In order to define the diagnostic criteria for diabetes mellitus in the elderly and to clarify how to manage the elderly diabetic patients, we examined risk factors for the development of diabetic retinopathy or ischemic heart disease in diabetics over 60 years old. Among 381 elderly diabetics, there were 127 patients with retinopathy at the first visit. Univariate analysis showed that the initial fasting plasma glucose (FPG) levels and the estimated duration of diabetes of patients with diabetic retinopathy were significantly higher than those of patients without diabetic retinopathy. The author studied 179 patients who were free of diabetic retinopathy on their first visit and were followed for at least 5 years in order to examine the relationships between the initial glucose levels and subsequent development of retinopathy. Eighty-one of the subjects developed diabetic retinopathy during follow-up period. The development of retinopathy was more common in patients wit higher FPG (>140mg/dl), HbA1 (>9%) or 2-h postload plasma glucose levels (>280mg/dl). Not only the initial FPG but also the mean FPG levels during the follow-up period were higher in subjects who developed retinopathy. These results indicate that 140mg/dl or more of fasting plasma glucose levels in an adequate criterion for diabetes mellitus in the elderly, as well as in young and middle age subjects. In elderly diabetic patients, not only diabetic retinopathy but also ischemic heart disease developed so frequently that the quality of life in those patients is often disturbed. Therefore, the relationship between clinical findings and the subsequent development of IHD were studied using a 7-year follow-up study of 362 patients who were free from IHD at baseline. Among these subjects, IHD developed in 44 patients during the follow-up period. Subjects who developed IHD during the follow-up period has a higher HbA1, systolic blood pressure and total cholesterol at baseline. But other variables including age, sex, degree of smoking and body mass index were not significantly different between subjects with and without IHD. By life table analysis, the incidence of IHD increased in subjects in whom the systolic blood pressure was more than 160mmHg, or in whom the total cholesterol levels were more than 220mg/dl. The incidence also increased when fasting plasma glucose levels were over 140mg/dl. Multivariate analysis usinga step-wise proportional hazards model revealed that systolic blood pressure, total cholesterol levels and HbA1 levels were significant variobles for the development of IHD during the follow-up period. These results suggest that, in addition to strict control for blood sugar levels, careful management of hypertension and hyperlipidemia are important in elderly diabetes mellitus as well as in younger patients.

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Hormonal and metabolic characteristics of diabetes mellitus in the elderly were investigated in the following groups; elederly DM subdivided into obese DM and non-obese DM, elderly non-DM subdivided into obese and non-DM and non-obese non-DM, adult DM and adult non-DM. Responses of plasma glucose, insulin and glucagon during oral glucose tolerance test (OGTT), arginine tolerance test (ATT) and intravenous glucose tolerance test (IVGTT) were measured individually and the daily urinary C-peptide excretion (U-CRP), fasting plasma levels of free fatty acid (FFA), triglyceride (TD), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also measured. In comparison with adults, insulin responses in IVGTT and ATT in elderly non-DM were low but not in OGTT. It was noteworthy that glucagon response during OGTT in elderly DM was considerably lower than adult DM, probably due to factors other than insulin deficiency. Comparing elderly DM and elderly non-DM, the initial response of insulin in OGTT was found to be low in elderly DM but not in total response. In the comparison between the obese and the non-obese, higher insulin levels in elderly obese DM than in elderly non-obese DM during OGTT, IVGTT and ATT were observed, implying decreased insulin sensitivity. This difference, however, was not apparent between elderly obese non-DM and non-obese non-DM. A good correlation between U-CPR and the response of plasma insulin in OGTT was shown even in the elderly but not between U-CPR and that of plasma insulin in IVGTT. In lipids, higher fasting levels of FFA and TG were observed in elderly DM and elderly obese non-DM. No significant changes in TC and HDL-C were observed in any of the groups. From these results the characteristics of diabetes mellitus in the elderly was pointed out to be a blunted glucagon response during oral glucose loading in elderly diabetics and decreased insulin sensitivity in elderly obese diabetics.

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Autopsy cases from Annual Report of Autopsy Cases published by the Japan Society of Pathology showed an increase of myocardial infarction from 13.2% in the years 1958-65 to 26.6% in the years 1983-85. However, cerebral infarction and hemorrhage showed no definite increase during the period. Frequency of diabetes mellitus was extremely increased among the cases of myocardial infarction who were admitted to our hospital. Arteriographic characteristics of coronary atherosclerosis in diabetics consist of multiple tight stenoses in one major artery and two or three arterial obstructions. Carotid arterial blood flow and plaque formation and calcification of the arteries were examined by doppler imaging technology and B-mode (5MHz) real time ultrasound using ultrasonographic equipment in diabetic patients. Both blood flow volume and blood flow velocity in the elderly patients with diabetes mellitus (over 65 years old) were significantly reduced compared with those in the younger patients with diabetes mellitus (7.4±0.4 vs. 8.5±0.2 in blood flow volumes. p<0.01; 12.4±0.8 in blood flow velocities. p<0.01). Plaque formation and calcification of carotid arteries were significantly more frequent in the elderly patients with diabetes mellitus than in the younger patients with diabetes mellitus (p<0.05). Asymptomatic cerebral infarction was studied in 37 diabetic patients by brain magnetic resonance imaging (MRI) in the absence of prior stroke. T₂ weighted MRI imaging showed 27 patients among 37 patients (73%) to suffer from lacunar infarction. Hyperintensities were seen in the brain stem (28.6%), white matter (62.9%), basal ganglia (60.0%), and paraventricular areas (PVH) (20.00). The frequency of increased signal intensity in white matter (81.0%) and paraventricular areas (28.6%) was far more common in the elderly diabetic patients (21 cases). The elderly patients with diabetes mellitus were thought to a high incidence of silent and multiple cerebro-vascular diseases. The elderly patients with diabetes mellitus have multiple organ impairment-form accelerated atherosclerosis.

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Course, prognosis and mortality in Japanese elderly diabetes mellitus were studied using a 7 year follow-up study of 424 elderly diabetics whose ages were 60 years old or more (mean age: 72.6±6.2, 144 males: 280 females) at baseline. The relationships between clinical findings at baseline and prognosis, causes of death and onset of ischemic heart disease during the follow-up period were also studied. A total of 133 (31%) deaths were observed during the follow-up period. Risk factors present at baseline which significantly influenced the patients' prognosis included age, male gender, previous cerebro-vascular disease, body mass index, pharmacological treatment of diabetes and persistent proteinuria. These factors were also related to the causes of death among the patients. Cardio-vascular disease deaths (n=66, 50%) tended to increase in patients with a relatively higher age, male gender, previous ischemic heart disease and persistent proteinuria. Malignant neoplasm deaths (n=28, 21%) tended to increase in patients with relatively higher age and previous cerebrovascular disease. Furthermore, infectious deaths (n=16, 12%) were relatively increased in patients with a relatively higher age, male gender, previous cerebro-vascular disease, relatively lower body mass index and higher fasting plasma glucose levels. Among various causes for cardio-vascular disease deaths, ischemic heart disease (n=40) was the leading cause of death. Therefore, risk factors for ischemic heart disease including both nonfatal (n=42) and fatal (n=40) ischemic heart disease were examined. Previous ischemic heart disease, relatively higher systolic blood pressure, higher glycohemoglobin A₁ levels and higher serum cholesterol levels were significant and independent risk factors for ischemic heart disease in elderly diabetics. The latter three factors were also significant risk factors for ischemic heart disease in patients without previous ischemic heart disease at baseline. From these results, it is possible to conclude that, even in the elderly, diabetes mellitus should be treated as carefully as in young or middle-aged cases.

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The clinical evaluation of exercise in elderly NIDDM was investigated with the following. Based on the questionnares filled in by 508 patients with NIDDM regarding whether they had regular exercise for treatment of diabetes mellitus or not, 53.4% and 41.4% of NIDDM men obtained regular exercise in the 30-40 and 50-59 age groups, respectively. On the other hand, the figures for the 60-69 and over 70 age groups were 67.0% and 73.3%, respectively. From these data, regular exercise in elderly NIDDM men was significantly more frequent than in middle aged NIDDM men. No similar tendency in NIDDM women was found. Regular exercise as a therapeutic approach was lowest in the insulin group compared to other types of therapy. We investigated heart rate pressure product, work rate, volume of oxygen uptake at anaerobic threshold (AT) during exercise on bicycle ergometer. These parameters in elderly NIDDM men and women aged over 60 were significantly lower compared to young and middle aged cases of NIDDM. But these clinical parameters at the anaerobic threshold (AT) after exercise training were significantly improved in work rate and blood pressure as compared to data before exercise training. We compared the effects of exercise at an intensity of AF for 30 minutes on glucose metabolism between middle aged and elderly NIDDM. Levels of blood glucose in elderly NIDDM after exercise was not changed, whereas that in middle aged NIDDM after exercise was significantly decreased. From the present study, many clinical differences were seen between elderly and young NIDDM. It is necessary to know more details because the clinical evaluation of regular exercise for diabetic control, especially in elderly NIDDM, is still unclear.

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There are many methods of screening for diabetes mellitus, for example, blood glucose test, urine sugar test, hemoglobin A_1C, fructosamine etc. For the purpose of more efficient screening of diabetes mellitus in elderly groups, these data were analyzed to evaluate validity and ability to estimate prognosis. 1) Validity for screening based on diabetic type was analyzed in 27, 074 cases. For screening with the standard level of fasting plasma glucose (FPG)≥120mg/dl, sensitivity was 70.5%, specificity, 94.5%, predictive value, 89.0%, hemoglobin A_1C≥6.5%, 62.7%, 91.2%, 81.5%, respectively, and fructosamine≥290μmol/L, 54.1%, 92.3%, 78.1%, respectivley. FPG had the highest validity. Comparison of validity between the≥65-yr group and the ≤55-yr group was mode. There was significant difference in specificity but sensitivity and predictive value were lower in the ≥65-yr group. 2) Mean blood glucose levels (BG)±S.D. by time after meal were studied. Fasting BG was 84.8±9.8 mg/dl, 0.5-1hr. BG after meal, 100.8±24.5mg/dl, and 4.5hr or more, 84.1±12.8mg/dl. Based on this data, standard levels for screening based on diabetic type using random blood glucose levels for 0.5-1hr BG after meals were ≥130mg/dl, 1.5-2hr BG≥120mg/dl, and 3.5hr or more BG and FBG≥100mg/dl. With screening using this standard, there is no difference in sensitivity according to age, but sensitivity of FBG≥100mg/dl was the highest, the rate being 93.3% in the ≤64-yr group, 83.3% in the ≥65-yr group, and the predictive values of positive tests were 62.2% and 55.6% respectively. 3) Criteria of diabetes in the elderly groups were studied using GTT follow-up and death data. The rate of development of diabetes with FPG≥140mg/dl from diabetic type with FPG<140mg/dl was lower in the ≥65-yr group than in the ≤49-yr group. Comparision of mean age at death among all dead cases, the onset age of diabetes mellitus ≤64-yr group, and the ≥65-yr group was made in cases with age at death ≥65yrs. No difference was found between all dead cases and the group of the onset age ≥65yrs (80.4yrs), but in the group of onset age ≤64yrs, the mean age at death was 73.0yrs, significantly lower than for the overall mean age at death. Mortality rate by FPG was compared between the group of onset age of diabetes mellitus ≤64 yrs and that of ≥65yrs in males. In the former group, mortality rate increased in cases with FPG≥170mg/dl, but in the latter, the rate in creased only with FPG≥200mg/dl. From these data, screening standards in the elderly group were FPG≥140mg/dl and FBG≥120mg/dl. If random blood glucose levels are used as a preliminary screening, the standards levels for 0.5-1hr BG after meal are≥130mg/dl (PG≥150mg/dl), 1.5-2 hr BG≥120mg/dl (PG≥140mg/dl), and 3.5hr or more BG and FBG≥100mg/dl (PG≥120mg/dl).

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[in Japanese]

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Diagnostic criteria of diabetes mellitus in elderly people are still controversial. The major questions are whether (1) effects of hyperglycemia in generating diabetic complications are the same as in younger diabetics, (2) too many diabetics might be diagnosed in the elderly by the criteria proposed by WHO and Japan Diabetes Society. To answer these questions, we carried out two studies. Blood glucose data were collected from population-based studies and from voluntary health check-up studies. Fasting blood glucose values were classified by sex and the age (-49, 50-64, 65-years old). Population-based studies showed no age-dependent change in blood glucose. However, data from health check-up studies showed an increase in median values from the group aged 50-64 and the 65 and older group. Two-hour values after glucose tolerance tests were classified by age and the fasting blood glucose (-99, 100-119, 120-139, and 140- mg/dl). The eldest and 140- mg/dl group showed the highest 2-hour values. Effects of hyperglycemia on the appearance of diabetic complications were studied in patients being followed-up in three diabetes clinics. Patients who has a history of one year or less and without any retinopathy on the first visit to the clinic were registered. Data were analyzed by the Kaplan-Meier method and the appearance of retinopathy was used as the end point. There were no difference in the rate of appearance of retinopathy between the age groups (-49, 50-64 and 65-years old). No age effect on the hyperglycemia-dependent appearance of retinopathy could be observed. These results indicate the effect of age on blood glucose level starts already from the 50-64- year-old-group. Furthermore, postprandial glucose levels tended to be higher in the group aged more than 64 and was related more to the fasting blood glucose than in younger age groups. The effect of hyperglycemia inducing diabetic complications does not differ according to age.

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Clinical characteristics of elderly patients who had been admitted in Sawauchi Hospital for more than 100 days between 1988 and 1992, were analyzed. The average hospital stay of inpatients was 38.0 days, and the longest hospitalization was observed at ages between 76 and 85 year old. During 4 years, there were 74 patients who were admitted for more than 100 days. Thirty- seven cases had serious and complicated conditions, while the remaining 37 cases did not have clear-cut reasons for such a long hospitalization. The latter group was significantly older than the former, and included more females (p<0.01, respectively; the care-forcussed group). Clinical characteristics of the care-forcussed group were degenerative bone/joint diseases with longstanding pain and uncertain complaints such as autonomic nerve dysfunction. These patients were often admitted to the hospital repeatedly, particularly in winter. Patients with multiple cerebral infarction or chronic respiratory disorders were mostly males (p<0.01). It is important to examine the clinical course and severity of elderly patients who are in hospital for long periods, particularly from the viewpoint of differentiating quality of treatment and care.

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We administered a highly purified icosapentaenoic acid ethyl ester (IPA-E) preparation orally for 12 weeks to 32 male and 22 female patients aged 43 to 85 (average 67 years) with arteriosclerosis to investigate the effects of various factors on changes in the levels of unsaturated fatty acid in plasma and serum lipids. On administration of 1800mg/day of IPA-E, the plasma level of IPA increased significantly, while the plasma level of DHLA decreased significantly, but no significant changes were observed in plasma DHA and AA concentrations. There were significant inverse correlations between the pretreatment levels of plasma IPA and IPA/AA, and the volumes and ratios of changes in their plasma levels following administration of IPA-E. There was no significant correlation between patient age or concomitant administration of calcium antagonists and baseline plasma IPA level and IPA/AA value or changes in these parameters after administration of IPA-E. In male patients, the plasma IPA level before treatment was higher than that in female patients, while the increase in plasma IPA level after administration of IPA-E tended to be smaller than in female patients. In diabetic patients and those receiving diuretics concomitantly, plasma IPA/AA values before treatment with IPA-E were higher, while the increase in IPA/AA values after treatment tended to be smaller than other groups of patients. On analysis of covariance on modified baseline volume before treatment, the effect of age, sex, presence of diabetes mellitus and concurrent use of calcium antagonist or diuretics was not significant. In patients given 900mg/day of IPA-E, plasma IPA level and IPA/AA value increased significantly, but the increase was significantly less than those observed in patients receiving 1800mg/day of IPA-E. Nevertheless, hypertriglyceridemia and hypercholesterolemia in both groups of patients improved, and the analysis of changes in serum lipids showed no significant difference between these two groups.

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It is known that asymptomatic MRI lesions of the brain are found in elderly subjects, but the significance of the lesions has not been determined. In previous reports, the prevalence of MRI lesions varied from 11% to 59%, but many of the authors indicated a close relationship with cerebrovascular risk factors. We evaluated 76 elderly subjects (over 60 years old, average age±SD was 66.7±4.5) without a history of cerebrovascular disease and dementia, and determined the prevalence of periventricular (PVH), white matter (WMH) and pontine (PH) hyperintensity and risk factors. The severity of MRI lesion was evaluated in T2-weighted images by Fazekas' scoring method of MRI hyperintense lesions. PVH, WMH and PH were graded visually from 0 to 3 by the author and these points are added to the MM score. In T1-weighted images, we also measured the diameter of the third ventricle, frontal horn and body of the lateral ventricle. Our results were that 62% of subjects had PVH, 64% had WMH and 8% had PH. In regard to risk factors, 38% of subjects had hypertension, 17% had diabetes mellitus, 8% had ischemic heart disease. The PVH(+)group was significantly older (p<0.01) and had larger lateral ventricles (p<0.05) than the PVH(-) group. The WMH(+)group was significantly older (p<0.05) and had higher risk of cerebrovascular disease (p<0.05) than the WMH(-)group. The MRI score was related, but not significantly, to a history of hypertension, diabetes mellitus and ischemic heart disease. The MRI score and index of ventricular enlargement correlated with age (p<0.05). In conclusion, PVH was related to aging and WMH was related to both aging and cerebrovascular risk factors. Therefore, PVH and WMH were suspected to have different pathogenesis and WMH was more closely related to risk factors. Our scoring method permits evaluation and comparison MRI lesions of different groups.

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A 73-year-old male was admitted to Tokyo University Hospital due to cardiac arrest secondary to ventricular arrhythmias. Although the patient survived after cardiopulmonary resuscitation, he needed mechanical ventilation. When we tried to wean the patient from mechanical ventilation, we found that he suffered from frequent sleep apneas of over 40times/hour. To evaluate the severity and frequency of the apneas, we performed polysomnographic study on the patient under assist ventilation. The polysomnographic study revealed that frequency of apneas was very high but the magnitude of desaturation was not so severe during the night. Since we confirmed the lowest SaO₂ in this patients was over 90% during day and night, we tried to wean from the patient from the ventilator again and succeeded. The clinical application and usefulness of nocturnal ventilatory monitoring for patients with mechanical ventilation was discussed.

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