Hospital Health Management Center Study Research Articles

Retrospective cohort study to examine the association between serum amylase and the incidence of type 2 diabetes mellitus, Toranomon Hospital Health Management Center Study 23 (TOPICS 23)

IntroductionLow serum amylase values are cross-sectionally associated with the prevalence of type 2 diabetes mellitus (T2DM) but have not been shown to be longitudinally associated with its incidence. This retrospective...

Association between dietary iron intake and the prevalence of nonalcoholic fatty liver disease: A cross-sectional study.

The aim was to test the association between dietary iron intake and the prevalence of nonalcoholic fatty liver disease (NAFLD) in a large sample of middle-aged and elderly Chinese population.The data included in this analysis were collected from a population-based cross-sectional study, that is, the Xiangya Hospital Health Management Center Study. Dietary iron intake was assessed using a validated semiquantitative food frequency questionnaire. The relationship between dietary iron intake and the prevalence of NAFLD was examined using logistic and spline regressions.A cross-sectional study including 5445 subjects was conducted. The prevalence of NAFLD was 36.9%. Compared with the lowest quintile, the energy-adjusted odds ratios (ORs) of NAFLD were 1.33 (95% confidence interval [CI]: 1.07-1.64), 1.80 (95% CI: 1.41-2.29) and 2.11 (95% CI: 1.60-2.80) in the 3rd, 4th, and 5th quintile of iron intake, respectively (P-value for trend <.001). In addition, dietary iron intake was positively associated with the OR of NAFLD in a dose-response relationship manner (test for trend P < .001). However, after stratifying the data by gender, such association only remained in the male, but not in the female population. With adjustment of additional potential confounders, the results did not change materially.Subjects with higher dietary iron intake were subject to a higher prevalence of NAFLD in a dose-response relationship manner. However, such association probably only exists in males, but not in females.

Association Between Dietary Selenium Intake and the Prevalence of Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Objective: The aim was to examine the association between dietary selenium intake and nonalcoholic fatty liver disease (NAFLD) in a large group of middle-aged and elderly Chinese persons.Method: The data included in this analysis were from a population-based study, the Xiangya Hospital Health Management Center Study. NAFLD was diagnosed by (1) imaging or histological evidence of hepatic steatosis; (2) absence of specific etiologies of NAFLD; and (3) no heavy consumption of alcohol. Dietary selenium intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary selenium intake and the prevalence of NAFLD was evaluated using logistic and spline regression in a cross-sectional study of 5436 subjects.Results: The prevalence of NAFLD was 36.8%. Compared with the lowest quintile, the energy-adjusted odds ratios for NAFLD were 1.27 (95% confidence interval [CI], 1.07–1.52), 1.30 (95% CI, 1.09–1.55), and 1.58 (95% CI, 1.33–1.89) for the third, fourth, and fifth quintiles of selenium intake, respectively, and there was a positive dose–response relationship (r = 0.88, p for trend = 0.008). Similar results were observed for men and women separately. The findings were not materially altered by adjustment for potential confounders (i.e., age, gender, body mass index, smoking status, diabetes, hypertension, activity level, nutritional supplements, energy intake, fat intake, fiber intake, cholesterol and saturated fatty acid intake).Conclusions: In this middle-aged and elderly population, subjects with higher dietary selenium intake, even below the recommended nutrient intake in China, had higher prevalence of NAFLD in a dose–response relationship manner.

White blood cell count: an independent predictor of coronary heart disease risk in middle-aged and elderly population with hyperuricemia.

Previous studies have shown that hyperuricemia is an independent risk factor for cardiovascular disease. The aim of the study was to examine the association between white blood cell (WBC) count and coronary heart disease (CHD) risk in middle-aged and elderly population with hyperuricemia.Data included in this analysis were from a population-based cross-sectional study, that is, the Xiangya Hospital Health Management Center Study. Hyperuricemia was defined as uric acid ≥416 μmol/L in male population and ≥360 μmol/L in female population. The WBC count was classified into 3 categories based on the tertile distribution of the study population. Framingham risk scores calculated by the Adult Treatment Panel III charts were used to estimate 10-year CHD risk for each participant. The relationship between WBC count and CHD risk in patients with hyperuricemia was examined using the multivariable logistic analysis.A total of 1148 hyperuricemia patients (855 males and 293 females) aged from 40 to 85 years were included and 418 (36.4%) of them were defined with relatively high 10-year CHD risk. Compared with the lowest tertile, the crude odds ratios (ORs) of high 10-year CHD risk were 1.43 (95% confidence interval [CI] 1.06–1.92) and 1.56 (95% CI 1.16–2.11) in the 2nd and 3rd tertiles of WBC count (P for trend = .004), and the multivariable adjusted ORs of high 10-year CHD risk were 1.39 (95% CI 1.03–1.89) and 1.47 (95% CI 1.08–2.00) in the 2nd and 3rd tertiles of WBC count (P for trend = .015).This study indicated that WBC count was associated with CHD risk in patients with hyperuricemia, suggesting that WBC count, an easily accessible biomarker, could probably predict CHD risk in middle-aged and elderly population with hyperuricemia.

Association between metabolic syndrome and knee osteoarthritis: a cross-sectional study

BackgroundOsteoarthritis (OA) is the most prevalent chronic joint disease in China. The aim of this study was to examine the association between metabolic syndrome (MetS) and knee OA in a population-based Chinese study.MethodsData included in this analysis is from a cross-sectional study, i.e., the Xiangya Hospital Health Management Center Study. MetS was diagnosed according to the criteria defined by the Chinese Diabetes Society. Radiographic knee OA was defined as changes equivalent to Kellgren-Lawrence (K-L) grade 2 or above at least one side. Associations between MetS and its components with OA were evaluated by conducting multivariable adjusted logistic regression.ResultsA total of 5764 participants were included in the present study. The unadjusted OR (1.27, 95%CI: 1.10–1.47, P = 0.001), age-sex adjusted OR (1.17, 95%CI: 1.01–1.36, P = 0.041) and multivariable adjusted OR (1.17, 95%CI: 1.01–1.36, P = 0.043) all suggested a positive association between MetS and knee OA. Besides, its components (e.g., overweight, hypertension and dyslipidemia) were also associated with the prevalence of radiographic knee OA respectively, after adjusting for some confounding factors. In addition, with the accumulation of MetS components, the prevalence of knee OA increased. Furthermore, MetS as a whole was associated with the prevalence of knee osteophyte (OSP) (OR = 1.72, 95%CI: 1.42–2.09, P < 0.001), but not joint space narrowing (JSN) (OR = 1.06, 95%CI: 0.91–1.23, P = 0.449).ConclusionsThe findings of the present study indicated that there was a positive association between the prevalence of MetS and knee OA. However, MetS as a whole was associated with the higher prevalence of knee OSP, but not JSN, which should shed light on our understanding the association between MetS and OA.

Dose-response relationship between lower serum magnesium level and higher prevalence of knee chondrocalcinosis

BackgroundThe aim was to assess serum magnesium levels in relation to prevalence of knee chondrocalcinosis in two population-based Chinese studies.MethodsData included in this analysis consisted of two population-based cross-sectional studies, i.e., the Xiangya Hospital Health Management Center Study and the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was present if there was definite linear cartilage calcification. Serum magnesium concentration was measured using the chemiluminescence method. We examined the relation of serum magnesium levels to prevalence of knee chondrocalcinosis using generalized estimating equations.ResultsThe prevalence of knee chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40–0.87) and 0.49 (95% CI 0.33–0.72) in the second and the third tertiles of serum magnesium, respectively (P for trend <0.001). The prevalence of knee chondrocalcinosis in the XO Study I (n = 1316) was 4.1%. The age, sex and BMI-adjusted ORs of chondrocalcinosis were 0.67 (95% CI 0.34–1.30) in the second and 0.45 (95% CI 0.21–0.94) in the third tertile of serum magnesium when compared with the lowest tertile (P for trend = 0.030). Similar results were observed in men and women in both studies. Adjusting for additional potential confounders did not change the results materially.ConclusionsSubjects with lower levels of serum magnesium, even within the normal range, had higher prevalence of knee chondrocalcinosis in a dose-response relationship manner, suggesting that magnesium may have a preventive or therapeutic potential for knee chondrocalcinosis.

Impact of individual components and their combinations within a family history of hypertension on the incidence of hypertension: Toranomon hospital health management center study 22.

Although a family history (FH) of hypertension is a risk factor for the development of hypertension, only a few studies have investigated in detail the impact of individual components of an FH on incident hypertension. We investigated the impact of individual components and their combinations on the presence or development of hypertension considering obesity, smoking habits, physical activity, and other metabolic parameters.Studied were 12,222 Japanese individuals without hypertension (n = 9,766) and with hypertension (n = 2,456) at the baseline examination. The presence or incidence of hypertension during 5 years after a baseline examination was assessed by the presence of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or a self-reported history of clinician-diagnosed hypertension. In this prospective study, the odds ratio for incident hypertension was 1.39 (95% confidence interval [CI], 1.22, 1.59) for individuals with any FH of hypertension compared with those without such an FH. Individuals with an FH of hypertension in both parents and one or more grandparents had an odds ratio of 3.05 (95% CI 1.74, 5.36) for hypertension compared with those without an FH of hypertension. FH was associated with incident hypertension independently of other modifiable risk factors such as obesity, smoking, physical inactivity, hyperglycemia, hyperuricemia, and hypertriglyceridemia.A parental history of hypertension was an essential component within an FH for incident hypertension. FH of hypertension over two generations with both parents affected was the most important risk factor for incident hypertension. Although an FH is not a modifiable risk factor, modifying other risk factors could contribute to reducing the risk of hypertension even among individuals with a family history of hypertension.

Assessment of kidney dysfunction with cystatin C- and creatinine-based estimated glomerular filtration rate and predicting type 2 diabetes: Toranomon Hospital Health Management Center Study 21

ObjectiveWhether early stages of kidney dysfunction assessed by the estimated glomerular filtration rate from cystatin C measurements (eGFRCysC) rather than from creatinine measurements (eGFRCr) would more precisely reflect the risk of developing type 2 diabetes (T2D) has not been clarified. We compared the risk of developing T2D associated with renal dysfunction indicated by eGFRCysC or eGFRCr measurements. MethodsStudied were 2131 Japanese individuals without diabetes. Hazard ratios (HRs) for the development of T2D over 3–5 y were calculated across categories of eGFRCysC and eGFRCr, respectively. ResultsReduced levels of eGFRCysC were associated with a step-wise increase in the cumulative incidence rate of T2D (p=0.007). In comparison with the eGFRCysC >85th percentile group (≥117.4ml/min/1.73m2), the lowest group, which was the eGFRCysC <15th percentile group (<86.2ml/min/1.73m2), had an adjusted HR of 2.30 (95% CI 1.13, 4.68) for T2D. Compared with the eGFRCr >85th percentile group, the lowest eGFRCr group (<15th percentile) had an HR of 1.19 (0.63, 2.24) for T2D. However, individuals with eGFRCr <60ml/min/1.73m2 had a significantly increased risk of T2D. Clustering of both low eGFRCysC and low eGFRCr further elevated the HR for T2D compared with the presence of either. ConclusionsAlthough eGFRCr in ranges indicating chronic kidney disease reflected an elevated risk of developing diabetes, earlier stages of kidney dysfunction indicated by reduced eGFRCysC, which could not be captured by reduced eGFRCr, would be a marker for an elevated risk of developing T2D.

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Trajectory of body mass index before the development of type2 diabetes in Japanese men: Toranomon Hospital Health Management Center Study 15.

Aims/IntroductionWe aimed to investigate the long-term trajectory of general adiposity assessed by the body mass index (BMI) before the onset of type 2 diabetes in Japanese individuals.Materials and MethodsWe retrospectively examined data on 1,553 Japanese men without diabetes. Mean BMI and incident cases of diabetes (diabetes indicated by fasting glucose concentrations ≥7.0 mmol/L, a self-reported history of clinician-diagnosed diabetes, or glycated hemoglobin ≥6.5% (≥48 mmol/mol) were assessed on an annual basis over a 10-year period after the baseline examination.ResultsMean (standard deviation) BMI at the time of diagnosis was 24.4 kg/m2 (3.1 kg/m2) among cases of diabetes (n = 191). An increasingly high BMI was associated with the early stage of the disease development, such as an 8- to 10-year prediagnosis period; individuals who developed diabetes experienced a prolonged and stable elevated BMI of ≥24.4 kg/m2 over the 8 years before the diagnosis of diabetes. The mean BMI among the non-cases of diabetes did not exceed 23.2 kg/m2 throughout the period.ConclusionsThese results suggested that Japanese men who eventually developed diabetes during the 10-year observation period were not characterized as obese, but had stable high-normal BMIs before the onset of diabetes. Previous evidence showed that values for glycemic markers rapidly increased before the development of diabetes; however, the present study showed a slight gain in BMI in the earlier stage of the natural history of diabetes followed by a prolonged period of overweight.

Fasting glucose and HbA1c levels as risk factors for the development of hypertension in Japanese individuals: Toranomon hospital health management center study 16 (TOPICS 16).

We investigated the effect of elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) on the risk of development of hypertension among apparently healthy Japanese. Studied were 9584 individuals without known diabetes and hypertension. During a 5-year follow-up period, 1098 individuals developed hypertension. Elevated concentrations of FPG, rather than of HbA1c, were significantly predictive of future hypertension. Compared with the lowest quartile category of FPG (<4.9 mmol l(-1)), the second (4.9-<5.2 mmol l(-1)), third (5.2-<5.6 mmol l(-1)) and highest (⩾ 5.6 mmol l(-1)) quartile categories had age-, sex- and body mass index-adjusted odds ratios (95% confidence interval) of 1.35 (1.10, 1.66), 1.39 (1.13, 1.71) and 1.85 (1.51, 2.28) for hypertension, respectively. In the highest quartile of FPG, the multivariate-adjusted OR was 1.37 (1.10, 1.70) compared with the lowest quartile. Results of these adjusted models showed no significant association across quartile categories of HbA1c concentrations and an increased risk of developing hypertension. The joint effect of hyperglycemia and overweight, older age or prehypertension resulted in further elevated ORs for hypertension than the absence of such an association. Higher FPG levels rather than HbA1c were strongly predictive of future hypertension among Japanese. Hyperglycemia along with older age, overweight and prehypertension contributed to identifying individuals at increased risk of developing hypertension.

Simple self-reported behavioral or psychological characteristics as risk factors for future type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 14.

Aims/IntroductionDepression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self-report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.Materials and MethodsWe investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7–13 years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.ResultsResults of Cox regression analysis showed that lack of perseverance (age- and sex-adjusted HR 1.41, 95% confidence interval 1.07–1.84), anger, (HR 1.51, 95% confidence interval 1.07–2.12) or memory loss (HR 1.47, 95% confidence interval 1.14–1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94-fold (95% confidence interval 1.19–3.15) increased risk of type 2 diabetes than those without those two symptoms.ConclusionsResponses to a simple self-report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type 2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals.

Potential impact of joint association of alanine aminotransferase and gamma-glutamyltransferase on insulin resistance in Japan: The Toranomon Hospital Health Management Center Study 19 (TOPICS 19)

To investigate the potential impact of joint association of alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) on insulin resistance and β-cell dysfunction in healthy Japanese individuals with a normal range of liver enzymes. This study included 1010 individuals (545 men and 465 women) aged 20-89 years who underwent an oral glucose tolerance test for health screening. Participants were divided into four groups on the basis of median values for ALT and GGT: (i) both ALT and GGT low (both-low); (ii) ALT high and GGT low (ALT-high); (iii) ALT low and GGT high (GGT-high); and (iv) both ALT and GGT high (both-high). Logistic regression analysis was used to investigate the relationship between liver enzyme and insulin dynamics, such as Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) and insulinogenic index (IGI). The insulin resistance was defined when HOMA-IR was 2.5 or more. IGI of less than 0.4 was considered to be decreased early-phase insulin secretion. Mean values of HOMA-IR in men was 1.5 in the both-low group, 1.8 in ALT-high, 1.8 in GGT-high and 2.8 in both-high. The mean HOMA-IR in women was 1.3 in the both-low group, 1.3 in ALT-high, 1.6 in GGT-high and 2.0 in both-high. HOMA-IR in the both-high group was significantly higher than that in the both-low group regardless of the difference of sex. Multivariate analysis showed that insulin resistance occurred when the patient had high liver enzymes. Combining the two liver function markers would be effective for identifying individuals with insulin resistance.

Metabolically healthy obesity, presence or absence of fatty liver, and risk of type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20).

We investigated whether the metabolically healthy obese (MHO) phenotype was associated with an increased risk of the development of diabetes. If so, we aimed to determine what factors could explain this finding. Studied were 8090 Japanese individuals without diabetes. Metabolic health status was assessed by common clinical markers: blood pressure, triglycerides, high-density lipoprotein-cholesterol, and fasting glucose concentrations. The cutoff value for obesity or normal weight (NW) was a body mass index of 25.0 kg/m(2). The 5-year incidence rate of diabetes was 1.2% (n = 58 of 4749) in metabolically healthy NW (MHNW) individuals, 2.8% (n = 20 of 719) in MHO individuals, 6.0% (n = 102 of 1709) in metabolically abnormal NW individuals, and 10.3% (n = 94 of 913) in metabolically abnormal obese individuals. Although MHO individuals had no or one metabolic factor, 47.8% had ultrasonographic fatty liver (FL). The MHO group had a significantly increased risk of diabetes compared with the MHNW group [multivariate adjusted odds ratio (OR) 2.23 (95% confidence interval [CI] 1.33, 3.75)], but this risk was attenuated after adjustment for FL. Compared with the MHNW/non-FL group, the risk of diabetes in the MHO/non-FL group was not significantly elevated [OR 1.01 (95% CI 0.35, 2.88)]. However, the MHO/FL and MHNW/FL groups had similarly elevated risks of diabetes [OR 4.09 (95% CI 2.20, 7.60) and 3.16 (1.78, 5.62), respectively]. Almost half of the MHO participants had FL, which partially explained the increased risk of diabetes among the obese phenotypes. The presence of FL should be evaluated to assess whether an individual was actually in a metabolically benign state for the prediction of diabetes.

Association of living alone with the presence of undiagnosed diabetes in Japanese men: the role of modifiable risk factors for diabetes: Toranomon Hospital Health Management Center Study 13 (TOPICS 13)

To investigate whether living alone was associated with the presence of undiagnosed diabetes and whether this association could be attenuated by modifiable lifestyle habits. This cross-sectional study included 6400 Japanese men without a history of diagnosed diabetes. Individuals with currently undiagnosed diabetes were identified through fasting glucose concentration ≥7.0mmol/l or HbA1c concentration ≥ 48mmol⁄mol (≥ 6.5%). Effect modification was examined using body mass index, hypertension, history of dyslipidaemia, drinking habits, smoking habits, physical activity, vegetable intake, emotional stress and depressed mood. Men who lived alone (n=1098) had a significantly elevated odds ratio for having undiagnosed diabetes in an age-adjusted model (odds ratio 1.45, 95% CI 1.07, 1.96; P=0.018). After adjustment for lifestyle factors, the association was slightly attenuated (odds ratio 1.40, 95% CI 1.02, 1.91; P=0.036). After further adjustment for all factors mentioned above, living alone was still marginally significantly associated with the presence of undiagnosed diabetes (odds ratio 1.38, 95% CI 1.003, 1.90; P=0.048). A significant association of living alone with the presence of undetected diabetes was particularly observed among men who were overweight, currently smoked and were physically inactive, or had any one of those three factors. The association between undiagnosed diabetes and living alone can be partially influenced by modifiable lifestyle factors. Men who lived alone, especially those who did not engage in favourable lifestyle habits, were more likely to have undiagnosed diabetes. Such individuals have a higher probability of having undetected diabetic hyperglycaemia and would need to undergo glucose tests to identify the disease.

Role of alcohol drinking pattern in type 2 diabetes in Japanese men: the Toranomon Hospital Health Management Center Study 11 (TOPICS 11)

Findings of past studies on the effect of drinking patterns on diabetes risk have been inconsistent. We aimed to investigate the role of drinking frequency and usual quantity consumed in the development of type 2 diabetes. Enrolled were 1650 Japanese men without diabetes (diabetes: fasting plasma glucose ≥7.0 mmol/L, glycated hemoglobin ≥6.5%, or self-reported clinician-diagnosed diabetes). Average alcohol consumption and 12 combinations of frequency and usual quantity per drinking occasion were assessed at the baseline examination. The absolute risk and HR for the development of diabetes were calculated. During a mean follow-up period of 10.2 y, 216 individuals developed diabetes. Lifetime abstainers (n = 153) had a relatively low incidence of diabetes (9.1/1000 person-years), similar to moderate consumers (99-160 g ethanol/wk; 9.0/1000 person-years). Increasingly higher quantities of alcohol usually consumed per occasion increased the risk of diabetes regardless of drinking frequency. The lowest incidence rate of diabetes (8.5/1000 person-years) was associated with the consumption of <1 drink (<23 g ethanol) per occasion over ≥6 times/wk. Binge drinking (≥3 drinks per occasion) significantly increased the risk of future diabetes regardless of frequency (HR: 1.79; 95% CI: 1.17, 2.74) compared with <1 drink per occasion. Among current drinkers, a drinking pattern of <1 drink per occasion regularly over 6 times within a week was associated with the lowest risk of developing diabetes. Usual quantity per drinking occasion was a more important determinant than was weekly drinking frequency in the association between alcohol consumption and risk of diabetes in Japanese men.

Development of a Screening Score for Undiagnosed Diabetes and Its Application in Estimating Absolute Risk of Future Type 2 Diabetes in Japan: Toranomon Hospital Health Management Center Study 10 (TOPICS 10)

The objective of the study was to develop a screening score for undiagnosed diabetes by eliciting information on noninvasive clinical markers and to assess its effectiveness for identifying the presence of diabetes and predicting future diabetes. A screening score was cross-sectionally developed for 33 335 Japanese individuals aged 18-88 years without known diabetes who underwent a health examination. We validated its utility and compared it with existing screening tools in an independent population (n = 7477). After initial assessment of the instrument, 7332 nondiabetic individuals were followed up for a mean 4.0 years. Prevalence of undiagnosed diabetes (fasting plasma glucose ≥ 7.0 mmol/L or glycated hemoglobin ≥ 6.5%) was 2.9% (n = 965). Diabetes score included age, sex, family history of diabetes, current smoking habit, body mass index, and hypertension with an area under the receiver-operating characteristics curve of 0.771. Screening with 8 or more points yielded a sensitivity of 72.7% and a specificity of 68.1%. In the validation cohort, the area under the receiver-operating characteristics curve was 0.806. The developed score with 8 or more points had better positive predictive value (9.6%) and positive likelihood ratio (2.52) compared with existing tools (positive predictive value, from 6.9% to 9.4%; positive likelihood ratio, from 1.77 to 2.46) in which each tool's highest combination of sensitivity and specificity was observed. The 4-year cumulative risk of developing diabetes gradually escalated in association with higher screening scores at the initial examination. Our algorithm could serve as a self-assessment tool for undiagnosed diabetic patients needing timely medical care and as a prognostic tool for individuals without present diabetes who must be closely followed up to prevent future diabetes.

High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)

We aimed to characterize the association of insulin resistance, impaired insulin secretion and β-cell dysfunction in relation to HbA(1c) levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. This cross-sectional study included 1444 individuals without a history of outpatient treatment of diabetes or use of insulin or oral hypoglycaemic agents. The homeostasis model assessment of insulin resistance and beta-cell function, insulinogenic index, Matsuda index and disposition index were calculated using data from 75-g oral glucose tolerance tests and compared across quintile (Q) categories of HbA(1c) levels. Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA(1c) exceeded 36 mmol/mol (5.4%). A HbA(1c) concentration of 36-37 mmol/mol (5.4-5.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of β-cell function value and 31% lower insulinogenic index value compared with HbA(1c) ≤ 32 mmol/mol (≤ 5.1%) (Q1) (P <0.01). Further, a HbA(1c) concentration of 38-40 mmol/mol (5.6-5.8%) (Q4) was associated with 17% (P <0.01) and 24% (P <0.05) reductions in those indexes, respectively. However, the homeostasis model assessment of insulin resistance was not significantly elevated and the Matsuda index was not significantly lower unless HbA(1c) exceeded 41 mmol/mol (5.9%). Individuals with HbA(1c) ≥ 41 mmol/mol (≥ 5.9%) (Q5) had a 69% lower disposition index than those with a HbA(1c) concentration of ≤ 32 mmol/mol (≤ 5.1%) (Q1). Elevated HbA(1c) levels ≥ 41 mmol/mol (≥ 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and β-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA(1c) levels of 36-40 mmol/mol (5.4-5.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.

Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6)

The aims of this study were to assess the clinical significance of introducing HbA(1c) into a risk score for diabetes and to develop a scoring system to predict the 5year incidence of diabetes in Japanese individuals. The study included 7,654 non-diabetic individuals aged 40-75years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0mmol/l, HbA(1c) ≥6.5% (48mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA(1c) or both to NLA. The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA(1c) scores was non-significant (0.836 vs 0.837; p = 0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA(1c) had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA(1c) resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p < 0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively. Information on HbA(1c) or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.

Low Lung Function and Risk of Type 2 Diabetes in Japanese Men: The Toranomon Hospital Health Management Center Study 9 (TOPICS 9)

ObjectiveTo evaluate the effect of elevated fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) concentrations on lung dysfunction and to prospectively investigate whether reduced lung function would be independently predictive of diabetes. Participants and MethodsFrom January 6, 1997, through December 22, 2008, we observed 5346 men with no history of diabetes or lung dysfunction. Hazard ratios (HRs) for incident diabetes (FPG ≥126 mg/dL, HbA1c ≥6.5%, or self-reported clinician-diagnosed diabetes) were estimated for spirometry indices as continuous and categorical variables. ResultsElevated HbA1c concentrations within the normal range were significantly and more strongly associated with reduced forced vital capacity and forced expiratory volume in the first second after expiration (FEV1) than were FPG concentrations. During a 4.0-year follow-up, diabetes developed in 214 individuals. A 10-point decrease in percentage of FEV1 predicted value was associated with an increased HR of 1.21 (95% confidence interval [CI], 1.09-1.34; P=.001) for diabetes after adjustment for demographic factors and body mass index. This association remained significant even after adjustment for metabolic factors, smoking status, and FPG or HbA1c concentrations but was attenuated substantially after adjustment for baseline HbA1c values (HR, 1.13; 95% CI, 1.01-1.26; P=.03). Lower quartile (Q) categories of percentage of FEV1 predicted value were associated with increased risk of diabetes independently of known predictors including HbA1c (HR, 1.73; 95% CI, 1.14-2.62 for Q1; and HR, 1.76; 95% CI, 1.15-2.69 for Q2). ConclusionReduced lung function was significantly related to chronic glycemic exposure within a normal range. Relatively low pulmonary function was an independent risk factor for diabetes in apparently healthy Japanese men.