Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia

OBJECTIVE: The purpose of this study was to evaluate the utility of the Functional Bowel Disorder Severity Index (FBDSI) as a measure of severity of disease among patients with the irritable bowel syndrome (IBS) and matched controls. METHODS: A total of 75 IBS patients and 69 matched controls completed questionnaires on bowel symptoms, health status, quality of life, psychological distress, concerns, anxiety, and sense of coherence. All participants also were tested for fibromyalgia (FS), a functional disorder of the musculoskeletal system. All participants were administered a questionnaire that included the FBDSI. On the basis of their responses to the questionnaire, the controls were subdivided as healthy controls (n = 48) or IBS nonpatients (n = 21). On the basis of the FS classification, 75 IBS patients were subdivided as IBS only (n = 50) or IBS and FS combined (n = 25). RESULTS: The mean FBDSI score was higher for the IBS patients than the controls (100.5+/-12.7 and 23.5+/-3.9, respectively; p < 0.001). IBS nonpatients had an intermediate score of 42.3+/-18.0. Patients with both IBS and fibromyalgia had the highest mean FBDSI score: 138.8+/-31.5. There was no association between FBDSI and age or gender, but FBDSI was significantly associated with other measures of health status. CONCLUSIONS: An association was found between the FBDSI and IBS patient status: IBS nonpatients, patients with IBS only, and patients with both IBS and fibromyalgia had increasingly severe scores. The results provide support for the validity of FBDSI as a measure of illness severity in functional gastrointestinal disorders.     

Fibromyalgia in the irritable bowel syndrome: studies of prevalence and clinical implications

OBJECTIVE: The irritable bowel syndrome (IBS) and the fibromyalgia syndrome (FS) coexist in many patients. We conducted complementary studies of the prevalence of FS in IBS patients and matched controls, and of IBS in FS patients and the implications of concomitant IBS and FS on health-related quality of life (HRQOL). METHODS: A study of 79 IBS patients with 72 matched controls (IBS study), and a study of 100 FS patients (FS study). All participants underwent tests of tender point sites and threshold of tenderness and answered questionnaires including personal and medical history, GI symptoms, and indices of HRQOL. RESULTS: In the IBS study, 25 of the 79 IBS patients (31.6%) and 3 of the 72 controls (4.2%) had FS (p < 0.001). Statistically significant differences were found among the study groups in terms of global well-being (p < 0.001), sleep disturbance (p < 0.001), physician visits (p = 0.003), pain (p < 0.001), anxiety (p < 0.001), and global severity index (SCL-90-R) (p < 0.001), with patients with IBS and FS having the worst results. IBS patients had significantly more tender points than controls (p < 0.001). In the FS study, 32 of the 100 FS patients (32%) had IBS. Patients with both disorders had significantly worse scores for physical functioning (p = 0.030) and for all but one of a 16-item quality of life questionnaire. CONCLUSIONS: FS and IBS coexist in many patients. Patients with both disorders have worse scores on HRQOL indices than patients with either disorder alone, or controls. Physicians treating these patients should be aware of the overlap, which can affect the presentation of symptoms, health care utilization, and treatment strategies.     

Noninvasive,continuous, real-time glucose measurements compared to reference laboratory venous plasma glucose values

Purpose: Current modalities for glucose monitoring are invasive and inconvenient. The search for a noninvasive technique is still ongoing, without a clinically viable product. The aim of our study was to evaluate the safety and accuracy of a novel non-invasive continuous glucometer – the Wizmi? device.

Methods: Prospective, observational, controlled clinical trial. We included healthy pregnant women designated to undergo a 3-hour oral glucose tolerance test. Each participant underwent synchronous and simultaneous glucose measurement by venous sampling of plasma glucose and non-invasive glucose by Wizmi device. Primary outcome was the accuracy of the Wizmi device as assessed by comparing between paired measurements, i.e. non-invasive glucose measurements by Wizmi versus standard plasma glucose levels, which were taken at the exact same time.

Results: Thirty-two women underwent oral glucose tolerance test (OGTT), contributing 224 paired glucose measurements. Of the 224 paired measurements, all were within the clinically appropriate zones of the Clarke error grid analysis zones ?208 (93%) in Zone A and 16 (7%) in zone B. Mean absolute relative difference of the Wizmi non-invasive glucose versus plasma glucose laboratory reference was 7.23% or 9.66?mg/dl. Overall, for all 224 paired measurements, across all Wizmi glucose ranges, the agreement was 86.6, 92.0, 97.8 and 99.5% for deviations within ±15, 20, 30, 40% (if glucose >80?mg/dl) or mg/dl (if glucose ≤80?mg/dl).

Conclusions: Wizmi device is novel non-invasive continuous glucose monitor, safe to use, with overall high accuracy compared to a gold standard reference of plasma glucose.     

Inflammation and stress-related candidate genes,plasma interleukin-6 levels,and longevity in older adults

Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%–20% higher baseline IL-6 concentration per copy among CHS European–American (EA) participants (all p < 10⁻⁴). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p = 0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415 – longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the “risk” of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62–1.02; p = 0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.     

Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity

We previously identified a functional variant of KLOTHO, termed KL-VS, that is associated with human aging and early-onset occult coronary artery disease. Here, we determine whether the KL-VS allele influences cardiovascular disease risk factors, cardiovascular events, and ultimately, mortality. A total of 525 Ashkenazi Jews composed of 216 probands (age > or =95 years) and 309 unrelated individuals (ages 51 to 94) were genotyped for the KL-VS allele. In concordance with our previous data in Czech individuals (age > or =79; P<0.01), a heterozygous advantage for longevity was observed for individuals > or =79 years of age (P<0.004). Combined analysis indicates a 1.57-fold (95% CI, 1.23 to 1.98) increased odds ratio (OR) for 5-year survival in two independent populations (P<0.0002). Cardiovascular disease risk factors were assessed through multivariate regression analysis, demonstrating that high-density lipoprotein cholesterol (HDL-C; P<0.05) and systolic blood pressure (SBP; P<0.008) are associated with KL-VS genotype. History of vascular events was analyzed using logistic regression, indicating that after adjustment for traditional risk factors, heterozygous individuals were at significantly lower risk for stroke than wild-type individuals (OR, 5.88; 95% CI, 1.18 to 29.41), whereas homozygous KL-VS individuals had the highest risk (OR, 30.65; 95% CI, 2.55 to 368.00). Similarly, prospective analysis of mortality in probands using Cox regression indicates that wild-type individuals have a 2.15-fold (95% CI, 1.18 to 3.91) and homozygous KL-VS individuals a 4.49-fold (95% CI, 1.35 to 14.97) increase in relative risk for mortality after adjusting for potential confounders. Thus, cross-sectional and prospective studies confirm a genetic model in which the KL-VS allele confers a heterozygous advantage in conjunction with a marked homozygous disadvantage for HDL-C levels, SBP, stroke, and longevity.     

Biological evidence for inheritance of exceptional longevity

Subjects with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. In a case control study, we aim to determine phenotype and genotype of exceptional longevity in a genetically homogenous population (Ashkenazi Jews), and their offspring, while an age-matched control group of Ashkenazi Jews was used as control groups. We demonstrated that exceptional longevity and healthy aging in humans is an inherited phenotype across three generations. Moreover, we demonstrated that subjects with exceptional longevity and their offspring have significantly larger high-density lipoprotein (HDL) levels and particle sizes and low-density lipoprotein (LDL) levels that reflect on their health and cognitive function performance. This phenotype have led us to study candidate genes involved in lipoprotein metabolism, and to the implication of homozygosity for the 405 valine (V) allele of cholesteryl ester transfer protein (CETP). A markedly higher frequency of a functional CETP variant that led to increased particle sizes of HDL and LDL and thus a better health performance is the first example of a phenotype and an associated genotype in humans with exceptional longevity. Hopefully, this line of research will lead us to establish which genotype is necessary (although not necessary sufficient) for a prolonged disease-free aging.     

The paradox of the insulin/IGF-1 signaling pathway in longevity

Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes, and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.     

Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action

While the incidence of diabetes increases with age, a decrease in beta-cell function independent of age-related insulin resistance has not been conclusively determined. We studied insulin secretion (by hyperglycemic clamp) in 3-, 9-, and 20-month-old chronically catheterized, awake, Sprague Dawley (SD) rats (n = 78). Insulin action was modulated in a group of old rats by caloric restriction (CR) or by surgical removal of visceral fat (VF-). During the first 2 h of the clamp (11 mmol/l glucose), insulin secretion and insulin resistance (S(i hyper clamp)) demonstrated the characteristic hyperbolic relationship. However, after hyperglycemia for an additional 2 h, the ability to maintain insulin secretion, commensurate with the degree of insulin resistance, was decreased in all aging rats (P < 0.05). Increasing plasma glucose levels to 18 mmol/l glucose, after clamp at 11 mmol/l, increased insulin secretion by approximately threefold in young rats, but failed to induce similar magnitude of response in the aging rats ( approximately 50%). However, elevation of plasma free fatty acid (FFA) levels by twofold (by intralipid infusion during 11 mmol/l glucose clamp) resulted in a robust, approximate twofold response in both young and old rats. Thus, prolonged stimulation by hyperglycemia unveiled a functional defect in insulin secretion with aging. This age-related defect is independent of insulin action and is specific to glucose and not FFAs. We suggest that prolonged hyperglycemic stimulation can be a tool to identify functional defects in insulin secretion, particularly in the context of the hyperbolic relationship with insulin action, in elderly subjects or those at risk for type 2 diabetes.     

Positive attitude towards life and emotional expression as personality phenotypes for centenarians

Centenarians have been reported to share particular personality traits including low neuroticism and high extraversion and conscientiousness. Since these traits have moderate to high heritability and are associated with various health outcomes, personality appears linked to bio-genetic mechanisms which may contribute to exceptional longevity. Therefore, the present study sought to detect genetically-based personality phenotypes in a genetically homogeneous sample of centenarians through developing and examining psychometric properties of a brief measure of the personality of centenarians, the Personality Outlook Profile Scale (POPS). The results generated two personality characteristics/domains, Positive Attitude Towards Life (PATL: optimism, easygoing, laughter, and introversion/outgoing) and Emotional Expression (EE: expressing emotions openly and not bottling up emotions). These domains demonstrated acceptable concurrent validity with two established personality measures, the NEO-Five Factor Inventory and Life Orientation Test-Revised. Additionally, centenarians in both groups had lower neuroticism and higher conscientiousness than the US adult population. Findings suggest that the POPS is a psychometrically sound measure of personality in centenarians and capture personality aspects of extraversion, neuroticism, and conscientiousness, as well as dispositional optimism which may contribute to successful aging.     

Genotyping of geographically diverse Druze trios reveals substructure and a recent bottleneck

Druze individuals rarely marry outside their faith (often practicing consanguinity) and are thus believed to form a genetic isolate. To comprehensively characterize the genetic structure of the Druze population, we recruited and genotyped 40 parent-offspring trios from the Upper Galilee in Israel and the Golan Heights, attempting to capture different extended families (clans) across various geographical locations. Principal component (PC) and ADMIXTURE analyses demonstrated that Druze are close to, yet distinct from, other Middle-Eastern groups (Bedouins and Palestinians), supporting the Druze''s Middle-Eastern origin and their recent genetic isolation. Reconstruction of the Druze demographic history using identical-by-descent (IBD) segments suggested an ≈15-fold reduction in population size taking place ≈22–47 generations ago, close to the documented time of the foundation of the Druze faith at the 11th century. Combining the Galilee and Golan Druze genotypes with previously published data on Druze from the Carmel (Israel) and Lebanon demonstrated that all four Druze communities are genetically distinct. The Lebanese group shared less IBD segments (within the group and with other groups) compared with the Israeli Druze and showed higher heterozygosity (suggesting less consanguinity), but was less diverse in PC space. These findings suggest complex recent and ancient demographic history of the Druze population.