Serum Alanine Transaminase as a Predictor of Type 2 Diabetes Incidence: The Yuport Prospective Cohort Study.

Prior studies have shown an association between the incidence of diabetes with liver enzymes, such as alanine transaminase (ALT). Liver fibrosis scores, such as the Fibrosis-4 index which indicates chronic liver damage, were also associated with diabetes development. However, no literature compared predictive accuracy between ALT and Fibrosis-4 index. Thus, we aimed to determine it, and to assess its association using inverse probability of treatment weighting. This was a non-concurrent prospective cohort study of 9,748 subjects without diabetes receiving Yuport Health Checkup in Japan between 1998 and 2006. ALT was categorized into three groups: the highest ALT group (men ≥ 30 U/L and women ≥ 20 U/L), the middle (men ≥ 20 and < 30 U/L, and women ≥ 14 and < 20 U/L), and the lowest (men < 20 U/L and women < 14 U/L). The primary outcome was the new onset of diabetes. The area under the receiver operating characteristic curves (AUC) of ALT for predicting the diabetes development was higher than that of any other markers of liver damage. The AUC for ALT was 0.71, while that for the Fibrosis-4 index was 0.51 (p < 0.001 for the difference between the AUCs). The highest and middle ALT groups had a significantly higher incidence of diabetes than the lowest group: adjusted relative risk 1.79 [95% confidence interval (CI): 1.29, 2.58], and 1.64 [95% CI: 1.17, 2.38] respectively. Of the various indicators of liver function, ALT is likely to be the most accurate and associated predictor of diabetes development.

A Slight Decrease in the Serum Albumin Level Is Associated with the Rapid Progression of Kidney Dysfunction, Even within the Normal Range.

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between the serum albumin level and the future decline in the kidney function is unclear. We evaluated the effect of the serum albumin level on the decline in the kidney function in the general population. Methods The data used were from 11,000 participants in a voluntary health checkup program conducted between 1998 and 2006 in Japan. The primary outcome for the kidney function was a difference in the estimated glomerular filtration rate (ΔeGFR) of≥3 mL/min/1.73 m2/year. The association of the risk of a decreased kidney function with the albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for the serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4-4.6 (n=5,427), and≥4.7 (n=3,043). Results Of the 11,000 participants, 346 had a ΔeGFR/year of≥3. Compared with the participants with albumin levels of≥4.7 g/dL, the risk of a decline in the kidney function was higher not only in those with albumin levels of ≤4.3 g/dL [adjusted odds ratio (OR) =2.10, 95% confidence interval (CI): 1.20-2.93] but also in those with levels of 4.4-4.6 g/dL (adjusted OR=1.53, 95% CI: 1.14-2.05). Conclusion A decreased albumin level is an independent risk factor for a rapid decline in the kidney function, even within the normal range.

Levels of fasting plasma glucose in non-hospitalized older people with high hemoglobin A1c levels.

Fasting plasma glucose levels in participants with diabetes in each age group and among those nested within glycated hemoglobin groups.

White Blood Cell Count and C-Reactive Protein Independently Predicted Incident Diabetes: Yuport Medical Checkup Center Study.

Aim: White blood cell (WBC) count or C-reactive protein (CRP) level alone may not fully indicate the chronic inflammation causing type 2 diabetes. We examined both WBC count and CRP level, independently and in combination, as predictive markers for type 2 diabetes and also considered the influence of obesity and other individual characteristics on the relationship. Materials and Methods: In total, 9,706 participants were enrolled with WBC < 10*109/L and CRP < 10 mg/L using data from the Yuport Medical Checkup Center Study. The cumulative incidence of type 2 diabetes [defined either as known diabetes, fasting plasma glucose ≥ 7.0 mmol/L, or HbA1c ≥ 6.5% (47.5 mmol/mol)] was measured. Hazard ratios (HRs) were estimated using a Cox proportional hazards model. Results: During study period, 272 men (5.5%) and 113 women (2.4%) progressed to diabetes. The progression to diabetes was predicted by both increased baseline levels of WBC count [adjusted HR = 1.29 (95% CI: 1.04-1.60)] and CRP level [1.39 (1.10-1.74)], even after adjusting for possible confounders. The combined presence was more predictive of diabetes than either alone in a four-groups analysis [1.75 (1.28-2.40)]. In addition, the elevated HRs of either or both higher WBC and CRP levels were observed across four subgroups of body mass index (BMI), including low BMI, and people who had at least one occurrence of dyslipidemia. Conclusion: Increased WBC counts and CRP levels were predictive for type 2 diabetes and the combination augmented the risk of diabetes, regardless of whether the BMI was high or low.

Prevalence and characteristics of non-obese diabetes in Japanese men and women: the Yuport Medical Checkup Center Study.

BACKGROUND: This study examined the prevalence and characteristics of type 2 diabetes in non-obese subjects to compare their cardiometabolic markers to those without diabetes. METHODS: Data were used from 17,098 men and 17,199 women from a voluntary health checkup program between 1998 and 2006 conducted in Japan. The prevalence of diabetes (fasting plasma glucose ≥ 7.0 mmol/L, hemoglobin A1c ≥ 6.5%, or known diabetes) was calculated in each subgroup of body mass index (group 1, <22; group 2, 22-25; group 3, 25-27.5; and group 4, ≥ 27.5). The effect of diabetes and obesity on risk of an abnormal level of cardiometabolic marker was evaluated with a logistic regression model. RESULTS: In men, the prevalence of diabetes was 9.5% in total, 6.4%, 9.4%, 11.3% and 16.2% in group 1 through 4, respectively. In women, it accounted for 4.3% in total, 2.4%, 4.5%, 8.7% and 12.3% per group, respectively. Non-obese diabetic subjects (in group 1 and 2) accounted for 60.8% and 62.0% of all the diabetic subjects in men and women, respectively. Non-obese population accounted for 71.2% and 83.6% of all men and women, respectively. Levels of cardiometabolic markers were higher in diabetic subjects than in non-diabetic subjects in each subgroup. Diabetes was associated with each abnormal level of cardiometabolic marker independent of obesity. CONCLUSION: Over 60% of the diabetic subjects in this Japanese population were not obese. Non-obese diabetes is not widely addressed and should be considered for increased public attention. The elevated levels of cardiometabolic markers may contribute to an increased risk of cardiovascular disease in non-obese diabetes.

Impaired fasting glucose as an independent risk factor for hypertension among healthy middle-aged Japanese subjects with optimal blood pressure: the Yuport Medical Checkup Centre retrospective cohort study.

BACKGROUND: This study aimed at investigating whether impaired fasting glucose (IFG) is an independent risk factor for incident hypertension among middle-aged Japanese subjects with optimal blood pressure (OBP). FINDINGS: This retrospective cohort study was conducted in 2943 non-diabetic and non-hypertensive subjects aged 40-64 years, who participated in a voluntary health check-up program during the baseline (1998-2002) and follow-up periods (2002-2006). A multiple logistic regression model was utilized to calculate the odds ratio (OR) of incident hypertension among men and women with IFG and OBP. OBP was defined as systolic blood pressure (SBP) <120 mmHg and diastolic blood pressure (DBP) <80 mmHg, with no known history of hypertension. In this study, hypertension was defined as SBP ≥140 mmHg and DBP ≥90 mmHg or by a self-reported clinical diagnosis of hypertension. After the mean follow-up period of 5.6 years, the incidence of hypertension in men and women was 5.7% (73/1270) and 3.8% (62/1673), respectively. The age-adjusted ORs for incident hypertension in men and women with IFG were 1.95 (95% CI, 1.21-3.15) and 3.54 (95% CI, 2.00-6.27), respectively. After adjusting for age, systolic blood pressure, body mass index, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and uric acid, the ORs for hypertension were 1.66 (95% CI; 1.02-2.70) for men and 2.62 (95% CI, 1.45-4.73) for women. CONCLUSION: The study results show that IFG may act as an independent risk factor for developing hypertension in individuals with OBP.

Undiagnosed diabetes has poorer profiles for cardiovascular and metabolic markers than known diabetes: The Yuport Medical Checkup Center Study.

We compared cardiovascular and metabolic markers between undiagnosed and known diabetes among 3045 subjects who had voluntary health check and no cardiovascular disease. Subjects with undiagnosed diabetes had poorer profiles of these markers than those with known diabetes. Undiagnosed diabetes should be recognized as a condition with these risks.

Do non-glycaemic markers add value to plasma glucose and hemoglobin a1c in predicting diabetes? Yuport health checkup center study.

BACKGROUND: Many markers have been indicated as predictors of type 2 diabetes. However, the question of whether or not non-glycaemic (blood) biomarkers and non-blood biomarkers have a predictive additive utility when combined with glycaemic (blood) biomarkers is unknown. The study aim is to assess this additive utility in a large Japanese population. METHODS: We used data from a retrospective cohort study conducted from 1998 to 2002 for the baseline and 2002 to 2006 for follow-up, inclusive of 5,142 men (mean age of 51.9 years) and 4,847 women (54.1 years) at baseline. The cumulative incidence of diabetes [defined either as a fasting plasma glucose (FPG) ≥7.00 mmol/l or as clinically diagnosed diabetes] was measured. In addition to glycaemic biomarkers [FPG and hemoglobin A1c (HbA1c)], we examined the clinical usefulness of adding non-glycaemic biomarkers and non-blood biomarkers, using sensitivity and specificity, and the area under the curve (AUC) of the receiver operating characteristics. RESULTS: The AUCs to predict diabetes were 0.874 and 0.924 for FPG, 0.793 and 0.822 for HbA1c, in men and women, respectively. Glycaemic biomarkers were the best and second-best for diabetes prediction among the markers. All non-glycaemic markers (except uric acid in men and creatinine in both sexes) predicted diabetes. Among these biomarkers, the highest AUC in the single-marker analysis was 0.656 for alanine aminotransferase (ALT) in men and 0.740 for body mass index in women. The AUC of the combined markers of FPG and HbA1c was 0.895 in men and 0.938 in women, which were marginally increased to 0.904 and 0.940 when adding ALT, respectively. CONCLUSIONS: AUC increments were marginal when adding non-glycaemic biomarkers and non-blood biomarkers to the classic model based on FPG and HbA1c. For the prediction of diabetes, FPG and HbA1c are sufficient and the other markers may not be needed in clinical practice.

Concordance of two diabetes diagnostic criteria using fasting plasma glucose and hemoglobin A1c: the Yuport Medical Checkup Centre study.

BACKGROUND: We tested the concordance of the two diagnostic criteria for diabetes using fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) by the Japan Diabetes Society (JDS) and American Diabetes Association (ADA). METHODS: We used data from 7,328 subjects without known diabetes who participated in a voluntary health checkup program at least twice between 1998 and 2006, at intervals ≤ 2 years. For repeat participants who attended the screening over two times, data from the first and second checkups were used for this study. At the first visit, diabetes was diagnosed both at FPG ≥ 7.0 mmol/L and HbA1c ≥ 6.5% using the JDS criteria. In addition, diabetes was diagnosed using two ADA criteria; ADA-FPG diabetes for persistent fasting hyperglycemia (FPG ≥ 7.0 mmol/L) or ADA-HbA1c diabetes for hyper-glycated hemoglominemia (HbA1c ≥ 6.5%), both at the first and second checkups. Subsequently, the concordance of diagnosis between the JDS and the ADA criteria was evaluated. RESULTS: At the first checkup, 153 (2.1%) persons were diagnosed with diabetes by the JDS criteria. They had higher levels of risk factors for diabetes than non-diabetic subjects. Using the first and second checkups, 174 (2.4%) and 175 (2.4%) were diagnosed with diabetes by the ADA-FPG criteria, respectively. Among 153 subjects diagnosed with diabetes by the JDS criteria, 125 (81.7%) and 129 (84.3%) had ADA-FPG and ADA-HbA1c diabetes, respectively. The kappa coefficients of the JDS criteria with ADA-FPG and ADA-HbA1c criteria were 0.759 and 0.782 (P<0.001), respectively. In the subgroup analysis stratified by sex, the concordance was well preserved at the kappa coefficients around 0.8 (between 0.725 and 0.836). CONCLUSION: The JDS diagnostic criteria for diabetes have a substantial and acceptable concordance with the ADA criteria. The JDS criteria may be a practical method for diagnosing diabetes that maintains compatibility with the ADA criteria.

Effects of age and sex in the diagnosis of type 2 diabetes using glycated haemoglobin in Japan: the Yuport Medical Checkup Centre study.

BACKGROUND: We examined how the prevalence of individuals diagnosed with diabetes differs by age and sex using the diagnostic criteria of fasting plasma glucose (FPG) and/or glycated haemoglobin (HbA1c) in a large Japanese population. METHODS: We conducted a cross-sectional study using a dataset of 33,959 people (16,869 men and 17,090 women) without known diabetes who underwent health checkups from 1998 to 2006. We divided the age range of the participants into six groups of similar numbers. We compared the prevalence of diabetes using the criteria of FPG ≥7.0 mmol/l (126 mg/dl), HbA1c ≥48 mmol/mol (6.5%), or both, in men and women in each age group. RESULTS: Men had higher prevalence of diabetes than women using the criterion of either FPG or HbA1c (7.5% men vs. 3.4% women, P<0.001), or both (4.3% men vs. 1.8% women, P<0.001). HbA1c increased steadily in women through the six age groups. In the oldest group (≥66 years), the proportion of women among those diagnosed with diabetes was as high as 42.3% (215/508) using the criterion of either FPG or HbA1c, and 41.6% (116/279) using both criteria. CONCLUSIONS: Using either FPG or HbA1c, the prevalence of people diagnosed with diabetes would almost double compared to using the criterion of both scores, and this would include more elderly women than men. The impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age and sex.

A two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.

BACKGROUNDS: We compared the usefulness of fasting plasma glucose (FPG), or hemoglobin A1c (HbA1c), or both in predicting type 2 diabetes. METHODS: This retrospective cohort study investigated 9,322 Japanese adults (4,786 men and 4,536 women), aged 19-69 yrs, free of diabetes at baseline. Usefulness was assessed by predictive values (PV), sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) maximised under the best cut-off point. RESULTS: During the average 6 years of follow-up, 221 men (4.6%) and 92 women (2%) developed diabetes. The best cut-off points for FPG (i.e., 5.67 mmol/l for men and 5.5 mmol/l for women) gave excellent AUROC, and the highest positive PV (13% for men and 9% for women) in predicting diabetes. In high risk subjects with FPG 6.1-6.9 mmol/l, 119 men (26.8%) and 39 women (28.3%) developed diabetes. Under the best cut-off points of FPG 6.39 mmol/l and A1c 5.8, AUROC and positive PV for FPG slightly decreased indicating FPG became less useful and were statistically indistinguishable from those for HbA1c in men. In fact, HbA1c was the most useful in women: HbA1c of 6.0% gave the highest positive likelihood ratio of 2.74 and larger AUROC than did FPG. Although AUROC for HbA1c was acceptable and indistinguishable from that for the combined use, HbA1c had higher specificity and positive LR than did the combined use. CONCLUSIONS: This study demonstrated that FPG was the most useful to predict diabetes in the general population. However, in subjects with FPG 6.1-6.9 mmol/l, FPG became less useful and diagnostic performance of FPG was indistinguishable from that of HbA1c in men whereas HbA1c was the most useful in women. Thus, a two-step screening, measurement of HbA1c in association with FPG, may be useful in predicting diabetes.

Fasting plasma glucose and HbA1c as risk factors for Type 2 diabetes.

AIMS: We examined the value of combining fasting plasma glucose (FPG) and glycated haemoglobin (HbA(1c)) as a predictor of diabetes, using the new American Diabetes Association (ADA) criteria of FPG and lower cut-off point of HbA(1c). METHODS: A retrospective cohort study was conducted from 1998 to 2006, inclusive, in 10 042 persons (55 884 person-years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes (defined either as an FPG > or = 7.0 mmol/l or as clinically diagnosed diabetes) was measured. RESULTS: The cumulative incidence and incidence density of diabetes were 3.7% (368 cases) and 6.6/1000 person-years over a mean follow-up period of 5.5 years. The cumulative incidence of diabetes in subjects with impaired fasting glucose (IFG) and HbA(1c) 5.5-6.4% was 24.8% (172/694 persons) compared with 0.4% (25/6698 persons), 2.5% (15/605 persons), 7.6% (156/2045 persons) in those with normal fasting glucose (NFG) and HbA(1c) < 5.5%, NFG and HbA(1c) 5.5-6.4% and IFG and HbA(1c) < 5.5%, respectively. The hazard ratio for diabetes, adjusted for possible confounders, was 7.4 (95% confidence interval, 4.70 to 11.74) for those with NFG and HbA(1c) 5.5-6.4%, 14.4 (11.93 to 27.79) for those with IFG and HbA(1c) < 5.5% and 38.4 (24.63 to 59.88) for those with IFG and HbA(1c) 5.5-6.4%. CONCLUSIONS: The combination of FPG and HbA(1c) identifies individuals who are at risk of progression to Type 2 diabetes at the new ADA criteria of FPG and a lower cut-off point of HbA(1c) than previous studies.