Fasting Plasma Immunoreactive Insulin Research Articles

Insulin resistance at diagnosis in Japanese children with type 2 diabetes mellitus

Insulin resistance at diagnosis was investigated in Japanese children with type 2 diabetes mellitus (T2DM). A total of 160 children with T2DM were divided into groups on the basis of percent overweight at time of diagnosis: group A (n = 28), <20%; group B (n = 55), 20-39%; group C (n = 37), 40-59%; group D (n = 40), ≥ 60%. Indicators of insulin resistance at diagnosis were compared among the four patient groups, and also between the children with T2DM and the 201 age-matched normal Japanese children. There were no significant differences in plasma glucose (PG) levels among the four patient groups. The mean concentration of fasting plasma immunoreactive insulin (IRI) was significantly higher in group D than in groups A and B (39.2 µU/mL vs 16.2 µU/mL and 24.1 µU/mL, P < 0.05, respectively). The mean homeostasis model assessment (HOMA-R) was significantly higher in group D than in all the other three groups (17.6 vs 7.8, 10.8 and 12.7, P < 0.05, respectively). The indicators HOMA-R and fasting IRI were significantly higher in each diabetes group, even in non-obese group A, than in normal children (P < 0.01, respectively). Japanese children with T2DM had insulin resistance at diagnosis regardless of percent overweight, and the degree of insulin resistance gradually increased with rise in percent overweight.

Glucose tolerance in amyotrophic lateral sclerosis.

Blood glucose and plasma insulin during an oral glucose tolerance test were determined in 21 patients with amyotrophic lateral sclerosis and in 10 control patients matched for age, obesity and physical activity. In addition, 125I-insulin binding to circulating erythrocytes were studied in a subgroup of 4 ALS patients and 8 controls. Both impaired glucose tolerance and diabetes mellitus were evenly distributed between the study groups, and no difference in mean blood glucose levels during the OGTT was found between ALS and control patients. Fasting plasma immunoreactive insulin concentration was significantly higher in ALS patients as compared to controls, but plasma IRI increments to the glycemic stimulus were similar in the 2 groups. The number of insulin binding sites per cell appeared lower in patients with ALS, but the difference in receptor concentration was not statistically significant. In addition, the specific bound fraction of 125I-insulin showed no difference between ALS and control patients. In conclusion, we were unable to demonstrate any marked deterioration of glucose tolerance or increase in insulin resistance in patients with ALS.

Cardiovascular disease and risk factors in adults with hypopituitarism.

In 1992, Cuneo et al. (1992) reviewed, in this journal, the consequences of growth (GH) deficiency during adult life and coined the term ‘Growth hormone deficiency (GHD) syndrome in adults’. Limited information was available then on cardiovascular disease and risk factors in adults with hypopituitarism. More data have been published since on cardiovascular morbidity in symptom-free hypopituitary adults. Several groups have also published results on the effects of GH therapy on cardiac structure and function and on the cardiovascular risk factors. We shall review here the epidemiological and experimental data on cardiovascular morbidity and mortality in adult hypopituitarism. We shall also examine the prevalence of cardiovascular risk factors in this group of patients and their potential causes focusing on the possible role of GH deficiency and the effects of GH replacement.

Extrapancreatic action of truncated glucagon-like peptide-I in otsuka long-evans tokushima fatty rats, an animal model for non—insulin-dependent diabetes mellitus

To clarify the mechanism(s) of the antidiabetic effects of truncated glucagon-like peptide-1 (GLP-1) in diabetics, we examined its insulinotropic and extrapancreatic effects in a newly established strain of spontaneously non—insulin-dependent diabetic (NIDDM) rats, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, that received a continuous infusion of truncated GLP-1 620 pmol/d/kg (G group, n = 12) or of vehicle (V group, n = 12) for 4 weeks by Alzet pump. Nonfasting plasma glucose levels were significantly lower ( P < .05) in the G group than in the V group (7.0 ± 0.67 v 9.1 ± 1.7 mmol/L), and fasting plasma immunoreactive insulin (IRI) levels were lower in the former than in the latter (0.63 ± 0.31 v 0.78 ± 0.25 nmol/L). At day 15 of infusion, the G group showed an attenuated plasma glucose response to an oral glucose load, but had plasma IRI levels comparable to those in the V group. A long-term infusion of truncated GLP-1 increased the glucose infusion rate (GIR) significantly ( P < .05) during a euglycemic-hyperinsulinemic clamp test (59.0 ± 14.8 μmol/kg/min for group G v 38.9 ± 12.2 for group V), but hepatic glucose output (HGO) did not differ significantly for either group. Uptake of 2-deoxy- d-glucose (2DG) by peripheral muscles in the G group was as much as 2.4-fold higher than in the V group (5.52 ± 2.04 v 2.29 ± 0.97 μmol/100 g muscle weight/min). We conclude from these data that truncated GLP-1, in addition to its well-known incretin effect, is capable of augmenting insulin action in peripheral tissues of diabetics, which can contribute, in part, to improve glucose intolerance in OLETF rats.

Carotid artery intima-media thickness in elderly patients with NIDDM and in nondiabetic subjects.

The risk of atherosclerotic vascular disease is increased both in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in those with impaired glucose tolerance compared with nondiabetic subjects. Although classic cardiovascular risk factors are operative in subjects with NIDDM, other factors closely related to insulin resistance syndrome such as diabetic dyslipidemia and hyperglycemia itself may contribute to an excessive cardiovascular disease risk in subjects with NIDDM. The purpose of this study was to investigate the carotid intimal-medial thicknesses (IMTs) and their determinants in elderly patients with NIDDM and in control subjects. We investigated the common carotid and carotid bifurcation IMTs and their determinants in groups of elderly patients (n = 84, age 67.2 +/- 0.6 years) with NIDDM and in 119 control subjects (21 with impaired and 98 with normal glucose tolerance; ages 67.5 +/- 1.0 and 65.1 +/- 0.6 years, respectively). Common carotid and carotid bifurcation IMTs were greater in the NIDDM group than in control subjects (P < .05 to .01). In NIDDM patients, the mean carotid IMT correlated with postglucose 1-hour plasma insulin (r = .305, P = .01, adjusted for age and sex), serum LDL triglyceride (r = .237, P < .05), and apolipoprotein B concentrations (r = .263, P < .05). Fasting plasma immunoreactive insulin, proinsulin, or specific insulin levels were not significantly associated with carotid IMT. Both diabetic status (P < .05) and the presence of clinical macrovascular disease (P < .01) contributed independently to carotid IMT. Carotid IMT was greater in NIDDM patients than in control subjects. The main determinants of IMT in NIDDM patients were related to both postglucose insulin levels and abnormal lipoprotein profiles characteristic of NIDDM and insulin resistance syndrome. Treatment of these factors is likely to reduce the atherosclerotic burden in NIDDM.

Fasting plasma insulin level is an important risk factor for the development of complications in Japanese obese children—Results from a cross-sectional and a longitudinal study

It is not known what types of factors may contribute to the development of complications in obese children. In the current investigation, we have performed a cross-sectional and a longitudinal study in Japanese obese children to clarify the relationship of the extent of obesity, fat distribution, insulin resistance, and aging to the development of obesity-related complications. In the cross-sectional study of 329 obese boys and 142 obese girls aged 7 to 15 years, the fasting plasma immunoreactive insulin (IRI) level was significantly higher than that of 46 non-obese boys and 48 non-obese girls (boys, 13.4 ± 6.7 v 4.9 ± 1.9 μU/mL, P < .001; girls, 14.0 ± 5.9 v 4.8 ± 1.8, P < .001). Linear regression analysis demonstrated that fasting plasma IRI correlated positively with fasting plasma glucose (FPG), triglycerides (TG), uric acid (UA), and systolic blood pressure (SBP) in obese boys, and with TG, SBP, and diastolic blood pressure (DBP) in obese girls, and negatively with serum high-density lipoprotein cholesterol (HDL-C) in both obese boys and girls. Multiple regression analysis demonstrated that fasting plasma IRI was independently and positively correlated with FPG, TG, and SBP in obese boys. Fasting plasma IRI in obese girls was positively correlated with TG, SBP, and DBP, and negatively with HDL-C. FPG decreased significantly in non-obese children at the onset of puberty, but it remained unchanged in obese children. Fasting plasma IRI and the IRI to glucose ratio increased with age in obese children, whereas they did not show any significant changes in non-obese children. Furthermore, in the longitudinal study of 42 obese children (32 boys and 10 girls) aged 7 to 15 years, significant increases in FPG ( P < .01), insulin, UA, and SBP ( P < .001, respectively) and a significant decrease in serum HDL-C ( P < .001) were observed. Significant positive correlations were also noted between the yearly changes for IRI and SBP, and between the changes for IRI and the number of obesity-associated complications. These results suggest that fasting plasma IRI can be one of the most useful indices for predicting the development of obesity-associated complications in children, especially hypertension, hyperlipidemia, and hyperuricemia.

Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction

A significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immunoenzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs = 0.43; p < 0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p < 0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p < 0.0001) and des-31,32-proinsulin (rs = 0.54; p < 0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.

Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin.

We studied insulin binding, receptor autophosphorylation, and insulin action in isolated adipocytes from 23 Pima Indians with varying degrees of obesity over a range of glucose tolerance. [125I]Insulin binding varied widely and did not correlate with fasting plasma immunoreactive insulin levels or insulin sensitivity, as assessed by the ED50 values of insulin stimulation of glucose transport or insulin inhibition of lipolysis in isolated abdominal wall adipocytes obtained by biopsy from the patients. In contrast there was a significant correlation between loss of stimulation of autophosphorylation in solubilized receptors and loss of insulin sensitivity for both stimulation of glucose transport (r = -0.59; P less than 0.005) and inhibition of lipolysis (r = -0.54; P less than 0.01). There was also a significant inverse correlation between insulin's ability to stimulate receptor autophosphorylation and in vivo insulin resistance, as assessed by fasting plasma insulin levels (r = -0.46; P less than 0.05). These data indicate a significant correlation between changes in sensitivity of glucose transport and antilipolysis to insulin and receptor kinase activity in those patients and suggest that defective coupling of insulin binding to insulin action at the level of phosphorylation of the insulin receptor may cause the insulin resistance in this group of patients.

Influence of endogenous hyperinsulinism on high density lipoprotein 2 level in type 2 (Non-insulin-dependent) diabetes mellitus and impaired glucose tolerance

We determined the insulin response to an oral glucose ingestion and levels of serum lipoproteins in 25 untreated patients with type 2 diabetes mellitus, in 26 subjects with impaired glucose tolerance (IGT), and in 35 non-diabetic control subjects. The three groups had similar compositions with respect to age and sex distribution. The levels of VLDL triglycende in the subjects with type 2 diabetes or IGT were higher than those in controls. Serum HDL- and HDL 2 cholesterol were significantly decreased in type 2 diabetics, and the subjects with IGT showed a similar tendency. Serum apolipoprotein A-II levels were lower in the male subjects with type 2 diabetes or IGT than in controls. Insulin reponse, i.e., sum of immunoreactive insulin (IRI) levels at basal, 30, 60, 90 and 120 min after a 75-g oral glucose load, negatively correlated to HDL and HDL 2 cholesterol levels ( r = −0.396, P < 0.05; r = −0.482, P < 0.001, respectively), and positively correlated to VLDL triglyceride values ( r = 0.485, P < 0.001) in the male subjects with type 2 diabetes or IGT. In the female subjects, fasting plasma IRI values significantly correlated to HDL cholesterol ( r = −0.496, P < 0.05). There was a significant negative correlation between the concentrations of HDL 2 cholesterol and VLDL trgglyceride. These data show that lipoprotein metabolism, not only in type 2 diabetics, but also in IGT tends to show changes such as decreased HDL 2 cholesterol and increased VLDL triglyceride levels, and which might be related to the hypersecretion of endogenous insulin.

Effect of fasting interval on CCK-8 suppression of food intake in the baboon

Baboons were infused intravenously for 5 min with the octapeptide of cholecystokinin (CCK-8) after either a 16.5- or 3.5-h fast. After a 3.5-h fast, food intake was significantly suppressed over the ensuing 30 min by 2 micrograms/kg of CCK-8 (-156 +/- 34 kcal compared with control days, P less than 0.02) and by 4 micrograms/kg of CCK-8 (-257 +/- 31 kcal, P less than 0.01). In contrast, CCK-8 had no reliable effect on food intake after the same baboons had been fasted for 16.5 h (2 micrograms/kg: -93 +/- 40 kcal, P greater than 0.05; 4 micrograms/kg: -30 +/- 82 kcal, P greater than 0.05). There was no reliable effect of 1 microgram/kg of CCK-8 on food intake at either deprivation interval. CCK-8 infusions resulted in a small increase of fasting plasma immunoreactive insulin (IRI); this effect was not related to either dose or deprivation length. Postprandial IRI and glucose concentrations were significantly suppressed by CCK-8 independently of its effect on food intake. Thus, after a 16.5-h fast, 4 micrograms/kg of CCK-8 decreased postprandial IRI from 145 +/- 65 to 29 +/- 4 microU/ml (P less than 0.01) and glucose from 101 +/- 5 to 80 +/- 3 mg/dl (P less than 0.02), despite no concomitant effect on food intake. Similar suppression of plasma IRI and glucose were observed after infusions of 1 and 2 micrograms/kg in 16.5-h-fasted animals. All doses of CCK-8 (1, 2, and 4 micrograms/kg) suppressed postprandial IRI and glucose after a 3.5-h fast.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a new diuretic piretanide on glucose tolerance, insulin secretion and 125I-insulin binding.

The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and 125I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glycohaemoglobin A1 measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 microU/ml; p less than 0.05). Glucagon - stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 microU/ml, p less than 0.05) and after 8 weeks (1.67 vs. 2.90 microU/ml, p less than 0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of 125I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.

Effect of caloric restriction on basal insulin levels and the in vivo lipogenesis and glycogen synthesis from glucose in the Koletsky obese rat

Fasting plasma immunoreactive insulin levels increased with age in hyperinsulinemic Koletsky obese rats, being almost four times as high as in lean siblings at 3 mo (40 ± 5 μU/ml) and rising steadily to 82 ± 4 μU/ml at 6 mo (about seven times higher than lean siblings). Restricting the food intake of the obese rats markedly reduced but did not normalize the hyperinsulinemia, which in these rats was accompanied by normal plasma glucose concentrations. The incorporation in vivo of D-U- 14C-glucose into tissue lipids and glycogen was measured 1 hr after the intravenous injection of 1 g glucose (containing 100 μCi D-U- 14C-glucose) per kg body weight in obese rats eating ad libitum, obese rats after 3 mo on a restricted food intake, and lean siblings. All tissues (heart, diaphragm, skeletal muscle, and adipose tissues and liver) of obese rats exhibited a significantly greater lipogenesis from glucose than those of lean siblings. Dietary restriction of the obese rats reduced the 14C incorporation into lipid to levels not significantly different from lean controls in all tissues except skeletal muscle and liver, where, although greatly reduced, lipogenesis was still significantly higher than in lean rats. Glycogen synthesis tended to be greater in all tissues of obese rats than in lean animals. Dietary restriction of obese rats did not greatly affect glycogen synthesis.

Studies on plasma insulin levels of diabetic patients in Karachi

The character of diabetes prevalent in Asian and other tropical countries differs greatly from that in temperate climates. We suggest that in the tropical type of diabetes there may not be insulin deficiency but that extra-pancreatic factors may play an important role in pathogenesis. Sixty-five untreated maturity-onset diabetic suspects were investigated by glucose tolerance test (GTT) and fasting plasma immuno-reactive insulin (IRI). The levels of fasting plasma IRI were significantly higher in both obese and non-obese diabetic patients as compared with the normal subjects. Obesity was associated with higher IRI levels both in normals as well as in diabetic patients. Socio-economic status does not significantly affect the IRI values. It is concluded that diabetes in these patients is not due to deficiency of insulin.

Physiologic changes in plasma chromium of normal and pregnant women: Effect of a glucose load

Plasma chromium (Cr) concentrations were determined for healthy nonpregnant women and also for women in late pregnancy of similar ages. Plasma Cr was found to be significantly lower in the fasting fireanant subjects (2.97 ± 0.11 standard error of the mean [S.E.M]) than in normal subjects (4.70 ± 0.15 S.E.M.). An intravenous glucose load (25 Gm.) produced a prompt and sustained fall in plasma Cr in normal women but it failed to change the plasma Cr level of pregnant subjects. A similar fall in plasma chromium was also observed in nonpregnant subjects after an oral glucose load. The plasma Cr response was specific in that plasma copper and iron were unaltered by the glucose load. The mean rate of glucose assimilation after intravenous glucose loading was nearly identical for the pregnant and nonpregnant subjects. Plasma inorganic phosphate decreased in both pregnant and nonpregnant subjects but the fall was diminished in pregnancy. Fasting plasma immunoreactive insulin (IRI) was not significantly different for pregnant and nonpregnant subjects, but the plasma IRI response to a glucose load was greatly increased in pregnancy. The significance of the plasma Cr changes and the other experimental results are discussed in relation to the known altered carbohydrate metabolism of pregnancy.