PubMed Health⌕ Search

Biomedical subjects

T Wasada

Publications and source records attributed to T Wasada.

At least 37 records · Page 2Linked to original sources
PubMed1996

Lack of C-peptide suppression by exogenous hyperinsulinemia in subjects with symptoms suggesting reactive hypoglycemia.

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.

Adolescent↗
PubMed1996

[Hyperuricemia and insulin resistance].

Hyperuricemia is often associated with obesity, hypertension and dyslipidemia, and is thought to be a risk factor for cardiovascular disease, thereby making resemblance to the insulin resistance syndrome. Our data showed a low, but significant correlation between serum uric acid concentration and the degree of insulin resistance (GIR) estimated by euglycemic hyperinsulinemic clamp method in 67 subjects with combined normal glucose tolerance and IGT(r = -0.278, p < 0.05). Plasma HDL-C and TG levels were also correlated with uric acid levels. One hundred sixty NIDDM patients who had undergone the clamp study were stratified into 5 groups according to the serum uric acid level. In the top quintile (UA : 7.8 +/- 0.8 mg/dl), BMI, male prevalence, plasma TG, HDL-C, fasting IRI, and total IRI response(0 + 60 + 120 min) during meal tolerance test were significantly higher, while age and GIR value tended to be lower without significance compared with those in the bottom quintile (UA : 3.4 +/- 0.5 mg/dl). These results, which are in agreement with the previous studies, support the notion that elevated serum uric acid is a feature of insulin resistance syndrome.

Cardiovascular Diseases↗
PubMed1995

Insulin resistance is associated with high plasma ouabain-like immunoreactivity concentration in NIDDM.

The aim of the present study was to elucidate the pathophysiologic significance of circulating ouabain as a link between insulin resistance (IR) and hypertension (HT) in NIDDM. Euglycaemic (4.5 mmol/l) hyperinsulinaemic (360-580 pmol/l) clamping was performed using an artificial endocrine pancreas. Plasma ouabain-like immunoreactivity (OLI) was determined by radioimmunoassay using a highly specific antibody to ouabain. HT was defined as systolic blood pressure > 140 mm Hg and/or diastolic > 90 mm Hg or being treated with antihypertensive agents. The values (mean +/- SEM) of glucose infusion rate (GIR) and plasma OLI were compared among the four groups classified using IR and HT as factors. Group I (IR-/HT-, n = 15): GIR 7.20 +/- 0.36 mg.kg-1.min-1, OLI 130.8 +/- 20.9 pmol/l, which was not different from that in eight normal control subjects (7.69 +/- 0.40 mg.kg-1.min-1 and 142.6 +/- 32.3 pmol/l, respectively); Group II (IR-/HT+, n = 13): 5.89 +/- 0.36 mg.kg-1.min-1, 172.5 +/- 35.0 pmol/l; Group III (IR+/HT-, n = 14) 1.91 +/- 0.28 mg.kg-1.min-1, 576.6 +/- 161.5 pmol/l (p < 0.01 vs Group I and II); Group IV (IR+/HT+, n = 15) 1.79 +/- 0.22 mg.kg-1.min-1, 703.1 +/- 170.1 pmol/l (p < 0.01 vs Group I and II), respectively. Six of 57 NIDDM patients studied exhibited very high (> 1500 pmol/l) plasma OLI concentrations, showed marked insulin resistance and were all hypertensive. When analysed as a whole, plasma OLI was negatively correlated with GIR (p < 0.001), but was not correlated with arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Hyperglycemia facilitates urinary excretion of C-peptide by increasing glomerular filtration rate in non-insulin-dependent diabetes mellitus.

We have evaluated the feasibility of monitoring the 24-hour urinary excretion rate of C-peptide (U-CPR) as a measure of integrated beta-cell function in patients with non-insulin-dependent diabetes mellitus (NIDDM). In 37 normoalbuminuric patients, U-CPR of 117.9 +/- 9.1 micrograms/d (mean +/- SEM) during the poorly controlled glycemic phase (fasting plasma glucose [FPG], 171 +/- 7 mg/dL; hemoglobin A1C [HbA1c], 8.8% +/- 0.4%) was significantly higher than the value of 83.3 +/- 13.7 micrograms/d (P < .001) during the well-controlled phase (FPG, 135 +/- 6 mg/dL; HbA1c, 7.0% +/- 0.2%), although the plasma insulin response to meals was lower during the former phase (53.3 +/- 6.3 microU/mL) versus the latter phase (65.7 +/- 6.6, P < .005). Endogenous creatinine clearance (Ccr) was significantly elevated during the poorly controlled phase (105.4 +/- 7.3 v 88.7 +/- 4.7 mL/min, P < .005). In 26 microalbuminuric patients, the plasma insulin response was greater during good glycemic control, but U-CPR did not differ between the two phases. Ccr was comparable at two phases in this group (92.7 +/- 7.4 v 91.1 +/- 5.9 mL/min, NS). U-CPR correlated positively with Ccr in both groups (r = .593, P < .001 in normoalbuminuria; r = .585, P < .001 in microalbuminuria). In addition, when biosynthetic human C-peptide was infused intravenously at an identical rate in two healthy subjects, resulting steady-state plasma levels of CPR were lower, and fractional U-CPR was higher during the moderately hyperglycemic phase versus the euglycemic phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevalence of macro- and microvascular diseases in non-insulin-dependent diabetic and borderline glucose-intolerant subjects with insulin resistance syndrome.

This study was undertaken to ascertain whether patients with insulin resistance syndrome, a cluster of risk factors for coronary artery disease (CAD), are really a high risk population for macro- and microvascular diseases in Japanese NIDDM and borderline glucose-intolerant subjects. A diagnosis of insulin resistance syndrome was made if four of the six following criteria are satisfied: glucose disposal rate < 2.2 mg/kg/min, fasting plasma IRI > 15 microU/ml or peak plasma IRI > 100 microU/ml during meal tolerance test, plasma triglyceride > 150 mg/dl at fasting or > 200 mg/dl after meal, serum HDL-cholesterol < 40 mg/dl, blood pressure > 140 mm Hg systolic and > 90 mm Hg diastolic or treatment with antihypertensive agents, and body mass index (BMI) > 27 for men or > 25 for women. We compared the prevalence of CAD, cerebral vascular disease (CVD), peripheral vascular disease (PVD), retinopathy and nephropathy between the insulin resistance syndrome group (group A, n = 57) and the remaining group (group B, n = 164). Both groups did not differ with respect to age, duration of diabetes, BMI, fasting plasma glucose, HbA1c, composition of NIDDM and borderline glucose-intolerance (BGI) or treatment modality. The prevalence of CAD was significantly higher in group A compared with that in group B (31.6% vs. 14.0%, P < 0.002), but not for CVD (8.8% vs. 3.7%, respectively, P = 0.12) or PVD (1.8% vs. 2.4%, respectively, P = 0.76). The prevalence of late-stage retinopathy in group A was significantly higher than that in group B (12.3% vs. 2.4%, respectively, P < 0.005). Macroalbuminuria, but not microalbuminuria, was significantly higher in group A than that in group B (12.3% vs. 3.6%, P < 0.02). We conclude that the insulin resistance syndrome preferentially increases the development of CAD, and is also involved in the progression of microvascular diseases.

Adult↗
PubMed1995

The relationship between insulin resistance and insulin secretion in Japanese subjects with borderline glucose intolerance.

Insulin resistance and impaired insulin secretion can be involved in the development of non-insulin-dependent diabetes mellitus (NIDDM), but their relative importance or temporal relationship are poorly understood. To elucidate this issue, we studied 51 subjects with borderline glucose intolerance (BGI) and 18 normal glucose tolerant subjects (NGT) according to the Japan Diabetes Society criteria. The glucose infusion rate (GIR, mg/kg/min), an index of whole body insulin resistance (IR), was measured by the euglycemic (80 mg/dl) hyperinsulinemic clamp technique (insulin infusion rate 1.12 mU/kg/min). Insulinogenic index (delta IRI/delta BS at 30 min) and the insulin area under the curve during a 75-g oral glucose tolerance test (OGTT) were estimated. In the BGI subjects, the GIR values showed marked variation ranging from 2.24 to 10.44 mg/kg/min (5.54 +/- 0.31, mean +/- S.E.M.). The GIR values were lower in obese BGI subjects compared with non-obese BGI and NGT subjects, and the insulin area was markedly higher in BGI subjects with increased insulin resistance. There was a significant negative correlation between the GIR values and the insulin area or delta IRI/delta BS (30') ratio in the subjects with BGI either in the whole group or solely in the non-obese group. We conclude that the increased insulin secretion compensates for the peripheral insulin resistance of subjects with slightly deteriorated glucose tolerance, implying that insulin resistance plays an important role in the pathogenesis of NIDDM in some fraction of Japanese population.

Adolescent↗
PubMed1995

Highly increased insulin secretion in a patient with postprandial hypoglycemia: role of glucagon-like peptide-1 (7-36) amide.

The mechanism(s) of an inappropriate secretion of insulin is poorly understood. We report a case of reactive hypoglycemia associated with an unusually exaggerated insulin secretion. The patient, a 32-year-old man, developed frequent episodes of postprandial hypoglycemia after interferon treatment was begun for chronic type C hepatitis. Oral glucose challenge test confirmed the patient's extremely high plasma IRI response, i.e., more than 1000 microU/ml, and that of plasma C-peptide 56.9 ng/ml at 90 min, followed by symptomatic hypoglycemia (plasma glucose 34 mg/dl) at 240 min. The plasma proinsulin level also was high, but the molar ratio of immuno reactive insulin (IRI)/plasma C-peptide and IRI/proinsulin was within the normal range. Antibodies to insulin or insulin-receptor were negative. Plasma IRI response was apparently greater when the glucose was given orally than when given intravenously. The response of plasma glucagon-like-peptide (GLP)-1 to oral glucose was quite high (from baseline of 45.5 to 303.2 pmol/L) and showed a close parallel with the change in the plasma IRI concentration. The greatly enhanced insulin secretion leading to reactive hypoglycemia in this patient may therefore be attributed to the increased secretion of GLP-1.

Adult↗
PubMed1995

Pathophysiological significance of plasma total renin and prorenin in patients with diabetes mellitus.

To seek the pathophysiologic significance of measuring the concentration of total renin instead of prorenin, we determined the plasma total renin concentration by immunoradiometric assay and correlated the results with various clinical features and laboratory parameters of diabetic complication in 108 patients with diabetes mellitus. The plasma prorenin concentration was estimated as the difference between the total and active renin concentrations. The plasma total renin and prorenin concentrations were high in patients with diabetes mellitus, in contrast to the active renin concentration which was slightly decreased. In addition, the plasma total renin and prorenin concentrations were higher in patients with diabetic complications than in patients without any complication. Multiple regression analysis showed that the presence of orthostatic hypotension, diabetic retinopathy, and proteinuria is significantly associated with the increased plasma total renin and prorenin concentrations. In addition, there was a significant positive correlation between the total renin and prorenin concentrations. These results suggest that both the plasma total renin concentration and the prorenin concentration are closely related to diabetic complications. Determination of the plasma total renin concentration by immunoradiometric assay as a substitute for prorenin could be a powerful tool in elucidating the mechanism for the increased plasma prorenin in diabetes mellitus.

Adult↗
PubMed1995

Insulin sensitivity and negative insulin feedback after pancreas transplantation in insulin-dependent diabetic patients.

The aims of this study were to determine the change in the rate of insulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreas-kidney transplant recipients with insulin-dependent diabetes mellitus. Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation. The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression. Physiological hyperinsulinemia (50-70 microU/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Taking into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subjects and evidence of increased insulin secretion in pancreas recipients, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pancreas in the absence of insulin resistance.

Adult↗
PubMed1995

Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations.

Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.

Acute Disease↗
PubMed1995

Association of sick sinus syndrome with hyperinsulinemia and insulin resistance in patients with non-insulin-dependent diabetes mellitus: report of four cases.

We report four non-insulin-dependent diabetic (NIDDM) patients accompanied by a unique combination of sick sinus syndrome (SSS) and hyperinsulinemia of unknown etiology. SSS of all four cases was due to sinus arrest in association with paroxysmal atrial fibrillation (Rubenstein-III). Of special interest is that one patient showed a high prevalence of SSS and NIDDM among her close relatives. Hyperinsulinemia of moderate degree was seen at fasting state or after carbohydrate ingestion in the absence of obesity. The resistance to the action of insulin on glucose metabolism which was evaluated in three patients by the euglycemic hyperinsulinemic clamp study was found to be comparable to the lowest quartile level for common NIDDM patients. Because insulin is a physiological regulator of cell-membrane Na+/K+-ATPase, we speculate that malfunction of the sinus node automaticity may be caused by chronic exposure to hyperinsulinemia secondary to insulin resistance in these NIDDM patients.

Aged↗
PubMed1994

Relationship between insulin resistance and risk factors for cardiovascular disease in Japanese non-insulin-dependent diabetic patients.

To investigate whether a resistance to insulin-stimulated glucose uptake (IR) is associated with the risk factors (RF) for cardiovascular disease (CVD) in non-insulin-dependent diabetic (NIDDM) patients, we determined the degree of IR in 135 adult NIDDM patients who had no advanced diabetic complications. The euglycemic (80 mg/dl) hyperinsulinemic clamp (insulin infusion rate 1.12 mU/kg per min) was performed and the average glucose infusion rate (GIR) during a steady-state euglycemia was determined as a measure of IR. Hypertension was more common among NIDDM patients with an increased IR and was highest in the group of patients with CVD. CVD-RF such as hypertension, hypertriglyceridemia, low HDL-cholesterol and obesity tended to cluster in the NIDDM patients who had lower GIR values and higher fasting IRI levels. GIR values were compared between a set of groups extracted from the 135 NIDDM patients that were matched for age, sex, body mass index and HbA1c levels. The CVD-positive group had the significantly lower GIR value than the CVD-negative group (2.06 +/- 0.66 vs. 3.45 +/- 1.75, P < 0.005). The GIR value was also significantly lower in the hypertriglyceridemic group compared with the normotriglyceridemic group (2.50 +/- 1.36 vs. 4.03 +/- 1.82, P < 0.0005). However, there was no significant difference between the hypertensive and normotensive groups and between the high cholesterol or low HDL-cholesterol groups and their respective control groups. In conclusion, these results suggest that IR contributes to the clustering of CVD-RFs which may accelerate the development of CVD in the subgroup of Japanese NIDDM patients.

Adult↗
PubMed1994

Physiological increase in plasma insulin concentration suppresses proinsulin secretion in normal controls but not in subjects with glucose intolerance.

Since insulin negatively controls its own secretion, we examined if insulin also inhibits the secretion of its precursor, proinsulin, in subjects with varying degrees of glucose tolerance. Under comparable hyperinsulinemia (50-70 microU/ml) achieved by the euglycemic insulin clamp technique, plasma C-peptide concentrations were equally suppressed to approximately 40-50% in nonobese subjects with normal glucose tolerance (NGT) (n = 13, 35.5 +/- 3.7%, M +/- SEM), borderline glucose intolerance (BGI) (n = 12, 46.7 +/- 5.6%), and non-insulin-dependent diabetes mellitus (NIDDM) (n = 12, 48.9 +/- 5.4%). In contrast, plasma proinsulin concentrations were slightly but significantly suppressed in NGT (4.1 +/- 0.2 to 3.7 +/- 0.2 pmol/L, P < 0.05), but not in patients with BGI (4.6 +/- 0.3 to 4.8 +/- 0.5 pmol/L, NS) and NIDDM (5.5 +/- 0.5 to 4.9 +/- 0.4 pmol/L, NS). The basal concentrations of proinsulin increased as glucose tolerance declined (P < 0.05 between NGT and NIDDM). These results suggest that the basal secretion of proinsulin by beta-cells seems relatively insensitive to insulin compared with C-peptide, and that the insulin-proinsulin feedback loop is disturbed in glucose-intolerant subjects. Therefore, a defective feedback inhibition of proinsulin secretion by insulin may be partly involved in the disproportionate increase of plasma proinsulin concentrations in patients with NIDDM.

Adult↗