Neutrophil gelatinase-associated lipocalin as a biomarker of nephropathy in sickle cell disease.

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.

Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

OBJECTIVE: To investigate the effect of the common fat mass and obesity-associated (FTO) gene polymorphism rs9939609 on body mass index (BMI) in one of the most obese populations worldwide. SUBJECTS AND METHODS: Genotypic data for FTO rs9939609 were available for 1,034 unrelated Kuwaiti adults obtained from Kuwait's Dasman Diabetes Institute and Kuwait University. The association between the FTO polymorphism with BMI as continuous and categorical (normal BMI [< 25] vs. overweight/obese [> 25]) variables was analyzed using both linear and logistic regression models, respectively, with the assumption of both dominant and additive genetic models performed using the SNPassoc package from R statistics. RESULTS: The A allele was associated with increased BMI (ß = 1.21; 95% CI = 0.16-2.26; p = 0.023). In concordance, the categorical BMI (normal vs. overweight/obese) also showed a significant association between the A allele and overweight/obesity (OR = 1.47; 95% CI = 1.01-2.12; p = 0.041). However, no association between the FTO variant was observed with cardiometabolic traits. CONCLUSION: We observed an association between the common FTO rs9939609 polymorphism and increased BMI (overweight/obesity) in Kuwaiti adults, which is consistent with previous research in other populations. Our findings encourage further investigation of genetic variants to elucidate the mechanisms involved in the development of obesity in such an obesogenic population.

Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus.

OBJECTIVE: We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. MATERIALS AND METHODS: This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy (DPN) and vitamin D [25(OH)D] deficiency. Patients were sequentially assigned to a treatment group (n = 57) and a placebo group (n = 55). DPN was assessed using a neuropathy symptom score (NSS), a neuropathy disability score (NDS) and a nerve conduction study (NCS). Vitamin D status was determined by measuring the serum total 25(OH)D concentration. Patients received either oral vitamin D3 capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. RESULTS: Serum 25(OH)D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group (32.8 ± 23.7 vs. 1.1 ± 3.6, p < 0.0001). Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group (-1.49 ± 1.37 vs. -0.20 ± 0.59, p < 0.001). No improvement was observed for NDS and NCS between the 2 groups after treatment. CONCLUSION: Short-term oral vitamin D3 supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes.

Transthoracic echocardiography and 6-minute walk test in Kuwaiti sickle cell disease patients.

OBJECTIVE: The aim of this study was to investigate cardiac abnormalities in Kuwaiti sickle cell disease (SCD) patients using markers such as tricuspid regurgitant jet velocity (TRJV), pulmonary artery systolic pressure (PASP), and the 6-minute walk (6MW) test and correlate these findings with clinical, hematological, and biochemical parameters. MATERIALS AND METHODS: Seventy-three patients with SCD and 70 matched controls were studied. The cardiac status was investigated using transthoracic echocardiography in 57 patients; the 6MW test was carried out in patients and controls. Complete blood counts and hemolytic parameters were assessed. RESULTS: Reticulocytes, bilirubin, and lactate dehydrogenase were significantly higher (p < 0.0001) in patients, while hemoglobin (Hb) and haptoglobin were lower (p < 0.0001) than in controls. The mean fetal Hb among patients was 15.85 ± 8.7%. Of the 57 patients, 14 (24.5%) and 15 (26%) had mild tricuspid and mitral regurgitation, respectively. The mean ejection fraction, TRJV, and PASP were 63.9 ± 6.3%, 1.7 ± 0.5 m/s, and 23.0 ± 7.3 mm Hg, respectively. Three (5.2%) patients had mildly raised TRJV (2.6-2.97 m/s, normal range <2.5 m/s) while 8 (14%) had high PASP (mean 35.3 ± 5.1 mm Hg, normal range <30 mm Hg). Hb, hematocrit, and reticulocytes were different (p = 0.010, p = 0.006, and p = 0.011, respectively) between patients with normal and high PASP. All 3 patients who had a high TRJV had a high PASP, and 2 of these patients died during follow-up. The systolic and diastolic blood pressure, oxygen saturation before and after the 6MW test, and distance walked were lower (p = 0.006, p = 0.000, p = 0.002, p = 0.000, and p = 0.000, respectively) in patients compared to controls. CONCLUSION: Raised PASP was common in Kuwaiti SCD patients while raised TRJV was not.

Associations of adipokines & insulin resistance with sex steroids in patients with breast cancer.

BACKGROUND & OBJECTIVES: Several studies have suggested an important, but conflicting and controversial role for adipose tissue mass in breast cancer risk. Factors such as insulin-like growth factors, sex steroids, adipokines and obesity-related inflammatory markers have been postulated as potential effectors of the mechanisms by which obesity and associated metabolic disorders influence breast cancer risk. In this study we evaluated the associations between obesity indices, insulin resistance, circulating adipokines, sex steroids and breast cancer. METHODS: Fasting adiponectin, leptin, insulin resistance (homeostasis model assessment, HOMA-IR), testosterone, estradiol, sex hormone binding globulin (SHBG), LH and FSH were determined in 144 newly-diagnosed histologically confirmed breast cancer patients and 77 controls. Univariate and multivariate regression analyses were used to find the associations of these variables with each other, indices of obesity and with breast cancer. RESULTS: BMI, waist circumference, HOMA-IR and leptin were significantly (P<0.001) higher in patients than in controls. Adiponectin level was also significantly (P<0.05) higher in patients compared to controls. Adiponectin and leptin showed significant correlations with insulin and HOMA-IR but only adiponectin was significantly correlated with estradiol and SHBG. Logistic regression analyses showed that factors associated with breast cancer were BMI [OR (95% CI) =2.8 (1.4-5.5), P=0.004]; high levels of adiponectin [5.1 (2.2-11.5), P<0.001); hyperinsulinaemia [1.1 (1.0-1.1), P=0.01], leptin [3.1 (1.7-5.7), P<0.0001], estradiol [2.5 (1.3-4.7), P=0.005] and testosterone [1.3 (1.03-1.7), P=0.03]. INTERPRETATION & CONCLUSIONS: Our findings confirm that adipokines, insulin resistance and sex steroids are associated with breast cancer. The paradoxical association of increased adiponectin with breast cancer is a novel finding that deserves further investigation.

Computational methods are significant determinants of the associations and definitions of insulin resistance using the homeostasis model assessment in women of reproductive age.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS), but identification of insulin-resistant individuals is difficult. The homeostasis model assessment (HOMA), a surrogate marker of IR, is available in 2 computational models: HOMA1-IR (formula) and HOMA2-IR (computer program), which differ in incorporated physiological assumptions. This study evaluates the associations of the 2 models as markers of IR, the metabolic syndrome (MS), and PCOS. METHODS: Anthropometric, hormonal, and biochemical parameters were measured in 92 PCOS women and 110 controls. HOMA1 and HOMA2 were used to assess IR. Regression analyses were used to find the associations of the 2 models with different variables, MS, and PCOS. RESULTS: The cutoff levels for definition of IR were HOMA1-IR ≥2.9 and HOMA2-IR ≥1.7. Mean HOMA1-IR (2.79) and HOMA2-IR (1.42) differed substantially. The difference (HOMA1-IR - HOMA2-IR) was significantly correlated with insulin, fasting plasma glucose, triglycerides, HDL cholesterol, waist circumference, leptin, and adiponectin (all P < 0.05). HOMA1-IR and HOMA2-IR were significantly associated with MS (odds ratio 5.7 and 4.2, respectively) and PCOS (odds ratio 3.7 and 3.5, respectively). CONCLUSIONS: HOMA computational methods significantly affect the associations and cutoff values used for definition of IR. The correlations of the difference in the computational methods corroborate differences in captured physiological mechanisms. As precise identification of IR in PCOS patients is of practical importance, practitioners and researchers should be aware of these differences in the HOMA computational methods.

Association between the lipoprotein lipase rs1534649 gene polymorphism in intron one with Body Mass Index and High Density Lipoprotein-Cholesterol.

Lipoprotein lipase (LPL) is an enzyme involved in lipid metabolism and distribution of fatty acids hence its role in the initiation and development of dyslipidemia and adiposity. Single nucleotide polymorphisms (SNPs) across the LPL gene have been associated with dyslipidemia, however, the association with obesity has been limited towards specific populations. This study examined the association between LPL gene polymorphisms with plasma lipid levels and body mass index (BMI) in the Kuwaiti population. We examined a total of 486 adults (303 and 183 females and males respectively) with plasma lipid levels and BMI. DNA samples were genotyped for two LPL gene polymorphisms (rs1534649 and rs28645722) using TaqMan allelic discrimination. The relationship between the genotypes with both plasma lipid levels and BMI were assessed using linear regression using "SNPassoc" package from R statistical software. Using an additive genetic model, linear regression analysis showed the T-allele of rs1534649 to be associated with increased BMI in a dose-dependent trend ß = 2.13 (95% CI 1.33-2.94); p = 1.7 × 10-7. In addition, a borderline significance was observed between the T-allele and low levels of high density lipoprotein-cholesterol ß = -0.04 (95% CI -0.08, -0.006); p = 0.02. There were no associations between rs28645722 and plasma lipid levels (p > 0.05). However, a trend was observed between the A-allele and increased BMI ß = 1.75 (95% CI 0.14-3.35); p = 0.03. Our study shows intron one polymorphism rs1534649 to increase the risk of obesity and dyslipidemia. Our findings warrant further investigation of the mechanism of LPL on the development of obesity along with the role of intron one and its impact on LPL gene activity.

Effect of homeostasis model assessment computational method on the definition and associations of insulin resistance.

BACKGROUND: Homeostasis model assessment (HOMA) is a surrogate index widely used to study the role of insulin sensitivity or resistance in associated disease states. However, reported values for the definition of insulin resistance (the top 25% of the distribution in non-diabetic subjects) vary widely. This study evaluates the effect of HOMA computational methods [original HOMA model formula (HOMA1) and online calculator computer model (HOMA2)] on the associations and cut-off limits for insulin resistance. METHODS: Anthropometric measurements, fasting adiponectin, leptin, leptin receptor, insulin, glucose, high-sensitivity C-reactive protein and a lipid profile were measured in type 2 diabetic patients (n=226) and their normoglycemic first degree relatives (n=319). HOMA1 and HOMA2 were used to estimate insulin resistance, ß-cell function and insulin sensitivity. Subjects were classified as metabolic syndrome positive or negative (International Diabetes Federation criteria). Bland-Altmann analysis was used to evaluate agreement between the computational methods. Univariate and multivariate logistic regression analyses were used to relate the HOMA computational methods with metabolic variables and metabolic syndrome status. RESULTS: The two computational methods had different cut-offs for the definition of insulin resistance: HOMA1 formula ≥2.5; HOMA2 calculator ≥1.4. Correlations of the two HOMA computational methods with anthropometric and metabolic variables showed some degree of variation. The odds ratios of the associations with the metabolic syndrome for the HOMA1 formula and HOMA2 calculator computational methods were 2.04 and 1.43, respectively. Receiver operating characteristic analysis for diagnosis of the metabolic syndrome showed that areas under the receiver operating characteristic curves for the HOMA1 formula and HOMA2 calculator computational methods were 0.741 and 0.680, respectively. CONCLUSIONS: The HOMA computational method is a significant determinant of the associations and classification of insulin resistance.

Variations in alanine aminotransferase levels within the normal range predict metabolic and androgenic phenotypes in women of reproductive age.

BACKGROUND AND AIMS: Obesity plays pathogenetic roles in nonalcoholic fatty liver disease (NAFLD) and hyperandrogenic states like polycystic ovary syndrome (PCOS). We tested the hypothesis that alanine aminotransferase (ALT), a marker of NAFLD, is associated with endocrine and metabolic abnormalities in women with normal ALT. METHODS AND RESULTS: Fasting glucose, insulin, total testosterone, DHEA-S, 17-hydroxyprogesterone, prolactin, leptin, soluble leptin receptor, free leptin index (FLI), lipid profile, ALT, gonadotropins, and sex hormone binding globulin (SHBG) were measured in 200 women aged 18-48 years. Beta cell function (%B), insulin sensitivity (%S) and insulin resistance were calculated using the homeostasis model assessment (HOMA-IR). Ninety-two women had PCOS (Rotterdam criteria); 64 had idiopathic hyperandrogenism; 44 were normal controls. ALT showed significant positive correlations with waist circumference (WC), systolic blood pressure, glucose, leptin, FLI, triglycerides, HOMA-IR and androgens and significant inverse correlations with leptin receptor, HDL-C, %S and SHBG. Correcting for WC and fat% showed that the associations between ALT and glucose, HOMA-IR, testosterone and free androgen index are independent of obesity. Binary logistic regression analyses showed significant association of ALT with PCOS and hyperandrogenemia. ALT ≥ 18 IU/L showed significant association with PCOS with Odds Ratio = 2.28 (95% Confidence Interval = 1.03-5.08), p = 0.043. CONCLUSIONS: In women of reproductive age, normal levels of ALT are associated with metabolic and androgenic phenotypes. We suggest a paradigm shift and extension of the routine use of ALT beyond the diagnosis of liver disease.

Bone mineral density in premenopausal Arab women with type 2 diabetes mellitus.

INTRODUCTION: This study compares an ethnically uniform group of premenopausal type 2 diabetic (T2DM) Arab women with a matched control group of nondiabetic subjects, in terms of their bone mineral density (BMD) and anthropometric measurements. METHODS: The study included 252 premenopausal Arab women. Their age ranged from 26 to 50 yr with a mean+/-SD of 43.65+/-8.97 yr. One hundred and twenty-two women were T2DM patients and 130 women were nondiabetic controls. The controls matched the subjects in gender, age, and body mass index (BMI). BMD was measured at total lumbar spine (L1-L4) and total left hip, using dual-energy X-ray absorptiometry (DXA; HOLOGIC, QRS SERIES, Europe, Belgium). Difference in BMD and its relationship to the anthropometric measurements in T2DM and control groups were assessed. RESULTS: Significant difference was found between T2DM patients and nondiabetic patients in their mean hip BMD (0.92+/-0.16 vs. 0.87+/-0.14, p<0.05) and spine BMD (0.93+/-0.15 vs. 0.88+/-0.14, p<0.01). No significant difference was found in age, height, weight, and BMI (p>0.05). The increase in hip BMD in T2DM patients normalized and the increase in spine BMD persisted after controlling for the confounding effect of age and anthropometric measurements. CONCLUSION: Premenopausal Arab women with T2DM have higher BMD at the spine than women without T2DM. The underlying mechanism causing this increase does not seem to be related to ethnicity, gender, hormonal status, or anthropometric measurements.

Which obesity index best explains the link between adipokines, coronary heart disease risk and metabolic abnormalities in type 2 diabetes mellitus?

OBJECTIVE: The aim of this study was to determine, which of: body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist circumference (WC) correlates best with adipokines and is, therefore, the most suitable for the assessment of insulin resistance (IR), metabolic syndrome (MS), type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) risk. SUBJECTS AND METHODS: We studied 248 T2DM patients classified by gender, IR, MS and CHD. Fasting adiponectin, leptin, resistin, high-sensitivity C-reactive protein (CRP), insulin, glucose, IR (HOMA), and lipid profile were measured. Univariate and multivariate regression analyses were used to find the associations of these variables with each other and with IR, MS and CHD. Receiver operating characteristic (ROC) analyses were used to find the best markers of IR, MS and CHD. RESULTS: There were gender differences in the correlations and associations of BMI, WHR, WHtR and WC with IR, MS and CHD; e.g. in males, WHR showed significant correlation with only resistin (r = 0.30) and leptin (r = 0.39) whereas in females, it showed significant correlations with only adiponectin (r = -0.33). In males and females WHR showed the weakest correlations with CRP and the adipokines and BMI showed the highest correlations. ROC analysis showed that the BMI had the highest diagnostic values for detection of IR, MS and CHD; WHR had the worst diagnostic value. CONCLUSION: Anthropometric indices show differences in performance and associations with adipokines, CRP, IR, MS and CHD. In patients with T2DM, BMI should be the preferred marker for risk assessment on account of its association with adipokines and diagnostic performance characteristics.

Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes.

BACKGROUND AND AIM: Studies suggest that iron plays a significant role in the development of diabetes and its complications. This study evaluates the associations of iron metabolism parameters with the metabolic syndrome (MS), control and complications in female patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Ferritin, soluble Transferrin Receptor (sTfR), sTfR/Log ferritin ratio (sTfR-F index), iron, full blood count and high-sensitivity C-reactive protein (hs-CRP) were determined in 110 female patients with T2DM. Steady state beta cell function (%B), insulin sensitivity (%S) and insulin resistance were assessed with homeostasis model. Patients were divided into tertiles of ferritin and sTfR-F index and according to the presence or absence of the MS and diabetic complications. Patients within the lowest tertile of the sTfR-F index had significantly higher fasting insulin, percent B, low-density lipoprotein cholesterol and Apolipoprotein B than those in the highest tertile. Ferritin showed significant correlations with insulin, percent B and inverse correlations with adiponectin and percent S. The sTfR-F index was significantly correlated with insulin, percent B and lipid parameters. Correcting for hs-CRP abolished the correlations with ferritin but not the sTfR-F index. Higher indices of body iron were significantly associated with diabetes complications but no associations were found with MS, glucose or glycemic control. Multiple regression analysis with confounding variables showed ferritin and the sTfR-F index were not independently associated with diabetes complications. CONCLUSIONS: Association of ferritin with metabolic derangements and complications in diabetes is partly dependent on association with inflammation. Iron status, estimated with the sTfR-F index, is associated with metabolic derangements and complications but the associations are dependent on other risk factors. Prospective studies that use the sTfR-F index as a marker of iron status are required to confirm the role of iron in the etiopathogenesis of T2DM and its complications.

Effect of smoking habit on circulating adipokines in diabetic and non-diabetic subjects.

BACKGROUND: Despite the well-known inverse association between smoking and body weight, there have been conflicting reports on the association between smoking and adipokines such as leptin and adiponectin. AIM: To determine and compare whether tobacco smoking (cigarettes or sheesha) affects circulating levels of adiponectin and/or influences leptin and leptin receptor (sOb-R) concentrations and free leptin in diabetic and non-diabetic subjects. METHODS AND SUBJECTS: Fasting plasma adiponectin, leptin, sOb-R, glucose, insulin, and lipid profile were determined in 236 subjects grouped as control subjects (n = 53); non-diabetic cigarette smokers (n = 34), non-diabetic sheesha smokers (n = 38), diabetic nonsmokers (n = 75) and diabetic smokers (n = 36). Uni- and multivariate regression analyses were used to determine the associations of these variables with body mass index (BMI) and smoking. RESULTS: When compared to control subjects, smoking cigarettes or sheesha was associated with significantly higher glucose, insulin resistance, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and lower serum leptin, sOb-R and free leptin. The effects of smoking on BMI, leptin and sOb-R were dose-dependent. Binary logistic regression analysis showed that smoking is a significant determinant of BMI; leptin, sOb-R, free leptin index, adiponectin and LDL-C. CONCLUSIONS: We conclude that smoking sheesha does not reduce the metabolic effects of smoking. Smoking may modify leptin receptors and modulate leptin synthesis but the weight-lowering effect may not be related to leptin-induced anorectic signals.

Determinants and associations of homocysteine and prothrombotic risk factors in Kuwaiti patients with cerebrovascular accident.

OBJECTIVE: The objective of this study was to evaluate the determinants and associations of some prothrombotic risk factors in patients with cerebrovascular accidents (CVAs). SUBJECTS AND METHODS: In this case-control study, plasma total homocysteine (tHcy), lupus anticoagulant, protein C, protein S, activated protein C resistance (APC-R) and antithrombin were measured in 102 patients (60 males and 42 females) and 167 controls (87 males, 80 females). Serum vitamin B(12), folate, red cell folate, creatinine, lipid profile and glucose were also determined. Glomerular filtration rate (GFR) was calculated. RESULTS: 13 (22%) of the 60 male patients, and 16 (39%) of the 42 female patients had hyperhomocysteinemia. Median (interquartile range) tHcy was higher in male patients [11.22 micromol/l (9.60-15.40)] than female patients [10.05 micromol/l (8.72-17.54)]. On binary logistic regression analysis, the significant (p < 0.05) determinants of tHcy were urea, creatinine and GFR. Comparing patients with control subjects showed that tHcy, age, fasting glucose, urea, serum creatinine, white blood cell count, protein S, APC-R and factor VIII were significantly higher, while protein C, factor II, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were significantly lower in patients. Lupus anticoagulant was not associated with tHcy and not detected in patients and controls. Low concentrations of vitamins B(12) and folate were not associated with tHcy. Logistic regression analysis showed a significant association of tHcy with CVA (OR = 9.55; p = 0.047) in males in the presence of other traditional CVA risk factors but tHcy is not independently associated with CVA in females. CONCLUSION: Hyperhomocysteinemia is common in Kuwaiti patients with CVA and tHcy probably interacts with prothrombotic factors (protein C, APC-R and factor VIII) to increase CVA risk. The main determinants, age and GFR markers, should be kept in mind when determining the risk associated with tHcy.

Clinical Applications of Adiponectin Measurements in Type 2 Diabetes Mellitus: Screening, Diagnosis, and Marker of Diabetes Control.

BACKGROUND: Adipose tissue-derived adiponectin has pleiotropic protective effects with suppression of inflammatory and metabolic derangements that may result in insulin resistance, metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The aim of this study was to evaluate adiponectin as a diagnostic marker of T2DM and diabetes control. METHODS: Fasting adiponectin, insulin, glucose, and HbA1c were determined in 376 patients with known T2DM and 575 subjects with undiagnosed diabetes but with family history of T2DM. Clinical and anthropometric data were recorded. Subjects were classified on the basis of degree of adiposity, insulin resistance (IR), and achievement of target HbA1c levels. Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance for undiagnosed DM. RESULTS: In undiagnosed subjects, adiponectin was significantly lower in subjects with IR and diabetic subjects compared with those without. The area under the adiponectin ROC curve for diagnosis of DM was 0.740. In known T2DM subjects, those with good control had significantly higher adiponectin (8.6 versus 7.4 µg/mL) compared to subjects with poor control. CONCLUSIONS: Adiponectin levels are associated with better glycemic control and could be a useful adjunct for screening for IR and T2DM. Therapeutic measures that increase adiponectin levels might be valuable targets for improving diabetes control and decreasing complications.

Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population.

Introduction: Studies have shown increased urine excretion of vitamin D-binding protein (VDBP) in patients with diabetic nephropathy (DN) resulting from postulated mechanisms linked to renal tubular damage. In this study, we evaluate the utility of VDBP clearance ratio as a novel determinant of glycemic status, DN, and other diabetes-associated complications. Methods: Levels of vitamin D, HbA1c, serum, urine concentrations of VDBP, and creatinine were measured in 309 subjects. The ratio of urine microalbumin to creatinine was determined to categorize subjects as normoalbuminuric (NAO), microalbuminuric (MIA), and macroalbuminuric (MAA). The VDBP clearance ratio was calculated. Results: Mean VDBP clearance ratios in NAO, MIA, and MAA were 0.7, 4, and 15, respectively. Significant positive correlations of VDBP clearance ratio were found with age, WC, SBP, DBP, TG, glucose, HbA1c, urine VDBP, urine microalbumin, and urine microalbumin/creatinine, and a significant negative correlation was found with the steady-state estimate of beta cell function (B%). Receiver operating curve (ROC) analyses of the use of VDBP clearance ratio for detection of albumin status shows a value of 0.81 for the area under the curve. Conclusions: The strong associations of VDBP clearance ratio with glycemic control and diabetes-associated complications suggest that this index could play a wider role in detection and/or pathogenesis and complications of diabetes.

Corrigendum to "Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population".

[This corrects the article DOI: 10.1155/2018/6239158.].

Determinants of glycated LDL levels in nondiabetic and diabetic hyperlipidaemic patients in Kuwait.

BACKGROUND: Glycation and oxidative modification of lipoproteins enhance the uptake of these lipids by macrophages in the early stages of atherogenesis. Measurement of blood levels of modified LDL particles could thus constitute another useful modality in identifying subjects at high risk of coronary atherosclerosis (CHD). OBJECTIVE: To measure the glycated LDL level and assess its associations with other metabolic parameters in diabetic and nondiabetic hyperlipidaemic subjects attending a Lipid Clinic in Kuwait. SUBJECTS AND METHODS: One hundred thirty-three hyperlipidaemic (HL) (72 nondiabetic (ND); 61 diabetic (D)) patients and 42 healthy control (HC) subjects had their fasting serum samples analyzed for glucose, total cholesterol (TC), triglycerides (TG), urate, HDL, LDL (by routine autoanalyzer methods), apolipoproteins A1 and B (by nephelometry), fructosamine (by spectrophotometry) and glycated LDL (gLDL) by ELISA. RESULTS: The serum gLDL level was significantly higher in HL [D+ND] than in HC (p<0.001). Within the HL group, the DHL patients had higher levels than the NDHL [p<0.001]. These differences were maintained when the gLDL level was also expressed as a percentage of the apo B concentration. The gLDL level correlated positively (p<0.01) with those of glucose, TC, TG and LDL and negatively with HDL (p<0.05) in all the subjects as a whole, healthy and hyperlipidaemia [HC+HL]. In the HL (D+ND) group as a whole, gLDL correlated significantly only with glucose [p<0.01]. In group DHL, however, gLDL correlated significantly with glucose, fructosamine and LDL [all p<0.05]. As expected, fructosamine levels were highest in the DHL group. The significant correlations established between fructosamine and the different analytes measured in the different subject groups were essentially similar to those observed for gLDL, except for the finding of persistent significant negative correlations of fructosamine with LDL in all the subject groups. CONCLUSIONS: (i) Serum gLDL levels are increased in hyperlipidaemic patients and are further increased with diabetes, suggesting that the significant glycation of LDL occurs in all hyperlipidaemic patients irrespective of their glycaemic status. (ii) The significant correlation of gLDL with glucose and fructosamine in diabetic patients would suggest its potential utility as another index of medium term glycaemic control. (iii) gLDL is easily measurable and its values could provide additional information in ascertaining an individual's aggregate CHD risk.

Evaluation of cystatin C and beta-2 microglobulin as markers of renal function in patients with type 2 diabetes mellitus.

BACKGROUND: Despite recent studies showing that serum cystatin C (CC) is a better marker for GFR than the ubiquitously used serum creatinine, its clinical utility remains under evaluation. METHODS: To evaluate their usefulness in patients with type 2 diabetes mellitus (DM), serum concentrations of CC, beta-2 microglobulin (B2M) and creatinine were measured in 105 (38 males, 67 females) Kuwaiti patients with type 2 DM. The results were compared with creatinine clearance (Ccr), which was measured (mCcr) and estimated (eCcr) with the Cockroft-Gault formula, and correlated with 24-h urine protein and early morning urine albumin/creatinine excretion ratio. RESULTS: In patients with eCcr and mCcr results (n=51), eCcr and mCcr showed significant correlation with each other (r's=.86, P<.0001) with no significant difference between the two. In all patients (n=105), CC and B2M showed significant correlation with each other (r's=.82, P<.0001) and with serum creatinine concentration (r's=.77 and.84, respectively, P<.0001). Serum CC, B2M and creatinine showed significant (P<.001) inverse correlation with eCcr (r's=-.63, -.61 and -.76, respectively). Partial correlations after correcting for age and sex improved the correlation of serum creatinine with eCcr (r=-.81, P<.0001), but there was no significant change in the correlations of CC and B2M with eCcr (r=-.65, P<.0001 and r=-.62, P<.0001, respectively). Receiver operating characteristic (ROC) plots for serum CC, B2M and creatinine for detection of changes in the eCcr showed that the area under the ROC curve+/-S.E. is 0.897+/-0.119 for CC, 0.871+/-0.091 for B2M and 0.785+/-0.087 for serum creatinine. There was no statistically significant difference between the areas under the curve (AUC) for serum creatinine and CC (P=.07) and B2M (P=.12). CC had the highest sensitivity for detection of eCcr (<60 ml/min/1.73 m(2)) at routinely used cutoff values. CC was also the best discriminator when patients with normoalbuminuria were compared with patients with microalbuminuria. CONCLUSION: Although there is no significant difference in the overall diagnostic accuracies of CC, B2M and creatinine for the detection of changes in the GFR, CC is the most sensitive marker at routinely used cutoff values and would be more clinically useful than B2M or serum creatinine in diabetic patients.