The peroxisome proliferator-activated receptor-gamma2 gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study

The peroxisome proliferator-activated receptor (PPAR)-gamma2 gene polymorphism Pro12Ala has been associated with increased insulin sensitivity in some but not all studies. Little is known about its effect on the tracking of insulin resistance status over time. These aspects were examined in a community-based sample of 686 white young adults, aged 20-38 years, and 426 white children, aged 4-17 years, and a subsample of a cohort (n = 362) who participated both as children and adults, with an average follow-up period of 13.4 years. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using fasting insulin and glucose. The frequency of the variant Ala12 allele was 0.104 in whites vs. 0.017 in blacks. After adjusting for sex, age, and BMI, adult subjects with the genotype Pro/Pro, Pro/Ala, and Ala/Ala, respectively, showed significant decreasing trends in fasting insulin (11.7, 10.3, and 8.8 micro U/ml; P = 0.002) and HOMA-IR (2.4, 2.1, and 1.7; P = 0.006). Similar but nonsignificant trends were noted in childhood. A significant genotype-BMI interaction effect on insulin (P = 0.020), glucose (P = 0.007), and HOMA-IR (P = 0.001) was found in adulthood, with carriers versus noncarriers showing attenuated association with BMI. The genotype-BMI interaction effect on these variables tended to be similar in childhood. With respect to tracking over time, of individuals in the top age- and sex-specific quartile of HOMA-IR in childhood, 48.7% (38/78) of noncarriers vs. 16.7% (2/12) of the carriers (P = 0.035) remained in the same quartile in adulthood. A similar trend was observed for insulin (2/13 vs. 35/77, P = 0.037). In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene beneficially influences insulin resistance and its tracking from childhood to adulthood. Further, the Ala12 allele attenuates the adverse association between adiposity and insulin resistance measures.     

Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heart Study

The age-related patterns of clustering of cardiovascular risk variables of Syndrome X from childhood to adulthood were examined in a community-based sample of black and white children (aged 5-10 years, n = 2,389), adolescents (aged 11-17 years, n = 3,371), and young adults (aged 18-37 years, n = 2,115). In the analysis of clustering, insulin resistance index, BMI, triglycerides/ HDL cholesterol ratio, and mean arterial pressure were used either as categorical variables (age-, race- and sex-specific values >75th percentiles) to calculate risk ratios (observed frequency/expected frequency) or as continuous variables (normal scores based on ranks) to compute intraclass correlations. In the total sample, the risk ratio for clustering of adverse levels of all 4 variables was 9.8 for whites (P < 0.01) versus 7.4 for blacks (P < 0.01); the intraclass correlation was 0.33 for whites (P < 0.001) versus 0.26 for blacks (P < 0.001). Both the risk ratio and intraclass correlation were significantly higher in whites than in blacks in the total sample. The intraclass correlations of the 4 variables were significant (P < 0.001) in all race and age-groups, and they were higher during preadolescence and adulthood than during adolescence. Furthermore, unlike risk ratios, intraclass correlations showed a continuous increase with age during adulthood. When BMI was adjusted, the intraclass correlations involving the other 3 variables were reduced by approximately 50%, and the age-related pattern was no longer evident. These results suggest that the degree of clustering of risk variables of Syndrome X varies with age from childhood to adulthood and is likely influenced by the age-related changes in obesity and the attendant insulin resistance.     

Black-white contrasts in insulin levels during pubertal development. The Bogalusa Heart Study.

Three hundred and seventy-seven children and adolescents aged 5-17 yr from the biracial (black-white) community of Bogalusa, Louisiana, were evaluated for Tanner stage of sexual development, plasma glucose, and insulin levels during an oral glucose tolerance test. Children of the two races were of similar age, weight, and height at each Tanner stage. Overall insulin response was compared by measuring the area under the insulin curve from the glucose tolerance test. Blacks, especially black females, had significantly higher insulin responses than their white counterparts. The insulin-glucose ratio at the initial t = 0 min baseline did not vary with race or sex throughout the Tanner stages. However, the 30 min postglucose data revealed clear differences between the races with blacks showing a higher insulin-glucose ratio. Ratios increased throughout puberty for both blacks and whites, boys and girls. The trends of racial contrasts seemed to be discernible even at the earliest stage of development. It is concluded that there is a clear difference between blacks and whites in insulin response to a glucose load early in childhood. These findings lead to the hypothesis that the greater prevalence of non-insulin-dependent diabetes mellitus seen in adult blacks, especially females, may be an expression of a difference in insulin secretion and related insulin resistance in early childhood.     

Association of the insulin resistance syndrome and microalbuminuria among nondiabetic native Americans. The Inter-Tribal Heart Project

This study investigated the association between microalbuminuria and the insulin resistance syndrome (IRS) among nondiabetic Native Americans. In a cross-sectional survey, age-stratified random samples were drawn from the Indian Health Service clinic lists for one Menominee and two Chippewa reservations. Information was collected from physical examinations, personal interviews, and blood and urine samples. The urinary albumin:creatinine ratio (ACR) was measured using a random spot urine sample. The IRS was defined by the number of composite traits: hypertension, impaired fasting glucose (IFG), high fasting insulin, low HDL cholesterol, and hypertriglyceridemia. Among the 934 eligible nondiabetic participants, 15.2% exhibited microalbuminuria. The prevalence of one, two, and three or more traits was 27.0, 16.6, and 7.4%, respectively. After controlling for age, sex, smoking, body mass index, education, and family histories of diabetes and kidney disease, the odds ratio (OR) for microalbuminuria was 1.8 (95% confidence interval [CI], 1.1 to 2.8) for one IRS trait, 1.8 (95% CI, 1.0 to 3.2) for two traits, and 2.3 (95% CI, 1.1 to 4.9) for three or more traits (versus no traits). The pattern of association appeared weaker among women compared with men. Of the individual IRS traits, only hypertension and IFG were associated with microalbuminuria. Among these nondiabetic Native Americans, the IRS was associated with a twofold increased prevalence of microalbuminuria. Health promotion efforts should focus on lowering the prevalence of hypertension, as well as glucose intolerance and obesity, in this population at high risk for renal and cardiovascular disease.     

Body mass index trajectories from childhood concerning emotional states in young adulthood: Tehran Lipid and Glucose Study

This study aimed to identify body mass index (BMI) trajectories from childhood and their relationships with depression, anxiety, and stress symptoms in young adulthood. A total of 687 children aged 4–18 years were recruited from the Tehran Lipid and Glucose Study. Throughout 18 years of follow-up, BMI was measured every 3 years for a maximum of 6 data points. Participants completed the depression, anxiety, and stress scale in their young adulthood (aged 22–36). The group-based trajectory modelling was applied to identify BMI patterns. The logistic regression model was used to assess the association between BMI trajectories and depression, anxiety, and stress symptoms in adulthood. Two BMI trajectories were identified from childhood to young adulthood: healthy weight (HW = 69.6%) and persistent increasing overweight/obesity (PIO = 30.4%). After adjusting for potential confounders, compared with the HW group, men in the PIO group were more likely to experience higher stress levels (OR: 1.62, 95% CI: 0.99–2.63; p = 0.05). No significant association was observed between the PIO trajectory and depression and anxiety among both sexes and stress symptoms in females. Our results highlight that developing overweight and obesity from childhood may be related to increased stress in males.     

Asymptomatic bronchial hyperresponsiveness to exercise in childhood and the development of asthma related symptoms in young adulthood: the Odense Schoolchild Study

BACKGROUND: Exercise testing may be of value in identifying a group of children at high risk of subsequently developing respiratory symptoms. As few longitudinal studies have investigated this issue, the bronchial hyperresponsiveness to exercise in asymptomatic children was evaluated as a risk factor for developing asthma related symptoms in young adulthood. METHODS: A community based sample of 1369 schoolchildren, first investigated in 1985 at a mean age of 9.7 years, was followed up after a mean of 10.5 years. Nine hundred and twenty children (67%) were asymptomatic in childhood and 777 (84.9%) of these were re-investigated at follow up. At the first examination a maximum progressive exercise test on a bicycle ergometer was used to induce airway narrowing. The forced expiratory volume in one second (FEV1) after exercise was considered abnormal if the percentage fall in FEV1 was more than 5% of the highest fall in the reference subjects characterised by having no previous history of asthma or asthma related symptoms. The threshold for a positive test was 8.6% of pre-exercise FEV1. RESULTS: One hundred and three subjects (13%) had wheeze within the last year at follow up and, of these, nine (9%) had been hyperresponsive to exercise in 1985. One hundred and seventy subjects (22%) had non-infectious cough within the previous year, 11 of whom (6%) had been hyperresponsive to exercise in 1985. Multiple regression analysis showed that subjects with hyperresponsiveness to exercise had an increased risk of developing wheeze compared with subjects with a normal response to exercise when the fall in FEV1 after exercise was included as a variable (threshold odds ratio (OR) 2.3 (95% CI 1.1 to 5.5)). The trend was not significant when exercise induced bronchospasm was included as a continuous variable (OR 1.02 (95% CI 0.97 to 1.06)). CONCLUSIONS: Asymptomatic children who are hyperresponsive to exercise are at increased risk of developing new symptoms related to wheezing but the predictive value of exercise testing for individuals is low.     

多囊卵巢综合征青年患者血清脂联素、胰岛素抵抗关系的研究

目的探讨多囊卵巢综合征（PCOS）青年患者血清脂联素（APN）、抵抗素（RST）水平与胰岛素抵抗（1R）的关系。方法PCOS组为38例青年PCOS患者,对照组为27例健康女性,两组中根据体重指数（BMI）分为肥胖组BMI（≥25kg／m^2）和非肥胖组（BMI〈25kg／m^2）。在月经第3～5天晨（PCOS闭经者B超检查无优势卵泡当天）留空腹血。采用酶联免疫吸附法（ELISA）测定血清APN和RST浓度,葡萄糖氧化酶法测定血糖浓度,化学发光法测定胰岛素浓度,根据后两者计算胰岛素敏感指数（ISI）。结果（1）肥胖组与非肥胖组空腹血糖水平比较,差异无统计学意义（P〉0．05）;（2）肥胖组与非肥胖组中,PCOS组的空腹胰岛素水平分别显著高于对照组（P〈0．05）;（3）肥胖组中,PCOS组血清APN和ISI水平显著低于对照组,血清RST水平显著高于对照组（P〈0．05）;（4）非肥胖组中,PCOS组血清APN和ISI水平显著低于对照组,血清RST水平显著高于对照组（P〈0．05）。结论（1）与对照组相比,青年PCOS患者血清中APN水平较低,RST水平较高,其中PCOS肥胖患者尤为明显。（2）青年PCOS患者血清中APN水平的下降和RST水平的升高可能与胰岛素敏感性及IR相关。     

Type 2 diabetes mellitus in childhood: obesity and insulin resistance

As rates of childhood obesity climb, type 2 diabetes mellitus has increasingly been diagnosed in children and adolescents, with the highest incidence occurring among youth from racial and ethnic minority backgrounds. The serious complications associated with type 2 diabetes mellitus make it essential for physicians to be aware of risk factors and screening guidelines, allowing for earlier patient diagnosis and treatment. It is also important for physicians to be aware of the treatment options available, including weight control through diet and exercise as well as common pharmacotherapeutic options.     

Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in adiposity and insulin resistance

Apolipoprotein A-II (apoA-II) is the second most abundant protein in HDLs. Genetic studies in humans have provided evidence of linkage of the apoA-II gene locus to plasma free fatty acid (FFA) levels and to type 2 diabetes, and transgenic mice overexpressing mouse apoA-II have elevated levels of both FFA and triglycerides. We now show that apoA-II promotes insulin resistance and has diverse effects on fat homeostasis. ApoA-II transgenic mice have increased adipose mass and higher plasma leptin levels than C57BL/6J control mice. Fasting glucose levels were similar between apoA-II transgenic and control mice, but plasma insulin levels were elevated approximately twofold in the apoA-II transgenic mice. Compared with control mice, apoA-II transgenic mice exhibited a delay in plasma clearance of a glucose bolus. Adipose tissue isolated from fasted apoA-II transgenic mice exhibited a 50% decrease in triglyceride hydrolysis compared with adipose tissue from control mice. This is consistent with a normal response of adipose tissue to the increased insulin levels in the apoA-II transgenic mice and may partially explain the increased fat deposition. Skeletal muscle isolated from fasted apoA-II transgenic mice exhibited reduced uptake of 2-deoxyglucose compared with muscles isolated from control mice. Our observations indicate that a primary disturbance in lipoprotein metabolism can result in several traits associated with insulin resistance, consistent with the hypothesis that insulin resistance and type 2 diabetes can, under certain circumstances, be related primarily to altered lipid metabolism rather than glucose metabolism.     

Overweight, insulin resistance and blood pressure (parameters of the metabolic syndrome) in uric acid urolithiasis

Overweight, arterial hypertension and disturbances of the carbohydrate metabolism are important parameters of the metabolic syndrome (MS). The most important factor regarding renal pathophysiology is insulin resistance resulting in alterations of urine acidification and low urine pH. Since low urine pH is the main risk factor for uric acid urolithiasis (UAU), UAU may be regarded as a renal manifestation of the MS. So far, there are only few data on the prevalence of parameters of the MS in UAU patients especially with regard to the severity of the disease and recurrence rate, respectively. The objective of this study was to know more about the prevalence of different parameters of the MS and their importance for the natural history of this type of renal stone disease using a total number of 167 consecutive patients with pure UA stones. Stone analysis was performed by polarization microscopy and X-ray diffraction. The following parameters were measured: age, sex, systolic and diastolic arterial blood pressure (RRs and RRd), number of stone episodes, diabetes mellitus (DM); serum: creatinine, calcium, sodium, potassium, uric acid, glucose; urine: pH-profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. The following results were obtained (means ± standard deviations): age 61 ± 13 years, BMI 30 ± 6 kg/m², BP 147/84 ± 22/13 mmHg, number of stone episodes 1.8 ± 1.2, DM 32%; serum: creatinine 1.3 ± 0.6 mg/dl, glucose 136 ± 52 mg/dl, UA 6.3 ± 1.8 mg/dl, calcium 2.4 ± 1.3 mmol/l, sodium 134 ± 18 mmol/l, potassium 4.1 ± 0.4 mmol/l; urine: pH 5.87 ± 0.27, volume 2.4 ± 1.1 l/d, calcium 3.5 ± 2.5 mmol/d, UA 3.9 ± 2.4 mmol/d, citrate 1.3 ± 1.1 mmol/d, ammonia 41 ± 26 mmol/d, urea 390 ± 176 mmol/d. A significant positive correlation could be found for BMI and urea excretion, BMI correlated negatively with RRs and RRd. There was no significant correlation between BMI, urine pH, citrate, ammonia and UA in serum and urine. Undue acidity and hyperuricosuria were found in two-thirds of the UAU patients, increased urea excretion and decreased excretion of ammonia in less than 25%, Hyperuricemia in 37%. There was no significant correlation between the number of stone episodes and any other parameter studied. Overweight, arterial hypertension and DM as parameters of the MS are frequent in many patients with UAU. However, these parameters do explain the pathogenesis in two-thirds of the patients. The severity of the disease and the recurrence are not influenced by the presence of these metabolic parameters. Therefore, MS is no prognostic factor in UAU.     

Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study

Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome, although it is not known whether markers of NAFLD, including elevated concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK), predict the development of metabolic syndrome. Our objective was to investigate the associations of elevated AST, ALT, and other liver markers, including C-reactive protein (CRP), with incident National Cholesterol Education Program-defined metabolic syndrome among 633 subjects in the Insulin Resistance Atherosclerosis Study who were free of metabolic syndrome at baseline. Insulin sensitivity (Si) and acute insulin response (AIR) were directly measured from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. After 5.2 years, 127 individuals had developed metabolic syndrome. In separate logistic regression models adjusting for age, sex, ethnicity, clinic, and alcohol consumption, subjects in the upper quartiles of ALT, ALK, and CRP were at significantly increased risk of incident metabolic syndrome compared with those in the lowest quartile: ALT, odds ratio 2.50 (95% CI 1.38-4.51); ALK, 2.28 (1.24-4.20); and CRP, 1.33 (1.09-1.63). Subjects in the upper quartile of the AST-to-ALT ratio were at significantly reduced metabolic syndrome risk (0.40 [0.22-0.74]). After further adjustment for waist circumference, Si, AIR, and impaired glucose tolerance, the associations of ALT and the AST-to-ALT ratio with incident metabolic syndrome remained significant (ALT, 2.12 [1.10-4.09]; the AST-to-ALT ratio, 0.48 [0.25-0.95]). These associations were not modified by ethnicity or sex, and they remained significant after exclusion of former and heavy drinkers. In conclusion, NAFLD markers ALT and the AST-to-ALT ratio predict metabolic syndrome independently of potential confounding variables, including directly measured Si and AIR.     

Preferential loss of central (trunk) adiposity in adolescents and young adults after laparoscopic gastric bypass

BACKGROUND: An increasing number of young people are developing severe obesity with adult-like co-morbidities and undergoing bariatric surgery. Although a number of studies have described major weight loss after bariatric surgery, none have examined the proportions of lean body and fat mass lost or the potentially more important issue of changes in regional fat mass distribution after laparoscopic gastric bypass surgery. METHODS: Five morbidly obese females (mean age 18) were evaluated by standard anthropometric measures and dual energy x-ray absorptiometry at baseline and 1 year after bariatric surgery. The mean and SD values for the anthropometric and dual energy x-ray absorptiometry body composition variables were calculated, and the differences were evaluated using paired t tests. RESULTS: Significant body mass index and weight loss were seen in all subjects at 1 year, with the percentage of excess weight loss at 63.4%. Overall fat mass loss exceeded lean mass loss by threefold in this cohort (P <.01), demonstrating the relative sparing of lean mass. Their waist circumference also decreased significantly. Using dual energy x-ray absorptiometry analysis, the vast majority (83%) of central mass loss consisted of adipose tissue. Central fat loss significantly exceeded peripheral fat loss by 1.6-fold (P = .03). CONCLUSION: These results have demonstrated the preferential loss of central adiposity in morbidly obese young women after 1 year of surgical weight loss and may be more informative than anthropometric measurements alone. Given the association between central adiposity and the risk of subsequent cardiovascular disease, these results are suggestive of reduced cardiac risk.     

Markers of insulin resistance in Polycystic ovary syndrome women: An update

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.     

Correlation of calculated indices of insulin resistance (QUICKI and HOMA) with the euglycaemic hyperinsulinaemic clamp technique for evaluating insulin resistance in critically ill patients

BACKGROUND AND OBJECTIVE: Insulin resistance is frequently observed in critical illness. It can be quantified by the expensive and time-consuming euglycaemic hyperinsulinaemic clamp technique (M-value) and calculated indices of insulin resistance (Quantitative Insulin Sensitivity Check Index; QUICKI and Homeostasis Model Assessment; HOMA) with lower costs and efforts. We performed an observational study to assess the reliability of QUICKI and HOMA to evaluate insulin resistance in critically ill patients compared with the current gold standard method, the euglycaemic hyperinsulinaemic clamp technique. METHODS: Insulin resistance was measured in 30 critically ill medical patients by the euglycaemic hyperinsulinaemic clamp technique (M-value) as well as calculated using QUICKI and HOMA. Correlations between the M-values as well as QUICKI and HOMA were assessed by means of the Pearson's correlation coefficient. RESULTS: M-value, QUICKI and HOMA indicated insulin resistance in all 30 patients. However, both indices QUICKI and HOMA did not correlate with the M-values in our patients (r2 = 0.008 and 0.0005, respectively). A significant negative correlation was found between the M-value and the severity of illness assessed by the APACHE (Acute Physiology and Chronic Health Evaluation) III score (r2 = 0.16; P < 0.05). In contrast, neither HOMA nor QUICKI correlated with the APACHE III score (r2 = 0.034 and 0.033, respectively). CONCLUSIONS: Although QUICKI and HOMA indicated insulin resistance in the critically ill medical patients, both indices did not correlate with the M-value. Therefore, the euglycaemic hyperinsulinaemic clamp technique remains the gold standard for estimating insulin resistance in critically ill patients.     

Histiocytosis X (Langerhans' cell granulomatosis) of the thymus. A clinicopathologic study of four childhood cases

Four cases of histiocytosis X (Langerhans' cell granulomatosis) involving the thymus are presented. All the patients were children, their age at diagnosis ranging from 2 months to 8 years. In two cases, the disease seemed restricted to the thymus; in the other two, there was extrathymic involvement. The treatment was generally in the form of surgical excision. All the patients are alive and well on follow-up. The light-microscopic appearance was that classically described for histiocytosis X in all cases. Staining for S-100 protein was strongly positive in the two cases in which it was carried out.