Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Correlation Between SNPs at the 3'UTR of the FGF2 Gene and Their Interaction with Environmental Factors in Han Chinese Diabetic Peripheral Neuropathy Patients.

FGF2 is a neurotrophic factor that can act as a key regulatory molecule of neuroprotection, neurogenesis, and angiogenesis in various injuries. To explore the genetic background of the FGF2 gene on DPN development, this study analyzed the correlation between SNPs in the 3'UTR of the FGF2 gene and their interaction with environmental factors in DPN patients of Han Chinese nationality. Sanger sequencing was used to analyze the FGF2 genotypes at the rs1048201, rs3804158, rs41348645, rs6854081, rs3747676, rs7683093, rs1476215, and rs1476217 loci in 150 DPN patients, 150 NDPN patients, and 150 healthy control patients. Plasma FGF2 levels were measured in all subjects by using ELISAs. Subjects carrying the T allele at the rs1048201 locus in the FGF2 gene had a significantly lower risk of developing DPN compared with subjects carrying the C allele (OR = 0.43, 95% CI = 0.33-0.56, p < 0.01). Subjects with the G genotype at the rs6854081 locus had an exceptionally higher risk of developing DPN than subjects with the T allele (OR = 1.66, 95% CI = 1.39-1.89, p < 0.01). Individuals harboring the G allele at the rs7683093 locus had a markedly higher risk of DPN than patients with the C allele (OR = 1.63, 95% CI = 1.36-1.87, p < 0.01). Finally, individuals having the A genotype at the rs1476215 locus had a significantly higher risk of DPN than individuals carrying the T allele (OR = 1.82, 95% CI = 1.53-2.02, p < 0.01). There was an interaction between age and alcohol consumption and the SNP rs7683093. SNPs at rs1048201, rs6854081, rs7683093, and rs1476215 in the FGF2 3'UTR were strongly associated with plasma levels of FGF2 (p < 0.05). SNPs at the rs1048201, rs6854081, rs7683093, and rs1476215 loci in the FGF2 gene were significantly associated with the risk of DPN. A possible mechanism is that these SNPs affect the expression level of FGF2 by interrupting the binding of microRNAs to target sites in the 3'UTR.

The prevalence of microvascular complications in Waikato children and youth with type 1 diabetes has reduced since 2003.

AIMS: To determine whether glycaemic control and the prevalence of microvascular complications in Waikato children/youth with type 1 diabetes (T1D) has changed since 2003. METHODS: A retrospective review was performed of clinical records of children and youth with T1D who were under the care of the Waikato Paediatric and Young Adult Diabetes Services between March 2016 and March 2017. Comparisons were made to published data from the same service in 2003. RESULTS: Despite a more than two-fold increase in insulin-pump therapy since 2003, glycaemic control was not significantly improved in either children or youth. However, since 2003 there has been a significant reduction in the prevalence of diabetic retinopathy (24.6% vs 6.0%; P=0.003) and nephropathy (6.0% vs 25.4%; P=0.002), while symptomatic diabetic neuropathy remains rare. This reduction occurred despite a significant increase in obesity and hypertension, and no significant difference in the rates of dyslipidaemia or smoking. CONCLUSIONS: There has been a marked reduction in microvascular complications in Waikato youth and young adults with type 1 diabetes, but the reasons for the reduction are not clear given there has been no significant improvements in glycaemic control.

The increased risk of microvascular complications in South Asians with type 1 diabetes is influenced by migration.

AIM: We aimed to explore the association between South Asian ethnicity and complications of type 1 diabetes, and whether this is affected by migration. METHODS: In this retrospective cohort study, data on diabetes control and complications were obtained for South Asians in India (South AsiansIndia , n = 2592) and the UK (South AsiansUK , n = 221) and white Europeans in the UK (n = 1431). Multivariable logistic regression was used to identify associations between ethnicity and diabetic kidney disease, retinopathy and neuropathy adjusting for age, sex, BMI, disease duration, HbA1c , blood pressure (BP) and cholesterol. RESULTS: South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease [odds ratio (OR) 5.0, 95% confidence intervals (CI) 3.6-7.1] and retinopathy (OR 1.8, 95% CI 1.2-2.5), but lower odds of neuropathy (OR 0.5, 95% CI 0.4-0.6) than white Europeans. South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease (OR 3.0, 95% 1.8-5.3) than South AsiansUK , but there was no significant difference in the odds of other complications. CONCLUSIONS: In this hypothesis-generating study, we report that South Asian ethnicity is associated with greater risk of diabetic kidney disease and retinopathy, and lower risk of neuropathy than white European ethnicity. Part of the excess diabetic kidney disease risk is reduced in South AsiansUK . These associations cannot be accounted for by differences in vascular risk factors. Our findings in South Asians with type 1 diabetes mirror previous findings in type 2 diabetes and now need to be validated in a study of the effect of ethnicity on type 1 diabetes complications where healthcare is provided in the same setting.

RANKL Gene Polymorphism as a Potential Biomarker to Identify Acute Charcot Foot Among Indian Population With Type 2 Diabetes: A Preliminary Report.

Studies addressing the link between gene polymorphism and Charcot neuropathic osteoarthopathy (CN) have been limited to analyse osteoprotegerin gene. Aim is to understand the association of RANKL gene variants on the susceptibility of diabetic neuropathy and CN and to measure the serum levels of sRANKL among Indian population with type 2 diabetes. 77 subjects (48 males: 29 females) were recruited and divided into 3 groups. Group 1 Control: normal glucose tolerance (NGT). Group 2: Type 2 diabetes mellitus and neuropathy (DPN). Group 3: Established type 2 diabetes mellitus, DPN, and CN. Subjects were genotyped for RANKL SNP 693 C/G and 643 C/T using polymerase chain reaction-restriction fragment length polymorphism. sRANKL levels were measured using ELISA (enzyme-linked immunosorbent assay). The serum levels of sRANKL were significantly different between the 3 groups. In RANKL -643 C/T the frequency of "CT" genotype and the minor allele "T" was greater among the DPN and CN group compared with the NGT. Further statistical analysis found a significant difference in genotypic frequencies between DPN and NGT subjects with CT genotype. In RANK L -693 C/G the frequency of homozygote mutant "GG" and the minor allele "G" was greater among the DPN and CN group compared with the NGT. Significant differences in genomic frequencies were observed among "GG" genotype. RANKL -643 C/T was significantly associated with DPN alone while -693 C/G was significantly associated with both DPN and CN. Thus, the study suggests RANKL polymorphism might be considered as an independent risk factor for the development of CN.

Risk Factors for Microvascular Complications of Diabetes in a High-Risk Middle East Population.

AIMS: Much of the diabetes burden is caused by its complications. This cross-sectional study aimed to determine the prevalence and risk factors for diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) in a high-risk population. METHODS: We collected information via a structured questionnaire and directly from the patient's record on 1034 adult type 2 diabetic patients who were attending outpatient clinics in Qatar. RESULTS: The mean age of the patients was 55 ± 10 years, and the mean duration of diabetes was 12.4 ± 8.9 years. Forty-five percent had one or more microvascular complications. Shared risk factors for multiplicity and for individual complications included family history, severity and duration of diabetes, and hypertension, but some risk factors were specific for individual microvascular complications. Early age at onset of diabetes was strongly associated with multiplicity of complications (P = 0.0003). CONCLUSIONS: About half the diabetics in this high-risk population had one or more microvascular complications. Several well-established risk factors were associated with multiplicity and individual microvascular complications, but each separate microvascular complication was linked to a somewhat different constellation of risk factors.

Explanations for less small fibre neuropathy in South Asian versus European subjects with type 2 diabetes in the UK.

BACKGROUND: Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans. METHODS: In a cross-sectional, population-based study, age- and sex-matched South Asians (n = 77) and Europeans (n = 78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage. RESULTS: Corneal nerve fibre length (22.0 ± 7.9 vs. 19.3 ± 6.3 mm/mm2 ; P = 0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7-246.2) vs. 46.0 (3.1-129.2) no./mm2 ; P = 0.021) and heart rate variability (geometric mean (range): 7.9 (1.4-27.7) vs. 6.5 (1.5-22.0); P = 0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3-43.0) vs. 7.2 (1.0-30.0); P = 0.006). Variables with the greatest impact on attenuating the P value for age- and HbA1C -adjusted ethnic difference in corneal nerve fibre length (P = 0.032) were pack-years smoked (P = 0.13), BMI (P = 0.062) and triglyceride levels (P = 0.062). CONCLUSIONS: South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers.

Osteopontin and clusterin levels in type 2 diabetes mellitus: differential association with peripheral autonomic nerve function.

Osteopontin (OPN) and clusterin are secreted glycoproteins potentially associated with nerve function. Sudomotor dysfunction is associated with the development of foot ulcerations. The purpose of this study was to investigate the potential relationship of OPN and clusterin with sudomotor function (i.e., autonomic nerves that control sweating) in participants with type 2 diabetes mellitus (T2DM). Sudomotor function was assessed using SUDOSCAN® which measures electrochemical skin conductance (ESC) of the hands and feet. Demographics (e.g., age, gender, race, body mass index (BMI)), HbA1c, 25-hydroxyvitamin D, creatinine, OPN, and clusterin were also determined for the participants. Fifty individuals with T2DM (age = 59±11 years; 23/27 male/female; 13 African Americans) participated in this study. Lower ESC for the hands and feet were observed in African Americans versus Caucasians/Asians (p < 0.05). No significant ESC differences were observed for good [HbA1c <7%] versus poor [HbA1c ≥7%] glycemic control. With regard to gender, ESC values were lower for the hands for females (p < 0.05). In linear regression with ESC for the hands or feet as the dependent variable, increased OPN levels, but not clusterin, were independently associated with reduced sudomotor function while adjusting for age, gender, race, BMI, and glycemic control (ESC hands model R 2 = 0.504, p < 0.001; ESC feet model R 2 = 0.534, p < 0.001). The association between OPN and reduced sudomotor function found in our study warrants further investigation to delineate the underlying mechanisms and determine if OPN is neuroprotective, involved in the pathogenesis of sudomotor dysfunction, or simply a bystander.

Association of apolipoprotein-CIII (apoC-III), endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes (T2D). Apart from hyperglycemia, its pathogenesis is poorly understood. Apolipoprotein-CIII (apoC-III) associated with triglyceride metabolism, is a risk factor for cardiovascular disease. Its role in DPN is not well-established. We studied the associations of apoC-III, endothelial function and DPN. METHODS: In patients with T2D, anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements (uACR). Endothelial function assessments were performed by laser Doppler flowmetry/imaging. DPN was considered present if there was an abnormal finding in monofilament (≤8 of 10 points) or neurothesiometer testing≥25V on either foot. Plasma apoC-III was assessed by ELISA. RESULTS: Monofilament and neurothesiometer readings were measured in 1981 patients, mean age 57.4±10.8 years old. DPN prevalence was 10.8% (n=214). Patients with DPN compared to those without, were significantly older (p<0.0001), with longer duration of T2D (p<0.0001), had higher BMI (p=0.006), higher glucose (p=0.015) and HbA1c (p<0.0001), Systolic blood pressure (SBP) (p<0.0001), lower eGFR (p<0.0001), higher urine ACR (p<0.0001), poorer endothelium-dependent and endothelium-independent vasodilation (both p<0.0001), higher VCAM-1 (p<0.0001) and higher apoC-III [285.3 (195.2-405.6) vs 242.9(165.0-344.0) µg/ml]. After adjustment, log transformed apoC-III, remained independently associated with the presence of DPN (B=0.965, SE=0.397, p=0.015). CONCLUSION: Plasma apoC-III is higher in patients with DPN. Apart from its known association with lipids and macrovascular complications, this study suggests its association with DPN. Whether regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidemia and microvascular complications in T2D remains to be proven in future mechanistic and clinical studies.

Acupuncture Treatment of Diabetic Peripheral Neuropathy in an American Indian Community.

Diabetic peripheral neuropathy (DPN) develops in 30% of type 2 diabetes patients, increases the risk for foot ulcers and amputation, and is a significant source of disability and medical costs. Treatment remains challenging, propelling research to focus on therapeutic methods that aim to improve blood circulation or ameliorate oxidative stress that drives development of DPN. The aim of this study was to assess the effectiveness of acupuncture treatment for DPN symptoms and lower extremity arterial circulation in people with type 2 diabetes. Twenty-five patients seen at a Southern California Tribal Health Center who reported a threshold level of diabetic neuropathy symptoms in the lower extremities during the previous 4 weeks received acupuncture treatment once per week over a 10-week period between 2011 and 2013. The Neuropathy Total Symptom Scale (NTSS-6), Neuropathy Disability Score (NDS), and laser Doppler fluxmetry (LDF) were used for assessment at baseline and 10 weeks. A total of 19 of 25 study participants completed the study and reported a significant reduction in the NTSS symptoms of aching pain, burning pain, prickling sensation, numbness, and allodynia. Lancinating pain did not decrease significantly. LDF measures improved but not significantly. Acupuncture may effectively ameliorate selected DPN symptoms in these American Indian patients.

Peripheral and Autonomic Neuropathy in South Asians and White Caucasians with Type 2 Diabetes Mellitus: Possible Explanations for Epidemiological Differences.

Objectives. To compare the prevalence of diabetic peripheral neuropathy (DPN) and that of cardiac autonomic neuropathy (CAN) between South Asians and White Caucasians with type 2 diabetes and to explore reasons for observed differences. Methods. A cross-sectional study of casually selected South Asian and White Caucasian adults attending a hospital-based diabetes clinic in the UK. DPN and CAN were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and heart rate variability testing, respectively. Results. Patients (n = 266) were recruited (47.4% South Asians). DPN was more common in White Caucasians compared to South Asians (54.3% versus 38.1%, p = 0.008). Foot insensitivity as assessed by 10 g monofilament perception was more common in White Caucasians (43.9% versus 23.8%, p = 0.001). After adjustment for confounders, White Caucasians remained twice as likely to have DPN as South Asians, but the impact of ethnicity became nonsignificant after adjusting for adiposity measures or height. No difference in prevalence of standardized CAN test abnormalities was detected between ethnicities. Skin microvascular assessment demonstrated that South Asians had reduced heating flux but preserved acetylcholine response. Conclusions. South Asians with type 2 diabetes have fewer clinical signs of DPN compared to White Caucasians. Differences in adiposity (and its distribution) and height appear to explain these differences.

Clinical Phenotype of Diabetic Peripheral Neuropathy and Relation to Symptom Patterns: Cluster and Factor Analysis in Patients with Type 2 Diabetes in Korea.

OBJECTIVES: Patients with diabetic peripheral neuropathy (DPN) is the most common complication. However, patients are usually suffering from not only diverse sensory deficit but also neuropathy-related discomforts. The aim of this study is to identify distinct groups of patients with DPN with respect to its clinical impacts on symptom patterns and comorbidities. METHODS: A hierarchical cluster analysis and factor analysis were performed to identify relevant subgroups of patients with DPN (n = 1338) and symptom patterns. RESULTS: Patients with DPN were divided into three clusters: asymptomatic (cluster 1, n = 448, 33.5%), moderate symptoms with disturbed sleep (cluster 2, n = 562, 42.0%), and severe symptoms with decreased quality of life (cluster 3, n = 328, 24.5%). Patients in cluster 3, compared with clusters 1 and 2, were characterized by higher levels of HbA1c and more severe pain and physical impairments. Patients in cluster 2 had moderate pain levels but disturbed sleep patterns comparable to those in cluster 3. The frequency of symptoms on each item of MNSI by "painful" symptom pattern showed a similar distribution pattern with increasing intensities along the three clusters. CONCLUSIONS: Cluster and factor analysis endorsed the use of comprehensive and symptomatic subgrouping to individualize the evaluation of patients with DPN.

Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes.

AIMS: Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic nephropathy (DN). We investigated the relationship between DN structural lesions and CAN. METHODS: Sixty three Pima Indians with type 2 diabetes underwent kidney biopsies following a 6-year clinical trial testing the renoprotective efficacy of losartan vs. placebo. CAN was assessed a median 9.2years later. CAN variables included expiration/inspiration ratio (E/I), standard deviation of the normal R-R interval (sdNN), and low and high frequency signal power and their ratio (LF, HF, LF/HF); lower values reflect more severe neuropathy. Associations of CAN with renal structural variables were assessed by linear regression adjusted for age, sex, diabetes duration, blood pressure, HbA1c, glomerular filtration rate, and treatment assignment during the trial. RESULTS: Global glomerular sclerosis was negatively associated with sdNN (partial r=-0.35, p=0.01) and LF (r=-0.32, p=0.02); glomerular basement membrane width was negatively associated with all measures of CAN except for LF/HF (r=-0.28 to -0.42, p<0.05); filtration surface density was positively associated with sdNN, LF, and HF (r=0.31 to 0.38, p<0.05); and cortical interstitial fractional volume was negatively associated with HF (r=-0.27, p=0.04). CONCLUSIONS: CAN associates with DN lesions.

Communication Barriers and the Clinical Recognition of Diabetic Peripheral Neuropathy in a Diverse Cohort of Adults: The DISTANCE Study.

The purpose of this study was to explore communication barriers as independent predictors and potential mediators of variation in clinical recognition of diabetic peripheral neuropathy (DPN). In this cross-sectional analysis, we estimated the likelihood of having a DPN diagnosis among 4,436 patients with DPN symptoms. We controlled for symptom frequency, demographic and clinical characteristics, and visit frequency using a modified Poisson regression model. We then evaluated 4 communication barriers as independent predictors of clinical documentation and as possible mediators of racial/ethnic differences: difficulty speaking English, not talking to one's doctor about pain, limited health literacy, and reports of suboptimal patient-provider communication. Difficulty speaking English and not talking with one's doctor about pain were independently associated with not having a diagnosis, though limited health literacy and suboptimal patient-provider communication were not. Limited English proficiency partially attenuated, but did not fully explain, racial/ethnic differences in clinical documentation among Chinese, Latino, and Filipino patients. Providers should be encouraged to talk with their patients about DPN symptoms, and health systems should consider enhancing strategies to improve timely clinical recognition of DPN among patients who have difficult speaking English. More work is needed to understand persistent racial/ethnic differences in diagnosis.

Cardiac autonomic neuropathy risk estimated by sudomotor function and arterial stiffness in Chinese subjects.

The SUDOSCAN test was recently developed to detect diabetic autonomic neuropathy early and screen for cardiac autonomic neuropathy (CAN) through assessment of sudomotor function. The aim of this study was to investigate the relationship of cardiac autonomic dysfunction estimated by the SUDOSCAN test with arterial stiffness. A total of 4019 subjects without diabetes or established cardiovascular disease were tested with SUDOSCAN, central systolic blood pressure (cSBP) and brachial-ankle pulse wave velocity (baPWV). Hands mean electrochemical skin conductance (ESC) measured by SUDOSCAN was 70±17 µS, feet mean ESC was 71±16 µS and the CAN risk score was 21±10%. The levels of cSBP and baPWV increased across quartiles of CAN risk score (P for trend <0.001 for all). In spearman correlation analyses, the CAN risk score was positively correlated with cSBP (r=0.391, P<0.001) and baPWV (r=0.305, P<0.001). In multivariable analyses, the values of cSBP and baPWV increased 0.17 mm Hg (P=0.002) and 2.01 cm per second (P=0.010), respectively, when CAN risk score increased 1%. The results were unchanged when stratified by glucose tolerance status. In conclusion, cardiac autonomic dysfunction estimated by sudomotor function was correlated with arterial stiffness independent of conventional factors and glucose tolerance status.

Diabetic neuropathy: comparison between Bangladeshi immigrants and Greek-born subjects.

The aim of this study was to compare Bangladeshi immigrants with diabetes to native Greeks with diabetes and to distinguish the different risk factors for polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82 men and 19 women of mean age 49 years) were included in the study. Sex, mean age, age at diabetes diagnosis, and diabetes duration did not differ between the two groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%) than in Greeks (53%) (p < 0.01). Small fiber neuropathy on the contrary were more frequent in Bangladeshis (18% vs. 7%) (p < 0.02). Regarding the risk factors for PN, Greek patients were taller, with higher BMI, and smoked more cigarettes (p < 0.001). They were also treated with more anti-lipid and antihypertensive agents. The higher percentage of SFN in Bangladeshi was mainly a result of the significantly greater incidence of erectile dysfunction (ED) in their group (68 Bangladeshi vs. 38 Greek men). It is well known that there are many causes of ED aside from SFN which were not evaluated in this study. Thus this conclusion should be taken with caution.

An additional cause of health care disparities: the variable clinical decisions of primary care doctors.

RATIONALE, AIMS AND OBJECTIVES: Decades of work on health disparities have culminated in identification of three contributors to variability in diagnosis and management of disease: (i) patient attributes; (ii) doctor's characteristics; and (iii) organizational factors. Understanding the relative influence of different contributors to variability in diagnosis and management of diabetes is important to improving quality and reducing disparities. This study was designed to examine the influence of patient, provider and organizational factors on the diagnosis and management of a major chronic disease - diabetes. METHOD: A factorial experiment using video vignettes was conducted among n = 192 primary care doctors. Doctors were interviewed after viewing vignettes of (1) a 'patient' with symptoms strongly suggestive of diabetes and (2) an already diagnosed diabetes 'patient' with emerging peripheral neuropathy. RESULTS: A total of 60.9% of doctors identified diabetes as the correct diagnosis, with significant variations depending on the patients' race/ethnicity. Many doctors offered competing diagnoses with high levels of certainty. For the 'patient' with emerging peripheral neuropathy, 42.2% of doctors would do all essential components of a foot examination, while 21.9% would do none. CONCLUSIONS: That half of all diabetes in the United States remains undiagnosed is unsurprising given only 60.9% of doctors would diagnose it when the condition is strongly suggested, and nearly one-quarter suspecting diabetes would not order tests necessary to confirm it. The diagnosis of diabetes is significantly influenced by a patient's race/ethnicity, and clinical management (specifically for foot neuropathy) is influenced by patient socio-economic status (SES), doctor's gender and access to clinical guidelines.

UK Renal Registry 16th annual report: chapter 6 demographics and outcomes of patients from different ethnic groups on renal replacement therapy in the UK.

INTRODUCTION: This chapter describes the patient characteristics and outcomes for the three main ethnic groups (White, South Asian, Black) on renal replacement therapy (RRT) in the UK. METHODS: Data on patients (>18 years old) from all 71 UK adult renal centres starting RRT between 2003 and 2012 were considered. Scottish centres were excluded due to poor ethnicity data. RESULTS: The age-gender standardized incidence ratio of RRT was higher (2-3 times) in regions with a high ethnic minority population compared to those with a low ethnic minority population. South Asian and Black patients were significantly younger than Whites; had more diabetes causing established renal failure and lived in more deprived areas. The proportion of patients with at least one comorbidity was greater amongst White patients compared to South Asian and Black patients. The proportion of patients starting PD and having preemptive transplantation was lower amongst both ethnic minorities. The attainment of various laboratory standards was comparable or better for the ethnic minorities compared to White patients except for calcium standard attainment (for South Asians) and haemodialysis dose attainment (for Black patients). Compared to White patients, both ethnic minorities had similar rates of listing for deceased donor kidney transplantation but had lower rates of transplantation once wait-listed, and lower rates of living kidney donor transplantation. One and five year kidney allograft adjusted survival was poorer for Black patients but similar for South Asians compared to White patients. Black and South Asian patients had a better adjusted survival on dialysis compared to White patients. CONCLUSIONS: The persistent high incidence of RRT, the better survival on dialysis and the poor access to kidney transplantation for South Asian and Black patients and early allograft loss for Black patients will impose a disproportionate demand on dialysis provision in those areas with a high ethnic minority population.

Quantitative vibration perception threshold in assessing diabetic neuropathy: is the cut-off value lower for Indian subjects? [Q-VADIS Study].

AIMS: The aim was to compute a normative data of VPT [Vibration Perception Threshold], compare results of VPT among type 2 diabetes patients with and without neuropathy, validate VPT taking NDS [Neuropathy Disability Scores] as gold standard and suggest a cut off value for the Indian population. MATERIALS AND METHODS: A clinic based case-control study was conducted at Nightingale Hospital (NH) in Kolkata for 2 months duration. Fifty type 2 diabetes patients (who were detected with by fasting plasma glucose or on medication) reporting at OPD (Out Patent Department) were randomly selected and informed consent was obtained. The age range was 20-65 years and other common causes of neuropathy were excluded. Same number of control patients without diabetes and reporting at the same hospital during the study period in the similar age range were selected. RESULTS: The normative data of VPT for mean of 4 sites (malleoli and great toe) was 11.3±4.9mV. The VPT value was significantly higher among diabetic patients with neuropathy compared to non-neuropathic and non-diabetic patients. Considering NDS score as gold standard lowering the cutoff value of VPT from 25mV to 20mV increased the sensitivity from 50% to 62.5% in detecting diabetic neuropathy compared to NDS taken as a gold standard. CONCLUSIONS: It was found that lowering the cut off value of VPT in Indian population increased the sensitivity of the test to detect diabetic neuropathy without hampering the specificity. There is however no indication that a lower cut off VPT value is justified as of now.