OBJECTIVE -To clarify mortality and morbidity of intensively managed elderly diabetic individuals and to explore factors predicting mortality and diabetes-related end points. RESEARCH DESIGN AND METHODS-A total of 390 elderly (Ն65 years of age) outpatients with type 2 diabetes ( 173 men and 217 women, mean age 73.0 years) were analyzed. The mean HbA 1c upon entry was 6.8% (332 receiving oral hypoglycemics and/or insulin) and blood pressure upon entry was 136/74 mmHg (219 receiving antihypertensive drugs). The patients have been followed-up for 3 years with HbA 1c Ͻ7.0% and blood pressure Ͻ145/80 mmHg as targets, with mortality and an aggregate of fatal and nonfatal diabetes-related events as end points. Mortality rate and causes of mortality, as well as risk factors for mortality and morbidity, were determined. RESULTS -The mortality rate, 2.9% per year, was comparable to that of the age-and sex-matched general population. Stroke was a leading cause of mortality after malignancy. By the univariate Cox proportional hazards model, only high serum creatinine and prior stroke were highly significant and strong risks for both end points. In those without prior stroke and receiving antihypertensive agents, the incidence of the diabetes-related end point based on their systolic blood pressure (SBP) quartile was U-shaped, with the nadir at the 3rd (SBP,(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147) and the peak at the 1st (SBP Յ 125 mmHg) quartile.CONCLUSIONS -In well-controlled elderly diabetic subjects, there was no excessive mortality compared to the age-and sex-matched general population. Renal dysfunction and prior stroke were independent risks for mortality and morbidity. In those without prior stroke, a risk of too much lowering of blood pressure was suggested. Diabetes Care 26:638 -644, 2003

Low molecular weight heparin (LMH) acts as an anticoagulation agent mainly through its anti-activated coagulation factor X (Xa) activity. Thrombelastography (TEG) is expected to be useful to monitor the dosage of LMH during hemodialysis because reaction time on TEG (TEG-r) is considered to reflect blood thromboplastin formation time, which depends on the formation of Xa. To test this possibility, we compared the usefulness of TEG, activated coagulation time (ACT), activated partial thromboplastin time (APTT), and anti-Xa activity in 28 hemodialysis patients using both conventional unfractionated heparin (UFH) and LMH on separate dialysis procedures. Anti-Xa activity of LMH was comparable to that of UFH when it was measured using both LMH and UFH as standards. Anti-Xa activity, which theoretically depended on the heparin concentration in blood samples, did not correlate with the degree of dialyzer clotting. The APTT correlated well with anti-Xa activity in patients using LMH (r = 0.686, p less than 0.01) and UFH (r = 0.906, p less than 0.01), but not with the degree of dialyzer clotting. The TEG-r correlated well with the degree of dialyzer clotting both in patients using LMH and those using UFH (measurements of samples obtained from the venous side of the extracorporeal circuit) and weakly correlated with anti-Xa activity in patients using LMH (r = 0.402, p less than 0.05). The ACT did not correlate with the degree of dialyzer clotting or anti-Xa activity. These results suggest that TEG-r reflects the efficacy of heparin in the extra-corporeal blood circuit, whereas APTT mainly reflects heparin concentration of the blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)

There are two forms of autoimmune thyroiditis that may cause hypothyroidism: autoimmune atrophic thyroiditis (primary idiopathic hypothyroidism or primary myxedema) and autoimmune goitrous thyroiditis (Hashimoto's disease). Patients with the former have impalpable thyroid glands, and those with the latter have goiters. We studied TSH binding inhibitory immunoglobulins (TBII), TSH-stimulated cAMP response inhibitory immunoglobulins (TSII), and TSH-stimulated cell growth inhibitory immunoglobulins (TGII) in 42 patients with the former (group 1) and 115 patients with the latter (group 2). Porcine thyroid cells in primary culture and rat thyroid cells in continuous culture (FRTL-5 cells) were used to study TSII and TGII activities, respectively; TSII was expressed as percent inhibition of 0.1 mU/ml TSH-stimulated cAMP response by the patient's immunoglobulin (IgG; 1 mg/ml) during 2-h incubation, and TGII was expressed as percent inhibition of 10 mU/ml TSH-stimulated [14C]thymidine incorporation by the patient's IgG (1 mg/ml) during 24-h incubation. The new findings in this report are: some patients in both groups had TBII, TSII, and/or TGII; the frequency of the presence of TBII, TSII, and TGII in the patients with autoimmune atrophic thyroiditis was higher than that in the patients with autoimmune goitrous thyroiditis, and TSII and TGII were significantly associated with autoimmune atrophic thyroiditis; no correlation was found between goiter size and TBII, TSII, or TGII activity; and there were good correlations between TBII, TSII, and TGII activities. We also found that TSH-stimulated thymidine incorporation was through cAMP production and that the inhibitory IgGs inhibited TSH-stimulated thymidine incorporation by decreasing cAMP production in FRTL-5 cells, but not in porcine or human thyroid cells.

Aim of this study was to formulate an index for glucose effectiveness (Sg), SgIo, based on 3-point (0, 30 and 120 min) 75 g oral glucose tolerance test (OGTT). The equation for SgI(O) was developed in the Chikuma cohort (n = 502). Firstly, post-loading plasma glucose without insulin action and Sg (PPG-without insulin and Sg) was calculated as follows: fasting plasma glucose (mg/dl) + [0.75 × 75,000]/[0.19 × BW(kg) × 10]. Secondly, 'PPG-without insulin/with Sg' was obtained from inverse correlation between log(10)DI(O) and 2-h post-glucose plasma glucose at OGTT (2hPG) in each glucose tolerance category: DI(O) denotes oral disposition index, a product of the Matsuda Index and δIRI(0-30)/δPG(0-30). Thirdly, expected 2hPG (2hPG(E)) of a given subject was obtained from the regression, and the ratio of 2hPG to 2hPG(E) (2hPG/2hPG(E)) was determined as an adjustment factor. Lastly, SgI(O) ([mg/dl]/min) was calculated as [PPG-without insulin and Sg]-[PPG-without insulin / with Sg] x [(2hPG) / 2hPG(E)]. SgI(O) was validated against Sg obtained by frequently sampled intravenous glucose tolerance test in the Jichi cohort (n = 205). Also, the accuracy of prediction of Sg by SgIo was tested by the Bland-Altman plot. SgI(O) was 3.61 ± 0.73, 3.17 ± 0.74 and 2.15 ± 0.60 in subjects with normal glucose tolerance (NGT), non-diabetic hyperglycemia and diabetes, respectively, in the Chikuma cohort. In the Jichi cohort, SgI(O) was significantly correlated with Sg in the entire group (r = 0.322, P < 0.001) and in subjects with NGT (r = 0.286, P < 0.001), and SgIo accurately predicted Sg. In conclusion, SgI(O) could be a simple, quantitative index for Sg.

In a Japanese population, (i) beta-cell starts to deteriorate during normoglycaemia with a minimal elevation of fasting plasma glucose, and (ii) there are glucose-tolerant subjects with beta-cell dysfunction.