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The effect of electrolytic lesions in the ventromedial hypothalamic nuclei (VMH) on somatostatin and insulin release was studied using the isolated perfused rat pancreas. Obesity gradually developed in the rats after placement of the VMH lesions, and fasting insulin levels determined immediately before the isolation of the pancreas were significantly higher than those in sham-operated controls. In the presence of 4.4 mM glucose, both perfusate somatostatin and insulin responses to arginine were significantly greater than in the controls, suggesting that VMH lesions cause not only hypersecretion of insulin but hypersecretion of somatostatin as well.

Oral glucose tolerance tests were performed in young and elderly subjects with minimal risk factors for diabetes mellitus. Compared to the normal glucose tolerance in the young there was a 45% rate of impaired tolerance in the elderly. Fasting insulin levels were significantly lower in the elderly but post-glucose insulin responses in the first hour were similar in young and elderly subjects. Peripheral insulin action was assessed in terms of the 125 monoiodoinsulin binding to specific insulin receptor sites on circulating lymphocytes in the young, the elderly and a group of age and sex matched obese maturity-onset diabetics. Specific insulin binding was not significantly different in the elderly than in the young but was significantly lower in the diabetics than the young and the elderly. The results suggest that neither defective insulin binding are major causative factors in the reduced glucose tolerance of the elderly.

Monocyte insulin receptor binding was studied in six nonpregnant control patients and in 40 pregnant patients with varying degrees of carbohydrate tolerance. Competitive binding assays were performed to determine insulin binding to monocytes. Fasting insulin levels were determined. We obtained the following results: (1) When compared to values not associated with pregnancy, the number of insulin receptor sites per cell increases twofold (31,000 versus 16,300); (2) Class A diabetic patients have higher numbers of receptor sites than normal pregnant patients (80,800 versus 31,000; (3) untreated Class B diabetic patients have markedly reduced receptor sites (4,575) and bind less insulin at physiologic concentrations (p less than 0.01); (4) insulin therapy of previously untreated Class B diabetic patients restored the number of receptor sites to normal pregnant levels (29,700); and (5) Classes C and D diabetic patients had similar numbers of receptor sites (30,140) and showed a greater receptor affinity for insulin than pregnant control subjects (p less than 0.01).

An isocaloric low-carbohydrate diet given to adolescent boys caused an increase in circulating levels of free fatty acids, glycerol and ketones and impairment of glucose tolerance. The fasting insulin levels as well as the response to glucose was either unchanged or reduced. The tenfold rise in ketones did not affect the insulin levels. Glucose and insulin values were closely related both on normal and low carbohydrate diets.

Body cell mass, body fat, and total number of fat cells were determined in young men and women. In addition, regional determinations of adipose tissue thickness, fat cell size, and fat cell number were also performed. The individuals studied were 11 male and 12 female medical students with a mean age of 22 yr. In order to avoid deviations from ideal body weights, the individuals were preselected by using anthropometric standards. The women had more body fat than the men, which was due to an increase in the total number of fat cells. Mean fat cell size did not differ significantly between sexes. The women had greater adipose tissue thickness than the men, which was primarily due to an increase in local fat cell number in all regions investigated (epigastric, hypogastric, femoral, and gluteal) except in the gluteal region, where the difference was mainly explained by larger fat cells in women. When expressed in per cent of maximum values, the intrasexual patterns of adipose tissue thickness and local fat cell number in different regions were similar in men and women, while the pattern concerning fat cell size was slightly different between the sexes. There were no differences between sexes in cholesterol, triglyceride, fasting blood sugar, or fasting insulin values. Middle-aged randomly selected men and women examined previously had a larger amount of body fat than the young men and women, respectively, examined in the present investigation. This difference in body fat with age was due to a larger mean fat cell size in the middle-aged populations, while there was no difference in total fat cell number.

Experience with three insulin immunoassays is reported. The main difficulties arise in the separation of free and antibody bound insulin. Separation by paper chromatography and filration on cellulose acetate membranes did not prove satisfactory. A double antibody precipitation system was successfully employed in the assay of normal fasting sera. The mean fasting insulin level found in 64 normal healthy subjects was 21.7 uU/ml.

Three types of experiment were carried out in normal subjects to determine the effect of therapeutic doses of oral Propranolol on 1. the blood sugar, plasma insulin and free fatty acids (FFA) during prolonged fasting and exercise, 2. intravenous glucose tolerance and the rise in insulin level after intravenous glucose, and 3. the intravenous glucose tolerance on exercise. Propranolol caused only slight lowering of the blood sugar in normals, even after 24 h fasting. This was most noticeable during exercise. There was no significant effect of Propranolol on fasting insulin levels, on glucose tolerance at rest or exercise, or on the response of plasma insulin levels to intravenous glucose. Lowering of plasma FFA levels was found in all subjects when taking Propranolol particularly during and after exercise. Possible mechanisms of hypoglycaemia in those cases reported in the literature are discussed. It is concluded that hypoglycaemia is not a major problem in Propranolol therapy.

Two groups of diabetics and 19 normal controls had their rate of acetylation of sulphadimidine measured. Among 47 patients with maturity onset diabetes the 29 fast acetylators were older at diagnosis and, at a given glucose concentration, had a higher pretreatment fasting insulin concentration than slow acetylators. They also had a larger first-phase insulin secretion in response to intravenous glucose both before and after one month's dietary treatment. The greatest difference between fast and slow acetylators was in the first-phase secretion of insulin after a month's treatment. The proportion of fast acetylators among the second group of diabetics, who had been admitted to improve their glucose concentrations or for treatment of tissue damage, was similar to that among the normal controls (50% and 47% respectively). The data seem to indicate that diabetics are fast acetylators unexpectedly often, but it is not clear whether the dimorphism according to acetylator status produces a differential risk of neuropathy or of any other type of diabetic tissue damage.

Twenty-seven normal volunteers whose ages ranged from 22 to 67 (mean, 37 years) were given intravenous glucose tolerance tests (IVGTT). Age was not correlated with the glucose disposal rate constant (KG), incremental insulin secretion (deltaI), or the "insulinogenic index (deltaI/DELATG). The volunteers were divided into three age groups: 1) mean age 25 years, 2) mean age 42 years, and 3) mean age 62 years. Groups 2 and 3 did not differ from Group 1 with respect to the mean level of fasting plasma glucose, KG, or deltaI/AG. Group 2 (but not Group 3) had a greater mean deltaI than Group 1, and Group 3 (but not Group 2) had a higher mean fasting insulin concentration than Group 1. No significant deterioration was detected in the intravenous glucose tolerance of healthy volunteers up to age 67. This may be attributable to the previously described feed-back system that calibrates the pancreatic beta-cell response according to the insulin sensitivity of the peripheral tissues.

Overnight basal insulin requirements to maintain eugycemia were determined in six insulin-requiring diabetic subjects using a feedback-controlled (closed loop) insulin infusion system. Mean hourly insulin infusion rates, required to maintain plasma glucose concentrations at approximately 100 mg/dl, were remarkably stable from 2400 h to 0600 h; however, a twofold to threefold increase in insulin requirements was observed in each subject between 0600 h and 0900 h. This increase in amount of basal insulin required was not associated with increases in plasma glucagon or growth hormone concentrations, but occurred simultaneously with normal diurnal increases in plasma cortisol. These findings suggest that normal diurnal increases in plasma cortisol, independent of the content of the morning meal, contribute to the increased amount of morning insulin required in diabetic subjects. Programs designed for optimal open loop insulin delivery may benefit from modifications designed to coincide with this increase in amount of basal insulin required in the early morning.

ObjectiveTo study the influence of Jiang Tang Fang Long formula on insulin production and function in an animal model of diabetic hearing loss.MethodsWistar rats (n=60) were randomly divided into 6 groups (10 in each) to receive no treatment (the normal control, Group A), or to receive intra-peritoneal 55 mg/kg streptozotocin with (Groups C, D and E) or without (Group B) subsequent Jiang Tang Fang Long formula treatment at various doses or Yu Long Wan treatment (Group F). After 60 days, fasting blood glucose (FBG), body weight (BW) and fasting insulin (FINS) were recorded and the HOMA-IR and HOMA-β calculated. Insulin expression in pancreatic tissues was measured by radioimmunoassay.ResultsCompared with animals that received streptozotocin without rescue treatment (Group B), animals that received higher doses of Jiang Tang Fang Long formula(Groups D and E) showed improved indices of diabetes manifestation (P< 0.05) and improved HOMA-β (P0.05).ConclusionOur results suggest that Jiang Tang Fang Long formula may improve pancreatic β-cells function which may explain its efficacy in treating diabetic hearing loss.

We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members.

A 24-year-old non-diabetic female was hospitalised because of recurrent attacks of hypoglycemia (up to 27 mg/dl blood glucose) lasting for 3 weeks. The findings of markedly elevated insulin levels (maximal fasting insulin up to 200 μU/ml and the clinical picture were suggestive of insulinoma, which was not localised by selective angiography. Nesidioblastosis was diagnosed on subtotal pancreatectomy, a finding extremely rare in this age group. The postoperative recurrence of hypoglycemic attacks raised a suspicion of self-inflicted hypoglycemia by abusing oral antidiabetic agents. A toxicological screen for sulfonylurea compounds in two preoperative and three postoperative blood samples revealed high serum chlorpropamide levels, i. e., 256, 230 μg/ml and 372,460,508 μg/m1 respectively, as compared to the levels obtained from 16 patients on maintenance therapy with 125–750 mg/day chlorpropamide, showing serum concentration of 135 ± 71 μg/ml.

SUMMARY The glucagon-stimulated insulin and C-peptide release in patients with active acromegaly, cured acromegalic patients and healthy controls were studied. There was an elevation of the fasting insulin levels in active acromegalics and the fasting C-peptide levels in both patient groups. After i.v. injection of glucagon the insulin and C-peptide levels increased. The highest levels were recorded in active acromegalics, but cured patients also had higher levels than the control group. The insulin/C-peptide ratio was increased in active acromegalics in comparison with that found for inactive acromegalics and normal controls. In addition, the plasma half-lives (T1/2) of endogenous insulin and C-peptide were measured. It was found that the T1/2 for insulin was increased in active acromegalics only. From this study we conclude that even when the treatment of acromegaly is effective insulin and C-peptide secretion do not normalize due, probably, to increased synthesis and release upon stimulation of the pancreatic β-cells. In active acromegaly the removal of insulin is probably also reduced.

Plasma insulin was measured fasting and after iv glucose in fifteen newly diagnosed non-grossly obese non-insulin dependent diabetics. Two-thirds had normal fasting insulin (< 13 mU/L) and all had sub-normal responses to iv glucose. There was no significant correlation between fasting or stimulated insulin concentrations and body weight. Six subjects with totally “flat” response to iv glucose were tested after a standard 4MJ meal and after 75 g oral glucose. They now showed normal profiles of later phase insulin release to the meal test or oral glucose and a significant increase in early phase insulin concentration, but this response was still blunted when compared with control subjects. We conclude that for non-grossly obese NIDDs (1) insulin deficiency is a common and important disorder and (2) there may be a loss of beta cell sensitivity to blood glucose with retention of sensitivity to gut mediated factors. (Aust NZ J Med 1983; 13: 621–624.)

The response of plasma immunoreactive insulin (IRI), free fatty acids (FFA), and blood glucose to intravenous (I.V.) glucagon is evaluated in ten healthy subjects and in 22 patients following acute myocardial infarction (MI). Heparinized venous blood samples were drawn from patients and subjects in the fasting state and 2, 5, 15, 30, 60, 90, and 120 min after 1 mg I.V. glucagon. Healthy subjects showed a significant increase in insulin (peak at 5 min) and blood glucose (peak 15 min), and a persistent fall in FFA (nadir 90 min). In patients in the first week after suffering an acute MI, there was a significant elevation in fasting blood glucose whereas fasting insulin was low and FFA, normal. After glucagon administration, there was a pronounced rise in insulin and a significant rise in glucose and FFA. Six weeks after the acute MI, the mean fasting blood glucose reading showed a fall whereas insulin rose to normal range. Glucagon elicited a rise in insulin, glucose, and FFA. These results suggest that after MI the insulin resistance is a stronger influence than failure of insulin secretion. The relevance of these results in relation to use of glucagon in large doses in cardiogenic shock of MI is discussed.

In contrast to previous reports, most patients (78%) with a successful renal transplant being followed up at the University of Kentucky Medical Center had a normal serum-lipid profile. The patients with hyperlipidaemia (22%) had normal fasting insulin levels; they received similar immunosuppressive therapy but were significantly older and more obese than those with normal lipids. This lower prevalence of hyperlipidaemia and the absence of fasting hyperinsulinaemia are tentatively attributed to the use of alternate-day corticosteroid therapy in stable renal-transplant patients. If confirmed, the relative infrequency of hyperlipidaemia in patients on alternate-day corticosteroid therapy would be an additional advantage of that therapy over a daily regimen.

We studied the effect of pubertal development on insulin secretion. Intravenous glucose tolerance tests were performed on 47 islet-cell antibody negative siblings of diabetic children and on 16 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I, stage 1 (n = 16); II, stages 2 and 3 (n = 15); III, stages 4 and 5 (n = 16); IV, adults (n = 16). Fasting insulin increased with advancing puberty (p = 0.59, P less than 0.001). The stimulated insulin response also rose with increasing pubertal development: for the 0-10 min insulin area, p = 0.46, P less than 0.001 and for the 10-60 min area, p = 0.68, P less than 0.001. There was a low positive correlation between insulin and age to 16 years but multiple regression analysis showed that this could be accounted for by puberty alone. Indeed prepubertal children and adults did not differ. There was no correlation between glucose (fasting and 0-60 min area) and puberty or age. These findings suggest that insulin resistance increases during puberty, and this may contribute to the frequency of presentation or worsening control of insulin dependent diabetes at this time.

Cyclosporin or placebo was administered in a randomized, double-blind fashion to 13 patients with multiple sclerosis for 1 yr to determine whether cyclosporin adversely affects glucose homeostasis or β-cell function. No significant differences were observed in fasting glucose, fasting insulin, intravenous glucose tolerance, or glucose-induced insulin secretion before treatment or at 3 wk, 6 mo, or 1 yr during treatment. Longer therapeutic trials with larger patient groups will be necessary to decide whether cyclosporin can be safely given for many years without risk of developing diabetes mellitus.

When adult male rats were fasted for 24 or 72 h there was no change in the pancreatic content of insulin or glucagon, but the somatostatin content increased at 72 h. This contrasts with earlier reports of reduced pancreatic somatostatin after fasting. After a 48-hour fast there was an increase in the concentration of duodenal somatostatin, and a tendency toward reduced concentrations in stomach, jejunum, and ileum. When duodenal mucosa and muscle extracts were chromatographed the relative amounts of putative somatostatin-28 and somatostatin-14 were unchanged. Insulin secretion from the perfused pancreata of 72-hour-fasted rats was markedly reduced, but glucagon and somatostatin secretion was indistinguishable from that of fed controls. These results indicate that in spite of the marked alterations of nutrient metabolism and insulin secretion which occur during fasting, the pancreatic content of insulin, glucagon and somatostatin and the gut concentration of somatostatin are well maintained.

A population sample of 142 men and 148 women aged 40-69 was drawn in Chittenden County, Vermont, and studied for interrelationships among several parameters of obesity, fasting serum cholesterol, triglycerides, glucose and insulin concentrations, and 2-hour post-Glucola glucose and insulin concentrations. No significant sex differences were observed with regard to mean fasting concentrations of glucose, insulin, cholesterol, or triglyceride. Post-Glucola insulin concentrations were higher in women, particularly in the older age groups. Positive correlations were observed between mean log fasting insulin concentration and all parameters of obesity except log triceps skinfold thickness in men. In addition, a positive correlation was present between mean log fasting insulin and fasting triglycerides. There was a positive correlation between fasting triglycerides and ponderal index and estimated percent body fat. Fasting triglycerides correlated with percent ideal weight in women but not in men and with log subscapular skinfold thickness in men but not in women. There was no correlation with either log triceps skinfold thickness or with combined triceps and subscapular skinfold thickness in either men or women. No positive correlations were observed with regard to serum cholesterol. The measurement of glucose and insulin concentrations 2 hours post-Glucola or the calculation of insulin-to-glucose ratios did not provide additional correlations to those observed from the fasting data alone and in some instances correlations which existed in the fasting state were largely obscured following carbohydrate administration.

Intravenous glucose tolerance tests were performed in eight adult cats before and after a 4-week treatment with thyroxine. The untreated cats had a mean fasting blood glucose concentration of 7·7 ± 0·3 mmol/l and a mean fasting insulin concentration of 88 ± 31 pmol/l which were not significantly different from mean fasting glucose and insulin concentrations after 4 weeks of thyroxine administration (6·9 ± 0·2 mmol/l and 101 ± 28 pmol/l respectively). At 120 min after glucose injection, the glucose concentration in untreated cats returned to baseline concentrations as did the insulin concentration. However, in the hyperthyroid cats both glucose and insulin concentrations were significantly (P < 0·001) higher (13·6 ± 0·8 mmol/l and 245 ± 17 pmol/l respectively) in comparison with the baseline and untreated cats. The t½ for glucose disappearance was significantly higher in the cats rendered hyperthyroid, and the glucose disposal rate constant (K) was significantly lower in this group. It is concluded that hyperthyroidism in cats leads to impairment of glucose tolerance possibly due to peripheral insulin resistance. Journal of Endocrinology (1989) 121, 249–251

1. Sixteen adult male volunteers were selected on the basis of body size and customary food intake: half could be described as‘lean’and habitually consuming large amounts of food (group mean ± SEM: 15·03± 1·13 MJ/d), the high-energy-intake group (HEI group), and half though‘lean’admitted to a weight problem and regularly consumed a lower than average food intake (group mean ± SEM: 6·90 ± 0·39 MJ/d), the low-energy-intake group (LEI group).2. Energy expenditure was measured by open-circuit indirect calorimetry. Resting metabolic rate (RMR) was recorded. A meal (Complan, either 2·1 MJ or 4·2 MJ), ephedrine hydrochloride (0·25 mg and 0·50 mg/kg body-weight) or a water control were then administered and metabolic rate (MR) was measured for 4 h. Blood was collected before and 1 h after the meal or drug, and the serum analysed for various hormones and blood metabolites.3. The size of the thermic response to feeding but not the time-course was related to meal size in both groups. MR increased by 21·6 and 28·6% in the HEI group and by 8·2 and 20·0% in the LEI group in response to the 2·1 and 4·2 MJ Complan meals respectively. Fasting insulin levels were similar in both groups but showed a significantly higher level in the LEI than HEI group after the Complan meals.4. The mean RMR increased by 5·2 and 10·3% in the LEI in response to ephedrine and by 15·7 and 11·2% in the HEI groups after 0·25 mg and 0·50 mg ephedrine/kg respectively. The rise in serum-free fatty acids in response to ephedrine was significantly higher in the HEI group than in the LEI group.5. These results suggest (1) the meal size required to promote a maximum thermic effect is smaller in energetically inefficient individuals (2) the sensitivity to a sympathomimetic drug is also increased in energetically-inefficient individuals.6. We conclude that in energetically-efficient individuals both the thermic response to a meal and the sympathetic-mediated thermogenesis are lower than in energetically-inefficient ones.

SUMMARY:Our prospective survey of 50 ataxic patients confirms the previous finding of frequent clinical or chemical diabetes in Friedreich's ataxia. Eighteen percent of our typical cases have clinical diabetes and 40% at least an abnormal glucose tolerance curve. However, this finding does not appear to be specific to that form of ataxia. Furthermore, we have shown that most patients with ataxia have normal or low fasting insulin levels, but a hyperinsulinic response to a glucose load.

SUMMARY Overnight basal insulin requirements to maintain euglycemia were determined in five insulin-dependent diabetic subjects using a closed-loop insulin infusion system. A significant increase in hourly insulin requirements occurred between 0600 h and 0900 h as compared with 0100 h–0600 h. Although the increased insulin requirement was coincident with only the physiologic diurnal increase in plasma cortisol, the oral administration of the 11-beta hydroxylase inhibitor, metyrapone, decreased only the total overnight (0100 h–0900 h) basal insulin requirement, but not the early morning (0600 h-0900 h) rise in insulin required to maintain euglycemia. It would appear that although cortisol is an important counterregulatory factor, its diurnal elevation cannot account for the increase in early morning basal insulin requirements to maintain euglycemia in insulin-dependent diabetics.

To investigate the hypothesis that insulin resistance is concerned in the pathogenesis of essential hypertension fasting glucose/insulin and fasting insulin/C-peptide ratios were measured in non-obese normotensive and hypertensive diabetic and non-diabetic subjects. Patients with essential hypertension had normal fasting serum insulin values and normal fasting glucose/ insulin ratios; by contrast, the hypertensive non-insulin-dependent diabetic subjects had higher fasting serum insulin and lower glucose/insulin ratios than either normotensive diabetic or non-diabetic patients. Both hypertensive and normotensive diabetic subjects had higher fasting C-peptide values than those without diabetes. Hypertensive diabetic patients had the highest insulin/C-peptide ratios, indicating low hepatic insulin extraction rates. These findings suggest that hyperinsulinaemia is not causally related to essential hypertension but that it may contribute to the hypertension of non-insulin-dependent diabetes in association with low hepatic insulin clearance.

1. The seasonal variation of fasting blood glucose, peroral glucose tolerance, fasting plasma insulin and triglycerides and the sum of insulin values during glucose tolerance test was studied in 100 patients who had suffered a myocardial infarction. These patients comprised a population of all men who had suffered a myocardial infarction below the age of 55 years and had survived. 2. The material was divided into four numerically equal groups covering two dark, cold periods and two warm, light periods of the year. 3. Lower fasting blood glucose and insulin values during glucose tolerance test as well as a trend to higher glucose tolerance were found during the warm, light part of the year in comparison with winter. Triglycerides and fasting insulin values did not vary significantly in these infarction patients. The variation could not be explained by a difference in age or body weight between the groups. 4. It is suggested that glucose tolerance and insulin secretion are subjected to seasonal variation in man as has previously been shown in laboratory animals.

We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome.

Plasma endothelin-1 (ET-1) levels were studied in 15 obese hypertensive (mean age 48.5 ± 3.9 years) and 15 obese normotensive men (mean age 49.5 ± 3.6 years) before and after weight loss due to an 800 kcal/day diet lasting 12 weeks. Circulating peptide concentrations were also assessed in nonobese hypertensive (n = 11) and normotensive men (n = 12). Baseline plasma ET-1 levels were similar in obese hypertensive (0.87 ± 0.22 pg/ml) and obese normotensive men (0.91 ± 0.30 pg/ml). In seven obese hypertensive men, caloric restriction normalized blood pressure levels (systolic: from 166.6 ± 8.1 to 145.0 ± 6.3 mmHg, P < 0.0001; diastolic: from 106.6 ± 5.1 to 89.1 ± 2.0 mmHg, P < 0.0001) and decreased body mass index (BMI) (from 33.4 ± 1.6 to 29.6 ± 2.1 kg/m2, P < 0.002) and plasma ET-1 levels (from 0.93 ± 0.21 to 0.64 ± 0.26 pg/ml, P < 0.05). In the remaining obese hypertensive men (n = 8), blood pressure levels were not normalized by caloric restriction despite a significant decrease of BMI and plasma ET-1 levels (from 0.83 ± 0.23 to 0.60 ± 0.16 pg/ml, P < 0.04). Weight loss also significantly decreased BMI and ET-1 (from 0.91 ± 0.30 to 0.65 ± 0.19 pg/ml, P < 0.01) in obese normotensive men. Baseline ET-1 and fasting insulin levels were significantly correlated in obese hypertensive (r = 0.518, P < 0.05) and obese normotensive men (r = 0.535, P < 0.04). Changes in fasting insulin levels correlated with corresponding changes in plasma ET-1 levels after weight loss in both obese hypertensive (r = 0.558, P < 0.04) and obese normotensive men (r = 0.596, P < 0.02). Moreover, plasma peptide levels were significantly higher (P < 0.02) in obese hypertensive and obese normotensive men than in nonobese normotensive men (0.58 ± 0.28 pg/ml). In conclusion, this study shows that plasma ET-1 concentrations are increased in human obesity. The increase could depend on fasting insulin concentrations, abnormal peptide clearance, or both. Hypertension does not influence the behavior of plasma ET-1 levels in obese men.

AIM: To examine treatment and glucose control in type 2 diabetes patients with and without hypertension, and to explore differences in markers for insulin resistance and beta cell function. METHODS: A community-based, cross-sectional observational study was carried out at the hypertension and diabetes outpatient clinic in primary health care, Skara, Sweden. The subjects were all the 400 patients with type 2 diabetes (202 men, 198 women) who underwent annual follow-up from May 1992 through September 1993; 204 of these also had hypertension. RESULTS: The patients with both type 2 diabetes and hypertension had a higher b.m.i. (mean; 28.9 kg m(-2) (s.d.; 4.4) vs. 27.4 kg m(-2)(4.6)), higher triglycerides (2.0 mmol l(-1)(1.1) vs. 1.7 mmol l(-1)(1.1)), higher LDL/HDL cholesterol ratio (4.3(1.4) vs. 4.1(1.2)) and higher fasting insulin (8.5 mU l(-1)(1.1) vs. 6.6 mU l(-1)(1.1)). Conversely, glucose levels were lower; HbA1c (6.4%(1.4) vs. 6.8%(1.6)) and fasting blood glucose (8.1 mmol l(-1)(2.3) vs. 8.9 mmol l(-1)(2.7)) than in patients with type 2 diabetes alone. By the homeostasis model assessment (HOMA), patients with type 2 diabetes alone had more impaired beta cell function. They also had a higher frequency of insulin treatment (20% vs. 12%) and were less often treated non-pharmacologically (33% vs. 50%). CONCLUSIONS: Patients with type 2 diabetes and hypertension constitute a high risk category with a more atherogenic risk factor profile related to the insulin resistance syndrome. Patients with type 2 diabetes without hypertension seem to constitute a subgroup of type 2 diabetes with predominately impaired beta cell function. (Less)

SummaryThe characteristic fasting insulin hypersensitivity of chronically underfed rats is gradually abolished by subsequent prolonged ad libitumfeeding and slowly returns during repeated undernutrition.

Up to 60% of children with CF develop glucose intolerance (GI). Many CF patients maintain a normal glucose tolerance (NGT) with a low insuline response during the oral glucose tolerance test (OGTT). We studied 48 CF pts. (aged 2-29 years) without clinical manifestations of diabetes mellitus. Assessment included OGTT, hemoglobin A1C, anti-islet antibodies, pulmonary status and liver involvement. The OGTT was considered abnormal when the 2h serum glucose level was higher than 140 mg/dl. There was no significant difference between the 15 pts. with and the 33 pts.without GI in terms of mean age, wheight index, degree of lung and liver involvement. Fasting insulin (ins.), peak ins. response, max. ins./max. glucose ratio, and area under the ins.response curve were not different in GI and NGT group. Peak glucose and peak ins. response were significantly delayed in GI vs NGT pts. (99 min and 117 min vs 55 min and 86 min) and Hb A1C was higher in the former (8,2% vs 7,5%). No circulating anti-islet antibodies were detected in either group. In conclusion, CF patients with GI differ from those with NGT by a delayed glucose and insuline response to OGTT. Serial Hb A1C levels can be used as a simple and reliable method for the prediction of GI in CF.

Insulin and IGF-1 are structurally very similar and there are many functional links between the two hormone systems. However normal relationships between insulin and IGF-1 have never been defined. We performed intravenous glucose tolerance tests (0.5g/g/ maximum 25g) on 59 islet-cell antibody negative siblings of diabetic children and on 43 adults (aged 5.6-50 years). Puberty was staged (Tanner) and subjects divided into 4 groups: I - stage 1 (n=22), II - stages 2 & 3 (n=17). III - stages 4 & 5 (n=20), IV - adults >17 years (n=43). The pattern of fasting IGF-1 concentrations, fasting insulin and incremental 0-60 minute insulin areas (following IV glucose) in Groups I to IV was markedly similar levels rose significantly throughout puberty (p

Growth retardation and malnutrition are common manifestations of cystic fibrosis (CF). Since chronic malnutrition is generally characterized by reduced somatomedin (SM) activity despite normal levels of growth hormone (GH), defects in the hypothalamic-pituitary-SM axis have been proposed as etiologic in the growth retardation of CF. Accordingly, we have measured GH, insulin, and SM levels in 15 adolescents with CF and compared them with 9 age matched controls of normal height and weight. All CF subjects were below the 30th percentile in height with 9/15 below the 5th percentile in height and 12/15 below the 5th percentile in weight. Weight to height percentile ratio was 50% or below in 11/15. Fasting 8 AM GH values were similar in both groups: 5.33±1.16 ng/ml (mean±SEM) in CF and 5.76±1.33 ng/ml in controls. Fasting insulin levels were moderately reduced in CF patients: 8.07±0.80μU/ml versus 12.94±1.89μU/ml (p

The oral glucose tolerance test in obese children is characterized by an increased insulin release. We could confirm this pattern in 16 obese (> 2 SD) children (10 girls and 6 boys). The basal fasting insulin level was also increased in obese children compared to 9 controls (23.6 vs 8.6 μU/ml). Previously obese children (n=8) had a mean fasting insulin level of 12.6 μU/ml and a moderately increased insulin response to glucose. Nine children with obesity had a glucose load before and after at least one week of phenantoin treatment which is reported to decrease the insulin response to oral glucose. The fasting insulin level was decreased by phenantoin (28.8 vs 16.1 μU/ml) and the high insulin response to oral glucose was reduced. Phenantoin also increased the plasma levels of free fatty acids and keton bodies. However, there was a marked difference in the responses to phenantoin between individuals with no measurable effect in some children. Phenantoin might be used in the treatment of obesity.

Results The study population included 49 (47.6%) males and 54 (52.4%) females with a mean age of 7.6 ± 1.6 years. The advanced bone age group defined as BA-CA>1 year (n=53) had significantly higher HOMA-IR, fasting insulin levels and lower quantitative insulin sensitivity check index (QUICKI). Also, BA-CA was significantly correlated with fasting insulin (r=0.315, P