Atherogenic cardiovascular risk plays a key role in prognosis in type 2 diabetes (T2D). Recent studies have shown increasing effects of chronic heart failure in cardiorenal syndrome on life expectancy in T2D. This work presents the frequency of chronic kidney disease (CKD) in T2D based on the literature and our own studies, ascertain cardiac risk due to cardiorenal syndrome, and suggest possible therapeutic approaches. International data as well as our own have shown 36 - 40% of diabetic patients to have CKD. Referring to the literature, we have presented pathophysiological interrelationships in heart and kidney organ damage while highlighting the pathogenic significance of HFpEF. An increase in perirenal and epicardial organ adipose tissue with adipokine release causes cytotoxic effects. This places additional significance on metabolic syndrome and organ damage with vascular accentuation. Recent therapeutic studies on using SGLT2 inhibitors or finerenone have shown a protective effect. The new therapeutic concept of cardiorenal syndrome is based on both groups of drugs.The established frequency of CKD in T2D warrants early renal function monitoring with attention to early signs of HFpEF or HFrEF in primary care. The traditional approach of measuring blood pressure as well as HbA(1c) and lipid levels is insufficient in atherogenic risk control.

Die diabetische Retinopathie (DR) und das Makulaödem (DMÖ) sind noch immer die häufigsten Ursachen für Sehverlust und erfordern eine aufwändige Diagnostik und Therapie. Die OCT als nicht-invasives Verfahren ermöglicht die frühe Erfassung von Zunahmen der Netzhautdicke und des Makulavolumens.

Type 2 diabetes patients aged 65 and over are a very heterogeneous group ranging from individuals in excellent condition with decades ahead of them to multimorbid patients with polypharmacy and short remaining life expectancy. This requires individual treatment strategies - including a realistic risk-benefit analysis - in consultation with patients on their expectations and living environments. Varying prioritization options should also be considered: Elderly people mainly value quality of life, maintaining health and autonomy, and safety and practicality in everyday life, followed by protection against stroke, cognitive failure, dementia and depression. Preventing cardiovascular disease, heart failure and chronic renal failure are major objectives in more "youthful" senior citizens with a long remaining life expectancy; CVOTs yielding evidence-based results from SGLT-2 inhibitors and three GLP-1 receptor agonists emphasise this point. Optimising nutrition and age-appropriate exercise take priority at advanced age. Naturopathic methods and concepts are especially beneficial, and elderly people use them by preference. Regarding risk factors in drug therapy, non-maleficence and the practical benefit of treatment should play a greater role the older and less healthy the patients are. There is therefore a genuine art to treating elderly people with diabetes as empowered patients and partners.

Nephropathy, retinopathy and macular edema constitute serious microvascular complications in diabetes mellitus. In contrast to macrovascular changes, these complications are closely linked with the quality of metabolic control, and often occur together. Survival prognosis is very poor for patients with diabetes and this fully manifested microvascular damage profile. The fifth and final part of the series on microangiopathy will cover the current state of knowledge in diagnosis and treatment for nephropathy, retinopathy and macular oedema in diabetes mellitus. This will include the risk factors, prognosis and therapy for diabetic nephropathy, including blood glucose and blood glucose control as well as lipid metabolism. Treatment options for end-stage renal deficiency such as haemodialysis, peritoneal dialysis, and kidney transplantation will also be given consideration. Treatment options for diabetic retinopathy and diabetic macular edema will also be presented; these include laser photocoagulation, intra-vitreal and systemic options, and surgical therapy.

The ACE study evaluated the efficacy and safety of acarbose in a large Chinese cardiovascular outcome trial on high-risk patients with coronary heart disease and IGT. The primary objective was a five-point MACE including heart failure and hospitalisation for instable angina. The major secondary endpoint was diabetes prevention. The hazard ratio for MACE was 0.9 (n. s.), whereas the incidence of newly diagnosed diabetes was reduced by 18 % (13 % vs. 16 %, p = 0.005). A reduction of morbidity and mortality may therefore be expected in the long run. This study did not confirm the positive effects on cardiovascular events as observed in the STOP-NIDDM trial. Limitations to the study comprised low acarbose dosage (3 x 50 mg/d) with no documented pleiotropic effects. The study confirms the drug's high safety and compliance in treating multimorbid patients with polypharmacy. Acarbose treatment according to IDF guidelines may therefore be recommended for early diabetes with postprandial hyperglycaemia as a first-line drug, and as an adjuvant to antidiabetic drugs in advanced diabetes.

A cost-benefit analysis for microvascular complications indicates that diabetic nephropathy (DN) and diabetic retinopathy (DR) require multifunctional therapy beyond antidiabetics-recently empagliflozin alongside metformin-by including anti hypertensives and lipid-lowering drugs in type 2 diabetes (T2DM) treatment. The real costs vary depending on whether the therapy includes a VEGF-antagonist against DR or haemodialysis against DN. This makes it difficult to compare costs for microvascular complications. New findings (2016) from the Steno-2 study have shown that intensified treatment reduces the risk (odds ratio) to 0.45 for DR within 7.8 years, and 0.27 for DN after 3.8 years. Older data may therefore be expected to change even in view of an ageing society (macrovascular DM complications of 43.8 %, microvascular complications on eyes and kidneys at 24.6%, foot complications at 25.1 % and metabolic complications at 75%). In any case, preventing microvascular disease is cost-effective in improving the fate of patients and the associated increase in costs for care management due to the harmful consequences of the severe kidney disease and dialysis as well as blindness, and also presents a great benefit in quality of life and physical and mental fitness.

A good blood glucose (BG) control in diabetic patients (commonly accepted range of HbAft: 6.5-7.5%; 48-58 mmol/mol) without hypoglycaemia and postprandial peaks, a strict control of blood pressure (today: <= 140/<90 mmHg) and lipid metabolism are the most important measures in evidence-based medicine for primary and secondary prevention of diabetic retinopathy (DR) and nephropathy (DN). Microvascular complications are so far only secondary endpoints in major studies aiming at life-threatening macro vascular complications, which are almost exclusively recorded as combined endpoint of major adverse cardiac events" (MACE) mostly including cardiovascular death by myocardial and brain infarction. Solely, an effective basis therapy can reduce the HbA(1c) by 0.5 to 2%. Such decrease also reduces microvascular complications. This paper summarises the results of the pivotal UKPD-33-study (1998), Cochrane meta-analyses and newer studies such as ADVANCE, ACCORD, EMPA-REG Outcome, IRIS, LEADER, PROactive or SUSTAIN-6, which are now the European wide basis of an up-to-date guideline oriented basis for the therapy of type 2 diabetes.

Zusammenfassung Das metabolische Syndrom beschreibt ein Cluster verschiedener Symptome und Erkrankungen, die mit einer erhöhten kardiovaskulären Morbidität assoziiert sind. Ursprünglich zählten dazu Adipositas, Dyslipidämie, Diabetes mellitus Typ 2, Gicht und arterielle Hypertonie. Diesen Merkmalen des metabolischen Syndroms liegt offenbar eine gemeinsame Pathophysiologie zugrunde, wobei die alimentäre Adipositas in Verbindung mit einer genetischen Prädisposition meist den Ausgangspunkt darstellt. In der Progression der metabolischen und vaskulären Störungen spielen Insulinresistenz und subklinische Inflammation eine entscheidende Rolle. Aufgrund der zumeist parallelen Entwicklung von metabolischen und vaskulären Schäden bietet das metabolische Syndrom gegenüber den klassischen Risikoscores keine zusätzlichen Informationen, es dient eher als Ansatz für die integrierte Diagnose und Therapie häufig gemeinsam auftretender Erkrankungen.

Das metabolische Syndrom beschreibt ein Cluster verschiedener Symptome und Erkrankungen, die mit einer erhöhten kardiovaskulären Morbidität assoziiert sind. Ursprünglich zählten dazu Adipositas, Dyslipidämie, Diabetes mellitus Typ 2, Gicht und arterielle Hypertonie. Diesen Merkmalen des metabolischen Syndroms liegt offenbar eine gemeinsame Pathophysiologie zugrunde, wobei die alimentäre Adipositas in Verbindung mit einer genetischen Prädisposition meist den Ausgangspunkt darstellt. In der Progression der metabolischen und vaskulären Störungen spielen Insulinresistenz und subklinische Inflammation eine entscheidende Rolle. Aufgrund der zumeist parallelen Entwicklung von metabolischen und vaskulären Schäden bietet das metabolische Syndrom gegenüber den klassischen Risikoscores keine zusätzlichen Informationen, es dient eher als Ansatz für die integrierte Diagnose und Therapie häufig gemeinsam auftretender Erkrankungen.

Hypoglycaemia can lead to severe cardiac arrhythmias, which are harmful for patients with type 2 diabetes and cardiovascular disease. Little is known about specific proarrhythmic ECG changes, which can occur during hypoglycemic events in a real world setting.

Despite significant improvements in diabetes mellitus therapy, increasing disease duration and diabetes-related complications such as microangiopathy and neuropathy remain a severe problem affecting quality of life, morbidity, and mortality in diabetes. Pathogenesis centres on chronic hyperglycaemia and denaturation of multiple functional proteins with HbA(1c) as the gold standard, and oxidative stress plays a key role in the degradation of endothelial layers in target organs. Excessive blood glucose excursions and dyslipidaemia with lipotoxicity interact with these pathogenic cascades in a vicious circle, requiring a holistic therapy approach.

Levels of vascular endothelial growth factors (VEGF) are regulated in a complex network of adipokines, glucose control, and low grade inflammation together with activated platelets, leucocytes, and endothelial dysfunction. Increased levels of VEGF are associated with enhanced angiogenesis and impaired repair mechanisms of vascular lesions in endorgans. Little is known about the interaction of systemic VEGF levels with quality of diabetes control, biomarkers of inflammation, and diabetic nephropathy. Moreover, it is unclear, whether serum and plasma VEGF levels are similarly suited to reflect risk associated with VEGF. In this case control study, we analyzed these parameters in serum and plasma of age and sex matched controls without diabetes (n=99) and type 2 diabetes (n=302). Serum VEGF-A was significantly increased in patients with T2DM while plasma levels were in the same range as for controls. Individual levels varied in a wide range. Serum levels were 4.9 times higher in controls and 7.3 times higher in T2DM as compared to plasma levels. T2DM was associated with significantly higher levels of hsCRP, ALAT, and albumin/creatinine ratio. When calculated for tertiles of HbA1c, we observed a highly significant increase from tertile one to the upper tertile for serum VEGF-A but not for plasma VEGF-A. Correlation analysis revealed a significant relationship between VEGF-A, HbA1c, inflammation, and diabetic nephropathy. Our results indicate that increased VEGF-A levels in T2DM significantly depend on quality of HbA1c control. Serum levels of VEGF-A, with a strong contribution of platelet derived VEGF, better reflect the glycemic burden than plasma levels of VEGF-A. Mechanistic studies are needed to explore links to inflammation and diabetic nephropathy.

VEGF sind potente angiogene Zytokine, die eine enge Beziehung zur Entwicklung einer Retinopathie und diabetischen Nephropathie haben. Bisher gibt es nur wenige systematische Untersuchungen über die Verbindungen von VEGF, Diabeteskontrolle und Biomarkern der Inflammation als Links zum Mikroangiopathierisiko.

Dans le but d'améliorer l'équilibre glycémique sous l'insuline basale (IB), nous avons étudié 3 options thérapeutiques d'intensification chez des adultes diabétiques de type 2 (DT2), majoritairement obèses, traités par IB (≥ 6 mois) ± 1-3 ADO). Si l'HbA1c est comprise entre 7-9 % après une phase préliminaire de 12 semaines d'optimisation de l'IG avec arrêt des autres ADO autres que la metformine, les patients étaient randomisés pour recevoir soit du lixisénatide 20 μg 1 fois par jour (LIXI), soit de l'insuline glulisine une fois par jour (GLU-1), soit de l'insuline glulisine 3 fois par jour (GLU-3), en association à l'insuline glargine (IG). Les co-critères primaires à 26 semaines étaient (1) la non-infériorité (limite supérieure de l'IC 95 % < 0,4 %) de baisse de l'HbA1c sous LIXI vs GLU-1 et (2) pour LIXI vs GLU-3 soit la non infériorité de baisse de l'HbA1c (2a), soit la supériorité (α unilatéral = 0,025) pour la variation de poids (2b). Les GAJ, GPP, doses d'IG, les EI et les hypoglycémies ont été évalués. 298 patients ont été randomisés dans chaque bras (durée du DT2 : 12 ans, durée d'IB : 3 ans, poids : 89 kg). Tous les co-critères primaires ont été atteints : LIXI n'était inférieur ni à GLU-1 ni à GLU-3 pour la baisse d'HbA1c (différence [IC 95 %] respectivement à − 0,05 % [− 0,17 ; 0,06] et 0,21 % [0,10 ; 0,33]) et était supérieur à chaque groupe pour la perte de poids (respectivement − 1,7 kg [− 2,3 ;− 1,1] p < 0,0001 et − 2,0 kg [− 2,6 ;− 1,4] p < 0,0001). Les hypoglycémies documentées étaient numériquement et significativement moins importantes sous LIXI que sous GLU-1 et GLU-3 respectivement. L'association IB + LIXI pourrait devenir une option de choix pour atteindre les objectifs glycémiques avec moins d'hypoglycémies et sans conséquence négative pour le poids vs l'insuline prandiale utilisée en schéma basal-plus ou basal-bolus chez des patients DT2 insuffisamment équilibrés sous IB et metformine.

Der Alpha-Glukosidaseinhibitor Acarbose hat neben der blutzuckersenkenden Wirkung durch Hemmung der Kohlenhydratresorption auch positive Effekte auf kardiovaskuläre Ereignisse und reduziert die Inzidenz von Diabetes, Hypertonie und Kolonkarzinomen. Wir untersuchten deshalb, ob Acarbose das intestinale Inflammasom beeinflusst, da die subklinische Inflammation eine mögliche Verbindung zwischen diesen Erkrankungen darstellt.

Die 3 wichtigsten Neuentwicklungen der medikamentösen Therapie des Typ-2-Diabetes in den vergangenen Jahren umfassen inkretinbasierte Medikamente, SGLT2-Inhibitoren und lang wirksame Insulinanaloga. Derzeit entwickelt sich die Therapie des Typ-2-Diabetes tatsächlich zu einer personalisierten Therapie, bei der die individuelle Abwägung von Wirksamkeits- und Sicherheitsaspekten der Arzneimitteltherapie im Vordergrund steht. Die neuen Therapieoptionen bei Typ-2-Diabetes ermöglichen eine Vielzahl von Kombinationen, für die individualisierte Therapieempfehlungen von Expertengruppen und Leitlinien vorliegen. Alle Empfehlungen für Kombinationen beruhen bisher auf kontrollierten klinischen Studien. Nur für DPP-4-Inhibitoren liegen zwei Outcomestudien vor. Deshalb kommt der Risiko-Nutzen-Abwägung eine wesentliche Rolle zu, mit stärkerem Fokus auf Lebensqualität und diabetesbezogenen Komplikationen. Mit so vielen Optionen wird die Behandlung des Typ-2-Diabetes mehr denn je zu einer ars curandi.