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First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD.

Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

Cardiovascular diabetology 21, 50 (2022). doi:10.1186/s12933-022-01481-0, Published by BioMed Central, London

Aims We aimed to assess the health status and quality of life (QoL) of patients with diabetes and explore the associated factors in a French-speaking region of Switzerland. Methods This cross-sectional study analyzed self-reported data from 585 patients with diabetes. We ran univariate and multivariate regressions analyses on health status (Physical and Mental Component Summary scores (PCS, MCS) of the SF-12) and diabetes-specific QoL (ADDQoL score). Results Mean PCS was 43.1 ± 10.4 and mean MCS was 46.7 ± 11.1. The overall ADDQoL score was −1.6 ± 1.6; the life domains of the ADDQoL with the lowest scores were freedom to eat, sex life and freedom to drink. Being older was independently and significantly associated with higher mental health and QoL, while lower income was associated with lower physical health, mental health, and QoL. Having diabetes for over 10 years was associated with lower QoL, while insulin treatment and complications were correlated with lower physical health and QoL. Conclusions This study provides key information on the health status and QoL of patients with diabetes in Switzerland and their associated factors, which can help healthcare providers to identify patients at higher risk of lower health and QoL.

New systemic cancer therapies are increasingly oriented towards specific signaling pathways involved in carcinogenesis. However, these new treatments may lead to disorders of glycemic homeostasis ranging from glucose intolerance, diabetes or the occurrence of severe acute hyperglycemic syndrome due to blockade of certain pathways common to glucose metabolism. This article discusses the estimated frequency of new-onset diabetes, the pathophysiological mechanisms as well as the diagnostic, therapeutic, monitoring and prognostic management of glycemic dysfunction in patients treated with these novel systemic cancer therapies.

Ethnopharmacological relevance The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally. Aim of the study To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action. Methods Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed. Results We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity. Conclusion Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.

AIM: To study the association between diabetes and the prevalence of and risk factors for polypharmacy among adults aged 50 and older in England.METHODS: A cross-sectional study (2012-2013) of the English Longitudinal Study of Ageing. Polypharmacy was defined as taking 5-9 long-term medications a day and heightened polypharmacy as 10 or more. Diabetes included diagnosed and undiagnosed cases (glycated haemoglobin ≥ 6.5% (48 mmol/mol)).RESULTS: Of 7729 participants, 1100 people had diabetes and showed higher prevalence rates of polypharmacy (41.1% vs 14.8%) and heightened polypharmacy (5.8% vs 1.7%) than those without diabetes, even when antihyperglycemic medications were excluded. Risk factors for polypharmacy also differed according to diabetes status. Among people with diabetes, risk factors for polypharmacy and heightened polypharmacy were having more long-term conditions (relative risk ratio (RRR) = 1.86; 3.51) and being obese (RRR = 1.68; 3.68), while females were less likely to show polypharmacy (RRR = 0.51) and heightened polypharmacy (RRR = 0.51) than males. Older age (RRR = 1.04) was only related to polypharmacy among people without diabetes.CONCLUSIONS: Adults with diabetes had higher prevalence rates of polypharmacy and heightened polypharmacy than those without diabetes, regardless of including antihyperglycemic drugs. Early detection of polypharmacy among older people with diabetes needs to focus on co-morbidities and obesity.

Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients.

Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.

Cognitive factors, like beliefs, have been studied extensively as determinants of medication adherence, while affect associated with taking medicines has been studied much less. In the present study (N = 525), we investigated affect by assessing patients’ first associations with taking their medicines. Results showed that these associations were related to self-reported medication adherence: Patients who associated taking medicines with negative affect were the least adherent, while those associating taking medicines with the need to take medicines were the most adherent. Our results support the idea that affect should be considered an important determinant of adherence.

A novel reverse phase, isocratic HPLC method is described to separate five anti-diabetic drugs i.e., glimepiride, metformin, sitagliptin, rosiglitazone and pioglitazone. Nucleosil C18 analytical column was used as stationary phase, while mobile phase consisted of acetonitrile:phosphate buffer: methanol (40/40/20, v/v) pH 2.0. Effluent was monitored at a flow rate 1 mL/min and detected at wavelength of 240 nm. This research produced excellent chromatography over a wide concentration range of 25‑10000 ng/mL. Sepprated and well resolved quantifiable peaks were obtained and test results were linear in this range. Correlation coefficient of more than 0.9990 was witnessed as well as Low %RSD values i.e., maximum 2.0% documented excellent precision of the method. Good recoveries from pharmaecutical (99-101%), urine and plasma samples (>96%) in a range of concentrtion granted very good linearity, accuracy and precision. The projected method has satisfactory applications in quality control of these molecules as well as quantification of these molecules in urine and plasma samples.

IntroductionAn adequate level of health literacy is regarded as a prerequisite for adequate medication self-management. Low health literacy skills are relatively more common in people with Diabetes Mellitus type 2. The aim of this study was to explore the needs regarding medication self-management of people with type 2 diabetes and low (functional, communicative and critical) health literacy, and their preferences for medication self-management support.Materials and methodsA two-stage qualitative needs assessment study was performed using in-depth individual interviews and focus groups.ResultsThe participants preferred to be supported with reliable and easily understandable information, adequate interactive communication with health care professionals and fellow people with diabetes and tools for medication self-management support.DiscussionFuture interventions should be created in co-creation with people with low health literacy and fulfill the expressed needs on information, communication and tools to improve self-management.

Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p=0.002), had a higher Short Blessed Test (SBT; p=0.022) and a lower Barthel Index (p=0.047). Polypharmacy (p=0.001), heart failure (p=0.005) and diabetes (p=0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p=0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.00, p=0.037], diabetes (OR 0.48, 95% CI 0.26–0.87, p=0.016) and polypharmacy (OR 0.58, 95% CI 0.34–0.99, p=0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p=0.89; and 15.9 vs. 14.1%, p=0.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.

This study aimed to assess the prevalence, the change, and the determinants of change in polypharmacy in a population-based sample. Baseline (2003–2006) and follow-up (2009–2012) data are from 4679 participants aged between 35 and 75 years (53.5% women, mean age 52.6 ± 10.6 years) from the population of Lausanne, Switzerland. Polypharmacy was defined by the regular use of ≥5 drugs. Four categories of change were defined: never (no polypharmacy at baseline and follow-up), initiating (no polypharmacy at baseline but at follow-up), maintaining, or quitting. Polypharmacy increased from 7.7% at baseline to 15.3% at follow-up. Cardiovascular drugs were the most prescribed medicines at baseline and follow-up. Gender, age, obesity, smoking, previously diagnosed hypertension, or diabetes or dyslipidemia were significantly and independently associated with initiating and maintaining polypharmacy. In a population-based sample, prevalence of polypharmacy doubled over a 5.6-year period. The main determinants of initiating polypharmacy were age, overweight and obesity, smoking status, and previously diagnosed cardiovascular risk factors.

BACKGROUND: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified.OBJECTIVE: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes.DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS):POPULATION: diabetes patients.EXPOSURE: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs.OUTCOME: Any incident cancer.STUDY DESIGN: Cohort and case-control studies.RESULTS: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer.LIMITATIONS: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders.CONCLUSIONS: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se.OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines.DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer".STUDY ELIGIBILITY CRITERIA: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included.RESULTS: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment).LIMITATIONS: Publication bias seemed to be present. Only published data were used in the analyses.CONCLUSIONS: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.

Background There are a lack of data regarding the effect of basal insulin analogues on rates of events like congenital malformation and perinatal mortality in diabetic pregnancy. Methods The present study is a prospective, non-interventional, multicentre cohort study conducted in seven countries, designed to assess the safety of insulin detemir during pregnancy, and to monitor the health status of resulting infants (exposed in utero) up to 1 year of age. The study population includes women with type 1 or type 2 diabetes, who are pregnant and being treated with insulin. Data will be collected in the context of routine practice. The primary endpoint is the proportion of pregnancies in women treated with insulin detemir, compared with other basal insulin regimens, which do not result in any of the following events: major congenital malformations, perinatal death or neonatal death. A sample size of 3075 pregnancies was calculated to provide an 80% power to detect a difference of 3.5% between groups in the primary endpoint at a 5% level. Discussion The study will also examine other important maternal endpoints (e.g., incidences of severe hypoglycaemia and pre-eclampsia) and perinatal outcomes such as overweight neonates, as well as infant outcomes at 1 year of age. It has a fixed recruitment period from 2013 to 2018, enrolling all eligible patients, and is expected to inform future prescribing with basal insulins in diabetic pregnancy. Trial registration ClinicalTrials.gov: NCT01892319 (date registered: 27.06.2013). Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1177-4) contains supplementary material, which is available to authorized users.

Summary Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalarial drugs and that the mechanism of action of these molecules depends on the enhancement of GABAA receptor signaling. Our results in zebrafish, rodents, and primary human pancreatic islets identify gephyrin as a druggable target for the regeneration of pancreatic β cell mass from α cells., Graphical Abstract, Highlights • Artemisinins inhibit ARX function and impair α cell identity • Compounds act by stabilizing gephyrin, thus enhancing GABAA receptor signaling • Artemisinins increase β cell mass in zebrafish and rodent models • Functional and transcriptional data indicate a conserved phenotype in human islets, The anti-malarial drug Artemisinin can drive the in vivo conversion of pancreatic α cells into functional β-like cells through enhanced GABA signaling and may have potential as a therapeutic for diabetes.

BACKGROUND: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. METHODS: We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analyzed to compare the congenital anomaly rate among fetuses of mothers using insulin analogues with fetuses of mothers using human insulin. RESULTS: Of 29 studies we included 1286 fetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 fetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn; NPH). The congenital anomaly rate was 4.84% and 4.29% among the fetuses of mothers using lispro and aspart. For glargine and detemir the congenital anomaly rate was 2.86% and 3.47% respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among fetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared to those exposed to human insulin or NPH insulin. CONCLUSION: The total prevalence of congenital anomalies was not increased for fetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. This article is protected by copyright. All rights reserved.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.

Aims Polypharmacy is associated with adverse events and multimorbidity, but data are limited on its association with specific comorbidities in primary care settings. We measured the prevalence of polypharmacy and inappropriate prescribing, and assessed the association of polypharmacy with specific comorbidities. Methods We did a cross-sectional analysis of 1002 patients aged 50–80 years followed in Swiss university primary care settings. We defined polypharmacy as ≥ 5 long-term prescribed drugs and multimorbidity as ≥ 2 comorbidities. We used logistic mixed-effects regression to assess the association of polypharmacy with the number of comorbidities, multimorbidity, specific sets of comorbidities, potentially inappropriate prescribing (PIP) and potential prescribing omission (PPO). We used multilevel mixed-effects Poisson regression to assess the association of the number of drugs with the same parameters. Results Patients (mean age 63.5 years, 67.5% ≥ 2 comorbidities, 37.0% ≥ 5 drugs) had a mean of 3.9 (range 0–17) drugs. Age, BMI, multimorbidity, hypertension, diabetes mellitus, chronic kidney disease, and cardiovascular diseases were independently associated with polypharmacy. The association was particularly strong for hypertension (OR 8.49, 95%CI 5.25–13.73), multimorbidity (OR 6.14, 95%CI 4.16–9.08), and oldest age (75–80 years: OR 4.73, 95%CI 2.46–9.10 vs.50–54 years). The prevalence of PPO was 32.2% and PIP was more frequent among participants with polypharmacy (9.3% vs. 3.2%, p Conclusions Polypharmacy is common in university primary care settings, is strongly associated with hypertension, diabetes mellitus, chronic kidney disease and cardiovascular diseases, and increases potentially inappropriate prescribing. Multimorbid patients should be included in further trials for developing adapted guidelines and avoiding inappropriate prescribing.

BACKGROUND: Intensification of pharmacotherapy in persons with poorly controlled chronic conditions has been proposed as a clinically meaningful process measure of quality. OBJECTIVE: To validate measures of treatment intensification by evaluating their associations with subsequent control in hypertension, hyperlipidemia, and diabetes mellitus across 35 medical facility populations in Kaiser Permanente, Northern California. DESIGN: Hierarchical analyses of associations of improvements in facility-level treatment intensification rates from 2001 to 2003 with patient-level risk factor levels at the end of 2003. PATIENTS: Members (515,072 and 626,130; age >20 years) with hypertension, hyperlipidemia, and/or diabetes mellitus in 2001 and 2003, respectively. MEASUREMENTS: Treatment intensification for each risk factor defined as an increase in number of drug classes prescribed, of dosage for at least 1 drug, or switching to a drug from another class within 3 months of observed poor risk factor control. RESULTS: Facility-level improvements in treatment intensification rates between 2001 and 2003 were strongly associated with greater likelihood of being in control at the end of 2003 (P < or = 0.05 for each risk factor) after adjustment for patient- and facility-level covariates. Compared with facility rankings based solely on control, addition of percentages of poorly controlled patients who received treatment intensification changed 2003 rankings substantially: 14%, 51%, and 29% of the facilities changed ranks by 5 or more positions for hypertension, hyperlipidemia, and diabetes, respectively. CONCLUSIONS: Treatment intensification is tightly linked to improved control. Thus, it deserves consideration as a process measure for motivating quality improvement and possibly for measuring clinical performance.

48歳女.主訴は発熱, 左側腹部痛.重篤な糖尿病であり, CTでは左腎周囲の多量の気腫と膿瘍と思われる液体貯留を認めた.DIPにては左腎を取り囲む多量のガス像を認め, 左腸腰筋の輪郭が不明瞭であったが結石や尿路の通過障害は認めなかった.入院時より抗生剤(セフォゾプラン)及びγグロブリン投与を行い, 食事は1200kcal/日とし, インスリンを用いた糖尿病の治療を開始した.入院後5日間保存的治療にても, 39℃台の発熱が軽快しない為, 全身麻酔下に左肋骨弓下に約5cmの切開を行いドレナージを行った.ドレナージ約2ヵ月後のCTでは, 左腎周囲の膿瘍は殆ど認められなくなった, A 48-year-old woman was referred to our hospital with high fever and left flank pain. She was diagnosed with diabetes mellitus (DM), and abdominal computed tomography (CT) revealed left perinephric abscess with much emphysema. She underwent drainage of the abscess by left flank incision after treatment with antibiotics and insulin. The pus culture revealed Escherichia coli. Immediately after drainage, the symptoms began to subside. At three months after drainage, abdominal CT revealed no emphysema around the left kidney. At 18 months after the discharge, left perinephric abscess was not seen and DM was well controlled with insulin.

OBJECTIVE: This study was set out to determine whether metformin use influences survival in breast cancer patients treated with antidiabetic drugs as compared to non-users.RESEARCH DESIGN AND METHODS: We used data from the Danish national registries (1996-2008) to identify adult female patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Coxproportional hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions.RESULTS: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of death for 152 cases. Compared to non-use, current metformin treatment was associated with a significant reduction in overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer-specific mortality, a non-significant risk reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed in the first 12 months after discontinuation of metformin.CONCLUSIONS: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these findings is needed.

Most cardiovascular researchers are familiar with intermediate-conductance KCa3.1 and small-conductance KCa2.3 channels because of their contribution to endothelium-derived hyperpolarization. However, to immunologists and neuroscientists, these channels are primarily known for their role in lymphocyte activation and neuronal excitability. KCa3.1 is involved in the proliferation and migration of T cells, B cells, mast cells, macrophages, fibroblasts, and dedifferentiated vascular smooth muscle cells and is, therefore, being pursued as a potential target for use in asthma, immunosuppression, and fibroproliferative disorders. In contrast, the 3 KCa2 channels (KCa2.1, KCa2.2, and KCa2.3) contribute to the neuronal medium afterhyperpolarization and, depending on the type of neuron, are involved in determining firing rates and frequencies or in regulating bursting. KCa2 activators are accordingly being studied as potential therapeutics for ataxia and epilepsy, whereas KCa2 channel inhibitors like apamin have long been known to improve learning and memory in rodents. Given this background, we review the recent discoveries of novel KCa3.1 and KCa2.3 modulators and critically assess the potential of KCa activators for the treatment of diabetes and cardiovascular diseases by improving endothelium-derived hyperpolarizations.

Item does not contain fulltext Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2alpha. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death. 01 november 2011

Arteriosclerotic vascular disease is a major cardiac health problem in westernized countries and the primary cause of mortality in diabetic patients. Recent data have raised serious safety concerns with the antidiabetic rosiglitazone, a thiazolidinedione with peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonistic activity, in regard to cardiovascular risks. A common feature of atherosclerosis is vascular mineralization. The latter is formed by vascular smooth muscle cells (VSMC) through complex processes that are similar to mineralization in bone. The aim of the current study was to investigate the effect of rosiglitazone on mineralization in cultured human VSMCs. We found that rosiglitazone stimulated mineralization by, at least in part, induction of caspase-dependent apoptosis. Furthermore, rosiglitazone-induced oxidative stress was correlated with stimulated osteoblast-like differentiation of VSMCs. Treatment of rosiglitazone-supplemented VSMC cultures with the caloric restriction mimetic and antioxidant resveratrol diminished rosiglitazone-induced oxidative stress, osteoblast-like differentiation and mineralization. In conclusion, this study reveals novel insights into the relationship of rosiglitazone and cardiovascular events by providing a model that links rosiglitazone-induced osteoblast-like differentiation, oxidative stress and apoptosis with mineralization in VSMCs. In addition, we position resveratrol in this model acting to reduce rosiglitazone-induced oxidative stress, osteoblast-like VSMC differentiation and mineralization. (C) 2011 Elsevier Ltd. All rights reserved.

Hypoglycemia is a potentially serious complication of insulin therapy. Some insulin-dependent diabetic patients can benefit from continuous subcutaneous insulin infusion therapy (an "insulin pump"), which in most case improves glycemia control and decreases the occurrence of hypoglycemic episodes. However, such events may occur, particularly during initial treatment phases or pregnancy. Severe hypoglycemia is mainly managed by stopping the insulin pump and insuring an adequate carbohydrate intake. Patients with insulin pumps and their entourage should receive specific instruction in the adjustment of pump flow in the presence of dysglycemia-inducing circumstances (illness, physical exertion), as well as in anticipation of high-risk situations, such as motor-vehicle driving.

Insulin treatment is associated with two important and frequent side effects: hypoglycemia and weight gain. Weight gain is in contradiction with the physiological central effect of insulin which leads to decreased food intake like leptin. However, decreased urinary caloric loss due to better glycemic control, prevention and correction of hypoglycemia, the anabolic effect of insulin and the possible central resistance to insulin explain the observed weight gain. Insulin is often necessary when oral antidiabetic treatment fails; the physician and the patient need to remain alert to minimize the side effects through adequate insulin regimen and life style.

Several insulin analogues have been developed in recent years and are increasingly being used in the treatment of diabetes. However, modifying the insulin molecule not only changes its metabolic effects, but can also alter its mitogenic potency. In vitro experiments had previously suggested a potential association between insulin analogues and cancer. In 2009 several articles were published in Diabetologia describing an association between administration of glargine (Lantus) and higher incidence of cancer rates. The present article aims at briefly presenting the state of the art based upon currently available data on insulin and cancer. We will summarize the mechanisms by which insulin can increase cell proliferation, the observations reported in recent publications and finally conclude with some practical recommendations.

BACKGROUND/AIM: Despite combined therapy consisting of surgery, external X-ray, and medical therapy, a significant number of acromegaly patients continue to have uncontrolled growth hormone (GH) secretion and active disease. These patients, particularly those with large or invasive tumors, require additional therapy to decrease their GH levels. Our aim was to investigate whether patients with documented GH-secreting pituitary adenomas leading to acromegaly would respond with attenuation of GH and insulin-like growth factor-1 (IGF-1) levels after treatment with a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. METHODS: We conducted prospective analyses in the Endocrinology Clinic of the Pamukkale University. Acromegaly patients who had active disease participated in two admissions: before and after 6 weeks of daily treatment with 8 mg of oral rosiglitazone. Four male and 3 female patients have completed the study. Basal and nadir GH levels during an oral glucose tolerance test were determined, and the IGF-1 and IGF-binding protein-3 levels were also measured both before and 6 weeks after the rosiglitazone treatment. RESULTS: Treatment with rosigitazone did not reduce basal and nadir GH levels during the oral glucose tolerance test and the IGF-1 levels in the patient population as a whole (p > 0.05). CONCLUSIONS: The PPAR-gamma activator rosiglitazone, used at maximum approved dosage, did not reduce plasma GH and IGF-1 levels in patients with acromegaly. Further studies with higher doses and longer duration of PPAR-gamma agonist administration would be required to determine its usefulness in the treatment in this group of patients.

A 48-year-old woman was referred to our hospital with high fever and left flank pain. She was diagnosed with diabetes mellitus (DM), and abdominal computed tomography (CT) revealed left perinephric abscess with much emphysema. She underwent drainage of the abscess by left flank incision after treatment with antibiotics and insulin. The pus culture revealed Escherichia coli. Immediately after drainage, the symptoms began to subside. At three months after drainage, abdominal CT revealed no emphysema around the left kidney. At 18 months after the discharge, left perinephric abscess was not seen and DM was well controlled with insulin.

To evaluate the data quality in the Danish National Registry of Patients (DNRP) and the Prescription Registry in the country of Northern Jutland (487,000 inhabitants) concerning insulin dependent diabetes mellitus (IDDM) and insulin treated diabetes mellitus, a comparison between data in the two registries was made. From the Regional Hospital Registry in the County of Northern Jutland, containing discharge diagnoses from all admissions to hospitals in the county, we identified all patients with the IDDM diagnosis between 1987 and 1993. From the Regional Prescription Registry all insulin prescriptions taken up at pharmacies in the county in 1993 were identified. All persons were identified by their individual identification number (CPR-number), and a record linkage between the two data sources was made. The predictive value of an IDDM-registration in the DNRP was 96% and the corresponding completeness 91%. In the Prescription Registry the completeness was 96%. Both registries seem to be valuable study bases for epidemiological research in diabetes mellitus.

Background Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. Methods data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. Results self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Conclusion in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.

The drug use in 228 persons with diabetes was studied and compared with that of sex- and age-matched non-diabetic controls--all of whom were found by the screening of a well-defined Danish population aged 60-74 years. Ninety per cent of the diabetics had non-insulin-dependent diabetes mellitus (NIDDM), as evaluated by a glucagon-C-peptide test. Information on daily use of prescribed and non-prescribed drugs was obtained by questionnaires and interviews. More than 80% of the diabetics used drugs daily, compared to 55% of control subjects (P less than 0.00001). Among subjects using drugs diabetics, on average, used 70% more defined daily doses (DDD) than controls, even when antidiabetics were excluded. There was no difference in the number of drug users among subgroups of diabetics when divided according to antidiabetic treatment but tablet-treated diabetics, on average, used 20% fewer DDD than other diabetics. Cardiovascular drugs were the most commonly used drugs. Diabetics in all antidiabetic treatment groups used significantly more cardiovascular drugs than non-diabetics. Diabetics treated with oral antidiabetics used fewer cardiovascular drugs than insulin- and diet-treated diabetics. The estimated cost of drug therapy was more than 2.5 times higher for diabetics than for the control group. Our results reflect the increased morbidity among elderly diabetics and emphasise, together with other aspects of costs of diabetes in the elderly, the need for allocating resources for the prevention of NIDDM instead of the treatment of its complications.

Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk.

BACKGROUND: As many challenges exist for access to diabetes care in developing countries, the International Insulin Foundation developed a Rapid Assessment tool and implemented this approach to identify barriers to care and propose concrete recommendations for decision makers. The objective of this paper is to identify the factors that contributed to informing and influencing policymakers with regards to this work. METHODS: A documentary review comprised Stage 1. Stage 2 used an online questionnaire to gain insight from users of the Rapid Assessment results. Based on Stages 1 and 2, Stage 3 comprised in-depth interviews with a total of nine individuals (one individual each from the six participating countries; two individuals from the World Health Organization; one "Global Diabetes Advocate"). Interviews were analyzed based on a list of themes developed from Stage 2. RESULTS: Stage 1 led to the identification of various types of documents referring to the results. The online questionnaire had a response rate of 33%. Respondents directly involved in the assessment had a "Good" or "Very Good" appreciation of most aspects and scored these higher than those not directly involved. From the interviews, formalized methods and close collaboration between the international team and local partners were strengths. Trust and a relationship with local partners were also seen as assets. All stakeholders valued the results and the credibility of the data generated. Local partners felt that more could have been done for dissemination. CONCLUSION: This study shows the importance of specific results from the different assessments. In addressing complex issues having external experts involved was seen as an advantage. The uptake of results was due to the credibility of the research which was influenced by a mix of the people involved, past assessments, trusted local partners, and the use of the results by knowledge brokers, such as the World Health Organization. Through these brokers, others gained ownership of the data. The methods used and the fact that this data was grounded in a local context also reinforced its value. Despite limitations, this study offers a unique perspective where a similar research approach was taken in six countries.

INTRODUCTION: Pancreatogenic diabetes develops in patients undergoing total pancreatectomy and complicates post-surgical management. The aim of this study was to compare parenteral nutrition (PN) with protocolled insulin treatment to intravenous glucose treatment after total pancreatectomy.METHODS: This was a retrospective study of 97 patients undergoing total pancreatectomy between 2009 and 2014. Patients were divided into a PN cohort (n = 57) and a glucose cohort (n = 40). The PN cohort was given PN with one international unit (IU) rapid-acting insulin per 10 g of carbohydrate. The glucose cohort was given a continuous 5% glucose infusion with 2 IU rapid-acting insulin per 10 g of carbohydrate. Both cohorts were given insulin detemir 0.2 IU/kg/day.RESULTS: Within the first 13 post-operative days, plasma glucose values were within the target range (4.0-10.0 mmol/l) in the PN cohort more frequently than in the glucose cohort (46% versus 42%, p = 0.01) without any increase in hypoglycaemia. Non-infectious complications occurred less frequently in the parenteral cohort than in the glucose cohort (23% versus 43%, p = 0.04). Infectious complications occurred in 19% versus 33% of patients, respectively (p = 0.14). The mean length of hospitalisation was 19.8 ± 12.7 versus 25.0 ± 21.5 days, p = 0.14.CONCLUSIONS: After total pancreatectomy, PN with insulin treatment per protocol improves glycaemic control compared with glucose infusion and reduces the number of non-infectious post-operative complications without increasing hypoglycaemia.FUNDING: none.TRIAL REGISTRATION: not relevant.

Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.