Insulin resistance syndrome in women with prior history of gestational diabetes mellitus.

The purpose of this study was to determine the prevalence of insulin resistance syndrome (IRS) and the risk factors for developing IRS among women with a history of gestational diabetes mellitus (GDM), compared with controls over 11 postdelivery years. Assessments of 106 women with a prior history of GDM and 101 controls were done on six occasions from 4-11 yr after delivery. Tests included glucose, insulin, lipids, blood pressure, and body measurements. The risk of IRS was analyzed by Cox regression. The results were that 27.2% of GDM and 8.2% of controls developed IRS by 11 yr after delivery. The hazard of developing IRS was 5.6 times (95% confidence interval = 2.6-12.3) among women with prepregnant obesity (body mass index >27.3 kg/m(2)), compared with women without prepregnant obesity and 4.4 times (95% confidence interval = 1.7-11.1) in women with a history of GDM, compared with controls. At 11 yr after delivery, the cumulative hazard for developing IRS in the next 2 yr was 26 times higher among GDM with prepregnant obesity, compared with controls without prepregnant obesity. We concluded that obesity and GDM in a prior pregnancy are significant risk factors for developing IRS over time. Early detection of markers of IRS is vital for possible prevention of type 2 diabetes and cardiovascular adverse events in women.

White blood cell count and clustered features of metabolic syndrome in Japanese male office workers.

We assessed the association of white blood cell (WBC) count with different components of metabolic syndrome (MS)-obesity, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol levels, hypertriglyceridemia, high fasting plasma glucose levels and hyperuricemia-in 5275 Japanese male office workers aged 23-59 years. After controlling for age, smoking and alcohol intake, the relative risks for the presence of 1, 2, 3, 4 and > or =5 features of MS compared with the lowest quintile of WBC count increased in a dose-dependent manner as WBC count increased (P for trend < 0.001 for all) and the increased relative risks for clustered features of MS were more pronounced as the number of features of MS increased. The WBC count increments in subjects with 1, 2, 3, 4 and > or =5 features of MS were 0.28, 0.45, 0.68, 0.76 and 1.40 x10(9) cells/l, respectively, compared with the subjects without features of MS (P for trend < 0.001). These findings indicate a strong association between WBC count and clustered features of MS in middle-aged Japanese men.

Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

Metabolic syndrome and aging in Wistar Ottawa Karlsburg W rats.

BACKGROUND AND OBJECTIVE: Comparative studies have shown that Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a nearly complete metabolic syndrome with obesity, moderate hypertension, dyslipidemia, hyperinsulinemia, and impaired glucose tolerance up to an age of 28 weeks. Because metabolic data thereafter are missing, WOKW and disease-resistant DA rats were studied for 12 months beginning at an age of 5 months. METHODS: Eighteen male inbred WOKW and DA rats were studied monthly from the 5th to the 17th month of life for traits of the metabolic syndrome such as body weight, body mass index (BMI), serum triglycerides, total cholesterol, leptin, insulin as well as glucose tolerance, 24 h excretion of urine total protein and creatinine including telemetric measurement of blood pressure in six males per each group. RESULTS: Except for serum total cholesterol, the measured values for most traits studied were significantly higher in WOKW than in DA rats at an age of 5 months. At an age of 17 months all traits were significantly elevated in WOKW compared with DA rats. WOKW rats were hypertensive, dyslipidemic, obese, glucose intolerant, hyperinsulinemic and proteinuric. CONCLUSION: Considering the phenotype of the WOKW rat described until now and the fact that the metabolic syndrome in this rat is polygenetically determined, the WOKW rat is the most suitable animal model to study the pathophysiology of the facets of the syndrome.

Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: a population-based study.

Serum ceruloplasmin was reported to be an independent risk factor for cardiovascular disease. We investigated whether serum ceruloplasmin level is elevated in subjects with metabolic syndrome (MS, insulin resistance syndrome) in a community-based population. A total 883 subjects over 40 years of age were studied among a population of the Chongup district, a rural area of South Korea. Serum ceruloplasmin levels were measured, and oral glucose tolerance tests were performed. Known cardiovascular risk factors, such as serum lipids, fasting insulin level, and urinary albumin excretion rate (UAER), were also measured. Serum ceruloplasmin levels in the subjects with MS (n = 167, 325 +/- 141 mg/L) were significantly higher than in those without MS (278 +/- 93 mg/L, P <.001). The mean ceruloplasmin level also increased as the glucose tolerance worsened (278 +/- 95 mg/L in normal glucose tolerance [NGT], 303 +/- 108 mg/L in impaired glucose regulation, and 328 +/- 148 mg/L in diabetes; P <.001). Serum ceruloplasmin level was positively correlated with age, fasting glucose, postload 2-hour glucose, total cholesterol, triglyceride, systolic blood pressure, diastolic blood pressure, and UAER and negatively with high-density lipoprotein (HDL)-cholesterol. In multiple regression analysis, serum ceruloplasmin level was independently associated with age, fasting glucose, triglyceride, HDL-cholesterol, and UAER. In conclusion, serum ceruloplasmin level is elevated in the subjects with MS, as well as in subjects with impaired glucose regulation or diabetes mellitus. In addition, serum ceruloplasmin level is associated with various cardiovascular risk factors. These results suggest that elevated serum ceruloplasmin level can be a marker for metabolic stresses associated with MS.

Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X.

Aging is the progressive accumulation of changes with time that are responsible for the ever-increasing likelihood of disease and death. The precise cascade of pathological events mainly responsible for aging are still not clearly understood, but enhanced production of free radicals and its deleterious effects on proteins, nucleic acids, and fats, as well as enhanced glycosylation of proteins and DNA are prevalent during aging. Insulin resistance may be a common etiology, at least in part, behind the pathobiological alterations of advancing age. Prevalent age-related disorders such as cardiovascular diseases, obesity, and cancer have been associated with impaired glucose/insulin metabolism and its consequences. This leads to future strategies to combat the aging process and chronic disorders such as the components of syndrome X associated with aging. Increasing the intake of antioxidants and/or substances recognized to enhance insulin sensitivity is a natural means of combatting the glucose/insulin perturbations and free radical damage. Accordingly, ingestion of niacin-bound chromium and natural antioxidants such as grape seed proanthocyanidin extract has been demonstrated to improve insulin sensitivity and/or ameliorate free radical formation and reduce the signs/symptoms of chronic age-related disorders including syndrome X. These natural strategies possess a highly favorable risk/benefit ratio.

A path model of chronic stress, the metabolic syndrome, and coronary heart disease.

OBJECTIVE: We tested a theoretical stress model cross-sectionally and prospectively that examined whether relationships of chronic stress, psychophysiology, and coronary heart disease (CHD) varied in older adult men (N = 47), older adult women not using hormone replacement therapy (HRT) (N = 64), and older adult women using HRT (N = 41). METHOD: Structural equations examined relationships of CHD with 1) chronic stress (caring for a spouse with Alzheimer's disease and patient functioning), 2) vulnerability (anger and hostility), 3) social resources (supports), 4) psychological distress (burden, sleep problems, and low uplifts), 5) poor health habits (high-caloric, high-fat diet and limited exercise), and 6) the metabolic syndrome (MS) (blood pressure, obesity, insulin, glucose, and lipids). RESULTS: Caregiver men had a greater prevalence of CHD (13/24) than did noncaregiver men (6/23) (p <.05) 27 to 30 months after study entry. This was influenced by pathways from caregiving to distress, distress to the MS, and the MS to CHD. In men, poor health habits predicted the MS 15 to 18 months later, and the MS predicted new CHD cases over 27 to 30 months. In women, no "caregiving-CHD" relationship occurred; however, 15 to 18 months after study entry women not using HRT showed "distress-MS" and "MS-CHD" relationships. In women using HRT, associations did not occur among distress, the MS, and CHD, but poor health habits and the MS were related. CONCLUSIONS: In older men, pathways occurred from chronic stress to distress to the metabolic syndrome, which in turn predicted CHD. Older women not using HRT showed fewer pathways than men; however, over time, distress, the MS, and CHD were related. No psychophysiological pathways occurred in older women using HRT.

[The metabolic syndrome and its epidemiologic dimensions in historical perspective]. / Das Metabolische Syndrom im Wandel: Historische Perspektive und epidemiologische Dimension.

During the last five decades the metabolic syndrome has turned into an epidemic in countries with overnutrition and low levels of physical activity. About 15% of the population aged 40-75 in these countries exhibit exhibit the 'metabolic syndrome' cluster diseases. We define the metabolic syndrome as a cluster of diseases with at least three of the following components diagnosed in any one subject: ITG/type 2 diabetes, android obesity, dyslipidemia, hypertension, hyperuricemia, albuminuria and atherosclerosis. Insulin resistance was found in more than 80% of both the clinical type 2 diabetics and the subjects with IGT in the RIAD study. Intra-abdominal obesity and lipotoxicity are other important causes. Today the metabolic syndrome is--and for the near future will continue to be--the most important source of new diabetics, as well as a major cause of coronary heart disease.

Relative associations of fitness and fatness to fibrinogen, white blood cell count, uric acid and metabolic syndrome.

OBJECTIVE: To examine the relation between fitness and fibrinogen, white blood cell count, uric acid and metabolic syndrome across levels of adiposity in apparently healthy, nonsmoking men. DESIGN: Cross-sectional study of 4057 men from the Aerobics Center Longitudinal Study examining the age-adjusted resting levels and risk of having a clinically significant elevation of fibrinogen, white blood cell count, uric acid and metabolic syndrome score across nine fitness-body fatness combinations. Fitness categories (low fitness, moderately fit or high fitness) were based on a maximal treadmill test. Body mass index (BMI) <25.0 was classified as normal weight, BMI > or = 25.0 but <30.0 as overweight and BMI > or = 30.0 as obese. RESULTS: Fitness (inversely) and BMI (directly) were independently related to the age-adjusted values of all four variables (P for trend P<0.0001 for each). For all four variables, the greatest age-adjusted risk of having a clinically relevant value was found in the low fitness-obese category and the lowest age-adjusted risk was found in the high fitness-normal weight group. CONCLUSION: Fibrinogen, white blood cells, uric acid and metabolic syndrome score are independently related to both fitness (inversely) and fatness (directly). Within levels of fatness, risk for significant elevations in fibrinogen, white blood cells, uric acid and metabolic syndrome score is lower for the higher fitness groups.

Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes.

Subclinical inflammation was shown to be a strong predictor of cardiovascular events and was suggested to be a part of the metabolic syndrome (MS). The aim of the present study was to investigate the relationship of the inflammatory parameters-leukocyte count, C-reactive protein (CRP), and fibrinogen level-to insulin resistance and insulin secretion, as well as to other components of the MS in a population at risk for diabetes. A total of 396 subjects (142 men and 254 women) were analyzed from the follow-up of the Risk Factors in Impaired Glucose tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study, who were at risk for type 2 diabetes, such as family history of diabetes, obesity, and/or hyper/dyslipoproteinemia. Subjects under lipid-lowering treatment or with acute infections were not eligible. A variety of risk factors within the MS were examined: lipids, glycemic parameters, coagulation, insulin fractions. and microalbuminuria. CRP was determined by a highly sensitive method, using an immunological agglutination test, and fibrinogen was measured by the method of Clauss. Insulin resistance was evaluated by the homeostasis model assessment (HOMA) and insulin secretion by HOMA and by insulin areas under curve in an oral glucose tolerance test (OGTT), insulin increment at 30 mnutes of OGTT, and insulin increment/glucose increment at 30 minutes of OGTT. By univariate analysis, fibrinogen level (r = 0.180, P <.001), leukocyte count (r = 0.162, P =.001), and CRP (r = 0.251, P <.001) were all highly significantly correlated to insulin resistance, but not to insulin secretion. A significant rise was found for the majority of the components of the MS in quartiles of the examined inflammatory parameters. In multivariate analysis of all analyzed metabolic parameters, including age, sex, physical activity, and smoking, body mass index (BMI) was found a strong independent determinant of all inflammatory markers examined. Thus, in a population at risk for type 2 diabetes we demonstrate that subclinical inflammation underlies the metabolic syndrome, through association to one of its primary anomalies-insulin resistance, whereas no association was found to impaired insulin secretion.

[Insulin resistance: organ manifestations and cellular mechanisms]. / Insulinresistens: organmanifestationer og cellulaere mekanismer.

Insulin resistance is an important issue in the understanding of the metabolic syndrome. Clinical insulin resistance is usually defined by reduced insulin-mediated uptake of glucose in skeletal muscle. However, new studies have shown that liver and fat cells may also develop insulin resistance in subjects with the metabolic syndrome, specifically when these subjects are hyperglycaemic. New investigations also indicate that the endothelial cell itself can be insulin-resistant, reduced blood flow and increased peripheral resistance as the outcome. Insulin resistance may not only induce hyperglycaemia, but also dyslipidaemia (increased plasma levels of free fatty acids and triglyceride, and reduced plasma HDL levels) and arterial hypertension. All these variables may provoke arteriosclerosis and ischaemic heart disease. Specifically, abdominal adiposity seems to be responsible for insulin resistance in subjects with the metabolic syndrome. The mechanism could be intracellular accumulation of acyl CoA and triglyceride. However, an increased production of peptides from the adipose tissue, such as TNF alpha and reduced production of adiponectine may also play a role. The mechanism by which FFA and triglyceride, together with the peptides mentioned, may induce insulin resistance at a cellular level, resulting in reduced glucose transport and intracellular glucose processing, is still being discussed. A change in the insulin signalling cascade is one possibility, but the results so far have been contradictory. Another possibility is, of course, that the cellular accumulation of acyl CoA itself intervenes with gene expression and with phosphorylation of proteins.

[Predictors of abnormal glucose tolerance in persons at risk of type 2 diabetes: the RIAD study]. / Prädiktoren von Glukosetoleranzstörungen in einer Risikopopulation für Typ-2-Diabetes: die RIAD-Studie.

BACKGROUND AND OBJECTIVE: Early detection of glucose intolerance is an important issue in diabetes care. In the metabolic syndrome it is associated with an increased incidence of cardiovascular events. So far it is not clear which anthropometric and metabolic/hormonal parameters are of importance in the conversion of normal to impaired glucose tolerance. PATIENTS AND METHODS: The participants of the RIAD (Risk factors in IGT for Atherosclerosis and Diabetes) study had to meet the following criteria: related to type 2 diabetic patients, obesity and/or dyslipidaemia. A total of 358 subjects (age: 40-70 years) with normal glucose tolerance (NGT) in an oral glucose tolerance test (OGTT, 75 g glucose), were examined after a follow-up of 2.90 +/- 0.47 years. 284 of them remained with normal glucose tolerance, while 64 developed an impaired glucose tolerance (IGT) and ten type 2 diabetes (T2DM). The data of the initial screening examination were analysed in three groups (NGT-NGT; NGT-IGT; NGT-T2DM). Plasma glucose (PG), insulin, C-peptide and proinsulin were measured in the fasting state, as well as every 30 minutes during an OGTT, and also basal plasminogen activator inhibitor (PAI) and inflammatory parameters. RESULTS: Subjects who converted to IGT or diabetes show, already in the stage of normal glucose tolerance, clear tendency for the development of the metabolic syndrome. They were more obese and had higher fasting and 2 hPG values. The early phase insulin secretion, calculated as a ratio of DeltaInsulin 30'/DeltaPG 30', was lower in the IGT and the diabetes groups (n. s.). Both groups showed a significantly increased insulin resistance. Both converter groups revealed significantly higher PAI (Plasminogen-Activator-Inhibitor) levels and a striking but not significant increase in inflammatory parameters. CONCLUSIONS: Subjects who develop IGT and type 2 diabetes, will already in the stage of NGT show an impairment of insulin secretion and higher insulin resistance. Both processes seem to develop parallel to each other and determine the progress of the glucose intolerance. Fasting and 2h post-challenge glucose were the most important predictors of subsequent glucose intolerance.

Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance.

To characterize a new insulin resistance syndrome in euglycemic midlife women and the relationship of its features (including hypertension and dyslipidemia), with hyperinsulinemia (AUC insulin > or = 100 microU/mL), retrospective cohort analysis was conducted in 278 consecutive women who presented to a Menopausal Health Program. Of 67 women with midlife weight gain "greater than 20 pounds since their twenties" and body mass indices (BMIs) between 25 and 32 kg/m(2), none of the subjects met criteria for Type 2 diabetes, 5 women had impaired glucose tolerance, and 36 women were hyperinsulinemic. Hyperinsulinemia was a highly statistically significant determinant of hypertension, dyslipidemia, and truncal obesity (Odds Ratios 10.6, 4.0, and 13.7; P values < or = 0.0001, < or = 0.007, and < or = 0.0001) in cross-tabulations. AUC insulin was the best predictor variable of hypertension and dyslipidemia in univariate and multivariate logistic regression models (univariate P values 0.0004 and 0.0088). After adjustment for BMI, age, and estrogen use, the final models, correctly classified, respectively, 74% and 69% of all cases in the dataset (model P values: < or = 0.0001 and < or = 0.0067) and AUC insulin had a log-linear (i.e., dose-dependent) relationship with hypertension and dyslipidemia, which suggests causality. We propose that the constellation of symptoms that includes midlife weight gain, "waist-gain," hypertension, dyslipidemia, and appetite dysregulation in euglycemic women with hyperinsulinemia be titled Syndrome W and suggest that the highly statistically significant relationship of hyperinsulinemia with the characteristic features are evidence of a causal role for insulin in its etiology. The identification of Syndrome W before the onset of overt impaired glucose tolerance, diabetes, or manifestations of coronary artery disease could have important clinical and public health implications for midlife women.

Insulin resistance and the metabolic syndrome-a challenge of the new millennium.

The term metabolic syndrome is used for describing a cluster of cardiovascular risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes mellitus, dyslipidaemia and hypertension. A concomitant presentation of all components of the syndrome is rare, therefore, in the view of most experts three out of the four main components are sufficient for defining the syndrome. Another recently identified component of high clinical significance is the impairment of the fibrinolytic system which is now frequently mentioned in extended definitions. This clustering of metabolic risk factors has been described in various combinations and given different names including insulin resistance syndrome or syndrome X. Unfortunately, there is no generally accepted definition so far. The original mentioning of the syndrome goes back to the late sixties, when the metabolic syndrome was described as a 'disorder of genetic adaptation becoming manifest following unrestricted food intake and/or muscular inacitvity'. In its modern meaning this term was propagated by Hanefeld and Leonhardt and by Kaplan, who also called the syndrome the 'deadly quartet' to emphasize its high atherogenic potential.

Type 2 diabetes in children: clinical aspects and risk factors.

In the past, type 2 diabetes mellitus was considered a disease of adults and older individuals, not a paediatric condition. Over the last decade, however, in the USA and the rest of the world there has been a disturbing trend of increasing cases of type 2 diabetes in children, mirroring increasing rates of obesity. The risk factors for paediatric type 2 diabetes are: (1) obesity and increased body mass index; (2) family history of type 2 diabetes; (3) membership of ethnic minority; (4) puberty (mean age of diagnosis is approximately 13.5 years); (5) female gender; and (6) features of 'syndrome X'. The common link among these risk factors is insulin resistance, which plays a pivotal role in the pathophysiology of type 2 diabetes. Both insulin resistance and beta-cell failure are present in the fully established diabetes state. Data will be presented on how these risk factors impact on insulin sensitivity and insulin secretion in childhood, ultimately leading to type 2 diabetes. The clinical presentation of type 2 diabetes in children and its distinction from type 1 diabetes will be discussed.