Comparison of different aspects of BMI history to identify undiagnosed diabetes in Japanese men and women: Toranomon Hospital Health Management Center Study 12 (TOPICS 12).

AIMS: To examine current BMI and various aspects of BMI history as pre-screening tools for undiagnosed diabetes in Japanese individuals. METHODS: This cross-sectional study included 16 226 men and 7026 women aged 30-75 years without a self-reported history of clinician-diagnosed diabetes. We estimated the probability of having undiagnosed diabetes (fasting glucose ≥ 7.0 mmol/l and/or HbA1c ≥ 48 mmol/mol (≥ 6.5%) for the following variables: current BMI, BMI in the early 20s (BMI(20y)), lifetime maximum BMI (BMI(max)), change between BMI in the early 20s and current BMI (ΔBMI(20y-cur)), change between BMI in the early 20s and maximum BMI (ΔBMI(20y-max)), and change between lifetime maximum and current BMI (ΔBMI(max-cur)). RESULTS: The prevalence of undiagnosed diabetes was 3.3% (771/23252) among participants. BMI(max) , ΔBMI(20y-max) and current BMI (1-sd increments) were more strongly associated with diabetes than the other factors (multivariate odds ratio 1.58 [95% CI 1.47-1.70] in men and 1.65 [95% CI 1.43-1.90] in women for BMI(max) ; multivariate odds ratio 1.47 [95% CI 1.37-1.58] in men and 1.61 [95% CI 1.41-1.84] in women for ΔBMI(20y-max) ; multivariate odds ratio 1.47 [95% CI 1.36-1.58] in men and 1.63 [95% CI 1.40-1.89] in women for current BMI). The probability of having diabetes was markedly higher in those with both the highest tertile of BMI(max) and greatest ΔBMI(20y-max) ; however, a substantially lower likelihood of diabetes was observed among individuals with the lowest and middle tertiles of current BMI (< 24.62 kg/m² in men and < 22.54 kg/m² in women). CONCLUSIONS: Lifetime maximum BMI and BMI changes from early adulthood were strongly associated with undiagnosed diabetes. Adding BMI history to people's current BMI would improve the identification of individuals with a markedly higher probability of having undiagnosed 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).

AIMS: To investigate whether living alone was associated with the presence of undiagnosed diabetes and whether this association could be attenuated by modifiable lifestyle habits. METHODS: 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 ≥7.0 mmol/l or HbA1c concentration ≥ 48 mmol/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. RESULTS: 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. CONCLUSIONS: 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.

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).

AIMS/HYPOTHESIS: 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 5 year incidence of diabetes in Japanese individuals. METHODS: The study included 7,654 non-diabetic individuals aged 40-75 years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/l, HbA(1c) ≥6.5% (48 mmol/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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: Information on HbA(1c) or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.

High normal HbA(1c) levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8).

AIMS: We aimed to characterize the association of insulin resistance, impaired insulin secretion and ß-cell dysfunction in relation to HbA(1c) levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. METHODS: 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. RESULTS: 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 ß-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). CONCLUSIONS: Elevated HbA(1c) levels ≥ 41 mmol/mol (≥ 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and ß-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.

Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA(1c) and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4).

AIM: To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA(1c) values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals. METHODS: The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA(1c) ≥ 48 mmol/mol (≥ 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l or 6.1-6.9 mmol/l) and elevated HbA(1c) [39-46 mmol/mol (5.7-6.4%) or 42-46 mmol/mol (6.0-6.4%)]. RESULTS: During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.5-32.0% reverted to the normoglycaemic state as having neither elevated HbA(1c) nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l had a 100% cumulative risk of developing diabetes. CONCLUSIONS: The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l would predict definite progression to diabetes.

Low serum potassium levels and risk of type 2 diabetes: the Toranomon Hospital Health Management Center Study 1 (TOPICS 1).

AIMS/HYPOTHESIS: Evidence has suggested that low serum potassium concentrations decrease insulin secretion, leading to glucose intolerance, and that hypokalaemia induced by diuretics increases the risk for diabetes in hypertensive individuals. However, no prospective study has investigated the association between serum potassium and the development of type 2 diabetes in a healthy cohort comprised of Asian individuals not being administered antihypertensive medications. This study aimed to investigate whether low serum potassium is associated with increased risk of type 2 diabetes in apparently healthy Japanese men. METHODS: We followed 4,409 Japanese men with no history of diabetes, use of antihypertensives, renal dysfunction or liver dysfunction (mean ± SD age, 48.4 ± 8.4 years). Cox proportional hazards regression was used to estimate HRs for incident diabetes (fasting plasma glucose level ≥ 7.0 mmol/l, HbA(1c) ≥ 6.5% or self-reported) including serum potassium concentration as either a categorical or a continuous variable. RESULTS: During a 5 year follow-up, 250 individuals developed type 2 diabetes. The lowest tertile of serum potassium (2.8-3.9 mmol/l) was independently associated with the development of diabetes after adjustment for known predictors (HR 1.57 [95% CI, 1.15-2.15]) compared with the highest tertile (4.2-5.4 mmol/l). Every 0.5 mmol/l lower increment in the baseline serum potassium level was associated with a 45% (12-87%) increased risk of diabetes. CONCLUSIONS/INTERPRETATION: Mild to moderately low serum potassium levels, within the normal range and without frank hypokalaemia, could be predictive of type 2 diabetes in apparently healthy Japanese men.

Reduced urinary insulin clearance in patient with abnormal insulinemia.

We recently reported a new case of abnormal insulinemia with LeuA3 insulin. Herein, we measured urinary insulin clearance during oral glucose tolerance tests in proband with abnormal insulinemia (44-yr-old female), three affected family members, two unaffected family members, two other hyperinsulinemic patients with obesity, five non-insulin-dependent diabetic patients, and five normal control subjects. Urinary insulin-to-creatinine clearance ratio in the proband and her affected family members was 0.22 X 10(-3) +/- 0.07 (mean +/- SD, n = 4) and was markedly reduced compared with those of other groups: 1.73 X 10(-3) in two unaffected family members, 2.77 X 10(-3) in two other hyperinsulinemic patients with obesity, 2.99 X 10(-3) +/- 1.48 in five non-insulin-dependent diabetic patients, and 2.54 X 10(-3) +/- 0.67 in five normal control subjects. In contrast, urinary C-peptide clearance in these groups was not significantly different from controls. Binding of immunopurified insulins extracted from urine of the patients with abnormal insulinemia to guinea pig kidney membrane was slightly decreased (71% of standard insulin), in contrast with the observation that serum insulin of the proband had much less receptor-binding activity. Reverse-phase HPLC analysis of the immunopurified insulin of the proband revealed that the ratios of normal insulin to abnormal insulin were 8:3 in urine and 1:7 in serum, respectively. These results suggest that excretion of abnormal insulin in urine is much less than that of normal insulin.

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.

Instability of fasting blood glucose values in noninsulin-dependent diabetic patients with long-term insulin treatment.

We studied serum free C-peptide immunoreactivity (CPR) and the coefficient of variation (CV) of fasting blood glucose values (FBG) in 26 insulin-treated patients with non-insulin-dependent diabetes mellitus (NIDDM) in relation to the duration of insulin treatment. Serum free CPR responses during 100 g oral glucose tolerance test (OGTT) were significantly lower in patients with insulin treatment for five years or more than in those with insulin treatment for less than five years although their previous immunoreactive insulin (IRI) responses during OGTT before insulin treatment showed no significant difference. CV of FBG was found to be significantly higher at the time of this study (20.6 +/- 7.8%, mean +/- SD) than at the second year of insulin treatment (15.3 +/- 7.7%, P less than 0.05) in the patients with insulin treatment for five or more years but did not show any significant difference in patients with insulin treatment for less than five years at the corresponding times. Thus we measured CV of the FBG in NIDDM patients at various intervals during the long-term insulin or oral hypoglycemic agent treatment in another study. In 20 patients with insulin treatment, CV of FBG was found to be significantly different among the various intervals during insulin treatment (P less than 0.0025). It was significantly higher at the eight year (22.2 +/- 8.6%) and 12th year (21.9 +/- 9.1%) than at the second year (14.9 +/- 6.1%) and fifth year (15.0 +/- 6.7%) of insulin treatment (P less than 0.025, P less than 0.025; P less than 0.05, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic beta-cell secretion after oral glucose and intravenous glucagon: different responses to dietary control of plasma glucose in newly diagnosed patients with NIDDM.

Pancreatic beta-cell secretion after oral glucose or intravenous glucagon stimulation was studied in newly diagnosed patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after glycemic control by diet treatment alone. Insulin secretion to oral glucose showed significant improvement, while C-peptide release by glucagon showed no significant difference before and after diet treatment. The finding suggests that pancreatic beta-cell response to oral glucose varies with different metabolic states, but this is not so after glucagon stimulation in NIDDM patients.

Serum free C-peptide response to oral glucose loading as a parameter for the monitoring of pancreatic B-cell function in diabetic patients.

As a parameter for evaluating pancreatic B-cell function, the accuracy of measuring serum free C-peptide immunoreactivity (CPR) was compared with that of measuring plasma immunoreactive insulin (IRI) and urine CPR in diabetic patients during a 100 g oral glucose tolerance test. In 25 non-obese patients receiving oral hypoglycemic agent or diet treatment alone, a positive correlation between the sum of serum free CPR (sigma serum free CPR) and the sum of plasma IRI (sigma plasma IRI) was noted (r = 0.68, P less than 0.001). However, the sum of blood glucose values was found to be negatively correlated to sigma free CPR (r = -0.56, P less than 0.0025), but not to sigma plasma IRI (r = -0.25, NS). In 23 patients receiving diet, oral hypoglycemic agent or insulin treatment, a positive correlation between sigma serum free CPR and urine CPR was noted (r = 0.75, P less than 0.001). However, no significant correlation was found when only insulin-treated patients were investigated (r = 0.37, NS, n = 17). In addition, patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus were better differentiated by measuring sigma serum free CPR than urine CPR. Thus, we concluded that the measurement of serum free CPR during OGTT provides an extremely valuable method for monitoring pancreatic B-cell function in diabetic patients, whether they are receiving insulin treatment or not.

Waist/height ratio as a simple and useful predictor of coronary heart disease risk factors in women.

To determine whether the waist/height ratio is a better predictor of coronary heart disease (CHD) risk factors in women than body mass index (BMI) or the waist/hip ratio, simple and multiple regression analysis for these obesity indices and CHD risk factor levels [systolic and diastolic blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), triglyceride, cholesterol, high density lipoprotein (HDL) cholesterol], prevalences (hypertension, abnormal glucose tolerance, hypertriglyceridemia, hypercholesterolemia, low HDL cholesterol) were measured in 1,077 women. The highest regression coefficients were consistently between the waist/height ratio and most of the risk factors by simple regression analysis. Furthermore, the waist/height ratio was the single independent variable to all or most of the risk factors by multiple regression analysis of the waist/height ratio and BMI or the waist/height ratio and the waist/hip ratio. These findings suggest that the waist/height ratio may be a better predictor of multiple CHD risk factors than BMI or the waist/hip ratio.

Abdominal fat distribution and coronary heart disease risk factors in men-waist/height ratio as a simple and useful predictor.

OBJECTIVE: To determine whether waist/height ratio is a useful predictor for coronary heart disease (CHD) risk factors in men. DESIGN: An epidemiologic study comparing relationships between waist/height ratio, body mass index, waist/hip ratio and CHD risk factor levels [continuous variables--systolic and dialostic blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), triglyceride, cholesterol, HDL cholesterol values] and the risk factor morbidity index (sum of the risk factor scores for hypertension, abnormal glucose tolerance, hypertriglyceridemia, hypercholesterolemia and low HDL cholesterol--one point each if present). SETTING: A health examination facility within a general hospital. SUBJECTS: 3131 men underwent routine health examination. RESULTS: Body mass index, waist/hip ratio and waist/height ratio were significantly associated with all of the risk factor levels and with the risk factor morbidity index according to the result of simple regression analysis. Multiple regression analysis for waist/hip ratio and body mass index showed that both of them were also significantly associated with all of the risk factor levels and with the risk factor morbidity index, except HbA1c levels with body mass index. According to the results of multiple regression analysis for waist/height ratio and body mass index, body mass index was not significantly associated with fasting blood glucose, HbA1c, cholesterol levels or the risk factor morbidity index whereas waist/height ratio was significantly associated with all of the variables. On the other hand, while waist/height ratio was significantly associated with all of the variables, waist/hip ratio was not significantly associated with most of the variables when waist/height ratio and waist/hip ratio were compared. CONCLUSION: Waist/height ratio, an index of abdominal obesity, may be a better predictor of multiple CHD risk factors in men than waist/hip ratio in mass epidemiologic studies.

Is there any difference in coronary heart disease risk factors and prevalence of fatty liver in subjects with normal body mass index having different physiques?

Levels of coronary heart disease (CHD) risk factors such as systolic and diastolic blood pressure, fasting blood glucose, hemoglobin A1c, triglyceride, cholesterol, HDL-cholesterol, prevalence of hypertension, abnormal glucose tolerance, hypertriglyceridemia, hypercholesterolemia, low HDL-cholesterol level, and fatty liver in normal body mass index (BMI) subjects with high or low waist/height ratios were investigated in middle aged men (45-54 years, BMI: 22-23.2 kg/m2) undergoing a routine health examination. The subjects were divided into two groups according to whether their waist/height ratios were > or = 0.5 (n = 131) or < 0.5 (n = 121). There was no significant difference in age or BMI between the two groups, however, fasting blood glucose, hemoglobin A1c, triglyceride, cholesterol levels, the prevalence of abnormal glucose tolerance, hypercholesterolemia, fatty liver (30.5% vs. 15.7%, p < 0.01), and morbidity index for CHD risk factors (sum of the five risk factors scored as one point each if present) (1.46 vs. 1.04, p < 0.01) were significantly higher in the high waist/height group. In conclusion, even normal BMI subjects should pay attention to their waist/height ratio because of higher CHD risk factor levels, prevalences, morbidity index for CHD risk factors, and higher prevalence of fatty liver.

Do people with similar waist circumference share similar health risks irrespective of height?

In order to know whether people of similar waist circumference having similar health risks irrespective of height, comparisons of odds ratios for coronary risk factors and fatty liver by echogram were made between the subjects from the first (short, < or = 164.5 cm) and fourth quartiles (tall, > or = 172.4 cm) of height from both the third (84.5 approximately < 89 cm) and fourth (> or = 89 cm) quartiles of waist circumference from 3117 men (ranging 35-64 years old) who underwent routine health examinations in Tokyo. After adjusting for age, and with tall subjects in the same waist circumference category as reference, the odds ratios were significantly higher for the short people from the third quartile of waist circumference for the risk of hypertension (1.62, 95% CI 1.002-2.63), hyperglycemia (3.34, 1.27-9.95) and fatty liver (2.12, 1.30-3.50). However, there were no significant differences in odds ratios of any risk health risks between short people and tall people from the fourth quartile of waist circumference. Although people of prominently large waist circumferences may have similar health risks of the above items irrespective of height, short people have higher health risks than tall people in the moderately large waist circumference population of Japanese men.

Reduction in urine C-peptide clearance rate after metabolic control in NIDDM patients.

One hour urine C-peptide and creatinine clearance rates were determined simultaneously in 25 hospitalized patients with non-insulin-dependent diabetes mellitus (NIDDM) undergoing sulfonylurea and/or diet treatment. The studies had been performed after an overnight fast on the second day of admission and on a day soon before discharge, with intervals of 18.9 +/- 7.0 days. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) values decreased significantly at the second examination as compared to the initial values (FPG: 101 +/- 20 mg/dl vs. 161 +/- 47 mg/dl, p less than 0.005; HbA1c: 7.3 +/- 1.5% vs. 8.4 +/- 1.7%, p less than 0.005). The urine C-peptide clearance rate also decreased significantly after metabolic control (0.75 +/- 0.36 l/hr vs. 1.06 +/- 0.54 l/hr, p less than 0.005). Meanwhile, the urine creatinine clearance rate tended to decrease, but the difference was not significant (3.69 +/- 2.04 l/hr vs. 4.87 +/- 2.98 l/hr) at the second examination. The data suggest that the urine C-peptide clearance rate is susceptible to the effects of the fluctuation of metabolic states in NIDDM patients. In order to use urinary C-peptide for a follow up study of pancreatic B-cell secretion, the changes in C-peptide clearance under various metabolic conditions must be taken into account.

Regular physical activity and coronary risk factors in Japanese men.

BACKGROUND: Physical activity decreases the risk of coronary heart disease (CHD), but its effects on risk factors require further exploration. METHODS AND RESULTS: The study included 3331 adult Japanese men in whom health benefits, especially CHD risk factors, were compared among those who were sedentary and those who were engaged in continuous physical activity of 30 minutes or more per day for 1, 2 and > or =3 days per week. Significantly higher HDL cholesterol values; lower triceps, scapula, and iliac subcutaneous fat thickness; and lower smoking rates were noted in all physically active groups compared with the sedentary group, whereas body mass index did not differ significantly. Waist-to-height ratios and the prevalence of fatty liver were significantly lower in the groups who exercised 2 or > or =3 days per week than in the sedentary group. The lowest triglyceride values were noted in the group who exercised > or =3 days per week. Multiple regression analysis revealed both the frequency of physical activity and smoking status to be independent positive and negative factors, respectively, for the HDL cholesterol value. The sum of the risk factor scores for hypertension, abnormal glucose tolerance, hypertriglyceridemia, hypercholesterolemia, and low HDL cholesterol level (one point for each if present) was highest in the sedentary group (1.38, 1.19, 1.19, 0.99 for the sedentary group and the groups who exercised 1, 2, and > or =3 days per week). CONCLUSIONS: Those who engaged in regular physical activity > or =3 days per week appeared to have the fewest coronary risk factors. However, even those engaged in physical activity once per week had fewer CHD risk factors than sedentary individuals.

A study of serum free C-peptide responses to oral glucose load in diabetic patients: with special reference to types of diabetes and methods of treatment.

Serum free C-peptide immunoreactivities (serum free CPR) during a 100 g oral glucose tolerance test (OGTT) were measured in 21 patients with insulin-dependent diabetes mellitus (IDDM, with abrupt onset and ketosis-prone), 57 insulin-treated patients with noninsulin-dependent diabetes mellitus ( INIDDM , with gradual onset and not ketosis-prone), 39 oral hypoglycemic agent-treated patients with noninsulin-dependent diabetes mellitus ( ONIDDM ) and 9 healthy young men for control study. Although the fasting blood glucose value of the INIDDM group was not significantly different from that of the IDDM and ONIDDM groups, the free CPR response at each interval during OGTT in the INIDDM group was significantly higher than that in the IDDM group and lower than that in the ONIDDM group. The sum of serum free CPR during OGTT (sigma serum free CPR) was found to be negatively correlated to the duration of insulin treatment either in bivariate or multivariate analysis in INIDDM patients. Using 9.5 ng/ml as an index, all sigma serum free CPR values in the ONIDDM group were above this index, whereas all the values except one in the IDDM group were below it. The values in the INIDDM were scattered within the ranges of the other two groups. The insulinogenic index delta serum free CPR/delta blood glucose (30 min-fasting) of the ONIDDM group was significantly lower than that of normal subjects, although sigma serum free CPR values were not significantly different. The results indicate that: 1. Residual pancreatic B-cell function in INIDDM patients is lower than that in ONIDDM patients and is negatively correlated to the duration of insulin treatment in INIDDM patients. 2. Measuring serum free CPR may be a discriminative method for establishing insulin dependency in insulin-treated patients. 3. Impairment of early insulin secretion after the oral glucose load is a distinguished characteristic of diabetic patients.

Waist-to-height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women.

OBJECTIVE: The normal body mass index (BMI) range, as defined by the World Health Organization (WHO), is quite wide, and some people within this range may have excessive central fat accumulation and elevated metabolic risks. We hypothesize that the waist-to-height ratio (W/Ht), an effective index for assessing central fat distribution among Japanese people, can be used to identify subjects who are at higher metabolic risk within the normal as well as the overweight range. METHODS: We investigated: (1). the values of BMI, waist circumference, and W/Ht in 6141 men and 2137 women at various age intervals and calculated gender (female to male) ratios for all these anthropometric indices; (2). the relation between age and each anthropometric index, between age and morbidity index for coronary risk factors (sum of the scores for hyperglycemia, hypertension, hypertriglyceridemia, hypercholesterolemia, and low HDL cholesterol; one point for each condition if present), and between morbidity index for coronary risk factors and each anthropometric index; (3). the distributions of the subjects, using various proposed indices of waist circumference (those suggested by WHO, the Japan Society for the Study of Obesity, and the Asia-Pacific perspective), and our proposed boundary value, W/Ht 0.5, among the WHO categories based on BMI; (4). the metabolic risks (coronary risk factors, hyperuricemia, high gamma-glutamyltransferase, and fatty liver diagnosed by ultrasonography), and exercise habits among normal-weight subjects with W/Ht<0.5 or >or=0.5. RESULTS: (1). For the various anthropometric indices in all age groups, the gender ratio for W/Ht was closest to 1, indicating that a single set of values for W/Ht can be used for men and women. (2). Height correlated negatively with age. Among the anthropometric indices, only W/Ht correlated positively with age for both men and women, while age and all anthropometric indices, except height, correlated positively with the morbidity index for coronary risk factors. For both men and women, the highest correlation coefficient was between W/Ht and the morbidity index for coronary risk factors. (3). Nearly all overweight men and women (BMI>or=25) had W/Ht>or=0.5 (98.5% of men and 97.5% of women). None of the underweight subjects had W/Ht>or=0.5. However, 45.5% of men and 28.3% of women of normal weight (BMI 18.5-<25) had W/Ht>or=0.5. W/Ht, of all the indices investigated, was the best index for signaling metabolic risk in the normal-weight subjects as well as the overweight subjects. (4). Age- and BMI-adjusted odds ratios for multiple metabolic risks, and history of no habitual exercise were significantly higher in normal-weight men and women with W/Ht>or=0.5 than in others of normal weight. CONCLUSIONS: Waist circumference is improved by relating it to height to categorized fat distribution of different genders and ages. W/Ht is a simple and practical anthropometric index to identify higher metabolic risks in normal and overweight Japanese men and women.

Pancreatic B-cell function in non-insulin-dependent diabetes mellitus during successive periods of sulfonylurea and insulin treatment: serum C-peptide response to glucagon and urine C-peptide excretion.

Serum C-peptide responses to glucagon and daily urine C-peptide excretion in successive periods of different treatment in two groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) (mean interval between two tests less than 1 month) were compared. In group A patients (n = 8), the glycemic control was improved after transferring the treatment from sulfonylurea (SU) to insulin (fasting plasma glucose: SU: 192 +/- 47, insulin: 127 +/- 21 mg/dl, mean +/- S.D., p less than 0.01). Fasting serum C-peptide immunoreactivity (CPR) was significantly lower at the period of insulin treatment (SU: 1.93 +/- 1.01, insulin: 1.47 +/- 0.79 ng/ml, p less than 0.05), but there was no difference in the increase in serum CPR (maximal--fasting) (delta serum CPR) during glucagon stimulation in the two periods of treatment (SU: 1.70 +/- 0.72, insulin: 1.47 +/- 0.98 ng/ml). In group B patients (n = 7), there was no significant difference in glycemic control after transferring the treatment from insulin to SU (fasting plasma glucose: insulin: 127 +/- 24, SU: 103 +/- 13 mg/dl). Fasting serum CPR was significantly lower during the period of insulin treatment (insulin: 1.39 +/- 0.64, SU: 2.21 +/- 0.86 ng/ml, p less than 0.025), but delta serum CPR during glucagon stimulation still showed no significant difference between the two periods (insulin: 1.97 +/- 1.16, SU: 2.33 +/- 1.57 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)