OBJECTIVE There are few data on the incidence rates of diabetes and prediabetes (dysglycemia) in Asian Indians. This article presents the incidence of diabetes and prediabetes and the predictors of progression in a population-based Asian Indian cohort. RESEARCH DESIGN AND METHODS Data on progression to diabetes and prediabetes from 1,376 individuals, a subset of 2,207 of the Chennai Urban Rural Epidemiology Study (CURES) cohort (phase 3) with normal glucose tolerance (NGT) or prediabetes at baseline, who were followed for a median of 9.1 years (11,629 person-years), are presented. During follow-up, 534 died and 1,077 with NGT and 299 with prediabetes at baseline were reinvestigated in a 10-year follow-up study. Diabetes and prediabetes were diagnosed based on the American Diabetes Association criteria. Incidence rates were calculated and predictors of progression to prediabetes and/or diabetes were estimated using the Cox proportional hazards model. RESULTS The incidence rates of diabetes, prediabetes, and “any dysglycemia” were 22.2, 29.5, and 51.7 per 1,000 person-years, respectively. Among those with NGT, 19.4% converted to diabetes and 25.7% to prediabetes, giving an overall conversion rate to dysglycemia of 45.1%. Among those with prediabetes, 58.9% converted to diabetes. Predictors of progression to dysglycemia were advancing age, family history of diabetes, 2-h plasma glucose, glycated hemoglobin (HbA_1c), low HDL cholesterol, and physical inactivity. CONCLUSIONS Asian Indians have one of the highest incidence rates of diabetes, with rapid conversion from normoglycemia to dysglycemia. Public health interventions should target modifiable risk factors to slow down the diabetes epidemic in this population.

Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5′ and 3′ flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5′ flanking region and one in 3′ flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4±1.42 fold increased compared to saphenous veins from 20 normal subjects (pT (rs34221221: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.

Motorist’s vestibular disorientation syndrome (MVDS) is a disorder in which patients experience dizziness while driving. MVDS is under-reported in the literature, and in clinical practice, it often goes unrecognized. We identified clinical characteristics of patients with MVDS using data from 24 patients who faced difficulties while driving and were diagnosed with MVDS. Their symptoms, duration of illness, precipitating factors, co-morbidities, history of other neuro-otological disorders, severity of symptoms, and associated anxiety and depression were reviewed. Ocular motor movements were recorded using video-nystagmography. Patients with vestibular disorders that can cause similar symptoms while driving were excluded. The mean age of the patients was 45.7 ± 8.7 years, and most were professional drivers (90.5%). The duration of the illness ranged from eight days to ten years. Most patients presented with disorientation (79.2%) exclusively while driving. The most common triggers for symptoms were higher speeds, i.e., >80 km/h (66.7%), multi-lane roads (58.3%), bends and turns (50%), and looking at other vehicles or signals while driving (41.7%). A history of migraines was reported in 62.5% of the patients, and motion sickness was reported in 50% of the patients. Anxiety was reported in 34.3% of patients, and 15.7% had depression. The video-nystagmography did not show any specific abnormalities. Patients responded to drugs used in prophylactic treatments for migraines such as Amitriptyline, Venlafaxine, Bisoprolol, and Magnesium, and to Pregabalin and Gabapentin. Based on these findings, a classification system and a diagnostic criterion for MVDS were proposed.