Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide,Cross-Sectional 3B Study

Background

There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients.

Methods

Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24–27.9kg/m² and ≥28.0kg/m². Central obesity was defined as a waist circumference ≥80cm in women and ≥85cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90mmHg and LDL-C<2.6mmol/L.

Results

Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals.

Conclusions

Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.     

Metabolic abnormalities in first-degree relatives of type 2 diabetics

Diabetic relatives and obese subjects are at increased risk for development of diabetes mellitus, and therefore are classed as potential abnormality of glucose tolerance (POT-AGT). Disturbances of lipid and purine metabolisms have been reported in diabetic and obese non-diabetic subjects. In obese subjects above alterations are probably due to hyperinsulinemia. This study aimed at verifying whether similar metabolic abnormalities could be found in relatives of non-insulin dependent diabetic patients and whether they could be related to possible glucose intolerance. We have studied 10706 outpatients and 95 hospitalized subjects, aged between 20 and 50 years. We have selected 4 groups according to diabetic relationship and body mass index: A (normal weight subjects), B (obese subjects), C (normal weight NIDDM-relatives), D (overweight NIDDM-relatives). The NIDDM-relatives showed higher prevalence of hyperglycemia, as expected; furthermore the relatives with normal glucose tolerance had higher glucose area during OGTT. Serum levels of uric acid and insulin response to oral glucose were increased in all obese subjects, but abnormalities of lipid metabolism and fasting hyperinsulinemia were found only in obese NIDDM-relatives. These results suggest that family history of diabetes mellitus can be a risk for metabolic disturbance even in absence of glucose intolerance. Furthermore some metabolic disorders observed in obese subjects could be due to an associated and not sufficiently investigated family history of diabetes.     

Serum Circulating microRNA Profiling for Identification of Potential Type 2 Diabetes and Obesity Biomarkers

Background and Aim

MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes.

Patients and Methods

Thirteen patients with type 2 diabetes, 20 obese patients, 16 obese patients with type 2 diabetes and 20 healthy controls were selected for this study. MiRNA PCR panels were employed to screen serum levels of 739 miRNAs in pooled samples from these four groups. We compared the levels of circulating miRNAs between serum pools of each group. Individual validation of the twelve microRNAs selected as promising biomarkers was carried out using RT-qPCR.

Results

Three serum microRNAs, miR-138, miR-15b and miR-376a, were found to have potential as predictive biomarkers in obesity. Use of miR-138 or miR-376a provides a powerful predictive tool for distinguishing obese patients from normal healthy controls, diabetic patients, and obese diabetic patients. In addition, the combination of miR-503 and miR-138 can distinguish diabetic from obese diabetic patients.

Conclusion

This study is the first to show a panel of serum miRNAs for obesity, and compare them with miRNAs identified in serum for diabetes and obesity with diabetes. Our results support the use of some miRNAs extracted from serum samples as potential predictive tools for obesity and type 2 diabetes.     

Pathophysiologic changes in obesity.

Obesity is the common expression of several diverse interacting genetic, familial and environmental factors. In addition to having hypertrophic fat cells because of inordinate triglyceride accumulation, many patients with childhood-onset obesity and those who are massively obese regardless of age at onset have an excessive number of adipocytes. Several endocrinologic and metabolic abnormalities are associated with obesity. Triglyceride formation in and lipid mobilization from hypertrophic adipocytes are exaggerated. The increased availability of free fatty acids to the liver contributes to the excessive synthesis of triglycerides and very-low-density lipoproteins; thus, hypertriglyceridemia is frequently associated with obesity. Hepatic synthesis and biliary excretion of cholesterol are also increased. Most of the excess cholesterol is stored in fat cells. The plasma concentrations of high-density lipoproteins are decreased. Hyperinsulinemia, which is characteristically found in the obese, leads to a decreased number of insulin receptors in target cells. The relative insulin insensitivity of the obese frequently results in glucose intolerance. The endocrinologic and metabolic abnormalities are correctable by an appropriate program of meal planning and physical activity.     

Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity

Objective : Allelic variation (rs738409C→G) in adiponutrin (patatin‐like phospholipase domain‐containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis. The physiologic impact of the PNPLA3 G allele may be exacerbated in patients with severe obesity. In this study, we investigated the interactions of PNPLA3 rs738409 with a broad panel of metabolic and histologic characteristics of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) in patients with medically complicated obesity. Design and Methods : Consecutive patients undergoing bariatric surgery were selected for a prospective study. They underwent extensive laboratory and histologic (liver biopsy) assessment, as well as evaluation of rs738409 polymorphism by TaqMan assay. Results : Only 12 (8.3%) of the 144 patients had normal liver histology, with 72 (50%) NASH, of whom 15 (10.4% of total patients) had fibrosis stage 2‐3. PNPLA3 GG genotype correlated positively (P < 0.05) with serum levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), glucose, fibrinogen, and insulin‐dependent diabetes mellitus, homeostasis model assessment—insulin resistance, and presence of NASH. Multivariate analysis indicated that PNPLA3 rs738409 G versus C allele remained an (independent) risk factor for NASH, in addition to CK‐18 >145 IU/l, glucose >100 mg/dl, and C‐reactive protein (CRP) >0.8 mg/dl. The probability of NASH increased from 9% (no risk factor) to 82% if all four risk factors were present. Conclusions : In this cohort of patients with medically complicated obesity, PNPLA3 rs738409 G allelic expression is associated with hepatic (NASH) and nonhepatic complications of obesity, such as insulin resistance. These novel findings may be related to a greater impact of PNPLA3 variant in magnitude and scope in patients with severe obesity than in less obese populations. Further studies are needed to characterize the nature of these associations.     

Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes

As a new mouse model of obesity-induced diabetes generated by combining quantitative trait loci from New Zealand Obese (NZO/HlLt) and Nonobese Nondiabetic (NON/LtJ) mice, NONcNZO10/LtJ (RCS10) male mice developed type 2 diabetes characterized by maturity onset obesity, hyperglycemia, and insulin resistance. To metabolically profile the progression to diabetes in preobese and obese states, a 2-h hyperinsulinemic euglycemic clamp was performed and organ-specific changes in insulin action were assessed in awake RCS10 and NON/LtJ (control) males at 8 and 13 wk of age. Prior to development of obesity and attendant increases in hepatic lipid content, 8-wk-old RCS10 mice developed insulin resistance in liver and skeletal muscle due to significant decreases in insulin-stimulated glucose uptake and GLUT4 expression in muscle. Transition to an obese and hyperglycemic state by 13 wk of age exacerbated insulin resistance in skeletal muscle, liver, and heart associated with organ-specific increases in lipid content. Thus, this polygenic mouse model of type 2 diabetes, wherein plasma insulin is only modestly elevated and obesity develops with maturity yet insulin action and glucose metabolism in skeletal muscle and liver are reduced at an early prediabetic age, should provide new insights into the etiology of type 2 diabetes.     

Screening for diabetes in general practice: cross sectional population study

ObjectiveTo assess the policy proposed by the American Diabetes Association of universal screening in general practice of all patients aged over 45 years for diabetes.Design Cross sectional population study.Setting Local general practice in the United Kingdom.Participants All patients aged over 45 not known to have diabetes.Results Of 2481 patients aged over 45 and not known to have diabetes, 876 attended for screening. There were no significant demographic differences between the screened and unscreened patients. Prevalence of diabetes in patients with age as a sole risk factor was 0.2% (95% confidence interval 0% to 1.4%). Prevalence of diabetes in patients with age and one or more other risk factors (hypertension, obesity, or a family history of diabetes) was 2.8% (1.6% to 4.7%). Four hours a week for a year would be needed to screen all people over 45 in the practice''s population; about half this time would be needed to screen patients with risk factors other than age. More than 80% of patients newly diagnosed as having diabetes had a 10 year risk of coronary heart disease >15%, 73% (45% to 92%) were hypertensive, and 73% (45% to 92%) had a cholesterol concentration >5 mmol/l.Conclusions Screening for diabetes in general practice by measuring fasting blood glucose is feasible but has a very low yield in patients whose sole risk factor for diabetes is age over 45. Screening in a low risk population would best be targeted at patients with multiple risk factors.

What is already known on this topic

Between a third and a half of cases of diabetes are undiagnosed at any one timeNew cases can be identified by screening groups of patients at riskThe American Diabetes Association has proposed the screening of all patients aged over 45 every three years

What this study adds

Screening for diabetes in general practice by measuring fasting blood glucose is feasible but requires much staff timeScreening solely on the basis of age has a very low yield and screening would best be targeted at patients with multiple risk factors for diabetes     

Diabetes, lipids, and adipocyte secretagogues.

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor alpha, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.     

Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes

The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.     

Programming of Obesity and Comorbidities in the Progeny: Lessons from a Model of Diet-Induced Obese Parents

Aim

To determine the impact of paternal obesity, maternal obesity or the combination of two obese parents on markers of adult offspring metabolism, with a focus on body mass (BM), lipid and carbohydrate, components of lipogenesis and beta-oxidation in the liver, sex dimorphism in the offspring that received a SC diet during the postnatal period.

Materials and Methods

Male and female C57BL/6 mice were fed a high-fat diet (HF; 49% lipids) or standard chow (SC; 17% lipids) for 8 weeks before mating until lactation. The offspring were labeled according to sex, maternal diet (first letters), paternal diet (second letters), and received a SCdiet until 12-weeks of age when they were sacrificed. BM, eating behavior, glucose tolerance, plasma analysis, gene and protein expression of the components of lipogenesis and beta-oxidation in the liver of offspring were evaluated.

Results

HF diet-fed mothers and fathers were overweight, hyperglycemic and glucose intolerant and had a deteriorating lipid profile. The adult male and female offspring of HF-mothers were overweight, with an increased adiposity index, hyperphagic, had an impaired glucose metabolism, increased total cholesterol and triacylglycerol levels, increased lipogenesis concomitant with decreased beta-oxidation resulting in liver steatosis. The male and female offspring of HF-father had impaired glucose metabolism, exacerbated lipogenesis without influencing beta-oxidation and enhanced hepatic steatosis. These findings are independent of BM. Male and female offspring of a mother and father that received a HF diet demonstrated these effects most prominently in adult life.

Conclusion

Paternal obesity leads to alterations in glucose metabolism, increase in components of lipogenesis and liver steatosis. In contrast, maternal obesity leads to overweight and changes in the metabolic profile and liver resulting from activation of hepatic lipogenesis with impaired beta-oxidation. When both parents are obese, the effects observed in the male and female offspring are exacerbated.     

Metabolic risk-factor clustering estimation in obese children

The purpose of this study was to apply the new approach for Metabolic Individual Risk-factor And Clustering Estimation (MIRACLE) score in a group of Spanish obese children and adolescents and to describe its relationship with other metabolic risk factors. 153 children with simple obesity were studied: 79 males and 74 females, mean age 11.2 +/- 2.2. Obesity was defined when BMI was higher than the age and sex specific equivalent to 30 kg/m2 in adults. MIRACLE score included: family history (early cardiovascular disease, type 2 diabetes, and hypertension), individual history (small for gestational age and ethnic origin), clinical features (BMI, waist circumference > 90th percentile and blood pressure > 95th percentile) and metabolic abnormalities (glucose intolerance or type 2 diabetes). It was assigned a value of 1 to "presence" and 0 to" absence" in every patient. The children were considered as having metabolic risk when at least 5 items were present. Triglycerides, HDL-cholesterol, apolipoprotein B, apolipoprotein A1, glucose and HOMA index, were measured too. The most frequent clinical features of MIRACLE score were: excess waist circumference (95.4%) and hypertension (41.8%). Family history criteria were frequent (55.3% for type 2 diabetes, 39.1% for hypertension and 31.3% for early cardiovascular disease). Individual risk factors were not frequent. Glucose intolerance was detected in 22.2% of the obese patients. A MIRACLE score > or = 5 was found in 37.4% of the children studied, being associated with a significant risk of dyslipidemia (triglycerides, p = 0.040; HDL-cholesterol, p = 0.006; LDL-cholesterol p = 0.038; apolipoprotein B, p = 0.008) only in females. In conclusion, the MIRACLE score is useful in order to detect metabolic risk in obese children but it seems necessary to improve the score, by including other features of the metabolic syndrome like lipid profile or indirect indicators of insulin resistance.     

Toll-like receptor 3 ablation prevented high-fat diet-induced obesity and metabolic disorder

Inflammation in insulin-sensitive tissues (e.g., liver, visceral adipose tissue [VAT]) plays a major role in obesity and insulin resistance. Recruitment of innate immune cells drives the dysregulation of glucose and lipid metabolism. We aimed to seek the role of Toll like receptor 3 (TLR3), a pattern recognition receptor involved in innate immunity, obesity and the metabolic disorder. TLR3 expression in liver and VAT from diet induced obese mice and in VAT from overweight women was examined. Body weight, glucose homeostasis and insulin sensitivity were evaluated in TLR3 wild-type and knockout (KO) mice on a chow diet (CD) or high-fat diet for 15 weeks. At euthanasia, blood was collected, and plasma biochemical parameters and adipokines were determined with commercial kits. Flow cytometry was used to measure macrophage infiltration and activation in VAT. Standard western blot, immunohistochemistry and quantative PCR were used to assess molecules in pathways about lipid and glucose metabolism, insulin and inflammation in tissues of liver and VAT. Utilizing human and animal samples, we found that expression of TLR3 was upregulated in the liver and VAT in obese mice as well as VAT in overweight women. TLR3-deficiency protected against high-fat diet induced obesity, glucose intolerance, insulin resistance and lipid accumulation. Lipolysis was enhanced in VAT and hepatic lipogenesis was inhibited in TLR3 KO animals. Macrophages infiltration into adipose tissue was attenuated in TLR3 KO mice, accompanied with inhibition of NF-κB-dependent AMPK/Akt signaling pathway. These findings demonstrated that TLR3 ablation prevented obesity and metabolic disorders, thereby providing new mechanistic links between inflammation and obesity and associated metabolic abnormalities in lipid/glucose metabolism.     

Effects of Fortunella margarita Fruit Extract on Metabolic Disorders in High-Fat Diet-Induced Obese C57BL/6 Mice

Introduction

Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice.

Methods

The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay.

Results

In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes.

Conclusion

Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances.     

Effects of fenofibrate on lipid parameters in obese rhesus monkeys

Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity. These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C.     

Association of resistin gene polymorphisms with insulin resistance in Egyptian obese patients

Background

Obesity associated insulin resistance is a major risk factor for type 2 diabetes mellitus. Resistin is recently reported to provide a link between obesity, insulin resistance and type 2 diabetes mellitus. We aimed to investigate the possible associations of resistin gene (RETN) polymorphisms with obesity, and to detect whether these polymorphisms are associated with glucose intolerance and type 2 diabetes mellitus in obese patients.

Methods

One hundred and forty-five Egyptian obese patients with or without glucose intolerance and 155 unrelated healthy controls were enrolled in this study. Polymorphisms of RETN + 299G>A and RETN –420 C>G gene were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Serum resistin was measured by ELISA.

Results

RETN + 299 AA and RETN − 420 GG genotypes were significantly associated with obesity in Egyptian population. Moreover, the mutant alleles or genotypes of both examined polymorphisms were associated with impaired glucose tolerance and diabetes mellitus compared to normal glucose tolerant obese patients. Furthermore, our results revealed elevated waist/hip ratio, BMI, blood pressure, fasting blood glucose level, HOMA-IR, triglycerides, total cholesterol, resistin level, and decreased HDL cholesterol level in homozygote mutant genotypes carriers of both RETN polymorphisms among obese patients.

Conclusion

Resistin gene polymorphisms may play an important role in pathogenesis and susceptibility to obesity, impaired glucose tolerance, and type 2 diabetes mellitus in Egyptian population.     

Glucose Intolerance and the Amount of Visceral Adipose Tissue Contribute to an Increase in Circulating Triglyceride Concentrations in Caucasian Obese Females

Context

Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2.

Methods

913 obese females unknown to have diabetes were recruited (mean age: 41.2±SD 12.3; median BMI: 36.2, IQR 32.9–40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test.

Results

Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared.

Conclusions

Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.     

Mechanistic model of fuel selection in the muscle

Fuel selection in human muscle is key to explaining insulin resistance. In obesity and type 2 diabetes mellitus, there is an increased content of lipid within and around muscle fibers. Changes in muscle fuel partitioning of lipid, between oxidation and storage of fat, contribute to the accumulation of intramuscular triglycerides and to the pathogenesis of both obesity and type 2 diabetes mellitus. A mathematical model of the aggregated metabolism in skeletal muscle was developed and the effects of fuel selection for lean and obese individuals under fasting conditions, insulin-stimulated conditions, and oscillating insulin conditions were examined. Model results were complementary to prior observations that elevated lipid oxidation during insulin-stimulated conditions is correlated with insulin resistance. The model also adequately simulated metabolic inflexibility between fat and glucose oxidation in the obese individual. A novel sensitivity analysis indicated the strong interaction effects of parameters of glucose and lipid oxidation pathways on the variables of each pathway.     

Hyperinsulinemia induced by canine distemper virus infection of mice and its correlation with the appearance of obesity

1. Weanling Swiss mice surviving an acute infection with canine distemper virus were persistently infected. Among these mice, up to 30% had hyperinsulinemia and this was followed by an obesity syndrome. 2. Analysis of the lipid composition of various organs revealed that compared to control animals, the obese had an accumulation of triglycerides in both liver and adipose tissue. 3. Studies on the lipid metabolism using a number of radioactive lipid precursors showed a specific accumulation of the triglycerides of the obese animals. 4. A decrease of lipogenesis was observed in white adipose tissue of obese mice. Glycogenesis and serum glucose levels were unaffected during obesity. 5. The model of canine distemper virus-induced obesity is compared with other experimental models.     

Psyllium fibre and the metabolic control of obese children and adolescents

In children and adolescents from developed countries, obesity prevalence has strongly increased in the last decades and insulin resistance and impaired glucose tolerance are frequently observed. Some dietary components such as low glycemic index foods and dietary fibre could be used in order to improve glucose homeostasis in these children. Psyllium or ispaghula husk (the husk of the seeds of Plantago ovata) is a mixture of neutral and acid polysaccharides containing galacturonic acid with a ratio of soluble/insoluble fibre of 70/30. Some foods could potentially be enriched with psyllium, like breads, breakfast cereals, pasta and snack foods. The aim of this review was to assess the usefulness of psyllium in the management of obese children and adolescents with abnormalities of carbohydrate and lipid metabolism. After psyllium supplementation, the percentage change in postprandial glucose in type 2 diabetes patients, ranged from -12.2 to -20.2%. In hypercholesterolemic children, the effect of psyllium in LDL-cholesterol serum concentrations ranged from 2.78 to -22.8%; the effect in HDL-cholesterol from -4.16 to 3.05%; and the effect on triglycerides from 8.49 to -19.54%. The reviewed evidence seems to show that psyllium improves glucose homeostasis and the lipid and lipoprotein profile; however, more well controlled trials and further studies are needed to clarify it's effects and the mechanisms involved.