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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., (© 2024. The Author(s).)

Aims: To analyse predictors for continuous glucose monitoring (CGM) use in people with diabetes aged ≥60 years using insulin therapy and to assess the rates of CGM use during recent years (2019-2021)., Research Design and Methods: Prospective study including 6849 individuals with diabetes and insulin therapy (type 2 diabetes: n = 5320; type 1 diabetes: n = 1529) aged ≥60 years. Data from 129 treatment centres were retrieved from the Diabetes Prospective Follow-up Registry (DPV) in March 2023., Results: Sensor use in individuals aged ≥60 years has increased in type 1 (2019: 28%, 2020: 39%, 2021: 45%) and type 2 diabetes (2019: 10%, 2020: 16%, 2021: 18%). Predictors for sensor use in older individuals with type 1 diabetes are younger age and CSII use (p < 0.001). Predictors in older individuals with type 2 diabetes are younger age, longer diabetes duration, higher BMI and CSII use (p < 0.001)., Conclusions: CGM has become more common in older adults with diabetes and will presumably increase further. Age is a predictor for sensor use in older adults with diabetes. Age-related physical barriers and insufficient usability of devices, lack of interest in technologies, but possibly also effects of prejudice on the grounds of age may contribute to this finding., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: Diabetic foot ulcer (DFU) is a leading cause of lower limb amputations in people with diabetes. This study was aimed to retrospectively analyze factors affecting DFU using real-world data from a large, prospective central-European diabetes registry (DPV [Diabetes-Patienten-Verlaufsdokumentation])., Materials and Methods: We matched adults with type 1 (T1D) or type 2 diabetes (T2D) and DFU to controls without DFU by diabetes type, age, sex, diabetes duration, and treatment year to compare possible risk factors. Cox regression was used to calculate hazard ratios for amputation among those with DFU., Results: In our cohort (N = 63 464), male sex, taller height, and diabetes complications such as neuropathy, peripheral artery disease, nephropathy, and retinopathy were associated with DFU (all p < .001). Glycated hemoglobin (HbA1c) was related to DFU only in T1D (mean with 95% confidence interval [CI]: 7.8 [6.9-9.0] % vs 7.5 [6.8-8.5] %, p < .001). High triglycerides and worse low-density lipoprotein/high-density lipoprotein ratio were also associated with DFU in T1D, whereas smoking (14.7% vs 13.1%) and alcohol abuse (6.4% vs 3.8%, both p < .001) were associated with DFU in T2D. Male sex, higher Wagner grades, and high HbA1c in both diabetes types and insulin use in T2D were associated with increased hazard ratios for amputations., Conclusions: Sex, body height, and diabetes complications were associated DFU risk in adults with T1D and T2D. Improvement in glycemic control and lipid levels in T1D and reduction of smoking and drinking in T2D may be appropriate interventions to reduce the risk for DFU or amputations., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection may negatively affect glucose metabolism. This study aims to assess glucose levels, prevalence of gestational diabetes mellitus (GDM) and perinatal outcome in women with history of COVID-19. To this purpose, a group of 65 patients with history of COVID-19 and 94 control patients were retrospectively recruited among pregnant women who attended the pregnancy outpatient department between 01/2020 and 02/2022. Glucose data from an oral glucose tolerance test (OGTT), GDM status and obstetric complications were assessed. We observed no differences in average ( p = 0.37), fasting ( p = 0.62) or post-load glucose concentrations (60 min: p = 0.19; 120 min: p = 0.95) during OGTT. A total of 15 (23.1%) women in the COVID-19 group and 18 (19.1%) women in the control group developed GDM ( p = 0.55). Moreover, caesarean section rate, weight percentiles and pregnancy outcomes were comparable between the groups ( p = 0.49). In conclusion, in this study we did not identify a possible impact of COVID-19 on glucose metabolism in pregnancy, especially with regard to glucose concentrations during the OGTT and prevalence of GDM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Monod, Kotzaeridi, Eppel, Linder, Bozkurt, Hösli, Göbl and Tura.)

Aims: Non-invasive hepatic steatosis indices can be used to assess the risk for metabolic (dysfunction) associated fatty liver disease (MAFLD). This may be helpful to detect metabolic disorders in pregnancy, specifically gestational diabetes (GDM). We aimto examine the association of these indices with parameters of glucose metabolism., Methods: 109 women underwent a metabolic characterization at 16 weeks of gestation andwere classified according to the fatty-liver index (FLI) andhepatic-steatosis index (HSI) into low (G1), intermediate (G2) and high risk (G3). At 26 weeks, participants received an oral glucose tolerance test (OGTT) to assess insulin action, β-cell function and GDM status., Results: Both MAFLD indices wereassociated with impaired insulin sensitivityand compensatory increase of insulin release. G3 groups showedimpaired insulin action. The higher circulating insulin concentrations were not able to compensate for insulin resistance in women with higher MAFLD scores, resulting in an increased risk of GDM(OR: 1.05, 95% CI 1.03 to 1.08, p < 0.001 for FLI). MAFLD scores were associated with fetal overgrowth., Conclusions: Maternal MAFLD represents a high-risk obstetric condition. Hepatic steatosis indices are associated with impaired glucose regulation and may provide a useful tool for early risk assessment for impaired glucose metabolism., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Insulin replacement in type 1 diabetes mellitus (T1DM) needs intensified treatment, which can either be performed by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). This retrospective analysis of a real-world scenario aimed to evaluate whether glycaemic and cardiovascular risk factors could be controlled with CSII outclass MDI as suggested by recent evidence. Data from patients with either insulin pump (n=68) or injection (n=224) therapy at an Austrian tertiary care centre were analysed between January 2016 and December 2017. There were no significant differences with regard to the latest glycosylated hemoglobin, cardiovascular risk factor control or diabetes-associated late complications. Hypoglycaemia was less frequent (P<0.001), sensor-augmented therapy was more common (P=0.003) and mean body mass index (BMI) was higher (P=0.002) with CSII treatment. This retrospective analysis of real-world data in T1DM did not demonstrate the superiority of insulin pump treatment with regard to glycaemic control or cardiovascular risk factor control.

Introduction: It is of current interest to assess eligibility of hemoglobin A1c (HbA1c) as a screening tool for earlier identification of women with risk for more severe hyperglycemia in pregnancy but data regarding accuracy are controversial. We aimed to evaluate if HbA1c mirrors pathophysiological precursors of glucose intolerance in early pregnancy that characterize women who develop gestational diabetes mellitus (GDM)., Research Design and Methods: 220 pregnant women underwent an HbA1c measurement as well as an oral glucose tolerance test (OGTT) with multiple measurements of glucose, insulin and C-peptide for evaluation of insulin sensitivity and beta-cell function at 16th gestational week (IQR: 14-18). Clinical follow-ups were performed until end of pregnancy., Results: Increased maternal HbA1c ≥5.7% (39 mmol/mol) corresponding to pre-diabetes outside of pregnancy was associated with altered glucose dynamics during the OGTT. Pregnancies with early HbA1c ≥5.7% showed higher fasting (90.4±13.2 vs 79.7±7.2 mg/dL, p<0.001), mean (145.6±31.4 vs 116.2±21.4 mg/dL, p<0.001) as well as maximum glucose concentrations and tended to a delay in reaching the maximum glucose level compared with those with normal-range HbA1c (186.5±42.6 vs 147.8±30.1 mg/dL, p<0.001). Women with increased HbA1c showed impaired beta-cell function and differences in disposition index independent of body mass index status. We observed a high specificity for the HbA1c cut-off of 5.7% for GDM manifestation (0.96, 95% CI 0.91 to 0.98) or need of glucose-lowering medication (0.95, 95% CI 0.90 to 0.98) although overall predictive accuracy was moderate to fair. Further, elevated HbA1c was associated with higher risk for delivering large-for-gestational-age infants, also after adjustment for GDM status (OR 4.4, 95% CI 1.2 to 15.0, p=0.018)., Conclusions: HbA1c measured before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Bariatric surgery confers a high risk for nutritional deficiencies that could affect physiologic adaptation of lipids during pregnancy. We aimed to evaluate differences in serum lipids in pregnant women after bariatric surgery compared to obese and lean mothers., Methods: 25 women with a history of Roux-en-Y gastric bypass (RYGB), 19 obese and 19 normal-weight controls were included at the 24th-28th gestational week for determination of fasting lipids with follow-up in a subgroup after delivery. Data on neonatal biometry were additionally assessed., Results: Women after RYGB showed lower total-cholesterol (TC), low-density lipoprotein C (LDL-C), non-high-density lipoprotein C (non-HDL-C) and triglycerides (TG) compared to obese mothers. Despite their higher BMI, women after RYGB showed lower TC, LDL-C and non-HDL-C than normal-weight mothers. Ultrasensitive C-reactive protein was lower in RYGB mothers than in obese ones, reaching values of lean controls. Differences remained unchanged in BMI-matched comparison. Birth weight percentiles of RYGB offspring were associated with maternal TC (r = 0.59, p = 0.021), LDL-C (r = 0.71, p = 0.003), non-HDL (r = 0.59, p = 0.021) but not HDL-C or TG. After delivery, lipids decreased in all women; however, TC and LDL-C showed more attenuated decline in mothers after RYGB than control women., Conclusion: Pregnancies after RYGB show alterations of physiologic patterns in lipid profile. Further studies are required to evaluate whether imbalances in maternal lipids constitute a risk for abnormal fetal growth in this special cohort., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB., Methods: In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1 H-magnetic resonance spectroscopy ( 1 H-MRS)., Results: RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group., Conclusion: GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS., Methods: An oral glucose tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1 H-magnetic resonance spectroscopy and imaging., Results: Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p = 0.001, fasting plasma glucose: p < 0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population., Conclusion: PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.

Aim: There is scarce information on associations of adipokines, and concurrent glucose disposal during early pregnancy as performance of oral glucose tolerance is uncommon before 24th gestational week. We sought to examine associations of leptin and adiponectin to insulin sensitivity already at early pregnancy before recommended screening for GDM and to describe trajectories of adiponectin in relation to GDM status., Methods: 216 pregnant women were prospectively included at 16th (IQR: 14-18) gestational week (GW) for fasting adiponectin and leptin with subsequent OGTT testing for evaluation of insulin sensitivity and β -cell function. Follow-ups of adiponectin were performed at further four visits until 8-12 weeks after delivery., Results: In early pregnancy, differences in adiponectin and leptin were significant between GDM women ( n = 82) and controls ( n = 134), whereby those with early GDM (<21st week, n = 49) showed more distinguishing levels (adiponectin: 8.5 ± 3.8 versus 10.4 ± 4.4  μ g/ml, p = 0.004; leptin 93.4 ± 38.5 versus 78.0 ± 39.2  μ g/ml, p = 0.005). Both adipokines were significantly associated with insulin sensitivity and β -cell function. Their attribution for GDM prediction was moderate to fair and more enhanced in early GDM. Trajectories of adiponectin remained constantly lower in GDM women, whereas dynamics in controls showed initially increased concentrations with decreasing tendency until 3rd trimester. After delivery, low adiponectin was associated with glucose dysregulation., Conclusion: Associations of adiponectin and leptin with features of deteriorated glucose metabolism at early gestation may be indicative for the endocrine involvement of adipose tissue in the manifestation of GDM and thus predictive for later impairments in metabolic flexibility in women at risk.

Aims/hypothesis: Roux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB., Methods: Sixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery., Results: We observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10 -4  min -1 [pmol/l] -1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB., Conclusions/interpretation: Pregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.

Background: Patients with hyperlipidemia are at high risk for developing a fatty liver. The fatty liver index (FLI) is a noninvasive and well-established method for the estimation of a fatty liver. However, little is known about the metabolic characterization of nondiabetic treated patients with hyperlipidemia who have different risk levels for a fatty liver., Methods: In this study, 74 nondiabetic patients with hyperlipidemia were divided into 3 groups according to their fatty liver index. A comparison of metabolic characteristics was done. These characteristics included intima media thickness (IMT) and nutritional habits, which were further divided into FLI subgroups with low, intermediate, and high risk for a fatty liver., Results: Patients with hyperlipidemia, with a high risk for a fatty liver (FLI ≥ 60), had subclinical elevations in parameters of carbohydrate metabolism (insulin, fasting plasma glucose, C-peptide) including a higher insulin resistance (quantitative insulin sensitivity check index, QUICKI) compared to lower FLI groups. These patients also presented a higher risk for a metabolic syndrome (p = 0.018), as well as an adverse lipid profile (e.g., high-density lipoprotein [HDL] cholesterol, triglycerides [TG]-HDL ratio). FLI group 3 was characterized by significantly lower levels of omega-3 fatty acids (p = 0.048)., Conclusion: The fatty liver index relates to diabetes-specific parameters and an adverse lipid profile and is an appropriate index for risk evaluation of metabolic syndrome.

Aims/hypothesis: A history of gastric bypass surgery can influence the results of the OGTT recommended during pregnancy. Therefore, we compared OGTT glucose kinetics and pregnancy outcome between pregnant gastric bypass patients and BMI-matched, lean and obese controls., Methods: Medical records were used to collect data on glucose measurements during the 2 h 75 g OGTT as well as on pregnancy and fetal outcome for 304 women (n = 76 per group, matched for age and date of delivery)., Results: Women after bariatric surgery had lower fasting glucose levels compared with lean, obese and BMI-matched controls, and showed altered postprandial glucose kinetics, including a rise at 60 min followed by hypoglycaemia with serum glucose of <3.34 mmol/l (which occurred in 54.8%). Moreover, their risk of pre-eclampsia or gestational hypertension was reduced, with an increased risk of delivering small for gestational age infants., Conclusions/interpretation: Alternative strategies to accurately define impaired glucose metabolism in pregnancies after bariatric surgery should be explored.

Aims: There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated., Methods: A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy., Results: Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index., Conclusions: Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile.

Growing challenges of maternal obesity necessitate to focus metabolic management on alternative factors than glycaemia. The objective is to assess longitudinal changes in lipids and inflammatory parameters during pregnancies stratified by pregestational BMI. Therefore, 222 pregnant women (normal-weight BMI < 25: n = 91 (41%), overweight BMI 25-29.9: n = 69 (31%), obese BMI ≥ 30: n = 62 (28%)) underwent a detailed metabolic characterization including fasting lipids and glucometabolic parameters at <21(st) gestational week (GW) with follow-up assessments at further three visits (24-28(th) GW, 32-34(th) GW, >36(th) GW). Overweight and obesity was related to dyslipidemia already at baseline, i.e. elevated triglycerides (TG, p < 0.001), decreased high-density-lipoprotein-C (p = 0.009) and increased ultrasensitive-c-reactive-protein (usCRP, p < 0.001) independent of gestational diabetes prevalence. Trajectories of lipids during pregnancy progress revealed an unexpected less pronounced increase in TG, low-density-lipoprotein-C and total-cholesterol in overweight/obese women. usCRP remained associated with higher BMI throughout pregnancy showing no time-dependent longitudinal changes. Newborns of obese/overweight women were affected by higher birth-weight percentiles. Regarding lipids only maternal TG showed tendency for relation to prevalence of large-for-gestational-age offspring, particularly at the end of pregnancy (p = 0.048). Overweight and obese women show significant differences in trajectories of lipids during pregnancy that distinguish them from normal-weight women. Further studies should evaluate if targeting lipid metabolism could improve clinical management of maternal obesity.

Background: Impaired glucose regulation (IGR) and hyperlipidemia (HL) are associated with an increased risk of developing a cardiovascular disease. Hyperlipidemic patients were shown to bear a greater risk for an increased intima media thickness (IMT). However little is known about differences between treated hyperlipidemic patients (HL) with normal (NGR) or impaired (IGR) glucose regulation., Methods: We performed a cross-sectional study, involving 96 non-diabetic HL patients with IGR (fasting plasma glucose of ≥ 100 mg/dl and < 126 mg/dl or/and HbA1c-level of ≥ 5.7 and < 6.5 %) or with NGR (HbA1c-level of < 5.7 % and a fasting glucose < 100 mg/dl). We compared metabolic characteristics and the IMT between the two groups. Insulin sensitivity in fasting conditions was described by HOMA-IR and QUICKI., Results: HL-IGR patients were older (57.6 ± 10.4 vs. 49.1 ± 8.7, p < 0.001), had higher carotid IMT measurements (IMT average: 0.68 ± 0.14 vs. 0.60 ± 0.09, p = 0.002; IMT right: 0.67 ± 0.15 vs. 0.60 ± 0.10, p = 0.013; IMT left: 0.63 vs. 0.57, p = 0.009), as well as a higher chance to exceed a cut-off value of ≥ 0.8 mm or insignificant stenosis within this investigation (OR: 3.9, 95 % CI: 1.15-13.22, p = 0.029) compared to HL-NGR-patients. Furthermore HL-IGR patients were characterised by a higher waist circumference (100.6 ± 10.1 vs. 91.6 ± 13.3, p < 0.001), higher fasting plasma glucose-levels (100.1 ± 10.8 vs. 88.1 ± 6.6, p < 0.001), higher HbA1c concentrations (5.8 ± 0.33 vs. 5.3 ± 0.24, p < 0.001) and C-peptide levels (2.70 vs. 2.10, p = 0.012). Age and CVD status were in general the only two variables which independently explained IMT., Conclusion: Our study showed that among patients with treated hyperlipidemia the presence of IGR characterised subjects who were older and had a significantly higher risk for an increased IMT compared with those maintaining NGR. Further studies are necessary to evaluate if this specific subpopulation with IGR can benefit from a more strict multifactorial management and perhaps from an additional early antihyperglycaemic treatment.

Objective . The aim of this study was to evaluate sex specific differences of metabolic and clinical characteristics of treated hyperlipidemic men and women (HL-men and HL-women). Methods . In this study vascular and metabolic characteristics of 35 HL-women and 64 HL-men were assessed. In addition a sex specific analysis of metabolic and nutritional habits of HL-patients with prediabetes (HL-IGR) was done. Results . HL-women were older and had favourable concentrations of high density lipoprotein cholesterol (HDL-cholesterol), triglycerides (TG), and triglyceride/HDL-cholesterol ratio (TG/HDL-ratio) but were also shown to have higher concentrations of lipoprotein-a compared to HL-men. HL-men were characterized as having higher levels of liver-specific parameters and body weight as well as being more physically active compared to HL-women. Brain natriuretic peptide (pro-BNP) was higher in HL-women than HL-men, while no differences in metabolic syndrome and glycemic parameters were shown. HL-IGR-women were also older and still had a better profile of sex specific lipid parameters, as well as a lower body weight compared to HL-IGR-men. No differences were seen in vascular parameters such as the intima media thickness (IMT). Conclusion . HL-women were older and had overall more favourable concentrations of lipid parameters and liver enzymes but did not differ regarding vascular morphology and insulin sensitivity compared to HL-men of comparable body mass index (BMI)., Competing Interests: The authors have no competing interests.

Background/aims: Intrauterine exposure to hyperglycemia might impact the risk for future metabolic deteriorations. The aim was to characterize the association between different adipokines and neuropeptides and insulin resistance and BMI-SDS in children affected by diabetes during pregnancy., Methods: 76 children (mean age: 6 years, male:female = 36:40) born to mothers with gestational or pregestational diabetes and nondiabetic women were consecutively included for clinical assessments comprising anthropometrics and metabolic characterization [2-hour glucose tolerance test, leptin, peptide YY (PYY), neuropeptide Y (NPY), ghrelin, growth differentiation factor 15 (GDF-15), and adiponectin]., Results: The level of insulin resistance was associated with BMI-SDS (p < 0.001), leptin (p < 0.001), ghrelin (p = 0.002), age (p < 0.002) and negatively with GDF-15 (p = 0.005). BMI-SDS, leptin and GDF-15 were shown to have independent effects on insulin resistance by using a multiple regression model (additionally including age, and maternal diabetes status), whereas ghrelin lost significance (p = 0.345). No differences were present in adipokines and insulin resistance when children were evaluated by maternal glucometabolic status. However, we observed more strengthened associations between insulin resistance and covariates BMI-SDS and leptin in offspring of diabetic pregnancies., Conclusions: Young children with elevated BMI or leptin are affected by higher indices of insulin resistance, particularly those who were born to mothers with diabetes during pregnancy. The impact of this special risk constellation should be considered in future studies., (© 2016 S. Karger AG, Basel.)

This paper aims to introduce penalized estimation techniques in clinical investigations of diabetes, as well as to assess their possible advantages and limitations. Data from a previous study was used to carry out the simulations to assess: a) which procedure results in the lowest prediction error of the final model in the setting of a large number of predictor variables with high multicollinearity (of importance if insulin sensitivity should be predicted) and b) which procedure achieves the most accurate estimate of regression coefficients in the setting of fewer predictors with small unidirectional effects and moderate correlation between explanatory variables (of importance if the specific relation between an independent variable and insulin sensitivity should be examined). Moreover a special focus is on the correct direction of estimated parameter effects, a non-negligible source of error and misinterpretation of study results. The simulations were performed for varying sample size to evaluate the performance of LASSO, Ridge as well as different algorithms for Elastic Net. These methods were also compared with automatic variable selection procedures (i.e. optimizing AIC or BIC).We were not able to identify one method achieving superior performance in all situations. However, the improved accuracy of estimated effects underlines the importance of using penalized regression techniques in our example (e.g. if a researcher aims to compare relations of several correlated parameters with insulin sensitivity). However, the decision which procedure should be used depends on the specific context of a study (accuracy versus complexity) and moreover should involve clinical prior knowledge.

Early reexamination of carbohydrate metabolism via an oral glucose tolerance test (OGTT) is recommended after pregnancy with gestational diabetes (GDM). In this report, we aimed to assess the dominant patterns of dynamic OGTT measurements and subsequently explain them by meanings of the underlying pathophysiological processes. Principal components analysis (PCA), a statistical procedure that aims to reduce the dimensionality of multiple interrelated measures to a set of linearly uncorrelated variables (the principal components) was performed on OGTT data of glucose, insulin and C-peptide in addition to age and body mass index (BMI) of 151 women (n = 110 females after GDM and n = 41 controls) at 3-6 mo after delivery. These components were explained by frequently sampled intravenous glucose tolerance test (FSIGT) parameters. Moreover, their relation with the later development of overt diabetes was studied. Three principal components (PC) were identified, which explained 71.5% of the variation of the original 17 variables. PC1 (explained 47.1%) was closely related to postprandial OGTT levels and FSIGT-derived insulin sensitivity (r = 0.68), indicating that it mirrors insulin sensitivity in the skeletal muscle. PC2 (explained 17.3%) and PC3 (explained 7.1%) were shown to be associated with β-cell failure and fasting (i.e., hepatic) insulin resistance, respectively. All three components were related with diabetes progression (occurred in n = 25 females after GDM) and showed significant changes in long-term trajectories. A high amount of the postpartum OGTT data is explained by principal components, representing pathophysiological mechanisms on the pathway of impaired carbohydrate metabolism. Our results improve our understanding of the underlying biological processes to provide an accurate postgestational risk stratification., (Copyright © 2015 the American Physiological Society.)

Context: Appropriate risk stratification is essential in gestational diabetes (GDM) diagnosis to optimize therapeutic strategies during pregnancy. However, there are sparse data related to the newly recommended International Association of Diabetes and Pregnancy Study Groups criteria and their use in early pregnancy., Objective: This study sought to evaluate clinical and pathophysiological characteristics less up to gestational week (GW) 21 in women with early and late GDM onset., Design and Setting: This was a prospective study conducted at the Medical University of Vienna., Patients and Interventions: Pregnant women (n = 211) underwent an oral glucose tolerance test at 16 GW (interquartile range, 14-18 wk) with multiple measurements of glucose, insulin, and C-peptide for evaluation of insulin sensitivity and ß-cell function in addition to detailed obstetrical risk assessment. Clinical followups were performed until end of pregnancy., Main Outcome Measure: We performed a metabolic characterization of early-onset GDM., Results: Of 81 women, 49 (23%) showed early (GDMEarly ≤ 21 GW) and 32 (15%) later manifestation (GDMLate ≥ 24 GW) whereas 130 (62%) remained normal-glucose-tolerant (NGT). In contrast with GDMLate, GDMEarly were affected by decreased insulin sensitivity (GDMEarly vs NGT, P < .001; GDMEarlyvs GDMLate, P < .001; GDMLate vs NGT, P = .410). However, both early and late manifested subjects showed impairments in ß-cell function. GDMEarly showed highest levels of preconceptional and actual body mass index (BMI), which was related to fasting glucose (r = 0.42, P < .001) and particularly insulin sensitivity (r = -0.51, P < .001). Differences in glucose disposal between the subgroups remained constant in multivariable analysis including the strongest risk factors for GDM, ie, age, history of GDM, and BMI in our population., Conclusions: Early manifestation of GDM is affected by insulin resistance that is partly explained by higher degree in obesity. However, ß-cell dysfunction was also detectable in GDMLate, indicating defective compensatory mechanisms emerging already in early pregnancy.

Background: History of gestational diabetes mellitus (GDM) identifies a very young population of females predisposed for type 2 diabetes and cardiovascular disease. Endothelial dysfunction might represent a shared precursor of both disorders. Hence, this study aimed to characterize endothelial biomarkers in relation to impaired insulin sensitivity and progression to overt diabetes early after index pregnancy., Methods: 108 women with previous GDM and 40 controls were included three to six months after delivery and underwent specific metabolic assessments including a frequently sampled intravenous glucose tolerance test and an oral glucose tolerance test. Diabetes progression was assessed in females with pGDM over 10 years of follow-up. Circulating sICAM-1 (intracellular-adhesion-molecule-1), sVCAM-1 (vascular-cell-adhesion-molecule-1) and sE-selectin, representing biomarkers of endothelial dysfunction were assessed at baseline and annually over five years., Results: Endothelial biomarkers were significantly associated with insulin sensitivity (sICAM-1: r = -0.23, p = 0.009; sVCAM-1: r = -0.22, p = 0.011; sE-selectin: r = -0.21, p = 0.018) as well as with GDM status and parameters of subtle inflammation. Analysis of long-term trajectories revealed constantly elevated sICAM-1 (p = 0.033) and sE-selectin (p = 0.007) in 25 subjects with diabetes progression. Accordingly, sE-selectin levels at the early post partum visit predicted a later development of the disease (HR =1.02 95%CI 1.01 to 1.04, p = 0.013), however, this was attenuated after adjustment for BMI., Conclusions: Elevated circulating markers of endothelial dysfunction in young females with GDM history might reflect an early stage on the pathway to the manifestation of future cardiometabolic disorders. Timely identification of women at high risk and optimization of follow-up management might provide an opportunity to prevent disease progression.

Compared to the 2-h oral glucose tolerance test (OGTT), the assessment of HbA1c was proposed as a less time-consuming alternative to detect pathologies in carbohydrate metabolism. This report aims to assess the predictive accuracy of HbA1c to detect alterations in glucose disposition early after gestational diabetes mellitus (GDM) pregnancy. A detailed metabolic characterization was performed in 77 women with previous GDM (pGDM) and 41 controls 3-6 month after delivery: 3-h OGTT, frequently sampled intravenous glucose tolerance test. Follow-up examinations of pGDMs were performed up to 10 years. HbA1c (venous samples, HPLC) was assessed at baseline as well as during the follow-up period (475 patient contacts). Moderate associations were observed between HbA1c and measurements of plasma glucose during the OGTT at the baseline examination: The strongest correlation was found for FPG (r = 0.40, p < 0.001), decreasing after ingestion. No associations were detected between HbA1c and OGTT dynamics of insulin or C-peptide. Moreover, baseline HbA1c showed only modest correlation with insulin sensitivity (r = -0.25, p = 0.010) and disposition index (r = -0.26, p = 0.007). A linear model including fasting as well as post-load glucose levels was not improved by HbA1c. However, pGDM females with overt diabetes manifestation during the follow-up period showed more pronounced increasing HbA1c in contrast to females remaining normal glucose tolerant or developing prediabetes. It is suggested that the performance of HbA1c assessed early after delivery is inferior to the OGTT for the detection of early alterations in glucose metabolism. However, an increase in HbA1c levels could be used as an indicator of risk for diabetes manifestation.

Risk stratification after pregnancy with gestational diabetes mellitus (GDM) is based on screening with the 2-h oral glucose tolerance test (OGTT). Actually, prediabetes and diabetes are diagnosed by impaired fasting [fasting plasma glucose (FPG)] and 120 min-postload glucose levels (120'-PLG). We hypothesized that the clinical information could be improved by including measurements at different time points from the OGTT in the medical decision-making process. One hundred ten women with previous gestational diabetes (pGDM) and 41 controls were included 3-6 mo after delivery and underwent specific metabolic assessments: 3-h OGTT, frequently sampled intravenous glucose tolerance test (FSIGT) with markers of inflammation and endothelial function. pGDMs were annually invited for reexaminations for a maximum of 10 yr. Multiple linear regression suggested that postload glucose levels at 60 min (60'-PLG) were a better predictor for insulin sensitivity [β: -0.10, 95% confidence interval (CI) -0.14 to -0.05, P < 0.001] and disposition index (DI) (β: -0.07, 95% CI -0.12 to -0.02, P = 0.004) estimated from the FSIGT compared with other time points during the OGTT. The association between 60'-PLG and insulin secretion was of particular importance in women after GDM. We further identified associations of 60'-PLG with ultrasensitive C-reactive protein, plasminogen activator inhibitor 1, tissue plasminogen activator, endothelial-leukocyte adhesion molecule 1, and intercellular adhesion molecule (ICAM)-1. There appeared to be no interactions between females with pGDM and controls, suggesting comparable effects. We observed that 60'-PLG levels were closely related to the later onset of diabetes independent from the routinely measured FPG and 120'-PLG levels. Our data suggest that the sole interpretation of FPG and 120'-PLG of the OGTT leads to significant loss of information. Particularly 60'-PLG was shown to distinguish women at low or high metabolic and cardiovascular risk.

Background: Time-dependent changes in glycemic control might represent a strong predictor for coronary artery disease. Since a higher benefit from outpatient appointments has been discussed for female gender, the aim of the study was to assess gender differences in HbA1c levels and metabolic parameters at baseline as well as over 3 years of follow-up., Methods: We analyzed the data of 54 female and 65 male type 1 diabetic patients, with comparable age and diabetes duration, who visited our diabetes outpatient clinic in the year 2006 as well as the follow-up visits until 2009., Results: In 2006, females showed higher HbA1c levels as compared to male subjects (8.59 ± 1.60 vs. 7.75 ± 1.41, p = 0.003). Longitudinal analysis revealed that the decrease in HbA1c until 2009 was more pronounced in women (decreased to 7.52 ± 1.00) than in men (decreased to 7.50 ± 0.99, p (sex:time) = 0.006); however, the significance was lost after adjusting for baseline levels. Further, females showed higher levels in total-cholesterol (p = 0.001), LDL-cholesterol (p = 0.033), and HDL-cholesterol (p < 0.001) at baseline, whereas males had higher creatinine (p = 0.001) and uric acid levels (p < 0.001). No differences between the two sexes were shown for triglycerides at 2006. Additionally, uric acid levels were negatively associated with long term glycemic control, particularly in male patients., Conclusions: Sex-related differences in metabolic parameters are present in patients with type 1 diabetes. Especially, our data suggests more adverse cardiometabolic risk markers in females. A potentially protective effect for hyperuricemia by hyperglycemia-related glucosuria is lacking in female patients with type 1 diabetes.

Background and Aims: Determinants of fatty liver (FL) might be predictive for further deterioration in insulin resistance (IR) in women with previous gestational diabetes (pGDM). The aim was to evaluate the association between pGDM, FL and future manifestation of type 2 diabetes (T2DM) by a detailed pathophysiological characterization early after pregnancy., Methods: 68 pGDM and 29 healthy controls were included 3-6 months after delivery and underwent specific metabolic assessments: status of IR was determined via oral- and intravenous-glucose-tolerance-tests with analysis of proinflammatory factors and kinetics of free-fatty-acids (FFA). According to the fatty-liver-index (FLI), pGDMs were categorized into three groups with low (FLI≤20), intermediate (20

Objective: To assess a cluster of risk factors, including parameters of the metabolic syndrome, in women with gestational diabetes mellitus (GDM) early after delivery, that features the best prediction for developing diabetes., Methods: Women with GDM 3-6 months after delivery received a complete metabolic characterization at baseline as well as annually for up to 10 years of follow-up (N=110). We used parameters characterizing the metabolic syndrome as well as demographic variables at baseline to predict diabetes manifestation., Results: Metabolic disturbances and insulin treatment during pregnancy were significantly associated with overt diabetes. Waist circumference of 80 cm or higher failed to show a significant effect on later development of the disease; however, it was significant when 88 cm or more was used as a cutoff value. We identified impaired glucose tolerance (13 [56.5%]; hazard ratio 6.77, confidence interval [CI] 2.96-15.45, P<.001) as well as high-density lipoprotein (HDL) cholesterol less than 50 mg/dL (14 [60.9%]; hazard ratio 2.88, CI 1.24-6.67, P=.010) and age older than 35 years (12 [52.2%]; hazard ratio 3.06, CI 1.32-7.12, P=.006) as the best predictors with additive effects. Women with at least two risk factors had a higher risk to develop the disease as compared with those women who showed only one risk factor (hazard ratio 3.2, CI 1.4-7.7, P=.008)., Conclusion: Impaired glucose tolerance, HDL cholesterol less than 50 mg/dL, and age older than 35 years were identified as the best predictors of developing diabetes after GDM.

Background: Both sexes are at different risks for cancers and gender-dependent fears and barriers might influence their attitude towards screening. The aim of the present study was to assess gender issues in demographic variables which could influence the use of screening examinations., Methods: A standardized questionnaire was used to assess data of 513 Austrians, with urban and rural location of residence, aged 35-65 years. An elderly age group was additionally assessed in the urban region., Results: Women of both age groups showed lower screening rates for bowel cancer. Living in partnership was predictive for breast cancer screening in females, whereas higher educational level was negatively associated with PSA screening in younger men. Additionally, increasing age was associated with less screening for breast and cervix cancer in older women., Conclusions: There is evidence for gender-related differences in the attitude towards screening in Austria. Different socio-demographic variables might be responsible.