Long-term Metabolic Outcomes Research Articles

Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring.

Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth. To promote an adverse phenotype in young adulthood, after weaning, offspring were reared under a low-activity obesogenic environment with the exception of a subgroup of IUGR offspring, reared as twins, maintained in a standard activity environment. We assessed glucose tolerance together with leptin and cortisol responses to feeding in young adulthood when the hypothalamus was sampled for assessment of genes regulating appetite control, energy and endocrine sensitivity. Caloric restriction reduced maternal plasma glucose, raised non-esterified fatty acids, and changed the metabolomic profile, but had no effect on insulin, leptin, or cortisol. IUGR offspring whose postnatal growth was enhanced and were obese showed insulin and leptin resistance plus raised cortisol. This was accompanied by increased hypothalamic gene expression for energy and glucocorticoid sensitivity. These long-term adaptations were reduced but not normalized in IUGR offspring whose postnatal growth was not accelerated and remained lean in a standard post-weaning environment. IUGR results in an adverse metabolic phenotype, especially when postnatal growth is enhanced and offspring progress to juvenile-onset obesity.

ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria.

Women with previous gestational diabetes (GDM) are a high-risk group for future development of diabetes, metabolic syndrome, and cardiovascular disease. The new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria significantly increase the number of women diagnosed with GDM. The long-term metabolic outcome in these women is unknown. We set out to determine the prevalence of metabolic syndrome, using adult treatment panel-III criteria; and insulin resistance, using HOMA2-IR, in white European women with previous GDM. Using a cohort design, we invited women meeting IADPSG GDM criteria across four Irish antenatal centres between 2007 and 2010 to participate. Two hundred and sixty-five women with previous values meeting IADPSG criteria for GDM participated (44 % of the population eligible for participation). Mean age was 36.7 years (SD 5.0). These women were compared with a randomly selected control group of 378 women (mean age 37.6 years, SD 5.1) known to have normal glucose tolerance (NGT) in pregnancy during the same period. A total of 25.3 % of women with previous IADPSG-defined GDM met metabolic syndrome criteria, compared to 6.6 % of women with NGT [at 2.6 (SD 1.0) vs. 3.3 years (SD 0.7) post-partum]. The prevalence of HOMA2-IR >1.8 was higher in women with previous IADPSG-defined GDM (33.6 vs. 9.1 % with NGT, p < 0.001). Women with previous GDM by IADPSG criteria demonstrate a greater than threefold prevalence of metabolic syndrome compared to women with NGT in pregnancy. Efforts to prevent projected long-term consequences of this should focus on interventions both in the preconception and post-partum periods.

Effects of Laparoscopic Adjustable Gastric Banding on Weight Loss, Metabolism, and Obesity-Related Comorbidities: 5-year Results in China

Despite some reports about the long-term metabolic outcomes after laparoscopic adjustable gastric banding (LAGB) in the Western populations, there are few reports on the Asian population whose body size and fat distribution are different. Therefore, this study was conducted to evaluate the medium-term effects of LAGB on weight loss and metabolic outcomes of obese patients with different body mass index (BMI) in China. A retrospective study was performed to review the 5-year follow-up data of 56 patients (18 males, 38 females) who received LAGB from November 2003 to May 2013 at the Shanghai Changhai Hospital. The patients were evaluated at years 1, 3, and 5 after operation in the outpatient clinic, and the weight loss, metabolic parameters, and remission of comorbidities were measured. The 56 patients preoperatively had BMI of 37.4 ± 6.0 kg/m2, with BMI < 35 kg/m2 in 19 patients (BMI <35 kg/m2 group), and BMI ≥ 35 kg/m2 in 37 patients (BMI ≥ 35 kg/m2 group). The percentages of excess weight loss (%EWL) of the BMI < 35 kg/m2 group at years 1, 3, and 5 were 65.2, 65.6, and 65.7%, respectively, indicating the majority of metabolic parameters were significantly improved (P < 0.05). However, in the BMI ≥ 35 kg/m2 group, the %EWL were 37.9, 34.8, and 26.5%, respectively, except at year 1 when the metabolic parameters improved significantly (P < 0.05), those at year 3 and year 5 did not significantly improve compared with the preoperative levels. Similar results were observed in the improvement of comorbidities. Relatively low medium-term weight loss, metabolic improvement, and resolution or remission of obesity-related comorbidities and high reoperation rate were observed in our population of patients with BMI ≥ 35 kg/m2 who underwent LAGB.

Severe hyperemesis gravidarum affects offspring metabolism in childhood

Hyperemesis gravidarum leads to alterations in maternal (and possibly fetal) nutrition throughout pregnancy, but there are no data on the long-term metabolic health outcomes in the offspring. We hypothesized that hyperemesis gravidarum could lead to fetal nutritional compromise or physiological stress, which may programme later metabolism and body composition. Two groups of healthy pre-pubertal children born at term, aged 4–11 years were studied: offspring of mothers who suffered hyperemesis gravidarum (HG group; n=36) and controls (n=54). Recruited HG children were born to mothers admitted to hospital with metabolic disturbance during pregnancy. Following an overnight fast, a frequently sampled intravenous glucose tolerance test modified by insulin was performed, and insulin sensitivity was measured using Bergman’s minimal model. Other assessments included fasting lipid and hormonal profiles, as well as body composition using whole-body dual-energy x-ray absorptiometry. Data were analysed separately using linear mixed models, controlling for appropriate confounders. Data are expressed as mean±SEM. Children born to mothers with severe HG had reduced SI (10.4±0.6 vs 13.4±0.9 x10 -4 min �1 ·(mU/L); p=0.016), increased fasting insulin (6.5±0.6 vs 4.9± 0.3 mIU/L; p=0.023), reduced IGFBP1 (13.0±1.3 vs 18.0±1.6 ng/ml; p=0.029) and IGFBP3 (3017±106 vs 3497±102 ng/ml; p=0.008) in comparison to controls. Baseline cortisol was higher in HG children (251±13 vs 218±11 nmol/l; p=0.007). DEXA-derived body composition was similar in HG and control groups. Children born to mothers who experienced severe hyperemesis gravidarum were less insulin sensitive and had elevated baseline cortisol compared to controls. We postulate that severe hyperemesis gravidarum reduces insulin sensitivity in the offspring due to fetal programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Long-term follow up of these offspring is essential to determine later risk of metabolic disease.

Benefits and Harms of Treating Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research

Outcomes of treating gestational diabetes mellitus (GDM) are not well-established. To summarize evidence about the maternal and neonatal benefits and harms of treating GDM. 15 electronic databases from 1995 to May 2012, gray literature, Web sites of relevant organizations, trial registries, and reference lists. English-language randomized, controlled trials (n = 5) and cohort studies (n = 6) of women without known preexisting diabetes. One reviewer extracted data, and a second reviewer verified them. Two reviewers independently assessed methodological quality and evaluated strength of evidence for primary outcomes by using a Grading of Recommendations Assessment, Development and Evaluation approach. All studies compared diet modification, glucose monitoring, and insulin as needed with no treatment. Women who were treated had more prenatal visits than those in control groups. Moderate evidence showed fewer cases of preeclampsia, shoulder dystocia, and macrosomia in the treated group. Evidence was insufficient for maternal weight gain and birth injury. Low evidence showed no difference between groups for neonatal hypoglycemia. Evidence was insufficient for long-term metabolic outcomes among offspring. No difference was found for cesarean delivery (low evidence), induction of labor (insufficient evidence), small-for-gestational-age neonates (moderate evidence), or admission to a neonatal intensive care unit (low evidence). Evidence is low or insufficient for many outcomes of greatest clinical importance. The strongest evidence supports reductions in intermediate outcomes; however, other factors (for example, maternal weight and gestational weight gain) may impart greater risk than GDM, particularly when glucose levels are modestly elevated. Treating GDM results in less preeclampsia, shoulder dystocia, and macrosomia; however, current evidence does not show an effect on neonatal hypoglycemia or future poor metabolic outcomes. There is little evidence of short-term harm of treating GDM other than an increased demand for services.

Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE).

OBJECTIVEThe epidemic of type 2 diabetes (T2DM) threatens to become the major public health problem of this century. However, a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted. GRADE, a pragmatic, unmasked clinical trial, aims to compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.RESEARCH DESIGN AND METHODSGRADE was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The consensus protocol was approved by NIDDK and the GRADE Research Group. Eligibility criteria for the 5,000 metformin-treated subjects include <5 years' diabetes duration, ≥30 years of age at time of diagnosis, and baseline hemoglobin A1c (A1C) of 6.8–8.5% (51–69 mmol/mol). Medications representing four classes (sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and insulin) will be randomly assigned and added to metformin (minimum–maximum 1,000–2,000 mg/day). The primary metabolic outcome is the time to primary failure defined as an A1C ≥7% (53 mmol/mol), subsequently confirmed, over an anticipated mean observation period of 4.8 years (range 4–7 years). Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C >7.5% (58 mmol/mol) and, ultimately, the need to implement an intensive basal/bolus insulin regimen. The four drugs will also be compared with respect to selected microvascular complications, cardiovascular disease risk factors, adverse effects, tolerability, quality of life, and cost-effectiveness.CONCLUSIONSGRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM. GRADE begins recruitment at 37 centers in the U.S. in 2013.

Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that reducing excess maternal inflammation may be a promising target for preventing adverse fetal metabolic outcomes in pregnancies complicated by maternal obesity.

Feeding Preterm Infants Today for Later Metabolic and Cardiovascular Outcomes

Preterm birth continues to contribute disproportionately to neonatal morbidity and subsequent physical and neurodevelopmental disabilities. Epidemiologic studies have described additional long-term health consequences of preterm birth such as an increased risk of hypertension and insulin resistance in adult life. It is not known whether the influence of infant and childhood growth rates and early nutrition on long-term outcomes is the same or different among preterm infants and neonates with intrauterine growth restriction. Our goal is to review the effects of fetal growth, postnatal growth, and early nutrition on long-term cardiovascular and metabolic outcomes in preterm infants. Present evidence suggests that even brief periods of relative undernutrition during a sensitive period of development have significant adverse effects on later development. Our review suggests that growth between birth and expected term and 12-18 months post-term has no significant effect on later blood pressure and metabolic syndrome, whereas reduced growth during hospitalization significantly impacts later neurodevelopment. In contrast, growth during late infancy and childhood appears to be a major determinant of later metabolic and cardiovascular well being, which suggests that nutritional interventions during this period are worthy of more study. Our review also highlights the paucity of well-designed, controlled studies in preterm infants of the effects of nutrition during hospitalization and after discharge on development, the risk of developing hypertension, or insulin resistance.

Economic Evaluation of Continuous Subcutaneous Insulin Infusion for Children with Diabetes—Part II

The aim of this study is to assess long-term metabolic outcomes in children with diabetes mellitus and to compare the efficacy, feasibility and metabolic control expenses for treatment with continuous subcutaneous insulin infusion (CSII), compared to human insulin treatment. The study sample included 34 children aged 3 to 18 years with type 1 diabetes, 17 with continuous subcutaneous insulin infusion (CSII) therapy and 17 with standard treatment with human insulin. The study observed for the following variables: duration of the disease, diabetic control, HbA1c deviation scores; height and weight deviation and price of the treatment. Methods applied include meta-analyses in the published medical literature, pharmacoeconomic analysis and statistical analysis. From the 34 children with diabetes type 1 observed retrospectively during the period 1999-2012, 17 were on CSII (mean age 10 years, mean duration of the disease—7 years, average usage of CSII—3 years). The test stripes cost 533 Euro/year (1100 stripes per year) and their average cost according to the duration of the disease is 3779.45 Euro since diagnosis. The blood glucose monitoring system costs 20 Euro and for the duration of the disease—4.96 Euro per patient per year. The average improvement of HbA(1c) after the CSII introduction is 1.85, while after the application of human insulin—0.28. The treatment with CSII leads to significant improvement in glycemic control compared to the treatment with human insulin. The reduced HbA(1c) shows good diabetes management, from one point of view, and good quality of life—from another.

Offspring’s blood pressure and metabolic phenotype after exposure to gestational hypertension in utero

The aim of the study was to investigate the impact of de novo hypertension in pregnancy, i.e. gestational (non-proteinuric) hypertension (GH) and preeclampsia (PE), on the long-term metabolic outcome of the offspring. Data was obtained from the Northern Finland Birth Cohort 1986 (NFBC 1986), including 9,362 pregnancies and subsequent births between 1985 and 1986. Pregnancies were categorised into three groups: (1) GH with blood pressure (BP) ≥ 140/90 mmHg, (2) PE with BP ≥ 140/90 mmHg and proteinuria, and (3) reference group with normal BP. The final study population included 331 offspring of mothers with GH, 197 with PE and 5,045 offspring of normotensive mothers. The main outcome measures were systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), body mass index (BMI), and serum lipid, glucose and insulin levels of the 16 year-old offspring. The children of mothers with GH had higher BP compared to the reference group (SBP percentage difference 2.7 (95% CI 1.6, 3.8); DBP 3.4 (2.1, 4.6); MAP 3.1 (2.0, 4.1), P < 0.001 for all) and a tendency towards higher cholesterol and apolipoprotein B values. The offspring of mothers with PE had higher DBP and MAP, however after the adjustments this difference disappeared. Maternal de novo hypertension during pregnancy is associated with offspring's elevated blood pressure level already in adolescence. GH may also be associated with unfavourable lipid profile of the offspring.

Science, clinical outcomes and the popularization of diabetes surgery

Bariatric surgery is an important option for the treatment of severe (type III) obesity. Its role in the management of type 2 diabetes in overweight and obese patients needs to be defined. Intensified medical therapy can achieve target metabolic goals in many but not all patients with type 2 diabetes. Bariatric surgery can normalize or improve glycemia in severely obese patients with type 2 diabetes. The complications of bariatric surgery are significant and include operative mortality, early and late surgical complications and late nutritional deficiencies. Comparative studies of bariatric surgery versus intensive medical therapy in the management and clinical outcomes of patients with type 2 diabetes are needed to evaluate relative risk/benefit of each. Bariatric surgery studies in type 2 diabetes are lacking long-term follow-up metabolic and clinical outcomes data. Current data are insufficient to recommend bariatric surgery as a primary treatment for type 2 diabetes. However, it can be recommended for patients whose target metabolic control cannot be achieved by intensive glycemic control because of intolerance or inadequate responses to nutritional and pharmacologic treatments.

Glucose Metabolism in 105 Children and Adolescents After Pancreatectomy for Congenital Hyperinsulinism

OBJECTIVETo describe the long-term metabolic outcome of children with congenital hyperinsulinism after near-total or partial elective pancreatectomy.RESEARCH DESIGN AND METHODSPatients (n = 105: 58 diffuse and 47 focal congenital hyperinsulinism) received operations between 1984 and 2006. Follow-up consisted of periodic measurements of pre- and postprandial plasma glucose over 24 h, OGTT, and IVGTT. Cumulative incidence of hypo- or hyperglycemia/insulin treatment was estimated by Kaplan-Meier analysis.RESULTSAfter near-total pancreatectomy, 59% of children with diffuse congenital hyperinsulinism still presented mild or asymptomatic hypoglycemia that responded to medical treatments and disappeared within 5 years. One-third of the patients had both preprandial hypoglycemia and postprandial hyperglycemia. Hyperglycemia was found in 53% of the patients immediately after surgery; its incidence increased regularly to 100% at 13 years. The cumulative incidence of insulin-treated patients was 42% at 8 years and reached 91% at 14 years, but the progression to insulin dependence was very variable among the patients. Plasma insulin responses to IVGTT and OGTT correlated well with glycemic alterations. In focal congenital hyperinsulinism, hypoglycemia or hyperglycemia were rare, mild, and transient.CONCLUSIONSPatients with focal congenital hyperinsulinism are cured of hypoglycemia after limited surgery, while the outcome of diffuse congenital hyperinsulinism is very variable after near-total pancreatectomy. The incidence of insulin-dependent diabetes is very high in early adolescence.

Metabolic Impact of Growth Hormone Treatment in Short Children Born Small for Gestational Age

Background: Growth hormone (GH) treatment in short children born small for gestational age (SGA) may result in metabolic changes with potential long-term effects. Methods: 149 short SGA children (mean birth weight 2.0 ± 0.6 kg, age 5.5 ± 1.5 years, height standard deviation score (SDS) –3.1 ± 0.6) were randomised to: low-dose GH therapy (0.033 mg/kg/day) for 2 years; high-dose GH therapy (0.100 mg/kg/day) for 1 year, or mid-dose GH therapy (0.067 mg/kg/day) for 1 year. Leptin, ghrelin, insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), lipids, fasting blood glucose and fasting insulin were assessed at baseline, 12 and 24 months. Results: After 1 year of active treatment, GH significantly reduced serum ghrelin and increased IGF-I SDS and insulin levels. Regression analysis showed an inverse correlation between ghrelin and IGF-I SDS (p < 0.001). Leptin and IGFBP-1 also declined (both p < 0.05). Changes in insulin levels reversed upon discontinuation. Improvements in lipid profile were nonsignificant and fasting blood glucose levels remained within the normal range. Conclusion: In short SGA children, ghrelin and leptin reductions associated with GH treatment may occur through a negative feedback loop of the GH–IGF-I axis. Consequently, via ghrelin and leptin suppression, GH treatment may modify food intake and body composition and potentially improve long-term metabolic outcomes.

Pathogenesis and treatment of HIV lipohypertrophy

This review addresses our current understanding of the pathogenesis of HIV-associated lipohypertrophy and describes an evidence-based approach to treatment. Although the pathogenesis of HIV-associated lipohypertrophy remains elusive, recent clinical and laboratory investigations in fatty acid metabolism and growth hormone dynamics have furthered our understanding of the condition. These findings have also paved the way for new therapeutic interventions, of which tesamorelin, an analog of growth hormone-releasing hormone (GHRH), has gained recognition as a promising treatment strategy against visceral fat accumulation. Recent randomized placebo-controlled trials of tesamorelin demonstrated significant reductions in visceral adipose tissue, improvement in lipid parameters, and minimal adverse effects on glucose tolerance. Optimal therapeutic dosing and treatment duration, though, are not yet known. Whether treatment with GHRH-analogs will translate into improved long-term metabolic and cardiovascular outcomes also remains to be seen. Although the pathogenesis of HIV lipohypertrophy remains unclear, several theories and observations have led to the development of treatment strategies to counter fat accumulation and its accompanying metabolic complications. Based on clinical trials, analogs of the growth hormone (GH)/GHRH axis appear to be most effective in reducing visceral adipose tissue.

Early postnatal nutrition and programming of the preterm neonate

Early postnatal nutrition is a vital determinant of adult health; this is particularly true for the infant born prematurely and cared for in a hospital setting such as the neonatal intensive care unit. Human and animal studies support the contribution of postnatal dietary composition and the rate of extrauterine growth to long-term metabolic outcomes. One mechanism by which postnatal nutrition affects long-term outcome is via developmental programming. Programming, or the modulation of gene expression to impart a short-term advantage accompanied by a long-term cost, may be achieved by epigenetic modifications to chromatin. This review summarizes the details of postnatal nutritional content and rate of growth on the development of metabolic disease. The role of epigenetics in developmental programming of the preterm infant is also discussed, with an emphasis on animal models of dietary manipulation and directions in which the field must move in order to formulate effective feeding strategies for the preterm infant.

Is Continuous Insulin Infusion 1st Line Rx for Diabetes Mellitus?

Research Article| October 01 2010 Is Continuous Insulin Infusion 1st Line Rx for Diabetes Mellitus? AAP Grand Rounds (2010) 24 (4): 46. https://doi.org/10.1542/gr.24-4-46 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Is Continuous Insulin Infusion 1st Line Rx for Diabetes Mellitus?. AAP Grand Rounds October 2010; 24 (4): 46. https://doi.org/10.1542/gr.24-4-46 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All AAP SitesAll PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP News Search Advanced Search Topics: diabetes mellitus, diabetes mellitus, type 1, infusion procedures, insulin, prescriptions, drug, subcutaneous insulin delivery, insulin administration Source: Sulmont V, Souchon P-F, Gouillard-Darnaud C, et al. Metabolic control in children with diabetes mellitus who are younger than 6 years at diagnosis: continuous subcutaneous insulin infusion as a first line treatment? J Pediatr. 2010; 157(1): 103– 107; doi: https://doi.org/10.1016/j.jpeds.2009.12.034Google Scholar Investigators from Reims, France studied the long-term metabolic outcomes of children with type 1 diabetes mellitus diagnosed prior to their 6th birthday with a treatment duration of at least five years. The participants fell into two groups: Group A consisted of 34 children who were initially treated with multiple daily subcutaneous insulin injections (MDI) and Group B consisted of 32 children who were treated by continuous subcutaneous insulin infusion (CSII) from the time of initial diagnosis. Children assigned to Group A received MDI treatment initially... Copyright © 2010 by the American Academy of Pediatrics2010 You do not currently have access to this content.

Long-term metabolic outcome and quality of life after laparoscopic adjustable gastric banding in obese patients with type 2 diabetes mellitus or impaired fasting glucose

The long-term outcome of type 2 diabetes mellitus after laparoscopic adjustable gastric banding (LAGB) is unknown. A longitudinal cohort study was undertaken of patients with grade 3 obesity and type 2 diabetes or impaired fasting glucose (IFG) undergoing LAGB. Metabolic outcomes and quality of life (QoL) were assessed before and 5 years after LAGB. At 5 years, data for 22 out of 23 patients with type 2 diabetes and 51 out of 53 with IFG were available. Mean(s.d.) excess weight loss was 41(25) and 41(27) per cent in patients with type 2 diabetes and IFG respectively, and was associated with a significant decrease in haemoglobin (Hb) A1c, fasting and postprandial blood glucose, insulin and triglyceride levels, and in liver steatosis. There were significant increases in insulin sensitivity, beta-cell function, disposition index, high-density lipoprotein-cholesterol and QoL (Nottingham Health Profile). Good metabolic control (HbA1c 7 per cent or less) was obtained in 13 diabetic patients, but complete diabetes remission was maintained in only four. Longer duration of diabetes, and poor preoperative glucose control and beta-cell function at baseline were associated with a less favourable outcome. LAGB improved metabolic outcomes and QoL in patients with grade 3 obesity with IFG or type 2 diabetes but rarely led to prolonged remission in long-standing diabetes.

Metabolic Control in Children with Diabetes Mellitus Who are Younger than 6 Years at Diagnosis: Continuous Subcutaneous Insulin Infusion as a First Line Treatment?

To assess long-term metabolic outcomes in children with diabetes mellitus that was diagnosed when they were <6 years old. A cohort of 66 children with diabetes mellitus that had a duration of at least 5 years and was diagnosed before they were 6 years old. Thirty-four children were treated at diagnosis with multiple daily subcutaneous insulin injections (MDI), and all these children, except 3, were switched to continuous subcutaneous insulin infusion (CSII; group A). Thirty-two children received CSII as initial treatment (group B). Hemoglobin A1c values were significantly lower in patients receiving CSII than MDI during all the 8 years of follow-up except one (year 1: 6.9%+/-0.9% versus 7.6%+/-1%, P=.011 ; year 4: 7.4%+/-0.8% versus 8.1%+/-0.9%, P=.006; year 7: 7.6%+/-0.5% versus 8.3%+/-0.8%, P=.001). The incidence of severe hypoglycemia was greatly decreased for the CSII group (9.8 versus 22.3 episodes/100 patient-years, P=.016). In group A, hemoglobin A1c values increased during the study period, and in group B, they increased only during the first 2 years and remained constant thereafter. Only 9.1% of patients did not use or abandoned CSII. CSII in children<6 years of age enables better long-term metabolic control and lowers the risk of severe hypoglycemia better than MDI, especially when initiated at diagnosis.

The long-term metabolic outcomes of dysglycemia during critical illness

Gornik and colleagues should be commended for providing the first report on the long-term glucose metabolism sequelae in survivors of critical illness with no apparent dysglycemia shortly after hospital discharge [1]. The authors hypothesized that hyperglycemia in the intensive care unit unmasks predisposition for future development of diabetes. The interpretation of their findings, however, is limited by several aspects of their methodology. No systematic control for covariates and confounders was performed. Their cohort was divided, as acknowledged by the authors, by an arbitrary (for the purpose of long-term prediction) glycemic cutoff value. While intuitively appealing, the latter is not necessarily the optimal predictor of future risk of impaired glucose metabolism. When considering the whole cohort of patients with a normal first postdischarge oral glucose tolerance test (the eligible cohort), what was the predictive role for traditional predictors of diabetes mellitus and prediabetes mellitus (DM/pre-DM) (for example, age, family history, body mass index) and for inhospital variables (for example, severity of illness)? It would also be instructive to explore the role of previously studied glycemic indices - such as admission, maximal and mean glucose values - to determine the best predictive cutoff value for future development of DM/pre-DM. In addition, almost 40% of the eligible cohort was excluded from analysis due to death or discontinuation of follow-up. How many of these patients who had at least the first 12-month follow-up were diagnosed with DM/pre-DM? Because DM/pre-DM are commonly under-recognized [2], these analyses can provide initial predictive modeling, which may inform future development of public health policy for earlier detection and intervention in survivors of critical illness.

Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing’s Disease or Non-Functioning Pituitary Adenoma

Previous exposure to hypercortisolism due to Cushing's disease (CD) may adversely affect long-term metabolic and cardiovascular outcomes. In particular, metabolic and cardiovascular outcomes of patients with previous CD who require GH replacement have not been fully established. The aim of the study was to compare the prevalence and incidence of metabolic syndrome (Adult Treatment Panel III criteria), diabetes mellitus, cardiovascular disease, and cerebrovascular disease in GH-treated subjects with previous CD with GH-treated subjects with previous nonfunctioning pituitary adenoma (NFPA). We conducted post hoc analysis of the observational Hypopituitary Control and Complications Study conducted at 362 international centers (1995-2006). We studied adult-onset GH-deficient subjects with previous CD (n = 160) or NFPA (n = 879). All subjects received GH replacement therapy and were GH naive at enrollment. Multiple pituitary deficits were prevalent in both groups. We measured the prevalence and incidence of metabolic syndrome, diabetes mellitus, cardiovascular disease, and cerebrovascular disease at baseline and at 3 yr, standardized for age and sex differences between groups. Compared with subjects with previous NFPA, subjects with previous CD had a significantly greater 3-yr incidence of metabolic syndrome (CD, 23.4%; NFPA, 9.2%; P = 0.01), baseline (CD, 6.3%; NFPA, 2.2%; P < 0.01) and 3-yr (CD, 7.6%; NFPA, 3.9%; P = 0.04) prevalence of cardiovascular disease, and baseline (CD, 6.4%; NFPA, 1.8%; P = 0.03) and 3-yr (CD, 10.2%; NFPA, 2.9%; P = 0.01) prevalence of cerebrovascular disease. Previous hypercortisolism may predispose GH-treated, GH-deficient subjects with prior CD to an increased risk of metabolic syndrome, cardiovascular disease, and cerebrovascular disease.