Pre-existing T2DM Research Articles

Maternal pre-gestational and gestational diabetes and risk of offspring epilepsy: A cohort study

Abstract Background Despite growing evidence linking maternal diabetes to impaired brain physiology and neurodevelopment in offspring, evidence on its effect on epilepsy remains scarce. This study aims to determine if intrauterine exposure to maternal pre-existing and gestational diabetes mellitus is associated with risk of offspring epilepsy. Methods We studied >2.3 million singletons live-born in Sweden between 1998 and 2021, with final follow up until October 31, 2023. The Swedish Medical Birth Register was linked to the National Patient Register to identify gestational diabetes (GDM), maternal pre-gestational type 1 (T1DM) and type 2 diabetes (T2DM), and offspring epilepsy. The incidence of epilepsy, comparing offspring of mothers with versus without diabetes, was calculated as hazard ratios (HR), adjusting for maternal education, smoking, body mass index, hypertension, epilepsy and other important confounders. Paternal T1DM and T2DM were additionally analysed as negative control exposures to assess genetic confounding. Results Of the 2,335,245 offspring analysed (48.9% female), 13,883 (0.6%) were exposed to maternal T1DM, 4477 (0.2%) to T2DM, and 37,253 (1.6%) to GDM. During a median follow up of 13 years (range 0-26 years), 18,732 offspring were diagnosed with epilepsy. Maternal T1DM (HR 1.27, 95% confidence intervals [CI] 1.08-1.49) and T2DM (HR 1.34, 95% CI 1.00-1.49) were associated with higher hazards of epilepsy in offspring, compared with no exposure to maternal diabetes. Preterm birth and birth-asphyxia jointly mediated 63% and 39% of these associations, respectively. No association was found between maternal GDM and epilepsy. Paternal T1DM and T2DM did not show association with epilepsy. Conclusions In this nationwide population-based cohort study, children of mothers with T1DM or T2DM showed an elevated risk of epilepsy. The results from paternal comparison and mediation analyses suggest a key role of the intrauterine environment in the aetiology of epilepsy. Key messages • Maternal pre-existing T1DM and T2DM might be risk factors for epilepsy in offspring and are likely to influence the risk through the intrauterine environment independent of genetic mechanisms. • In the context of a globally rising prevalence of diabetes in women who get pregnant, it is crucial that the diabetes is well-regulated and birth complications associated with diabetes are prevented.

Safety and efficacy of semaglutide in post kidney transplant patients with type 2 diabetes or Post-Transplant diabetes

ObjectiveType 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are common in renal transplant recipients. Semaglutide has demonstrated efficacy and safety in patients with T2DM. To date, only a limited number of studies have investigated its use in renal transplant patients. This study assessed the safety and efficacy of semaglutide in post-renal transplant patients. MethodsA retrospective study was conducted at king Abdulaziz Medical City-Riyadh, Saudi Arabia. The subjects of the study were adults and adolescents (>14 years) who had undergone a kidney transplant and had pre-existing T2DM or PTDM. The study subjects were given semaglutide during the study period, from January 2018 to July 2022. The data were collected over a period of 18 months. ResultsA total of 39 patients were included, 29 (74 %) of whom were male. A significant decrease in hemoglobin A1c (HbA1c) was observed during the follow-up period when compared to baseline (8.4 %±1.3 % at baseline vs. 7.4 %±1.0 % at 13–18 months (p < 0.001). A significant reduction in weight was also noted at follow-up as compared to baseline (99.5 kg ± 17.7 vs 90.7 kg ± 16.8 at 13–18 months (p < 0.001). No significant changes were found in renal graft function markers. ConclusionSemaglutide was found to significantly reduce HbA1c levels and weight in post renal transplant patients with diabetes. No significant changes in markers of renal graft function were observed.

662-P: Diabetes Self-Management in Breast Cancer Survivors—Racial and Ethnic Disparities

Type 2 diabetes (T2DM) is associated with 40% increased breast cancer (BC) mortality. Black and Latina BC survivors have worse BC mortality outcomes and are more likely to have T2DM. We aimed to assess the association of race/ethnicity with adherence to T2DM self-management behaviors (SMBs), medication beliefs, and control in BC survivors. We recruited Stage 0-III BC survivors ≥ 55 years who had preexisting T2DM taking ≥ 1 oral DM medications. Adherence to T2DM SMBs and medication beliefs were assessed with validated questionnaires. Hemoglobin A1c (A1c) was measured at recruitment to assess T2DM control. We compared variables by race/ethnicity using the Fisher's exact (categorical) and Kruskal Wallis (continuous) tests. Multivariable linear regression evaluated the relationship between race/ethnicity and T2DM variables and adjusted for age, education and BC stage. Of 194 participants, median age was 67 years (interquartile range [IQR] 60-72), A1c was 7.4% (IQR 6.4-7.9); 27% self-identified as Black, 41% as non-Hispanic white (NHW), 18% as Latina, and 14% as other/unknown race. NHWs (70 years, IQR 56-83) were older than Black (63 years, IQR 55-87), Latina (64 years, IQR 56-83), and other/unknown race (64 years, IQR 55-77) participants (p=0.01). Black (76%), Latina (49%), and other/unknown race (83%) participants were less likely to have some college education than NHWs (88%, p&amp;lt;0.01). BC stage did not significantly differ by race/ethnicity. In multivariate analyses, Latina participants were more likely to believe T2DM medications disrupted their lives and were not important for their health. However, race/ethnicity was not associated with adherence to T2DM SMBs nor A1c in multivariate analyses. In summary, race/ethnicity was not correlated with T2DM SMBs or control in BC survivors, but Latinas differed regarding some medication beliefs. Future studies should explore other T2DM-related factors, potentially related to medication beliefs, to improve outcomes for Black and Latina BC survivors. Disclosure A. Leiter: None. E. Doron: Other Relationship; Teva Pharmaceutical Industries Ltd. M.S. Goel: None. J.J. Lin: None.

Impact of Perineural Invasion and Preexisting Type 2 Diabetes on Patients with Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoradiotherapy

Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the cornerstone treatment strategy in locally advanced esophageal squamous cell carcinoma (ESCC). Despite this high- intensity multimodality therapy, most patients still experience recurrences and metastases, especially those who do not achieve a pathological complete response (pCR) after neoCRT. Here, we focused on identifying poor prognostic factors. In this retrospective cohort study; we enrolled 140 patients who completed neoCRT plus surgery treatment sequence with no interval metastasis. Overall, 45 of 140 patients (32.1%) achieved a pCR. The overall survival, disease-free survival (DFS), and metastasis-free survival was significantly better in patients with a pCR than in patients with a non-pCR. In the non-pCR subgroup, the presence of perineural invasion (PNI) and preexisting type 2 diabetes (T2DM) were two factors adversely affecting DFS. After adjusting for other factors, multivariate analysis showed that the hazard ratio (HR) was 2.354 (95% confidence interval [CI] 1.240-4.467, p = 0.009) for the presence of PNI and 2.368 (95% CI 1.351-4.150, p = 0.003) for preexisting T2DM. Patients with a combination of both factors had the worst survival. In conclusion, PNI and preexisting T2DM may adversely affect the prognosis of patients with ESCC receiving neoadjuvant chemoradiotherapy.

PSUN261 Diabetic Ketoacidosis Complicating Gestational Diabetes Mellitus: A Case Report

Abstract Diabetic ketoacidosis (DKA) in pregnancy is a rare but serious medical emergency. Its incidence ranges between 0.2%-9% and carries a fetal mortality rate up to 90%. DKA remains to be an extremely rare complication of gestational diabetes (GDM). Early diagnosis and management may be delayed due to its atypical presentation. We present a case of DKA in GDM with no pre-existing diagnosis of type 1 diabetes (T1DM) or type 2 diabetes (T2DM). A 33-year-old African American woman G2P0010 with GDM on insulin diagnosed in current pregnancy, presented at 30-weeks of gestation with a 3-day history of general malaise, altered mentation, and emesis. Severe DKA (blood glucose 920 mg/dL, pH 7.02, anion gap 38, bicarbonate 5.0 mEq/L, and positive serum ketones), systemic inflammatory response syndrome (tachycardia, WBC of 24,000/mcL), and intrauterine fetal demise via ultrasound were determined upon presentation. MICU admission for prompt and vigorous medical management with intravenous fluid resuscitation, insulin and bicarbonate infusions, and broad-spectrum antibiotic therapy was required. Clinical course was complicated by worsening hypokalemia. Spontaneous vaginal delivery of a non-viable fetus occurred at the MICU. After delivery, resolution of DKA was achieved. Once the patient's mentation was back to her baseline, she admitted complete cessation of insulin 1-week prior to admission. Workup revealed negative glutamic acid decarboxylase, islet cell, and zinc transporter-8 autoantibodies in addition to normal C-peptide levels. A new HbA1C of 9% compared to HbA1C of 5.5% at 6 weeks of gestation, made pre-existing T2DM unlikely. Eventually, the patient was downgraded to the medicine wards for continuity of care. DKA in pregnancy is a rare complication typically associated with T1DM. It may occur at near-normal blood glucose levels, known as euglycemic DKA, causing a delay in diagnosis. Physiologic changes during the last trimester of gestation explain the higher incidence of DKA at this stage. These include the relative state of insulin resistance, which in addition to insulin-antagonistic hormones such as human placental lactogen, prolactin, cortisol, and progesterone contribute to this state. Furthermore, a relative accelerated state of starvation with an increase in maternal ketone body formation, and a reduction in the buffering capacity when exposed to ketonemia places gravida women with impaired glucose tolerance at higher risk to develop DKA. Fetal loss may result from reduced uteroplacental perfusion and fetal hypokalemia leading to fatal arrhythmia. The most common precipitating factors of DKA in pregnancy are infection, including COVID-19, insulin therapy non-adherence, steroid use, dehydration, and unrecognized new-onset diabetes which accounts for up to 30% of cases. It has been described that a genetic polymorphism in SLC26A6 gene may increase the susceptibility to develop DKA in GDM. Prevention, early diagnosis, and vigorous medical management of DKA in pregnancy may possibly reduce maternal and fetal mortality. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Association between type II diabetes mellitus and 90-day mortality in a large multicenter prospectively collected cohort. A FROG ICU post-hoc study

PurposeFactors associated with adverse outcomes in ICU patients with type II (T2DM) are poorly defined. The main goal of this study is to determine the impact of pre-existing T2DM on 90-day mortality post ICU admission. MaterialPost-hoc analysis from the FROG-ICU cohort. All patients admitted to ICU who were ventilated and/or treated by a vasoactive agent for >24 h were included.Association between T2DM and 90-day mortality was analyzed in unmatched, and populations matched by propensity score (PS) method to balance confounders recorded before ICU admission. Analysis was performed in non-imputed and imputed datasets. Results2002 patients were included, and 16% had a history of T2DM. The latter were at inclusion more severely ill (SAPSII score 51(39–67) vs 48(35–61), p < 0.0001; Charlson score 2(1–3) vs 0(0–2), p < 0.0001). In the unmatched cohort, T2DM patients had a higher 90-day risk of death compared to no-DM patients (HR 1.35(1.1–1.65)). The 90-day risk of death was not significantly different T2DM and no T2DM patients after PS matching (HR: 0.81 (0.56–1.18). Results were similar with the analysis performed on imputed datasets (pooled HR: 0.95 (0.69–1.30)). ConclusionsIn the present study, T2DM was not associated with 90-day mortality post ICU admission.

Impact of Type 2 Diabetes Mellitus on Endometrial Cancer Survival: A Prospective Database Analysis

PurposeType 2 diabetes mellitus (T2DM) is an established risk factor for endometrial cancer but its impact on endometrial cancer survival outcomes is unclear. The aim of this study was to investigate whether pre-existing T2DM impacts survival outcomes in endometrial cancer.Patients and MethodsWomen diagnosed with endometrial cancer were recruited to a single centre prospective cohort study. Relevant sociodemographic and clinico-pathological data were recorded at baseline. T2DM status was based on clinical and biochemical assessment, verified by general practitioner records and analysed in relation to overall, cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox-regression.ResultsIn total, 533 women with median age and BMI of 66 years (Interquartile range (IQR), 56, 73) and 32kg/m2 (IQR 26, 39) respectively, were included in the analysis. The majority had low-grade (67.3%), early-stage (85.1% stage I/II), endometrial cancer of endometrioid histological phenotype (74.7%). A total of 107 (20.1%) had pre-existing T2DM. Women with T2DM had a two-fold increase in overall mortality (adjusted HR 2.07, 95%CI 1.21-3.55, p=0.008), cancer-specific mortality (adjusted HR 2.15, 95% CI 1.05-4.39, p=0.035) and recurrence rates (adjusted HR 2.22, 95% CI 1.08-4.56, p=0.030), compared to those without, in multivariable analyses.ConclusionT2DM confers an increased risk of death in endometrial cancer patients. Well-designed longitudinal studies with large sample sizes are now needed to confirm these findings.

IGF-1 contributes to liver cancer development in diabetes patients by promoting autophagy

Introduction and objectivesType 2 diabetes mellitus (T2DM) increases the occurrence and mortality of liver cancer. Insulin growth factor (IGF) plays a crucial role in the development of diabetes and liver cancer, and specifically, IGF-1 may be involved in the development of liver cancer with preexisting T2DM. Autophagy contributes to cancer cell survival and apoptosis. However, the relationship between IGF-1 and autophagy has rarely been evaluated. The purpose of this study was to investigate whether IGF-1 promotes the development of liver cancer in T2DM patients by promoting autophagy. Materials and methodsThirty-three hepatocellular carcinoma (HCC) patients with T2DM and 33 age-matched patients with HCC without T2DM were included in this study. We analyzed the expression of IGF-1 and autophagy-related LC3 and p62 mRNA and the prognosis of two groups. In vitro, we stimulated HepG2 cells with IGF-1 and then detected changes in autophagy and cell proliferation, apoptosis, and migration in the presence/absence of wortmannin, an autophagy inhibitor. ResultsIGF-1 promoted autophagy, resulting in inhibition of apoptosis and induction of growth and migration of HepG2 cells. Inhibition of autophagy by wortmannin impaired IGF-1 function. Higher expression of IGF-1 was detected in HCC patients with T2DM. IGF-1 expression was higher in liver cancer tissue compared to paracancerous tissue. Elevated IGF-1 was associated with a poor prognosis in patients with HCC. ConclusionsIGF-1 participates in the development of liver cancer by inducing autophagy. Elevated IGF-1 was a prognostic factor for patients with HCC, especially when accompanied by T2DM.

Effect of COVID-19 lockdown on glycemic status of patients with T2DM and effects of various factors involved

Background: The recent coronavirus disease 2019 lockdowns forced people to stay indoors, resulting in lower physical activity, and change in dietary patterns, impacting glycemic control in the diabetic population. We aimed to assess the impact of the 3-month lockdown on glycemic control among outpatients with type 2 diabetes (T2DM) being treated at our hospital. Study Design: This retrospective study included data of outpatients aged ≥30 years with preexisting T2DM, regularly attending the clinic during the prelockdown period and who came for follow-up postlockdown. The primary outcome measures were change in glycated hemoglobin (HbA1c), fasting blood glucose sugar (FBG), and postprandial blood sugar (PPBG) compared to the last value before the lockdown. Results: A total of 200 (male: female – 83:117) patients with a mean (standard deviation [SD]) age of 58.0 (10.8) years were included. The mean (SD) interval between the pre- and post-lockdown visit was 3.9 (0.9) months, and 58.5% of the patients were compliant with the medication. The mean HbA1c levels increased significantly by 1.1 (P = 0.000), FBG by 21.9 mg/dL (P = 0.000), PPBG by 28.0 mg/dL (P = 0.000), and weight by 1.6 kg (P = 0.000), from pre- to post-lockdown visit. The patients noncompliant to therapy had a significantly higher increase in glycemic parameters. The results showed a significant correlation between the interval of follow-up and treatment compliance with increase in glycemic parameters and weight. Conclusion: The results of this study revealed that there was a negative impact of lockdown on glycemic control in T2DM patients, highlighting the need for telehealth strategies to ensure the well-being of diabetic patients during such calamities.

Clinical presentation and outcome of COVID-19 infection in Type 2 Diabetes Mellitus: a preliminary data from a tertiary hospital in Jakarta during the early days of the pandemic

Introduction. This study aimed to review the clinical characteristics and outcomes of COVID-19 patients presented with in-hospital hyperglycemia or pre-existing type 2 diabetes (T2DM).Methods. This is a retrospective study conducted in Fatmawati General Hospital, Indonesia, from March 18th-Apr 30th, 2020. We reviewed medical records of 27 COVID-19 patients presented with either in-hospital hyperglycemia (11, 12.2%) or pre-existing T2DM (16, 17.8%) from a total of 90 confirmed COVID-19 cases admitted in our hospital.Results. Critical conditions occurred in 50% of T2DM and 54.55% of the in-hospital hyperglycemia group. Mortality was documented in 68.75% of T2DM and 81.82% of in-hospital hyperglycemia group. Hypoglycemia, diabetic ketoacidosis, lactic acidosis and ketosis were found in 12.5%, 25%, 18.75%, and 25% of individuals with T2DM, respectively, resulting in a high mortality rate. Meanwhile, diabetes-related complications were rare among the in-hospital hyperglycemia group. However, respiratory failure (45.45% vs. 6.25%) and septic shock (27.27% vs. 6.25%) were more frequent than in the T2DM group.Conclusion. In this preliminary study, a high mortality rate was documented among COVID-19 patients with preexisting T2DM and in-hospital hyperglycemia. In T2DM subjects, diabetes related-complications contributed to a higher mortality rate, while in-hospital hyperglycemia group, respiratory failure and septic shock were more frequent.

Abundance of undiagnosed cardiometabolic risk within the population of a long-stay prison in the UK.

The health of people in prisons is a public health issue. It is well known that those in prison experience poorer health outcomes than those in the general community. One such example is the burden of non-communicable diseases, more specifically cardiovascular disease (CVD), stroke and type 2 diabetes (T2DM). However, there is limited evidence research on the extent of cardiometabolic risk factors in the prison environment in Wales, the wider UK or globally. Risk assessments were performed on a representative sample of 299 men at HMP Parc, Bridgend. The risk assessments were 30 min in duration and men aged 25-84 years old and free from pre-existing CVD and T2DM were eligible. During the risk assessment, a number of demographic, anthropometric and clinical markers were obtained. The 10-year risk of CVD and T2DM was predicted using the QRISK2 algorithm and Diabetes UK Risk Score, respectively. The majority of the men was found to be either overweight (43.5%) or obese (37.5%) and/or demonstrated evidence of central obesity (40.1%). Cardiometabolic risk factors including systolic hypertension (25.1%), high cholesterol (29.8%), low HDL cholesterol (56.2%) and elevated total cholesterol: HDL ratios (23.1%) were observed in a considerable number of men. Ultimately, 15.4% were calculated at increased risk of CVD, and 31.8% predicted at moderate or high risk of T2DM. Overall, a substantial prevalence of previously undiagnosed cardiometabolic risk factors was observed and men in prison are at elevated risk of cardiometabolic disease at a younger age than current screening guidelines.

Does the NHS Diabetes Prevention Programme prevent diabetes? A population-based matched cohort study

Abstract Background To reduce the incidence of type 2 diabetes (T2DM) in England, the National Health Service piloted the Diabetes Prevention Programme (DPP). The DPP aims to prevent T2DM by providing high-risk adults with access to 13 face-to-face sessions over nine months that focus on diet and weight management. The DPP has been shown to improve intermediate outcomes for T2DM prevention (weight loss and glycated haemoglobin (HbA1c) reduction). However, there is a lack of evidence examining incident T2DM as the outcome. Methods We conducted a retrospective observational cohort study using linked electronic health records from primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care for June 2016 to January 2019. We compared rates of new T2DM diagnoses among eligible adults who were referred to the DPP with rates for propensity score-matched (ratio of 1:4) controls who were eligible for the DPP but were not invited. DPP eligibility was defined as having HbA1c levels of 42-47 mmol/mol or fasting plasma glucose (FPG) levels of 5.5-6.9 mmol/L. Adults with pre-existing T2DM were excluded. Time to the first record of T2DM was modelled using Cox regression with age, alcohol intake, body mass index, ethnicity, sex, HbA1c, index of multiple deprivation and smoking status included as covariates. Results We identified 2205 individuals who participated in the DPP and 8820 matched controls with a similar breakdown in age, sex, HbA1c and FPG. During the 2.5-year study period, 4.13% of DPP individuals developed T2DM vs 6.42% of controls. Our results indicate that DPP referrals were associated with a 59% reduction T2DM incidence rates [adjusted hazard ratio=0.41;95%CI=0.38-0.44]. Conclusions This is the first study to investigate the impact of the DPP on T2DM, relative to usual care. Our results provide support for the effectiveness of DPP in preventing T2DM onset and are compatible with findings for similar interventions in other settings. Key messages The evidence suggests that providing consistent face-to-face sessions which concentrate on diet and weight management can reduce short-term T2DM incidences in high-risk adults. With a 59% reduction in T2DM rates in DPP referees relative to eligible adults who were not referred, the DPP is effective in reducing short-term T2DM incidences in high-risk adults.

The significance of hyperglycaemia and other comorbidities during the COVID‐19 pandemic

The significance of hyperglycaemia and other comorbidities during the <scp>COVID</scp>‐19 pandemic

1364-P: Barriers and Facilitators of Diabetes Self-Management among Pregnant Women with Preexisting Type 2 Diabetes: A Scoping Review

Background: Pregnant women with pre-existing type 2 diabetes (T2DM) are at risk for poor maternal and neonatal outcomes. Previous systematic reviews in women with T2DM have focused on physical activity, blood glucose monitoring, and insulin injections. The purpose of this review was to examine the barriers and facilitators of diabetes self-management. Method: PubMed, CINAHL, and EMBASE databases were searched using PRISMA-ScR guidelines from January 1, 2009, to July 30, 2019. Inclusion criteria included manuscripts written in English and qualitative studies. Themes were compared and contrasted to identify areas of congruence and discrepancy. Results: The review included ten manuscripts with 241 pregnant women with pre-existing T2DM, and eight family members were enrolled with sample sizes ranging from 5-89. First, barriers to knowledge about diabetes in pregnancy, physical activity, dietary control, medication adherence, financial constraints, stress, lack of social support, and cultural beliefs. Second, stress related to the diagnosis, infant outcomes, and cultural expectations. Third, barriers to access to care and disrespect from health care providers. Fourth, a loss of self-control. Fifth, facilitators of diabetes self-management in pregnancy were related to support from family, financial support, support from health care providers. Discussion: Pregnant women with pre-existing T2DM have multiple barriers. Only one manuscript incorporated family members. Further qualitative research may need to seek the perspectives of family members about diabetes self-management in pregnancy and examine how they can provide support to the women. Conclusion: This supports an integrative model of maternity care to overcome critical barriers and optimize key facilitators to enhance diabetes self-management behaviors and improve maternal and neonatal health outcomes. Disclosure R. Phonyiam: None. D.C. Berry: None.

Screening and follow-up of pregestational diabetes and gestational diabetes mellitus: A survey of primary care physicians in Belgium

AimsConsensus regarding the best screening and follow-up strategy for gestational diabetes mellitus (GDM) is lacking, resulting in heterogeneity in clinical practice. We aimed to evaluate screening and follow-up practices for pregestational type 2 diabetes (T2DM) and GDM in primary care in Belgium. MethodsWe performed an online survey among primary care physicians (PCPs) in the northern part of Belgium, Flanders. ResultsResponses were obtained from 379 PCPs. Approximately two thirds of participants estimated the prevalence of pregestational T2DM and GDM in Flanders at 5% and <10%, respectively. The risk of developing T2DM within 10 years after a history of GDM was estimated at <30% by nearly half of all participants. The majority of interviewed PCPs screen for pre-existing T2DM and GDM. For T2DM, fasting glycaemia was used by 92.2% whereas for GDM, 75.2% used the 50g glucose challenge test (GCT). Fasting glycaemia was the preferred test for postpartum follow-up. ConclusionsWhile overall guideline adherence appears favourable, the prevalence of GDM is underestimated. Increased awareness on the long-term risk for women with a history of GDM is needed. The overall preference for the two-step strategy with GCT indicates that the 2019 Flemish guidelines on GDM screening are attainable in primary care.

Clinical practice guidelines on diabetes mellitus and pregnancy: Ι. Pre-existing type 1 and type 2 diabetes mellitus.

Women with type 1 (T1DM) or type 2 diabetes (T2DM) diagnosed prior to pregnancy are classified as having pre-existing diabetes mellitus (DM). The prevalence of hyperglycemia in pregnancy has been estimated at 17% globally and 5.4% in Europe, differences existing among racial and ethnic groups, following the prevalence of type 2 diabetes. Only a minority (approximately 15%) of the cases of diabetes during pregnancy represent women with pre-existing diabetes. Because of the rising prevalence of obesity and limited screening for diabetes in young women, there has been, globally, an increase in the diagnosis of previously unknown overt diabetes early in pregnancy; these women should be treated as women with pre-existing diabetes, as they may already have unrecognized complications (e.g., nephropathy and retinopathy). The Hellenic Endocrine Society and the Hellenic Society of Maternal-Fetal Medicine commissioned an expert group to construct national guidelines on "Diabetes mellitus and pregnancy: Pre-existing type 1 and 2 diabetes mellitus". Following a search for the best available evidence and critical appraisal of the search results, the writing group generated a series of consensus recommendations regarding preconception counseling and care, care during pregnancy, and care after the pregnancy in cases of pre-existing T1DM and T2DM.

Linagliptin Attenuates the Cardiac Dysfunction Associated With Experimental Sepsis in Mice With Pre-existing Type 2 Diabetes by Inhibiting NF-κB.

The mortality rate of patients who develop sepsis-related cardiac dysfunction is high. Many disease conditions (e.g., diabetes) increase the susceptibility to infections and subsequently sepsis. Activation of the NF-κB pathway plays a crucial role in the pathophysiology of sepsis-associated cardiac dysfunction and diabetic cardiomyopathy. The effect of diabetes on outcomes in patients with sepsis is still highly controversial. We here hypothesized that type 2 diabetes (T2DM) augments the cardiac (organ) dysfunction associated with sepsis, and that inhibition of the NF-κB pathway with linagliptin attenuates the cardiac (organ) dysfunction in mice with T2DM/sepsis. To investigate this, 10-week old male C57BL/6 mice were randomized to receive normal chow or high fat diet (HFD), 60% of calories derived from fat). After 12 weeks, mice were subjected to sham surgery or cecal ligation and puncture (CLP) for 24 h. At 1 hour after surgery, mice were treated with linagliptin (10 mg/kg, i.v.), IKK-16 (1 mg/kg, i.v.), or vehicle (2% DMSO, 3 ml/kg, i.v.). Mice also received analgesia, fluids and antibiotics at 6 and 18 h after surgery. Mice that received HFD showed a significant increase in body weight, impairment in glucose tolerance, reduction in ejection fraction (%EF), and increase in alanine aminotransferase (ALT). Mice on HFD subjected to CLP showed further reduction in %EF, increase in ALT, developed acute kidney dysfunction and lung injury. They also showed significant increase in NF-κB pathway, iNOS expression, and serum inflammatory cytokines compared to sham surgery group. Treatment of HFD-CLP mice with linagliptin or IKK-16 resulted in significant reductions in (i) cardiac, liver, kidney, and lung injury associated with CLP-sepsis, (ii) NF-κB activation and iNOS expression in the heart, and (iii) serum inflammatory cytokine levels compared to HFD-CLP mice treated with vehicle. Our data show that pre-existing type 2 diabetes phenotype worsens the organ dysfunction/injury associated with CLP-sepsis in mice. Most notably, inhibition of NF-κB reduces the organ dysfunction/injury associated with sepsis in mice with pre-existing T2DM.

Strontium Ranelate Combined with Insulin Is as Beneficial as Insulin Alone in Treatment of Fracture Healing in Ovariectomized Diabetic Rats.

BackgroundType 2 diabetes mellitus (T2DM) and estrogen deficiency both predispose fracture patients to increased risk of delayed union or nonunion. The present study investigated the effects of strontium ranelate (SR) on fracture healing in ovariectomized (OVX) diabetic rats.Material/MethodsA mid-shaft fracture was established in female normal control (CF), diabetic (DF), and OVX diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after fracture. Fracture healing was evaluated using radiological, histological, immunohistochemical, and micro-computed tomography analyses.ResultsAt 3 weeks after fracture, radiological and histological evaluations demonstrated delayed fracture healing in the DF group compared with the CF group, which was exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD, BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in the DOF group. All these changes were prevented by insulin alone or combined with SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3 weeks after fracture.ConclusionsThese results demonstrated delayed fracture healing with preexisting estrogen deficiency and T2DM. While insulin alone and combined with SR were both effective in promoting bone fracture healing in this model, their combined treatment showed significant improvement in promoting osteogenic marker expression, but not of the radiological appearance, compared with insulin alone.

Prevalence of Gestational Diabetes and Preexisting Type 2 Diabetes in a 10-Year Multistate Hospital Discharge Cohort

Background: Gestational diabetes (GDM) and preexisting type 2 diabetes (T2DM) in pregnancy are important public health challenges. Our study updates previous literature, using hospital discharge data to define the trends in GDM and preexisting T2DM in multiple states over 10 years. Methods: Utilizing a validated ICD-9 code algorithm, we defined a retrospective cohort of deliveries from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) for FL, NY, and NE from 2005-2014. The HCUP SID contains hospital discharge data for all hospitalizations within a year. Prevalence of GDM and preexisting T2DM were calculated by state and year. Associations with race and socioeconomic status were explored. Results: Of 4,690,551 births in the cohort, 270,623 were complicated by GDM (5.8%) and 26,261 (0.6%) were complicated by preexisting T2DM. The prevalence of GDM increased from 4.8% in 20to 6.7% in 2014. The prevalence of preexisting T2DM increased from 0.5% in 20to 0.7% in 2014. Native Americans had the highest rates of both preexisting T2DM (0.8-1.7%) and GDM (8.0-15.1%). Preexisting T2DM was next most common among African Americans (0.7% in 20to 1.1% in 2014), and GDM was next most common among Asian/Pacific Islanders (8.1% in 20to 13.1% in 2014). Rates of preexisting T2DM were higher in the lowest income compared to the highest income zip codes (0.8 vs. 0.5% FL, 0.6 vs. 0.3% NY, 0.7 vs. 0.3% NE), with rates declining across income quartiles. Women missing income quartile data had higher rates of preexisting T2DM (0.8-0.9%). GDM did not show a similar trend with socioeconomic status. Conclusions: The prevalence of GDM and preexisting T2DM increased between 20and 2014 with rates varying by race. Lower socioeconomic status was associated with higher rates of preexisting T2DM. We will use multivariable analysis to explore associations between GDM and preexisting T2DM and demographic, clinical, and healthcare system access variables. Disclosure C.J. Herrick: Stock/Shareholder; Spouse/Partner; Cardinal Health. M. Keller: None. M.A. Olsen: Research Support; Self; Sanofi Pasteur. Consultant; Self; Pfizer Inc.. Research Support; Self; Pfizer Inc..

A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus.

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.