Metabolic Syndrome and Insulin Resistance Are Associated with Chronic Kidney Disease in Nondiabetic Adults with Abdominal Obesity

Aims: we investigate whether insulin resistance is associated with an increased prevalence for chronic kidney disease irrespective of the concurrent presence of metabolic syndrome. Methods: 1638 patients with abdominal obesity were selected. Metabolic syndrome and abdominal obesity were defined according to the International Diabetes Federation criteria. Insulin resistance was defined by Homeostasis Model Assessment Index >P75. Chronic kidney disease was defined by the presence of a low estimated glomerular filtration rate (Results: metabolic syndrome was present in 1030 (62.9%) patients and insulin resistance in 787 (48%). Conversely 61% of those with metabolic syndrome were insulin resistant and 79% of those with insulin resistance had metabolic syndrome. Chronic kidney disease was present in 18%. In multivariate analysis, chronic kidney disease was increased in subjects with insulin resistance (odds ratio [OR] = 1.350;CI 95%: 1.021 - 1.785;p = 0.035) and in those with metabolic syndrome (OR = 1.417;CI 95%: 1.045 - 1.922;p = 0.025). Conclusions: Metabolic syndrome and insulin resistance were significant and independently associated with chronic kidney disease in nondiabetic adults with abdominal obesity.

Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index(BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome(MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods(fat). However, high-carbohydrate rich(CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.

Insulin resistance as the molecular link between diabetes and Alzheimer's disease

Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.

Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.

Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment （HOMA [fasting glucose × fasting insulin]/22.5） and quantitative insulin sensitivity check index （QUICK/; 1/[log （fasting insulin） ＋ log （fasting glucose）]）. Age-adjusted body mass index （BMI） was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance （ANOVA） test and Duncan＇s multiple comparison test （P 〈 0.001）, but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICK/（P 〈 0.001）. Age, BMI, insulin resistance by HOMA or QUICK/were significantly independent variables to serum PSA level in a multivariate linear regression analysis （P 〈 0.001）. Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Coexistence of ovarian serous papillary cystadenofibroma and type A insulin resistance syndrome in a 14-year-old girl: A case report

BACKGROUND Type A insulin resistance syndrome is a rare disorder caused by mutations in the gene encoding the insulin receptor.Its coexistence with ovarian serous papillary cystadenofibroma is even rarer.CASE SUMMARY A 14-year-old girl developed type A insulin resistance syndrome and showed high fasting insulin,glucose,and hemoglobin A1c(HbA1c)levels.The girl suffered from ovarian serous papillary cystadenofibroma.The laboratory results were as follows:fasting insulin was 2624.90 pmol/L and HbA1c was 8.5%.A heterozygous missense mutation on exon 20 of the insulin receptor gene(c.3601C>T,Arg1201Trp)was observed.The histopathological diagnosis was a cystic lesion that extended to the upper right uterus,indicating a right ovarian serous papillary cystadefibroma accompanied by focal interstitial hyperplasia.The patient was treated with metformin for over 6 mo.Additionally,laparoscopic resection(bilateral)of the ovarian lesion and laparoscopic intestinal adhesiolysis were performed under general anesthesia.Diet therapy combined with exercise was then initiated.The patient had an uneventful recovery.The patient also showed improved blood glucose control,with reduced levels of fasting insulin(857.84 pmol/L)and HbA1c(7.0%).CONCLUSION Insulin resistance may play a significant role in the induction of tumors.It is important to investigate further the association between insulin resistance and tumors and the underlying mechanism.

Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality.

Metabolic syndrome as a risk factor for gallstone disease

AIM: To establish an association between the presence of metabolic syndrome and the development of gallstone disease. METHODS: We carried out a cross-sectional study in a check-up unit in a university hospital in Mexico City. We enrolled 245 subjects, comprising 65 subjects with gallstones (36 women, 29 men) and 180 controls (79 women and 101 men without gallstones). Body mass index, waist circumference, blood pressure, plasma insulin, and serum lipids and lipoproteins levels were measured. Insulin resistance was calculated by homeostasis model assessment. Unconditional logistic regression analysis (univariate and multivariate) was used to calculate the risk of gallstone disease associated with the presence of at least three of the criteria (Adult Treatment Panel Ⅲ). Analyses were adjusted for age and sex. RESULTS: Among 245 subjects, metabolic syndrome was present in 40% of gallstone disease subjects, compared with 17.2% of the controls, adjusted by age and gender (odds ratio (OR) = 2.79; 95%CI, 1.46-5.33; P= 0.002), a dose-dependent effect was observed with each component of metabolic syndrome (OR=2.36, 95%CI, 0.72-7.71; P= 0.16 with one component and OR = 5.54, 95%CI, 1.35-22.74; P = 0.02 with four components of metabolic syndrome). Homeostasis model assessment was significantly associated with gallstone disease (adjusted OR = 2.25; 95%CI, 1.08-4.69; P= 0.03). CONCLUSION: We conclude that as for cardiovascular disease and diabetes mellitus, gallstone disease appears to be strongly associated with metabolic syndrome.

Metabolic syndrome and risk of subsequent colorectal cancer

The metabolic syndrome and visceral obesity have anincreasing prevalence and incidence in the generalpopulation. The actual prevalence of the metabolicsyndrome is 24% in US population and between24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES , INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer. Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944 717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical signifi cance and may have profound health benefi ts on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.

Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis

AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS： Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS： NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 （OR 20.98, 95% CI 3.22-136.62; P 〈 0.001） and visceral fat area 〉 158 cm^2 （OR 18.55, 95% CI 1.60-214.67; P = 0.019） were independent predictors for NASH. Advanced stage of NASH was found in 15 （50%） patients. HOMA-IR 〉 3.5 （OR 23.12, 95% CI 2.00-266.23; P = 0.012） and grading of portal inflammation （OR 7.15, 95% CI 1.63-31.20; P = 0.009） were determined as independent risk factors for advanced stage of NASH. CONCLUSION： Obesity （especially central obesity） and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.

Association between Adiponectin and Metabolic Syndrome in Older Adults from Major Cities of China

Objective To investigate the association between adiponectin and metabolic syndrome （MetS） and related diseases in older adults from major cities of China. Methods A total of 2 049 adults at the age of 60-96 years from18 major cities of China were enrolled in the study. Plasma adiponectin and insulin concentrations were measured. Insulin resistance was assessed by homeostasis model assessment of insulin resistance （HOMA-IR）. The definitions proposed by International Diabetes Federation （IDF） and American Heart Association/National Heart, Lung, and Blood/nstitute （AHA/NLHBI） were used to identify MetS. Results The adiponectin concentration increased with the advance of age and was higher in women than in men. The sex specific adiponectin concentration was inversely correlated with body mass index （BMI）, waist circumference, diastolic blood pressure, triglycerides, glucose and fasting blood insulin, and positively correlated with HDL-C （P〈0.001）. The adiponectin concentration decreased with increasing MetS components. Compared with the 4th sex-specific adiponectin quartile, the odds ratio （OR） for prevalent MetS-IDF and MetS-AHA/NLHBI in subjects of the 1st quartile group was 3.25 （95% CI： 2.24, 4.71） and 3.21 （95% CI： 2.26, 4.55）, respectively. The association was independent of age, sex, life-style factors, medication, family history of chronic diseases, BMI, and HOMA-IR, The OR for MetS was much higher than those of MetS components and its related diseases. Conclusion Adiponectin is strongly associated with MetS independent of insulin resistance and obesity in older adults from major cities in China. The adiponectin concentration is a useful predictor for the risk of MetS.

Metabolic Syndrome and Perioperative Complications during Scheduled Surgeries with Spinal Anesthesia

Background: Metabolic syndrome (MS) is a constellation of factors associated with increased risk of developing cardiovascular diseases and Diabetes Mellitus. Despite of the many studies related to MS, little is known about its impact on scenarios such as surgical anesthesia. Objective: To examine the correlation between demographic and metabolic variables with the occurrence of perioperative complications in patients with MS undergoing scheduled surgeries using a spinal anesthesia technique in the surgery department at the University Clinic San Juan de Dios in Cartagena de Indias, Colombia. Methods: Observational, analytical, cross-sectional, single-center study of 150 subjects with MS and 150 control subjects. Perioperative complications, socio-demographic, hemodynamic and respiratory variables were registered. Groups were compared using t test, Fisher’s exact test or Chi-square, as appropriate. We applied a logistic multiple regression model, adjusted by backward stepwise at 0.25 and forward at 0.05, to find possible incompatible associations. p value < 0.05 was considered significant. Results: There were significant differences between groups in age, American Society of Anesthesiologists physical status classification, frequency of diseases associated to MS and perioperative complications. There were no cases of mortality among patients. There was statistically significant difference between the two groups for intraoperative hypotension and hypertension with p values of <0.0001 and 0.034. Among postoperative complications there was statistically significant difference in pain (13.3% vs 5.3% in patients without MS) and nausea and/or postoperative vomiting (8% vs 2% in patients without MS) with a p value of 0.027 and 0.015 (by Fisher) respectively. Conclusions: Metabolic abnormalities in MS are a risk factor for developing complications in the perioperative period of patients scheduled for surgeries using the subarachnoid anesthesia technique. Accordingly, it is appropriate to implement health intervention strategies by the surgical team, aiming at their prevention and management.

Metabolic syndrome and gastro-esophageal reflux:A link towards a growing interest in developed countries

The aim of this Editorial is to describe the growing possibility of a link between gastro-esophageal reflux disease (GERD) and metabolic syndrome on the light of recent epidemiological and pathophysiological evidence. The state of the art of GERD is described,based on recent definitions,pathophysiological evidence,epidemiology in developed countries,clinical subtypes together with a diagnostic approach specifically focussed on the appropriateness of endoscopy. Metabolic syndrome is accurately defined and the pivotal role of insulin resistance is emphasized. The strong relationship between GERD and metabolic syndrome has been pathophysiologically analyzed,taking into account the role of obesity,mechanical factors and metabolic changes. Data collected by our group regarding eating habits and GERD are briefly summarized at the end of a pathophysiological analysis. The literature on the subject strongly supports the possibility that lifestyle and eating habits may be involved in both GERD and metabolic syndrome in developed countries.

Evaluate the effects of metabolic syndrome in adolescents and children

The metabolic syndrome(MS)in adolescents and children can cause serious consequences that lead researchers to pay efforts to study in such area.Presently,MS definition is still not standardized.Different versions of MS definition have been used by numerous studies,which may be a problem to identify MS and then to predict and prevent clinical diseases.The pediatric literature shows that insulin resistance and obesity might be the key underlying pathophysiology of MS to cause many related diseases.High prevalence of MS is in overweight and obese children and adolescents.This article focuses on such above issues and also effects of MS on two main disease outcomes:cardiovascular disease and type 2 diabetes.

Metabolic syndrome in the development and progression of prostate cancer

Prostate cancer(PCa)is the most common noncutaneous malignancy and second leading cause of cancerspecific mortality for men in the United States.There is a wide spectrum of aggressiveness ranging from biologically significant to indolent disease,which has led to an interest in the identification of risk factors for its development and progression.Emerging evidence has suggested an association between metabolic syndrome(MetS)and PCa.MetS represents a cluster of metabolic derangements that confer an increased risk of cardiovascular disease and type 2 diabetes mellitus.Its individual components include obesity,dyslipidemias,high blood pressure,and high fasting glucose levels.Met S has become pervasive and is currently associated with a high socioeconomic cost in both industrialized and developing countries throughout the world.The relationship between MetS and PCa is complex and yet to be fully defined.A better understanding of this relationship will facilitate the development of novel therapeutic targets for the prevention of PCa and improvement of outcomes among diagnosed men in the future.In this review,we evaluate the current evidence on the role of MetS in the development and progression of PCa.We also discuss the clinical implications on the manage-ment of PCa and consider the future direction of this subject.

Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome(MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance(IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor

Polycystic ovary syndrome(PCOS)is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences.A plethora of symptoms and their severity differentiate on an individual level,giving the syndrome numerous phenotypes.Due to menstrual cycle abnormalities,women suffer from irregular menstrual bleeding,difficulty in conception,and infertility.Furthermore,the risk of pregnancy complications such as gestational diabetes mellitus,hypertensive disorders of pregnancy,and preterm birth are higher in women with PCOS than in the general population.Often,women with PCOS have comorbidities such as dyslipidemia,obesity,glucose intolerance or diabetes type 2,non-alcoholic fatty liver disease,and metabolic syndrome,which all influence the treatment plan.Historic insulinsensitizing agents,although good for some of the metabolic derangements,do not offer long-term cardiovascular benefits;therefore,new treatment options are of paramount importance.Sodium-glucose co-transporter-2(SGLT-2)inhibitors,a new class of antidiabetic agents with beneficial cardiovascular,bodyweight,and antihyperglycemic effects,although not approved for the treatment of PCOS,might be an attractive therapeutic addition in the PCOS armamentarium.Namely,recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS.It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic,reproductive,and psychological consequences.

Metabolic regulation by protein tyrosine phosphatases

Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.

Fetal programming of obesity and type 2 diabetes

The prevalence of obesity and type 2 diabetes mellitus has increased rapidly over the past few decades,and prevention efforts have not been successful.Fetal programming involves the earliest stage of obesity development,and provides a novel concept to complement other strategies for lifelong prevention of obesity and type 2 diabetes mellitus.The World Health Organization now advocates a life-course approach to prevent/control obesity,starting with pre-conceptional and antenatal maternal health.Maternal overnutrition,gestational diabetes mellitus and excessive gestational weight gain lead to fetal overgrowth,and“programs”the offspring with an increased risk of obesity and type 2 diabetes mellitus in childhood and adulthood.This review summarizes current data on fetal programming of obesity and type 2 diabetes mellitus including potential causative factors,mechanisms and interventions to reduce its impact.