Comparison among different insulin sensitivity indices in obese patients.

AIMS: Recently, several indices have been proposed for the measurement of insulin sensitivity (IS). We set out to make a comparison between fasting insulin, and different IS indices in obese subjects. PATIENTS AND METHODS: Fasting and post load (75 g) glucose and insulin were measured in a consecutive series of 767 (626 F, 141 M) obese (body mass index > 30 kg/m(2)) out-patients, with no known history of diabetes (DM). Mean (+/- sd) age was 46.7 +/- 13.8 years in females and 45.6 +/- 14.3 years in males. Indices of IS based on fasting homeostasis assessment model (HOMA) and post-load (ISI) glucose and insulin and either parameter (1A, and 1B scores) were determined. RESULTS: DM was diagnosed in 21.4% of females, and 20.6% of males, and impaired glucose tolerance in 24% females and 21.3% males. Fasting and post-load glucose, triglyceride and HDL-cholesterol were correlated with all indices in both sexes (P < 0.05). The relative risk of different conditions in the upper quartile of ISI was similar to that observed in the upper quartile of HOMA. The HOMA index was similarly associated with low HDL-cholesterol and hypertriglyceridaemia as fasting insulin, while it showed a greater association with diabetes; ISI was similarly associated with all three conditions as the HOMA index. CONCLUSIONS: Indices of IS based on fasting glucose and insulin show a greater association with diabetes, but not with other abnormalities related to insulin resistance, when compared with fasting insulin levels. Indices based on post-load glucose and insulin do not offer any advantage over those based on fasting values.     

Increased insulin resistance in salt sensitive essential hypertension

OBJECTIVE: To determine the possible relationship between insulin resistance and salt sensitivity in essential hypertension. DESIGN AND METHODS: We studied 17 non-obese, essential hypertensive patients (24-h blood pressure: 149 +/- 15/94 +/- 5 mm Hg) with normal glucose tolerance. Salt sensitivity was diagnosed in the presence of a significant increase (P < 0.05, more than 4 mm Hg) in 24-h mean blood pressure (MBP) when patients switched from a low-salt intake (50 mmol/day of Na(+)) to a high-salt intake (240 mmol/day of Na(+)), each period lasting 7 days. The insulin sensitivity index was determined by the euglycaemic hyperinsulinaemic clamp. RESULTS: Six patients were classified as salt sensitive (24-h MBP increase: 6.2 +/- 1.1 mm Hg), and 11 as salt resistant (24-h MBP increase: -1.2 +/- 3.8 mm Hg). No significant differences were observed between salt sensitive and salt resistant patients regarding baseline characteristics, fasting serum insulin, fasting serum glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, uric acid and microalbuminuria. Salt sensitive patients exhibited a reduced insulin sensitivity index compared with salt resistant patients (1.7 +/- 1.1 vs 3.5 +/- 1.2 mg/kg/min; P = 0.009). An inverse relationship (r -0.57; P = 0.016) between the insulin sensitivity index and 24-h MBP increase with high salt intake was found. CONCLUSION: Salt sensitive essential hypertensive patients are more insulin resistant than salt resistant patients when both salt sensitivity and insulin resistance are accurately measured. Indirect measures of both insulin and salt sensitivity and/or the presence of modifying factors, such as obesity or glucose intolerance, may account for differences in previous studies.     

Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention.

The aim of the present study was to evaluate the recently defined simple insulin sensitivity check index QUICKI (Katz et al. 2000) for insulin resistance diagnostics in common clinical and epidemiological practice. Both the QUICKI (1/log insulin + log glycemia in mg/dL) and HOMA (insulin * glycemia in micromol/L/22.5) indexes were calculated from fasting values in 259 adult healthy volunteers and patients, and in 47 healthy and obese children of prepubertal age of both sexes. In adults, a fall in the QUICKI index (mean +/- SEM in healthy subjects = 0.366 +/- 0.029) as well as an increase in the HOMA index (in healthy subjects 1.57 +/- 0.87) corresponded to metabolic and clinical manifestations of insulin resistance in various groups of outpatients. The QUICKI index had lower dispersion variances and the 95% confidence limits displayed a higher discrimination capacity. Patients with glucose intolerance or diabetes, hyperlipidemia typical for insulin resistance, or with combination of these metabolic disorders were characterized by QUICKI index values that were significantly lower than those of healthy volunteers. The QUICKI index in healthy prepubertal children indicated a higher insulin resistance compared to adults (mean 0.339 +/- 0.020); an increase in the QUICKI index in obese children with BMI over 25 was not significant, although obese children showed a significant increase of serum leptin and triglycerides and a decrease of HDL-cholesterol. Adult patients with QUICKI index below 0.357 (which is at the lower limit of 95% confidence limits in healthy persons) represented a group with typical manifestations of metabolic syndrome, differing in these parameters significantly from the group of patients of comparable age with a QUICKI index greater than 0.357. The present study suggests suitability of the QUICKI index for diagnosis of insulin resistance in clinical and epidemiological practice. However, a normal QUICKI index range needs to be established for each laboratory with an appropriate control group because of significant interlaboratory variations in insulin determinations and/or possible differences in various populations.     

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

OBJECTIVE: To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes.CONCLUSIONS:Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.     

Surrogate estimates of insulin sensitivity in Chinese diabetic patients and their offspring.

AIMS: To evaluate the relationship between surrogate measures of insulin sensitivity and results from euglycaemic insulin clamp in Chinese diabetic patients and their offspring. METHODS: The study included 59 volunteers from 20 diabetic families. Each participant completed a 75-g oral glucose tolerance test (OGTT) and a euglycaemic insulin clamp. We tested the correlation of surrogate measures of insulin sensitivity with M-values and M/I ratios (the amount of glucose infused during 90-120 min of the clamp was defined as M, and the mean values of plasma insulin during 90-120 min as I) from the euglycaemic insulin clamp. These measures included fasting insulin (FPI), insulin at 120 min of OGTT, insulin area under the curve of OGTT, fasting glucose-to-insulin ratio, homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and the Matsuda-DeFronzo index from OGTT. RESULTS: The Matsuda-DeFronzo index closely correlated to M-value and M/I in 21 diabetic, 38 non-diabetic individuals and the 59 participants overall (with M-value, r = 0.68, 0.84 and 0.84; with M/I, r = 0.71, 0.72 and 0.75, respectively, all P < 0.001). Without OGTT, HOMA %S was a good surrogate index for diabetic (correlated to M-value and M/I, r = 0.71 and 0.68, P = 0.001) and for non-diabetic subjects (to M-value, r = 0.73; to M/I, r = 0.55, both P < 0.001). FPI was as good as HOMA %S and Matsuda-DeFronzo index. CONCLUSIONS: The Matsuda-DeFronzo index, HOMA %S and FPI are good surrogate estimates of insulin sensitivity in Chinese diabetic subjects and their offspring.     

Effect of atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome

Large interventional studies have shown that statins may reduce the incidence of type 2 diabetes mellitus. However, it is uncertain whether short-term statin therapy can affect insulin sensitivity in patients with the metabolic syndrome. We evaluated the effect of atorvastatin (10 mg/day) in 10 insulin-resistant subjects (age 40 +/- 12 years, body mass index 33.6 +/- 5.2 kg/m(2), triglycerides 2.84 +/- 1.99 mmol/L [249 +/- 175 mg/dl], glucose 6.06 +/- 0.67 mmol/L [109 +/- 12 mg/dl)] using the homeostasis model assessment (HOMA) index (parameter of insulin resistance derived from fasting glucose and fasting insulin concentrations; 5.7 +/- 2.6) in a randomized placebo-controlled, double-blind, crossover study. Subjects were randomized to receive placebo or atorvastatin, each given for 6 weeks separated by a 6-week wash-out period. At the beginning and end of each treatment phase, the patients underwent an oral glucose tolerance test, a 72-hour continuous glucose measurement, and a detailed lipid determination, including a standardized fat tolerance test. Compared with placebo, atorvastatin resulted in a significant (p = 0.05) reduction in the HOMA index (-21%), fasting C-peptides (-18%), glucose (area under the curve during the oral glucose tolerance test, -7%), and a borderline (p = 0.08) reduction of insulin (-18%). The parameters derived from the continuous 72-hour glucose monitoring did not change. A significant reduction also occurred in the total and low-density lipoprotein cholesterol concentrations, although the fasting and postprandial triglyceride concentrations did not change significantly. However, we found a significant correlation between atorvastatin-induced changes in the HOMA and baseline HOMA and between the atorvastatin-induced changes in triglycerides and insulin concentrations. The free-fatty acid, interleukin-6, and high sensitivity C-reactive protein concentrations did not change. Our data indicated that in insulin-resistant, nondiabetic subjects, 6 weeks of atorvastatin (10 mg/day) resulted in significant improvement in insulin sensitivity.     

Leptin is associated with insulin resistance in Japanese migrants

Background: Leptin and insulin are both influenced by body adiposity. Insulin plays an important role in the context of the metabolic syndrome (MS). We evaluated whether leptin was associated with insulin resistance and MS after adjusting for confounders in Japanese-Brazilian women. Methods: A total of 717 Japanese-Brazilian women aged >/=30 years were investigated for the presence of MS. They were submitted to clinical examination and laboratory measurements, including oral GTT, lipid profile, uric acid, C-reactive protein (CRP), insulin, and leptin levels. Insulin sensitivity was assessed by HOMA. Diagnosis of MS was based on the National Cholesterol Education Program criteria modified for Asians. Pearson correlation coefficient and logistic regression analysis were used. Results: MS was diagnosed in 56% (95% CI 52-59); these subjects were older and had higher body mass index (BMI) and fat mass, and worse metabolic profile. Leptin and CRP levels were statistically greater in women with MS when compared to those without the syndrome (8.6 +/- 8.0 vs. 7.2 +/- 5.9 ng/mL and 0.219 +/- 0.848 vs. 0.360 +/- 0.852 mg/dL, p < 0.05). Leptin was significantly correlated to BMI, fat mass, waist circumference, HOMA-IR, and insulin but not to other components of MS, such as fasting plasma glucose, blood pressure, HDL-cholesterol, triglyceride, and CRP levels. Correlation between leptin and HOMA-IR or fasting insulinemia was maintained after adjustments for body adiposity. However, in logistic regression model, age, BMI, 2-h glucose, and uric acid were independently associated with MS, but not leptin. Conclusions: Adiposity-adjusted correlation of leptin with HOMA-IR and fasting insulinemia suggested that the former is associated with insulin resistance, despite the lack of independent association with the definition of the MS according to NCEP-ATP III. These findings in such Japanese-Brazilian population of high prevalence of MS need to be confirmed in other populations.     

Rational approach to selection of antihypertensive therapy in persons with metabolic syndrome: efficacy of monotherapy with spirapril and its combination with retard form of nifedipine

AIM: Achievement of target blood pressure (BP) levels in subjects with metabolic syndrome (MS) by the method of stepwise antihypertensive therapy and assessment of metabolic effects of combination of spirapril and nifedipine retard. MATERIAL AND METHODS: Patients (n=20, 12 women, 8 men, mean age 54+/-3 years) with MS were first given spirapril (6 mg/day). Nifedipine retard (40 mg/day) was added if target BP was not achieved after 4 weeks. Study duration was 12 weeks. The following parameters were measured at baseline and at study end: heart rate, blood pressure, body mass, waist circumference, parameters of lipid spectrum, content of insulin including index HOMA IR, blood glucose (fasting and during oral glucose tolerance test). RESULTS: Target BP levels were achieved in 18 patients (90%)--in 11 with moexipril monotherapy, in 9--after addition of nifedipine. Lowering of systolic and diastolic BP from baseline was 11 and 14%, respectively. After 3 months of combination antihypertensive therapy triglyceride levels decreased by 28% while high density lipoprotein cholesterol (CH) increased 6%. Total, low density lipoprotein CH and coefficient of atherogenecity did not change as well as fasting blood glucose after fast and oral glucose tolerance test. Concentration of fasting immunoreactive insulin significantly decreased by 34% entailing 35% decrease of insulin resistance. Therapy was well tolerated, side effects were transitory and did not cause withdrawal of treatment. CONCLUSION: In patients with MS and mild hypertension monotherapy with spirapril and combination of spirapril with nifedipine retard caused lowering of BP to target level in 55 and 90%, respectively. Combination of spirapril and nifedipine retard exerts positive metabolic action.     

Association of insulin resistance and nocturnal fall of blood pressure in GH-deficient adults during GH replacement

The GH deficiency syndrome in adults is characterized by changes in body composition, metabolic, cardiovascular and psychological profile. Such alterations fit the metabolic syndrome. Changes of blood pressure (BP) levels related to the presence of insulin resistance (IR) may be present in the GH-deficient adult prior to or after therapy with recombinant GH (hGH). The purpose of the study was to assess the relationship between BP and IR in GH-deficient adults after 24 months of replacement with hGH. Thirteen GH-deficient adults were studied [7 men and 6 women, with an average age of 38.6+/-14.14 yr body mass index (BMI) 25.83+/-2.26 kg/m2]. The BP was assessed by means of ambulatory monitoring of BP (AMBP), prior to the treatment and 12 and 24 months after replacement with hGH. Glucose metabolism was assessed by the homeostatic model assessment (HOMA), during the same periods. The average dosage of hGH utilized was 0.67+/-0.15 mg/day. In the analysis of BP levels, we observed a decrease of the diurnal systolic BP (SB P) (p=0.043) and a reduction of the diurnal systolic (p=0.002) and diastolic pressure loads (p=0.038). During the night there were no changes in BP levels. We observed an increase in the percentage of patients with a non-physiological nocturnal fall (non dippers) after replacement with hGH (61.53%). The mean HOMA, insulin and glucose in the fasting state did not present any statistically significant changes. Although the patients within the nondipper group had higher HOMA and insulin levels throughout the study, there were no changes in any of these parameters after GH replacement. All patients with HOMA >2.5 were within the non-dipper group, whereas all dippers had HOMA <2.5. In conclusion, 24 months of therapy with hGH do not seem to have affected glucose homeostasis, and since there is no relationship with the increase of the percentage of non-physiological nocturnal fall, we will need a longer observation time to discover the effects of this finding.     

Metabolic syndrome and morphofunctional characteristics of the left ventricle in clinically hypertensive nondiabetic subjects

BACKGROUND: The study was aimed to evaluate the impact of the metabolic syndrome on left ventricular (LV) structure and function in nondiabetic patients, never treated with antihypertensive or lipid-lowering drugs. METHODS: Eighty-eight patients, with recent finding of clinic BP >140 or 90 mm Hg, underwent 24-h blood pressure (BP) monitoring, echocardiogram, evaluation for metabolic syndrome (Adult Treatment Panel III criteria). RESULTS: Metabolic syndrome was diagnosed in 38 subjects (43.2%) (metabolic syndrome+). Age, gender, 24-h systolic and diastolic BP were similar between metabolic syndrome+ and metabolic syndrome- groups, whereas body mass index, clinic and 24-h heart rate, fasting glycemia, and triglycerides were significantly higher and HDL-cholesterol lower in metabolic syndrome + subjects. The prevalence of sustained hypertension (24-h BP >125 or 80 mm Hg) was similar between the two groups. Relative wall thickness and LV mass were significantly greater in the metabolic syndrome+ group, also after correction for body mass index. The LV systolic function was similar between the two groups, whereas all the parameters of diastolic function, but the mitral E/A ratio, were significantly lower in the metabolic syndrome+ group. From multiple regression analysis the main independent determinant of LV mass index was the presence of metabolic syndrome, followed by the 24-h systolic BP. CONCLUSIONS: Nondiabetic patients with metabolic syndrome showed more pronounced alterations of LV geometry and function compared with subjects without metabolic syndrome. These greater preclinical myocardial abnormalities were not accounted for by difference in age, gender, or 24-h BP and can be reasonably ascribed to the interplay of the metabolic syndrome components, making the metabolic syndrome in itself a relevant clinical problem, possibly a cardiovascular disease equivalent, that deserves aggressive treatment.     

Homeostasis model assessment of insulin resistance,quantitative insulin sensitivity check index,and oral glucose insulin sensitivity index in nonobese,nondiabetic subjects with high-normal blood pressure

To investigate the relationships between high-normal blood pressure (BP) and insulin resistance, we examined insulin sensitivity in 306 nonobese and nondiabetic Japanese subjects with various BP categories (optimal BP, normal BP, high-normal BP, and hypertension). Insulin sensitivity was measured from fasting plasma glucose and insulin values and those during a 75-g oral glucose tolerance test by five formulas: the homeostasis model assessment of insulin resistance (HOMA-R), the quantitative insulin sensitivity check index (QUICKI), the oral glucose insulin sensitivity (OGIS) index, and two insulin sensitivity indexes (ISI-composite and ISI-stumvoll). The HOMA-R was significantly higher, and the QUICKI was significantly lower in subjects with hypertension than in subjects with optimal BP. Both HOMA-R and QUICKI values showed that high-normal BP patients had a higher (but not significant) degree of insulin resistance than optimal BP patients. The OGIS index was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP. The ISI-composite was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP, and it was also significantly lower in subjects with hypertension than in subjects with normal BP. The ISI-stumvoll was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP. The OGIS index, ISI-composite, and ISI-stumvoll significantly decreased with increasing severity of BP status among the normotensive groups (optimal BP, normal BP, and high-normal BP). These findings indicate that insulin resistance is present even in the high-normal BP categories of nonobese and nondiabetic Japanese individuals.     

Adrenal incidentaloma: a new cause of the metabolic syndrome?

A number of patients with adrenal incidentaloma are exposed to a slight degree of cortisol excess resulting from functional autonomy of the adrenal mass (usually a cortical adenoma). At present, there are only scant data on the unwanted effects of this endocrine condition referred to as subclinical Cushing's syndrome. The aim of the present study was to look for some features of the metabolic syndrome in patients with incidental adrenal adenoma. Forty-one patients (9 men and 32 women) bearing adrenal incidentaloma with typical computed tomography features of cortical adenoma were studied. For both patients and controls, exclusion criteria were age equal to 70 yr or greater, previous history of fasting hyperglycemia, or impaired glucose tolerance (IGT), severe hypertension, current use of medication or concomitant relevant illnesses, and body mass index (BMI) equal to 30 kg/m(2) or greater. Forty-one patients with euthyroid multinodular goiter accurately matched for sex, age, and BMI served for a 1:1 case-control analysis. The study design included an oral glucose tolerance test (75 g) and an endocrine workup aimed at the study of the hypothalamic-pituitary-adrenal axis. Age and BMI were fully comparable between patients (54.0 +/- 10.7 yr, 23.8 +/- 2.4 kg/m(2)) and controls (52.2 +/- 11.6 yr, 23.5 +/- 2.8 kg/m(2)). Fasting glucose and fasting insulin levels were not different between the two groups (4.96 +/- 0.61 mmol/liter vs. 4.88 +/- 0.58 mmol/liter; 67 +/- 34 pmol/liter vs. 59 +/- 32 pmol/liter), but the 2-h postchallenge glucose was significantly higher in patients than in controls (7.43 +/- 2.49 mmol/liter vs. 6.10 plus minus 1.44 mmol/liter, P = 0.01). Fifteen patients (36%) reached the World Health Organization criteria for IGT and two other patients (5%) reached those for diabetes, and 14% of the controls qualified for IGT (P = 0.01). No difference in the lipid pattern was seen between the two groups, but either systolic or diastolic blood pressure were higher in patients (135.4 +/- 15.5 mm Hg vs. 125.0 +/- 15.6 mm Hg, P = 0.003; 82.9 +/- 9.1 mm Hg vs. 75.3 +/- 6.6 mm Hg, P < 0.0001). We calculated the whole-body insulin sensitivity index derived from the oral glucose tolerance test that was significantly reduced in the patients (4.3 +/- 1.7 vs. 5.7 +/- 2.5, P = 0.01). In a multiple regression analysis, 2-h glucose was associated with BMI and midnight cortisol values (r(2) = 0.36, P = 0.002). The comparison of the patients with nonfunctioning adenoma (n = 29) with those with subclinical Cushing's syndrome (n = 12) yielded significant differences as to 2-h glucose and triglyceride levels, which were significantly higher in the second group (7.02 +/- 1.76 mmol/liter vs. 8.72 +/- 3.17 mmol/liter, P = 0.03; 1.06 +/- 0.4 mmol/liter vs. 1.73 +/- 0.96 mmol/liter, P = 0.002), but the insulin sensitivity index was conversely reduced (5.2 +/- 1.4 vs. 2.9 +/- 1.2, P < 0.0001). In conclusion, many patients with incidental adrenal adenoma display altered glucose tolerance, that may be explained by reduced insulin sensitivity, and increased blood pressure levels in comparison with carefully age- and BMI-matched controls. The slight hypercortisolism observed in some such patients may significantly contribute to this state of insulin resistance. Midnight serum cortisol appears as a sensitive marker of the metabolic effects of subclinical Cushing's syndrome.     

Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from young insulin-resistant Japanese men

The metabolic syndrome is characterized by a blunted insulin-mediated glucose uptake in various cell types. We compared the glucose uptake characteristics of Epstein-Barr virus (EBV)-transformed lymphoblasts obtained from young men with vs without metabolic and cardiovascular evidence of metabolic syndrome. From a population of 218 men, 20- to 25-year-old, 10 men with a systolic blood pressure (BP) > or =130 mm Hg and family history of hypertension were assigned to a high BP (HBP) group, and 10 with a BP < or =110 mm Hg, and no family history of hypertension was assigned to a low BP (LBP) group. Multiple clinical and metabolic characteristics were examined in both groups and compared. Peripheral lymphocytes from HBP and LBP subjects were EBV-transformed, and the glucose transporter (Glut)-mediated glucose uptake from each group was compared in lymphoblasts. Body mass index, fasting glucose, immunoreactive insulin, insulin resistance index based on a homeostasis model assessment (HOMA-R), and total and low-density lipoprotein cholesterol were significantly higher in the HBP than the LBP subgroup (whole-body insulin resistance). Baseline Glut-mediated and Glut-mediated insulin-stimulated glucose uptake by lymphoblasts from the HBP group were significantly lower than by lymphoblasts from the LBP group (cellular insulin resistance). The net increment in Glut-mediated glucose uptake by insulin was inversely correlated with HOMA-R. In conclusion, cellular insulin resistance in EBV-transformed lymphoblasts is associated with young Japanese subjects with HBP. The net increment in Glut-mediated glucose uptake by insulin in lymphoblasts may be a useful intermediate phenotype to study genetic aspects of the metabolic syndrome.     

Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes

BACKGROUND: To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. METHODS: A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. RESULTS: The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. CONCLUSIONS: Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.     

Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance.

It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulin-resistant state. Fourteen PCO women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (SI) index was determined by the minimal model method. Systolic and diastolic blood pressure were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echocardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PCO (8.0 +/- 0.5 vs. 5.6 +/- 0.3 mmol/L; P less than 0.001). Compared to controls, PCO women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and SI (28.3 +/- 6.7 vs. 68.3 +/- 10.0 min-1/nmol.mL; P less than 0.01). Average ambulatory systolic (121 +/- 2 vs. 118 +/- 2 mm Hg) and diastolic (76 +/- 2 vs. 73 +/- 2 mm Hg) blood pressures were similar for PCO and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PCO do not have increased arterial pressure or left ventricular mass.     

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.     

Microalbuminuria,a parameter independent of metabolic influences in hypertensive men

OBJECTIVE: To evaluate the relationship of albuminuria and microalbuminuria (overnight urine albumin > or = 15 micro g/min) with insulin resistance and related metabolic abnormalities in patients with essential hypertension. DESIGN: Cross-sectional evaluation of 271 (age range, 19-77 years) never-treated, non-diabetic, uncomplicated hypertensive men. MAIN OUTCOME MEASURES: Triplicate overnight urine albumin determination and homeostasis model assessment (HOMA) of insulin resistance as a surrogate measure of insulin sensitivity. Additional parameters were fasting and post-load circulating glucose and insulin, lipids, body mass index, blood pressure and echocardiographic left ventricular mass. RESULTS: HOMA, fasting and post-challenge glucose and insulin, percentages of glucose-intolerant patients, triglycerides and high-density lipoprotein cholesterol levels did not differ across ascending urine albumin quartiles. Body mass index, blood pressure and ventricular mass were significantly greater in the upper quartiles, and the prevalence of obesity fivefold more frequent in the top as compared with the bottom urine albumin fourth. The statistical trend was unchanged after adjustment for HOMA, while accounting for systolic blood pressure and left ventricular mass by co-variance analysis abolished it. Eighty-eight patients bearing the phenotypic traits of the metabolic syndrome and a striking degree of insulin resistance and hyperinsulinemia showed urine albumin rates and prevalence of microalbuminuria comparable with the 183 patients who were not affected by that syndrome. CONCLUSIONS: Albuminuria is independent of insulin resistance and other phenotypic components of the metabolic syndrome in never-treated, non-diabetic essential hypertensive men. Microalbuminuria is more frequent in obese hypertensives but this association is explained by higher blood pressure more than insulin resistance.     

Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy

Lipodystrophy (lipo) and metabolic derangements associated with an increased cardiovascular risk are observed frequently in human immunodeficiency virus (HIV)-infected patients who receive antiretroviral treatment (ART). The objective of the study was to provide detailed biochemical information about metabolic syndrome in this condition. One hundred forty-six HIV-infected male and female patients on ART for more than 6 months were compared with 156 body mass index (BMI)-matched healthy subjects. Lipodystrophy was diagnosed upon patient and physician concordance. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Plasma adiponectin (AD) and leptin were measured by radioimmunoassay. Insulin resistance (IR) was assessed by the homeostasis model assessment (HOMA). The prevalence of metabolic syndrome was higher in HIV-infected patients on ART than in non-HIV-infected healthy controls (15.8% vs 3.2%; P < .001). Patients with metabolic syndrome are older (44.6 +/- 6 vs 39.8 +/- 8 years; P = .004), have an increased BMI (24.9 +/- 3.8 vs 22.9 +/- 9.8 kg/m(2); P = .01), present with a reduced AD-to-leptin ratio log(10) (-0.19 +/- 0.4 vs 0.5 +/- 0.4; P = .04), and show increased IR (HOMA, 5.6 +/- 2.7 vs 3.8 +/- 2.2; P = .001; plasma fasting insulin, 22.9 +/- 9.8 vs 16.6 +/- 9.7 ng/mL; P < .001). In multivariate analysis, the diagnosis of lipo and HOMA were independently and significantly related to metabolic syndrome. In conclusion, the prevalence of metabolic syndrome is significantly increased in HIV-infected patients on ART and its presence is associated with lipo, increased age and BMI, IR, and a reduced plasma AD-to-leptin ratio.     

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.     

A relationship between serum ferritin and the insulin resistance syndrome is present in non-diabetic women but not in non-diabetic men

BACKGROUND: Previous studies have suggested that serum ferritin is one of the components of the insulin resistance syndrome in Caucasians. Because serum ferritin levels differ significantly between men and women, variation in the role of ferritin in insulin resistance between the sexes, particularly in Asian populations, is still unknown. OBJECTIVE: To examine whether the association between serum ferritin and insulin resistance differs between men and women in randomly selected non-diabetic Chinese subjects. DESIGN: A retrospective study. PATIENTS: Four hundred and seventeen non-diabetic Chinese subjects (140 men and 277 women) were studied. MEASUREMENTS: Fasting plasma glucose, insulin, lipoproteins and serum ferritin concentrations, as well as plasma glucose and insulin responses to a 75-g oral glucose test (n = 219), were determined. RESULTS: Fasting serum ferritin concentrations (mean +/- SEM) were significantly higher in men than in women (504 +/- 33 vs. 242 +/- 18 pmol/l, P < 0.001). In women, fasting serum ferritin concentrations correlated significantly with age, body mass index (BMI), amount of body fat, fasting plasma glucose, insulin, cholesterol, triglyceride concentrations, glucose response to an oral glucose load, and homeostasis model assessment (HOMA) of insulin resistance but not with blood pressure, high density lipoprotein (HDL) cholesterol levels and insulin response to oral glucose. On the contrary, none of the above anthropometric and metabolic variables was related to fasting serum ferritin levels in men. HOMA insulin resistance increased progressively across three different tertiles for measured serum ferritin concentrations in women (P < 0.003). In men, HOMA insulin resistance levels were not different among three differing measured serum ferritin levels (P = 0.424). Adjustment for age, BMI and menopause status did not change the significant relationship between HOMA insulin resistance and serum ferritin in women. CONCLUSIONS: We observed that a relationship between serum ferritin levels and insulin resistance exists in women but not in men. This sexual dimorphism merits further investigation.