Long-term Metabolic Complications Research Articles

The development of novel glucocorticoid receptor antagonists: From rational chemical design to therapeutic efficacy in metabolic disease models

Glucocorticoids regulate numerous processes in human physiology, but deregulated or excessive glucocorticoid receptor (GR) signaling contributes to the development of various pathologies including metabolic syndrome. For this reason, GR antagonists have considerable therapeutic value. Yet, the only GR antagonist that is clinically approved to date - mifepristone - exhibits cross-reactivity with other nuclear steroid receptors like the progesterone receptor. In this study, we set out to identify novel selective GR antagonists by combining rational chemical design with an unbiased in vitro and in vivo screening approach. Using this pipeline, we were able to identify CORT125329 as the compound with the best overall profile from our octahydro series of novel GR antagonists, and demonstrated that CORT125329 does not exhibit cross-reactivity with the progesterone receptor. Further in vivo testing showed beneficial activities of CORT125329 in models for excessive corticosterone exposure and short- and long-term high-fat diet-induced metabolic complications. Upon CORT125329 treatment, most metabolic parameters that deteriorated upon high-fat diet feeding were similarly improved in male and female mice, confirming activity in both sexes. However, some sexually dimorphic effects were observed including male-specific antagonism of GR activity in brown adipose tissue and female-specific lipid lowering activities after short-term CORT125329 treatment. Remarkably, CORT125329 exhibits beneficial metabolic effects despite its lack of GR antagonism in white adipose tissue. Rather, we propose that CORT125329 treatment restores metabolic activity in brown adipose tissue by stimulating lipolysis, mitochondrial activity and thermogenic capacity. In summary, we have identified CORT125329 as a selective GR antagonist with strong beneficial activities in metabolic disease models, paving the way for further clinical investigation.

Long-term outcomes of sigmoid neobladder after radical cystectomy in Indian population: a single centre experience

Background: Radical cystectomy with orthotopic neobladder is the standard of care for MIBC. Long-term data on sigmoid neobladder is limited. Sigmoid neobladder offers the advantage of low long-term metabolic and nutritional complications, due to sparing of ileum and ileo-caecal valve. We present our experience and long-term results of orthotopic sigmoid neobladder reconstruction after radical cystectomy.Methods: The study included 57 male patients who underwent radical cystectomy and orthotopic sigmoid neobladder for muscle-invasive carcinoma of bladder from January 2002 to December 2019. Data was collected with regards to complication rate, voiding patterns, continence status, recurrence-free and overall survival.Results: Mean age was 52.7 years (range 35 to 74). Median duration of follow-up was 62 months. There were 3 (5.3%) perioperative deaths. 15 patients (26.3%) developed early and 5 patients (8.7%) developed delayed complications. Node positive disease (N+) was found in 11 (19.3%) patients and 17 (29.8%) required adjuvant chemotherapy. 94.7% patients were continent and 42 (82.4%) patients had spontaneous voiding pattern. Daytime and nocturnal incontinence rate were 5.3% and 24.6%, respectively. Clean intermittent catheterization (CIC) was required in 8 (14.1%) cases. The recurrence-free survival (RFS) and overall survival (OS) were 57% and 50% at 5 years and 62.5% and 35.8% at 10 years, respectively.Conclusions: Sigmoid neobladder remains a viable form of orthotopic urinary diversion and provides satisfactory long-term continence and voiding results with acceptable rate of complications. Good long-term results in sigmoid neobladder in Indian population may be due to long sigmoid colons in Indian patients with low incidence of diverticulosis.

Prevalence of Endocrine and Metabolic Comorbidities in a National Cohort of Patients with Craniopharyngioma

Objective: The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria. Design: A retrospective-prospective longitudinal cohort analysis. Methods: Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3–22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients’ records and re-evaluated if tissue samples were available (n = 32). Results: Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At follow-up, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110). Conclusions: Long-term endocrine and metabolic complications are very frequent in childhood- and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.

Long-Term Metabolic Consequences of Intrauterine Growth Restriction

To summarize recent findings on the associations of intrauterine growth restriction (IUGR) and long-term metabolic consequences such as obesity, type 2 diabetes (T2D), and cardiovascular diseases and the underlying mechanisms. Recent evidence suggests that metabolic diseases such as obesity, T2D, hypertension, and coronary artery disease are related to developmental programming in fetal period and early childhood. Rapid postnatal catch-up growth is also an important factor that contributes to the development of these long-term metabolic complications. The underlying mechanisms include oxidative stress, changes in hormonal milieu, vascular endothelial dysfunction, epigenetic regulation, and the potential alteration of microbiome. Fetal and early life environment is an important determinant of long-term cardiometabolic risks. Children with IUGR need close follow-up for early detection of these complications.

Gestational Diabetes Mellitus and the Long-Term Risk for Glucose Intolerance and Overweight in the Offspring: A Narrative Review.

Gestational diabetes mellitus (GDM) is a common condition with increasing prevalence worldwide. GDM is associated with an increased risk for maternal and neonatal complications. In this review we provide an overview of the most recent evidence on the long-term metabolic risk associated with GDM in the offspring. We conducted an extensive literature search on PubMed and Embase between February 2019 and December 2019. We performed a narrative review including 20 cohort studies, one cross-sectional study, and two randomized controlled trials. Our review shows that the prevalence of overweight/obesity and glucose intolerance is higher in children exposed to GDM compared to unexposed children. Maternal overweight is an important confounding factor, but recent studies show that in general the association remains significant after correction for maternal overweight. There is limited evidence suggesting that the association between GDM and adverse metabolic profile in the offspring becomes more significant with increasing offspring age and is also more pronounced in female offspring than in male offspring. More research is needed to evaluate whether treatment of GDM can prevent the long-term metabolic complications in the offspring.

A global perspective on newborn congenital hypothyroidism screening

Congenital hypothyroidism (CH) is a thyroid hormone deficiency syndrome in newborns resulting from incomplete thyroid development and decreased thyroid hormone biosynthesis or thyroid-stimulating hormone secretion. Without early treatment, newborns with CH have irreversible neurological deficits and long-term metabolic complications. Therefore, several countries have implemented widespread newborn screening to identify and treat CH in newborns. Although newborn screening has improved diagnosis and treatment outcomes for CH, several questions remain concerning the etiology and increased incidence of CH in different populations. Moreover, the increase in the number of preterm, low-birth-weight newborns and of newborns admitted to the neonatal intensive care unit presenting with CH requires additional research to detect and treat all forms of CH.

Avoiding the Need for Bowel Anastomosis during Pelvic Exenteration—Urinary Sigmoid or Descending Colon Conduit—Short and Long Term Complications

ObjectiveTo educate surgeons of distal colon urinary diversion as an alternative to ileal conduit. To assess perioperative outcomes of distal colon conduit in pelvic exenteration including conduit-related, gastrointestinal, infectious, metabolic, and wound complications within 30 days, 31-89 days, and greater than 90 days from the time of surgery. Materials and MethodsForty-one patients who underwent distal colon urinary diversion for malignancy, fistula, or neurogenic bladder were identified in our IRB approved database from 1/2007 to 7/2017. ResultsTwenty-six (63.4%) were male with mean age of 54.1 years. Complications were stratified by early (≤30 days), intermediate (31-89 days), and late (≥90 days). Within 30 days, 2 (4.9%) had partial small bowel obstructions requiring nasogastric tube (NGT) placement and total parenteral nutrition (TPN); 8 (19.5%) prolonged ileus with 6 (14.6%) requiring TPN and 5 (12.2%) requiring NGT placement; 1 (2.4%) enterocutaneous fistula; 1 (2.4%) conduit hemorrhage, 10 (24.4%) treated urinary tract infections (UTIs). Between 31 and 89 days, 1 patient (2.4%) had urinary conduit leak and 3 (7.3%) treated UTIs. At ≥90 days, 2 (4.9%) had partial small bowel obstructions requiring NGT placement, 4 (9.8%) ureterocolonic strictures and 1 (2.4%) parastomal hernia, 3 (7.3%) treated UTIs. Readmission rate in ≤30 days was 10 (24.4%), 31-89 days was 13 (31.7%), and 90+ days was 16 (39%). Long-term metabolic complications at ≥90 days included 16 (39%) with hypokalemia, 10 (24.4%) with hyperchloremia, and 14 (34.1%) with metabolic acidosis. ConclusionDistal colon urinary conduit is a relatively safe and feasible option and obviates the need for small bowel anastomosis and possible associated complications.

Molecular Control of Phosphorus Homeostasis and Precision Treatment of Hypophosphatemic Disorders.

Serum phosphorus is maintained in a narrow range by balancing dietary phosphate absorption, influx and efflux of phosphorus from bone and intracellular stores, and renal reabsorption of filtered phosphate. Acute hypophosphatemia, typically caused by transient increases in cellular uptake, can lead to severe complications such as cardiopulmonary dysfunction and rhabdomyolysis that can warrant parenteral phosphate repletion. Chronic hypophosphatemia, however, generally represents true phosphate deficiency and may result in long-term metabolic and skeletal complications, particularly in children due to the critical importance of phosphorus to skeletal mineralization and longitudinal growth. In addition to the well characterized roles of vitamin D and parathyroid hormone (PTH), a new bone-kidney axis has been discovered that regulates phosphate homeostasis through the bone-derived hormone Fibroblast Growth Factor 23 (FGF23) and its phosphaturic actions that are mediated by activation of fibroblast growth factor receptors (FGFRs) complexed with α-Klotho in renal tubules. Chronic hypophosphatemia can now be classified as FGF23 dependent or independent. In cases of FGF23 dependent hypophosphatemia, traditional non-specific treatments with elemental phosphorus and 1,25(OH)2 vitamin D (calcitriol) can now be replaced with a targeted approach by using an FGF-23 blocking antibody (Burosumab).

Metabolic disturbances in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis

To explore metabolic disturbances in nonobese women with polycystic ovary syndrome (PCOS) compared with nonobese healthy controls. Systematic review and meta-analysis. Not applicable. Nonobese women with PCOS and nonobese healthy controls. None. Prevalence of metabolic disturbances including hyperinsulinemia, insulin resistance (IR), impaired fasting glucose (IFG), impaired glucose intolerance (IGT), prediabetes, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein (low-HDL), as well as other metabolic outcomes such as type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome (Mets), myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease. Compared to nonobese controls, nonobese women with PCOS showed a higher prevalence of hyperinsulinemia (odds ratio [OR], 36.27; 95% confidence interval [CI] 1.76-747.12), IR (OR, 5.70; 95% CI 1.46-22.32), IGT (OR, 3.42; 95% CI 1.56-7.52), T2DM (OR, 1.47; 95% CI 1.11-1.93), hypertriglyceridemia (OR, 10.46; 95% CI 1.39-78.56), low-HDL (OR, 4.03; 95% CI 1.26-12.95), and Mets (OR, 2.57; 95% CI 1.30-5.07). No significant difference was observed for IFG, pre-DM, dyslipidemia, hypercholesterolemia, and hypertension. In subgroup analysis, Whites exhibited increased risks of IR, IGT, IFG, T2DM, hypertension, and Mets, whereas no significant metabolic change was found in Asians. No study reported specifically an incidence of myocardial infarction, stroke, cerebrovascular accident, arterial occlusive disease, and coronary heart disease in nonobese women with PCOS. Nonobese women with PCOS also suffer from metabolic disturbances and the risk of long-term metabolic complications. Further efforts should be made to elucidate underlying mechanisms and possible interventions in the early phase.

Pregnancy after Obesity and Metabolic Surgery - Risks and Complications

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications - such as nutrient deficiencies - are the main risks of metabolic surgery and the resulting malabsorption. Obesity, especially morbid obesity, is associated with a high incidence of female infertility. One important cause of female infertility in obese women is the polycystic ovary syndrome, with 6 - 10%. Metabolic surgery significantly increases the fertility of obese women. The positive effect of obesity surgery on weight loss, remission of comorbidities, psychological outcome and fertility (in comparison with the effect of conservative treatment) has led to an increase in the number of metabolic operations. Nutrient deficiencies after restrictive, combined and malabsorptive procedures must be considered. Prophylaxis of these deficiencies during pregnancy after obesity surgery must be based on intensive interdisciplinary treatment. The aim of this overview is to characterise the metabolic complications and their prophylaxis, which are specific for the various bariatric procedures and which, subsequently, require temporary or permanent surveillance and supplementation.

Biomaterials and Regenerative Medicine in Urology.

Autologous gastrointestinal tissue is the gold standard biomaterial for urinary tract reconstruction despite its long-term neuromechanical and metabolic complications. Regenerative biomaterials have been proposed as alternatives; however many are limited by a poor host derived regenerative response and deficient supportive elements for effective tissue regeneration in vivo. Urological biomaterials are sub-classified into xenogenic extracellular matrices (ECMs) or synthetic polymers. ECMs are decellularised, biocompatible, biodegradable biomaterials derived from animal organs. Synthetic polymers vary in chemical composition but may have the benefit of being reliably reproducible from a manufacturing perspective. Urological biomaterials can be 'seeded' with regenerative stem cells in vitro to create composite biomaterials for grafting in vivo. Mesenchymal stem cells are advantageous for regenerative purposes as they self-renew, have long-term viability and possess multilineage differentiation potential. Currently, tissue-engineered biomaterials are developing rapidly in regenerative urology with many important clinical milestones achieved. To truly translate from bench to bedside, regenerative biomaterials need to provide better clinical outcomes than current urological tissue replacement strategies.

Group-based developmental BMI trajectories, polycystic ovary syndrome, and gestational diabetes: a community-based longitudinal study

BackgroundObesity is common in young women, increasing insulin resistance (IR) and worsening pregnancy complications, including gestational diabetes (GDM). Women with polycystic ovary syndrome (PCOS) are commonly obese, which aggravates the severity of PCOS clinical expression. Relationships between these common insulin-resistant conditions, however, remain unclear.MethodsWe conducted a secondary analysis of the Australian Longitudinal Study on Women’s Health (ALSWH) database, including data from 8009 women aged 18–36 years across six surveys. We used latent-curve growth modelling to identify distinct body mass index (BMI) trajectories and multinomial logistic regression to explore sociodemographic and health variables characterizing BMI group membership. Logistic regression was used to assess independent risk of GDM.ResultsA total of 662 women (8.29%, 95% CI 7.68–8.89) reported PCOS. Three distinct BMI trajectories emerged, namely low stable (LSG) (63.8%), defined as an average trajectory remaining at ~25 kg/m2; moderately rising (MRG) (28.8%), a curvilinear trajectory commencing in a healthy BMI and terminating in the overweight range; and high-rising (HRG) (7.4%), a curvilinear trajectory starting and terminating in the obese range. A high BMI in early reproductive life predicted membership in higher trajectories. The HRG BMI trajectory was independently associated with GDM (OR 2.50, 95% CI 1.80–3.48) and was a stronger correlate than PCOS (OR 1.89, 95% CI 1.41–2.54), maternal age, socioeconomic status, or parity.ConclusionOur results suggest heterogeneity in BMI change among Australian women of reproductive age, with and without PCOS. Reducing early adult life weight represents an ideal opportunity to intervene at an early stage of reproductive life and decreases the risk of long-term metabolic complications such as GDM.

Metabolic surgery and nutritional deficiencies.

The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity and is present in about 2-6% of all pregnancies in Europe, making it one of the most common pregnancy disorders. Aside from the short-term maternal, fetal and neonatal consequences associated with GDM, there are long-term consequences for both mother and child. Although maternal glucose tolerance often normalises shortly after pregnancy, women with GDM have a substantially increased risk of developing type 2 diabetes later in life. Studies have reported that women are more than seven times as likely to develop diabetes after GDM, and that approximately 50% of mothers with GDM will develop diabetes within 10years, making GDM one of the strongest predictors of type 2 diabetes. In women with previous GDM, development of type 2 diabetes can be prevented or delayed by lifestyle intervention and/or medical treatment. Systematic follow-up programmes would be ideal to prevent progression of GDM to diabetes, but such programmes are unfortunately lacking in the routine clinical set-up in most countries. Studies have found that the risks of obesity, the metabolic syndrome, type 2 diabetes and impaired insulin sensitivity and secretion in offspring of mothers with GDM are two- to eightfold those in offspring of mothers without GDM. The underlying pathogenic mechanisms behind the abnormal metabolic risk profile in offspring are unknown, but epigenetic changes induced by exposure to maternal hyperglycaemia during fetal life are implicated. Animal studies indicate that treatment can prevent long-term metabolic complications in offspring, but this remains to be confirmed in humans. Thus, diabetes begets diabetes and it is likely that GDM plays a significant role in the global diabetes epidemic. This review summarises a presentation given at the 'Gestational diabetes: what's up?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Marja Vääräsmäki, DOI: 10.1007/s00125-016-3976-6 , and by Cuilin Zhang and colleagues, DOI: 10.1007/s00125-016-3979-3 ) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10.1007/s00125-016-3975-7 ).

Drosophila melanogaster: An emerging model of transgenerational effects of maternal obesity

The prevalence of obesity in the world is endemic with one rapidly growing health concern being maternal obesity. Obesity during pregnancy increases the risk of gestational diabetes, miscarriage, and preeclampsia, while rendering offspring susceptible to developmental anomalies and long-term metabolic complications including type 2 diabetes and cardiovascular disease. Several studies in humans and rodents demonstrate a correlation between the risks of maternal overnutrition and factors such as epigenetics, mitochondrial dysfunction, insulin resistance, ER stress, and immune system disruption. At present, the molecular mechanisms connecting these factors to maternal obesity are unknown. This review focuses on the use of Drosophila melanogaster to study human metabolic diseases, including obesity, and its emerging use to elucidate the mechanisms of maternal overnutrition and the impact on offspring.

Basic science: Pathophysiology: the CardioRenal Metabolic Syndrome

Basic science: Pathophysiology: the CardioRenal Metabolic Syndrome

Complications from micronutrient deficiency following bariatric surgery

We report a case of clinically significant micronutrient deficiencies following biliary pancreatic diversion (BPD) surgery. Our patient was admitted to hospital six years after BPD surgery following a low impact humeral fracture complicated by postoperative wound infection. On presentation she complained of a widespread rash and loss of night vision. Laboratory testing confirmed hypoalbuminaemia, deficiencies of vitamins A, E and D and of the trace elements copper, zinc and selenium. Bone densitometry confirmed osteoporosis. The skin rash was thought to be due to zinc deficiency and improved with conservative measures and trace element replacement. Her night blindness resolved 48 hours after receiving high dose parenteral vitamin A. Six months later she was readmitted to our intensive care unit with wound dehiscence at her fracture site and clinical features of sepsis and encephalopathy. This case highlights the importance of devising treatment and follow-up guidance prior to surgery and multidisciplinary team involvement including the patient so that long-term metabolic complications are avoided.

Zinc and Homocysteine Levels in Polycystic Ovarian Syndrome Patients with Insulin Resistance

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

Cost-effectiveness of asenapine in the treatment of schizophrenia in Canada

Objective:Asenapine is the first tetracyclic antipsychotic approved in Canada for the treatment of schizophrenia (SCZ). Asenapine has shown a comparable efficacy profile to other atypical antipsychotics and it is associated with a favourable metabolic profile and less weight gain. This study aimed to assess the economic impact of asenapine compared to other atypical antipsychotics in the treatment of SCZ in Canada.Methods:A decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with other atypical antipsychotics. The decision tree takes into account the occurrence of extrapyramidal symptoms, the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases, and stroke. In the base-case analysis, asenapine was compared to olanzapine. Asenapine was also compared with other atypical antipsychotics commonly used in Canada in alternative scenarios. Analyses were conducted from both Canadian Ministry of Health (MoH) and societal perspectives over a 5-year time horizon.Results:In the treatment of SCZ, asenapine is a dominant strategy over olanzapine from both MoH and societal perspectives. Compared to quetiapine, asenapine is also a dominant strategy. Furthermore, asenapine has a favorable economic impact compared to ziprasidone and aripiprazole, as these antipsychotics are not cost-effective compared to asenapine from both MoH and societal perspectives.Conclusion:Despite the short time horizon, the lack of compliance data and the assumptions made, this economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most of the atypical antipsychotics frequently used in Canada.

Metabolic monitoring of obese children born small for gestational age

The "catch-up growth" phenomenon in children born small for gestational age (SGA) has been linked to early onset obesity with the subsequent emergence of metabolic syndrome (MetS) or its components. It has been postulated that the prevalence of MetS and its components increases strongly with age. A retrospective study was carried out over a 5 year period (2007-2011) to determine long-term metabolic complications in obese children born with normal weight for gestational age (appropriate for gestational age: AGA) and SGA. 517 patients were qualified into the study. According to birth weight and gestational age they were first divided into SGA (107 patients--20%) and AGA (410 patients--80%) and then by age into three subgroups: prepubertary group, pubertary group and adolescents. Blood pressure, lipids and glucose were measured. Oral glucose tolerance tests (oGTT) were performed in all subjects. Prepubertary patients showed no significant differences between SGA and AGA; 4.8% met the framing criteria (according to Weiss) for MetS. Pubertary patients showed a slightly increased prevalence of MetS among SGA patients 10.8%, compared to AGA patients 7.3%. MetS prevalence was significantly higher in obese adolescents born SGA 26.3% compared to AGA 15.7%. MetS or its components develop progressively with age. Increased prevalence of MetS in SGA patients indicates that being born SGA appears to be an additional risk factor in the development of MetS starting with puberty.