Yoshitada Yajima

Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients

It has been reported that excessive intake of sugar-containing soft drinks results in diabetic ketoacidosis (DKA) or ketosis (DK) in obese patients with non-insulin dependent diabetes mellitus (NIDDM). We describe the clinical characteristics and results of long-term follow-up for 24 newly-diagnosed patients with acute-onset NIDDM presenting with DKA or DK. A history of excessive intake of sugar-containing soft drinks was found in 19 (Group A); serious non-diabetic illnesses were found in 5 (Group B). The range of patient ages in Group A was 16 to 57 years while all patients in Group B were 60 years or older. In Group A, no patient was positive for autoantibodies, specific HLAs for Japanese insulin dependent diabetes mellitus, or mutation of the beta-3-adrenergic receptor gene. The body mass indices (BMIs) at onset and admission and serum C-peptide immunoreactivities at admission and discharge were significantly higher in patients in Group A than in patients Group B. In conclusion, we reconfirmed that excessive intake of sugar-containing soft drinks is one of the contributing factors in DKA or DK-onset NIDDM patients. We found no autoimmune mechanism involved in the pathogenesis and that a polymorphism in the beta-3-adrenergic receptor gene could be associated with the development of soft-drink ketosis.

Usefulness of anaerobic threshold in estimating intensity of exercise for diabetics

We examined the utility of the anaerobic threshold (AT) for quantifying the intensity of exercise that a diabetic patient is capable of handling. Thirteen diabetic patients treated with buformin exercised on a bicycle ergometer, and comparison was made with 20 healthy subjects matched for age and sex. The AT was determined from VO2 and VE with a personal computer. The intensity of exercise at the AT was 93 +/- 6 W in diabetic men and 80 +/- 10 W in diabetic women, values that were less than those of healthy subjects (P less than 0.05). There was a negative correlation between the intensity of exercise at the AT and the plasma concentration of buformin (P less than 0.01). There were no significant differences in either plasma lactic acid or pyruvic acid concentration at the AT between healthy subjects and diabetics. The plasma glucose at the AT or after exercise was lower than the baseline values in all subjects (P less than 0.01). The plasma insulin at the AT was lower than the baseline values in healthy subjects (P less than 0.01), but not in diabetics. There were no changes in plasma glucagon in any group. We concluded that determination of the AT is a simple, non-invasive procedure useful for ascertaining the optimal intensity of exercise for diabetics.

Is ACE Gene Polymorphism a Useful Marker for Diabetic Albuminuria in Japanese NIDDM Patients

OBJECTIVE We studied the relationship between an insertion/deletion (I/D) polymorphism in the ACE gene and albuminuria/proteinuria in Japanese NIDDM patients. RESEARCH DESIGN AND METHODS A total of 142 Japanese NIDDM patients (89 men, 53 women) with a known diabetes duration of 14 ± 5 (mean ± SD) years and an age of 56 ± 6 years were divided into three groups according to the stage of nephropathy: 41 patients with normoalbuminuria, 47 patients with microalbuminuria, and 54 with overt proteinuria. The three groups were similar in age, diabetes duration, and recent HbA1c level. RESULTS The distribution of DD, ID, and II genotypes of the ACE gene did not differ among the three groups (10, 46, and 44% in the normoalbuminuric patients; 13, 53, and 34% in the microalbuminuric patients; and 15, 46, and 39% in the proteinuric patients, respectively). Meanwhile, the frequency of the D allele in the proteinuric male patients was slightly higher than in the normoalbuminuric male patients (45 vs. 27%, X 2 = 3.9, P < 0.05), while the D allele frequency was nonsignificantly lower in the proteinuric female patients than in the normoalbuminuric female patients. CONCLUSION These results did not support the hypothesis that the genotype of the ACE gene would be a clinically useful genetic marker for predicting the development of nephropathy in Japanese NIDDM patients. However, the role of D allele of ACE gene in the progression of nephropathy in male patients remains to be seen.

Urinary Albumin as an Indicator of Diabetic Nephropathy Lesions in Japanese Type 2 Diabetic Patients

Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 ± (SD) 8 years, known duration 11 ± (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. In conclusion: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.

Relationship between age-adjusted heart rate and anaerobic threshold in estimating exercise intensity in diabetics

We compared heart rates at the anaerobic threshold (AT) with age-adjusted heart rates in two groups of diabetics (DMY, mean age 31; and DMO, mean age 48) to ascertain whether the AT is useful for evaluating the intensity of exercise therapy for diabetics. In both the DMY and DMO groups the AT was reached at lower heart rates than in control groups of healthy subjects, indicating that the metabolism of diabetics may become anaerobic if their age-adjusted heart rate is higher than their heart rate at the AT. In this study, 86% of the DMY and 50% of the DMO group had age-adjusted heart rates, at 70% of maximum, that were higher than the heart rates at the AT. Thus, exercise intensity with an age-adjusted heart rate at 70% of maximum may induce anaerobic metabolism in some diabetics. We also studied the relationship between exercise intensity and the glycosylated hemoglobin (HbA1c) level at the AT in order to understand why the heart rate at the AT in diabetics was less than in healthy subjects. Exercise intensity at the AT in both diabetic groups was less than in healthy groups, and so did not increase the heart rates. Both exercise intensity and the heart rate at the AT were inversely related to the HbA1c level, suggesting that HbA1c may be important for keeping low the exercise intensity and the heart rate at the AT. As far as possible, we excluded cardiovascular autonomic neuropathy, so that it could not explain the mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Resistance in Mitochondrial Gene Mutation

From the Saiseikai Central Hospital (Y.S., K.H., Y.A., K.M.); Institute for Diabetes Care and Research, Asahi Life Foundation (H. Kadowaki); Third Department of Internal Medicine (H. Katagiri, T.K., Y.O., Y.Y.), Faculty of Medicine, University of Tokyo; and the Department of Biochemistry (M.S.), School of Medicine, Keio University, Tokyo, Japan. Address correspondence to Yoshihiko Suzuki, MD, at Saiseikai Central Hospital, 1-417, Mita, Minato-ku, Tokyo 108, Japan.

Loss of glomerular anionic sites and the development of albuminuria in rats with streptozotocin-induced diabetes.

Examination was made of changes in the anionic sites of the glomerular basement membrane (GBM) in rats with streptozotocin (STZ)-induced diabetes by the immersion method of polyethyleneimine (PEI). PEI particles in GBM of diabetic rats significantly decreased from the 1st through the 8th week. Urinary albumin excretion in diabetic rats significantly increased at the 2nd but not earlier week. Insulin treatment effectively prevented decrease in PEI particles in STZ-injected rats. In rats with STZ-induced diabetes, initial renal alteration was disturbance of the charge barrier, followed by the development of albuminuria. Continued deterioration of anionic sites and possibly additional disturbance of size barrier were considered responsible for the development of albuminuria. Insulin treatment appears to prevent the loss of anionic sites of GBM.

Anaerobic threshold can provoke microalbuminuria in non-insulin-dependent diabetics

We examined two groups of non-insulin-dependent diabetic men (group A, 13 patients without microalbuminuria; group B, 9 patients with intermittent microalbuminuria) to ascertain whether the anaerobic threshold (AT) can provoke microalbuminuria, comparing them with 12 healthy subjects matched for age and sex (group C). All subjects exercised on a bicycle ergometer until the AT was reached. In intermittent microalbuminuria, the albumin:creatinine ratio (ACR) was over 0.25 mg/mmol.Cr 1-3-fold in 5 measurements. The ACR after exercise was increased to over 0.25 mg/mmol.Cr in 4/9 cases in group B (P < 0.05), in 2/13 cases in group A, but not at all in group C. We also studied the mechanism of exercise-induced microalbuminuria. In group B, ACR before exercise correlated positively with the baseline plasma glucose. Furthermore, positive correlation was found between ACR after exercise and HbA1c in group B. The AT did not affect the urinary beta 2-microglobulin in any groups. The plasma atrial natriuretic factor (ANF) after exercise was elevated most prominently in group B (P < 0.05). Positive correlation was found between increments of ACR and increments of plasma ANF after exercise in group B. We conclude that the AT can provoke microalbuminuria in some non-insulin-dependent diabetics. The plasma ANF and metabolic control may play an important role in the pathophysiology of exercise-induced microalbuminuria.

Inhibition Of Kinin Degradation On The Luminal Side Of Renal Tubules Reduces High Blood Pressure In Deoxycorticosterone Acetate Salt‐Treated Rats

1. To determine whether the antihypertensive response in deoxycorticosterone acetate (DOCA) salt‐treated rats was mediated by kinins on the luminal side of renal tubules or in the circulation, selective urinary kininase inhibitors were administered to normal Brown Norway Kitasato (BN‐Ki) rats and kininogen‐deficient Brown Norway Katholiek (BN‐Ka) rats.

Three-Dimensional Ultrastructure of Human Glomerular Basement Membrane by a Quick-Freezing and Deep-Etching Method

The three-dimensional ultrastructure of glomerular basement membrane (GBM) in surgically resected human kidneys was observed by the quick-freezing and deep-etching method. In three layers of human GBM, the middle layer exhibited polygonal meshwork structures, which were composed of fine fibrils. In addition, the outer and inner layers were formed by lines of perpendicular fibrils, which connected the epithelial or endothelial cell surfaces with the meshwork structures of the middle layer. These ultrastructures might correspond to the three layers, such as lamina densa and laminae rara externa and interna, which were also observed on conventional ultrathin sections. It is concluded that the human GBM has the same meshwork structures and perpendicular fibrils as those previously observed in animals and that these structures may act functionally as size and/or charge barriers.