Familial partial lipodystrophy (FPLD) is a rare genetic syndrome characterised by persistent, selective loss of adipose tissue and is closely associated with severe metabolic disturbances. Pregnancy in women with FPLD is associated with a high risk for both mother and foetus, while clinical experience remains very limited. Evidence from case reports and small series is essential for risk stratification, multidisciplinary management, and optimization of maternal and foetal health. Here, we report the case of a woman at 18 weeks of gestation with very severe hypertriglyceridaemia complicated by acute pancreatitis. The patient had a history of young-onset diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS) and previously known hypertriglyceridaemia, accompanied by characteristic loss of gluteofemoral and lower limb adipose tissue, raising the clinical suspicion of FPLD. Molecular genetic analysis was performed using next-generation sequencing-based gene panel diagnostics. Variants were described according to Human Genome Variation Society (HGVS) nomenclature and classified according to the American College of Medical Genetics and genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. We made the initial diagnosis of severe FPLD3 syndrome and detected a novel heterozygous c.380A>C, p.(Glu127Ala) variant in the peroxisome proliferator-activated receptor gamma gene (PPARG), classified as likely pathogenic and considered causative for the patient´s phenotype. In addition, a heterozygous variant of uncertain significance c.328G>A, p.(Ala110Thr) in the ATP-binding cassette transporter sub-family C member 8 gene (ABCC8), was detected. High-dose intensive insulin therapy in combination with metformin and omega-3 fatty acids resulted in a marked reduction in triglyceride levels, normalised blood glucose levels until delivery and avoided further episodes of pancreatitis. Early recognition of FPLD is crucial, particularly in high-risk settings such as pregnancy. Intensive, multidisciplinary metabolic management can stabilize severe metabolic complications and may enable favourable maternal and foetal outcomes.

OBJECTIVE:To obtain clinical features of diabetic ketoacidosis (DKA) in adults leading to hospital admission. METHODS:Multicenter observational study investigating DKAs treated in five German tertiary hospitals between 2022 and 2023. RESULTS:A total of 179 patients with 203 episodes of DKA were registered: 64% of cases in pre-existing type 1 diabetes mellitus (T1DM), 14% in new-onset T1DM, 14% in pre-existing type 2 diabetes mellitus (T2DM), 3% in new-onset T2DM, 6% in latent autoimmune diabetes in adults, and 6% in pancreatogenic diabetes. Seven cases of SGLT 2 inhibitor (SGLT 2-I)-associated euglycemic DKA (EDKA) were encountered. In pre-existing T1DM, DKA occurred despite continuous glucose monitoring in 51% of patients and insulin pumps or automated insulin delivery in 24%. Only 21% of individuals with T1DM were in possession of ketone test and only 6% applied ketone testing. In total, 71% of patients with pre-existing T1DM experienced recurrent episodes of DKA. Suboptimal adherence to diabetes therapy was the most common triggering factor for DKA in known T1DM (56%), whereas infections contributed most in pre-existing T2DM (32%). The entirety of patients pretreated with SGLT2-Is and particularly also those with SGLT2-I associated EDKA were not educated concerning sick-day-rules. The inpatient mortality risk of DKA was 2.3% and restricted to multimorbid patients with known T2DM. CONCLUSIONS:The clinical and etiological pattern of DKA is heterogeneous. Patients with pre-existing T1DM showed educational deficits concerning diagnostic and therapeutic measures to prevent DKA. Individuals with recurrent episodes of DKA require individual therapeutic concepts within the multidisciplinary diabetes care team. Emphasizing sick-day-rules in patients being treated with SGLT 2-Is is indispensable to prevent EDKA. Individuals with pre-existing T2DM represent a vulnerable group with severe comorbidities and high mortality risk due to DKA.

AIMS:To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020.METHODS:A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001.RESULTS:The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001).CONCLUSION:Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams.

Aim To collect and analyze representative data on relevant indicators of structural and process quality in the management of diabetic emergencies in Germany.

BACKGROUND:A global cross-sectional survey (CRASH) was designed to provide information about the experiences of people with diabetes (PWD) and their caregivers in relation to severe hypoglycaemic events.METHODS:Adults with type 1 diabetes or insulin-treated type 2 diabetes who had experienced one or more severe hypoglycaemic events within the past 3 years, and adult caregivers for such people, were recruited from medical research panels using purposive sampling. We present here results from Germany.RESULTS:Approximately 100 individuals in each of the four participant groups completed a 30-minute online survey. Survey results indicated that the most recent severe hypoglycaemic event made many participants feel scared (80.4%), unprepared (70.4%), and/or helpless (66.5%). Severe hypoglycaemia was discussed by healthcare professionals at every visit with only 20.2% of participants who had ever had this conversation, and 53.5% of participants indicated that their insulin regimen had not changed following their most recent event. 37.1% of PWD/people with diabetes cared for by caregivers owned a glucagon kit at the time of survey completion.CONCLUSIONS:The survey identified areas for improvement in the prevention and management of severe hypoglycaemic events. For healthcare professionals, these include enquiring more frequently about severe hypoglycaemia and adjusting blood glucose-lowering medication after a severe hypoglycaemic event. For individuals with diabetes and their caregivers, potential improvements include ensuring availability of glucagon at all times. Changes in these areas could lead not only to improved patient wellbeing but also to reduced use of emergency services/hospitalisation and, consequently, lower healthcare costs.

A 63-year-old man was brought to the hospital with massive peranal loss of bright-red blood. Three months earlier, p-ANCA/MPO-positive (ANCA, antineutrophil cytoplasmic antibody; MPO, myeloperoxidase), rapidly progressive glomerulonephritis had been diagnosed against a background of polyangiitis with acute-on-chronic renal failure requiring dialysis. The initial treatment was prednisolone and cyclophosphamide pulse therapy with plasmapheresis, but by the time of presentation to our department this had been switched to long-term treatment with prednisolone 7.5 mg/day. Emergency endoscopy revealed no source of bleeding in the upper intestinal tract down to beyond the ligament of Treitz, and ileocolonoscopy was also negative. Subsequent angiographic computed tomography found a solitary acute hemorrhage in the jejunum (Figure a). Because the patient had symptoms of shock, we proceeded to explorative laparotomy (Figure b) and intraoperative endoscopy via a lower intestinal enterotomy. This revealed segmental inflammation of the ileojejunum with fresh blood from ulcerations. Histological examination of resected jejunal tissue demonstrated granulomatous vasculitis. The patient was discharged 14 days later after renewed cyclophosphamide and cortisone pulse therapy without further complications. Systemic vasculitis of the gastrointestinal tract manifests itself in 30 to 55% of cases, depending on type; biopsy rarely confirms the diagnosis. Involvement of the small intestine has a potentially grave prognosis, as perforations or hemorrhages can very quickly become life-threatening.

ZUSAMMENFASSUNGSchwere Hypoglykämien führen häufig zu Verletzungen und sind mit einer mehr als 2-fach erhöhten kardiovaskulären Mortalität und Morbidität assoziiert. Hauptrisikofaktoren für Hypoglykämien bei Typ-1-Diabetes sind Störungen der Hypoglykämie-Wahrnehmung bzw. rekurrente Hypoglykämien, während bei Typ-2-Diabetes komplexe geriatrische Multimorbidität und kognitive Einschränkungen dominieren. Individuelle (Re-)Schulungen der Patienten bilden die Grundlage der Prävention. Therapieziele sollten unter Wertung des Patientenwunsches, der Komorbiditäten, des Hypoglykämierisikos, der Lebenserwartung u.a. individuell festgelegt werden. Bei Typ-2-Diabetes und Hypoglykämie-Vulnerabilität sind Antidiabetika ohne intrinsisches Hypoglykämierisiko (DPP-4-Hemmer, GLP-1-Analoga, SGLT-2-Hemmer) in der Zweitlinien-Therapie nach Metformin zu bevorzugen. Moderne CGM-Technologien tragen dazu bei, insbesondere gefährliche nächtliche Hypoglykämien zu reduzieren und die Hypoglykämie-Wahrnehmung zu verbessern. Auch CSII und wahrscheinlich der Einsatz moderner Basalinsulinanaloga senken das Hypoglykämierisiko bei Typ-1- bzw. Typ-2-Diabetes. Die simultane Transplantation von Pankreas und Niere, die isolierte Pankreastransplantation und Inseltransplantation führen nicht nur zur (temporären) Insulinunabhängigkeit, sondern vermeiden auch Hypoglykämien. Die primäre Therapie bei bewusstseinsgestörten Patienten mit schwerer Hypoglykämie besteht in der streng intravenösen Gabe von 50 ml 40 %iger Glukose als Bolus. Alternativ kann die Gabe von 1 mg Glukagon intramuskulär erfolgen. Ältere komorbide oder verletzte Diabetespatienten, Sulfonylharnstoff-Hypoglykämien und Hypoglykämien unter Alkoholkonsum oder Analgetika-/Sedativa-Medikation bedürfen obligat der stationären Überwachung.

It has been estimated that 15% up to one third of cases of deaths due to diabetic ketoacidosis occur in individuals with so far unknown diabetes. Moreover, cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke lethal arrhythmias. As postmortem capillary glucose concentrations have no diagnostic value, the postmortem forensic proof of hyperglycaemia or hypoglycaemia remains a challenge. The established but rarely applied method of postmortem determination of glucose and lactate in vitreous humor with or without calculation of the sum formula of Traub could provide reliable exclusion or proof of severe antemortem disorders in glucose metabolism. To date, diagnostic puncture of vitreous humor is more established for the postmortem detection of diabetic ketoacidosis than for the exclusion or proof of lethal hypoglycaemia. Vitreous humor is protected from postmortem degradation and contamination due to its isolated localization. The autolytic process in vitreous humor is considerably delayed compared to blood or liquor. In vitreous humor also the triggering agent of hypoglycaemia (insulin, insulin analogues) is easier to be detected than in blood since insulins are very unstable in postmortem blood. Furthermore, parameters of long term glycaemic control such as 1,5-anhydroglucitol, HbA1c and fructosamine can be determined in vitreous humor. However, limitations and interference factors of this method should be carefully considered. So far, clinical diabetology has taken no broad notice of this useful forensic procedure.

We thank Gentile et al. [ [1] Gentile S. Guarino G. Marino G. Strollo F. Risk factors for severe hypoglycemia in people with insulin-treated diabetes: are we sure we took into account all variables involved?. Nutr Metab Cardiovasc Dis. 2017; 27: 415-416 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ] for their interest and comments on our recent article focusing on risk factors for restrictively defined severe hypoglycaemia (SH) in people with type 1 diabetes (T1DM) [ [2] Wohland T. Holstein J.D. Patzer O.M. Mende M. Tiemann T. Koch-Tessarek C. et al. New risk and protective factors for severe hypoglycaemia in people with type 1 diabetes. Nutr Metab Cardiovasc Dis. 2017; 27: 407-414 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar ].

Data concerning true hypoglycaemic incidence in insulin-treated patients with diabetes in real-world clinical practice are lacking in Germany. The aim of this analysis was to determine the incidence of hypoglycaemia experienced by the German cohort of patients enrolled in the global Hypoglycaemia Assessment Tool (HAT) study. This was a non-interventional, 6-month retrospective and 4-week prospective study using self-assessment questionnaires and patient diaries assessing patients aged 18 years in Germany, with type 1 diabetes (T1D) (n=811) or type 2 diabetes (T2D) (n=1619) treated with insulin for >12 months. The primary endpoint was the percentage of patients experiencing 1 hypoglycaemic event during the prospective observational period (4 weeks after baseline). Predictive and continuous factors (such as age, gender, duration of insulin use and HbA(1c)) contributing to hypoglycaemia risk were explored. During the prospective period, at least one hypoglycaemic event was reported by 81.3% of patients with T1D and 39.7% of patients with T2D, indicating that hypoglycaemia is a common acute complication among patients with insulin-treated diabetes. Severe hypoglycaemia was reported by 9.1% of patients with T1D and 5.4% of patients with T2D. Higher rates of any and severe hypoglycaemia were reported prospectively than retrospectively, regardless of diabetes type, indicating that patients retrospectively under-report hypoglycaemia. Prospective rates (events per patient-year) of any, nocturnal and severe hypoglycaemia were 80.3, 9.9 and 3.0 for T1D and 15.6, 2.4 and 1.1 for T2D, respectively. Given the potential for recall bias in retrospective reporting, this prospective assessment of hypoglycaemia appears more reliable than retrospective assessment.

Aims: To evaluate risk factors for severe hypoglycaemia (SH) in patients with type 1 diabetes (T1DM).Methods and Results: Retrospective observational and comparative study. All SH occurring between 2007 and 2014 in a German population (Lippe-Detmold) were captured. Characteristics of patients with T1DM and SH were compared with a control group being equivalent concerning age, diabetes duration, HbA1c, comorbidity, and beta-blocker treatment. SH was defined as a symptomatic event requiring treatment with intravenous glucose or glucagon administration and being confirmed by a blood glucose measurement of < 2.8 mmol/l. Predictive factors for SH were analysed by a multivariable regression model. As many as 405 cases of SH in T1DM occurred in 206 subjects; 50% of episodes were related to 31 patients who experienced >= 3 SH. Need for nursing care (OR 4.88), treatment with NPH (OR 3.68), and impaired hypoglycaemia awareness (OR 2.06) were the strongest risk factors for SH (all p < 0.05, all p(FDR)-adjusted < 0.10; false discovery rate (FDR)). Depression (OR 0.14), treatment with CSII (OR 0.39) and short-acting insulin analogues (OR 0.31) appeared to be protective (all p < 0.10; FDR-adjusted). The probability of SH onset was significantly higher in patients who had previously experienced recurrent SH episodes. beta-Blocker treatment did not appear to be a risk factor.Conclusion: The complex risk for SH in people with T1DM can be reduced by treatment with CSII and short-acting analogues. Future structures of diabetes care will be challenged by the need of treating increasingly geriatric subjects with T1DM having a high risk of SH. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

AimsTo determine the influence of daytime, weekdays and seasons on the frequency of severe hypoglycemia (SH) in a German population.MethodsProspective population-based observational study capturing all episodes of SH between 2007 and 2014 in the Lippe-Detmold area. SH was defined as a symptomatic event requiring treatment with intravenous glucose or administration of glucagon and being confirmed by a blood glucose measurement of <2.8mmol/l.ResultsA total of 1080 episodes of SH in 747 patients were registered. 37.5% of cases (405/1080) were related to T1DM, 51.9% (561/1080) to T2DM, 3.2% (35/1080) to pancreatic diabetes and 7.3% (79/1080) to non-diabetic individuals. In cases with T1DM we observed a significantly higher event rate of SH at weekends versus the rest of the week: 2.87 events/weekend-hour versus 2.15 events/weekday-hour (p=0.004), especially on Saturdays. We found significantly increased incidences of SH in spring (31.2%) and summer (26.7%) versus autumn (20.3%) and winter (21.8%). There were no corresponding significant seasonal variations of HbA1c and insulin doses. The seasonal distribution of SH in subjects with T2DM was balanced with no peak incidence at weekends.ConclusionsFor the risk of SH, time factors appear to contribute more substantially in individuals with T1DM than in patients with T2DM. The enhanced frequency of SH in patients with T1DM at weekends and in warm seasons was probably caused by short-term changes in behavior. Intensification of diabetes care and education with better adjustment of insulin doses in these susceptible periods could be an appropriate approach to prevent SH.

Aims: Severe hypoglycaemia (SH) may increase cardiovascular and all-cause mortality in patients with long-standing complicated diabetes. We investigated whether in patients with T2DM who had experienced SH individual morbidity and treatment targets had sufficiently been respected.