Features Of Insulin Resistance Syndrome Research Articles

A high-fat diet catalyzes progression to hyperglycemia in mice with selective impairment of insulin action in Glut4-expressing tissues

Insulin resistance impairs postprandial glucose uptake through glucose transporter type 4 (GLUT4) and is the primary defect preceding type 2 diabetes. We previously generated an insulin-resistant mouse model with human GLUT4 promoter-driven insulin receptor knockout (GIRKO) in the muscle, adipose, and neuronal subpopulations. However, the rate of diabetes in GIRKO mice remained low prior to 6 months of age on normal chow diet (NCD), suggesting that additional factors/mechanisms are responsible for adverse metabolic effects driving the ultimate progression of overt diabetes. In this study, we characterized the metabolic phenotypes of the adult GIRKO mice acutely switched to high-fat diet (HFD) feeding in order to identify additional metabolic challenges required for disease progression. Distinct from other diet-induced obesity (DIO) and genetic models (e.g., db/db mice), GIRKO mice remained leaner on HFD feeding, but developed other cardinal features of insulin resistance syndrome. GIRKO mice rapidly developed hyperglycemia despite compensatory increases in β-cell mass and hyperinsulinemia. Furthermore, GIRKO mice also had impaired oral glucose tolerance and a limited glucose-lowering benefit from exendin-4, suggesting that the blunted incretin effect contributed to hyperglycemia. Secondly, GIRKO mice manifested severe dyslipidemia while on HFD due to elevated hepatic lipid secretion, serum triglyceride concentration, and lipid droplet accumulation in hepatocytes. Thirdly, GIRKO mice on HFD had increased inflammatory cues in the gut, which were associated with the HFD-induced microbiome alterations and increased serum lipopolysaccharide (LPS). In conclusion, our studies identified important gene/diet interactions contributing to diabetes progression, which might be leveraged to develop more efficacious therapies.

Type 2 Diabetes Mellitus in Children and Adolescents: An update

Childhood type 2 Diabetes Mellitus (DM) has increasingly been reported worldwide. It is commonly associated with childhood obesity.It may be presented with classical manifestation of DM such as polyuria, polydipsia, weight lossor acute complications like Diabetic ketoacidosis (DKA), Hyperglycemic Hyperosmolar State (HHS) or features of insulin resistance syndrome. Many a cases it may remain asymptomatic and hence undiagnosed.So,overweight children and adolescents who met screening criteria such as family history of type 2 DM, signs of insulin resistance, and high risk ethnics should undergo screening. Emphasis should be given on early diagnosis and optimum management plan to avoid grave consequences of it in early part of life. Diagnosis of type 2 Diabetes Mellitus in children should be done on the basis of standard diagnostic criteria such as American Diabetic Association (ADA) criteria. Both non-pharmacological and drug management are important equally. Multidisciplinary team approach including self-management plan is mandatory for obtaining optimal therapeutic goals of type 2 DM in children and adolescents. Lifestyle modification, dietary intervention, weight reduction, patient education, psychological support, and oral anti diabetic drugs and insulin therapy should be included in comprehensive diabetic management plan. Complications of type 2 DM should be minimized by all means with strict glycemic control and management of co-morbidity if any. Emphasis should also be given on prevention of type 2 DM by adopting a healthy lifestyle characterized by healthy eating behavior, regular physical activity and subsequent modest weight loss that can prevent the progression of impaired glucose tolerance to clinical diabetes mellitus.J Bangladesh Coll Phys Surg 2017; 35(1): 24-30

In Vivo Interrelationship between Insulin Resistance and Interferon Gamma Production: Protective and Therapeutic Effect of Berberine.

This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ.

Effects of early reperfusion on creatine kinase release in patients with acute myocardial infarction: Implications for reperfusion injury

[1] Dekker JM, Schouten EG, Klootwijk P, Pool J, Swenne CA, Kromhout D. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study. Am J Epidemiol 1997;145:899–908. [2] Pikkujamsa SM, Huikuri HV, Airaksinen KE, Rantala AO, Kauma H, Lilja M, et al. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens 1998;11:523–31. [3] Beske SD, Alvarez GE, Ballard TP, Davy KP. Reduced cardiovagal baroreflex gain in visceral obesity: implications for the metabolic syndrome. Am J Physiol Heart Circ Physiol 2002;282:H630–5. [4] LindgrenK, Hagelin E, HansenN, Lind L. Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance. J Hypertens 2006;24: 143–50. [5] Lucini D, Cusumano G, Bellia A, Kozakova M, Difede G, Lauro R, et al. Is reduced baroreflex gain a component of the metabolic syndrome? Insights from the LINOSA study. J Hypertens 2006;24:361–70. [6] Barthelemy JC, Pichot V, Dauphinot V, Celle S, Laurent B, Garcin A, et al. Autonomic nervous system activity and decline as prognostic indicators of cardiovascular and cerebrovascular events: the ‘PROOF’ Study. Study design and population sample. Associations with sleep-related breathing disorders: the ‘SYNAPSE’ Study. Neuroepidemiology 2007;29:18–28. [7] Parlow J, Viale JP, Annat G, Hughson R, Quintin L. Spontaneous cardiac baroreflex in humans. Comparison with drug-induced responses. Hypertension 1995;25: 1058–68. [8] Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment Panel III). JAMA 2001;285:2486–97. [9] Erdogan D, Gonul E, Icli A, Yucel H, Arslan A, Akcay S, et al. Effects of normal blood pressure, prehypertension, and hypertension on autonomic nervous system function. Int J Cardiol 2011;151:50–3. [10] Arrone LJ, Mackintosh R, Rosenbaum M, Leibel RL, Hirsch J. Cardiac autonomic nervous system activity in obese and never-obese young men. Obes Res 1997;5: 354–9.

Insulin sensitivity in chronic pancreatitis and features of insulin resistance syndrome

Chronic pancreatitis predisposes to diabetes. Loss of endocrine function by beta-cells in the Langerhans islets is considered to be the main causative factor, although several studies have also suggested insulin resistance as a possible additional mechanism. The aim of the study was to estimate insulin sensitivity in chronic pancreatitis in view of the coexisting meta bolic syndrome components. The study involved 30 patients (mean age 50.83 +/-6.61 years; 23.33% women, 76.66% men) diagnosed with chronic pancreatitis (using imaging tests). Insulin sensitivity with regard to the coexistent obesity, dyslipidemia, and arterial hypertension was measured using the euglycemic clamp method. Diabetes was present in 22 patients, impaired glucose tolerance in 4, and no carbohydrate metabolism disturbances in 4. Insulin resistance was present in 22 patients (73.33%), in whom a higher prevalence of diabetes (77.27% vs. 62.5%) and prediabetes (13.63% vs. 12.5%) was observed. The analysis of anthropometric para meters revealed that individuals with a high index of central obesity had a statistically significantly lower tissue glucose utilization (TGU) (3.23 vs. 4.89 mg/kg/min; P = 0.02), although there were no obese patients in the study group according to the body mass index. No statistically significant differences in TGU were observed in relation to lipid disorders (total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides) and arterial hypertension. In patients with chronic pancreatitis, lack of correlation between insulin sensitivity and meta bolic syndrome components may indicate that insulin resistance is related to primary disease or that an additional mechanism underlying pancreatic diabetes operates.

Uric acid is associated with features of insulin resistance syndrome in obese children at prepubertal stage

1. Sin dudas un trabajo interesante considerando que la hiperuricemia es un potencial factor de riesgo para la mortalidad y morbilidad por enfermedad cardiovascular 2 . No obstante proponer un mecanismo fisiopatogenico que relacione a la obesidad con la hiperuricemia, si bien es necesario, no es nada sencillo. La hiperuricemia predice de modo independiente el surgimiento de diabetes mellitus tipo 2, la hipertension arterial y el actualmente discutido sindrome metabolico (condiciones relacionadas con altos indices de resistencia a la insulina y obesidad) 2

The importance of endothelin-1 for microvascular dysfunction in diabetes

Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ET(A) receptor antagonists are discussed.

Cardiovascular Autonomic Dysfunction as a Link Between Insulin Resistance and Nocturnal Blood Pressure Elevation

HomeHypertensionVol. 51, No. 4Cardiovascular Autonomic Dysfunction as a Link Between Insulin Resistance and Nocturnal Blood Pressure Elevation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBCardiovascular Autonomic Dysfunction as a Link Between Insulin Resistance and Nocturnal Blood Pressure Elevation Antonio Perciaccante Antonio PerciaccanteAntonio Perciaccante Internal Medicine, “San Giovanni Decollato-Andosilla” Hospital, Civita Castellana, Italy Search for more papers by this author Originally published3 Mar 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.110361Hypertension. 2008;51:e30Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 3, 2008: Previous Version 1 To the Editor:I read with interest the article by Lurbe et al1 on the relationship between insulin resistance and the ambulatory blood pressure components in obese children and adolescents. The authors have observed that nocturnal systolic blood pressure and heart rate were significantly higher in subjects in the highest homeostasis model assessment index tertile. They conclude that the increased nocturnal blood pressure and heart rate associated with hyperinsulinemia may contribute to heightened cardiovascular risk associated with this condition. I agree with the authors, and I want suggest cardiovascular autonomic function as a possible link between insulin resistance and increased nocturnal blood pressure.This hypothesis is supported by several pieces of evidence. Scherrer and Sartori2 have observed that hyperinsulinemia activates the central sympathetic drive. Several studies performed by spectral analysis of heart rate variability have shown sympathetic hyperactivity in insulin-resistant subjects with normoglycemia.3,4 In a previous study performed in adult subjects, Perciaccante et al5 have reported a relationship between insulin resistance and cardiovascular autonomic dysfunction, characterized by an impaired circadian rhythm of heart rate variability with a sympathetic hyperactivity at nighttime. Moreover, the authors have reported that this hyperactivity of sympathetic component at nighttime (evaluated by heart rate variability analysis in the frequency domain as low frequency expressed in normalized units and the low frequency:high frequency ratio) is correlated with the highest homeostasis model assessment index.I conclude that insulin resistance has an impact on nocturnal blood pressure and heart rate, and this may be because of the effect of the insulin resistance on the cardiovascular autonomic activity.DisclosuresNone.1 Lurbe E, Torro I, Aguilar F, Alvarez J, Alcon J, Pascual MJ, Redon J. Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescent. Hypertension. 2008; 51: 635–641.LinkGoogle Scholar2 Scherrer U, Sartori C. Insulin as a vascular and sympathoexcitatory hormone. Implications for blood pressure regulation, insulin sensitivity and cardiovascular morbidity. Circulation. 1997; 96: 4104–4114.CrossrefMedlineGoogle Scholar3 Laitinen T, Vauhkonen IK, Niskanen LK, Hartikainen JE, Lansimies EA, Uusitupa MI, Laakso M. Power spectral analysis of heart rate variability during hyperinsulinemia in nondiabetic offspring of type 2 diabetic patients: evidence for possible early autonomic dysfunction in insulin-resistant subjects. Diabetes. 1999; 48: 1295–1299.CrossrefMedlineGoogle Scholar4 Pikkujamsa SM, Huikuri HV, Airaksinen KE, Rantala AO, Kauma H, Lilja M, Savolainen MJ, Kesaniemi YA. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens. 1998; 11: 523–531.CrossrefMedlineGoogle Scholar5 Perciaccante A, Fiorentini A, Paris A, Serra P, Tubani L. Circadian rhythm of the autonomic nervous system in insulin resistant subjects with normoglycemia, impaired fasting glycemia, impaired glucose tolerance, type 2 diabetes mellitus. BMC Cardiovasc Disord. 2006; 2: 6: 19–28.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByLurbe E (2008) Response to Cardiovascular Autonomic Dysfunction as a Link Between Insulin Resistance and Nocturnal Blood Pressure Elevation, Hypertension, 51:4, (e31-e31), Online publication date: 1-Apr-2008. April 2008Vol 51, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.108.110361PMID: 18316649 Originally publishedMarch 3, 2008 PDF download Advertisement SubjectsObesity

Effect of tempol on altered angiotensin II and acetylcholine-mediated vascular responses in thoracic aorta isolated from rats with insulin resistance

The altered vascular responses to various vasopressors and relaxants have been well reported in various animal models of hypertension, insulin resistance and diabetes. Though the role of oxidative stress (increased superoxide levels) associated with these altered vascular responses in hyperglycemic/diabetic state is well documented, the role of the same remains to be largely unknown in vascular dysfunction coupled with prediabetic insulin resistant state. The objective of the present study was therefore to elucidate the role of free radicals particularly superoxides if any associated with vascular dysfunction in diet-induced insulin resistance of rats. In this regard, the effect of tempol (a membrane permeable superoxide dismutase mimetic/free radical scavenger) on the enhanced Ang II-induced contraction and impaired-ACh mediated relaxation in thoracic aorta of rats with insulin resistance was studied. Ang II-induced contraction and ACh-mediated relaxation responses were recorded isometrically in endothelium intact and denuded thoracic aortic ring preparations isolated from male Sprague–Dawley rats which were fed with either normal pellet diet (NPD) (control group) or high fat diet (HFD) (insulin resistant group) for 4 weeks. The HFD-fed rats exhibited characteristic features of insulin resistance syndrome viz., obesity, hyperinsulinaemia, mild hyperglycemia, hypertriglyceridemia, hypercholesterolemia, glucose intolerance and hypertension. Maximal contractile response ( E max) to Ang II was increased in endothelium intact aortic ring preparations obtained from HFD-fed rats as compared to NPD-fed control rats. Denudation of endothelium significantly increased Ang II-mediated E max responses in thoracic aortic rings of NPD-fed rats, whereas it produced only minimal alteration to the E max in the HFD-fed rats. In addition, ACh-mediated relaxation response was impaired in endothelium intact aortic rings isolated from HFD-fed rats. Tempol (30–300 μM) significantly and dose dependently inhibited enhanced vascular responses ( E max) of Ang II in endothelium intact, but not in endothelium denuded aortic ring preparations. Tempol (30 μM) reversed the impaired acetylcholine (ACh)-mediated relaxations in endothelium intact aortic ring preparations of HFD-fed rats. Endothelium independent vasorelaxations (EIV) to sodium nitroprusside (SNP) were similar for both NPD and HFD. In conclusion, our results indicate that superoxide radicals play crucial role in enhanced contractile and impaired vasodilatory responses to Ang II and ACh, respectively, in thoracic aortic rings isolated from diet-induced insulin resistant rats.

Relationship among urinary albumin excretion rate, lipoprotein lipase PvuII polymorphism and plasma fibrinogen in type 2 diabetic patients

Plasma fibrinogen level represents a strong cardiovascular risk factor and is regulated by an interplay of genetic and environmental factors. Hyperfibrinogenemia frequently occurs in cluster with dyslipidemia within the frame of insulin resistance syndrome (IRS) and type 2 diabetes mellitus. Genetic variants with a pleiotropic effect have been proposed to cause IRS features including hyperfibrinogenemia. We studied the influence of polymorphisms in lipoprotein lipase (LPL) gene, beta-fibrinogen gene (FIBB) and environmental factors on plasma fibrinogen levels in type 2 diabetes patients. 131 type 2 diabetes patients (mean age 62+/-10 years, 33% male) were genotyped for polymorphisms in LPL gene (intron 6 PvuII, intron 8 HindIII) and FIBB gene (-148C/T, -455G/A) by PCR-RFLP method. Fibrinogen was measured by thrombin coagulation method, albuminuria by immunoturbidimetric assay. Polymorphism LPL PvuII showed a gene-dose effect on fibrinogen levels, with the highest fibrinogen in P-P- homozygotes (p = 0.05, analysis of variance). P-carriers (P-P- and P+P- combined) had significantly higher fibrinogen levels compared with P+P+ homozygotes (3.74+/-1.40 g/l vs 3.06+/-1.20 g/l, p=0.03). Other studied polymorphisms were not significantly related to fibrinogen levels. Age- and sex-adjusted fibrinogenemia correlated significantly with albuminuria (r = 0.48, p=0.001), serum uric acid (r = 0.42, p=0.006) and serum creatinine (r = 0.32, p=0.04). Multiple stepwise linear regression identified interaction term of LPL PvuII and albuminuria as an independent predictor of fibrinogen level, explaining 18% of fibrinogen variance. Albuminuria thus appears to be the best predictor of fibrinogen plasma levels in type 2 diabetic patients. Relationship between albuminuria and fibrinogenemia may be modified by the genotype LPL PvuII, which also shows a weak association with plasma fibrinogen level in type 2 diabetes patients.

Insulin Resistance in Cognitive Impairment

To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population. Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI). A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score < 25), 21 of whom had both cognitive impairment and subcortical features (CI/SF+ group). Control groups contained 23 individuals with a history of stroke and 381 individuals with no cognitive impairment (no CI group, MMSE score > or = 25). Indicators of insulin resistance were the fasting plasma insulin level, insulin resistance index (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and insulin sensitivity index (Quantitative Insulin Sensitivity Check Index [QUICKI]). The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF- group) was similar to that of individuals in the no CI group. Patients in the CI/SF- group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively). Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.

Insulin resistance syndrome, body mass index and the risk of ischemic heart disease.

Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Quebec Cardiovascular Study. A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression. Although obese men (BMI > or = 30 kg/m2) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m2) (RH 1.26, 95% confidence interval [CI] 0.88-1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02-3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70-5.32). Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.

Lack of Arg972 polymorphism in the IRS1 gene in Parakanã Brazilian Indians.

Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 polymorphism in Parakanã Indians and found a lack of this polymorphism in the Parakanã population.

Association of heart rate with coronary risk factors and increased white blood cell counts in healthy Japanese people.

Elevated resting heart rate (HR) is associated with hypertension in addition to or similar to increased incidence of cardiovascular morbidity and mortality. Subjects with high HR exhibit the characteristic features of insulin resistance syndrome. Sympathetic overactivity underlies this clinical condition. However, the true mechanism of high HR is unclear. We examined the relation between resting HR and age, gender, traditional coronary risk factors, and white blood cell (WBC) count in urban Japanese. The study population comprised 2,736 people aged 40, 50, and 60 years old. Multiple regression analysis of the total population showed that gender (p < 0.001), systolic and diastolic blood pressure (SBP, DBP; p < 0.001), serum triglycerides (TG; p < 0.001), fasting plasma glucose (FPG; p < 0.001) and WBC count (p < 0.001) had significant correlations with HR in the total population. Exercise was negatively correlated with HR (p < 0.001). In the age-adjusted profiles, gender (p < 0.001), SBP (p < 0.001), FPG (p < 0.001, p < 0.01 at age 40 years) and WBC count (p < 0.001) showed a significant correlation with HR among all three age groups. A negative association between HDL cholesterol (HDLc) and HR was seen at age 60 years (p < 0.01). A negative correlation between exercise and HR was seen at age 40 years (p < 0.001) and age 50 years (p < 0.01). It is suggested that the WBC count is one of the important determinants of resting HR regardless of age. Further studies are necessary to clarify the link between HR, coronary risk factors, and chronic infections.

Increased fibrinogen, von Willebrand factor and tissue plasminogen activator levels in insulin resistant South Asian patients with ischaemic stroke

The aim of this study was to determine differences in atherothrombotic risk factors in South Asian subjects with a history of ischaemic stroke and South Asian subjects free from personal and family history of clinically detectable stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial computerised scan) and 80 South Asian controls with similar age and gender distributions were recruited at random. The frequency of hypertension ( P=<0.0001), myocardial infarction ( P=0.003) and diabetes mellitus (<0.0001) were significantly higher in stroke patients. Stroke patients had lower high-density lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA 1C (6.4 vs. 6.0%, P=0.09). There was no difference in insulin levels but insulin resistance was significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients disappeared after adjustment for features of insulin resistance syndrome but persisted after adjustment for presence of diabetes, confirming that these changes are essentially dependant on features of insulin resistance syndrome. A prospective study would be required to elucidate the role of thrombotic risk factors in South Asians with ischaemic stroke.

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study.

Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity.

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m(2)). Plasma CRP levels showed positive and significant correlations with body fat mass (r=0.41, P<0.0001), waist girth (r=0.37, P<0.0001), and visceral AT accumulation measured by computed tomography at L4 to L5 (r=0.28, P<0.0003). Although CRP levels were associated with plasma insulin levels measured in the fasting state and after a 75-g oral glucose load, no significant correlations were found with plasma lipoprotein levels. Finally, comparison of body fatness, of abdominal fat accumulation, and of the features of the insulin resistance syndrome across quintiles of CRP revealed major differences in body fatness and in indices of abdominal AT accumulation between the lowest and the highest CRP quintiles, whereas no significant differences were found for variables of the plasma lipoprotein-lipid profile. These results suggest that obesity and abdominal AT accumulation are the critical correlates of elevated plasma CRP levels found in men with atherogenic dyslipidemia of the insulin resistance syndrome.

Microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes in the Korean population

To investigate whether microalbuminuria is associated with the insulin resistance syndrome independent of hypertension and type 2 diabetes, we studied the association between microalbuminuria and features of insulin resistance syndrome in Korean general population. We selected 1006 subjects by a random cluster sampling among residents aged >40 years living in the Chung-Up district, a rural area of South Korea. Subjects were stratified by oral glucose tolerance status [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus], and by the presence or absence of hypertension. Urinary albumin excretion rate (UAER) was determined using timed overnight urine collection. Various cardiovascular risk factors including anthropometric indices, serum lipid, true insulin and proinsulin concentrations were also measured. The prevalence of microalbuminuria (UAER between 20 and 200 μg/min) increased as the glucose tolerance worsened (6.0% in NGT, 11.8% in IGT, and 21.8% in diabetes; χ 2 trend=25.9, P<0.001). Subjects with microalbuminuria had a higher body mass index (BMI), waist-to-hip circumference ratio (WHR), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose, fasting plasma insulin and proinsulin levels, and lower HDL-cholesterol level than subjects without microalbuminuria. In multiple regression analysis, BMI, diastolic BP, 2 h plasma glucose, and fasting plasma insulin levels were found to be independent factors associated with UAER. Multiple logistic regression analysis showed that not only diabetes mellitus and hypertension, but also fasting hyperinsulinemia and waist-to-hip ratio were independent factors associated with the presence of microalbuminuria. When the normotensive, non-diabetic subjects were analyzed separately, fasting hyperinsulinemia and impaired glucose tolerance remained independent variables associated with the presence of microalbuminuria. These results show that microalbuminuria in the Korean general population is associated with hyperinsulinemia and central obesity, and suggest that microalbuminuria is a feature of the insulin resistance syndrome independent of hypertension or type 2 diabetes.

Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).

Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), S(I), and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and S(I) were related to CRP levels in a multivariate linear regression model. We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to S(I). These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.

Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean ± SEM, 8.1 ± 0.6 v 6.8 ± 0.2 μmol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index ( P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 ± 0.5 v 7.2 ± 0.5 v 8.4 ± 0.6 μmol/L; P = .148) or normotensive subjects (6.3 ± 0.4 v 8.0 ± 0.8 v 7.0 ± 0.8 μmol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.