Quality of life, patient satisfaction, and cardiovascular outcomes of the randomised 2 x 3 factorial Copenhagen insulin and Metformin therapy (CIMT) trial - A detailed statistical analysis plan.

Background: The evidence on the effects of metformin and insulin in type 2 diabetes patients on quality of life, patient satisfaction, and cardiovascular outcomes is unclear. Methods: The Copenhagen Insulin and Metformin Therapy (CIMT) trial is an investigator-initiated multicentre, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark. Participants with type 2 diabetes were randomised to metformin (n = 206) versus placebo (n = 206); in combination with open-label biphasic insulin aspart one to three times daily (n = 137) versus insulin aspart three times daily in combination with insulin detemir once daily (n = 138) versus insulin detemir once daily (n = 137).We present a detailed description of the methodology and statistical analysis of the clinical CIMT outcomes including a detailed description of tests of the assumptions behind the statistical analyses. The outcomes are quality of life (Short Form Health Survey (SF-36)), Diabetes Medication Satisfaction Questionnaire, and Insulin Treatment Satisfaction Questionnaire (assessed at entry and 18 months after randomisation) and cardiovascular outcomes including time to a composite of either myocardial infarction, stroke, peripheral amputation, coronary revascularisation, peripheral revascularisation, or death. Discussions: This statistical analysis plan ensure the highest possible quality of the subsequent post-hoc analyses. Trial registration: The protocol was approved by the Regional Committee on Biomedical Research Ethics (H-D-2007-112), the Danish Medicines Agency (EudraCT: 2007-006665-33 CIMT), and registered within ClinicalTrials.gov (NCT00657943, 8th of April 2008).

Real life evaluation of sodium-glucose cotransporter 2 inhibition in type 1 diabetes and the risk of diabetic ketoacidosis.

BACKGROUND: The indication for treatment of type 1 diabetes(T1D) with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark. METHODS: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics. Electronic health records made the search for DKA accurate. RESULTS: From a population of 10.500 we observed 134 people treated with SGLT2i over a total period of 222 patient-years. Of those 72% were female, mean age (SD) was 51.4 (13.6) years and median duration of treatment (median, IQR) with an SGLT2i were 12.0 (6.0-29.0) months. The incidence of DKA was zero%. CONCLUSION: In 134 people with T1D treated with SGLT2i we found that none of the participants developed DKA during the treatment.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Explanatory Factors for Disease-Specific Health-Related Quality of Life in Women with Anorexia Nervosa.

A better understanding of explanatory factors for disease-specific health-related quality of life (HRQoL) in anorexia nervosa (AN) could help direct treatment providers to aspects of the most relevance for patient wellbeing and recovery. We aimed to investigate whether factors associated with HRQoL are the same for women with AN and normal-weight controls. The participants in this study were women with AN recruited from specialized eating disorder centers in Denmark and healthy, normal-weight controls invited via online social media. Participants completed online questionnaires on medical history, disease-specific HRQoL (Eating Disorders Quality of Life Scale, EDQLS) and generic HRQoL (SF-36), eating disorder symptomatology, depression, psychological wellbeing, and work and social adjustment. Questionnaires were fully completed by 211 women with AN (median age 21.7 years) and 199 controls (median age 23.9 years). Women with AN had poorer scores on all measures, i.e., worse HRQoL, psychological health, and work/social functioning. Eating disorder symptomatology affected EDQLS score in both groups, but poorer HRQoL in women with AN was also significantly associated with worse scores on bulimia, maturity fears, depression, vitality, and with older age. The factors investigated together explained 79% of the variance in EDQLS score. Management of disordered self-assessment and thought processes may be of particular importance to women with AN. Greater emphasis on these aspects alongside weight gain could enhance patient-clinician alliance and contribute to better treatment outcomes.

Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment.

BACKGROUND: Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services-related studies are lacking. The present study was a descriptive exploration of time-trends in treatment modes of patients with free and equal access to health services. METHODS: The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994-2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered. RESULTS: The cohort of patients with AN with at least 5 years of follow-up amounted to N = 7,505. A clear trend was observed in the per patient five-year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five-year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits. CONCLUSIONS: The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.

High depletion of breast cancer cells from the peripheral blood with the method of non-specific separation.

Circulating epithelial tumour cells (CETCs) play an important role in the formation of metastases in breast cancer patients. The depletion of such CETCs from peripheral blood of breast cancer patients using non-specific separation (without antibodies) of tumour cells from normal blood leucocytes might contribute to reduce the load of the patient's blood with tumour cells and subsequently reduce the probability of metastasis formation. This method is based on cell type-specific interaction of living cells with Carboxymethyl Dextrane (CMD) coated magnetic nanoparticles. We have developed a mild flow separation method using CMD-coated magnetic nanoparticles (core size ca. 25 nm) along with a low-field gradient magnetic separator and an external separation column (blood bag). The ability of tumour cells to preferentially bind such particles and to separate tumour cells from the white blood cells from blood samples of 25 breast cancer patients (fresh and 24-hour stored blood samples) were tested. The circulating tumour cells were quantified before and after separation by maintrac analysis. We achieved a very high depletion rate of tumour cells to < 3% remaining in the investigated 24 hours stored blood samples and ≤14% in all fresh blood samples concurrent with maintaining 56% ± 4% of vital leukocytes in all fresh blood samples.

Experience of family function, family involvement, and self-management in adult patients with type 2 diabetes: A thematic analysis.

AIM: To describe the patient's experience of family function and its importance in diabetes-related self-management. BACKGROUND: Many patients fail to reach the targeted glycemic level due to low self-management adherence. Knowledge is needed regarding the impact of family function on diabetes self-management. DESIGN: A qualitative descriptive design. METHODS: A purposive sample of 20 patients with type 2 diabetes. Data were collected in March-June 2017 via audio-recorded semi-structured interviews, field notes and Eco-maps. Analysed using thematic framework matrix and thematic analysis. RESULTS: Four themes were identified: (1) Downplaying disease. The disease was trivialized creating a barrier to family involvement; (2) Second guessing. When diabetes was not discussed, patient and family made their own assumptions; (3) Going it alone. The participants preferred sole disease responsibility to maintain usual family life; (4) No regrets. The participants managed their disease with medications only to maintain family cohesion and 'the good life'. CONCLUSION: The participants in our study downplayed the consequences of type 2 diabetes and chose to control their disease medically rather than by lifestyle changes. They renounced family involvement to maintain their lifestyle and promote family cohesion. IMPACT: During clinical check-ups, patients should be encouraged to involve their family in lifestyle changes. Healthcare professionals need to recognize illness- and treatment beliefs and the impact of family function in disease management.

[Autonomy and Participation As Common Goals of Nursing, Therapy and Social Medicine: Proposal for an Organizational Configuration Model on the Basis of Service Blueprinting]. / Selbstbestimmung und Teilhabe als gemeinsame Ziele von Pflege, Therapie und Sozialmedizin: Entwurf eines Organisationsmodells auf Basis einer Kontaktpunktanalyse.

BACKGROUND: Every person who is in the need of long-term care (according to German Social Code SGB XI §14) fulfills the requirements of disability according to German Social Code SGB IX, § 2. The right of participation and autonomy must be specially protected and realized for persons with long-term care needs because these persons have a limited capacity to advance their interests. The rights of people in the need of long-term care or assistance are protected not only by the national constitution but also by the UN Disability Rights Convention. Participation is an important principle of these extra-statutory regulations and has an extraordinary significance and individual meaning for quality of life. For concretizing the aim of participation and for realizing participation in daily practice, the following question arises: How must organizations be configured to achieve individual aims of participation for persons with long-term care need, complex health care needs and with potential for rehabilitation across sectoral, disciplinary and professional borders? This analysis focuses on people older than 70 years with geriatric-relevant multimorbidity and with potential for rehabilitation. AIM: The aim of this study was to create a configuration model for the organization of interdisciplinary cooperation in rehabilitation out of a case study and on the basis of the service blueprinting method [1]. In a next step this configuration model can be evaluated concerning its effectiveness for achieving individual participation goals and quality of life of persons with long-term care need and with potential for rehabilitation. METHOD: For creating the configuration model, the service blueprinting method [1] on the basis of Dervin's sense making theory [11] was applied to a case vignette of geriatric rehabilitation against a background of organization theories and nursing science concepts. With the case study the configuration model can be applied exemplarily at the setting of restorative care, therapy and rehabilitation. With the service blueprinting method, the rehabilitation process is aligned onto the geriatric patient's individual health care needs, perceptions of participation and quality of life. RESULTS: As a result of the sequencing and service blueprinting process we offer a dynamic model for the coordination of responsibility of interdisciplinary rehabilitation teams with a user-centered alignment. Its effectiveness (and side-effects) for interdisciplinary cooperation and for patient's individual goals of participation and quality of life must be evaluated in further studies. A mixed-method design should be used to evaluate objective outcome parameters such as dependency on nursing care, hospital admission rates and subjective outcome parameters such as patient's perception of participation, autonomy and quality of life. IMPLICATIONS FOR HEALTHCARE PRACTICE: The configuration model can be used for evaluating already implemented geriatric rehabilitation processes and organizations. The configuration model can be used in health care research or organizational research. After more evidence for desirable effects, it can be implemented into the health care system. Side effects should be monitored.This paper was written in cooperation with the working group "Nursing", department "Practical Social Medicine and Rehabilitation" of the German Society of Social Medicine and Prevention (Deutsche Gesellschaft für Sozialmedizin und Prävention DGSMP e.V.).

Clinical potential of treatment with semaglutide in type 2 diabetes patients.

Glucagon-like receptor agonists (GLP-1RAs) are included in current national and international guidelines as second-line treatment especially in patients with type 2 diabetes and concomitant cardiovascular disease (CVD). First-generation GLP-1RAs were two- or once-daily injectables, but longer-acting GLP-1RAs have now been developed for once-weekly administration - e.g., exenatide ER, dulaglutide and semaglutide. With semaglutide, the same prolongation principle as designed in liraglutide is used (spacer and fatty acid chain). However, the similarity to endogenous human GLP-1 is well preserved, sharing 94% homology. It is administered with a simple device and without resuspension before use. The efficacy and safety of semaglutide have been investigated in an extensive clinical development program including more than 9,000 patients with type 2 diabetes. Semaglutide has been compared head-to-head with a dipeptidyl peptidase-4 (DPP4)-inhibitor, GLP-1RAs and basal insulin. Further head-to-head studies are awaiting that compare semaglutide against a sodium-dependent-glucose transporter-2 (SGLT2)-inhibitor. In these studies, semaglutide was found to provide significant and clinically relevant reductions in HbA1c, fasting plasma glucose (FPG), glucose excursions, body weight and blood pressure. The reduction in glycaemic parameters was more pronounced than that in the comparator GLP-1RAs. The rate of hypoglycemia is very low during treatment with semaglutide if not combined with sulphonylureas or insulin. A cardiovascular outcome trial (CVOT) was performed before the approval of semaglutide, at the request of legal authorities. Not only non-inferiority was confirmed, but also superiority compared with placebo used in a population of patients with type 2 diabetes and CVD treated with oral antihyperglycaemic drugs (OADs) and/or insulin with regard to the primary composite endpoint: death from cardiovascular (CV) causes, nonfatal myocardial infarction or nonfatal stroke. The safety of treatment with semaglutide in patients with type 2 diabetes has been extensively investigated. Overall, gastrointestinal side effects dominate, as observed with other GLP-1RAs, and was observed in the same range as for comparator GLP-1RAs. As observed with other GLP-1RAs, side effects such as nausea and vomiting diminished over time during continuous treatment. Regarding microvascular complications, an unexpected increase in diabetes-related retinopathy was observed in the CVOT; Semaglutide Unabated Sustainability in Treatment of Type 2 diabetes' [SUSTAIN 6]), but not in other studies. The reason for this increase is not finally elucidated, but may be due to a nonspecific effect of a rapid decrease in glycaemic parameters in patients with preexisting retinopathy with high HbA1c at the start of the treatment. There is currently a warning in the Summary of Product Characteristics (SmPC) for semaglutide concerning treatment in patients with preexisting retinopathy. Further studies are needed to clarify this.

Differences in the Level of Electronic Health Literacy Between Users and Nonusers of Digital Health Services: An Exploratory Survey of a Group of Medical Outpatients.

BACKGROUND: Digitalization of health services ensures greater availability of services and improved contact to health professionals. To ensure high user adoption rates, we need to understand the indicators of use and nonuse. Traditionally, these have included classic sociodemographic variables such as age, sex, and educational level. Electronic health literacy (eHL) describes knowledge, skills, and experiences in the interaction with digital health services and technology. With our recent introduction of 2 new multidimensional instruments to measure eHL, the eHL questionnaire (eHLQ) and the eHL assessment (eHLA) toolkit, eHL provides a multifaceted approach to understand use and nonuse of digital health solutions in detail. OBJECTIVE: The aim of this study was to investigate how users and nonusers of digital services differ with respect to eHL, in a group of patients with regular contact to a hospital outpatient clinic. Furthermore, to examine how usage and nonusage, and eHL levels are associated with factors such as age, sex, educational level, and self-rated health. METHODS: Outpatients were asked to fill out a survey comprising items about usage of digital services, including digital contact to general practitioner (GP) and communication via the national health portal sundhed.dk, the eHLQ, and the eHLA toolkit, as well as items on age, sex, education, and self-rated health. In total, 246 patients completed the survey. A Mann-Whitney test was used to test for differences between users and nonusers of digital services. Correlation tests described correlations between eHL scales (eHEALSs) and age, education, and self-rated health. A significance level of .0071 was used to reject the null hypothesis in relation to the eHEALSs and usage of digital services. RESULTS: In total, 95.1% (234/246) of the participants used their personal digital ID (NemID), 57.7% (142/246) were in contact with their GPs electronically, and 54.0% (133/246) had used the national health portal (sundhed.dk) within the last 3 months. There were no differences between users and nonusers of sundhed.dk with respect to age, sex, educational level, and self-rated health. Users of NemID scored higher than nonusers in 6 of the 7 dimensions of eHLQ, the only one which did not differ was dimension 2: Understanding of health concepts and language. Sundhed.dk users had a higher score in all of the 7 dimensions except for dimension 4: Feel safe and in control. The eHLA toolkit showed that users of sundhed.dk and NemID had higher levels of eHL with regard to tools 2, 5, 6, and 7. Furthermore, users of sundhed.dk had higher levels of eHL with regard to tools 3 and 4. CONCLUSIONS: Information about patients' eHL may provide clinicians an understanding of patients' reasons for not using digital health services, better than sociodemographic data or self-rated health.

Patient Assessment of Family Function, Glycemic Control and Quality of Life in Adult Patients With Type 2 Diabetes and Incipient Complications.

OBJECTIVES: Family affects the perception of diabetes self-management in patients with diabetes. Family-related questionnaires have been used to assess family function, but the Brief Family Assessment Measure (Brief FAM-III) has not been used previously in a diabetes population. We aimed to determine whether the family function is associated with glycated hemoglobin levels and quality of life as potential predictors of diabetes self-management. METHODS: An exploratory study of patients with type 2 diabetes and incipient complications and their relatives using the Brief FAM-III, a self-report questionnaire comprising 3 scales assessing family function according to different perspectives: a general score, a dyadic relationship score and a self-rating score. RESULTS: We included 127 patients: 72.4% males, mean age 65.23 (SD=10.26) years; glycated hemoglobin levels, 6.9% (SD=0.9%); diabetes duration, 9.1 (SD=0.6) years; and body mass index, 30.8 (SD=0.5) kg/m2. Mean FAM-III scores for the 3 scales were 41.7 (SD=1.0), 41.5 (SD=0.9) and 38.5 (SD=1.1), respectively. Correlation coefficients were -0.06 (p=0.37), -0.09 (p=0.18) and -0.12 (p=0.06), showing no significant correlation between scales and glycated hemoglobin levels levels in the 3 perspectives before and after adjustment for confounders. Family function correlated with burden of diabetes at 0.14 (p=0.02), 0.24 (p=0.0003) and 0.16 (p=0.01), respectively, and mental health at -0.21 (p=0.0007), -0.23 (p=0.0005) and -0.25 (p<0.0001), respectively. CONCLUSION: The results of our study suggest that in patients with type 2 diabetes, family function does not predict the level of glycemic control. However, we found an association among healthy family function, low burden of diabetes and strong mental health, issues that are important for the patients' quality of life, compliance with lifestyle factors and diabetes self-management.

[Cholesterol-lowering treatment with PCSK9-inhibitors].

Monoclonal antibodies inhibiting proprotein convertase subtilisin-kexin type 9 constitute a new class of lipid-lowering drugs. Currently, evolocumab and alirocumab are marketed. A recent cardiovascular outcome study with evolocumab has shown a cardiovascular (CV) event reduction of 15% in high-risk individuals at very low levels of low-density lipoproteins. The adverse event profile up to two years is mild. Treatment is very costly, and data on CV endpoints are still limited. Treatment is restricted to patients at very high risk of getting CV diseases and on a maximal tolerated statin and ezetimibe treatment in addition to dietary intervention.

[Combination therapy of thyroxine and triiodothyronine in hypothyroid patients].

Decreased quality of life is described more often in hypothyroid patients, who are treated with a synthetic form of thyroxine (L-T4), than in euthyroid controls. A combination of L-T4 and a synthetic form of triiodothyronine (L-T3) has been suggested; however, previous meta-analyses on unselected patients did not find any effect. Recent studies demonstrate, that the overall hypothalamic-pituitary-thyroid-tissue homeostasis could be more complex than previously suggested. Polymorphisms in deiodinase and thyroid hormone transporter genes could theoretically explain, why a minor subgroup of hypothyroid patients seem to have an effect of L-T4/L-T3 combination therapy.

[Cross-sectoral collaboration in type 2 diabetes management in Denmark].

To optimize medical care, Danish guidelines for type 2 diabetes emphasize cross-sectoral collaboration. Risk stratification is recommended as a model of organizing care in terms of distributing tasks and responsibilities between primary and secondary healthcare sectors. Collaboration between the sectors is expected to be beneficial for patients and ensure rational utilization of resources. Challenges such as inter-sectoral communication, sharing of data and unambiguous responsibility underline the need for continuous optimization of the organization of cross-sectorial diabetes management.

Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential.

Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed.

[Social Medicine and Interfaces in Sectoral Health Care Provision]. / Sozialmedizin und Schnittstellen in der sektoralen Versorgung.

In addition to the consideration of individual medicine, social medicine focuses on the social references of health and sickness. In this context, it reflects the structures of the entire health care system, its functions and its functional deficits. It deals with the specific interaction between medicine and society and functions such as a link to the classical social sciences (1). Of particular interest in this context are the interfaces to sectoral health care provision. The working group "Nursing Care" of the Department "Practical Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention examines the fundamental interfaces in our sectoral health care system from the perspective of social medicine in their current functions and perspectives, particularly in view of the future demographic challenges to be faced. Of particular importance is the interface between medicinal and nursing care in the areas of acute inpatient and homecare as well as in the area of geriatric care, including preventive measures. The aim of this article is to start a discussion on this subject.

Supportive and non-supportive interactions in families with a type 2 diabetes patient: an integrative review.

BACKGROUND: Type 2 diabetes and its management affect the patient and the close family potentially causing either psychological distress or increased sense of responsibility and collaboration in these families. Interactions between patient and family play an important role in maintaining lifestyle changes and diabetes self-management. The purpose of this integrative review was to summarise and assess published studies on the intra-family perspective of supportive and non-supportive interactions in families with a type 2 diabetes patient. METHODS: Included in the review were published qualitative and quantitative studies that examined the intra-family perspective on supportive and non-supportive interactions. We searched the literature from 2000 to 2016 and the search strategy comprised the following databases: Cochrane, PubMed, CINAHL, Web of Science, PsycINFO and Psyc-ARTICLES as well as hand searching of reference lists. Quality assessment, data extraction and analysis were undertaken on all included studies. RESULTS: We identified five eligible research papers. Employing content analysis three categories describing interactions were refined: Impact of practical action, impact of emotional involvement, and impact of communication content. Supportive interactions included encouraging communication and family collaboration in managing diet, medications, and blood glucose checking. Non-supportive interactions were visible irritation, nagging behaviour and refusing to share the burden of living with diabetes. CONCLUSION: The findings stress the importance of including both patient and family in clinical practice to target diabetes self-management adherence and well-being of the whole family. The majority of self-management occurs within the family environment. Therefore, the intra-family perspective of supportive and non-supportive interactions should be understood and addressed as the family members are interdependent and affected by each other. Future research assessing the impact of professional support and the family function will have the potential to improve the daily life and well-being of patients with type 2 diabetes as well as the whole family.

Hyperproinsulinemia in obesity and in type 2 diabetes and its relation to cardiovascular disease.

INTRODUCTION: Disproportionately elevated fasting levels of proinsulin immunoreactive material (PIM)relative to insulin immunoreactivity (IRI) are a well-established abnormality in type 2 diabetes. Thesignificance of this abnormality has been investigated and discussed in several studies. Areas covered: The present review focuses on the role of proinsulin and its conversion intermediates inthe development of type 2 diabetes, obesity and insulin resistance, and the potential role as a marker ofcardiovascular risk, including the most important studies in this field. Expert commentary: The composition of plasma PIM is heterogeneous comprising des(31,32)-proinsulin,intact proinsulin and small amounts of des(64,65)-proinsulin. Disproportionate hyperproinsulinemiaseems to occur early in the development and before the diagnosis of type 2 diabetes, and seemsassociated to disease progression. Obesity and insulin resistance does not influence fasting PIM/IRI levels in type 2 diabetes. Fasting PIM/IRI levels in type 2 diabetes are closely associated with the degree of impairment in insulin secretory capacity. Different type 2 diabetes alleles have been described associated with elevated PIM/IRI levels. Recent data suggests that proinsulin and its conversion intermediates may have a role as markers of increased risk of cardiovascular disease in glucose intolerance and type 2 diabetes.

[Sodium-glucose cotransporter 2 (SGLT-2) inhibitors for patients with Type 2 diabetes].

The sodium-glucose cotransporter 2 inhibitor (SGLT-2i)-class is efficacious as monotherapy and as add-on therapy with an expected lowering of the glycated haemoglobin (HbA1c) concentration of approximately 7 mmol/mol. Side effects relate to the mode of action, genital infections are the main problem. Extremely rare cases of ketoacidosis are reported, mostly in patients with Type 1 diabetes. One SGLT-2i, empagliflozin, has been shown to reduce cardiovascular mortality and progression of kidney disease in patients with Type 2 diabetes and cardiovascular disease. Outcome trials for other SGLT-2i are pending. SGLT-2i are now in guidelines as a possible second-line therapy or in case of metformin intolerance.