Lipid Testing Trends Before and After Hospitalization for Myocardial Infarction Among Adults in the United States, 2008-2019.

Background: Routine monitoring of low-density lipoprotein cholesterol (LDL-C) identifies patients who may benefit from modifying lipid-lowering therapies (LLT). However, the extent to which LDL-C testing is occurring in clinical practice is unclear, specifically among patients hospitalized for a myocardial infarction (MI). Methods: Using US commercial claims data, we identified patients with an incident MI hospitalization between 01/01/2008-03/31/2019. LDL-C testing was assessed in the year before admission (pre-MI) and the year after discharge (post-MI). Changes in LDL-C testing were evaluated using a Poisson model fit to pre-MI rates and extrapolated to the post-MI period. We predicted LDL-C testing rates if no MI had occurred (ie, based on pre-MI trends) and estimated rate differences and ratios (contrasting observed vs predicted rates). Results: Overall, 389,367 patients were hospitalized for their first MI during the study period. In the month following discharge, 9% received LDL-C testing, increasing to 27% at 3 months and 52% at 12 months. Mean rates (tests per 1000 patients per month) in the pre- and post-MI periods were 51.9 (95% CI: 51.7, 52.1) and 84.4 (95% CI: 84.1, 84.6), respectively. Over 12 months post-MI, observed rates were higher than predicted rates; the maximum rate difference was 66 tests per 1000 patients in month 2 (rate ratio 2.2), stabilizing at a difference of 15-20 (ratio 1.2-1.3) for months 6-12. Conclusion: Although LDL-C testing increased following MI hospitalization, rates remained lower than recommended by clinical guidelines. This highlights a potential gap in care, where increased LDL-C testing after MI may provide opportunities for LLT modification and decrease risk of subsequent cardiovascular events.

Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy.

BACKGROUND: This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. METHODS: In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period. RESULTS: Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively). CONCLUSIONS: Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm.

National Prevalence of Self-Reported Coronary Heart Disease and Chronic Stable Angina Pectoris: Factor Analysis of the Underlying Cardiometabolic Risk Factors in the SuRFNCD-2011.

BACKGROUND: Coronary heart disease (CHD) is one of the most common causes of mortality worldwide. The national prevalence remains unclear in most of the developing countries. OBJECTIVE: This study sought to estimate national prevalence of self-reported CHD and chronic stable angina pectoris in the general adult population of Iran using data from the fourth round of the Surveillance of Risk Factors of Non-Communicable Diseases (SuRFNCD-2011) survey. METHODS: The analysis comprised data of 11,867 civilian, nonhospitalized and noninstitutionalized residents ages 6 to 70 years of age. The calculated prevalence of self-reported CHD and chronic stable angina pectoris were extrapolated to the Iranian adult population who were >20 years old using the complex sample analysis. The factor analysis was performed for clustering of the associated cardiometabolic risk factors among people ages >40 years of age. RESULTS: The estimated national prevalence of self-reported CHD and chronic stable angina pectoris were 5.3% (95% confidence interval: 4.6 to 5.9) and 7.7% (95% confidence interval: 4.6 to 8.7), respectively. Higher prevalence of these conditions were observed among the older people, urban residents, and women. Factor analysis generated 4 distinct factors that were mainly indicators of dyslipidemia, hypertension, central obesity, hyperglycemia, and tobacco smoking. The factor incorporating hypertension was a significant correlate of self-reported CHD. CONCLUSIONS: We report concerning prevalence of self-reported CHD and chronic stable angina pectoris in the adult population of Iran. The constellation of raised systolic and diastolic blood pressures was significantly predictive of the presence of self-reported CHD.

Intercellular adhesion molecule-1 in diabetic patients with and without microalbuminuria.

BACKGROUND: Nephropathy is a major complication of type 2 diabetes mellitus (T2DM) and is heralded by the insidious development of microalbuminuria (MA). It is suggested that the serum levels of Intercellular Adhesion Molecule-1 (ICAM-1) is correlated with diabetic nephropathy. In this cross-sectional study, we evaluated serum ICAM-1 level in diabetic patients with and without MA. METHODS: A total of 187 participants were enrolled and were classified into three groups including 40 healthy controls and 2 diabetic groups with (n = 59) or without MA (n = 88). Serum levels of ICAM-1, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and C-reactive protein (CRP) were measured in all three groups. Statistical analyses were performed using the SPSS software. A P-value less than 0.05 was considered statistically significant. RESULTS: Serum levels of ICAM-1 were significantly higher in diabetic patients irrespective of MA. Moreover, ICAM-1 levels in patients with MA were significantly higher than patients without MA. Patients with MA had significantly higher age and blood pressure compared to those without MA (P = 0.001). Serum levels of ICAM-1 were significantly correlated with age and HbA1c. CONCLUSIONS: Overall, serum ICAM-1 levels were significantly higher in T2DM patients with MA and it may be associated with the severity of diabetic kidney disease.

Zero and Five End-Digit Preference and Blood Pressure Quality of Care Revisited.

BACKGROUND: To determine the rate of zero and five end-digit preference (EDP) for systolic and diastolic blood pressures (SBP and DBP, respectively) and risk factors amongst a representative sample of Iranian adults in the year 2011. METHODS: Data gathered from 7997 Iranian adults aged 25-70 were extracted from the database of the sixth Survey of Surveillance of Risk Factors of Non-communicable Diseases, which surveyed a total of 11,864 individuals aged 6 to 70 years. Multilevel multiple logistic regression was used to identify the independent factors associated with zero or five EDP. RESULTS: The prevalence of three serial zero or five EDP for SBP and DBP were 18.5% (95% CI: 11.3%-25.7%). SBP ≥140 mmHg (OR = 0.78; 95% CI: 0.65-0.95), DBP ≥90 mmHg (OR = 0.71; 95% CI: 0.58-0.88), and a positive family history of diabetes (OR = 0.77; 95% CI: 0.66-0.9) were found as protective factors against zero or five EDP in blood pressure recording the male gender (OR = 1.18; 95% CI: 1.04-1.35) was found to be its independent risk factor. CONCLUSION: Sex, SBP, DBP and family history of diabetes were found to be the main independent determinants of EDP in our country which underscores the importance of assessing the many patient-related factors in the studies involving EDP as part of BP monitoring in public health care.

Inverse Association of Peripheral Orexin-A with Insulin Resistance in Type 2 Diabetes Mellitus: A Randomized Clinical Trial.

AIMS: To investigate the association between serum orexin concentrations and insulin resistance/sensitivity in a sample of patients with type 2 diabetes mellitus, and to study the effects of anti-hyperglycemic treatment on orexin concentrations over three months. METHODS: This study was designed as a randomized, open-label, clinical trial. Before allocation, sixty medication-naïve, newly-diagnosed, type 2 diabetes patients underwent a 75 g oral glucose tolerance test (OGTT). Afterwards, using a randomized trial design (IRCT201102275917N1) patients were allocated to either the metformin (1000 mg daily) or pioglitazone (30 mg daily) arm, and were reexamined after three months. Serum insulin, plasma glucose, and orexin concentrations were measured at baseline, during OGTT, and after three months. RESULTS: Orexin concentrations significantly decreased after OGTT (0 vs. 120 min: 0.63 ± 0.07 vs. 0.31 ± 0.03 ng/ml, p < 0.001). Insulin resistance determined by homeostasis model assessment of insulin resistance (HOMA-IR) was significantly and negatively correlated with orexin (r = -0.301, p = 0.024). Furthermore, orexin concentrations were significantly and positively correlated with the insulin sensitivity index derived from OGTT (r = 0.326, p = 0.014). Three-month treatment with metformin and pioglitazone significantly improved insulin sensitivity and increased orexin concentrations by 26% (p = 0.025) and 14% (p = 0.076), respectively. Between-group analysis showed that changes in orexin concentrations with metformin and pioglitazone were not significantly different (p = 0.742). CONCLUSIONS: There was a negative association between peripheral orexin concentrations and insulin resistance in type 2 diabetes patients. Three-month anti-hyperglycemic treatment with proportionate doses of metformin or pioglitazone increased orexin concentrations via amelioration of insulin resistance and improvement of glycemic control.

Diabetes in Iran: Prospective Analysis from First Nationwide Diabetes Report of National Program for Prevention and Control of Diabetes (NPPCD-2016).

We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015-2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.

Association of Human Leukocyte Antigens Class I and II with Graves' Disease in Iranian Population.

BACKGROUND: Graves' disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA) and GD among Iranians is scarce. OBJECTIVE: To identify HLA polymorphisms that might confer susceptibility or protect against GD. METHODS: Eighty unrelated patients with a confirmed diagnosis of GD were included in the case group. The control group consisted of 180 unrelated healthy individuals with normal thyroid function tests. The polymerase chain reaction with sequence specific primers (PCR-SSP) method was used for HLA typing. RESULTS: Frequencies of HLA-A*68 (15.6% vs. 4.2%, p=0.004) and B*08 (8.8% vs. 2.5, p=0.030) were significantly higher in patients with GD compared with healthy controls. No patients with GD had HLA-A*33, whereas it was found in 7.0% of the controls (p=0.011). HLA-DQB1*0201 was significantly less frequent among patients with GD (15.6% vs. 26.8%, p=0.040). Additionally, patients with GD were significantly less bound to have HLA-DQA1*0201 (6.2% vs. 15.1%, p=0.045). Concerning allelic distributions, no noticeable difference was found between GD patients with and without Graves' ophthalmopathy (p>0.05 in all cases). CONCLUSION: In the Iranian population, HLA-A*68 and -B*08 confer susceptibility to GD, whereas HLA-A*33, -DQB1*0201, and -DQA1*0201 appear to have protective roles.

Association of peripheral nesfatin-1 with early stage diabetic nephropathy.

BACKGROUND: Nesfatin-1 is a newly found anorectic neuropeptide with potent metabolic regulatory effects that its circulating levels are shown to be elevated in diabetes. We compared serum nesfatin-1 in patients with type 2 diabetes and microalbuminuria (30mg/day≤urinary albumin excretion (UAE) <300mg/day) with their control patients with type 2 diabetes and normoalbuminuria (UAE <30mg/day). PATIENTS AND METHODS: In a cross sectional setting, 44 adult patients with type 2 diabetes and microalbuminuria and 44 control patients with type 2 diabetes and normoalbuminuria were evaluated. Serum levels of nesfatin-1 along with demographic, clinical and biochemical factors associated with diabetes was measured. RESULTS: Mean peripheral concentrations of nesfatin-1 were significantly higher in patients with diabetes who had microalbuminuria compared to normoalbuminuric control patients (175.27±25.96pg/ml vs. 134.66±23.18pg/ml, respectively; p value<0.001). Significant positive correlations were found between circulating nesfatin-1 levels and the following case-mix variables: duration of diabetes, glycated hemoglobin, plasma creatinine, UAE and serum uric acid. In the multivariate logistic regression and after adjustment for a constellation of potentially confounding variables associated with diabetic kidney disease (DKD), circulating nesfatin-1 was the only variable significantly associated with microalbuminuria (odds ratio [95% confidence interval]=1.224 [1.007-1.487], p value=0.042). CONCLUSION: In patients with type 2 diabetes, circulating nesfatin-1 appears to be associated with microalbuminuria independent of other established risk factors of DKD. The underlying pathophysiological mechanisms and the prognostic significance of this association remain to be elucidated.

Prevalence of metabolic syndrome in Iran: A 2011 update.

BACKGROUND: The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. METHODS: Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. RESULTS: In 2007, the prevalence of metabolic syndrome among adults aged 25-64 years was 35.95 (95% confidence interval [CI] 34.27-37.63), which decreased to 32.96 (95% CI 30.73-35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97-54.79), 36.99 (95% CI 34.52-39.45), 54.72 (95% CI 50.87-58.57), 38.92 (95% CI 36.19-41.64), and 24.97 (95% CI 22.02-27.93) respectively. CONCLUSIONS: Over the period 2007-11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome.

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes.

BACKGROUND AND AIMS: We aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. METHODS: In an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. RESULTS: We found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060-0.689], pfor trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%-10.22%), p value < 0.05). CONCLUSIONS: Serum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure.

Awareness, Treatment and Control of Pre-hypertension and Hypertension among Adults in Iran.

BACKGROUND: Hypertension is a major risk factor for non-communicable diseases. Yet, Nation-wide prevalence and trend reports in developing countries are sparsely available. METHODS: Data from three cycles of Survey of Risk Factors of Non-communicable Diseases (SuRFNCD) 2005 - 2011 were aggregated. In 2011, 8218 adults aged 25 - 70 years were enrolled. For trend analysis 68850, 4184, and 7416 adults aged 25 - 64 years were included from 2005, 2007, and 2011 surveys, respectively. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or receiving anti-hypertensive medication. Pre-hypertension was defined as SBP between 120 - 139 or DBP between 80 - 89 mmHg. The status of awareness, non-pharmacologic treatment (management), pharmacologic treatment, and control (SBP < 140 mmHg, and DBP < 90 mmHg) among hypertensive individuals were also determined. RESULTS: 25.6% (95%CI: 23.5 - 27.5) of the adults aged 25 - 70 years had hypertension and 39.8% (95%CI: 37.8 - 41.9) had pre-hypertension. The prevalence of hypertension was greater among older adults (P < 0.001), women (P = 0.013), and urban-dwellers (P = 0.027). In 2005 - 2011, the proportion of adults with hypertension (25.7% to 24.1%) and pre-hypertension (45.5% to 40.4%) significantly decreased. In 2011, rates for awareness, management, treatment, and control among hypertensives were 43.2% (95%CI: 40.0 - 46.4), 40.3% (95%CI: 37.0 - 43.6), 34.8% (95%CI: 31.5 - 38.2), and 38.6% (95%CI: 33.1 - 44.2), respectively. Over time, status of awareness, management, treatment and control was significantly improved and was more salient among men (P < 0.05 for all analyses). CONCLUSIONS: The prevalence of hypertension and pre-hypertension is gradually declining. Despite improvements in awareness, management, treatment and control, these decline rates are still low and initiative strategies need to be implemented to further improve the current status.

Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study.

BACKGROUND: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). METHODS: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. RESULTS: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. CONCLUSIONS: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

Raised serum 25-hydroxyvitamin D levels in patients with active diabetic foot ulcers.

Studies have emerged to demonstrate bidirectional changes in circulating cytokines of inflammation in active diabetic foot ulcers (DFU). To further expand the understanding of inflammatory status present in chronic active DFU, we comparatively assessed the associations of selected pro-inflammatory cytokines and 25-hydroxyvitamin D (25(OH)D) with the presence of DFU. In a cross-sectional setting, thirty patients with type 2 diabetes and active DFU matched with thirty control non-ulcerative patients with type 2 diabetes and twenty-eight healthy subjects underwent anthropometric and biochemical assessment of study parameters. Recruited patients with DFU were selected from the grade II active chronic DFU at the time of hospitalisation according to the University of Texas wound classification system. Patients with DFU and controls had comparable age, sexual distribution, diastolic blood pressure and TAG, LDL-cholesterol and glycated Hb. The trend changes from healthy controls towards DFU showed a significant increase for serum monocyte chemoattractant protein-1, IL-6, 25(OH)D and highly sensitive C-reactive protein and a decrease for IL-8. In the multivariate adjusted logistic regression model, 25(OH)D emerged as the only independent correlate of DFU (OR 2·194; 95 % CI 1·003, 4·415). Unprecedented increase of serum 25(OH)D in chronic active DFU is possibly related to a selective alteration in the inflammatory status. In particular, 25(OH)D and IL-8 seem to share a common pathway in the pathogenesis of diabetic foot.

Serum fibroblast growth factor 21 concentrations in type 2 diabetic retinopathy patients.

AIMS/PURPOSE: Fibroblast growth factor 21 (FGF21) is a major metabolic regulator in the body that has been shown to be elevated in a number of metabolic disturbances including type 2 diabetes mellitus (T2DM) and the metabolic syndrome. However, little is known regarding the circulating levels of FGF21 in type 2 diabetic retinopathy (T2DR) and its association with the severity of the condition. METHODS: In a cross-sectional setting, 142 individuals, consisting of (1) T2DM patients without T2DR, (2) T2DM patients with T2DR, and (3) healthy control subjects were recruited for this study. Various clinical and biochemical parameters were assessed and entered for analysis. RESULTS: Serum FGF21 levels were significantly elevated in T2DM subjects without retinopathy (103.50 [75.75] pg/mL) compared with healthy controls (99.00 [126.75] pg/mL). Circulating FGF21 levels were comparable across different stages of T2DR (233.00 [109.00] for nonproliferative type 2 diabetic retinopathy [NPT2DR] vs. 215.00 [122.00] for proliferative type 2 diabetic retinopathy [PT2DR] groups, P=361). FGF21, triglycerides, and duration of diabetes mellitus were significantly associated with T2DM in baseline models. However, after adjustment for potential confounders, in the final multivariate model, FGF21 emerged as the only significant factor associated with T2DM (OR=13.772, 95% CI=3.062-61.948, P=001). CONCLUSIONS: Serum FGF21 concentrations are markedly elevated in patients with T2RN. The association between FGF21 and T2DR appears to be independent of the effects of potential confounding variables. These findings may suggest FGF21 as a novel surrogate diagnostic biomarker in initial stages of T2DR (particularly with FGF21 values above 135.5pg/mL).

Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis.

OBJECTIVE: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS). METHODS: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms. RESULTS: Two SCN10A polymorphisms in high linkage disequilibrium (r(2) = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10(-4); rs6801957: p = 0.0025). Patients with MS with rs6795970(AA) genotype performed significantly worse than rs6795970(G) carriers in MSFC (p = 1.8 × 10(-4)) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970(AA) carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A-genotype effect was observed on MSFC performance in healthy participants. CONCLUSIONS: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.

Association of osteoprotegerin with peripheral artery disease in patients with type 2 diabetes.

BACKGROUND: Osteoprotegerin plays a critical role in the pathogenesis of atherosclerosis. Elevated osteoprotegerin concentrations have been reported in microvascular complications of diabetes. Patients with diabetes are at increased risk of macrovascular complications, particularly peripheral artery disease (PAD). AIM: To investigate the association between osteoprotegerin concentration and PAD in diabetes. METHODS: In a cross-sectional setting, patients with type 2 diabetes for>5 years and no apparent diabetic foot ulcer were recruited. Patients underwent colour Doppler ultrasonography of lower limbs and were designated PAD+ if arterial narrowing was detected. Ankle-brachial index (ABI) was measured. Serum osteoprotegerin concentrations were determined. RESULTS: Ninety-eight patients (47 PAD+, 51 PAD-) were recruited. Osteoprotegerin concentrations (median [interquartile range]) were significantly higher in PAD+ versus PAD- patients (0.80 [0.50-1.95] ng/mL vs 0.30 [0.25-0.40] ng/mL; P<0.001). In logistic regression, log-osteoprotegerin was a predictor of PAD in univariate and multivariable analyses. In the final multivariable model, adjusting for age, sex, body mass index, smoking, hypertension, glycaemic control, lipid profile, renal function and C-reactive protein, one standard deviation increase in log-osteoprotegerin was associated with a more than twofold increase in the risk of having PAD (odds ratio 2.26, 95% confidence interval 1.50-3.40). In PAD+ patients, osteoprotegerin was a significant predictor of disease severity, determined by ABI and percentage of vessel occlusion in univariate and multivariable models. CONCLUSIONS: Osteoprotegerin concentrations are increased in patients with diabetes and PAD. Osteoprotegerin is an independent predictor of the presence and severity of PAD in diabetic patients.

Complementary and alternative medicine for the treatment of obesity: a critical review.

CONTEXT: Obesity and its associated morbidities pose a major health hazard to the public. Despite a multiplex of available diet and exercise programs for losing and maintaining weight, over the past years, interest in the use of complementary and alternative medicine (CAM) for obesity treatment has greatly increased. EVIDENCE ACQUISITION: We searched PubMed, Google scholar and the Cochrane databases for systemic reviews, review articles, meta-analysis and randomized clinical trials up to December 2013. RESULTS: In this review, the efficacy and safety of the more commonly used CAM methods for the treatment of obesity, namely herbal supplements, acupuncture, and non-invasive body-contouring, are briefly discussed. The evidence supporting the effectiveness and safety of these methods is either lacking or point to a negligible clinical benefit, barely surpassing that of the placebo. Furthermore, several limitations are observed in the available scientific literature. These shortcomings include, without being limited to, uncontrolled trial designs, non-random allocation of subjects to treatment arms, small number of patients enrolled, short durations of follow-up, and ambiguous clinical and laboratory endpoints. CONCLUSIONS: Further investigations are necessary to accurately determine the efficacy, safety, standard dosage/procedure, and potential side effects of the various CAM methods currently in use.