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ZUSAMMENFASSUNGSchwangerschaften mit präkonzeptionell bekanntem Typ-1- und Typ-2-Diabetes sind Hochrisiko-Schwangerschaften und bedürfen einer interdisziplinären Betreuung. Kinder diabetischer Mütter haben ein im Mittel 1,5- bis 3-fach erhöhtes Risiko für angeborene Fehlbildungen, Frühgeburtlichkeit, Hypertrophie, Atemstörungen, Plexusparese und Asphyxie. Das Risiko für Totgeburt und Tod in den ersten 7 Lebenstagen ist bei prägravidem Diabetes erhöht. Die mit Abstand häufigste Komplikation bei Neugeborenen diabetischer Mütter ist die postnatale Hypoglykämie. Diabetesassoziierte Begleiterkrankungen und maternale Adipositas sind unabhängige Risikofaktoren für Schwangerschaftskomplikationen und ein ungünstiges fetales Outcome. Für die Blutglukoseeinstellung während der Schwangerschaft wurde ein klarer Zusammenhang höherer Werte mit ungünstigen fetalen und maternalen Ereignissen gezeigt. Analoginsuline sind mittlerweile die Insuline der Wahl. Darüber hinaus konnte eine Überlegenheit einer CGM-Versorgung während der Schwangerschaft gegenüber der konventionellen Blutglukosemessung gezeigt werden. Die Rate an Sektiones ist bei Frauen mit Diabetes nach wie vor gegenüber der Grundgesamtheit in der Perinatalstatistik deutlich erhöht. Evidenzbasierte Erkenntnisse zum intrapartalen Vorgehen liegen nicht vor. Die Einstellungsziele orientieren sich daher an den während der Schwangerschaft geltenden Zielen.

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years’ follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was −0.29 mmol/L [95% CI −0.54; −0.04], P = 0.025. Liver fat (−1.34 percentage points [95% CI −2.17; −0.50], P = 0.002) and cardiovascular risk (−1.82 percentage points [95% CI −3.13; −0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype–based LI may be beneficial for the prevention of diabetes.

The design of active and selective co-catalysts constitutes one of the major challenges in developing heterogeneous photocatalysts for energy conversion applications. This work provides a comprehensive insight into thermally induced bottom-up generation and transformation of a series of promising Cu-based co-catalysts. We demonstrate that the volcano-type HER profile as a function of calcination temperature is independent of the type of the Cu precursor but is affected by changes in oxidation state and location of the copper species. Supported by DFT modeling, our data suggest that low temperature (200 °C) do not affect the Cu oxidation state, but induce a gradual, temperature-dependent surface-to-bulk diffusion of Cu, which results in interstitial, tetra-coordinated Cu+ species. The disappearance of Cu from the surface and the introduction of new defect states is associated with a drop in HER performance. This work examines electronic and structural effects that are in control of the photocatalytic activity and can be transferred to other systems for further advancing photocatalysis., Calcination of Cu/TiO2 is detrimental to its photocatalytic HER performance. We relate this to heat-activated Cu diffusion into the TiO2 lattice, which decreases accessibility of the Cu sites on the surface and generates charge recombination centers.

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6–14.57) vs. 5.52(3.15–10.02); p

Aims/hypothesis Many individuals who develop type 2 diabetes also display increased glucagon levels (hyperglucagonaemia), which we have previously found to be associated with the metabolic syndrome. The concept of a liver–alpha cell axis provides a possible link between hyperglucagonaemia and elevated liver fat content, a typical finding in the metabolic syndrome. However, this association has only been studied in individuals with non-alcoholic fatty liver disease. Hence, we searched for a link between the liver and the alpha cells in individuals with non-steatotic levels of liver fat content. We hypothesised that the glucagon–alanine index, an indicator of the functional integrity of the liver–alpha cell axis, would associate with liver fat and insulin resistance in our cohort of women with low levels of liver fat. Methods We analysed data from 79 individuals participating in the Prediction, Prevention and Subclassification of Type 2 Diabetes (PPSDiab) study, a prospective observational study of young women at low to high risk for the development of type 2 diabetes. Liver fat content was determined by MRI. Insulin resistance was calculated as HOMA-IR. We conducted Spearman correlation analyses of liver fat content and HOMA-IR with the glucagon–alanine index (the product of fasting plasma levels of glucagon and alanine). The prediction of the glucagon–alanine index by liver fat or HOMA-IR was tested in multivariate linear regression analyses in the whole cohort as well as after stratification for liver fat content ≤0.5% (n = 39) or >0.5% (n = 40). Results The glucagon–alanine index significantly correlated with liver fat and HOMA-IR in the entire cohort (ρ = 0.484, p ρ = 0.417, p 0.5% (liver fat, ρ = 0.550, p ρ = 0.429, p = 0.006). In linear regression analyses, the association of the glucagon–alanine index with liver fat remained significant after adjustment for age and HOMA-IR in all participants and in those with liver fat >0.5% (β = 0.246, p = 0.0.23 and β = 0.430, p = 0.007, respectively) but not in participants with liver fat ≤0.5% (β = −0.184, p = 0.286). Conclusions/interpretation We reproduced the previously reported association of liver fat content and HOMA-IR with the glucagon–alanine index in an independent study cohort of young women with low to high risk for type 2 diabetes. Furthermore, our data indicates an insulin-resistance-independent association of liver fat content with the glucagon–alanine index. In summary, our study supports the concept that even lower levels of liver fat (from 0.5%) are connected to relative hyperglucagonaemia, reflecting an imminent impairment of the liver–alpha cell axis.

Aims To evaluate the cost-effectiveness of a mobile phone text messaging program for people with type 2 diabetes mellitus. Methods We performed a generalized cost-effectiveness analysis in a randomized controlled trial in Bangladesh. Patients with type 2 diabetes were randomized (1:1) to a text messaging intervention plus standard-care or standard-care alone. Intervention participants received a text message daily for 6 months encouraging healthy lifestyles. Costs to users and the health systems were measured. The EQ-5D-3L was used to measure improvements in health-related quality-adjusted life years (QALYs). Intervention costs were expressed as average cost-effectiveness ratios (cost-per 1% unit-reduction in glycated haemoglobin HbA1c and cost per QALY gained), based on the World Health Organization cost effectiveness and strategic planning (WHO-CHOICE) method. Results In 236 patients [mean age 48 (SD9.6) years] the adjusted difference in accumulated QALYs between the intervention and the control group over the 6-month period was 0.010 (95%CI: 0.000; 0.021). Additional costs per-patient averaged 24 international dollars (Intl.$), resulting in incremental cost-effectiveness ratios of 38 Intl.$ per % glycated haemoglobin (HbA1c) reduction and 2406 Intl.$ per QALY gained. The total intervention costs for the mobile phone text messaging program was 2842 Int.$. Conclusion Text messaging might be a valuable addition to standard treatment for diabetes care in low-resource settings and predicted to lead an overall saving in health systems costs. Studies with longer follow-up and larger samples are needed to draw reliable conclusions.

Objective Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components. Design The analyses included 1088 participants of the population-based KORA F4 study aged 62–81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome. Methods The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models. Results Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high-sensitivity C-reactive protein (OR 0.65; 95% CI 0.56–0.76 per standard deviation uromodulin; P Conclusions Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit from conventional LI and individuals with high risk benefit from an intensification of LI in a multi-center randomized controlled intervention over 12 months with 2 years follow up. 1105 prediabetic individuals based on ADA glucose criteria were stratified into a high- and low-risk phenotype, based on previously described thresholds of insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI according to the DPP protocol or control (1:1), high-risk individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In high-risk individuals, the difference between conventional and intensified LI in post-challenge glucose change was -0.29 mmol/l [CI:-0.54;-0.04], p=0.025. Liver fat (-1.34 percentage points [CI:-2.17;-0.50], p=0.002) and cardiovascular risk (-1.82[CI:-3.13-0.50],p=0.007) underwent larger reductions with intensified than with conventional LI. During a follow up of 3 years, intensified compared to conventional LI had a higher probability to normalize glucose tolerance (p=0.008). In conclusion, it is possible in high-risk individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk-phenotype-based LI may be beneficial for the prevention of diabetes.

Background: Diabetes mellitus is a major health problem in Southeast Asia and diabetic retinopathy is one of its most debilitating complications. Nevertheless, fundoscopy and systematic evaluation of non-adherence to drug therapy are not regularly done in individuals with diabetes in Bangladesh due to limited resources. Therefore, the prevalence of diabetic retinopathy and its determinants with non-adherence to drug therapy are not known. We, therefore, screened for diabetic retinopathy, non-adherence to drug therapy and other associated factors at a tertiary care hospital in Bangladesh.Methods: Between May 2017 to September 2017, we conducted a cross-sectional study of 489 systematically recruited asymptomatic, at least one-year type-2 diabetic individuals on medication and attending the outpatient department of the BIHS tertiary care centre in Dhaka, Bangladesh. We obtained a medical history, physical examination, routine laboratory tests, questionnaires, and fundus photography.Results: The prevalence of diabetic retinopathy among T2DM patients was 18.8%. Clinical factors associated with the presence of diabetic retinopathy were uncontrolled fasting blood glucose, known duration of diabetes of ≥10 years and self-reported non-adherence to drug therapy. With a known duration of diabetes of 15 years or more, the prevalence of diabetic retinopathy rose to 40%.Conclusions: Undiagnosed diabetic retinopathy is still common among patients in Bangladesh, even at tertiary care centres. It is associated with longer disease duration, poor metabolic control and self-reported non-adherence to therapy. Regular screening for diabetic retinopathy should therefore be implemented also in resource-limited settings and further efforts should be made to improve the patients’ drug adherence and metabolic control.

Background The myokine myostatin regulates muscle mass and has been linked to insulin resistance and metabolic syndrome. However, data on its role in humans is still limited. We, therefore, investigated the associations of serum myostatin with muscle mass, physical fitness, and components of the metabolic syndrome in a cohort of premenopausal women. Methods We undertook a cross-sectional analysis of 233 women from the monocenter study PPSDiab, conducted in Munich, Germany. Participants had recently completed a pregnancy with or without gestational diabetes. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, cardiopulmonary exercise testing, and magnetic resonance imaging (n=142) of visceral fat volume, left quadriceps muscle mass, and muscle fat content. Serum myostatin was quantified by a competitive enzyme-linked immunosorbent assay. Results We observed positive correlations of serum myostatin with body mass index (ρ=0.235; p=0.0003), body fat percentage (ρ=0.166; p=0.011), waist circumference (ρ=0.206; p=0.002), intraabdominal fat volume (ρ=0.182; p=0.030) and high-sensitivity C-reactive protein (ρ=0.175; p=0.008). These correlations were reproduced in linear regression analyses with adjustment for age and time after delivery. We saw no correlations with muscle mass, physical fitness, insulin sensitivity, triglycerides, HDL cholesterol, and blood pressure. Conclusions Our observation of elevated serum myostatin in women with a higher body fat percentage, visceral obesity, and elevated c-reactive protein suggests that this myokine contributes to the altered muscle-adipose tissue crosstalk in metabolic syndrome. Elevated myostatin may advance this pathophysiologic process and could also impair the efficacy of exercise interventions. Further mechanistic studies, therefore, seem warranted.

Aims Women after gestational diabetes mellitus (GDM) are a risk group for cardiometabolic diseases but are hard to reach by conventional lifestyle programs. Therefore, we tested whether a novel, smartphone-delivered intervention, TRIANGLE, is accepted by women after GDM and alters cardiometabolic risk behaviors and outcomes. TRIANGLE targets gradual habit change of mind and emotion, physical activity, nutrition, and sleep. Methods We conducted a 6-month multicenter, randomized-controlled trial of TRIANGLE versus standard care with 66 women 3–18 months after GDM in Germany. The primary outcome was the proportion of women achieving ≥3 out of 5 Diabetes Prevention Program goals, i.e. physical activity ≥150 min/week (moderate to high intensity), fiber intake ≥15 g/1,000 kcal, fat intake 2 or weight maintenance if BMI 2. Intervention participants also rated the TRIANGLE app in the Mobile Application Rating Scale (uMARS). Results In the predefined, modified intention-to-treat analysis including 64 women, 6 out of 27 women in the intervention group [22%(10–40)] and 3 out of 27 women in the control group [11%(3–27)] reached the primary outcome (p = 0.47). In the predefined per-protocol intervention subgroup, the proportion was 4 out of 14 women [29%(11–55); p = 0.20 vs. control]. TRIANGLE app users were active on 42% of days and rated the app’s quality and perceived impact with 4.3±0.8 out of 5 uMARS points. Conclusions This first trial did not show the efficacy of the TRIANGLE intervention. However, the app was well accepted and considered helpful by most users. Therefore, this trial supports further development and testing of TRIANGLE and other app interventions for women after GDM. Additionally, it identifies necessary adaptations in trial design to better accommodate non-intensive lifestyle interventions for this target group. Trial registration Trial registration at drks.de (DRKS00012996).

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs), which are anchored at the surface of mammalian cultured and tissue cells through a carboxy-terminal GPI glycolipid, are susceptible to release into incubation medium and (rat and human) blood, respectively, in response to metabolic stress and ageing. Those GPI-APs with the complete GPI still attached form micelle-like complexes together with (lyso)phospholipids and cholesterol and are prone to degradation by serum GPI-specific phospholipase D (GPLD1), as well as translocation to the surface of acceptor cells in vitro. In this study, the interaction of GPI-APs with GPLD1 or other serum proteins derived from metabolically deranged rat and humans and their translocation were measured by microfluidic chip- and surface acoustic wave-based sensing of micelle-like complexes reconstituted with model GPI-APs. The effect of GPI-AP translocation on the integrity of the acceptor cell surface was studied as lactate dehydrogenase release. For both rats and humans, the dependence of serum GPLD1 activity on the hyperglycemic/hyperinsulinemic state was found to be primarily based on upregulation of the interaction of GPLD1 with micelle-like GPI-AP complexes, rather than on its amount. In addition to GPLD1, other serum proteins were found to interact with the GPI phosphoinositolglycan of full-length GPI-APs. Upon incubation of rat adipocytes with full-length GPI-APs, their translocation from the micelle-like complexes (and also with lower efficacy from reconstituted high-density lipoproteins and liposomes) to acceptor cells was observed, accompanied by upregulation of their lysis. Both GPI-AP translocation and adipocyte lysis became reduced in the presence of serum proteins, including (inhibited) GPLD1. The reduction was higher with serum from hyperglycemic/hyperinsulinemic rats and diabetic humans compared to healthy ones. These findings suggest that the deleterious effects of full-length GPI-APs following spontaneous release into the circulation of metabolically deranged rats and humans are counterbalanced by upregulated interaction of their GPI anchor with GPLD1 and other serum proteins. Thereby, translocation of GPI-APs to blood and tissue cells and their lysis are prevented. The identification of GPI-APs and serum proteins interacting within micelle-like complexes may facilitate the prediction and stratification of diseases that are associated with impaired cell-surface anchorage of GPI-APs, such as obesity and diabetes.

ObjectiveMany anecdotal reports indicate the presence of ‘long COVID’ – COVID-19-related symptoms weeks to months after the acute illness. However, frequency and symptom-pattern of ‘long COVID’ in relation to acute disease severity are uncertain. As part of an ongoing, prospective cohort study we therefore conducted an online survey among adults 6 months after acute COVID-19.MethodsThe prospective online study Life&Covid is ongoing in Germany since May 2020. Participants were recruited 0 to 4 months after their SARS-CoV-2 infection und followed up by subsequent surveys. The survey 6 months after the infection was completed by 127 out of 148 individuals invited by email (86%). All grades of acute disease severity were included and 91% of the participants had been treated as outpatients during their acute illness.ResultsSix months after the infection, 67% of the study participants reported at least one symptom as a consequence of COVID-19. Exertional dyspnea (30% of participants), fatigue (25%) and diminished sense of taste/smell (19%) were the most common individual symptoms. At least one symptom, exertional dyspnea, and fatigue were reported more often after a severe acute illness, but diminished sense of taste/smell was unrelated to acute severity. Age group and sex did not associate with the frequency of symptoms at 6 months.ConclusionsBased on this study, the prevalence of COVID-19-related symptoms 6 months after the infection is high. Some bias for overestimation may have affected this result. Nevertheless, ‘long COVID’ requires attention in medical care and a better scientific understanding.

BackgroundLifestyle intervention (LI) can successfully prevent type 2 diabetes, but response to LI strongly varies depending on risk subphenotypes. We tested if individuals with prediabetes and a high-risk phenotype benefit from an intensification of LI.Methods and findingsWe conducted a risk stratified multicenter randomized controlled intervention study over 12 months with additional 2 year follow up. In eight University Hospitals in Germany, 1105 individuals (female 59%, age 58±11 years, BMI 31.1±6.0 kg/m2 (mean±SD)) with impaired fasting glucose and/or impaired glucose tolerance were included between May 2012 and May 2016 in the study. Participants were stratified into 2 groups; a high- and low-risk phenotype, based on insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI or control (1:1), high-risk individuals to conventional or intensified LI (1:1), each over one year. Intensified LI included doubling of physical exercise and time of counselling. The primary endpoint was change in post-challenge glucose levels, assessed by frequently sampled oral glucose tolerance tests. Secondary endpoints included changes in liver fat content, assessed by magnetic resonance spectroscopy. A total of 908 (82%) participants completed the study after 12 months of LI. In high-risk individuals, the mean difference estimate between conventional and intensified LI in change in post-challenge glucose levels from baseline was −0.290 mmol/l [CI: −0.544;−0.036], p=0.025. Liver fat content was more reduced by intensified LI than by conventional LI (mean difference estimate: −1.34 percentage points [CI: −2.17;−0.50], p=0.002), and cardiovascular risk decreased stronger with intensified LI than with conventional LI (mean difference estimate −1.82 [CI: −3.13−0.50], p=0.007). In low-risk individuals, conventional LI was not superior to control in reducing postprandial glucose, liver fat or cardiovascular risk. During the total observation period of 3 years, high-risk participants with intensified LI had a higher probability to normalize glucose tolerance compared to conventional LI (p=0.003). The limitations of this study include a relative short duration of LI, a non-completer rate of 18% and an underrepresentation of low risk individuals.ConclusionsIn high-risk individuals with prediabetes it is possible to improve glycemic and cardiometabolic outcomes by intensification of the commonly recommended conventional LI. Our results show that individualized, risk-phenotype-based LI can be implemented for the prevention of diabetes.RegistrationNCT01947595Author summaryWhy Was This Study Done?Clinical trials in individuals with prediabetes have shown that the onset of type 2 diabetes can be delayed or prevented with lifestyle intervention.Among individuals with prediabetes, there is a large variability in the response to lifestyle intervention.It is unknown whether an intensification of intervention is able to improve the beneficial response.What Did the Researchers Do and Find?The present multicenter, risk stratified randomized and controlled intervention trial in 1105 German individuals with prediabetes prospectively confirms the existence of a high-risk prediabetes phenotypeThe intensification of lifestyle intervention in high-risk individuals improves the glycemic outcome after 1 year of lifestyle intervention, and additionally results in a higher frequency of regression to normal glucose tolerance after 3 years of follow up..Intensification of lifestyle intervention results in a larger reduction of liver fat content and stronger improves cardiometabolic outcomes in high-risk individuals.What Do These Findings Mean?Strategies for the prevention of type 2 diabetes should include risk stratification and individualised interventions.Our results highlight a dose-effect relationship for lifestyle intervention and suggest that “one size fits NOT all” in the field of diabetes prevention.It remains to be clarified whether low risk individuals benefit from lifestyle intervention, as there was a low number of individuals in this risk group in the current study.

Objective Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we re-evaluated this hypothesis. Research Design and Methods We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3 to 9 of the Whitehall II study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. Results We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the National Cholesterol Education Program Adult Treatment Panel III score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, high-density lipoprotein cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. Conclusions Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.

BACKGROUND Gestational diabetes mellitus (GDM) is the most common complication during pregnancy and is associated with an increased risk for the development of cardiometabolic diseases. Behavioral interventions can reduce this risk, but current solutions insufficiently address the requirements for such a program. The systematic development of a scalable mobile health (mHealth) promotion program for mothers during the first years post-GDM may contribute to solving this problem. OBJECTIVE The aim of this project was to systematically plan and develop a theory- and evidence-based mHealth intervention to change cardiometabolic risk behaviors in women during the first 5 years post-GDM that meets women’s expected standards of commercial health apps. METHODS The intervention mapping steps 1 to 4 structured the systematic planning and development of the mHealth program described in this paper. Steps 1 and 2 led to a theory- and evidence-based logic model of change for cardiometabolic health. Based on this model, the prevention program was designed (step 3) and produced (step 4) in cooperation with industrial partners to ensure a high technological standard of the resulting smartphone app for the iPhone (Apple Inc). Step 4 included a user study with women during the first 5 years post-GDM once a beta version of the app (“TRIANGLE”) was available. The user study comprised 2 test rounds of 1 week (n=5) and 4 weeks (n=6), respectively. The tests included validated questionnaires on user acceptance, user logs, and think-alouds with semistructured interviews. RESULTS The novel TRIANGLE app is among the first self-paced smartphone apps for individual habit change in the 3 lifestyle areas of physical activity, nutrition, and psychosocial well-being. The 3 core features—a challenge system, human coaching, and a library—address 11 behavioral determinants with 39 behavior change methods to support lifestyle changes. Participants in the user study showed a high acceptance, high perceived quality, and high perceived impact of the TRIANGLE app on their health behaviors. Participants tested the app regularly, used it intuitively, and suggested improvements. We then adapted the TRIANGLE app according to the insights from the user study before the full TRIANGLE program production. CONCLUSIONS The intervention mapping approach was feasible to plan and develop an innovative and scalable smartphone solution for women during the first 5 years post-GDM. The resulting TRIANGLE intervention has the potential to support behavior change for cardiometabolic disease prevention. However, the app needs further refinement and testing in clinical trials. Intervention mapping steps 5 (implementation plan) and 6 (evaluation plan) may support the integration of the TRIANGLE intervention into routine care. CLINICALTRIAL German Clinical Trials Register DRKS00012736; https://www.drks.de/DRKS00012736