Biomedical subjects

V Anyaoku

Publications and source records attributed to V Anyaoku.

36 records · Page 2Linked to original sources

PubMed1993

Response of sex hormone binding globulin and insulin-like growth factor binding protein-1 to an oral glucose tolerance test in obese women with polycystic ovary syndrome before and after calorie restriction.

OBJECTIVE: We determined the relationship of short-term changes in circulating insulin concentrations, resulting from an oral glucose load, to those in both sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein 1 (IGFBP-1) and assessed the effect of a short-term low calorie diet on the levels of SHBG and IGFBP-1 during an oral glucose tolerance test. DESIGN: A within-group comparison of biochemical indices during an oral glucose tolerance test before and after calorie restriction. PATIENTS AND METHODS: Six obese women with polycystic ovary syndrome with mean (SD) BMI 34.2 (3.4) kg/m2 were studied before and after one month on a very low calorie diet (350 kcal/day; Cambridge diet). Each subject was given a 75-g oral glucose load after an overnight fast and blood samples were taken every 30 minutes for 3 hours. These were analysed for glucose, insulin, SHBG, and IGFBP-1. RESULTS: All the women lost weight (range 1.7-9.5 kg). The SHBG concentrations did not change significantly during the oral glucose tolerance test but there was a highly significant decline in IGFBP-1 levels both before (0 min, mean (SD) 27.3 (10.6); 180 min, 8.9 (4.2) micrograms/l) and after (0 min, 28.4 (12.1); 180 min, 6.2 (2.1) micrograms/l, P < 0.001) dieting. The sum of the SHBG concentrations during the test, however, was significantly lower prior (129.9 (40.5) nmol/l) to calorie restriction than after (164.3 (70.6) nmol/l), whereas there was no significant effect of dieting on the IGFBP-1 response to glucose. CONCLUSIONS: The changes in insulin and SHBG concentrations found after dieting have been confirmed. SHBG levels, in contrast to IGFBP-1, do not change in response to a short-term increase in insulin or glucose concentrations. The difference in the response of the two binding proteins may be explained by differences in their half-lives in the circulation or the regulation of mRNA for the peptides by insulin. This study confirms that insulin regulates both SHBG and IGFBP-1 but that there is a difference in the time course of the response of the two proteins to insulin.

Carrier Proteins↗

PubMed1993

Insulin insensitivity is associated with a decrease in postprandial thermogenesis in normal pregnancy.

Insulin sensitivity and postprandial thermogenesis were investigated at various stages of pregnancy to assess if changes in insulin sensitivity contribute to energy conservation during pregnancy. Cross-sectional and longitudinal studies were undertaken. Sixteen control non-pregnant women were compared with 10 women in the second trimester (2nd) and thirteen women in the third trimester (3rd) of uncomplicated pregnancy. Six women were studied at all three time points. The slope of plasma glucose decline following a bolus of intravenous insulin was used as an index of insulin sensitivity. Resting energy expenditure was measured with continuous indirect calorimetry. Postprandial thermogenesis was measured as the change in energy expenditure for the 2 h after a mixed meal. Results are expressed as mean +/- SEM or median (interquartile range). Insulin sensitivity was lower as pregnancy progressed (non-pregnant control 181 (177-205) vs 2nd 111 (100-112) vs 3rd 96 (80-109) mumol l-1 min-1, p < 0.001). Fasting insulin levels were significantly higher in the third trimester but not in the second trimester (non-pregnant control 1.9 (1.5-6.0) vs 2nd 3.1 (2.8-5.2) vs 3rd 8.6 (4.8-9.7) mU l-1, p < 0.05). Meal stimulated insulin levels were higher in the second and third trimesters compared to non-pregnant women (insulin area over 2 h, postmeal, non-pregnant control 78 +/- 10 vs 2nd 92 +/- 14 vs 3rd 145 +/- 14 mU l-1 h-1, p < 0.005). Postprandial thermogenesis was lowest in the third trimester (non-pregnant control 103 +/- 5 vs 2nd 74 +/- 8 vs 3rd 48 +/- 8 kJ, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Differential metabolic actions of biosynthetic insulin analogues in normal man assessed by stable isotopic tracers.

Insulin analogues have been produced with high affinity for the insulin receptor and with affinity lower than that of native insulin, but differences in activity when administered in vivo to man are unconvincing. We have used very low dose insulin (0.005 units kg-1 h-1) to investigate possible differences in effect of these insulin analogues on lipolysis in seven healthy subjects. Only minor effects on blood glucose concentration were observed and glucose turnover measured isotopically with 6,6 2H glucose and leucine turnover measured with 1-13C leucine did not change significantly. Fatty acid levels decreased with insulin (area under curve, median (range) -23 (-41-10) mmol l-1) and with the low affinity analogue (-28 (-42-19) mmol l-1 h,), but the high affinity analogue had no significant effect compared with controls (high affinity analogue -8 (-28-35) mmol l-1 h; control +15 (11-53) mmol l-1). Glycerol production measured isotopically decreased with insulin (-0.54 (-1.50-0.63) mumol kg-1 min-1) and with the low affinity analogue (-0.74 (-1.76-0.72) mumol kg-1 min-1), but the high affinity analogue at these doses had no significant effect on glycerol turnover (-0.19 (-0.74-1.13) mumol kg-1 min-1). Thus at these low infusion rates insulin itself and the low affinity analogue suppressed lipolysis, as assessed by glycerol turnover and by circulating fatty acid concentrations. The high affinity analogue was cleared rapidly from the circulation producing no measurable increase in immunoreactive insulin concentrations, and no effect was observed on lipolysis.

Adult↗

PubMed1992

Abnormalities of intermediary metabolism following a gestational diabetic pregnancy.

OBJECTIVE: The aim of this study was to compare intermediary metabolism in glucose tolerant women with previous gestational diabetes and control women without a history of gestational diabetes. SUBJECTS: Fifteen women with previous gestational diabetes and 15 controls individually matched for race, age and body mass index were included. Only subjects with normal glucose tolerance were included in this study. METHODS: Plasma glycerol, 3-OH butyrate, non-esterified fatty acids (NEFA), glucose and insulin were measured fasting and following a 75 g oral glucose load. RESULTS: The women with previous gestational diabetes and their matched controls were of similar racial origin, age and body mass index. There was no difference between those with previous gestational diabetes and controls in fasting glycerol, 3-OH butyrate, NEFA, glucose or insulin concentrations. Following the oral glucose load, glycerol, 3-OH butyrate and NEFA concentrations fell in both groups. However, compared with controls at 120 minutes, those with previous gestational diabetes had significantly higher concentrations of glycerol (median 57, range 24-216 vs 27, range 8-89 mumols/l, P less than 0.005) and 3-OH butyrate (9, range 1-18 vs 5, range 2-11 mumols/l, P less than 0.01). NEFA concentrations were similar in the two groups. Despite similar glucose concentrations during the oral glucose tolerance test the insulin response during the first 60 minutes following oral glucose was significantly reduced in the subjects with previous gestational diabetes when compared with controls (insulin area, 0-60 minutes; 2172, range 788-4767 vs 2830, range 996-4784 pmol min/l, P less than 0.05). CONCLUSIONS: Women with a previous history of gestational diabetes, despite having normal glucose tolerance, have defective insulin release with resultant abnormalities of intermediary metabolism.

3-Hydroxybutyric Acid↗

PubMed1992

Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance.

OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.

Adult↗

PubMed1992

Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.

OBJECTIVE: Obese women with polycystic ovary syndrome have a greater frequency of menstrual disturbance and of hirsutism than lean women with the syndrome. Initial studies have demonstrated a marked improvement in endocrine function following a short-term, very low calorie diet. The purpose of this study was to examine the effect of long-term calorie restriction on clinical as well as biochemical abnormalities in obese women with polycystic ovary syndrome. DESIGN: We performed a within-group comparison of clinical and biochemical indices before and during dietary treatment. PATIENTS: Twenty-four obese women with polycystic ovary syndrome (mean weight 91.5 (SD 14.7) kg) were scheduled for treatment for 6-7 months with a 1000 kcal, low fat diet. Nineteen of the 24 had menstrual disturbances, 12 had infertility and 19 were hirsute. MEASUREMENTS AND RESULTS: Thirteen subjects lost more than 5% of their starting weight (range 5.9-22%). In this group there was no significant change in gonadotrophin or total serum testosterone levels but there was a marked increase in concentrations of sex hormone-binding globulin (pretreatment: 23.6 (9.5); post-treatment 36.3 (11.8) nmol/l, P = 0.002) and a reciprocal change in free testosterone levels (77 (26) vs 53 (21) pmol/l, P = 0.009). These changes were accompanied by a reduction in fasting serum insulin levels (median (range) 11.2 (5.2-32) vs 2.3 (0.1-13.8) mU/l, P = 0.018) and the insulin response to 75 g oral glucose. There were no significant changes in these indices in the group who lost less than 5% of their initial body weight. Of the 13 women who lost greater than 5% of their pretreatment weight, 11 had menstrual dysfunction. Amongst these women, nine of 11 showed an improvement in reproductive function, i.e. they either conceived (five) or experienced a more regular menstrual pattern. There was a reduction in hirsutism in 40% of the women in this group. By contrast, in the group who lost less than 5% of their initial weight, only one of the eight with menstrual disturbances noted an improvement in reproductive function and none had a significant reduction in hirsutism. CONCLUSIONS: These data indicate that moderate weight loss during long-term calorie restriction is associated with a marked clinical improvement which reflects the reduction in insulin concentrations and reciprocal changes in SHBG. The improvement in menstrual function and fertility may therefore be consequent upon an increase in insulin sensitivity which, directly or indirectly, affects ovarian function.

Body Mass Index↗

PubMed1992

Ethnic differences in insulin secretion in women at risk of future diabetes.

The plasma glucose and insulin responses to oral glucose were studied in 44 women who had previously had gestational diabetes, but had reverted to normal glucose tolerance. Twenty were White, 14 Black, and 10 Asian. A group of race-, age- and weight-matched controls was also studied. Fasting values of glucose and insulin did not differ significantly between the study group and controls. During the 2 h 75-g OGTT the White and Black previously gestational-diabetic women had similar plasma glucose values to their controls, while the Asian previously gestational-diabetic women had significantly higher glucose values at 30 min (9.2 +/- 0.6 (+/- SE) vs 7.1 +/- 0.3 mmol l-1, p less than 0.02) and at 60 min (8.6 +/- 0.8 vs 6.2 +/- 0.4 mmol l-1, p less than 0.02). Compared with their race-matched controls, the White previously gestational-diabetic women had significantly lower insulin values at 60 min (median 41 range 2-91) vs 56 (15-118) mU l-1, p less than 0.05), and the Black previously gestational-diabetic women had lower values at both 30 min (17 (4-116) vs 53 (22-197) mU l-1) and 60 min (36 (4-148) vs 99 (12-169) mU l-1, p less than 0.05). The insulin values were similar during the OGTT in the Asian previously gestational-diabetic women and their controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

A defect in insulin release in women at risk of future non-insulin-dependent diabetes.

1. A study on seven Caucasian glucose-tolerant women with previous gestational diabetes and seven matched control subjects is presented. The insulin response to oral glucose, insulin sensitivity and fasting glucose production rates were measured by using a 75 g oral glucose tolerance test, an insulin tolerance test and a non-radioactive tracer, [6,6-2H]glucose, respectively. 2. Fasting plasma glucose levels were similar between the women with previous gestational diabetes and the control subjects (4.8 +/- 0.3 versus 4.7 +/- 0.2 mmol/l), as were fasting plasma insulin levels (median 4 m-units/l, range 1-13 m-units/l versus median 4 m-units/l, range 1-24 m-units/l). After oral glucose the 60 min plasma glucose levels in the women with previous gestational diabetes were significantly higher (8.5 +/- 0.6 versus 6.7 +/- 0.8 mmol/l, P less than 0.05), whereas the plasma insulin level was significantly lower at both 30 min (median 23 m-units/l, range 4-47 m-units/l versus median 55 m-units/l, range 23-100 m-units/l, P less than 0.02) and at 60 min (median 23 m-units/l, range 4-43 m-units/l versus median 60 m-units/l, range 16-126 m-units/l, P less than 0.02). 3. Insulin sensitivity, expressed as the slope of the regression line of plasma glucose level against time after intravenous infusion of insulin (0.05 unit/kg), was similar in the women with previous gestational diabetes and the control subjects (mean slope, -0.17 +/- 0.01 versus -0.17 +/- 0.01). 4. Fasting glucose production rates were similar in the women with previous gestational diabetes and the control subjects (2.2 +/- 0.3 versus 1.9 +/- 0.1 mg min-1 kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Feedback inhibition of insulin secretion in type 2 diabetes.

1. The purpose of the present study was to examine the ability of insulin to inhibit its own secretion in type 2 diabetes independently of the prevailing plasma glucose concentration. 2. The responses of the plasma C-peptide concentration to sustained hyperinsulinaemia were assessed during a 200 min isoglycaemic clamp study in 14 patients with type 2 diabetes and seven age- and weight-matched control subjects. The arterialized venous plasma glucose concentration was clamped at approximately 0.3 mmol/l below each subject's own basal level and was not permitted to rise above the basal level. 3. In the fasting state, the plasma C-peptide concentration was slightly, but not significantly, higher in the diabetic patients than in the control subjects (667 versus 413 pmol/l, respectively, P = 0.07), but it remained significantly higher in the diabetic patients during the clamp studies in absolute terms (minimum plasma C-peptide concentration 400 pmol/l in diabetic patients versus 151 pmol/l in control subjects, P less than 0.05) and was suppressed to a lesser extent when expressed as a percentage change from basal (35.8% in diabetic patients versus 59.4% in control subjects, P less than 0.01). 4. In order to investigate whether a high plasma glucose concentration was maintaining the plasma C-peptide concentration in the diabetic patients, six of these patients underwent a second clamp study at euglycaemia (plasma glucose concentration 5.2 mmol/l). Under these conditions, the plasma C-peptide concentration was suppressed to the same extent as in the control subjects (from 623 to 195 pmol/l, a change of 62.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Abnormalities in fasting circulating proinsulin concentration in mild gestational diabetes.

Fasting plasma proinsulin, insulin and glucose concentrations were measured in ten women with mild gestational diabetes and ten controls matched for race, age (32 +/- 6 vs 31 +/- 6 years), body mass index (28 +/- 8 vs 27 +/- 6) and gestational week (24 +/- 4 vs 25 +/- 4 weeks). There was no significant difference in fasting plasma glucose between these gestational diabetics and their controls (median 4.7, range 3.7-6.0 mmol/l vs 4.5, range 3.4-5.3 mmol/l). The fasting proinsulin levels were significantly higher in the gestational diabetics compared with the controls (median 12.2, range less than 4-14.8 pmol/l vs 5.8, range less than 4-12.8 pmol/l, P less than or equal to 0.02, Wilcoxon Summed Rank Test), while the calculated intact insulin levels (immunoreactive insulin minus proinsulin) were significantly lower (median 14.5, range 6.3-81.8 pmol/l vs 51.6, range 11.7-312 pmol/l, P less than or equal to 0.01). The ratio of proinsulin to calculated intact insulin was significantly higher in the gestational diabetics than the controls (median 0.66, range 0.16-2.04 vs 0.12, range 0.03-0.62), P less than or equal to 0.01). These results demonstrate that gestational diabetics, with normal fasting plasma glucose values, have abnormalities in pancreatic beta-cell secretion, which are likely to be important both in the aetiology of gestational diabetes and non-insulin dependent diabetes.

Adult↗

PubMed1991

Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen transport and metabolism in women with PCOS. DESIGN: Within-group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women. PATIENTS: Forty-seven women who presented with hirsutism, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6 +/- 0.7 years (mean +/- SEM), BMI 27.3 +/- 1.2 kg/m2. MEASUREMENTS: Plasma insulin levels were measured at 30-minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (fT), sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS: Neither basal insulin nor the sum of insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with irregular cycles or amenorrhoea than in those with regular ovulatory menses (8.0 +/- 1.1 vs 3.1 +/- 1.5 mU/l, P less than 0.01) despite similarly raised androgen levels. Both basal insulin and sumINS correlated with BMI in women with PCO (r = 0.37, P less than 0.05 and r = 0.64, P less than 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF-I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an inverse correlation and fT correlated positively with sumINS (r = -0.51, P less than 0.01; r = 0.39, P less than 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens. CONCLUSIONS: These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes in SHBG rather than by direct stimulation of ovarian androgen production. Higher insulin concentrations in anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that insulin resistance in the ovary contributes to the mechanism of anovulation in PCOS.

Adult↗

PubMed1991

The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh.

OBJECTIVES: To investigate whether growth hormone (GH) absorption is site dependent. DESIGN AND MEASUREMENTS: Human growth hormone (hGH, Norditropin) 4 IU, was injected subcutaneously on two separate occasions: into the thigh on one occasion and into the abdomen on a second occasion. Blood was sampled for GH, insulin, glucose, non-esterified fatty acids and glycerol at baseline and hourly for 12 hours. Serum insulin-like growth factor I was measured at baseline, and after 12 and 24 hours. SUBJECTS: Eleven healthy young adults (8 M, 3 F). RESULTS: Following the injection serum GH had risen by 1 hour and peaked by 3-6 hours. The peak GH and growth hormone area under the curve were significantly higher after injection in the abdomen compared with the thigh (GH peak (mean +/- SEM) 103 +/- 20 vs 41 +/- 8 mU/l, P = 0.002 and GH area 528 +/- 86 vs 239 +/- 34 mU/l h, P = 0.003 respectively). Serum insulin-like growth factor I at 12 and at 24 hours showed a significant rise from the baseline level, but no significant difference was observed between the two injection sites. No significant difference in plasma insulin, glucose, non-esterified fatty acids or glycerol was observed between the two methods of injection. CONCLUSION: Subcutaneously injected GH is better absorbed from the abdominal site than from the thigh.

Abdomen↗

PubMed1991

The influence of regional adiposity on atherogenic risk factors in men and women with type 2 diabetes.

To determine firstly whether body fat distribution could predict the presence of atherogenic risk factors better than overall adiposity in Type 2 diabetes, and secondly whether sex differences in these risk factors could be explained by sex differences in fat distribution, waist-to-hip girth ratio (WHR), serum lipids, lipoproteins, apolipoproteins, plasma lipolytic activity, and blood pressure were assessed in 47 patients with Type 2 diabetes, 21 women matched for age, body mass index (BMI) and blood glucose control with 26 men. The men had higher WHR (0.95 (range 0.83-1.07) vs 0.82 (0.74-0.94), p less than 0.001), lower HDL-cholesterol (1.03 +/- 0.05 vs 1.38 +/- 0.06 mmol l-1, p less than 0.001) and apolipoprotein A1 (1.40 +/- 0.06 vs 1.76 +/- 0.06 gl-1, p less than 0.001) concentrations, and higher hepatic lipase activities (16.2 (6.4-38.0) vs 8.6 (2.3-23.1) mmol h-1 l-1, p less than 0.01). In both men and women, BMI and WHR were positively related to serum triglyceride, insulin and C-peptide concentrations. In women, HDL-cholesterol was negatively related to BMI (r = -0.45, p less than 0.05) but only possibly related to WHR (r = -0.33, NS). In men, by contrast, WHR was related negatively to HDL-cholesterol (r = -0.60, p less than 0.005), HDL2-cholesterol (r = -0.43, p less than 0.05), and apolipoprotein A1 (r = -0.70, p less than 0.001) and positively to hepatic lipase activity (r = 0.65, p less than 0.001), whereas the same relationships with BMI were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1991

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.

Adult↗

PubMed1990

The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.

BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Adolescent↗

PubMed1990

Abnormalities of glucose tolerance following gestational diabetes.

Glucose tolerance and insulin secretion were studied in 56 women 6-12 years following a pregnancy complicated by gestational diabetes, and in 23 matched controls. At recall 14 women were known to have diabetes and five were again pregnant with recurrent gestational diabetes. The early development of diabetes was associated with a fasting plasma glucose greater than 6 mmol/l during pregnancy and with a high plasma glucose response to oral glucose which persisted after delivery. Obesity was predictive of non-insulin-dependent diabetes whereas those that later required insulin were not obese. At recall, seven of the remaining 37 women were found to have unrecognized diabetes, 13 had impaired glucose tolerance (IGT) and 17 were normal by WHO criteria using a 75 g oral glucose tolerance test. In these 37 women, fasting plasma glucose and the glucose response to oral glucose in pregnancy were not predictive of subsequent diabetes or impaired glucose tolerance. Obesity in pregnancy and subsequent weight gain were associated with non-insulin-dependent diabetes and impaired glucose tolerance at recall. Insulin deficiency was observed during the oral glucose tolerance test in the diabetics (the mean +/- SEM ratio insulin area:glucose area 4.1 +/- 1.3 diabetics, 10.7 +/- 1.8 controls, p less than 0.05), whereas in the group with impaired glucose tolerance insulin levels were high and in proportion to their hyperglycaemia (insulin area:glucose area 10.9 +/- 1.4 IGT, 9.4 +/- 1.4 controls). Women with normal glucose tolerance and previous gestational diabetes had significantly lower insulin responses than their controls, despite mild hyperglycaemia (insulin area:glucose area 4.0 +/- 0.7 normal glucose tolerance, 7.6 +/- 1.1 controls, p less than 0.02). Abnormalities of glucose tolerance and insulin secretion are present following a gestational diabetic pregnancy. Gestational diabetes identifies women at risk for developing diabetes and impaired glucose tolerance, both of which are risk factors for premature vascular disease.

Adult↗

PubMed1990

Direct gonadotrophic effect of growth hormone on oestradiol production by human granulosa cells in vitro.

In-vitro studies in both rodents and man suggest that GH can stimulate ovarian steroidogenesis, but it is not clear whether this effect is mediated by changes in circulating concentrations of insulin-like growth factor-1 (IGF-1) or whether it is a direct action on the ovary (or, indeed, both). In this study the effects of biosynthetic human GH (hGH) on the production of oestradiol and IGF-1 by human granulosa cells in culture were examined using ovarian tissue (from both normal and polycystic ovaries) which had not previously been exposed to exogenous gonadotrophin therapy. Addition of hGH (1 or 10 ng/ml) to the incubation medium resulted in a significant (1.7 to 3.6 fold) increase in oestradiol accumulation after 48h in culture. Human GH also had a significant additive effect on the dose-related responsiveness of granulosa cell oestradiol production to hFSH. Concentrations of IGF-1 in the medium were undetectable in each of these experiments. These studies demonstrate that hGH has a potent, direct stimulatory effect on production of oestradiol by the human ovary which is independent of the effect of FSH. These findings have important implications for understanding the physiological role of hGH in human ovarian function as well as for therapeutic use of biosynthetic hGH for induction of ovulation.

Cells, Cultured↗

PubMedDate not supplied

Insulin resistance, cardiovascular risk factors and ultrasonically measured early arterial disease in normotensive Type 2 diabetic subjects.

BACKGROUND: The objective of the study was to examine the relationship between serum fasting insulin, insulin sensitivity S(i), cardiovascular risk factors, and asymptomatic early atherosclerosis in normotensive Type 2 diabetic subjects. METHODS: Specific insulin was measured using an enzyme-linked immunosorbent assay (ELISA) and insulin sensitivity was assessed with an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT). Early atherosclerotic change was assessed using carotid intima media thickness (IMT) and an arterial ultrasound score (AUS) measured by high-resolution B-mode ultrasound. RESULTS: On bivariate analysis, there was a positive correlation between S(i) and high density lipoprotein (HDL) cholesterol (r(s)=0.27, p<0.05), and a negative correlation between S(i) and body mass index (BMI) (r(s)=-0.42, p<0.001), HbA(1c) (r(s)=-0.29, p<0.05) and serum triglyceride (r(s)=-0.30, p<0.05). There was a positive correlation between carotid IMT and age (r(s)=0.41, p<0.0005), and a positive association with male sex (p<0.0001) as well as with smoking (p<0.0001). However, we found no correlation between carotid IMT and fasting specific insulin (r(s)=-0.04) or S(i) (r(s)=-0.08). On multiple regression analyses, only age and serum triglycerides appeared to be significant independent variables with respect to carotid IMT whereas age, male sex and smoking emerged jointly significant with respect to AUS. There were no independent associations between carotid IMT or AUS with other variables including using either fasting specific insulin or S(i) as markers on insulin resistance separately. CONCLUSION: Carotid IMT and AUS in Type 2 diabetes are closely associated with age, male sex and smoking. The relationships between serum insulin and insulin resistance with ultrasonically measured early arterial disease in Type 2 diabetes remain unclear.

Analysis of Variance↗