Peter Wiesli

Modern treatment of type 2 diabetes considers the use of three medications in all patients regardless of HbA1c (metformin, SGLT-2i, and GLP-1(+)-RA) as well as achieving three target values (HbA1c, blood pressure, and LDL cholesterol). These three target values are set individually. Ideally, most patients with type 2 diabetes should have HbA1c 6.5 %, blood pressure 130/80 mmHg, and LDL cholesterol 1.8 mmol/l. In patients with established cardiovascular disease should have LDL cholesterol 1.4 mmol/l.

Zusammenfassung: In den vergangenen Jahren wurde im Rahmen von Studien zur kardiovaskulären Sicherheit mit SGLT-2-Hemmern und den GLP-1-Rezeptor-Agonisten gezeigt, dass sie das Risiko kardiorenaler Endpunkte bei Patientinnen und Patienten mit Typ-2-Diabetes verglichen mit den anderen Antidiabetika signifikant senken, dies unabhängig von den zeitgleich eingesetzten anderen Therapien. Dieser Zusatznutzen der SGLT-2-Hemmer ist in der Praxis bereits gut etabliert und diese Substanzklasse wird immer häufiger eingesetzt, aber gemäss der aktuellsten Evidenz sollten auch GLP-1-Rezeptor-Agonisten früh in der Behandlung des Diabetes mellitus Typ 2 eingesetzt werden. Bei Personen mit sehr hohem kardiovaskulärem Risiko ist die Kombinationstherapie eines GLP-1-Rezeptor-Agonisten mit einem SGLT-2-Hemmer eine interessante Therapieoption.

Aims This study evaluated effectiveness and safety of switching the basal insulin (BI) in a BI supported oral therapy (BOT) to insulin glargine 300 U/mL (Gla-300) in adult people with inadequately controlled type 2 diabetes (T2D). Materials and methods This non-interventional, multicentre, prospective 12-month study, conducted in Germany, Austria and Switzerland, documented people with T2D with an HbA_1c between 7.5-10.0%, currently treated by a non-Gla-300 BOT regimen, after the physician had decided to switch the BI to Gla-300. Primary endpoint was the proportion of patients achieving fasting plasma glucose (FPG; ≤110 mg/dL) target. Results 1,194 participants comprised the full analysis set, of which 793 completed documentation of 12 months Gla-300 treatment (FAS-M12). Main previous BI was insulin glargine 100 U/mL (Gla-100; 47.2%). Twelve months after switching to Gla-300, 27.0% of FAS-M12 participants achieved the FPG target and 44.8% their individualized HbA_1c target. Greatest FPG target achievements were seen in previous Gla-100 (29.3%), and greatest HbA_1c target achievements in previous insulin detemir users (57.7%). Mean FPG decreased by –36.3±51.2 mg/dL to 135.5±36.9 mg/dL and mean HbA_1c by –0.79±1.01% to 7.45±0.94%. Symptomatic and nocturnal hypoglycaemia incidence significantly decreased over 12 months of Gla-300 treatment. Body weight remained unchanged. Conclusions Switching the BI to Gla-300 in a BOT regimen improved metabolic control and treatment satisfaction in a substantial proportion of patients with T2D and inadequate target achievement within 12 months in clinical practice with decreased risk of symptomatic and nocturnal hypoglycaemia and without weight gain.

Zusammenfassung. Bei einer Hypercholesterinämie mit einem LDL-Cholesterin von >5 mmol/l sollte an das Vorliegen einer familiären Hypercholesterinämie (primäre Hypercholesterinämie) gedacht werden, da bei dieser genetisch vererbbaren Erkrankung eine frühzeitige Behandlung der Patientin/des Patienten und das Screening der Angehörigen sehr wichtig ist. Neben der Höhe der Cholesterinwerte können auch Familienanamnese und klinische Befunde auf das Vorliegen einer familiären Hypercholesterinämie hinweisen. Die Wahrscheinlichkeit für das Vorliegen einer familiären Hypercholesterinämie kann mit dem Dutch Lipid Clinic Network Score abgeschätzt werden. Es gibt allerdings auch eine Reihe exogener Faktoren, die den Lipoproteinstoffwechsel beeinflussen und zu einer sekundären Hypercholesterinämie führen können. Mögliche Ursachen einer sekundären Hypercholesterinämie sind u.a. Hypothyreose, Cholestase, nephrotisches Syndrom und verschiedene Medikamente. Diese sekundären Ursachen einer Hypercholesterinämie müssen vor Beginn einer Behandlung der Hypercholesterinämie beziehungsweise Diagnose einer familiären Hypercholesterinämie ausgeschlossen werden.

Introduction: Somatostatin‐secreting neuroendocrine tumours may present with diabetes, cholelithiasis and steatorrhoea. In addition, hypoglycaemia has been associated with somatostatinomas. However, the mechanism of hypoglycaemia in patients with somatostatinomas has not been well characterized.Methods: We describe two patients with recurrent neuroglycopenic episodes caused by somatostatin‐secreting neuroendocrine tumours in the liver, detected by abdominal CTs and whole‐body octreotide scintigraphy scans and confirmed by biopsy.Results: Pancreatic islet hyperplasia and co‐secretion of insulin (in addition to somatostatin) from tumour cells, respectively, have been characterized as completely distinct mechanisms of hypoglycaemia at both the functional and morphological levels in these two patients.Conclusions: Hypoglycaemia may be caused by different mechanisms in patients with somatostatinomas.

Insulin glargine 300 U/mL (Gla-300, Toujeo^®) is a long-acting, once-daily basal insulin with improved—more stable and smoother—pharmacokinetic and pharmacodynamic profiles compared to insulin glargine 100 U/mL (Gla-100) and insulin degludec (IDeg). These properties have been shown to translate into an effective HbA1c reduction with the advantage of a lower risk of hypoglycemia in randomized controlled trials of Gla-300 versus Gla-100. In this study, we assessed the effectiveness and safety of Gla-300 under real-world conditions in Switzerland.

The objective was to test whether chromogranin A (CgA), neuron-specific enolase (NSE), and pancreatic polypeptide (PP) are released from the pancreas during the selective arterial calcium stimulation and hepatic venous sampling test (ASVS) in patients with insulinomas. We determined CgA, NSE, PP, insulin, C-peptide, and proinsulin in blood samples obtained during the ASVS test in 19 patients with insulinomas. Levels following calcium injection into the arteries supplying the tumor were compared with levels following calcium stimulation of arteries supplying healthy pancreatic tissue. After calcium injection into the artery supplying the insulinoma, a significant 8-fold increase in insulin (range, 2.3-117; P < 0.001), a 3.8-fold increase in C-peptide (1.7-32.4; P < 0.001), and a 1.9-fold increase in proinsulin (0.7-5.3, P < 0.001) were detectable whereas NSE and CgA did not increase. No significant increases in insulin, C-peptide, proinsulin, CgA, and NSE concentrations were found after calcium injection into control arteries. Pancreatic polypeptide increased 1.5-fold (0.8-4.5; P = 0.017) after calcium injection into the tumor artery and 2.4-fold (0.8-7.9; P = 0.016) after injection into the control artery. Insulin, C-peptide, and proinsulin are released by insulinoma cells in response to arterial calcium stimulation, whereas CgA and NSE are not released. Also from our study it seems that PP may be released by healthy islet cells after calcium stimulation.

Diabet. Med. 29, 128–131 (2012) Aim  To investigate the effect of acute psychological stress on glucose concentrations in patients with Type 2 diabetes, in the fasting state as well as in the postprandial state.Methods  Thirty patients (12 female) with Type 2 diabetes were included. Mean ± sd age was 60 ± 12 years, BMI 28.8 ± 4.2 kg/m², diabetes duration 8.9 ± 6.7 years and HbA_1c 51 ± 9 mmol/mol (6.8 ± 0.8%). Using a non‐randomized approach, all participants were exposed to moderate psychological stress by means of the Trier Social Stress Test: 10 participants in the fasting state and 20 participants 75 min after intake of a standard meal. Blood pressure, heart rate and salivary cortisol were monitored on the control day and the stress‐test day. Glucose concentrations were assessed using a continuous glucose monitoring system.Results  On the stress‐test day, blood pressure rose from 117/73 ± 13/12 to 155/92 ± 22/14 mmHg, heart rate from 77 ± 11 to 91 ± 25 b min⁻¹ and salivary cortisol concentrations from 8.5 ± 3.7 to 26.4 ± 12.1 nmol/l (P < 0.001); these measurements remained unchanged on the control day. On the stress‐test day, when the Trier Social Stress Test was applied 75 min after the intake of a standard meal, the glucose concentrations were significantly higher compared with the control day (mean difference 1.5 mmol/l, 95% CI 0.5–2.4, P = 0.003). In the fasting state, glucose concentrations slightly decreased during the control day but remained stable on the stress‐test day (mean difference compared with the control day 0.7 mmol/l, 95% CI −0.7 to 2.0, P = 0.31).Conclusions  When stress is experienced in the postprandial period, acute psychological stress significantly increases glucose concentrations in patients with Type 2 diabetes.