with pancreatic cancer. METHODS: Patients with pancreatic cancer and diabetes between 2000 and 2015 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database. Cohort members were classified into six groups according to type 2 diabetes mellitus treatment: sulfonylurea monotherapy; metformin monotherapy; insulin monotherapy; metformin and sulfonylurea combination; metformin and other antihyperglycemic medications; all other combinations of oral antihyperglycemic medications. Survival was calculated from the date of cancer diagnosis to the date of death or the end of follow-up (31 December 2018). RESULTS: Study group included 454 diabetic patients with pancreatic cancer. We found no statistically significant differences in overall survival between patients by glucose-lowering therapy. However, highest mortality risk was observed in patients on insulin monotherapy, and better survival was observed in the groups of patients using antihyperglycemic medication combinations, metformin alone, and metformin in combination with sulfonylurea. Analysis by cumulative dose of metformin showed significantly lower mortality risk in the highest cumulative dose category (HR 0.76, 95% CI 0.58-0.99). CONCLUSIONS: Our study showed that metformin might have a survival benefit for pancreatic cancer patients, suggesting a potentially available option for the treatment.

Preexisting diabetes, metformin use and long-term survival in patients with prostate cancer.

OBJECTIVE: To assess prostate cancer-specific and overall survival in prostate cancer patients with or without preexisting type 2 diabetes mellitus (T2DM) with regards to metformin use. METHODS: Patients diagnosed with prostate cancer in the Lithuanian population between 2001 and 2005 were identified through the Lithuanian Cancer Registry and followed until 2016, date of death, loss to follow-up or whichever came first. Information regarding the diagnosis of T2DM and antihyperglycemic medications were obtained from the National Health Insurance Fund database. Prostate cancer-specific and overall survival outcomes were analysed using univariate and multivariate Cox proportional hazard models. RESULTS: Out of 6689 men included, 254 (3.8%) had preexisting T2DM. There were 4807 deaths during follow-up, including 2084 from prostate cancer. No differences were found in prostate cancer-specific survival between men with or without T2DM. The risk of overall mortality was higher (HR = 1.24, 95% CI = 1.07-1.43) in diabetic men. Univariate analysis showed cancer stage at diagnosis and age to be significant predictors of survival. After adjustment for age and stage at diagnosis, there was no difference in prostate-specific survival between non-diabetic patients compared to metformin users or metformin non-users. However, overall survival was lower in T2DM patients, with a higher mortality risk for metformin non-users (HR = 1.63, 95% CI = 1.27-2.10). Prostate cancer-specific mortality risk was insignificantly lower in diabetic men on metformin (HR = 0.74, 95% CI = 0.54-1.02). CONCLUSION: There was no difference in long-term prostate cancer-specific survival in patients with or without T2DM. Overall survival was lower in T2DM patients not treated with metformin.

Increased Mortality Risk in People with Type 2 Diabetes Mellitus in Lithuania.

This retrospective cohort study aimed to analyze overall and cause-specific mortality risk in people with type 2 diabetes mellitus (T2DM) in Lithuania. Information on the diagnosis of T2DM and glucose-lowering medication was obtained from the National Health Insurance Fund database, causes of death-from death certificates. Sex, age, and calendar period-standardized mortality ratios (SMRs) were calculated. In addition, 89,512 patients were followed-up between 2010 and 2017, contributing to the observation period of 592,321 person-years. Overall mortality risk was increased for both sexes (overall SMR = 1.35, 95% confidence interval (CI) 1.34-1.37). Greatest mortality risk was in the age group of 40-49 years at diabetes diagnosis (SMR = 1.68, 95% CI 1.60-1.76) and among those who had died before the age of 50 (SMR = 22.04, 95% CI 18.82-25.81). Patients treated with insulin only had the highest SMR (2.43, 95% CI 2.32-2.55). Mortality risk increased with increasing diabetes duration and was higher in women in all these groups. The highest cause-specific SMRs were infection-related causes (SMR = 1.44), particularly septicemia (SMR = 1.78), diseases of the circulatory system (SMR = 1.42), especially ischemic heart (SMR = 1.46) and cerebrovascular diseases (SMR = 1.38), as well as diseases of the digestive system (SMR = 1.35). Cancer mortality risk was elevated for women (SMR = 1.13), but not for men (SMR = 0.93). In conclusion, people with T2DM had an excess mortality risk, which was higher in women compared to men, younger people, in those who were diagnosed with T2DM at a younger age, had longer diabetes duration, and who required treatment with insulin.