Activated eosinophils in esophagitis in children: a transmission electron microscopic study

OBJECTIVE: To describe the interval between first appearance of mild nonproliferative diabetic retinopathy (NPDR) and first appearance of neovascularization (NV) in type I diabetes. SETTING: A longitudinal study of 269 patients followed up annually. PARTICIPANTS: Participants had insulin-dependent diabetes and were free of proliferative diabetic retinopathy in both eyes at the baseline visit. MAIN OUTCOME MEASURE: Stereoscopic color fundus photographs of each eye at each study visit, graded for features of retinopathy. RESULTS: Among the 305 eyes for which the duration of diabetes at the first appearance of mild NPDR could be determined, NV developed in 28 by the end of the study. Survival analysis showed that the later the onset of mild NPDR was, the shorter the time from onset of mild NPDR to onset of NV (relative hazard for each additional year to onset of mild NPDR, 1.22; 95% confidence interval, 1.10-1.35). Adjustment for systolic and diastolic blood pressure, proteinuria, and glycosylated hemoglobin (Hgb A10) levels did not change the relative hazard estimate for onset of mild NPDR. Higher levels of Hgb A10 were associated with a shorter time from onset of mild NPDR to onset of NV (relative hazard, 1.26; 95% confidence interval, 1.05-1.51 [after adjusting for time at onset of mild NPDR]), as were higher levels of diastolic blood pressure, although not significantly (relative hazard for 10-mm Hg increase in diastolic blood pressure, 1.52; 95% confidence interval, 0.82-2.83 [adjusting for onset of mild NPDR, Hgb A10 level, systolic blood pressure, and proteinuria]). Neither proteinuria nor systolic blood pressure had an effect on time from onset of mild NPDR to onset of NV, after adjustment for time at onset of mild NPDR, Hgb A10 level, and diastolic blood pressure. CONCLUSION: Later onset of mild NPDR is not necessarily associated with delayed development of NV in patients with type I diabetes. Caution must therefore be used in assessing the value of interventions that delay the onset of mild NPDR without evidence of delayed onset of NV.     

Abnormal characteristics in young offspring of parents with non-insulin-dependent diabetes mellitus. The Bogalusa Heart Study

Non-insulin-dependent (type II) diabetes has a strong familial component. In 1989-1991, a community-based study of young Caucasian offspring (mean age, 15.3 years) of non-insulin-dependent (type II) diabetics (n = 25) and nondiabetics (n = 27) representing 13 and 12 families, respectively, was conducted in Bogalusa, Louisiana, to determine whether metabolic abnormalities could be detected in early life. All offspring were given a 1-hour oral glucose tolerance test. The offspring of diabetics (versus nondiabetics) had significantly increased measures of body fatness; blood pressure; and fasting levels of glucose, insulin, glucagon, insulin-to C-peptide ratio, and triglycerides. The increases of systolic blood pressure, glucose, and glucagon remained significant after adjustment for differences in body mass index (BM). After glucose challenge, only plasma glucose response was significantly higher in the offspring of diabetics, even after controlling for differences in BMI. None of the offspring of nondiabetics had 30-minute (peak) glucose levels above 161 mg/dl (8.9 mmol/liter), compared with 41% of the offspring from diabetics. High glucose response and BMI were independently associated with parental diabetes. These results indicate that it is possible to identify multiple abnormalities in some offspring of type II diabetics at an early age that may presage the onset of overt adult diabetes.     

Nocturnal blood pressure elevation in patients with type 1 diabetes receiving intensive insulin therapy compared with that in patients receiving conventional insulin therapy

Studies have shown that type 1 diabetic patients may suffer from nocturnal elevation in blood pressure and that this elevation may be related to hyperinsulinemia. In this study we tested the hypothesis that tight type 1 diabetes control, which is usually accompanied by hyperinsulinemia and subclinical nocturnal hypoglycemia, may result in a higher rise in nocturnal blood pressure compared with conventional type 1 diabetes control. Eighteen patients treated with intensive insulin therapy (multiple daily injections; IIT) were compared with 18 patients treated with conventional insulin regimens (twice daily injections of regular and intermediate acting insulin; CIT). Both groups were matched for age, sex, duration of diabetes, body weight, body mass index, baseline daytime blood pressure, and microalbuminuria levels. Hemoglobin A1c was lower in the IIT group compared with that in the CIT group (8.1 +/- 1.2% vs. 11.0 +/- 3.2%; P < 0.01). The amount of insulin/body weight (units per kg) was higher in the IIT group than that in the CIT group (1.0 +/- 0.2 vs. 0.7 +/- 0.2 U/kg; P < 0.05). In all patients, a 24-h ambulatory blood pressure was recorded. The nocturnal diastolic blood pressure was higher in the IIT group (66 +/- 9 mm Hg) than in the CIT group (55 +/- 4 mm Hg; P < 0.01). The nocturnal decline in both systolic and diastolic blood pressure was lower in the IIT group (7 +/- 5 and 6 +/- 4 mm Hg, respectively) compared with that in the CIT group (13 +/- 6 and 16 +/- 6 mm Hg, respectively; P < 0.01). The nocturnal heart rate was higher in IIT group than in the CIT group (81 +/- 12 vs. 67 +/- 9/min; P < 0.05). These findings show that the intensive insulin therapy regimen may have a more deleterious effect than the conventional insulin therapy regimen on the nocturnal blood pressure of patients with type 1 diabetes.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Dangerousness: a mutating concept passes through the literature

OBJECTIVE: To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35-64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS: Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 +/- 1.9 vs. 300.2 +/- 3.0 mg/dl, mean +/- SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as > or = 350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS: The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.     

The insulin resistance syndrome in native Hawaiians. Native Hawaiian Health Research (NHHR) Project

OBJECTIVE: To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians. RESEARCH DESIGN AND METHODS: A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity. RESULTS: Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation. CONCLUSIONS: This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.     

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents

Insulin is one of the hormonal regulators of leptin synthesis and participates in adipose tissue maintenance. The present study was undertaken to clarify the association of endogenous insulin secretion and mode of therapy with body fat and serum leptin levels in diabetic subjects. We measured the fasting serum C-peptide level, as an estimate of endogenous insulin secretion, and the serum leptin level in 176 Japanese diabetic subjects (79 men and 97 women; age, 55.9+/-14.3 years; body mass index [BMI], 23.8+/-4.1 kg/m2 [mean+/-SD]). Thirty-one subjects were treated with diet therapy alone, 66 with sulfonylurea (SU), and 79 with insulin (including 29 with type I diabetes mellitus). Body fat was analyzed by the impedance method. Serum leptin levels significantly correlated with the BMI and body fat and were higher in women, mainly because of their greater body fat. Serum C-peptide concentrations positively correlated with body fat and serum leptin in subjects treated with diet and SU. In insulin-treated type II diabetic subjects, both serum C-peptide and the daily insulin dose were weakly associated with body fat and serum leptin. In those subjects, despite a lower percent body fat and body fat mass, serum leptin concentrations (10.3+/-8.4 ng/mL) were comparable to the levels in subjects treated with diet (8.8+/-8.5 ng/mL). When compared within the same BMI and body fat groups (BMI 20 to 25 and > 25 kg/m2) including the control subjects matched for age and sex, serum leptin levels were higher in insulin-treated type II diabetic subjects versus the control subjects and diabetic patients treated with diet or SU. Stepwise regression analysis for all of the diabetic subjects showed that both the serum C-peptide level and exogenous insulin administration, as well as the BMI, gender, and age, were determinants of the serum leptin level. In conclusion, endogenous insulin secretion is closely associated with body fat and serum leptin in diabetic subjects treated with diet therapy and SU. In Japanese insulin-treated type II diabetic subjects, both endogenous and exogenous insulin are associated with body fat and serum leptin, which is maintained at levels comparable to or somewhat higher than the levels in control subjects and diabetic patients treated without insulin.     

Systematic analytic procedure for identification of unknown medicaments in biological material

Increase in blood pressure and its circadian alterations in Type 1 diabetes are usually associated with diabetic nephropathy. To evaluate if diabetes itself could be responsible for the observed increase in blood pressure levels, we studied a group of 17 normotensive, normoalbuminuric Type 1 diabetic patients with a disease duration more than 15 years, with no clinical evidence of autonomic neuropathy or ischaemic heart disease, and without any known determinant of hypertension, and a control group of 17 normal subjects, normotensive, each matched for sex, age, BMI, albumin excretion rate, and clinical blood pressure to a diabetic subject. In both groups an ambulatory blood pressure monitoring was performed through an oscillometric recorder. The mean systolic and diastolic ambulatory blood pressure values were significantly higher in diabetic patients (p < 0.001) in the 24-h analysis and during waking and sleeping periods. The night/day ratio of systolic and diastolic blood pressure were not significantly different in patients and controls, as well as heart rate values and heart rate variability. We conclude that mechanism(s) inherent to the diabetic condition other than diabetic nephropathy or autonomic neuropathy could be responsible for blood pressure evaluation in normotensive Type 1 diabetes with normoalbuminuria.     

Inadequate management of blood pressure in a hypertensive population

BACKGROUND: Many patients with hypertension have inadequate control of their blood pressure. Improving the treatment of hypertension requires an understanding of the ways in which physicians manage this condition and a means of assessing the efficacy of this care. METHODS: We examined the care of 800 hypertensive men at five Department of Veterans Affairs sites in New England over a two-year period. Their mean (+/-SD) age was 65.5+/-9.1 years, and the average duration of hypertension was 12.6+/-5.3 years. We used recursive partitioning to assess the probability that antihypertensive therapy would be increased at a given clinic visit using several variables. We then used these predictions to define the intensity of treatment for each patient during the study period, and we examined the associations between the intensity of treatment and the degree of control of blood pressure. RESULTS: Approximately 40 percent of the patients had a blood pressure of > or =160/90 mm Hg despite an average of more than six hypertension-related visits per year. Increases in therapy occurred during 6.7 percent of visits. Characteristics associated with an increase in antihypertensive therapy included increased levels of both systolic and diastolic blood pressure at that visit (but not previous visits), a previous change in therapy, the presence of coronary artery disease, and a scheduled visit. Patients who had more intensive therapy had significantly (P<0.01) better control of blood pressure. During the two-year period, systolic blood pressure declined by 6.3 mm Hg among patients with the most intensive treatment, but increased by 4.8 mm Hg among the patients with the least intensive treatment. CONCLUSIONS: In a selected population of older men, blood pressure was poorly controlled in many. Those who received more intensive medical therapy had better control. Many physicians are not aggressive enough in their approach to hypertension.     

Assessment of ventricular diastolic function in AIDS patients from Congo: a Doppler echocardiographic study

The aim of this study was to evaluate the effect of transdermal clonidine on hemodynamic and metabolic parameters in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in placebo period, 20 NIDDM patients who had diastolic blood pressure in the range of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled, cross-over study of 4 week treatment with clonidine (transdermal patch 2.5 mg/week) or placebo (inactive patch). Compared with placebo, clonidine significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v 98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99 +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P < .01). Oxidative glucose disposal (indirect calorimetry) was also greater after clonidine. Plasma glucose, insulin, and C-peptide responses following oral glucose (75 g) were significantly lower after clonidine, as well as urinary albumin excretion. Transdermal clonidine is effective in reducing blood pressure in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce the cardiovascular impact of hypertension in diabetes mellitus.     

Insulin sensitivity and blood pressure in a biethnic sample: the Miami Community Health Study

An association between blood pressure and insulin sensitivity among normotensive African-Americans has not been demonstrated consistently in epidemiologic studies. Part of the discrepancy may be due to studying persons with profound obesity-an insulin-resistant state itself. The association between insulin-mediated glucose uptake (i.e., insulin sensitivity) and blood pressure was examined among 25 nondiabetic African-American and 28 white non-Hispanic persons aged 25-44 years who ranged from normal weight to obese, using the hyperinsulinemic euglycemic clamp technique. In bivariate analyses, insulin sensitivity was inversely related to systolic (p < 0.01) and diastolic blood pressure (p = 0.08) among African-American persons and to diastolic blood pressure among white non-Hispanic subjects (p < 0.05). Covariate adjustment for age and sex had only a marginal effect on these results. When the data were pooled and further adjusted for ethnicity, insulin sensitivity remained significantly associated with both systolic and diastolic blood pressure (p < 0.01 for each). To consider the effect of obesity, body mass index (BMI) was divided at the sample median (26.5 kg/m2) and the analyses were repeated within each stratum. Among those whose BMI was below the median value, each increment in insulin sensitivity was associated with a 2-mmHg decrease in systolic blood pressure (p = 0.02). These results suggest that ethnicity was not a strong effect modifier in this sample and indicated that insulin sensitivity was inversely related to blood pressure level in these normotensive African-American and white, non-Hispanic participants.     

The human FE65 gene: genomic structure and an intronic biallelic polymorphism associated with sporadic dementia of the Alzheimer type

This study aimed to investigate the relationship of systolic and diastolic blood pressure (BP) with a series of metabolic and nonmetabolic cardiovascular risk variables in a random sample of Turkish general adult population. Values of systolic and diastolic BP on the one hand and of six variables including body mass index (BMI), waist/hip ratio (W/H), grade of physical activity (PhA), plasma lipids and cigarette smoking from 1046 men and 1095 women aged 225 years were included in the analysis. Participants were classified into tertiles according to systolic and diastolic BP measurements, and were stratified in two age categories: 25-44 years (young) and 45-74 years (elderly). Plasma total cholesterol and triglyceride (Trg) concentrations were measured by the enzymatic method with the Reflotron apparatus. In multiple regression analysis, age proved the strongest independent determinant of BP. BMI was a strong independent marker of systolic and diastolic pressures in women, while in men the determinant value of the W/H was equivalent to BMI. For each increment of 1 kg/m2 of BMI was associated in men an increase of over 8 and 16 mmHg in diastolic and systolic pressure, respectively, regardless of age group. Corresponding figures in women were roughly 6 and 10 mmHg. Though plasma Trg were not independently associated with BP in either gender, the independent contribution of plasma cholesterol level in women to systolic and diastolic pressures was small but significant. BP was related to mean concentrations of plasma Trg in young adults only, total cholesterol levels were associated with diastolic pressure in young men only, whereas PhA grade was not associated with BP. These findings are consistent with the theory that, in the normal state, functions such as regulation of BP, body weight and lipid metabolism are closely linked to each other.     

Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed neuronal death induced by ischemia in gerbils

BACKGROUND: The difference between clinic and ambulatory average daytime blood pressures is frequently taken as a surrogate measure of the 'white-coat effect' (i.e. the pressor reaction triggered in the patient by the physician's visit). OBJECTIVE: To assess the reproducibility of this difference and its relationship with clinic and average ambulatory daytime blood pressure levels. DESIGN AND METHODS: These issues were addressed with two large groups of subjects in whom both clinic and ambulatory blood pressures were measured, namely 783 outpatients with systolic and diastolic essential hypertension [Group 1, aged 50.8+/-9.4 years (mean +/- SD)], participating in standardized Italian trials of antihypertensive drugs, and 506 elderly patients (group 2, age 71+/-7 years) with isolated systolic hypertension, participating in the European Syst-Eur trial. RESULTS: The clinic-daytime blood pressure difference for the essential systolic and diastolic hypertensive patients (group 1) was 13.6+/-14.3 mmHg for systolic and 9.1+/-8.6 mmHg for diastolic blood pressure (P always < 0.01). This difference for the elderly patients with isolated systolic hypertension (group 2) was 21.2+/-16.0 mmHg for systolic and only 1.3+/-10.2 mmHg for diastolic blood pressure (P < 0.01 and P < 0.05, respectively). In both studies little or no systematic clinic-daytime difference could be observed for heart rate. The reproducibility of the clinic-daytime blood pressure difference, tested for 108 essential systolic and diastolic hypertensive patients from group 1 and 128 isolated systolic hypertensives from group 2, was invariably lower than that both of daytime and of clinic blood pressure values. Finally, the clinic-daytime blood pressure difference was progressively higher for increasing levels of clinic blood pressure and progressively lower for higher levels of ambulatory daytime blood pressure. CONCLUSIONS: Thus, the clinic-daytime blood pressure difference has a limited reproducibility; depends not only on clinic but also on daytime average blood pressure, which means that its size is a function of the blood pressure criteria employed for selection of the patients in a trial; and is never associated with a systematic clinic-daytime difference in heart rate, which further questions its use as a reliable surrogate measure of the true pressor response induced in the patient by the doctor's visit.     

Blood pressure levels in diabetes mellitus

Levels of fasting plasma glucose, body mass index, serum total lipids, serum total cholesterol, serum triglycerides and blood pressure of 177 Libyan diabetic patients were determined. The respective mean values were 212.4 +/- 5.6 mg/dl, 26.6 +/- 0.45 kg/m2, 825.7 +/- 20.5 mg/dl, 176.4 mg/dl, 144 +/- 5.8 mg/dl and 135.3 +/- 1.7/83 +/- 0.89 mm Hg. The mean levels of all variables except plasma glucose are significantly higher in the female patients than their male counterparts. Correlations were present between blood pressure levels and age/body mass index/serum total lipids. There was a significant correlation between systolic pressure levels and the duration of diabetes. Serum cholesterol and serum triglyceride levels correlated with diastolic blood pressure levels only.     

Comparative effects of atenolol versus celiprolol on serum lipids and blood pressure in hyperlipidemic and hypertensive subjects

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus celiprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-blind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and diet constancy monitoring. Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than celiprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with celiprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.     

Effect of bacille Calmette-Guérin vaccination on C-peptide secretion in children newly diagnosed with IDDM

OBJECTIVE: To determine whether administration of bacille Calmette-Guérin (BCG) vaccination to newly diagnosed IDDM patients can help preserve C-peptide secretion over the subsequent 18 months. RESEARCH DESIGN AND METHODS: Twenty-six IDDM patients, all of whom had been diagnosed within the previous year, had basal C-peptide levels >0.06 nmol/l, and had negative reactions to Mantoux's test, were randomized pairwise as they presented and were given either 0.1 ml (100 microg) BCG vaccine or 0.1 ml saline intradermally Both the patients and the investigators were blinded to the treatment. Fasting and glucagon-induced C-peptide levels and HbA1c were measured in all patients at enrollment and at 1, 3, 6, 9, 12, and 18 months after vaccination, and insulin dose was recorded at each visit. RESULTS: At enrollment, there was no significant difference in age, duration of diabetes, insulin dose, HbA1c, or fasting C-peptide levels between the BCG-vaccinated and control groups. The mean basal and stimulated C-peptide levels in the BCG-treated group did not differ significantly from those in the control group at any time during the 18 months of follow-up, and there was no difference in insulin dose or HbA1c at any time between the groups. CONCLUSIONS: BCG vaccination in children who have been recently diagnosed with IDDM does not affect the progressive decline in C-peptide levels or alter the clinical course of the disease.     

Lack of association between both insulin resistance and plasma insulin levels with blood pressure values in essential hypertension

AIM: To evaluate the role of insulin resistance and hyperinsulinaemia in the genesis of essential arterial hypertension (EAHT). SUBJECTS AND METHODS: We studied 49 patients (age 44 +/- 8 y., body mass index (BMI: 29.5 +/- 3.2 kg.m-2) with mild or moderate EAHT (systolic blood pressure: 156 +/- 13 mmHg, diastolic blood pressure: 100 +/- 6 mmHg). Patients with BMI > 27 kg.m-2 were classed as obese. Arterial pressure was measured with a mercury sphygmomanometer after the patient had been lying down for 15 min. For each patient, the results of a frequently sampled intravenous glucose tolerance test (FSIGT) were used to estimate insulin sensitivity (using the minimal model of glucose metabolism) and to characterize insulin secretion in response to intravenous glucose (area of the insulin curve above basal during the 180 min of the FSIGT test). Correlations were evaluated by means of Spearman's correlation coefficient. RESULTS: Neither fasting insulinaemia, glucose-induced insulin secretion nor insulin sensitivity correlated significantly with arterial pressure, either in the whole sample or in the obese and non-obese subsamples. CONCLUSIONS: These results suggest that neither insulin nor insulin sensitivity are important physiological regulators of arterial pressure, and lend no support to the hypothesis that insulin is related to essential arterial hypertension.     

Summary measures of the insulin resistance syndrome are adverse among Mexican-American versus non-Hispanic white children: the Corpus Christi Child Heart Study

BACKGROUND: Mexican-American (MA) adults are known to have a greater burden of diabetes and insulin resistance than non-Hispanic white (NHW) people. In this report, we examined data obtained from MA and NHW third-grade children for evidence of a pattern consistent with the insulin resistance syndrome. In addition, we developed two summary measures characterizing insulin resistance syndrome to compare measures of this syndrome among our population. METHODS AND RESULTS: Data regarding fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and body mass index (BMI) were available for 403 third-grade children. Median levels of insulin and glucose were significantly higher in MA boys and girls than in NHW boys and girls. Risk factors characterizing insulin resistance, including levels of insulin, triglycerides, systolic blood pressure, HDL cholesterol, and BMI were categorized as above or below the total population median. MA children were more likely than NHW children to have three or more adverse risk factors (55% versus 37%). When risk factors were converted to Z scores, and the five Z scores were summed for each individual, MA boys and girls had higher mean scores than NHW boys and girls (means for boys, 0.65 versus -0.97, P<.0001; girls, 0.52 versus -0.30, P<.04). Principal components analysis was used to create a summary score or index representing the insulin resistance syndrome. This summary score was significantly higher among MA boys and girls than NHW boys and girls (means for boys, 0.34 versus -0.72, P<.0001; girls, 0.35 versus -0.04, P=.056). CONCLUSIONS: Our results support the hypothesis that MA children exhibit a greater degree of the insulin resistance syndrome than NHW children, especially among boys. We conclude that some of the factors responsible for the increased risk of NIDDM seen among MA adults are demonstrable in childhood.     

A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors

OBJECTIVE: To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy. DESIGN: Cross-sectional study. SETTING: Outpatient clinic of a university teaching hospital. PATIENTS: HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47). INTERVENTIONS AND MAIN OUTCOME MEASURES: Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed. RESULTS: HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus. CONCLUSION: A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.