Elevated cystatin-C concentration is associated with progression to prediabetes: the Western New York Study

OBJECTIVE – We conducted a nested case-control investigation to examine if elevated baseline concentrations of cystatin-C predicted progression from normoglycaemia to prediabetes over 6 years of follow-up from the Western New York Health Study. RESEARCH DESIGN AND METHODS – 1,455 participants from the Western New York Health Study, free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001), were reexamined in 2002-2004. An incident case of prediabetes was defined as one with fasting glucose below 100 mg/dl at the baseline examination and ≥ 100 mg/dl and ≤ 125 mg/dl at the follow-up examination. All cases (n=91) were matched 1:3 to control participants based upon sex, race/ethnicity and year of study enrollment. All controls had fasting glucose levels < 100 mg/dl at both baseline and follow-up examinations. Cystatin-C concentrations and the urinary albumin to creatinine ratio were measured from frozen (-196 Cº) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination. RESULTS –Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, HOMA-IR, body mass index, hypertension, eGFR, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to prediabetes among those with elevated baseline concentrations of cystatin-C (Odds Ratio, 95% CI: 3.04, 1.34, 6.89) (upper quintile vs. the remainder). Results of secondary analyses that considered hs-CRP, IL-6, E-selectin, or sICAM did not alter these results. CONCLUSIONS - These results suggest that early renal impairment indexed with cystatin-C imparted a three-fold excess risk of progression to prediabetes in this study population. Recent evidence from randomized clinical trials (1,2) among people with prediabetes have provided convincing evidence that early intervention can significantly delay or prevent the progression to type 2 diabetes. The identification of those with prediabetes is assuming greater importance (3) especially in light of the fact that approximately 35 million adults aged 40-74 years old in the United States have prediabetes defined as impaired fasting glucose (4). Microalbuminuria occurs frequently in nondiabetic subjects and places them at increased risk for cardiovascular disease (5-7). The mechanisms behind this observation are poorly understood, however. Albuminuria may reflect underlying vascular damage (8), hypertension (9, 10) endothelial dysfunction (11, 12) and/or low-grade inflammation (13). A large percentage of type 2 individuals pass through a period of prediabetes (14) and may experience early renal dysfunction e.g., a glomerular filtration rate (GFR) above 60 ml/minute per 1.73m2. Currently used estimating equations are poor at identifying early renal impairment and better indices are of great interest (15, 16). Recently, several studies have suggested that cystatin-C levels may be a more sensitive marker of early renal impairment than either albuminuria or serum creatinine concentration (17-20). Therefore, a better understanding of a putative role for cystatin-C in the etiology of prediabetes could shed light on the renal/heart disease connection (21). Given the reported superiority of cystatin C over conventional measures of renal function, we hypothesized that cystatin-C would predict progression to prediabetes independent of serum creatinine or estimated GFR. We also investigated the role of intervening mechanisms including hypertension, insulin resistance, endothelial dysfunction and inflammation

Fasting Blood Glucose and Depressive Mood among Patients with Mental Illness in a Medicaid Managed Care Program

Objective. This study explores the relationship between depressive symptoms, as measured by the PHQ-9 depression screen and blood glucose levels among patients with diabetes enrolled in Gold Choice, a Medicaid managed care program for individuals with mental illness and/or substance abuse. Methods. The PHQ-9 was mailed to 454 Gold Choice members and a questionnaire was mailed to their physicians requesting current HbA1c% and fasting blood glucose (FBG) levels. The pearson product-moment correlation was used to describe the association between PHQ-9 scores and FBG levels. Results. The PHQ-9 response rate was 55% (N = 249). Laboratory results were received for 141 patients. The correlation between FBG and PHQ-9 scores was modest but statistically significant: r = 0.21 , P = 0.015. Conclusion. A statistically significant association was found between FBG and PHQ-9 depression scores. This finding supports current recommendations that physicians be alert to depressive symptoms among patients with diabetes or impaired glucose metabolism

The association between acanthosis nigricans and dysglycemia in an ethnically diverse group of eighth grade students

The purpose of this study was to describe the prevalence of acanthosis nigricans (AN) and to quantify its association with dysglycemia in an ethnically diverse group of eighth grade students. Data were collected in 2003 from a cross-sectional study of students from 12 middle schools in three U.S. states. Sex, race/ethnicity and pubertal status were self-reported. Anthropometric measures were recorded. Trained staff identified the presence and severity of AN by inspection of the back of the neck. Fasting and 2hr blood samples were analyzed for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and high-risk glycated hemoglobin (A1C), respectively defined as ≥100 mg/dl, ≥140 mg/dl, and ≥ 5.7-6.4%. Overall, 25.0%, 58.2%, and 16.8% were Black, Hispanic and White, respectively. AN was present among 406 /1438 (28.2%) of students: 39% among Black, 30% among Hispanic, and 5.4% among White. IGT and highArisk A1C were present among 2.1%, and 12.4%, respectively. In multivariate logistic modeling after adjusting for gender, family history of diabetes, BMI percentile and pubertal staging, the presence (vs. absence) of AN was associated with a 59% increased likelihood of highArisk A1C: (P = 0.04), twice the likelihood of IGT (P=0.06), and 47% greater likelihood of IGT/IFG combined (P<0.0001). Adjustment for insulin attenuated the ORs by 25-70%. In a racially/ethnically diverse sample of U.S. adolescents, AN was common, occurring in 28% of the sample. AN was associated with a 50-100% increased likelihood of dysglycemia even after consideration of established diabetes risk factors

Short sleep duration is associated with progression to impaired fasting glucose: the western New York health study

Background: Screening of elevated blood pressure (BP) in children has been advocated to early identify hypertension. However, identification of children with sustained elevated BP is challenging due to the high BP variability. The value of an elevated BP measure during childhood and adolescence for the prediction of future elevated BP is not well described. Objectives: We assessed the positive (PPV) and negative (NPV) predictive value of high BP for sustained elevated BP in cohorts of children of the Seychelles, a rapidly developing island state in the African region. Methods: Serial school-based surveys of weight, height, and BP were conducted yearly between 1998-2006 among all students of the country in four school grades (kindergarten [G0, mean age (SD): 5.5 (0.4) yr], G4 [9.2 (0.4) yr], G7 [12.5 (0.4) yr] and G10 (15.6 (0.5) yr]. We constituted three cohorts of children examined twice at 3-4 years interval: 4,557 children examined at G0 and G4, 6,198 at G4 and G7, and 6,094 at G7 and G10. The same automated BP measurement devices were used throughout the study. BP was measured twice at each exam and averaged. Obesity and elevated BP were defined using the CDC (BMI_95th sex-, and age-specific percentile) and the NHBPEP criteria (BP_95th sex-, age-, and height specific percentile), respectively. Results: Prevalence of obesity was 6.1% at G0, 7.1% at G4, 7.5% at G7, and 6.5% at G10. Prevalence of elevated BP was 10.2% at G0, 9.9% at G4, 7.1% at G7, and 8.7% at G10. Among children with elevated BP at initial exam, the PPV of keeping elevated BP was low but increased with age: 13% between G0 and G4, 19% between G4 and G7, and 27% between G7 and G10. Among obese children with elevated BP, the PPV was higher: 33%, 35% and 39% respectively. Overall, the probability for children with normal BP to remain in that category 3-4 years later (NPV) was 92%, 95%, and 93%, respectively. By comparison, the PPV for children initially obese to remain obese was much higher at 71%, 71%, and 62% (G7-G10), respectively. The NPV (i.e. the probability of remaining at normal weight) was 94%, 96%, and 98%, respectively. Conclusion: During childhood and adolescence, having an elevated BP at one occasion is a weak predictor of sustained elevated BP 3-4 years later. In obese children, it is a better predictor

Short sleep duration is associated with the development of impaired fasting glucose : the Western New York health study

PURPOSE: To examine whether sleep duration was associated with incident-impaired fasting glucose (IFG) over 6 years of follow-up in the Western New York Health Study. METHODS: Participants (N = 1,455, 68% response rate) who were free of type 2 diabetes and known cardiovascular disease at baseline (1996-2001) were reexamined in the period 2003-2004. A nested case-control study was conducted. Cases had fasting plasma glucose (FPG) less than 100 mg/dL at baseline and 100 to 125 mg/dL at follow-up: controls (n = 272) had FPG less than 100 mg/dL at both exams. Cases (n = 91) were individually matched to three controls (n 272) on sex, race, and year of study enrollment. Average sleep duration was categorized as short ( 8 hours). RESULTS: In multivariate conditional logistic regression after adjustment for several diabetes risk factors, the odds ratio (OR) of IFG among short sleepers was 3.0 (95% confidence limit [CL]: 1.05, 8.59) compared to mid-range sleepers. There was no association between long sleep and IFG: OR 1.6 (95% CL: 0.45, 5.42). Adjustment for insulin resistance attenuated the association only among short sleepers: OR 2.5 (95% CL: 0.83, 7.46). CONCLUSIONS: Short sleep duration was associated with an elevated risk of IFG. Insulin resistance appears to mediate this association. Ann Epidemiol 2010;20:883-889. (C) 2010 Elsevier Inc. All rights reserved

Additional contribution of emerging risk factors to the prediction of the risk of type 2 diabetes : evidence from the Western New York Study

Objective: To examine whether several biomarkers of endothelial function and inflammation improve prediction of type 2 diabetes over 5.9 years of follow-up, independent of traditional risk factors. Methods and Procedures: A total of 1,455 participants from the Western New York Study, free of type 2 diabetes at baseline, were selected. Incident type 2 diabetes was defined as fasting glucose exceeding 125 mg/dl or on antidiabetic medication at the follow-up visit. Sixty-one people who met the case definition ( 8/1,000 person years) were identified and individually matched with up to three controls on gender, race, year of study enrollment, and baseline fasting glucose (<110 or 110-125 mg/dl). Biomarkers were measured from frozen baseline samples. Results: In conditional logistic regression analyses accounting for traditional risk factors ( age, family history of diabetes, smoking, drinking status, and BMI), E-selectin was positively related (3rd vs. 1st tertile: odds ratio 2.77, 95% confidence interval (CI) 1.13-6.79, P for linear trend = 0.023) and serum albumin was inversely related ( 3rd vs. 1st tertile: odds ratio 0.36, 95% CI 0.14-0.93, P for linear trend = 0.032) to type 2 diabetes incidence. The addition of E-selectin, serum albumin, and leukocyte count to a basic risk factor model including only traditional risk factors significantly increased the area under the receiver operating characteristic curve (AUC) ( from 0.646 to 0.726, P value = 0.04). Discussion: These results support the role of endothelial dysfunction and subclinical inflammation as important mechanisms in the etiopathogenesis of type 2 diabetes; moreover, they indicate that novel biomarkers may improve the prediction of type 2 diabetes beyond the use of traditional risk factors alone