Further support for heterogeneity of insulin response and insulin sensitivity in non-obese subjects with glucose intolerance

The relationship of insulin secretion and insulin sensitivity was studied in 67 age- and body weight-matched non-obese subjects, classified as having a normal glucose tolerance or glucose intolerance (50 g oral glucose load). Insulin response was studied by means of a 2 h glucose infusion. For the determination of insulin sensitivity a 1 h priming dose-constant insulin infusion technique was used. The per cent decrease of plasma glucose level at comparable steady-state insulin levels served as a measure of body sensitivity to exogenous insulin. In patients with glucose intolerance the early (delta IRI area 0-5 min) and late (delta IRI area 30-120 min) insulin responses to iv glucose were significantly reduced in comparison to controls. Controls and subjects with glucose intolerance showed considerable heterogeneity of insulin responses. Patients with glucose intolerance and relative insulin deficiency were not less responsive to insulin than subjects with normal glucose tolerance. There was, however, a wide variation of insulin sensitivity within the two groups. There was a weak significant inverse correlation between insulin response to glucose and insulin sensitivity for the two groups combined and for controls and subjects with glucose intolerance separately. The results demonstrate that the majority of non-obese patients with glucose intolerance and relative insulin deficiency does not exhibit a reduced responsiveness to insulin and therefore hypoinsulinaemia but not insulin resistance is the primary defect for an abnormal glucose tolerance in these group of subjects.     

Insulin secretion and sensitivity in non-obese and obese Japanese patients with coronary artery disease

In a cross-sectional study of 240 patients with angiographically documented coronary artery disease (CAD), we investigated whether obese and non-obese subjects differed as to the influence of insulin deficiency and insulin resistance on glucose intolerance and cardiovascular risk. Patients were classified according to a 75-g oral glucose tolerance test as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes mellitus (DM). We defined obesity as a body mass index (BMI) exceeding 25 kg/m(2). Early phase insulin secretion (insulinogenic index) declined with worsening glucose intolerance in non-obese (tau = -.216, P <.001; Kendall's correlation coefficient) and obese subjects (tau = -.392, P <.001). Total insulin secretion was higher in obese subjects with NGT or IGT than in controls and decreased in association with worsening glucose intolerance in obese subjects (tau = -.239, P <.001). Insulin sensitivity was calculated by 3 proposed indices. The first of these decreased in association with worsening in glucose tolerance in non-obese subjects (tau = -.137, P <.01). The second showed such a pattern in both groups (non-obese, tau = -.407, P <.001; obese, tau = -.311, P <.001), as did the third (non-obese, tau = -.512, P <.001; obese, tau = -.488, P < 0.001). Because even prediabetic Japanese subjects with CAD showed a latent insulin secretion defect in response to a glucose load, as well as impaired insulin sensitivity, compensatory hyperinsulinemia is not a sensitive indicator of coronary risk.     

I.V. Glucose tolerance test: Correlation between FFA,glucose and IRI in normal,obese and diabetic subjects

Summary Insulin response and FFA behavior have been evaluated during an IVGTT in 63 subjects of whom 18 were normal, 31 were obese (with varying degrees of carbohydrate tolerance) and 14 were mild non insulin-dependent diabetics. The extreme reduction of insulin secretion in the early phase (Δ 0–15 min) and the less severe impairment of the late phase (Δ 15–60 min) have been confirmed; obese subjects showed on the average an active insulin response to venous loading; this was more marked and more consistent in the late phase. Compared to controls, FFA concentration both in basal conditions and during IVGTT was progressively higher in obese and diabetic patients. When analyzing the interplay between IRI, K_G and FFA in the course of IVGTT, it was observed that: (1) a close correlation exists between K_G and early insulin response (r=0.72); (2) a correlation between Δ IRI 0–15 min and percentage decrease of FFA at 45 min is found only in normal subjects; (3) a negative highly significant correlation is found between K_g and mean FFA plasma level 0–60 min. This last correlation is evidence of the important role played by FFA in carbohydrate tolerance. The conflicting results reported by others have been discussed.     

Insulin secretion and body composition in obesity

Plasma immunoreactive insulin levels were measured before and for 6 hr following a 100 g oral glucose load in ten normal volunteers and 17 grossly obese subjects. Eleven of the obese had an abnormal glucose tolerance, five of whom were overt diabetics. Twelve of the obese were restudied after significant weight reduction (thinned obese). Eight thinned obese subjects were also restudied 6–12 mo after completion of the weight reduction protocol. Body composition was measured in each subject prior to testing. Obesity was associated with hyperinsulinemia in the fasting state and in response to oral glucose. The obese diabetics demonstrated a delay and an impairment of insulin secretion in response to glucose. After weight reduction, elevated fasting plasma insulin levels fell in all. Insulin response to oral glucose was not different in the thinned obese with normal glucose tolerance from that observed in the normal volunteers. There was significant correlation between both fasting plasma insulin and total measurable insulin following the glucose load, and total body fat in the obese and thinned obese nondiabetics, but not in the obese overt diabetics. There was, however, significant correlation between fasting plasma insulin levels and total body fat in the diabetics who had a normal fasting blood sugar. These data indicate that the hyperinsulinemia of obesity is clearly related to the increase in total body fat. Carbohydrate intolerance occurs in those obese individuals with a limited pancreatic insulin secretory reserve, which fails to compensate for the increase in total body fat.     

肥胖症患者和新诊断的2型糖尿病患者真胰岛素和前胰岛素的改变

目的 了解真胰岛素（ｔｒｕｅ ｉｎｓｕｌｉｎ，ＴＩ）和前胰岛素（ｐｒｏｉｎｓｕｌｉｎ，ＰＩ）在肥胖症和２型糖尿病患者中的改变，了解免疫活性胰岛素（ｉｍｍｕｎｏｒｅａｃｔｉｖｅ ｉｎｓｕｌｉｎ，ＩＲＩ）能否准确反映ＴＩ。方法 ３３例糖耐量正常（ＮＧＴ），２４例糖耐量减低（ＩＧＴ）和５３例新诊断的２型糖尿病患者行口服葡萄糖耐量实验，并根据体重指数（ＢＭＩ）分为肥胖和非肥胖组；采用ＥＬＩＳＡ方法（其单克     

Insulin response in obese and nonobese offspring of conjugal Indian diabetic parents with increasing glucose intolerance

Pancreatic beta cell function in response to glucose was assessed in three different groups of offspring of conjugal diabetic parents (OCDP): those with normal glucose tolerance, those with impaired glucose tolerance (IGT), and those with diabetes. Serum immunoreactive insulin (IRI), C-peptide (CP), insulin/glucose (I/G) ratio, and IRI/CP ratios were estimated at fasting and 90 min after glucose load. Insulin secretion, measured as CP, was found to be low even in normal nonobese OCDP, but the change was not reflected in IRI value as the IRI/CP ratio was found to be elevated. The values decreased with increasing glucose intolerance. In obese OCDP, all the parameters were abnormal even among those with normal glucose tolerance, and further deterioration occurred with increasing glucose intolerance. The study shows that insulin secretory defects are detectable even in normal OCDP, and these changes deteriorate with increasing glucose intolerance. Differences are noted in the peripheral concentrations of IRI and CP between obese and nonobese OCDP before development of diabetes. After development of diabetes mellitus, these differences disappear, and the CP and IRI values in both groups are similar and low.     

Gastric inhibitory polypeptide (GIP) and insulin in obesity: Increased response to stimulation and defective feedback control of serum levels

Summary To investigate the possibility that an abnormality of the entero-insular axis is responsible for the hyperinsulinaemia of obesity, serum immunoreactive gastric inhibitory polypeptide (IR-GIP) and insulin (IRI) were measured after the ingestion of a liquid mixed test meal, glucose or fat, in normal weight and obese subjects. The latter were divided into a group with normal oral glucose tolerance (nOGT) and a group with pathological glucose tolerance (pOGT). Fasting levels of IR-GIP were significantly elevated in the obese group with pOGT. After the mixed meal the overweight subjects showed a significantly greater response of IR-GIP than the controls, with highest levels in the pOGT group. Simultaneously, the IRI response was significantly greater in the obese subjects than in the controls. The increases of IR-GIP and IRI after an oral load of 100 g glucose were normal in the obese subjects, but showed a significantly greater integrated response in the obese patients with pOGT. The ingestion of 100 g fat induced no IRI release but a significantly greater release of IR-GIP in the obese subjects, irrespective of their glucose tolerance. It is concluded that fat is a stronger releaser of IR-GIP than glucose. The effect of a combined load of glucose (30 g) and fat (100 g) was also compared in obese and normal weight subjects with the effect of either alone. Fat but not glucose released significantly more IR-GIP in obese subjects. In normal weight controls, but not in obese subjects, the IR-GIP release after fat plus glucose became significantly smaller than after fat alone. Since only the combined ingestion of glucose and fat and not fat alone releases insulin it is suggested that endogenous insulin inhibits GIP release and that this feedback control between insulin and GIP is defective in patients with obesity.     

The effect of ambient temperature on glucose tolerance.

Standard (75 g) oral glucose tolerance tests were performed at two different ambient temperatures (23 and 33 degrees C) in random order in 16 (eight obese) diabetic and 16 (eight obese) non-diabetic Nigerian subjects. Consistently higher plasma glucose values were found 120 min post-glucose ingestion at 33 degrees C, with mean differences of 0.5 (SE 0.3) and 4.5 (SE 1.5) mmol l-1 in the non-diabetic and diabetic subjects, respectively. This caused reclassification of two of the non-diabetic subjects as Impaired Glucose Tolerance at 33 degrees C, applying the WHO criteria. The difference was consistently greater (p less than 0.01) in the non-obese subjects (non-diabetic 0.8 (0.4), diabetic 6.9 (2.8) mmol l-1) than in the obese (non-diabetic 0.2 (0.4), diabetic 2.1 (0.9) mmol l-1). In the diabetic subjects, a negative correlation (r = -0.50, p less than 0.01) was established between the difference and the body mass index. This variability in responses to ambient temperature between the obese and non-obese subjects could be due to a variable influence of heat on arm blood flow consequent on differences in amounts of subcutaneous fat. The ambient temperature for the conduct of the oral glucose tolerance test is important.     

Lactate generation following glucose ingestion: relation to obesity, carbohydrate tolerance and insulin sensitivity

To examine early metabolic abnormalities in obesity prior to the development of carbohydrate intolerance, we studied 14 lean and 37 obese subjects with normal glucose tolerance. All subjects underwent a standard 75 g oral glucose tolerance test (OGTT) with the addition of lactate measurement. As expected, there was a positive relationship between basal insulin and body mass index (BMI kg/m2;r=0.64, P less than 0.0001). In addition, even though the subjects had normal glucose tolerance, both basal glucose and sum of glucose during OGTT showed significant positive associations with obesity. Basal lactate correlated significantly and positively with obesity (r = 0.29, P = 0.04). When incremental areas during OGTT were examined, glucose area during OGTT was positively associated with BMI and insulin area was positively associated with both BMI and sum of glucose. Conversely, the incremental area of lactate decreased as BMI increased (r = -0.41, P = 0.003), despite the increasing glucose area. The results indicate that even prior to frank carbohydrate intolerance, progressive changes in basal levels of glucose, insulin, and lactate, as well as sum of glucose, accompany the expansion of adipose mass in obesity. Two different aspects of lactate metabolism have been examined in obesity. First, the association of increased basal lactate levels with increased obesity may reflect increased lactate production from enlarged adipocytes and an increased fat mass. Secondly, the inverse association between acute lactate generation following glucose ingestion and obesity, despite the increased sum of glucose in obese subjects, may reflect a decreased ability of adipose and/or extra-adipose tissues to convert glucose to lactate due to insulin resistance.     

Serum lipids, serum insulin, plasma fibrinogen and aerobic capacity in obese and non-obese Singaporean boys.

OBJECTIVES: To compare blood lipids, lipoproteins, apoproteins, fibrinogen, insulin and aerobic capacity in obese and non-obese Chinese Singaporean boys. To examine relationships between blood metabolites, body composition and aerobic capacity in these groups. DESIGN: Cross-sectional. SUBJECTS: Forty Chinese Singaporean boys aged 13-15 y. Classified as obese (n=20) or non-obese (n=20) based on adiposity (fat mass/fat free mass): >0.60=obese, <0.40=non-obese. MEASUREMENTS: Body composition (dual energy X-ray absorptiometry), waist circumference, peak oxygen consumption (VO(2) peak), serum concentrations of total cholesterol, triacylglycerol, high density lipoprotein cholesterol (HDL-C), total cholesterol/HDL-C, apoproteins AI and B, lipoprotein(a), insulin and glucose. Plasma concentration of fibrinogen. RESULTS: Obese boys had significantly (P<0.01) higher (mean+/-s.d.) concentrations of serum triacylglycerol (1.51+/-0.65 vs 1.04+/-0.34 mmol/l), serum insulin (24.1+/-11.5 vs 12.3+/-4.45 mU/l) and plasma fibrinogen (4.01+/-0.54 vs 3.35+/-0.76 g/l) than non-obese boys. Within the non-obese group plasma fibrinogen concentration was significantly related to percentage body fat (r=0.546, P<0.05). VO(2) peak relative to body mass (ml/kg/min or ml/kg(-0.67)/min) was significantly (P<0.001) lower in obese compared to non-obese boys but absolute VO(2) peak (l/min), adjusted for fat-free mass via analysis of covariance, was higher in obese than non-obese boys (P<0.01). Partial correlations revealed that none of the blood metabolites were significantly related to VO(2) peak independent of body fatness. CONCLUSIONS: Obesity was related to elevated concentrations of serum triacylglycerol, serum insulin and plasma fibrinogen in Chinese Singaporean boys. These elevated concentrations did not appear to be associated with a lower aerobic capacity (independent of body fatness) in the obese.     

Immunoreative insulin in obesity of adult women

The levels of immunoreactive insulin (IRI) in 58 obese women and 14 controls were studied. The investigation revealed: (1) higher IRI levels in obese patients compared to controls, with a tendency to normalization after weight reduction (2) a correlation between IRI values and the degree of obesity, the amount of fat and lean body mass. The closest relation was found between stimulated IRI values and the Broca index (3) the ratio glucose/insulin was lower in the obese women before and after a glucose load. After a decrease of body weight by 11 per cent this ratio did not change significantly (4) a negative correlation between the glucose/insulin ratio and body weight, overweight, body fat and lean body mass.     

Plasma islet amyloid polypeptide levels in obesity, impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

We examined the response of plasma islet amyloid polypeptide (IAPP) to an oral glucose load in non-obese and obese subjects with normal glucose tolerance or impaired glucose tolerance (IGT), and in non-obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma IAPP response to intravenous glucagon injection in NIDDM patients was also studied. Plasma IAPP concentration was determined by a sensitive and specific radioimmunoassay. Basal levels of plasma IAPP in non-obese subjects with normal glucose tolerance, IGT and NIDDM were not significantly different from each other. Non-obese subjects with IGT showed delayed and higher plasma IAPP response to oral glucose load compared to normal non-obese subjects. In NIDDM patients, IAPP response to glucose was delayed and lower when compared to normal non-obese subjects. Basal levels of plasma IAPP in normal obese subjects and obese subjects with IGT were significantly higher than those in normal non-obese subjects. Plasma IAPP response to glucose load in these obese subjects was higher than that in normal non-obese subjects. Plasma IAPP response was decreased in diabetic patients treated with diet, oral hypoglycemic agents and insulin in that order. We conclude that the secretion of IAPP is reduced with progression of NIDDM, although it appears to be rather augmented in IGT compared to normal non-obese subjects.     

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome.

OBJECTIVES: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) >28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waist-to-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 microg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P < 0.05) in obese subjects than in controls, whereas no significant difference in cortisolAUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coefficients between total and incremental ACTH(AUC 0-30 min) and CortisolAUC 0-30 min and all other variables were analyzed. A significant correlation coefficient was present between them and all anthropometric parameters, fasting insulin and insulinAUC, but not with androgens and gonadotrophins. In addition, a significant correlation was present between total and incremental ACTH(AUC 0-30 min) and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coefficients became non-significant, except the one between incremental ACTH(AUC 0-30 min) and insulinAUC (P < 0.05). CONCLUSION: These findings indicate that obese men may also have an altered pituitary response to combined CRH/AVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRH/AVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.     

Glucose variability in subjects with normal glucose tolerance: Relations with body composition,insulin secretion and sensitivity

Background and aimsTo estimate the determinants of glucose variability (GV) in young and middle-aged non-obese subjects with normal glucose tolerance (NGT) we assessed relations between GV parameters, body composition, insulin secretion and sensitivity indices.MethodsThirty individuals with normal body mass index (BMI) and twenty overweight subjects were included. 24-hour mean glucose, time in range, time above range (TAR), time below range (TBR), standard deviation (SD), coefficient of variation (CV), mean amplitude of glucose excursions (MAGE), continuous overlapping net glycemic action (CONGA), J-index, lability index (LI), mean absolute glucose (MAG), M-value, high blood glucose index (HBGI), low blood glucose index (LBGI) were derived from continuous glucose monitoring. Body composition was assessed by DEXA. Insulin secretion and sensitivity was estimated by HOMA-IR and HOMA-B scores.ResultsOverweight subjects demonstrated higher mean glucose, CONGA, J-index and lower TBR, M-value and LBGI values. Mean glucose correlated positively with total, trunk, gynoid and android fat mass, while M-value and LBGI demonstrated negative correlations with these parameters. In multiple stepwise regression analysis, android fat mass was a predictor of mean glucose, CONGA, J-index, SD and MAGE, gynoid fat mass predicted J-index only, and total fat mass was associated inversely with MAG. Fasting insulin was a predictor of TAR, SD, CV, MAGE, MAG, LI and HBGI. HOMA-B was associated with CONGA, M-value and LBGI.ConclusionIn non-obese subjects with NGT mean glucose and GV parameters are related to fat mass and fat distribution. These relations can be mediated through insulin secretion and sensitivity.     

Excess body fat distribution and glucose homeostasis in obese Arab women

The relationship of body fat distribution to glucose intolerance and non-insulin-dependent diabetes mellitus in Arab women was studied in 102 obese non-diabetic and 40 obese women with diabetes. The obese women underwent a glucose tolerance test. Linear regression analysis revealed a significant correlation between the waist/hip ratio and the plasma glucose concentration at 120 min. When divided into two groups according to the median of their waist/hip ratio (0.815), obese women without history of diabetes but with high waist/hip ratio (0.86 +/- 0.07, mean +/- SD) had significantly higher prevalence of glucose intolerance and of diabetes mellitus than those with the low ratio (0.78 +/- 0.03, chi 2 = 9.32, p less than 0.001). The highest ratio (0.89 +/- 0.06) was observed in the obese women with known diabetes mellitus.     

Glucose storage and oxidation in different degrees of human obesity measured by continuous indirect calorimetry

Summary Glucose disposal of a 100 g glucose load has been determined in 26 obese compared with 10 non-obese subjects by means of a new application of continuous indirect calorimetry. The obese subjects were divided into 4 groups, according to their degree of glucose intolerance and their insulin response to the glucose load. Through this division it appeared that subjects with no glucose intolerance were moderately obese while the groups with glucose intolerance showed a higher degree of obesity, glucose intolerance increasing with age. The 10 obese subjects with no glucose intolerance (group A) presented values for glucose disposal similar to those of the control subjects. The 4 obese subjects with impaired glucose tolerance (group B) showed no significant changes in glucose storage and in basal oxidation, but a significant decrease in oxidation in response to the load (11±2g vs 19±1 g in the control group, p <0.02). The 6 obese subjects with overt diabetes and elevated insulin response to the glucose load (group C) showed a significant decrease in glucose storage (34±6 g vs 63±1 g, p < 0.001) but not in oxidation. The 6 obese subjects with overt diabetes and decreased insulin response (group D) showed a significant decrease in glucose storage (25±4 g vs 63 ±1 g, p < 0.001) and oxidation (12±1 g, vs 19+1 g, p < 0.005). These observations show that in obese diabetics, glucose intolerance results primarily from decreased glucose storage and to a lesser extent from a decrease in glucose oxidation.     

Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients

Summary The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 ± 1.2 kg. Subsequent surgical reduction of BFM by 6.0 ± 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargementper se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM. Preliminary results of this study were presented at the 9th Congress of the International Diabetes Federation, held in New Delhi in 1976 (abstract ≠ 333).     

Modifications of abdominal fat and hepatic insulin clearance during severe caloric restriction

Using computed tomography on 19 obese female subjects, we determined abdominal adipose tissue, both subcutaneous and visceral adipose tissue, before and after 2 weeks of a very low caloric diet (VLCD). The following parameters were also determined before and after 15-20 days of VLCD: plasma glucose and insulin levels, oral glucose tolerance test, basal pancreatic insulin secretion estimated by fasting C peptide (Cp), and fasting insulin hepatic clearance calculated by Cp/insulin molar ratio. After VLCD the body weight and body mass index significantly declined (p less than 0.01); whereas abdominal adipose tissue and visceral abdominal tissue (VAT) significantly decreased (p less than 0.01), modifications of subcutaneous abdominal tissue (SAT) were not significant. Fasting insulin levels and plasma glucose response to oral glucose load significantly decreased (p less than 0.05). Insulin response remained unchanged. Cp immunoreactive insulin (IRI) significantly increased (p less than 0.01). A significant positive correlation was found between delta VAT and delta Cp/IRI before and after VLCD (p less than 0.01). Our data seem to suggest that the weight loss induced by VLCD fundamentally involves a decrease in VAT. The reduction in visceral fat could be associated with an increase in hepatic insulin clearance.     

Glucose tolerance, serum insulin and lipid abnormalities in patients with coronary heart disease.

Blood glucose, free fatty acid and insulin responses to oral glucose and the fasting serum lipids were measured in 3 groups: 32 non-obese (mean age: 47.5 years) and 9 obese (mean age: 84.5 years), male patients with coronary heart disease and 12 non-obese male controls (mean age: 46.5 years). The oral glucose tolerance tests were repeated after 3 years in 16 of the non-obese patients with coronary heart disease. The results were as follows: 1) Glucose tolerance was impaired in 19 of 32 non-obese patients (59.4%). There was a significant correlation between impaired glucose tolerance and hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia). 2) In obese patients FFA levels at 30, 60, and 120 min after oral glucose administration were significantly elevated and FFA decrease was delayed with a drop to minimum levels at 180 min. 3) The insulin response after oral glucose administration in the group of non-obese patients with normal glucose tolerance was similar to that of non-obese controls. In the group of non-obese patients with impaired glucose tolerance, serum insulin levels went up to normal levels, but the peak was delayed. The serum insulin levels in obese patients were significantly higher than those of controls of 0, 60, 120, and 180 min. After 3 years the change in insulin response to oral glucose was not related to anginal symptoms or ECG findings, but was related to body weight change in patients with minor changes in glucose tolerance. 4) The metabolic pattern in the non-obese group with impaired glucose tolerance resembled that of "mild diabetes" in delayed response of insulin and FFA, and mild hyperlipidemia. These findings suggest that obesity may contribute to hyperinsulinemia in patients with coronary heart disease and that impaired glucose tolerance observed in patients with coronary heart disease is in part due to "latent diabetes".     

Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance

Summary Serum proinsulin is disproportionately elevated compared to insulin in Type 2 (non-insulin-dependent) diabetes mellitus. We studied the effect of obesity on serum proinsulin with varying degrees of glucose intolerance. Serum proinsulin and insulin were measured during a 75 g oral glucose tolerance test in 73 obese and 74 non-obese subjects with normal, borderline or diabetic-type glucose tolerance. Proinsulin was assayed by a direct radioimmunoassay using proinsulin-specific antiserum. Fasting serum proinsulin and insulin and the summed values of proinsulin and insulin during oral glucose tolerance test were significantly, or tended to be, higher in obese subjects than in those without obesity in each category of glucose tolerance. However, the molar ratio of proinsulin to insulin was nearly the same between obese and non-obese groups with a similar degree of glucose tolerance. On the other hand, the proinsulin/insulin ratio increased progressively with the deterioration of glucose tolerance. We conclude that proinsulin secretion is disproportionately increased in the presence of glucose intolerance but not by obesity itself. Each Beta cell seems to function normally in obese subjects while glucose tolerance remains normal.This work was presented at the 6th International Congress on Obesity in October 1990, Kobe, Japan