Motoji Naka

Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control

To determine whether left ventricular (LV) filling abnormalities in diabetes are associated with diabetic microangiopathy, and to evaluate the effect of a short-term glycemic control on the filling abnormalities, diastolic filling dynamics were assessed by pulsed Doppler echocardiography in 246 patients with non-insulin-dependent diabetics. Isovolumic relaxation time and the ratio of peak flow velocity of atrial filling wave to peak flow velocity of early filling wave (A/E) were significantly greater in diabetic patients than in age- and sex-matched control subjects. Diabetic patients with retinopathy had significantly greater isovolumic relaxation time and A/E values than those without retinopathy. A/E was significantly decreased 1 month after insulin treatment in those without, but not with retinopathy. It is concluded that LV diastolic filling is impaired in mildly hyperglycemic patients with non-insulin-dependent diabetes mellitus without severe complications, the abnormality being more intense in patients with retinopathy. A short-term glycemic control results in a marked decrease in abnormalities in patients without, but not with retinopathy.

TWO TYPES OF THYROID FUNCTION‐BLOCKING ANTIBODIES IN AUTOIMMUNE ATROPHIC THYROIDITIS AND TRANSIENT NEONATAL HYPOTHYROIDISM DUE TO MATERNAL IgG

We examined the effects of IgG from four patients with autoimmune atrophic thyroiditis on cAMP responses and iodine metabolism (post‐receptor processes), using cultured thyroid cells. We found two types of thyroid function‐blocking antibodies: (1) one blocks TSH binding to its receptors and inhibits TSH‐stimulated cAMP responses but does not block cAMP‐stimulated iodine uptake and organification; (2) the other blocks TSH binding to its receptors, inhibits TSH‐stimulated cAMP responses and does block cAMP‐stimulated iodine uptake and organification (post‐receptor processes). Among the four patients with autoimmune atrophic thyroiditis, three had TSH binding blocking antibodies only and one had antibodies which block post‐receptor processes. These antibodies might be responsible for thyroid dysfunction in autoimmune atrophic thyroiditis. The daughter of one of the women with autoimmune atrophic thyroiditis had transient neonatal hypothyroidism and recovered spontaneously from the hypothyroid state with the disappearance of the maternal blocking antibodies.

The effect of long-term treatment with sulindac on the progression of diabetic retinopathy

ABSTRACT Objective: To evaluate the effects of long-term treatment with sulindac on the progression of diabetic retinopathy (DR). Research design and methods: 40 Japanese patients with type 2 diabetes were enrolled in a randomized, single-blind controlled trial in which the effects of sulindac (200 mg/day, 100 mg twice a day; n = 16 patients) on the progression of DR were compared to controls (24 patients) for 3 years. All patients were comparable in their age, gender, duration of disease, body mass index, dipstick proteinuria, insulin therapy, glycemic control, and clinical stages of DR. Outcome was determined by comparing parameters of retinopathy in fundus photographs that were taken at time 0 to those taken 1, 2, and 3 years after the initiation of treatment. Results: Patients in the sulindac group did not develop DR during the course of treatment nor was there progression of pathology in those who began the study with mild non-proliferative DR (NPDR). On the other hand, six patients progressed to mild NPDR in the control group – three at year 1 and three at year 3 – and an additional patient progressed to severe NPDR from mild NPDR by year 1 and to proliferative DR by year 2. The findings at year 3 in the sulindac group were significantly ( p < 0.05) different from the control group. None of the patients experienced any adverse effects of treatment. Conclusions: Long-term treatment with sulindac was clinically effective in decreasing the progression of mild DR in type 2 diabetic patients in this pilot study.

Development, worsening, and improvement of diabetic microangiopathy in older people : Six-year prospective study of patients under intensive diabetes control

OBJECTIVES: To examine retinopathy and nephropathy in elderly patients with diabetes mellitus (DM) under intensive multifactorial DM control.

POSTPRANDIAL HYPERGLYCEMIA IS AN INDEPENDENT RISK FOR RETINOPATHY IN ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS, ESPECIALLY IN THOSE WITH NEAR‐NORMAL GLYCOSYLATED HEMOGLOBIN

To the Editor: Data on the risk of retinopathy with high postprandial glucose (PPG) in patients with type 2 diabetes mellitus are controversial. It was found that PPG was significantly related to incidence of retinopathy and was a significant risk for worsening of retinopathy. A 6-year prospective study also found that PPG is a significant predictor for development of retinopathy in elderly patients. In these studies, PPG was significantly related to retinopathy even after adjustment for glycosylated hemoglobin (HbA1c), indciating that it is a risk for retinopathy in addition to high mean glucose. One study reported that PPG was significantly related to incidence of retinopathy, and PPG was a significant risk for development of retinopathy in the Kumamoto Study, but its independence from HbA1 as a risk was not examined in these studies. Two other studies found that PPG was not significantly related to incidence, development, or worsening of retinopathy. Levels of glycemic control have tended to be low in the studies with positive results, except for one, in which duration of diabetes mellitus was short as a group. Although duration of diabetes mellitus was long in the cohort in the 6-year prospective study, glycemic and blood pressure control was strict, and the patients were elderly. Good glycemic control as indexed according to lower HbA1c, short duration of diabetes mellitus, and older onset age of diabetes mellitus are all protective factors for retinopathy. Thus, it can be hypothesized that high PPG is a significant risk for retinopathy, especially in the patients with low risk of it. As far as the authors are aware, the cohort in the 6-year prospective study was an invaluable one, in which the relationship between PPG and risk of retinopathy in elderly patients can be analyzed in detail. Based on these considerations, and in view of recent attention to the detrimental effect of PPG on complications of diabetes mellitus, a focused analysis was performed on the relationship between PPG and retinopathy in the previously reported cohort. The characteristics of the patients (N 5 413) have been previously reported. Briefly, of 413 participants, 312 survived, and 168 (male/female 82/86, mean age 72, duration of diabetes mellitus 13 years, PPG 9.3 mmol/L, HbA1c 6.6%, use of oral hypoglycemic agents 58%, use of insulin 25%) had no retinopathy upon entry. Retinopathy developed in 45 (27%) during a 6-year observation. At baseline, the mean from two PPG (plasma glucose 2–4 hours after breakfast) values obtained at an outpatient clinic 1 to 2 months apart was calculated and recorded as a PPG for each patient. Glycemic control had been satisfactory for 6 years; the mean interim and closing HbA1c were both 6.7%. PPG was more significantly related to retinopathy than HbA1c (P 5.01 for PPG, P 5.03 for HbA1c). 3