Requiring Insulin Treatment Research Articles

Predictors of Insulin Treatment During Pregnancy and Abnormal Postpartum Glucose Metabolism in Patients with Gestational Diabetes Mellitus.

BackgroundTo investigate the potential predictors of insulin treatment during pregnancy and abnormal postpartum glucose metabolism in gestational diabetes mellitus (GDM).MethodsA total of 534 patients with GDM, who were diagnosed based on 75 g oral glucose tolerance test (OGTT) during pregnancy, were divided into the diet group (n=354) and insulin group (n=180) according to the treatment of hyperglycemia in pregnancy. Based on 75 g OGTT after delivery, 178 of the 534 patients were divided into the normal glucose tolerance (NGT; n=104) and the abnormal glucose tolerance (AGT; n=74) groups. Characteristics and metabolic indicators were compared. Logistic regression analysis was developed to assess the potential predictors of insulin treatment and abnormal postpartum glucose metabolism. Receiver operating characteristic curve was performed to determine the cut-off values.ResultsFasting plasma glucose (FPG), 1 h plasma glucose, and hemoglobin A1c (HbA1c) at GDM diagnosis were higher in the insulin group compared with the diet group (P <0.05). FPG, 1 h plasma glucose, HbA1c, maternal age, pre-gestational weight and maximum weight, pre-gestational body mass index, maternal birth weight, family history of diabetes in first-degree relatives, acanthosis nigricans, and prenatal weight were risk factors for insulin treatment (P <0.05), and the cut-offs of FPG, 1 h plasma glucose and HbA1c were 5.7 mmol/L, 11.4 mmol/L and 5.3%. Simultaneously, FPG at GDM diagnosis, insulin treatment during pregnancy, maternal age, family history of diabetes in first-degree relatives, acanthosis nigricans, and prenatal weight were risk factors of abnormal postpartum glucose metabolism (P <0.05), and the cut-off of FPG was 5.7 mmol/L.ConclusionPatients with FPG >5.7 mmol/L, 1 h plasma glucose >11.4 mmol/L, or HbA1c >5.3% at GDM diagnosis required insulin treatment, and patients with FPG >5.7 mmol/L had a greater risk of abnormal postpartum glucose metabolism. FPG at GDM diagnosis was the most important predictor.

Risk factors and management of corticosteroid‐induced hyperglycaemia in paediatric acute lymphoblastic leukaemia

Corticosteroids are incorporated into protocols for the treatment of acute lymphoblastic leukaemia, and hyperglycaemia is a recognised side effect. Corticosteroids exert their hyperglycaemic effect with a multifactorial mechanism. Complications of hyperglycaemia include an increased risk of infection - bacterial, viral and fungal. Approximately half of the children who develop corticosteroid-associated hyperglycaemia are predicted to require insulin treatment, with age and obesity having found to be predictive factors. Fasting and random glucose values can be used to define hyperglycaemia. This review focuses on the published evidence for significant predictive factors for the development of corticosteroid-induced hyperglycaemia and provides guidance on management.

Association of Body Mass Index and Outcome in Acutely Ill Patients With Chronic Kidney Disease Requiring Intensive Care Therapy

An association of body mass index (BMI) and outcome, the "obesity paradox," has been described in patients with chronic kidney disease (CKD) and end-stage renal disease. We sought to assess whether a potential beneficial effect of a high body mass is also seen in CKD patients with critical illness. In a retrospective analysis of a prospectively collected database of 123,416 patients from 107 Austrian intensive care units (ICUs) in whom BMI was available, the association of 6 groups of BMI and hospital mortality was assessed in 12,206 patients with CKD 3-5 by univariate and multivariate logistic regression analyses. Patients with CKD were sicker, had a longer ICU stay, and had a higher ICU and hospital mortality than those without. The association of BMI and outcome in CKD patients indicated a U-shaped curve with the highest mortality in patients with BMI <20 and ≥40, and the lowest with a BMI between ≥25 and <40. This relationship was also significant in a multivariate analysis adjusted for severity of illness assessed by Simplified Acute Physiology Score III score, age, gender, admission diagnosis, and pre-existing comorbidities. It was not found in patients with CKD 5 on renal replacement therapy, in patients below 60years of age, and those with diabetes mellitus requiring insulin treatment. BMI is associated with better outcomes in CKD 3-5 patients who have acquired acute intermittent diseases and are admitted to an ICU, but not those requiring renal replacement therapy. This higher tolerance to acute disease processes may in part explain the "obesity paradox" observed in CKD patients.

The effect of smoking on the risk of gestational diabetes mellitus and the OGTT profile during pregnancy

ObjectiveTo analyze the relationship between smoking and the risk of GDM, as well as with the OGTT profile during pregnancy. Patients and methodsA total of 7437 pregnant women were studied. OGTT was performed at the 3rd trimester. Women were categorized as non-smokers (A), as those who ceased smoking at pregnancy (B), and as smokers (C). Results5434 (73.1%) women were group A, 1191 (16%) group B and 812 (10.9%) group C. The rates of GDM among the groups were: A 33.7%, B 34.2%, C 34.2% (ns). However, the number of individuals requiring insulin treatment was significantly different: A 39.2%, B 47.5%, C 50.6% (p < 0.001). Regarding OGTT, fasting glucose levels were significantly higher in group C (89 ± 13 vs 86 ± 12 mg/dl) compared to A, whereas 3-h glucose values were significantly lower (104 ± 33 vs 112 ± 32 mg/dl) (p < 0.001). Group B demonstrated intermediate glucose concentrations. Similar findings were observed in women without GDM. In women with GDM, higher 1-h glucose levels were measured in group C (210 ± 31 vs 205 ± 28 mg/dl) compared with A (p = 0.024). Further, group C sub-analysis found that those who smoked more than 10 cigarettes showed significantly lower 3-h glucose levels (111 ± 31 vs 128 ± 40 mg/dl) compared to those who smoked less than 10 (p = 0.006). HbA1c in women with GDM was higher in group C (4.6 ± 0.6 vs 4.5 ± 0.6%) compared with A (p = 0.027). ConclusionsThe present study did not show any correlation between smoking and GDM risk. However, OGTT profile and HbA1c differed according to smoking status in women with and without GDM.

Effectiveness and safety of sotagliflozin adjuvant therapy for type 1 diabetes mellitus: A protocol for Systematic review and Meta-analysis.

Background:Type 1 Diabetes Mellitus (T1DM) has long required insulin treatment. Sotagliflflozin (SOTA), as a dual SGLT-1/2 inhibitor, has the potential to be the first oral antidiabetic drug (OAD) to be approved for T1DM in the US market. It is important to evaluate the effectiveness of SOTA for T1DM.Methods:Web of Science, PubMed datebase, Cochrane Library, Embase, Clinical Trials, and CNKI will be searched to identify randomized controlled trials (RCTs) exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluation will be performed on the obtained literature independently by 2 researchers; outcome indexes will be extracted. The bias risk of the included studies will be evaluated based on Cochrane assessment tool. Meta-analysis will be performed on the data using Revman 5.3 software.Result:We will provide practical and targeted results assessing the efficacy and safety of SOTA for T1DM patients, to provide reference for clinical use of SOTA.Conclusion:The stronger evidence about the efficacy and safety of SOTA for T1DM patients will be provided for clinicians.Trial registration number:PROSPERO CRD42019133099.

OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients

BACKGROUND: Adrenal incidentalomas (AI) are frequently associated with mild autonomous cortisol excess (MACE). The 1mg-dexamethasone suppression test (1mg-DST) differentiates MACE into MACE-1 (possible MACE; post-Dex cortisol 50-138 nmol/L) and MACE-2 (definitive MACE; post-Dex cortisol >138 nmol/L). MACE patients do not show clinically overt signs of hypercortisolism but are thought to carry a higher metabolic risk than nonfunctioning (NF) AIs. However, large-scale data about the metabolic impact of MACE are lacking. METHODS: We included 1208 patients with benign AIs and 1mg-DST results prospectively recruited as part of the ENSAT EURINE-ACT study. Clinical information and 24-h urines were available for all patients. Results of mass spectrometry-based urinary steroid profiling were compared to 162 healthy controls and 56 patients with overt adrenal Cushing’s syndrome (CUSH), using a sex- and age-adjusted linear regression model. RESULTS: MACE was found in 48% of adrenal incidentaloma patients (MACE-1 37%, MACE-2 11%), predominantly affecting women (NF 64%, MACE-1 67%, MACE-2 77%). MACE patients were significantly older than those with NF (p<0.001). MACE AIs were larger (median 32mm vs. 22mm in NF) and more often bilateral (31% vs. 17% in NF). The presence and grade of MACE were significantly linked to metabolic risk as assessed by prevalence of hypertension (NF 64%, MACE-1 75%, MACE-2 78%), type 2 diabetes (NF 20%, MACE-1 27%, MACE-2 30%), use of lipid-lowering medications (NF 40%, MACE-1 54%, MACE-2 52%), and osteopenia/osteoporosis (NF 37%, MACE-1 50%, MACE-2 56%) (all p<0.01 by Fisher’s exact test). Patients with MACE and type 2 diabetes more frequently required insulin treatment (31% vs. 15% in NF; p<0.01), and those with hypertension more often needed ≥3 medications (42% vs. 35% in NF; p<0.01). Urinary steroid metabolome analysis of MACE urines revealed a profile characterized by decreased androgen metabolites and increased glucocorticoid metabolites, resembling the profile of CUSH patients, with the latter also showing significantly increased mineralocorticoid precursor excretion (corticosterone and 11- deoxycorticosterone metabolites) (all p<0.001 vs. controls). CONCLUSIONS: MACE is highly prevalent in AIs and associated with an increased burden of metabolic co-morbidities. In addition, the similarities between the MACE and CUSH steroid metabolomes suggests that MACE is both a highly relevant clinical and biochemical entity.

Two Cases of Type 2 Diabetes Treated With Abiraterone Acetate/steroid Combination Therapy for Prostate Cancer Requiring Insulin Treatment

Two Cases of Type 2 Diabetes Treated With Abiraterone Acetate/steroid Combination Therapy for Prostate Cancer Requiring Insulin Treatment

Insulin-dependent diabetes: A chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia.

Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death. Here, we provide novel data on seven patients diagnosed with diabetes after pancreatitis and still requiring insulin treatment after a median follow-up of 4.2years (range: 1.7-9.2). We describe the clinical course of pancreatitis and illustrate the association between pancreatic pseudocysts, older age, and development of insulin-dependent diabetes. Together, this study documents the persisting burden of pancreatitis in childhood ALL and underlines the need for plasma glucose level monitoring.

Prevalence of Impaired Awareness of Hypoglycemia and Severe Hypoglycemia among People with Type 2 Diabetes Treated with Insulin—The Dutch Diabetes Pearl Cohort

Aim: Most people with type 2 diabetes eventually require insulin treatment because of progressive loss of beta-cell function. The most common adverse effect of insulin therapy is hypoglycemia. Recurrent hypoglycemia may lead to impaired awareness of hypoglycemia (IAH) and a consequently high risk for severe hypoglycemia. The aim of this study was to determine the prevalence of IAH and severe hypoglycemia in a large cohort of people with insulin-treated type 2 diabetes. Methods: The Dutch Diabetes Pearl is a contemporary cohort of people with type 2 diabetes from primary, secondary and tertiary medical centers in the Netherlands. We collected data from people on insulin therapy who had completed the validated Dutch version of the Clarke questionnaire on IAH, where 3 out of 5 points indicate IAH. Descriptive statistics, T-tests and Chi-square tests were performed. Results: Our study included 1923 patients of whom 59% were men. Median age was 62.1 years (interquartile range 55.1-68.3), median diabetes duration was 13.9 years (8.8-20.1) and median HbA1c was 7.6 % (7.0-8.5). 2individuals (10.8%) were classified as having IAH; these people were more likely to be non-Caucasian and have a lower educational level, and less likely to have a partner. Severe hypoglycemia was reported in 617 patients (32.1%) and severe hypoglycemia requiring medical intervention in the past year in 166 patients (8.6%). People with severe hypoglycemia were more likely to be non-Caucasian, to have a lower educational level, to have a history of cardiovascular events and neuropathic pain, and to use over 10 different types of drugs. No significant associations between HbA1c-levels and IAH or severe hypoglycemia were observed. Conclusion: IAH and severe hypoglycemia are common in people with type 2 diabetes treated with insulin. Non- Caucasian ethnicity, lower educational level, and being single may be risk factors for IAH in patients with type 2 diabetes. Disclosure L. van Meijel: None. F. de Vegt: None. C. Tack: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Novo Nordisk A/S. E.J. Abbink: None. F. Rutters: None. J.M. Dekker: None. B.H. Wolffenbuttel: None. F. Holleman: Other Relationship; Self; Sanofi-Aventis, Bioton, AstraZeneca. J. DeVries: Research Support; Self; Dexcom, Inc., Medtronic, Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Sanofi. Research Support; Self; Senseonics. Speaker's Bureau; Self; Senseonics. Advisory Panel; Self; Zealand Pharma A/S. N. Masurel: None. H. Pijl: None. B. Ozcan: None. B. Silvius: None. B.E. de Galan: Research Support; Self; AstraZeneca, Sanofi. Advisory Panel; Self; Novo Nordisk A/S.

Effects of inositol on glucose homeostasis: Systematic review and meta-analysis of randomized controlled trials

The effect of inositol on glucose homeostasis is not well characterized. The aim of the present meta-analysis is to synthesize the effects of inositol on glucose homeostasis in different clinical conditions. We performed a systematic review (CRD42017057927) following PRISMA guidelines. Web of Science and Medline were searched for randomized controlled trials (RCTs) that addressed supplementation with compounds of the inositol family in humans and assessed their effects on glucose homeostasis. We screened 476 abstracts and included 20 RCTs with a total of 1239 subjects. Meta-analysis showed in the treatment arm a reduction in fasting plasma glucose (Mean difference (MD)-0.44mmol/l, 95% CI-0.65,-0.23), 2h PG after 75g OGTT (MD-0.69mmol/l, 95% CI-1.14,-0.23), abnormal glucose tolerance (Relative risk (RR) 0.28, 95% CI 0.12, 0.66), fasting insulin (MD-38.49pmol/l, 95% CI-52.63,-24.36), and HOMA-IR (MD-1.96mmol×mUI/l, 95% CI-2.62,-1.30). No differences were observed in BMI, HbA1c and % of patients requiring insulin treatment. Sensitivity analysis did not change treatment estimates. Mention to adverse events was only present in 13 articles with no sign of seriousness. Inositol supplementation decreases blood glucose through an improvement in insulin sensitivity that is independent of weight. Assessment of adverse effects is scarce among published trials and should be fully addressed before considering inositol as a therapeutic agent for glucose-related outcomes. The characterization of the subjects achieving benefit from the intervention and the formulations to be used should also be known.

Association between CEL-HYB1 allele and idiopathic/familial chronic pancreatitis in Polish pediatric patients

There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth.This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017.Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3–15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection.In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant.

Longitudinal Study of Rhesus Monkeys Determines That Amylase and Lipase Levels Are Significant Risk Factors for Type 2 Diabetes Mellitus

Decreased levels of amylase have been reported in type 2 diabetes (T2DM), however, longitudinal within subject study ranging from healthy normal levels to preT2DM and overt DM has not previously been conducted in humans or in nonhuman primates. Rhesus monkeys provide the ideal subjects for this study as they are maintained under constant dietary and environmental conditions, and have, to date, been shown to have the same gastrointestinal/pancreas physiology and pathophysiology as humans. They frequently develop T2DM spontaneously and naturally, with no experimental intervention, and with life time rates of T2DM estimated to be 20 to 30 %. Adult rhesus monkeys were studied for a minimum of 3 years and a maximum of 20 years, with a minimum of 2 metabolic parameter measurements per year. These parameters included fasting plasma glucose (FPG), fasting plasma insulin (FPI), complete blood chemistry, and lipid profiles. Body fat was determined by the tritiated water dilution method or by the dual energy xray absorptiometry (DEXA). Insulin sensitivity was quantified by the euglycemic hyperinsulinemic clamp method. These parameters were used to identify the phases in the progression of monkeys from normal to overt diabetes as follows: normal = phases 1–3; metabolic syndrome = phases 4–6, impaired glucose tolerance= phase 7, and overt type 2 diabetes = phase 8. Diabetic monkeys requiring insulin treatment were excluded from this study. Human criteria were used to define MetSyn, IGT and T2DM. Normal healthy serum amylase levels were determined for the first time and shown to be 253 ±5.1 U/L for adults 7 to 11 yrs old (“human years” about 21 to 35 yrs), with normal lipase levels of 29.7± 1.6 U/L. Serum amylase levels declined with age by about 25%, with no change in serum lipase levels with age. In those that progressed through phases 4 to 8 reaching overt type 2 diabetes, serum amylase showed significantly greater declines from ages 13 to 20 yrs with progressive and parallel declines in metabolic parameters, including insulin sensitivity, and HDL cholesterol levels and increases in serum triglycerides and subsequently increases in fasting plasma glucose. The significant rise in serum triglycerides and the decline in amylase together serve as excellent early predictors of the progression to overt T2DM. These risk factors were highly predictive of both early and late onset diabetes. The lower amylase levels observed previously in people with diabetes were clearly not a consequence of diabetes, but were in fact markers of impending diabetes. Such biomarkers are likely to be useful in predicting the development of T2DM in patients years before the disease becomes overt.This study was carried out in accord with the FASEB principles for the use of animals in research.Support or Funding InformationThe work was supported by NIA N01AG31012 and NIA HHSN2532008002C to BCH, and the Department of Health Research, Government of India Human Resources Development Fellowship to UKC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The impact of a daily smartphone-based feedback system among women with gestational diabetes on compliance, glycemic control, satisfaction, and pregnancy outcome: a randomized controlled trial

Patient compliance and tight glycemic control have been demonstrated to improve outcome in pregnancies complicated by gestational diabetes mellitus. The use of advanced technological tools, including smartphone-based platforms, to improve medical care and outcomes has been demonstrated in various fields of medicine, but only a few small studies were performed with gestational diabetes mellitus patients. We aimed to study the impact of introducing a smartphone-based daily feedback and communication platform between gestational diabetes mellitus patients and their physicians, on patient compliance, glycemic control, pregnancy outcome, and patient satisfaction. This is a prospective, single-center, randomized controlled trial. Newly diagnosed gestational diabetes mellitus patients presenting to our multidisciplinary diabetes-in-pregnancy clinic were randomized to: (1) routine biweekly prenatal clinic care (control group); or (2) additional daily detailed feedback on their compliance and glycemic control from the clinic team via an application installed on theirsmartphone (smartphone group). The primary outcome was patientcompliance defined as the actual blood glucose measurements/instructed measurements×100. The secondary outcomes included diabetes-control parameters, pregnancy, and neonatal outcomes. The study was adequately powered to detect a 20% difference in patient compliance, based on a preliminary phase that demonstrated 70% baseline compliance to glucose measurements. A total of 120 newly diagnosed gestational diabetes mellitus patients were analyzed. The 2 groups did not differ in terms of age, parity, education, body mass index, family history, maternal comorbidities, oral glucose tolerance test values, and hemoglobin A1C at randomization. Thesmartphone group demonstrated higher level of compliance (84 ± 0.16% vs 66 ± 0.28%, P < .001); lower mean blood glucose (105.1 ± 8.6 mg/dL vs 112.6 ± 7.4 mg/dL, P < .001); lower rates of off-target measurements both fasting (4.7 ± 0.4% vs 8.4 ± 0.6%, P < .001) and 1-hour postprandial (7.7 ± 0.8% vs 14.3 ± 0.8%, P < .001); and a lower rate of pregnancies requiring insulin treatment (13.3% vs 30.0%, P= .044). The rates of macrosomia, neonatal hypoglycemia, shoulder dystocia, and other delivery and neonatal complications did not differ between the groups. Patients in the smartphone group reported excellent satisfaction from the use of the application and from their overall prenatal care. Introduction of a smartphone-based daily feedback and communication platform between gestational diabetes mellitus patients and the multidisciplinary diabetes-in-pregnancy clinic team improved patient compliance and glycemic control, and lowered the rate of insulin treatment.

625: The intricate interface between metabolic and inflammation regulation: Placental expression of Semaphorin 3E and its receptor, PlexinD1, are associated with obesity and insulin resistance in normal pregnancy and gestational diabetes mellitus

Semaphorin 3E (Sema3E) is a novel adipokine implicated in the crosstalk between inflammation, obesity and insulin resistance. The aims of this study were to determine whether there is placental expression of Sema3E and its receptor, PlexinD1, in human placenta, and whether the expression is different in pregnancies complicated by gestational diabetes mellitus. This was a cross sectional study. Placental mRNA expression for Sema3E and its receptor, PlexinD1, was determined in two groups: 1. uncomplicated pregnant women (n=24) and 2. pregnant women with gestational diabetes mellitus (GDM) requiring insulin treatment (n=9). Non-parametric statistical methods were employed. 1. Placental mRNA expression of PlexinD1 was significantly higher in patients with GDM compared to women with normal gestation (1.32 vs. 0.82, p=0.02), but no difference was found in placental mRNA expression of Sema3E between these two groups (1.33 vs. 1.11, p=0.28); 2. In pooled analysis (normal pregnant women and patients with GDM), placental mRNA expression of both PlexinD1 and Sema3E were higher in obese versus lean/normal weight women (1.25 vs. 0.68, p=0.001; 1.43 vs. 0.98, p=0.04, respectively); 3. Among women with normal gestation, obese women had a higher placental mRNA expression of both PlexinD1 (p=0.001) and Sema3E (p=0.05) than normal weight women, while among patients with GDM, placental mRNA expression of both PlexinD1 and Sema3E (p=0.9 for both comparisons) was comparable between obese and normal weight women. The results of this study indicate that the human placenta constitutively expresses Sema3E and its high-affinity receptor, PlexinD1. Higher placental mRNA expression of PlexinD1 in patients with GDM compared to women with normal gestation, as well as higher placental mRNA expression of both PlexinD1 and Sema3E in obese compared to normal weight pregnant women, suggest that higher placental mRNA expression of PlexinD1 and Sema3E might be associated with increased insulin resistance, and that Sema3E and its receptor may be considered a regulatory mediators involved in metabolic adaptations to normal pregnancy as well as in the pathophysiology of pregnancy-related metabolic complications.

Pancreatectomies for pancreatic neoplasms in pediatric and adolescent age: A single institution experience

BackgroundThere are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth. MethodsThis is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017. ResultsOverall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3–15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection. ConclusionsIn our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant.

Preconception Optimization of Glucose and Insulin Metabolism in Women Wanting to Conceive - High Rate of Spontaneous Conception Prior to Planned Assisted Reproduction.

Background A hyperglycemic metabolic status with insulin resistance can have a negative effect on fertility and pregnancy outcomes. The aim of this retrospective study was to investigate disorders of glucose and insulin metabolism in women wanting to conceive who conceived spontaneously prior to planned assisted reproduction (ART). Associated risk factors of patients in terms of live births and miscarriages were also analyzed. Method Out of total study population of 589 pregnancies, the pregnancies of 129 women wishing to have children who conceived spontaneously prior to planned ART were analyzed in more detail. A 75 g OGTT (OGTT: oral glucose tolerance test) was carried out prior to conception and after determination of pregnancy, including glucose measurement and testing of insulin resistance. If anomalies or risk factors for gestational diabetes (GDM) were detected, patients received metformin therapy prior to conception (off-label use). The course and outcome of pregnancies in the defined cohort were recorded. Results The rate of spontaneous conception before planned ART after treatment for disorders of glucose/insulin metabolism was 21.9% (n = 129/589). 66.7% of the 129 pregnancies resulted in a live birth, 32 patients had a miscarriage. 76.0% of patients were treated with metformin (off-label use) for polycystic ovary syndrome (PCOS), positive risk profile for GDM, or abnormal glucose/insulin metabolism prior to conception. 55.8% of the cohort developed GDM. The insulin requirements of patients with GDM differed significantly depending on their metformin intake. 24.6% of GDM patients receiving metformin treatment developed GDM requiring insulin treatment compared to 53.8% who did not receive metformin medication. The PCOS rate in the study population who had live births was significantly higher (57.0%) than in the group who had miscarriages (31.3%). There were no significant differences with regard to rate of live births and rate of miscarriages with/without metformin treatment and GDM and metformin intake. Conclusion The high rate of spontaneous conceptions in the cohort of women wishing to conceive emphasizes the importance of optimizing glucose/insulin metabolism prior to conception. The high rate of GDM in a cohort of pregnant women with a history of sterility also emphasizes the importance of expanding diagnostic testing for sterility to include the investigation of glucose metabolism and testing for insulin resistance. It is possible that PCOS patients in particular could benefit from treatment with metformin prior to conception, and this could explain the high rate of live births in this patient cohort.

Adjunctive corticosteroid therapy for inpatients with Mycoplasma pneumoniae pneumonia

BackgroundThere is conflicting evidence regarding the benefit of adjunctive corticosteroid therapy in patients with Mycoplasma pneumoniae pneumonia. We hypothesised that corticosteroid therapy could reduce mortality and length of stay (LOS) in such patients.MethodsAdult patients with M. pneumoniae pneumonia from January 2010 to December 2013 were identified from the Japanese Diagnosis Procedure Combination inpatient database. The effects of low-dose and high-dose corticosteroid therapies on mortality, LOS, drug costs and hyperglycaemia requiring insulin treatment were evaluated using propensity score analyses.ResultsEligible patients (n = 2228) from 630 hospitals were divided into no-corticosteroid (n = 1829), low-dose corticosteroid (n = 267) and high-dose corticosteroid (n = 132) groups. The propensity score-matched pairs were generated from no-corticoid and low-dose corticoid groups (251 pairs), or no-corticoid and high-dose corticosteroid groups (120 pairs). Adjunctive corticosteroid therapy did not decrease 30-day mortality. In addition, both low-dose and high-dose corticosteroid therapies were associated with increases in LOS. Furthermore, hyperglycaemia requiring insulin treatment and drug cost increased with corticosteroid use.ConclusionsAdjunctive treatment with low-dose or high-dose corticosteroids may not be beneficial in M. pneumoniae pneumonia.

Adult-onset autoimmune diabetes: current knowledge and implications for management.

Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.

Effects of inositol on glucose homeostasis: systematic review and meta-analysis of randomized controlled trials

Summary Background & aims The effect of inositol on glucose homeostasis is not well characterized. The aim of the present meta-analysis is to synthesize the effects of inositol on glucose homeostasis in different clinical conditions. Methods We performed a systematic review (CRD42017057927) following PRISMA guidelines. Web of Science and Medline were searched for randomized controlled trials (RCTs) that addressed supplementation with compounds of the inositol family in humans and assessed their effects on glucose homeostasis. Results We screened 476 abstracts and included 20 RCTs with a total of 1239 subjects. Meta-analysis showed in the treatment arm a reduction in fasting plasma glucose (Mean difference (MD) −0.44 mmol/l, 95% CI −0.65, −0.23), 2 h PG after 75 g OGTT (MD −0.69 mmol/l, 95% CI −1.14, −0.23), abnormal glucose tolerance (Relative risk (RR) 0.28, 95% CI 0.12, 0.66), fasting insulin (MD −38.49 pmol/l, 95% CI −52.63, −24.36), and HOMA-IR (MD −1.96 mmol × mUI/l, 95% CI −2.62, −1.30). No differences were observed in BMI, HbA1c and % of patients requiring insulin treatment. Sensitivity analysis did not change treatment estimates. Mention to adverse events was only present in 13 articles with no sign of seriousness. Conclusions Inositol supplementation decreases blood glucose through an improvement in insulin sensitivity that is independent of weight. Assessment of adverse effects is scarce among published trials and should be fully addressed before considering inositol as a therapeutic agent for glucose-related outcomes. The characterization of the subjects achieving benefit from the intervention and the formulations to be used should also be known.

GCK, GCKR, FADS1, DGKB/TMEM195 and CDKAL1 Gene Polymorphisms in Women with Gestational Diabetes.

Gestational diabetes mellitus (GDM) is the carbohydrate intolerance that can occur in pregnancy. Genetic polymorphisms associated with type 2 diabetes could be considered as genetic determinants of GDM. The aim of this study was to examine the association between GCK, GCKR, FADS1, DGKB/TMEM195 and CDKAL1 gene polymorphisms and the development of gestational diabetes. These genetic polymorphisms are involved in glucose and lipid metabolism and are associated with increased risk for diabetes type 2. This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-gram oral glucose tolerance test at 24 to 28 weeks' gestation. There was a statistically significant association between FADS1 rs174550 gene polymorphism and GDM. Among women with GDM, a predominance of C-allele carriers (CC and TC genotypes) was observed (CC+TC vs. TT; p=0.00065; OR=1.97, 95% CI, 1.33 to 2.92), and this association remained significant after correction for multiple testing. In the case of the GCK rs1799884 polymorphism, there was a predominance of the T allele in women with GDM; however, this association reached only borderline statistical significance (p=0.08). Women with higher numbers of GCK rs1799884 T alleles more commonly required insulin treatment; likewise, the CDKAL1 rs10946398 CC genotype was associated with the need for insulin therapy. However, these associations do not pass the statistical significance threshold after correction for multiple testing. The results of our study suggest an association between the rs174550 FADS1 polymorphism and GDM risk.