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.].

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.

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.

Musculoskeletal pain: should physicians test for vitamin D level?

AIM: The aim of this study was to evaluate vitamin D levels using a reliable method in patients with regional and generalized musculoskeletal (MSK) pain in comparison to healthy controls. METHODS: A consecutive prospective case control cohort was recruited. Patients with generalized MSK pain, for example, fibromyalgia (FM), and regional MSK pain, for example, nonspecific low back pain (LBP) and knee osteoarthritis (OA) were screened for 25 hydroxy-vitamin D [25(OH)D3 ] levels over a period of 9 months in a hospital-based setting. RESULTS: One hundred and twenty-four patients and 82 age-sex matched controls were evaluated. The mean age for patients was 41.71 ± 13.86 years. Of the 124 patients, 118 (95%) were female, 77 (62.6%) had FM, 18 (14.6%) had LBP and 28 (22.8%) had knee OA. All patients had normal muscle power; 83.7% of females wore long garments, 11.4% wore veils, 95.5% had sun exposure < 10 min/day and 58.5% were multiparaous; 7.3% were strict vegetarians, 45.5% took inadequate dairy products. The mean calcium, parathyroid hormone, alkaline phosphatase and albumin levels were within normal limits for all study subjects. The vitamin D level was deficient in all patients. There was no statistical difference between the mean vitamin D values of the patients and controls, 27.61 ± 13.06 and 25.82 ± 15.06 nmol/L respectively, (P = 0.368). CONCLUSION: Our findings suggest that it is unlikely that measuring vitamin D will be of diagnostic value in the routine assessment of regional and generalized MSK pain.

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.

Higher levels of alanine aminotransferase within the reference range predict unhealthy metabolic phenotypes of obesity in normoglycemic first-degree relatives of patients with type 2 diabetes mellitus.

Obesity is a heterogeneous disorder with metabolically healthy and unhealthy phenotypes and varying degrees of cardiometabolic complications. To evaluate whether alanine aminotransferase (ALT) could be used for identification of obese phenotypes, the authors measured ALT, adiponectin, leptin, leptin receptor, free leptin index, high-sensitivity C-reactive protein, fasting insulin, glucose, and full lipid profile in 486 (176 men and 310 women) normoglycemic first-degree relatives of patients with type 2 diabetes mellitus with negative medication history and hepatitis screen. Patients were classified into obesity phenotypes on the basis of the degree of adiposity and the International Diabetes Federation criteria for the metabolic syndrome. One hundred and thirty-seven (28%) patients were positive for the metabolic syndrome, 32 (7%) had normal weight but metabolically unhealthy phenotype, and 201 (41%) were obese but metabolically healthy. ALT showed significant positive correlations with body mass index, waist circumference, beta-cell function, insulin, homeostasis model assessment for insulin resistance, high-sensitivity C-reactive protein, total cholesterol, and triglycerides and increased with increasing number of metabolic syndrome components. Binary logistic regression analyses showed that higher ALT levels within the normal range were significantly associated with the metabolic syndrome. ALT could be used for identification of the metabolically obese phenotype. Lowering the ALT upper normal reference limit will facilitate earlier detection of risky phenotypes of obesity.

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.

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.

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.

Plasma concentrations of C-reactive protein and total homocysteine in relation to the severity and risk factors for cerebrovascular disease.

Higher C-reactive protein (CRP) and plasma homocysteine (tHcy) concentrations have been shown to indicate increased risk of coronary heart disease and cerebrovascular disease (CVD), but the mechanisms by which they increase the risk of atherothrombotic disease are under investigation. This study evaluates the associations of high-sensitivity C-reactive protein (hs-CRP) and tHcy with the risk factors, severity, and outcome on discharge in patients with CVD. hs-CRP, fasting tHcy, and lipid profile were determined in 50 patients with CVD and 20 healthy control subjects. Clinical data, National Institutes of Health stroke scale (NIHSS) on admission and disability Rankin scale on discharge, were recorded. Based on epidemiologic studies, cutoff points of 1.5 mg/L (hs-CRP) and 15mumol/L (tHcy) were used to indicate increased risk. Univariate and multivariate logistic regression analyses were used to relate tHcy with other CVD risk factors, NIHSS on admission and the disability Rankin scale on discharge. Overall, 38% of patients had increased hs-CRP and 26% had elevated tHcy. hs-CRP (P = 0.005) and tHcy (P < 0.0001) concentrations were significantly higher in patients compared with controls, and these differences remained significant after correction for age and sex. tHcy showed significant correlations with hs-CRP (rs = 0.35; P = 0.003) and low-density lipoprotein-cholesterol (LDL-C; rs = 0.49; P = 0.005). Logistic regression analysis with CVD as the dependent variable showed significant association with hs-CRP (P = 0.01) and tHcy (P < 0.0001) after adjustment for potential confounders. hs-CRP showed increased trend with disease severity and significant association with the disability Rankin scale (P = 0.033). These data support 4 main conclusions: (1) Elevation of hs-CRP and tHcy are common in CVD; (2) the significant relationship between tHcy and hs-CRP suggests that the association of tHcy with CVD risk may be dependent on inflammation-related mechanisms; (3) increased hs-CRP and tHcy show that patients with CVD may be at greater risk of subsequent coronary heart disease; and (4) admission hs-CRP could be used as an indicator of prognosis.

Determinants of plasma homocysteine in relation to hematological and biochemical variables in patients with acute myocardial infarction.

BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. This study evaluates the determinants and associations of tHcy in patients presenting with acute myocardial infarction (AMI). METHODS: Plasma concentration of tHcy, protein C, protein S, and antithrombin were measured in 210 (177 males and 33 females) patients with first AMI and 167 (87 males and 80 females) controls. Serum vitamin B12, folate, creatinine, lipid profile, fasting glucose, full blood count and red cell folate were determined. Creatinine clearance was calculated using the modification of diet in renal disease formula. Univariate and multivariate analyses were used to determine the associations of tHcy. RESULTS: Mean tHcy was higher in male than female patients. On logistic regression analysis, the most important determinants oftHcy in the patients were age, creatinine, creatinine clearance, vitamin B12 and red cell folate. When study patients were compared with the controls, tHcy, fasting glucose and serum creatinine were significantly higher, while creatinine clearance and HDL cholesterol were significantly lower in the study patients. Logistic regression analysis showed significant association of tHcy with AMI, odds ratio = 1.39, in the presence of other confounding factors. CONCLUSIONS: Our results show that tHcy is a significant risk factor for CAD in our patient population. The determinants in the patients are age, glomerular filtration rate and the status of vitamins B12 and folate. The above determinants should be kept in mind when using tHcy as a risk factor for CAD.

Cysticercosis: imported and autochthonous infections in Kuwait.

Intracerebral and non-central nervous system (non-CNS) cysticercosis caused by the larval pork tapeworm Taenia solium was diagnosed in patients in an Islamic state. The mode of transmission and challenges in diagnosis are highlighted. Sixteen patients with neurocysticercosis and six with non-CNS lesions were diagnosed by imaging studies (computerized tomography [CT]/magnetic resonance imaging [MRI]) and serology (ELISA and/or enzyme-linked immunoelectrotransfer blot assay [EITB]). Four of 55 family members, including servants, tested for antibodies were positive by the EITB and ELISA. Only one of these sera tested for antibodies to adult T. solium was positive: that of the cook, the probable source of the infection. We postulate a similar mode of transmission in the other Kuwaitis. Evaluation of several commercially available ELISA kits showed they were of poor specificity. Even in countries where pork consumption is proscribed by religious laws, physicians should include cysticercosis in their differential diagnosis in patients with neurological symptoms or non-CNS lesions, especially in non-endemic countries with a large expatriate population such as Kuwait. In children particularly, and in this region, suspected tuberculous lesions on CT must be investigated to rule out cysticerci by a more diligent use of the sensitive and specific EITB assay. Failure to understand the local epidemiology leads to empirical, inappropriate and prolonged therapy for chronic disease.