Shared Decision Making, Diagnostic Evaluation, and Pharmacotherapy in Type 2 Diabetes.

BACKGROUND: Type 2 diabetes is one of the most important widespread diseases worldwide. In Germany, nearly one in five persons over age 65 has type 2 diabetes. The German National Disease Management Guideline for Type 2 Diabetes (NDMG; in German: Nationale Versorgungsleitlinie, NVL) contains updated recommendations for the diagnostic evaluation and pharmacotherapy of this disease as well as information about specific groups of people for whom early detection may be useful. METHODS: The guideline has been updated, chapter by chapter, since 2018. Its recommendations are based on systematically searched and evaluated scientific evidence, the clinical expertise of a multidisciplinary panel of experts, and patient perspectives. RESULTS: The new chapter on shared decision making includes a description of a structured approach that can be used when individual treatment goals have not been achieved. The diagnosis of diabetes newly requires at least two abnormally elevated laboratory values: e.g., fasting plasma glucose ≥ 126 mg/dL (≥ 7.0 mmol/L), HbA1c ≥ 6.5 % (≥ 48 mmol/mol) and/or casual plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L). Cardiovascular and renal risks are to be considered in the choice of drug. Studies have shown that, in persons with cardiovascular disease, treatment with GLP-1 receptor agonists (GLP-1, glucagon-like peptide-1) or SGLT2 inhibitors (SGLT2, sodium-glucose co-transporter-2) was less likely than the comparison intervention to lead to certain patient-relevant endpoints, including all-cause mortality (OR = 0.88 and 0.84, respectively), hospitalization for heart failure (SGLT2 inhibitors: OR = 0.65), and worsening of renal function (OR = 0.61 and 0.59, respectively). CONCLUSION: Current evidence continues to support the recommendations on pharmacotherapy of the 2021 guideline. The Guideline Group did not find evidence of adequate certainty to inform recommendations about the screening of persons at risk, HbA1c target values, or screening for sequelae and comorbidities. Better evidence on these matters would be desirable.

The Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Empagliflozin Reverses Hyperglycemia-Induced Monocyte and Endothelial Dysfunction Primarily through Glucose Transport-Independent but Redox-Dependent Mechanisms.

PURPOSE: Hyperglycaemia-induced oxidative stress and inflammation contribute to vascular cell dysfunction and subsequent cardiovascular events in T2DM. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin significantly improves cardiovascular mortality in T2DM patients (EMPA-REG trial). Since SGLT-2 is known to be expressed on cells other than the kidney cells, we investigated the potential ability of empagliflozin to regulate glucose transport and alleviate hyperglycaemia-induced dysfunction of these cells. METHODS: Primary human monocytes were isolated from the peripheral blood of T2DM patients and healthy individuals. Primary human umbilical vein endothelial cells (HUVECs) and primary human coronary artery endothelial cells (HCAECs), and fetoplacental endothelial cells (HPECs) were used as the EC model cells. Cells were exposed to hyperglycaemic conditions in vitro in 40 ng/mL or 100 ng/mL empagliflozin. The expression levels of the relevant molecules were analysed by RT-qPCR and confirmed by FACS. Glucose uptake assays were carried out with a fluorescent derivative of glucose, 2-NBDG. Reactive oxygen species (ROS) accumulation was measured using the H2DFFDA method. Monocyte and endothelial cell chemotaxis were measured using modified Boyden chamber assays. RESULTS: Both primary human monocytes and endothelial cells express SGLT-2. Hyperglycaemic conditions did not significantly alter the SGLT-2 levels in monocytes and ECs in vitro or in T2DM conditions. Glucose uptake assays carried out in the presence of GLUT inhibitors revealed that SGLT-2 inhibition very mildly, but not significantly, suppressed glucose uptake by monocytes and endothelial cells. However, we detected the significant suppression of hyperglycaemia-induced ROS accumulation in monocytes and ECs when empagliflozin was used to inhibit SGLT-2 function. Hyperglycaemic monocytes and endothelial cells readily exhibited impaired chemotaxis behaviour. The co-treatment with empagliflozin reversed the PlGF-1 resistance phenotype of hyperglycaemic monocytes. Similarly, the blunted VEGF-A responses of hyperglycaemic ECs were also restored by empagliflozin, which could be attributed to the restoration of the VEGFR-2 receptor levels on the EC surface. The induction of oxidative stress completely recapitulated most of the aberrant phenotypes exhibited by hyperglycaemic monocytes and endothelial cells, and a general antioxidant N-acetyl-L-cysteine (NAC) was able to mimic the effects of empagliflozin. CONCLUSIONS: This study provides data indicating the beneficial role of empagliflozin in reversing hyperglycaemia-induced vascular cell dysfunction. Even though both monocytes and endothelial cells express functional SGLT-2, SGLT-2 is not the primary glucose transporter in these cells. Therefore, it seems likely that empagliflozin does not directly prevent hyperglycaemia-mediated enhanced glucotoxicity in these cells by inhibiting glucose uptake. We identified the reduction of oxidative stress by empagliflozin as a primary reason for the improved function of monocytes and endothelial cells in hyperglycaemic conditions. In conclusion, empagliflozin reverses vascular cell dysfunction independent of glucose transport but could partially contribute to its beneficial cardiovascular effects.

Salvation Expectations of Patients of Medicine, Complementary and Alternative Medicine and Religion.

Health and holistic quality of life, physical and emotional needs, somatic and spiritual aspects contain a comprehensive promise of healing. The aim of the current study is to measure the expectations of patients of medicine, alternative medicine and religion related to health and illness. The survey was carried out among 103 patients of a rural general practitioner from May to June 2013 and among 103 patients of the outpatient department for endocrinology and metabolic disease of the Jena University Hospital in 2013. All patients were asked by one interviewer (HM) on fears in relation to health/illness and expectations of help for its own life, medicine, alternative medicine and religion. The biggest fear of patients is "being in need of help of others." There is no significant difference between religious and non-religious patients. Overall, the expectations of medicine were significantly higher in all sectors than in alternative medicine or religion. Comparing alternative medicine and religion, the expectations of alternative medicine were significantly higher excluding consolation and inner peace. The expectations for medicine in general and for the physician are very high and comprehensive and go beyond diagnosis and realization of therapies. Patients expect hope, guidance, support, comfort, inner peace and advice most from medicine. This results in considerable challenges for the physician, especially in a healthcare system with limited resources and without suitable offers. There is an urgent need to integrate these requirements into daily routine.

Progression of Diabetic Complications in Subgroups of People with Long Term Diabetes Type 1 According to Clinical Course.

AIMS: Prevention and prediction of microvascular complications are important aims of medical care in people with type 1 diabetes. Since the course of the disease is heterogenous, we tried to identify subgroups with specific risk profiles for microvascular complications. METHODS: Retrospective analysis of a cohort of 285 people (22637 consultations) with >10 years of type 1 diabetes. Persons were grouped into slow (<15 years), fast (>15 years) and non progressors according to the average onset of microvascular complications. Generalized estimating equations for binary outcomes were applied and pseudo coefficients of determination were calculated. RESULTS: Progression to microvascular disease was associated with age (OR: 1.034 [1.001-1.068]; p=0.04), diabetes duration (OR: 1.057 [1.021-1.094]; p=0.002), HbA1c (OR: 1.035 [1.011-1.060]; p=0.005), BMI (OR: 0.928 [0.866-0.994]; p=0.034) and the social strata index (OR: 0.910 [0.830-0.998]; p=0.046). Generalized estimating equations predicted 31.02% and exclusion of HbA1c marginally reduced the value to 28.88%. The proportion of patients with LADA was higher in fast than slow progressors [13 (26.5%) vs. 14 (11.9%); p=0.019]. A generalized estimating equation comparing slow to fast progressors revealed no significant markers. CONCLUSION: In our analysis, we were able to confirm known risk factors for microvascular disease in people with type 1 diabetes. Overall, prediction of individual risk was difficult, the effect of individual markers minor and we could not find differences regarding slow or fast progression. We therefore emphasis the need for additional markers to predict individual risk for microvascular disease.

The High-Resolution Three-Dimensional Magnetic Detector System 3D-Magma Accurately Measures Gastric and Small Bowel Motility in People with Type 2 Diabetes with Neuropathy.

Gastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.

Is there an HbA1c Threshold for Symptoms of Chronic Hyperglycemia?

AIMS OF THE STUDY: The minimum therapeutic goal regarding metabolic control for people with diabetes mellitus is the "absence of symptoms of hyperglycemia." However, it is uncertain whether a level of HbA1c can be defined that guarantees the absence of these symptoms. The aim was to define an HbA1c threshold above which most patients show hyperglycemic symptoms. METHODS: In a multicenter cross-sectional study, 137 patients with type 1 and 285 with type 2 diabetes were asked about their symptoms during periods of hyperglycemia with a standardized questionnaire. Seventeen symptoms of hyperglycemia were summarized to the total hyperglycemia symptom score (THSS; min. 0; max. 68). The answers could be given according to the frequency and intensity in the last 4 - 6 weeks. RESULTS: The HbA1c threshold above which most patients showed hyperglycemic symptoms was 10.05% for patients with diabetes type 1 and 8.9%. for patients with type 2. Most confidence was reached on the symptoms of frequent urination" and "tiredness." The mean THSS was 19.4 (±9.0) and showed a positive correlation with age (r=0.167; p<0.001) and HbA1c (r=0.254; p<0.001). CONCLUSIONS: We identified an HbA1c threshold above which most patients show symptoms of hyperglycemia. In the treatment of people with diabetes mellitus, a safety margin to this threshold should be maintained to preserve well-being and avoid distress. However, since hyperglycemia symptoms are subject to many influencing factors, an adjustment of the therapy-both intensification and de-intensification-should always be carried out in combination with the requested hyperglycemia symptoms and HbA1c value.

Effectiveness and Safety of SGLT2 Inhibitors in Clinical Routine Treatment of Patients with Diabetes Mellitus Type 2.

The aim of this study was to investigate the effectiveness of SGLT2 inhibitors with regard to metabolic parameters and patient safety under routine ambulatory conditions. Retrospective longitudinal study of 95 patients with type 2 diabetes (diabetes duration 13.3 y; HbA1c 8.9%; eGFR 80.1 mL/min) receiving SGLT-2-inhibitors. Metabolic control and adverse event profile were evaluated. The mean follow-up time was 1.2 ± 0.8 years. The following changes were observed: HbA1c -1.0% ± 1.9 (p < 0.001), eGFR -7.0 mL/min ± 13.3 (p < 0.001), albuminuria -23.9 mg/g creatinine ± 144.5 (p = 0.118), bodyweight -3.0 kg ± 5.8 (p < 0.001), systolic blood pressure -6 mmHg ± 22 (p = 0.01), diastolic blood pressure -2 mmHg ± 14 (p = 0.243). 53 participants continuously applied the therapy. Twenty-eight participants discontinued SGLT-2-inhibitors due to various reasons: 20 participants because of genital- or urinary tract infections. One for dysuria, seven due to reduced eGFR below 45 mL/min. This study showed a considerable reduction of HbA1c and a modest reduction of eGFR, bodyweight and systolic blood pressure under clinical routine conditions. Genital infections occurred markedly more often than in randomized controlled trials. To apply SGLT-2-inhibitors more safely in clinical routine individual risks for genital and urinary tract infections should be considered and re-evaluated during therapy.

Reduction of Severe Hypoglycaemia in People with Type 2 Diabetes after a Structured Inpatient Intervention.

OBJECTIVE: The aim of this longitudinal study was to assess outcomes before and one year after participation in a structured inpatient intervention including participation in an education programme for people with type 2 diabetes. METHODS: In 2014, 81 individuals, who were admitted to optimise insulin therapy, participated in a structured inpatient intervention and were invited to participate in a follow-up visit after one year. RESULTS: Seventy participants (46.9% female, age 68.3 y, diabetes duration 17.9 y, HbA1c 9.7%/82.5 mmol/mol) were followed-up after 1.2 y (3 died by non-diabetic causes, 8 declined/were not available). HbA1c decreased by 1.1% (p<0.001) without change of insulin dose (79.7 vs. 79.3 IU, n.s.) or BMI (33.6 vs. 33.8 kg/m2, n.s.). 5 people admitted because of severe hypoglycaemia (one person with 5 episodes and 4 with one episode in the year prior to participation) did not experience another event in the evaluation period, nor did anyone in the rest of the cohort (frequency of severe hypoglycaemia 0.12 events/year before and 0.0 after intervention). CONCLUSIONS: In people admitted for optimising insulin therapy or severe hypoglycaemia, metabolic control improved substantially and frequency of severe hypoglycaemia was significantly reduced after participation in a structured inpatient intervention. Reasons could be motivational and better adapted eating habits, tailoring individual therapy solutions and deescalating diabetes therapy in people after severe hypoglycaemia.

Antidiabetic Therapy and Rate of Severe Hypoglycaemia in Patients with Type 2 Diabetes and Chronic Kidney Disease of Different Stages - A Follow-up Analysis of Health Insurance Data from Germany.

BACKGROUND: The presence of chronic kidney disease (CKD) influences the type of antiglycaemic therapy and the risk for hypoglycaemia. METHODS: In 2006, 2011 and 2016 health insurance data of people with diabetes type 2 were screened for CKD and the presence of severe hypoglycaemia (sHypo). The type of antihyperglycaemic therapy was recorded due to Anatomical Therapeutic Chemical (ATC) codes up to 3 months before suffering sHypo. RESULTS: The prevalence of CKD increased from 5.3% in 2006 to 7.3% in 2011 and 11.2% in 2016. Insulin-based therapies were used in 39.0, 39.1, and 37.9% of patients with, but only in 17.7, 17.4, and 18.8% of patients without CKD. Although the proportion of the CKD stages 1, 2 and 5 decreased, CKD stages 3 and 4 increased. The proportion of sHypo in CKD declined from 2006 (3.5%) to 2011 (3.0%) and 2016 (2.2%) but was still more than 10 times higher as compared to type 2 diabetic patients without CKD (0.3/0.2/0.2%) conferring a significantly higher probability of sHypo (OR 9.30, 95%CI 9.07-9.54) in CKD. The probability of sHypo was significantly lower in 2016 than in 2006 both in patients with (OR 0.58; CI 0.55-0.61) and without CKD (OR 0.70; CI 0.68-0.73). CONCLUSION: The prevalence of CKD increased from 2006 to 2016. Patients with CKD exhibited a 9-fold increased probability of sHypo, especially in patients treated with insulin plus oral anti-diabetic drugs. However, the rate and risk for sHypo decreased over time, probably as a consequence of new antidiabetic treatment options, better awareness of sHypo, and changed therapy goals.

Association between Flash Glucose Monitoring and Metabolic Control as well as Treatment Satisfaction in Outpatients With Diabetes Type 1.

OBJECTIVE: The aim of this study was to follow-up people with diabetes type 1 and Flash Glucose Monitoring (FGM) regarding metabolic control and treatment satisfaction. METHODS: 40 people with diabetes type 1 and FGM use of ≥6 months were included in the study (female 55%, age 50.9 y, diabetes duration 21.9 y, HbA1c 7.4%, 57.6 mmol/mol, insulin pump therapy 32.5%). The number of scans per day and time/frequency of hypoglycaemia (interstitial glucose value ≤3.9 mmol/l) was recorded from 28 days of the glucose readings. Change of treatment satisfaction was assessed with the DTSQc questionnaire at follow-up (range-18 to+18). RESULTS: Mean time of follow-up was 1.0±0.4 y. At follow-up, all participants scanned interstitial glucose 11.9±7.7 times/day. Number of self-monitoring of blood glucose decreased from 6.7±4.2 (baseline) to 0.9±1.8 (follow-up) per day (p<0.001). In individuals with baseline HbA1c ≤7.5%, HbA1c increased (from 6.6±0.7% to 7.0±0.4%, p=0.020). On the contrary, in people with HbA1c>7.5%, HbA1c decreased (from 8.2±0.7% to 7.8±0.7%, p=0.001). In all participants, there were no differences regarding insulin dosage (33.8±12.9 vs. 34.6±13.9 IU/day, p=0.679) and number of insulin injections/day (3.9±2.3 vs. 4.0±2.6, p=0.813) between baseline and follow-up. Frequency of symptomatic hypoglycaemia was at baseline 0.3±0.3 events/day and 0.48±0.36 events/day (recognised, symptomatic events) at follow-up, respectively. In addition, 0.26±0.21 unrecognised hypoglycaemic events/day occurred at follow-up. Treatment satisfaction increased by+12.6 points. CONCLUSIONS: FGM was associated with an enormous increase in treatment satisfaction and slightly improved metabolic control in people with baseline HbA1c>7.5%. The number of capillary glucose measurements decreased significantly.

Association Between Glycaemic Control and the Intake of Thiazide Diuretics, Beta Blockers and Levothyroxine in People Without Diabetes.

OBJECTIVE: The pharmacological additional information for many medications includes warnings stating that the blood sugar control may be worsened by the intake of certain drugs. However a quantification of the effects is missing. This may result in confusion for patients as well as for their physicians. The aim of this study was to assess a potential association between medication (beta blockers, thiazides, levothyroxine) and HbA1c in people without diabetes. METHODS: In this cross-sectional study we analysed data from 2 921 people (7 699 visits) without diabetes (age 46.6 y; 69.1% women; BMI 27.6±6.4 kg/m²; HbA1c 5.2%) who had at least one HbA1c determination and a complete documentation of their drug intake. An oral glucose tolerance test was not performed. The participants were divided in 8 groups (no regular drug intake, levothyroxine alone, beta blockers alone, thiazides alone, combination 2 of 3, combination of all 3). Patients with known distorting influences of the HbA1c were excluded. RESULTS: People with no regular drug intake had an HbA1c of 5.4% [35.8 mmol/mol]. The HbA1c of the group that took all 3 drugs in combination was 5.6% [38.2 mmol/mol]. A multiple linear mixed model showed an increase in HbA1c for thiazides (ß=0.0558, p=0.025) and a decrease for combination of levothyroxine and thiazide (ß=-0.0765, p=0.010). CONCLUSION: Thiazides and the combination of levothyroxine and thiazides were associated with slight changes in HbA1c. In this study there was no association between the intake of beta blockers and HbA1c. At least for people without diabetes these effects seem to be of minor importance.

Successful Treatment with Bedtime Basal Insulin Added to Metformin without Weight Gain or Hypoglycaemia over Three Years.

The aim of this observational study was to follow-up patients with bedtime basal insulin (NPH insulin) added to metformin. In 285 patients with type 2 diabetes, a therapy with bedtime basal insulin added to metformin was started due to failure to achieve a glycaemic goal. Up until July 2019, 272 patients (95.4%) were followed-up (59.5 y, 92.6 kg, diabetes duration 6.6 y, HbA1c 8.4%/68.6 mmol/mol). HbA1c decreased by -1.2% and bodyweight by -1.7 kg after a duration of 31.7 ± 29.1 (range 2-133) months. Severe hypoglycaemia did not occur. In 144/272 patients (52.9%), the therapeutic goal for HbA1c was achieved over 32.7 months. In 69/272 patients (25.4%), the HbA1c target was achieved over 25.0 months (afterwards, therapy with basal insulin was discontinued because HbA1c was under target). In 36/272 patients (13.2%), the HbA1c goal was achieved until the submission of this manuscript (mean duration of treatment 57.4 ± 28.2 (range 13-121) months). Over 90% of patients with type 2 diabetes and failure of metformin reached their HbA1c goal with additional basal insulin at bedtime over several years in association with a reduction of bodyweight and without any event of severe hypoglycaemia.

Adequate Structured Inpatient Diabetes Intervention in People With Type 1 Diabetes Improves Metabolic Control and Frequency of Hypoglycaemia.

OBJECTIVE: Several studies evaluated inpatient diabetes teaching and treatment programmes (DTTP) in diabetes type 1 (DM1) many years ago, but in these studies insulin treatment was not yet intensified before the DTTP. Today, most patients are already on intensified insulin treatment before entering a DTTP. The aim of this trial was to evaluate the outcome one year after participation in an inpatient intervention including a DTTP in a longitudinal study. METHODS: 109 patients participated in an inpatient intervention in 2014. All individuals were invited to participate in an outpatient follow-up visit after one year. RESULTS: Ninety participants (52.2% female, age 48.0 y, diabetes duration 19.1 y, 31.1% CSII, HbA1c 7.9% / 63.3 mmol/mol) were followed-up after 1.2±0.3 y [1 died, 18 declined / were not available]. 83 / 90 individuals participated to optimise diabetes therapy, 7 / 90 had newly-diagnosed DM1. In the optimisation group, HbA1c decreased by 0.4% (p=0.009) without change of insulin dose (54 IU/day before and after) or BMI (26 kg/m2 before and after). In people with baseline HbA1c ≥7.5% (n=26 / 83), HbA1c decreased by 0.9%. The frequency of severe hypoglycaemia decreased from 0.22 to 0.05 events / year (p=0.045). In people with frequent non severe hypoglycaemia (n=8), events decreased from 4.5±2.0 to 2.8±0.9 / week (p=0.358). Systolic (-6.5 mmHg, p=0.035) and diastolic (-3.4 mmHg, p=0.003) blood pressure improved without change of number of antihypertensive medication (1.9±2.1 vs. 1.8±2.0, p=0.288). CONCLUSIONS: In people with DM1, metabolic control improved after the inpatient intervention without increasing insulin dosage or BMI. The inpatient intervention remains effective to substantially improve metabolic control under the present circumstances of care.

Correction to: Agonistic autoantibodies against adrenergic receptors correlating with antihypertensive therapy in long-standing diabetes type 2.

Unfortunately, the Conflict of interest statement was found incomplete in the original publication and now revised by the authors. The updated version is provided here.

Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts.

BACKGROUND: Measurement of gylcated hemoglobin A1c (HbA1c) plays a central role in monitoring quality of antidiabetic therapy and in the diagnosis of diabetes. Several studies report increased levels of HbA1c in nondiabetic elderly. However, this observation did not reach incorporation into daily clinical practice or the respective guidelines. The present study aimed to evaluate HbA1c levels in relation to age in two independent population-based cohorts and to derive age-specific reference intervals. METHODS: Four thousand two hundred sixty three participants from the Study of Health in Pomerania (SHIP-0) and 4402 participants from the independent study SHIP-Trend were included. HbA1c was determined by means of high-performance liquid chromatography. Multivariable linear regression models were performed. Reference intervals for HbA1c were determined. RESULTS: Reference intervals were derived from a healthy subpopulation with the upper reference limit (URL) for HbA1c of 42.1 mmol/Mol (6.0%) for individuals aged 20-39 years increasing to 43.2 mmol/Mol (6.1%) for individuals aged 40-59 years. For people aged ≥60 years the URL was 47.5 mmol/Mol (6.5%). In both study populations an increase in HbA1c with age was observed. ANOVA revealed up to 8.5 mmol/Mol (0.77%) or 7.3 mmol/Mol (0.68%) higher estimated mean levels of HbA1c in the oldest compared to the youngest age group in SHIP-0 or SHIP-trend, respectively. Linear regression analyses confirmed the positive associations of HbA1c with age which was independent of BMI CONCLUSION: The present study confirmed the previously observed increase of HbA1c with increasing age in non-diabetic individuals. As a consequence age-dependent reference values for HbA1c were derived from two large and well defined reference populations. Implementation of them into daily practice may improve patient care and diagnosis of diabetes and reduce the risk of misdiagnosis and subsequent overtreatment of diabetes in elderly patients.

Agonistic autoantibodies against B2-adrenergic receptors correlating with macrovascular disease in longstanding diabetes type 2.

AIMS: Agonistic autoantibodies directed against adrenergic, endothelin, and angiotensin receptors are known as pathogenic factors in disease-causing vascular impairments such as Buergers' disease, dilatative cardiomyopathy, dementia, and preeclampsia. Diabetes mellitus also causes micro- and macrovascular damages, but pathogenesis is still not fully understood. Following indications for a pathogenic role of the mentioned antibodies from our preliminary investigations, we investigated the prevalence in a bigger cohort of patients with longstanding diabetes with or without diabetic complications. METHODS: We included 200 patients in four groups (grouping due to duration of diabetes and presence of complications) from our university polyclinic with longstanding diabetes mellitus type 2 and evaluated the prevalence of the agonistic autoantibodies using ELISA technique. RESULTS: Antibodies directed against the alpha1-(39%), the first extracellular loop of the beta2-(34,5%), and the first extracellular loop of the beta1-adrenergic receptor (29,0%) were the most often detectable. With progression of diabetes and its complications, we found a decrease in the prevalence of the antibodies. Regression analyses revealed a positive association of antibodies against the first loop of the beta2-receptor and the presence of macrovascular complications. CONCLUSIONS: This investigation found mid frequent prevalence of agonistic autoantibodies in patients with longstanding diabetes mellitus type 2. The association between an antibody against one epitope and the presence of macrovascular complications may indicates a pathogenic linkage. This finding is inconsistent with our preliminary data and needs further evaluation, maybe by follow-up.

Informed shared decision-making programme for patients with type 2 diabetes in primary care: cluster randomised controlled trial.

OBJECTIVE: To translate an informed shared decision-making programme (ISDM-P) for patients with type 2 diabetes from a specialised diabetes centre to the primary care setting. DESIGN: Patient-blinded, two-arm multicentre, cluster randomised controlled trial of 6 months follow-up; concealed randomisation of practices after patient recruitment and acquisition of baseline data. SETTING: 22 general practices providing care according to the German Disease Management Programme (DMP) for type 2 diabetes. PARTICIPANTS: 279 of 363 eligible patients without myocardial infarction or stroke. INTERVENTIONS: The ISDM-P comprises a patient decision aid, a corresponding group teaching session provided by medical assistants and a structured patient-physician encounter.Control group received standard DMP care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary endpoint was patient adherence to antihypertensive or statin drug therapy by comparing prescriptions and patient-reported uptake after 6 months. Secondary endpoints included informed choice, risk knowledge (score 0-11 from 11 questions) and prioritised treatment goals of patients and doctors. RESULTS: ISDM-P: 11 practices with 151 patients; standard care: 11 practices with 128 patients; attrition rate: 3.9%. There was no difference between groups regarding the primary endpoint. Mean drug adherence rates were high for both groups (80% for antihypertensive and 91% for statin treatment). More ISDM-P patients made informed choices regarding statin intake, 34% vs 3%, OR 16.6 (95% CI 4.4 to 63.0), blood pressure control, 39% vs 3%, OR 22.2 (95% CI 5.3 to 93.3) and glycated haemoglobin, 43% vs 3%, OR 26.0 (95% CI 6.5 to 104.8). ISDM-P patients achieved higher levels of risk knowledge, with a mean score of 6.96 vs 2.86, difference 4.06 (95% CI 2.96 to 5.17). In the ISDM-P group, agreement on prioritised treatment goals between patients and doctors was higher, with 88.5% vs 57%. CONCLUSIONS: The ISDM-P was successfully implemented in general practices. Adherence to medication was very high making improvements hardly detectable. TRIAL REGISTRATION NUMBER: ISRCTN77300204; Results.

Complete evaluation of pituitary tumours in a single tertiary care institution.

INTRODUCTION: We retrospectively evaluated all patients with pituitary tumours treated in our department from 1/1/1997 to 01/11/2014. PATIENTS AND METHODS: Two hundred and fifteen patients (124 females, 91 males, mean age 50.9 years) were treated because of pituitary tumours. All patients underwent basal hormonal analysis and when required dynamic testing in order to check for hormonal activity. Pituitary masses were divided into groups concerning their hormonal status and were further classified according to gender, age at diagnosis, tumour size, and the development of postoperative pituitary insufficiency when neurosurgical intervention was conducted. RESULTS: One hundred and twenty-one patients had hormonally inactive tumours (non-functional adenomas; 56.3%), 57 prolactinomas (26.5%), 17 growth hormone secreting adenomas (7.9%), 16 Cushing's disease (7.4%), and 4 craniopharyngiomas (1.9%). Tumours with maximum size <1 cm (microadenomas) were detected in 62 patients (28.8%) and ≥1 cm (macroadenomas) in 153 (71.2%) of all cases (rate 1:2.5). Ninty eight patients (45.6%) had surgery (87 transsphenoidal and 11 transcranial), of this group 34 with hormonally active tumours (37.8% of the 90 patients of this subcohort). Indications for surgery were an increased risk or manifestation of chiasma syndrome and clinical symptoms due to hormonal hypersecretion. Complete [32 cases (32.6%)] or partial [33 cases (33.7%)] postoperative insufficiency in minimum one pituitary axis was present in 65/98 (66.3%) of the operated patients. CONCLUSIONS: Pituitary adenoma prevalence is rising due to widely available imaging procedures. The majority of the tumours in our cohort were macroadenomas and hormonally inactive. Tumour extirpation via the transsphenoidal or transcranial route resulted in functional pituitary impairment of variable extent in 2/3 of the patients.

No selection, but higher satisfaction of people participating in the disease management programme diabetes type 2 in Germany.

AIMS: We analysed metabolic control, complications and satisfaction in people with and without DMP participation. METHODS: We retrospectively analysed the German data of the GUIDANCE study. The general practices included (n = 38) were selected from the physicians' register of the Thuringian Association of Statutory Health Insurance Physicians. Half of the practices (n = 19) participated in the DMP "Diabetes mellitus type 2". RESULTS: Nine hundred and fifty-nine people were included in the analysis. Of these, 541 (56.4%) were enrolled in the DMP and 418 (43.6%) not. There was no difference between the two groups (DMP vs. no DMP) regarding age (67.8 vs. 67.6y), gender (female 50.6 vs. 52.2%), diabetes duration (9.8 vs. 9.5y), BMI (31.3 vs. 30.7 kg/m2), HbA1c (7.2 vs. 7.2%), systolic blood pressure (139 vs. 140 mm Hg) or antihypertensive drug (89.5 vs. 88.8%). More DMP participants had regular screening of diabetic late complications: retinopathy 84.7 versus 69.9% (p < 0.001); polyneuropathy 93.0 versus 52.6% (p < 0.001). Chronic kidney disease was more frequent in DMP participants (15.0 vs. 9.3%, p = 0.005). Treatment satisfaction was higher in participants enrolled in the DMP (31.1 vs. 30.0; p = 0.002). CONCLUSIONS: DMP participants do not exhibit positive selection. Process quality and treatment satisfaction are higher in DMP participants.