[Breasts and congenital chest-wall deformities: Surgical strategy with 3D implants]. / Le sein et les malformations thoraciques : stratégie chirurgicale et implants.

Computer-aided design and manufacturing of custom-made elastomer implants leads from a CT scan to fill in with precision, a congenital chest wall congenital deformity, both bone (pectus excavatum) and muscle (Poland Syndrome), resulting in a natural repositioning of the breasts. We report our 25 years' experience in 301 women (234 Pectus+64 Poland). Parietal correction must always be done in first intention. It is common to have to carry out a second stage in women with an additional mammaplasty especially in the presence of insufficient glandular volume or a fairly frequently associated tuberous breast.

[Place of 3D custom-made implants after failure of modeling steno-chondro-plasties]. / Place des implants sur mesure 3D après échec des sterno-chondro-plasties modelantes.

Most common congenital malformation of the thorax, Pectus Excavatum affects about one in 500 people. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results even though their constant functional value is highly controversial. Secondary surgery with a deep customized 3D elastomer implant, may be an elegant effective and safe solution compared to others; it allows a good aesthetic result expected by patients in the absence of any respiratory or cardio-vascular functional context.

[Congenital thoracic deformities and 3D custom-made implants. New classification based on a series of 789 treated cases]. / Malformations thoraciques congénitales et implants sur mesure 3D. Nouvelle classification basée sur une série de 789 cas traités.

The authors present a new study on 789 cases of congenital thoracic malformations including 638 pectus excavatum and 151 Poland syndromes, according to a new classification which completes Chin's one. All these malformations were treated with silicone elastomer implants. The contribution of computer-aided design and manufacturing (CAD/CAM) since 2008 is essential. The one-stage surgical protocol is precisely described. The results are impressive, permanent, for life, and complications are rare. The authors evoke a common vascular etiopathogenesis theory at the embryonic stage and question the heavy techniques of invasive remodeling that are most often unjustified.

Male secretory breast cancer: case in a 6-year-old boy with a peculiar gene duplication and review of the literature.

PURPOSE: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms. METHODS: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity. RESULTS: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy's genomic profile revealed not only positivity for the typical SBC's translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity. CONCLUSIONS: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

Spinal infection multidisciplinary management project (SIMP): from diagnosis to treatment guideline.

Spine infections require a multidisciplinary approach to be treated and solved. A guide line to drive physicians in the deep complexity of such a disease is extremely helpful. SIMP suggests a flow-chart built up on clear concepts such as right and well managed antibiotic therapy, sound stability of the spine, correct and smart use of the standard and functional imaging techniques, such as f18 FDG PET/CT. In 16 months a total of 41 patients have been treated for spondylodiscitis, discitis and vertebral osteomyelitis by our team of physicians and 25 patients have been enrolled in a prospective study whose target is the assessment of the SIMP flow-chart and of every single aspect that characterize it.

Aspirin induced asthma (AIA) with nasal polyps has the highest basal LTE4 excretion: a study vs AIA without polyps, mild topic asthma, and normal controls.

UNLABELLED: Cysteinil Leukotrienes (LTs) are products of the arachidonic acid cascade which are synthetised by 5-lipoxigenase in inflammatory cells, particularly in eosinophils. Urinary leukotriene E4 concentration (LTE4), that reflects the whole body production of cysteinil-leukotrienes, is particularly increased in patients with aspirin-intolerant asthma (AIA). Aim of the present study was to assess basal urinary LTE4 levels from AIA patients with nasal polyps to those from AIA patients with only rhinitis (without polyps), and those from mild atopic asthmatics and normal controls. SUBJECTS & METHODS: 34 normal subjects (N; 19 - 57y, FEV1 = 102.1% pred. +/- 8.2 sd; negative MCh challenge; negative prick test); 39 mild-persistent atopic asthmatics (A; 18-66y, FEV1 = 92.1 %pred. +/- 14.6 sd; PD20 FEV1 = 380.7mcg +/- 481.2 sd); 24 subjects with AIA with rhinitis (AIA/R; 18 - 56y, FEV1 = 71.6%pred +/- 15.5 sd; reversibility = 15.1% bsln +/- 2.1 sd after salbutamol 200mg), and 10 subjects with AIA and nasal polyposis (AIA/NP; 22-49 y; FEV1 = 70.6%pred. +/- 7.1 sd; reversibility = 13.2% bsln +/- 1.6 sd after salbutamol 200 microg) were studied. After their informed consent, urine were collected in the morning for the LTE4 quantitative immunoenzimatic assay (pg/mg creatinine; Cayman Chemical, Ann Arbour, Mi, USA). STATISTICS: Wilcoxon signed rank test was used, and p<0.05 accepted as the lowest level of statistical significance. RESULTS: AIA/NP subjects had the highest levels of urinary LTE4 (432.3 pg/mg +/- 88.1 sd) compared to AIA/R (330.7 pg/mg +/- 72.3s, p < 0.01), to A (129.1 pg/mg +/- 74.8sd, p < 0.001), and to N controls (66.5 pg/mg +/- 20.6 sd, p < 0.001). Moreover, urinary LTE4 levels measured in AIA/R subjects proved significantly higher than those measured in A (p < 0.001) and in N controls (p<0.001), while LTE4 levels in A proved significantly higher than those in N controls (p<0.001). Furthermore, basal LTE4 levels seem inversely related to those of basal FEV1 (102.1 % pred. +/- 8.2sd in N, 92.1 % pred +/- 14.6 sd in A, 71.6 % pred. +/- 15.5 sd in AIA/R, 70.6 % pred +/- 7.1 sd in AIA/P, respectively). Respiratory function in the two sub-groups of AIA patients proved reduced than in atopic asthmatics (p<0.001) and in normal controls (p < 0.001), even though the difference between these two subgroups of subjects did not reach the statistical significance. CONCLUSIONS: Cys-LTs confirm their relevant pathogenetic role in AIA, but also in early stages of atopic asthma. Urinary LTE4 exexcretion proves directly proportional to the extent of nasal structural changes occurring in ASA-intolerant asthmatics, being subjects with nasal polyps those with the highest LTE4 values, immediately followed by those with hypertrophic rhinitis. Routinary measurements of urinary LTE4 should be regarded as a sensitive indicator in monitoring the clinical evolution of nasal involvement in AIA.

Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity.

OBJECTIVE: To test the hypothesis that insulin-mediated glucose uptake is enhanced in light-to-moderate alcohol consumption. RESEARCH DESIGN AND METHODS: This is a case-control study of healthy volunteers, divided into nondrinkers and light-to-moderate drinkers based on their history of alcohol consumption. The study was performed at the General Clinical Research Center at Stanford University Medical Center and involved 40 volunteers, 20 men and 20 women. Measurements were made of the plasma glucose and insulin responses to an oral glucose challenge, fasting plasma lipid and lipoprotein concentrations, and steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of somatostatin, insulin, and glucose. RESULTS: Light-to-moderate drinkers (10-30 g/day) had lower integrated plasma glucose (17.8 +/- 0.8 vs. 19.8 +/- 0.9 mM/h, P < 0.02) and insulin (600 +/- 65 vs. 1,075 +/- 160 pM/h, P < 0.01) responses to the glucose challenge and higher fasting plasma high-density lipoprotein (HDL) cholesterol concentrations (1.46 +/- 0.08 vs. 1.25 +/- 0.08, P < 0.02). Despite similar SSPI concentrations of approximately 300 pM, SSPG concentrations were lower (P < 0.01) in light-to-moderate drinkers (6.7 +/- 0.8 vs. 10.7 +/- 1.2 mM). Results were independent of age, body mass index, ratio of waist-to-hip girth, and estimates of level of habitual physical activity. CONCLUSIONS: Light-to-moderate alcohol consumption in healthy men and women is associated with enhanced insulin-mediated glucose uptake, lower plasma glucose and insulin concentrations in response to oral glucose, and a higher HDL-cholesterol concentration. The changes in glucose and insulin metabolism may contribute to the lower risk of coronary heart disease described in light-to-moderate drinkers.

Dabigatran etexilate and LMWH for the prevention of venous thromboembolism in 532 patients undergoing hip surgery.

OBJECTIVE: Patients undergoing total hip replacement (THR) are at high risk of venous thromboembolism (VTE) and according to guidelines they should receive pharmacological prophylaxis. We would like to compare the efficacy, adherence and safety of dabigatran and low molecular weight heparins (LMWH) for the prevention of VTE in patients who underwent THR. PATIENTS AND METHODS: This study enrolled patients undergoing THR treated with dabigatran (110 mg loading dose then 220 mg/day for 34 days) or the LMWH dalteparin (2500 IU, 6-8 hours before surgery then 5000 IU/day for 35 days). The primary endpoint was adherence to treatment. RESULTS: Of the 532 patients screened and enrolled in the study, 407 (mean age 57.7 ± 12.3 years) completed the study (211 dabigatran, 196 LMWH). Over the 35 days of treatment, adherence was comparable between dabigatran and LMWH: 10.9% and 14.3% of patients receiving dabigatran and LMWH treatment missed > 1 dose of the drug, respectively. There was a lower need for external support in patients who received dabigatran (8.5% vs 58.2%; p < 0.0001) and a lower number of patients receiving dabigatran required support by a professional nurse (1.4% vs 17.3% of patients with LMWH; p < 0.0001). Dabigatran and LMWH were similarly well tolerated; however, fewer patients receiving dabigatran reported bleeding events. CONCLUSIONS: This study demonstrates that dabigatran is associated with high adherence. A lower need for external support in patients who received dabigatran may provide an added benefit compared with other oral treatments for VTE prophylaxis.

Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease.

Resistance to insulin-mediated glucose disposal has been postulated to predispose individuals to a cluster of associated abnormalities (Syndrome X) known to increase risk of cardiovascular disease (CVD). Although several abnormalities subsumed under the rubric of Syndrome X have been shown to predict CVD, there has been no prospective study evaluating the power of insulin resistance, the putative fundamental defect in the syndrome, in this context. Therefore, this study was initiated to evaluate the hypothesis that resistance to insulin-mediated glucose disposal would predict the development of CVD in healthy volunteers. To accomplish this goal, 147 normal, healthy, nonobese, volunteers were evaluated [4.7 +/- 0.1 yr (mean +/- SEM)] after baseline measurements of steady state plasma glucose concentration (an estimate of insulin-mediated glucose disposal), as well as other CVD risk factors. Clinical end points developed in 13 subjects during the follow-up period; hypertension in 5, coronary artery disease in 4, cerebrovascular accident in 3, and peripheral vascular disease in 1. There was a significant univariate relationship between SSPG and CVD (P < 0.002), with the majority of the events taking place in the tertile of subjects with the highest SSPG concentration, i.e. the greatest degree of insulin resistance. In contrast, no CVD events were observed in the tertile with the lowest SSPG concentrations; the most insulin sensitive. SSPG was also related significantly to diastolic blood pressure, triglyceride, and low-density lipoprotein and high-density lipoprotein cholesterol concentrations, and the glucose and insulin responses to oral glucose. All of these relationships were independent of age, gender, body mass index, estimates of physical activity, and smoking history. When SSPG was paired with each of the other variables in a series of multiple regression models, only SSPG, or insulin response, were independent predictors of CVD events. In conclusion, approximately one of every five healthy, nonobese subjects in the most insulin-resistant tertile, followed for approximately 5 yr, had a serious clinical event. These data highlight the importance of insulin resistance as a predictor of CVD.

Insulin resistance as a predictor of age-related diseases.

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.

Measurements of insulin-mediated glucose disposal are stable over time.

To evaluate the stability of insulin-mediated glucose disposal, over time, we measured the steady-state plasma insulin (SSPI) and steady-state plasma glucose (SSPG) concentrations in response to a continuous infusion of SRIF (5 microg/min), insulin (25 microU/m2 x min), and dextrose (240 microg/m2 x min). These measurements were made in 15 healthy volunteers, studied before and after a mean (+/-SEM) interval of 48 +/- 2 months. The mean (+/-SEM) weight of the volunteers did not increase with time (75.4 +/- 3.1 vs. 76.6 +/- 3.2 kg), and there was no significant variation between the 2 mean (+/-SEM) values of either SSPI (324 +/- 18 vs. 372 +/- 24 pmol/L) or SSPG (8.4 +/- 1.0 vs. 8.2 +/- 1.0 mmol/L). Given the similarity of both SSPI and SSPG concentrations at baseline and follow-up, it can be concluded that insulin-mediated glucose disposal was stable in these 15 individuals over an interval of approximately 4 yr.

Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake.

Hyperinsulinemia: the missing link among oxidative stress and age-related diseases?

Mounting evidence supports Harman's hypothesis that aging is caused by free radicals and oxidative stress. Although it is known that oxidant species are produced during metabolic reactions, it is largely unknown which factor(s), of physiological or pathophysiological significance, modulate their production in vivo. In this hypothesis paper, it is postulated that hyperinsulinemia may have such function and therefore promote aging, independently of elevations of glycemia. Hyperinsulinemia is secondary to impaired insulin stimulated glucose metabolism at the level of skeletal muscle (insulin resistance) and is seen in about one third of glucose tolerant humans following dietary carbohydrate intake. If other insulin-stimulated (or inhibited) pathways retain normal sensitivity to the hormone, hyperinsulinemia could, by its effects on antioxidative enzymes and on free radical generators, enhance oxidative stress. Other proaging effects of insulin involve the inhibition of proteasome and the stimulation of polyunsaturated fatty acid (PUFA) synthesis and of nitric oxide (NO). The hypothesis that hyperinsulinemia accelerates aging also offers a metabolic explanation for the life-prolonging effect of calorie restriction and of mutations decreasing the overall activity of insulin-like receptors in the nematode Caenorhabditis elegans.

Relation between dietary vitamin intake and resistance to insulin-mediated glucose disposal in healthy volunteers.

The relation between the self-reported intake of various dietary constituents and insulin-mediated glucose disposal was evaluated in 52 healthy volunteers. Insulin-mediated glucose uptake was independently associated with degree of obesity (inversely) and estimates of level of physical activity (directly). An independent relation between increased intake of vitamin A and insulin action was shown, ie, the greater the intake of vitamin A, the more effective was insulin in stimulating glucose disposal. However, there was no independent relation noted between insulin-mediated glucose disposal and estimates of the intake of carbohydrate, protein, amount or kind of fat, fiber, or vitamins C and E. Furthermore, the 20 individuals with estimates of vitamin A consumption > 10 000 IU/d had significantly lower plasma glucose (P < 0.01) and insulin (P < 0.05) responses to oral glucose, and insulin-mediated glucose disposal values that were higher (P < 0.005) than those of the 20 individuals whose estimated vitamin A intake was < 8000 IU/d. These results suggest that vitamin A intake, but not intakes of vitamin C and E, fiber, fat, or carbohydrate is associated with enhanced insulin-mediated glucose disposal.

Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols.

BACKGROUND: It is not known whether total circulating lipid hydroperoxides are increased in insulin-resistant individuals and whether this correlates with depletion of liposoluble antioxidant vitamins that are consumed during lipid peroxidation. OBJECTIVE: The goal of this study was to define the relation between resistance to insulin-mediated glucose disposal and plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy volunteers. DESIGN: Insulin-mediated glucose disposal was determined in 36 healthy, nondiabetic volunteers by measuring their steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant infusion of octreotide, insulin, and glucose. In addition, fasting plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were determined by using the FOX 2 assay and liquid chromatography. RESULTS: Statistically significant direct relations were observed between SSPG and mean arterial blood pressure (r = 0.44, P: = 0.008) and plasma lipid hydroperoxide concentrations (r = 0.42, P: = 0.01), whereas significant inverse correlations were found between SSPG and alpha-carotene (r = -0.58, P: = 0.0002), beta-carotene (r = -0.49, P: = 0.004), lutein (r = -0.35, P: = 0.04), alpha-tocopherol (r = -0. 36, P: = 0.04), and delta-tocopherol (r = -0.45, P: = 0.007). CONCLUSIONS: Variations in insulin-mediated glucose disposal in healthy individuals are significantly related to plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.

Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal.

This study was initiated to test the hypothesis that plasma homocysteine concentrations are increased in insulin resistant individuals. For this purpose, the relationship between insulin resistance, as assessed by the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, and fasting plasma homocysteine concentration was defined in 55 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of SSPG concentrations (r = 0.02, P = 0.88). Furthermore, mean (+/- S.E.M.) plasma homocysteine concentrations were similar (8.2+/-0.4 vs. 8.7+/-0.7 micromol/l) in individuals classified as being either insulin sensitive (SSPG <100 mg/dl) or insulin resistant (SSPG >180 mg/dl). On the other hand, SSPG concentration was significantly correlated with fasting plasma insulin (r = 0.58, P<0.001), triglycerides (r = 0.34, P<0.05), and HDL-cholesterol (r = -0.36, P = 0.04) concentrations. These data strongly suggest that the increased risk of atherosclerosis associated with increased plasma homocysteine concentrations is unrelated to insulin resistance and/or the metabolic abnormalities associated with it.

Unravelling migrations in the steppe: mitochondrial DNA sequences from ancient central Asians.

This study helps to clarify the debate on the Western and Eastern genetic influences in Central Asia. Thirty-six skeletal remains from Kazakhstan (Central Asia), excavated from different sites dating between the fifteenth century BC to the fifth century AD, have been analysed for the hypervariable control region (HVR-I) and haplogroup diagnostic single nucleotide polymorphisms (SNPs) of the mitochondrial DNA genome. Standard authentication criteria for ancient DNA studies, including multiple extractions, cloning of PCR products and independent replication, have been followed. The distribution of east and west Eurasian lineages through time in the region is concordant with the available archaeological information: prior to the thirteenth-seventh century BC, all Kazakh samples belong to European lineages; while later an arrival of east Eurasian sequences that coexisted with the previous west Eurasian genetic substratum can be detected. The presence of an ancient genetic substratum of European origin in West Asia may be related to the discovery of ancient mummies with European features in Xinjiang and to the existence of an extinct Indo-European language, Tocharian. This study demonstrates the usefulness of the ancient DNA in unravelling complex patterns of past human migrations so as to help decipher the origin of present-day admixed populations.

Enhanced sympathetic nervous system activity. The linchpin between insulin resistance, hyperinsulinemia, and heart rate.

This study was undertaken to see whether insulin resistant individuals, who are chronically hyperinsulinemic, have a higher heart rate (HR) than insulin sensitive, normoinsulinemic subjects. A total of 45 normotensive, nondiabetic individuals had insulin-mediated glucose disposal quantified by the insulin suppression test. In an effort to minimize variables known to modify heart rate, such as diet, exercise, and emotional distress, heart rate was continuously monitored during sleep by an electronic device measuring RR intervals. The average heart rate (as calculated by a mean of 30,720 +/- 208 beats per subject over a monitoring time of 6.9 +/- 0.6 h) was significantly related (r = 0.61; P < .001) to insulin resistance as expressed by the steady-state plasma glucose (SSPG) response to a continuous infusion of glucose, insulin and somatostatin and to the plasma insulin response to a 75 g of oral glucose challenge (r = 0.51; P < .001). These significant relationships between HR and both SSPG and plasma insulin response persisted after adjustment by stepwise regression analysis for age, gender distribution, body mass index, physical activity, and family history of either diabetes or hypertension. These results show that insulin resistant individuals, with compensatory hyperinsulinemia, have a higher nocturnal heart rate: a finding consistent with the possibility that the increased nocturnal heart rates are secondary to insulin-induced sympathetic activity.

Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension.

Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension.

Insulin resistance in patients with essential hypertension can occur in the absence of microalbuminuria.

This study was initiated to see if the presence of resistance to insulin-mediated glucose disposal, glucose intolerance, and hyperinsulinemia in healthy patients with hypertension was dependent upon the coexistence of microalbuminuria. For this purpose we compared these variables in 68 individuals: 34 patients with hypertension and 34 normal volunteers. The two groups were similar in terms of age, gender distribution, body mass index, and ratio of waist to hip girth. Furthermore, although four patients with hypertension satisfied the criteria for microalbuminuria, as compared to one normal volunteer, the urinary albumin excretion (UAE) rates were similar in the two groups (8.07 +/- 1.08 v 7.67 +/- 1.12 micrograms/min). Despite the similarities, both the plasma glucose and insulin responses to a 75 g oral glucose challenge were significantly higher (P < .01) in those with high blood pressure. In addition, the steady-state plasma glucose (SSPG) concentrations at the end of a 180 min continuous infusion of somatostatin, insulin, and glucose was significantly higher in those with hypertension (156 +/- 13 v 107 +/- 10 mg/dL, P < .01). Since the steady-state plasma insulin levels were also somewhat higher in those with hypertension, the higher SSPG values indicate that these individuals were relatively insulin resistant as compared to the control population. Finally, UAE rates were not correlated with either the plasma glucose or insulin responses to oral glucose or to the SSPG concentrations--either in the entire group of 68, or when the 34 patients in each group were considered separately. These results demonstrate that insulin resistance, glucose intolerance, and hyperinsulinemia can occur independently of microalbuminuria in patients with hypertension.