French practical guidelines for the diagnosis and management of AA amyloidosis.

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future.

Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. DESIGN: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. METHODS: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. RESULTS: The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

Dairy consumption is associated with lower plasma dihydroceramides in women from the D.E.S.I.R. cohort.

AIM: In the D.E.S.I.R. cohort, higher consumption of dairy products was associated with lower incidence of hyperglycaemia, and dihydroceramide concentrations were higher in those who progressed to diabetes. Our aim here was to study the relationships between dairy consumption and concentrations of dihydroceramides and ceramides. METHODS: In the D.E.S.I.R. cohort, men and women aged 30-65 years, volunteers from West-Central France, were included in a 9-year follow-up with examinations every 3 years, including food-frequency questionnaires. Two items concerned dairy products (cheese, other dairy products except cheese). At each examination, dihydroceramides and ceramides were determined by mass spectrometry in a cohort subset; in the present study, the 105 people who did not progress to type 2 diabetes were analyzed, as the disorder per se might be a confounding factor. RESULTS: Higher consumption of dairy products (except cheese) was associated with total plasma dihydroceramides during the follow-up, but only in women (P=0.01 for gender interaction). In fact, dihydroceramide levels were lower in women with high vs low consumption (P=0.03), and were significantly increased during follow-up (P=0.01) in low consumers only. There was also a trend for lower ceramides in women with high dairy (except cheese) intakes (P=0.08). Cheese was associated with dihydroceramide and ceramide changes during follow-up (P=0.04 for both), but no clear trend was evident in either low or high consumers. CONCLUSION: These results show that, in women, there is an inverse association between fresh dairy product consumption and predictive markers (dihydroceramides) of type 2 diabetes.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients.

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.

Insulin secretion and its association with physical activity, fitness and screen time in children.

OBJECTIVES: To determine the independent associations of moderate to vigorous physical activity (MVPA), fitness, screen time, and adiposity with insulin secretion in children. DESIGN AND METHODS: Caucasian youth (n = 423/630), 8-10 years old, with at least one obese biological parent, were studied (QUALITY cohort). Insulin secretion was measured using HOMA2-%B, area under the curve (AUC) of insulin to glucose over the first 30 minutes (AUC I/G(t30min)) of the OGTT and AUC I/G(t120min) over 2 hours. Fitness was measured by VO2peak ; percent fat mass (PFM) by DXA; 7-day MVPA by accelerometry; self-reported screen time included television, video game, or computer use. Models were adjusted for age, sex, season, puberty, PFM, and insulin sensitivity [IS] (HOMA2-IS, Matsuda-ISI). RESULTS: PFM was strongly associated with insulin secretion, even after adjustment for IS: for every 1% increase in PFM, insulin secretion increased from 0.3% to 0.8% across indices. MVPA was negatively associated with HOMA2-%B (P < 0.05), but not with OGTT-derived measures. Fitness was negatively associated with AUC I/G(t120min) (P < 0.05). Screen time showed a trend toward higher HOMA2-%B in girls (P = 0.060). CONCLUSIONS: In children with an obese parent, lower insulin secretion is associated with lower adiposity, higher MVPA, better fitness, and possibly reduced screen time.

Relevance of increased serum cystatin C to vascular alterations in obese children.

OBJECTIVE: Epidemiological studies report a positive relationship between serum cystatin C and cardiovascular outcomes in adults. Here, we tested the relevance of cystatin C as a biomarker for early vascular alterations in severely obese children. METHODS: Two hundred nineteen obese (140 girls; age = 11.7 ± 2.7 years, BMI Z-score = 4.7 ± 1.2 SD) and 262 non-obese children (129 girls; age = 11.6 ± 0.6 years, body mass index [BMI] Z-score = 0.1 ± 1.0 SD). Serum cystatin C was measured by immunonephelometry. Intima media thickness (IMT), incremental elastic modulus, and flow-mediated and glyceryl-trinitrate-mediated dilations were determined at the common carotid artery and the brachial artery in obese children. RESULTS: Obese children had significantly higher serum cystatin C than normal weight controls (0.86 ± 0.01 vs. 0.80 ± 0.01, P < 0.0001). In obese children, serum cystatin C correlates positively with BMI and the homeostasis model assessment index and negatively with the quantitative insulin sensitivity check index and adiponectin. A positive relationship was found between serum cystatin C and carotid IMT (r = 0.23, P = 0.0005), which remained significant in multivariate models adjusted for BMI (P = 0.01) and adiponectin with a trend towards significance (P = 0.05). CONCLUSION: This study positions cystatin C and adiponectin as covariables associated with arterial wall thickness in obese children. Although the underlying pathophysiology linking cystatin C to early vascular disease remains to be deciphered, cystatin C may represent a novel adipose tissue-derived biomarker implicated in obesity-related comorbidities early in life.

Evaluation of two new surrogate indices including parameters not using insulin to assess insulin sensitivity/resistance in non-diabetic postmenopausal women: a MONET group study.

AIM: The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women. METHODS: A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot. RESULTS: A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively). CONCLUSION: The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use.

How can we measure insulin sensitivity/resistance?

Insulin resistance represents a major public health problem, as it plays a major role in the pathophysiology of type 2 diabetes mellitus; it is also associated with increased cardiovascular risk and atherogenic dyslipidaemia, and is a central component of the cluster of metabolic abnormalities that comprise the metabolic syndrome. Thus, the development of tools to quantify insulin sensitivity/resistance has been the main objective of a number of studies. Insulin resistance can be estimated with the use of several biological measurements that evaluate different aspects of this complex situation. To that end, it requires various resources, ranging from just a single fasting blood sample for simple indices, such as the HOMA or QUICKI, to a research setting in which to perform the gold-standard hyperinsulinaemic-euglycaemic clamp test. The choice of method for evaluating insulin resistance depends on the nature of the information required (classification of individual subjects, group comparisons, precise measurement of either global, muscle or liver insulin sensitivity/resistance) and on the available resources. The aim of this review is to analyze the most frequently used assay methods in an attempt to evaluate when and why these methods may be useful.

Measuring insulin sensitivity in youth: How do the different indices compare with the gold-standard method?

AIM: The objective of the study was to examine the correlation between three methods of measuring insulin sensitivity (IS) - namely, the frequently sampled intravenous glucose tolerance test (FSIVGTT), indices derived from the oral glucose tolerance test (OGTT) and fasting indices (HOMA-IR, QUICKI, fasting insulin [INS(0)]) - and the gold-standard method, the hyperinsulinaemic-euglycaemic clamp (HEC) test, in children. METHODS: A total of 20 children [nine boys and 11 girls; mean (SD) age: 9 (2) years] were studied. Their mean (SD) BMI Z score was 1.5 (0.8). All participants had normal glucose metabolism. Each child underwent a 3-h HEC (40 mU/m(2)/min of insulin), an insulin-modified minimal-model FSIVGTT and a 3-h OGTT. The clamp-derived IS was calculated, using DeFronzo's metabolized glucose index and Bergman's IS index. Correlations were established using Spearman's rank correlations. RESULTS: The two clamp-derived measures were highly correlated (r=0.85), and the IS measured from the FSIVGTT was well correlated with both clamp measures [r=0.69, 0.74]. Of the nine indices derived from the OGTT, the three with the highest correlation with clamp results were the ISI Matsuda [r=0.63, 0.68], SI(is)OGTT [r=0.53, 0.65] and log sum insulin [r=-0.64, -0.75]. Fasting indices of IS had similar correlations to clamp results: HOMA-IR [r=-0.55, -0.56]; QUICKI [r=0.55, 0.57]; and INS(0) [r=-0.59, -0.63]. CONCLUSION: While fasting-based indices of IS are a suitable option for large cohorts, OGTT-derived indices may represent a useful compromise for obtaining both clinical (glucose tolerance) and physiological (insulin sensitivity) information, making them particularly useful for large-scale physiological and epidemiological studies.

Adiponectin and leptin in Afro-Caribbean men and women with HIV infection: association with insulin resistance and type 2 diabetes.

AIM: Insulin resistance and type 2 diabetes (T2D) are commonly seen in human immunodeficiency virus (HIV) infection and are related to antiretroviral therapy. Adiponectin and leptin secreted by adipocytes are both linked to body-fat distribution and insulin sensitivity. The present study aimed to assess the prevalence of insulin resistance and T2D, and their association with adiponectin and leptin, in Afro-Caribbean men and women with HIV infection. METHODS: This cross-sectional study was conducted in an unselected sample of 237 HIV-1-infected patients. Clinical and metabolic parameters were measured, including fasting and postload plasma insulin, and circulating adiponectin and leptin levels. Insulin resistance was estimated by homoeostasis model assessment (HOMA-IR). Adjusted multiple logistic regressions were used to estimate the association of insulin resistance with adipokine levels and patients' characteristics. RESULTS: A total of 132 men (mean age: 49 years) and 105 women (mean age: 48 years) were included in the study. Prevalences of T2D and insulin resistance were higher in women than in men [16.2% vs 8.3% (P = 0.06) and 24% vs 9.9% (P < 10⁻³), respectively]. Abdominal obesity was found in 47% of women and in 7% of men (P < 10⁻4). Insulin resistance was independently associated with adiponectin in women and with leptin in men. CONCLUSION: Insulin resistance is frequent in Afro-Caribbean women with HIV infection. Overweight and obesity are major risk factors in such a population. Systematic screening for insulin resistance should be carried out in this population, which has a high prevalence of T2D.

Association between physical activity energy expenditure and inflammatory markers in sedentary overweight and obese women.

OBJECTIVE: Chronic subclinical inflammation and regular physical activity have opposing relationships to obesity-related metabolic diseases. Yet, the association between chronic inflammation and physical activity has rarely been examined in obese subjects. We examined the association between physical activity energy expenditure (PAEE), total (TEE) and resting energy expenditure (REE) and cardiorespiratory fitness (VO(2)peak) with inflammatory markers in overweight/obese women. DESIGN: Cross-sectional study. METHODS: The study included 152 overweight/obese postmenopausal women who were sedentary and free of chronic/inflammatory diseases (mean age: 57.5 (95% confidence interval (CI) 56.7-58.3) years, body mass index (BMI): 32.5 (95% CI 31.8-33.2) kg m(-2)). The following parameters were measured: TEE (doubly labeled water), REE (indirect calorimetry), PAEE (as (TEE x 0.90)-REE), VO(2)peak (ergocycle) and serum high-sensitive C-reactive protein (hsCRP), haptoglobin, soluble tumor necrosis factor-α receptor 1 (sTNFR1), interleukin-6, orosomucoid and white blood cells. RESULTS: Sedentary women with the highest tertile of PAEE (1276 (1233-1319) kcal day(-1)) had lower concentrations of hsCRP and haptoglobin than those in the lowest tertile (587 (553-621) kcal day(-1)) after adjustment for fat mass (P<0.05). Soluble TNFR1 was positively correlated with VO(2)peak, TEE and REE (P<0.05), and hsCRP and orosomucoid were positively associated with REE (P<0.01), whereas haptoglobin was negatively associated with PAEE (P<0.05). In stepwise regression analyses that examined the concomitant associations of components of energy expenditure with inflammatory markers, PAEE remained the only predictor of hsCRP and haptoglobin (P<0.05), explaining 14 and 5%, respectively, of their variation,whereas REE was the only predictor of orosomucoid (r (2) = 0.05, P = 0.02) after adjustment for fat mass. Adding leptin to the regression models results in similar relationships between inflammatory markers and components of energy expenditure. CONCLUSION: PAEE is an independent predictor of hsCRP and haptoglobin in sedentary overweight/obese postmenopausal women free of chronic disease. Our data support the role of physical activity in reducing subclinical inflammation and risk of metabolic and cardiovascular diseases.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: a MONET study.

BACKGROUND AND AIMS: The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women. METHODS AND RESULTS: This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6 kg/m(2); body fat: 38.6+/-9.2 kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI(is)) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15-28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15-17% of the variance. CONCLUSION: The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.

A lipid-parameter-based index for estimating insulin sensitivity and identifying insulin resistance in a healthy population.

AIM: Insulin resistance needs to be identified as early as possible in its development to allow targeted prevention programmes. Therefore, we compared various fasting surrogate indices for insulin sensitivity using the euglycaemic insulin clamp in an attempt to develop the most appropriate method for assessing insulin resistance in a healthy population. METHODS: Glucose, insulin, proinsulin, glucagon, glucose tolerance, fasting lipids, liver enzymes, blood pressure, anthropometric parameters and insulin sensitivity (Mffm/I) using the euglycaemic insulin clamp were obtained for 70 normoglycaemic non-obese individuals. Spearman's rank correlations were used to examine the association between Mffm/I and various fasting surrogate indices of insulin sensitivity. A regression model was used to determine the weighting for each variable and to derive a formula for estimating insulin resistance. The clinical value of the surrogate indices and the new formula for identifying insulin-resistant individuals was evaluated by the use of receiver operating characteristic (ROC) curves. RESULTS: The variables that best predicted insulin sensitivity were the HDL-to-total cholesterol ratio, the fasting NEFA and fasting insulin. The use of the lipid-parameter-based formula Mffm/I=12x[2.5x(HDL-c/total cholesterol)-NEFA] - fasting insulin appeared to have high clinical value in predicting insulin resistance. The correlation coefficient between Mffm/I and the new fasting index was higher than those with the most commonly used fasting surrogate indices for insulin sensitivity. CONCLUSION: A lipid-parameter-based index using fasting samples provides a simple means of screening for insulin resistance in the healthy population.

HOMA or QUICKI: is it useful to test the reproducibility of formulas?

AIM: HOMA and QUICKI are the most widely used indices for assessing insulin sensitivity. Both are based on fasting glucose and insulin measures, and mainly differ by the log transformation of these variables in QUICKI. However, HOMA is less reproducible than QUICKI, and log HOMA does not improve its reproducibility. The aim of this study was to investigate the various mathematical transformations of HOMA and to assess its reproducibility. METHOD: We used data from a clamp study involving 123 non-diabetic overweight and obese postmenopausal women. Fasting insulin and glucose were measured in two visits 15 and 30 days apart. This allowed us to calculate HOMA as (fasting glucose [mmol/L] x fasting insulin [microU/mL])/22.5 and QUICKI as 1/(log fasting glucose [mg/dL]+log fasting insulin [microU/mL]) twice for subjects who were weight-stable between visits. RESULTS: QUICKI had better reproducibility (CV=3.9%) than either HOMA (CV=26.7%) or log HOMA (CV=22.0%). However, log-transforming HOMA using log (glucose x insulin)/log (22.5) and log-transforming HOMA without transforming the constant denominator improved its CV to 6.5% and 5.7%, respectively. CONCLUSION: By modifying the mathematical expression of HOMA, we were able to achieve comparable CVs for QUICKI and HOMA. However, the CV should be used to assess the reproducibility of techniques to measure glucose and insulin, not of mathematical formulas. When evaluating indices for the assessment of insulin sensitivity, the key point is how well they correlate with the 'gold-standard' glucose clamp.