Elevated Cystatin C Concentration and Progression to Pre-Diabetes

Abstract

OBJECTIVE -We conducted a nested case-control investigation to examine whether elevated baseline concentrations of cystatin C predicted progression from normoglycemia to prediabetes over 6 years of follow-up from the Western New York Health Study. participants from the Western New York Health Study, who were free of type 2 diabetes and known cardiovascular disease at baseline (1996 -2001), were reexamined. An incident case of pre-diabetes was defined as an individual with fasting glucose Ͻ100 mg/dl at the baseline examination and Ն100 and Յ125 mg/dl at the follow-up examination, thereby eliminating individuals with prevalent prediabetics. All case patients (n ϭ 91) were matched 1:3 to control participants based on sex, race/ethnicity, and year of study enrollment. All control subjects had fasting glucose levels Ͻ100 mg/dl at both baseline and follow-up examinations. Cystatin C concentrations and the urinary albumin-to-creatinine ratio were measured from frozen (Ϫ196°C) baseline blood and urine samples. Serum creatinine concentrations were available from the baseline examination only. RESEARCH DESIGN AND METHODSRESULTS -Multivariate conditional logistic regression analyses adjusted for age, baseline glucose level, homeostasis model assessment of insulin resistance, BMI, hypertension, estimated glomerular filtration rate, cigarette smoking, and alcohol use revealed a significantly increased risk of progression to pre-diabetes among those with elevated baseline concentrations of cystatin C (odds ratio 3.28 [95% CI 1.43-7.54]) (upper quintile versus the remainder). Results of secondary analyses that considered high-sensitivity C-reactive protein, interleukin-6, E-selectin, or soluble intercellular adhesion molecule-1 did not alter these results.CONCLUSIONS -These results suggest that cystatin C was associated with a threefold excess risk of progression to pre-diabetes in this population. Diabetes Care 30:1724-1729, 2007R ecent evidence from randomized clinical trials (1,2) among people with pre-diabetes have provided convincing evidence that early intervention can significantly delay or prevent the progression to type 2 diabetes. The identification of those with pre-diabetes is assuming greater importance (3), especially in light of the fact that ϳ37% of adults aged 40 -74 years in the U.S. have prediabetes defined as impaired fasting glucose (4). Microalbuminuria occurs frequently in nondiabetic subjects and places them at increased risk for cardiovascular disease (CVD) (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 individuals with type 2 diabetes pass through a period of pre-diabetes (14) and may experience early renal dysfunction, e.g., a glomerular filtration rate (GFR) Ͼ60 ml/min per 1.73 m 2 . Currently used estimating equations are poor at identifying early renal impairment and better indexes are of great interes...

Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study

“…The first of these reports from the Western New York Study compared the baseline hsCRP, IL-6 and adiponectin levels of individuals who progressed from normal fasting glucose (NFG) to IFG during a mean follow-up of 5.9 years with individuals who had NFG at both time points [16]. HsCRP levels were higher in men with IFG and adiponectin levels were lower in women with IFG, which is generally consistent with our data.…”

“…Two smaller studies provided data on associations between inflammation-related biomarkers and the incidence of IFG [16] or IGT [15]. The first of these reports from the Western New York Study compared the baseline hsCRP, IL-6 and adiponectin levels of individuals who progressed from normal fasting glucose (NFG) to IFG during a mean follow-up of 5.9 years with individuals who had NFG at both time points [16].…”

“…Only a few prospective studies have tested the hypothesis that circulating levels of immune mediators can predict the deterioration of glycaemic control before the manifestation of type 2 diabetes [15][16][17]. In two studies, deterioration of glycaemia was assessed as the incidence of IFG or IGT [15,16]; another study used increases in HOMA-IR as the outcome [17].…”

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

“…To date, two small studies have failed to provide evidence for an association of proinflammatory cytokines or adiponectin with incident IFG or IGT (6,7). An alternative approach with higher statistical power is to investigate whether baseline levels of biomarkers of subclinical inflammation are associated with subsequent changes in measures of glucose metabolism (8,9).…”

Renal dysfunction in patients with myocardial infarction concurrent with type 2 diabetes mellitus

“…В последние десятилетия установлено, что ранняя диагно-стика ХБП и проведение нефропротективной терапии позволяют снизить риск развития терминальной стадии почечной недоста-точности и способствуют снижению риска развития ССЗ [39,40]. Подтверждено, что при воздействии на модифицируемые ФР развития ХБП (достижение целевых уровней АД, строгий кон-троль гликемии у пациентов с НУО, изменение образа жизни, прекращение курения, нормализация массы тела), терапия инги-биторами ангиотензинпревращающего фермента (АПФ) -бло-каторами рецепторов АТII связана с более низкими показателя-ми прогрессирования ХПН и значительным снижением сердеч-но-сосудистой заболеваемости и смертности [41].…”