[Position paper: Open-source technology in the treatment of people living with diabetes mellitus-an Austrian perspective : Technology Committee of the Austrian Diabetes Association]. / Positionspapier: Open-source-Technologie in der Behandlung von Menschen mit Diabetes mellitus ­ eine österreichische Perspektive : Technologieausschuss der Österreichischen Diabetes Gesellschaft.

People living with diabetes mellitus can be supported in the daily management by diabetes technology with automated insulin delivery (AID) systems to reduce the risk of hypoglycemia and improve glycemic control as well as the quality of life. Due to barriers in the availability of AID-systems, the use and development of open-source AID-systems have internationally increased. This technology provides a necessary alternative to commercially available products, especially when approved systems are inaccessible or insufficiently adapted to the specific needs of the users. Open-source technology is characterized by worldwide free availability of codes on the internet, is not officially approved and therefore the use is on the individual's own responsibility. In the clinical practice a lack of expertise with open-source AID technology and concerns about legal consequences, lead to conflict situations for health-care professionals (HCP), sometimes resulting in the refusal of care of people living with diabetes mellitus. This position paper provides an overview of the available evidence and practical guidance for HCP to minimize uncertainties and barriers. People living with diabetes mellitus must continue to be supported in education and diabetes management, independent of the chosen diabetes technology including open-source technology. Check-ups of the metabolic control, acute and chronic complications and screening for diabetes-related diseases are necessary and should be regularly carried out, regardless of the chosen AID-system and by a multidisciplinary team with appropriate expertise.

Increased GH/IGF-I Axis Activity Relates to Lower Hepatic Lipids and Phosphor Metabolism.

CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is a leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/insulin-like growth factor I (IGF-I) excess, suggest an inverse relationship with intrahepatic lipid (IHL) content, less is known about the impact of the GH/IGF-I axis on IHL, lipid composition, and phosphor metabolites in individuals without disorders of GH secretion. OBJECTIVE: The aim was to investigate the relation between activity of the GH/IGF-I axis and IHL content and phosphor metabolism. METHODS: We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5.6%. The GH/IGF-I axis was evaluated in a fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index), and phosphate metabolites were analyzed by using 1H/31P magnetic resonance spectroscopy. RESULTS: In the overall cohort (40.6 ± 15 years; body mass index: 24.5 ± 3 kg/m2; IGF-I: 68.0 ± 17% upper limit of normal), fasting GH (R = -0.31; P = .02), GH during oral glucose tolerance test (R = -0.51; P < .01), and IGF-I (R = -0.28; P = .03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD than in controls (47.7 [22; 143] ng/mL/min vs 16.8 [7; 32] ng/mL/min; P = .003). GH/IGF-I axis activity correlated with lipid composition and with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. CONCLUSION: GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH axis activity is associated with higher IHL and an unfavorable lipid composition, probably mediated by changes in hepatic energy metabolism.

[Other specific types of diabetes and exocrine pancreatic insufficiency (update 2023)]. / Andere spezifische Diabetesformen und exokrine Pankreasinsuffizienz (Update 2023).

The heterogenous category "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e.g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART), checkpoint inhibitors), genetic forms of diabetes (e.g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down­, Klinefelter- and Turner Syndrome), pancreatogenic diabetes (e.g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2023)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2023).

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

[Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2023)]. / Diagnostik und Therapie des Typ 1 Diabetes mellitus (Update 2023).

This guideline summarizes diagnosis of type 1 diabetes, including accompanying autoimmune disorders, insulin therapy regimens and glycemic target values.

[Clinical practice recommendations for diabetes in pregnancy (Update 2023)]. / Gravidität bei vorbestehendem Diabetes (Update 2023).

In 1989 the St. Vincent Declaration aimed to achieve comparable pregnancy outcomes in women with diabetes and those with normal glucose tolerance. However, currently women with pre-gestational diabetes still feature a higher risk of perinatal morbidity and even increased mortality. This fact is mostly ascribed to a persistently low rate of pregnancy planning and pre-pregnancy care with optimization of metabolic control prior to conception. All women should be experienced in the management of their therapy and on stable glycemic control prior to conception. In addition, thyroid dysfunction, hypertension as well as the presence of diabetic complications should be excluded or treated adequately before pregnancy in order to decrease the risk for a progression of complications during pregnancy as well as maternal and fetal morbidity. Near normoglycaemia and HbA1c in the normal range are targets for treatment, preferably without the induction of frequent resp. severe hypoglycaemic reactions. Especially in women with type 1 diabetes mellitus the risk of hypoglycemia is high in early pregnancy, but it decreases with the progression of pregnancy due to hormonal changes causing an increase of insulin resistance. In addition, obesity increases worldwide and contributes to higher numbers of women at childbearing age with type 2 diabetes mellitus and adverse pregnancy outcomes. Intensified insulin therapy with multiple daily insulin injections and pump treatment are equally effective in reaching good metabolic control during pregnancy. Insulin is the primary treatment option. Continuous glucose monitoring often adds to achieve targets. Oral glucose lowering drugs (Metformin) may be considered in obese women with type 2 diabetes mellitus to increase insulin sensitivity but need to be prescribed cautiously due to crossing the placenta and lack of long-time follow up data of the offspring (shared decision making). Due to increased risk for preeclampsia in women with diabetes screening needs to be performed. Regular obstetric care as well as an interdisciplinary treatment approach are necessary to improve metabolic control and ensure the healthy development of the offspring.

[Gestational diabetes mellitus (Update 2023)]. / Gestationsdiabetes (GDM) (Update 2023).

Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset during pregnancy and is associated with increased feto-maternal morbidity as well as long-term complications in mothers and the offspring. Women detected to have diabetes early in pregnancy receive the diagnosis of overt, non-gestational, diabetes (glucose: fasting ≥ 126 mg/dl, spontaneous ≥ 200 mg/dl or HbA1c ≥ 6.5% before 20 weeks of gestation). GDM is diagnosed by an oral glucose tolerance test (oGTT) or increased fasting glucose (≥ 92 mg/dl). Screening for undiagnosed type 2 diabetes at the first prenatal visit is recommended in women at increased risk (history of GDM/pre-diabetes; malformation, stillbirth, successive abortions or birth weight > 4500 g previously; obesity, metabolic syndrome, age > 35 years, vascular disease; clinical symptoms of diabetes (e.g. glucosuria) or ethnic origin with increased risk for GDM/T2DM (Arab, South- and Southeast Asian, Latin American)) using standard diagnostic criteria. Performance of the oGTT (120 min; 75 g glucose) may already be indicated in the first trimester in high-risk women but is mandatory between gestational week 24-28 in all pregnant women with previous non-pathological glucose metabolism. Following WHO recommendations, which are based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, GDM is defined, if fasting venous plasma glucose is ≥ 92 mg/dl or 1 h ≥ 180 mg/dl or 2 h ≥ 153 mg/dl after glucose loading (international consensus criteria). In case of one pathological value a strict metabolic control is mandatory. After bariatric surgery we do not recommend to perform an oGTT due to risk of postprandial hypoglycemia. All women with GDM should receive nutritional counseling, be instructed in blood glucose self-monitoring and motivated to increase physical activity to moderate intensity levels-if not contraindicated (Evidence level A). If blood glucose levels cannot be maintained in the therapeutic range (fasting < 95 mg/dl and 1 h after meals < 140 mg/dl, Evidence level B) insulin therapy should be initiated as first choice (Evidence level A). Maternal and fetal monitoring is required in order to minimize maternal and fetal/neonatal morbidity and perinatal mortality. Regular obstetric examinations including ultrasound examinations are recommended (Evidence level A). Neonatal care of GDM offspring at high risk for hypoglycaemia includes blood glucose measurements after birth and if necessary appropriate intervention. Monitoring the development of the children and recommendation of healthy lifestyle are important issues to be tackled for the whole family. After delivery all women with GDM have to be reevaluated as to their glucose tolerance by a 75 g oGTT (WHO criteria) 4-12 weeks postpartum. Assessment of glucose parameters (fasting glucose, random glucose, HbA1c or optimally oGTT) are recommended every 2-3 years in case of normal glucose tolerance. All women have to be instructed about their increased risk of type 2 diabetes and cardiovascular disease at follow-up. Possible preventive meassures, in particular lifestyle changes as weight management and maintenance/increase of physical activity should be discussed (evidence level A).

[Diabetes mellitus, coronary artery disease and heart disease (Update 2023)]. / Diabetes mellitus, koronare Herzkrankheit und Herzinsuffizienz (Update 2023).

Diabetes mellitus, cardiovascular disease and heart failure are interacting dynamically. Patients being diagnosed with cardiovascular disease should be screened for diabetes mellitus. Enhanced cardiovascular risk stratification based on biomarkers, symptoms and classical risk factors should be performed in patients with preexisting diabetes mellitus. In patients with previously diagnosed arterosclerotic cardiovascular disease an agent proven to reduce major adverse cardiovascular events or cardiovascular mortality is recommended.

[Diagnosis and management of patients with diabetes and co-existing osteoporosis (Update 2023) : Common guideline of the Austrian Society for Bone and Mineral Research and the Austrian Diabetes Society]. / Diagnose und Management der Osteoporose bei Diabetes mellitus (Update 2023) : Gemeinsame Leitlinie der Österreichischen Gesellschaft für Knochen- und Mineralstoffwechsel und der Österreichischen Diabetes Gesellschaft.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. The identification and management of fracture risk in these patients remains challenging. This manuscript explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated areal bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (FRAX) in these patients. It further reviews the impact of diabetes drugs on bone tissue as well as the efficacy of osteoporosis treatments in this population. An algorithm for the identification and management of diabetic patients at increased fracture risk is proposed.

HbA1c and Glucose Management Indicator Discordance Associated with Obesity and Type 2 Diabetes in Intermittent Scanning Glucose Monitoring System.

Glucose management indicator (GMI) is frequently used as a substitute for HbA1c, especially when using telemedicine. Discordances between GMI and HbA1c were previously mostly reported in populations with type 1 diabetes (T1DM) using real-time CGM. Our aim was to investigate the accordance between GMI and HbA1c in patients with diabetes using intermittent scanning CGM (isCGM). In this retrospective cross-sectional study, patients with diabetes who used isCGM >70% of the time of the investigated time periods were included. GMI of four different time spans (between 14 and 30 days), covering a period of 3 months, reflected by the HbA1c, were investigated. The influence of clinical- and isCGM-derived parameters on the discordance was assessed. We included 278 patients (55% T1DM; 33% type 2 diabetes (T2DM)) with a mean HbA1c of 7.63%. The mean GMI of the four time periods was between 7.19% and 7.25%. On average, the absolute deviation between the four calculated GMIs and HbA1c ranged from 0.6% to 0.65%. The discordance was greater with increased BMI, a diagnosis of T2DM, and a greater difference between the most recent GMI and GMI assessed 8 to 10 weeks prior to HbA1c assessment. Our data shows that, especially in patients with increased BMI and T2DM, this difference is more pronounced and should therefore be considered when making therapeutic decisions.

Increased ATP synthesis might counteract hepatic lipid accumulation in acromegaly.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent 31P/1H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Ectopic Cushing's syndrome in a patient with inferior petrosal sinus sampling indicating pituitary-dependent ACTH secretion.

In an unclear case of Cushing's syndrome, IPSS identifies the origin of ACTH secretion, and together with MRI enables the localization of an ectopic corticotroph adenoma in the parasellar or cavernous sinuses region.

Plasma renin levels are associated with cardiac function in primary adrenal insufficiency.

BACKGROUND: Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease. The role of MC replacement is not known. Therefore, we assessed whether renin concentrations during routine GC and MC substitution therapy are associated with heart function and morphology. METHODS: Thirty two patients with primary AI were included in a cross-sectional case-control study. In total, 17 patients and 34 healthy controls (age: 48 ± 12 vs. 46 ± 18 years; BMI: 23 ± 3 vs. 24 ± 3 kg/m2) underwent magnetic resonance spectroscopy and imaging measurements to assess cardiac function, morphology, ectopic lipids, and visceral/subcutaneous fat mass. Patients were divided according to their actual plasma renin concentration at the study visit (Actual-Reninlow vs. Actual-Reninhigh) and their median plasma renin concentration of previous visits (Median-Reninlow vs. Median-Reninhigh). RESULTS: Ejection fraction was higher (67 ± 5 vs. 55 ± 3%; p = 0.001) and left ventricular mass was lower (60 ± 9 vs. 73 ± 10 g/m2; p = 0.025) in Actual-Reninhigh. Median-Reninhigh was associated with lower cardiac mass (64 ± 9 vs. 76 ± 11 g/m2; p = 0.029). Blood pressure, glucose, and lipid metabolism, as well as ectopic lipid content, pericardial fat mass, and visceral/subcutaneous fat were not different between the groups. Compared with controls, ejection fraction was significantly lower in patients with AI (56 ± 4 vs. 63 ± 8%; p = 0.019). No differences were found in patients with ≤20 mg compared with >20 mg of hydrocortisone per day. CONCLUSIONS: Higher renin concentrations are associated with more favorable cardiac function and morphology in patients with primary AI.

Identifying a disease-specific renin-angiotensin-aldosterone system fingerprint in patients with primary adrenal insufficiency.

BACKGROUND: In patients suffering from primary adrenal insufficiency (AI) mortality is increased despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, mainly due to an increased cardiovascular risk. Since activation of the renin-angiotensin-aldosterone system (RAAS) plays an important role in the modulation of cardiovascular risk factors, we performed in-depth characterization of the RAAS activity. METHODS: Eight patients with primary AI (female = 5; age: 56 ± 21 years; BMI: 22.8 ± 2 kg/m2; mean blood pressure: 140/83 mmHg; hydrocortisone dose: 21.9 ± 5 mg/day; fludrocortisone dose: 0.061 ± 0.03 mg/day) and eight matched healthy volunteers (female = 5; age: 52 ± 21 years; BMI: 25.2 ± 4 kg/m2; mean blood pressure:135/84 mmHg) were included in a cross-sectional case-control study. Angiotensin metabolite profiles (RAS-fingerprints) were performed by liquid chromatography mass spectrometry. RESULTS: In patients suffering from primary AI, RAAS activity was highly increased with elevated concentrations of renin concentration (P = 0.027), angiotensin (Ang) I (P = 0.022), Ang II (P = 0.032), Ang 1-7 and Ang 1-5. As expected, aldosterone was not detectable in the majority of AI patients, resulting in a profoundly suppressed aldosterone-to-AngII ratio (AA2 ratio, P = 0.003) compared to controls. PRA-S, the angiotensin-based marker for plasma renin activity, correlated with plasma renin activity (r = 0.983; P < 0.01) and plasma renin concentration (r = 0.985; P < 0.001) and was significantly increased in AI patients. CONCLUSIONS: AI is associated with a unique RAAS profile characterized by the absence of aldosterone despite strongly elevated levels of angiotensin metabolites, including the potent vasoconstrictor AngII. Despite state-of-the-art hormone replacement therapy, the RAAS remains hyperactivated. The contribution of Ang II in cardiovascular diseases in AI patients as well as a potential role for providing useful complementary information at diagnosis and follow up of AI should be investigated in future trials.

MARKEDLY DELAYED INSULIN SECRETION AND A HIGH RATE OF UNDETECTED OVERT DIABETES CHARACTERIZE GLUCOSE METABOLISM IN ADULT PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION.

OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). METHODS: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. RESULTS: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. CONCLUSION: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism. ABBREVIATIONS: AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.

Reduced hepatocellular lipid accumulation and energy metabolism in patients with long standing type 1 diabetes mellitus.

The prevalence of obesity and metabolic syndrome increases in patients with type 1 diabetes mellitus (T1DM). In the general population this is linked with ectopic lipid accumulation in liver (HCL) and skeletal muscle (IMCL), representing hallmarks in the development of insulin resistance. Moreover, hepatic mitochondrial activity is lower in newly diagnosed patients with T1DM. If this precedes later development of diabetes related fatty liver disease is currently not known. This study aims to investigate energy metabolism in liver (kATP) and skeletal muscle (kCK) and its impact on HCL, IMCL, cardiac fat depots and heart function in 10 patients with long standing T1DM compared to 11 well-matched controls by 31P/1H magnetic resonance spectroscopy. HCL was almost 70% lower in T1DM compared to controls (6.9 ± 5% vs 2.1 ± 1.3%; p = 0.030). Also kATP was significantly reduced (0.33 ± 0.1 s-1 vs 0.17 ± 0.1 s-1; p = 0.018). In T1DM, dose of basal insulin strongly correlated with BMI (r = 0.676, p = 0.032) and HCL (r = 0.643, p = 0.045), but not with kATP. In the whole cohort, HCL was significantly associated with BMI (r = 0.615, p = 0.005). In skeletal muscle kCK was lower in patients with T1DM (0.25 ± 0.05 s-1 vs 0.31 ± 0-04 s-1; p = 0.039). No significant differences were found in IMCL. Cardiac fat depots as well as heart function were not different. Our results in patients with long standing T1DM show that HCL is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle.

Overweight and obesity in type 1 diabetes equal those of the general population.

BACKGROUND: The obesity epidemic might affect patients with type 1 diabetes (T1DM), historically described as lean and insulin-sensitive subjects. Insulin resistance in T1DM might increase diabetic complications, especially cardiovascular disease. Therefore, the body mass index (BMI) in T1DM patients was analyzed in comparison to the general population. Furthermore, the impact of increased BMI on glycemic control and metabolic alterations was assessed. METHODS: Body mass index was compared overall and among four different age groups between adult T1DM (n = 186), treated in the outpatient clinic between 2014 and 2016, and 15,771 individuals from the general population who took part at an Austrian health survey. Furthermore, parameters of glycemic control, lipid state, blood pressure and additional medication were compared between T1DM with a BMI under or above 27.5 kg/m2. RESULTS: Patients with T1DM had significantly higher BMI values than general population (25.9 ± 4.2 kg/m2 vs. 25.3 ± 4.5 kg/m2; p = 0.027), controlling for age group; however, prevalence of overweight (39.8% vs. 33.1%) and obesity (14% vs. 13.8%) was not significantly different. Within the 4 age groups only T1DM patients between 30 years and 49 years old had significantly higher BMI values compared to the general population (mean difference 1.9 kg/m2; 95% confidence interval, CI: 0.96-2.83 kg/m2). In T1DM, a BMI ≥27.5 kg/m2 was associated with increased rates of hypertension, dyslipidemia, microalbuminuria, and increased insulin demand, whereas glycemic control was not affected. CONCLUSIONS: In contrast to common descriptions T1DM patients have a higher BMI compared to the general population. Rates of overweight and obesity in T1DM equal those of the general population. Therefore, it is concluded that the obesity epidemic has reached T1DM patients and "double diabetes" might be an entity to consider.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.

BACKGROUND: Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE: To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS: The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

CONTEXT: Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. CASE DESCRIPTION: Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A, suggesting a role of this gene in the pituitary adenoma development. CONCLUSION: PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients.

Heart, lipids and hormones.

Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.