Effects of short-term clofibrate administration on glucose tolerance and insulin secretion in patients with chemical diabetes or hypertriglyceridemia

The effect of 1-wk administration of clofibrate on plasma glucose and insulin (IRI) before and during oral glucose tolerance tests (OGTT), as well as on serum lipids, uric acid, growth hormone (GH), and cortisol, were evaluated in 18 nondiabetic patients with hypertriglyceridemia and in 28 patients with chemical diabetes. Fasting plasma glucose, OGTT-glucose, and IRI areas were significantly decreased in both groups of patients, though the effects on glucose metabolism were much more marked in diabetics; 30-min IRI relative increase was unchanged; fasting plasma IRI was reduced in diabetics only. Glucose utilization during insulin tolerance tests carried out in 6 diabetics was significantly enhanced after treatment. Serum triglycerides (TG) and cholesterol (Chol) were significantly decreased in both groups of patients, as were serum free fatty acids and uric acid in diabetics; plasma GH and cortisol did not change. Significant correlations were found in diabetics between the postclofibrate decrease in OGTT-glucose area and the following: pretreatment values of serum Chol (r + 0.42, p < 0.05) and of 30-min IRI absolute and relative increase (r + 0.44 and + 0.38, respectively, p < 0.05); postclofibrate decreases in serum TG (r + 0.40, p < 0.05), in fasting plasma glucose (r + 0.73, p < 0.001), and in OGTT-IRI area (r + 0.57, p < 0.01). These data suggest that the improvement in glucose metabolism observed during short-term clofibrate administration may be due to increased insulin sensitivity.     

Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.     

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.     

Metasomatotrophic diabetes and its induction: Basal insulin secretion and insulin release responses to glucose,glucagon, arginine and meals

Summary Growth hormone treatment produced somatotrophic diabetes, with hyperglycaemia, polyuria, glycosuria and elevation in serum non-esterified fatty acids (NEFA) in dogs. Early in this diabetes, fasting serum immunoreactive insulin (IRI) rose 20-fold, the insulin/glucose (I/G) ratio rose 10-fold and in response to glucose infusion, the rise in IRI was twice the normal. In the latter half of the continued growth hormone treatment, the intensity of the diabetes increased, serum IRI declined to the normal level and the I/G ratio became subnormal. Late in the treatment, following glucose infusion, there was no change in serum IRI, no fall in NEFA and further depression of glucose tolerance. In metasomatotrophic diabetes, in which hyperglycaemia, glycosuria and high NEFA level persisted, fasting serum IRI was normal during several months, then became subnormal and the I/G ratio was diminished further. Following glucose IV there was no change in serum IRI, no fall in NEFA and low glucose tolerance. The normally-occurring rises in serum IRI following arginine and glucagon IV and after the ingestion of a meal were absent. These permanently diabetic dogs were responsive to insulin IV. The insulin content of the pancreas was reduced to about 1.2% of the normal after 14 months of this diabetes. From the sequence of change it is concluded that growth hormone induced metasomatotrophic diabetes by causing excessive secretion of insulin under basal and stimulative conditions, leading to permanent loss of function of the beta cells of the pancreatic islets, to such an extent that basal insulin secretion was low and the ability to secrete extra insulin in response to stimuli was lost.     

Studies in congenital generalized lipodystrophy. IV. Effect of muscular exercise on carbohydrate and fat metabolism including plasma levels of IRI and HGH.

Two patients with congenital generalized lipodystrophy have been studied at rest, and during and after long-term exercise at different carefully measured work loads. The two patients represented different stages of diabetes development. Both patients derived most of their energy used during muscular exercise from carbohydrate, and comparatively little from fat. FFA levels remained low throughout the period of observation in contrast to normal individuals and patients with juvinile diabetes. The data presented seem to show that deposition of glucose and free fatty acids (FFA) as triglyceride, must be impaired and are not compatible with the concept of increased triglyceride turnover in the adipocytes. The fall in blood glucose concentration (BCG) was less than in normal individuals and juvenile diabetes during exercise, and the glucose tolerance remained unchanged following work stop in both patients (k-values unchanged), in contrast to normal persons and patients with juvenile diabetes. Both patients showed significant falls in circulating immuno-reactive insulin (IRI) levels during exercise irrespective of a rise or fall in BGC. Thus, the exercise itself might activate endogenous mechanisms which could, on the one hand increase the circulating BGC, and at the same time force circulating IRI to decrease, thus disturbing the well-known relationship between circulating glucose and IRI levels as has been exhibited in normal subjects. The high IRI levels, also during exercise in these patients, indicate a relative insulin resistance in the muscles, but less marked than the insulin resistance in the adipose tissue. The IRI response after glucose infusion did not change significantly with increasing work loads with one exception. Exercose did not alter significantly the human growth hormone (HGH) levels in either the diabetic or the non-diabetic patient indicating an abnormal regulation of the HGH secretion in congenital lipodystrophy.     

Effect of insulin immunization on glucose tolerance in normal rats

Normal rats were immunized with insulin and Freund's adjuvant and submitted to an intravenous glucose tolerance test. Plasma glucose and free and total IRI levels were determined and compared to those observed in untreated rats, and in animals injected with the Freund's adjuvant used for the immunization procedure. In six of the 15 insulin injected animals, a significant amount of IRI (more than 100 mU/l) was found to circulate in bound form. In these animals, the fasting plasma glucose concentrations, and glucose disappearance rates were not different from those observed in all the other groups. However, the rise in their free IRI level was delayed, as was the return to basal level: 45 min after glucose injection, the free IRI concentration was still 98 +/- 29 mU/l in the six immunized rats vs 14 +/- 6 mU/l in those treated with Freund's adjuvant (p less than 0.01). Furthermore, the secondary nadir in the plasma glucose concentration observed at 60 min after glucose injection, was lower in the immunized rats (5.4 +/- 0.5 vs 6.8 +/- 0.3 mmol/l, p less than 0.05). It is concluded that in normal animals, IRI binding in proportions similar to those commonly observed in insulin-treated diabetic patients does not alter glucose tolerance but might lead to abnormal insulin kinetics and secondary hypoglycemia. These results might have implications for the use of closed-loop insulin delivery systems in type 1 (insulin-dependent) diabetic patients with insulin antibodies.     

Differences in Plasma Insulin Responses in Urban and Rural Indians: A Study in Southern-Indians

Fasting and 2 h post glucose plasma immunoreactive insulin (fasting IRI and 2 h IRI) responses were measured in urban (n = 149) and rural (n = 40) individuals with normal glucose tolerance during an epidemiological survey. In this survey, 900 urban and 1038 rural subjects were screened for glucose intolerance by capillary blood sampling. The respective response rates were 91% and 88%. We had planned to collect venous blood for IRI estimation, i.e. from 180 urban and 200 rural subjects. The compliance for the same was poor from the rural subjects and therefore the number available for IRI estimation was small. The mean ± SD ages of the urban and rural groups were similar (35.3 ± 9.9 and 38.6 ± 13.1 years, respectively). The rural population had lower body mass index (BMI) and subscapular:triceps ratio compared to the urban group (p < 0.001). The total calorie consumption was lower and physical activity was higher in rural population. Fasting and 2 h insulin values in urban population were 16.6 ± 9.4 mU I^?1 and 60.6 ± 42.5 mU I^?1 and in rural 6.7 ± 5.1 mU I^?1 and 32.4 ± 27.8 mU I^?1, respectively; the values being significantly lower in the rural population (p < 0.001). Multiple regression analysis showed that in urban population the fasting insulin was correlated to the BMI and the 2h IRI to 2 h glucose, BMI and the subscapular:triceps ratio. In the rural population, similar results were obtained, except in that the 2 h IRI was influenced by the gender also. This study showed that the fasting IRI and 2 h IRI responses in normoglycaemic urban and rural populations differed widely, probably related to the differences in body mass and adiposity distribution. The higher IRI concentrations in normoglycaemic urban subjects suggest a relative insulin resistance and this may be a contributory factor for the higher prevalence of diabetes in urban Indians.     

Glucose turnover and insulin secretion in dogs with pancreatic allografts

Summary The endocrine function of pancreaticoduodenal allografts was studied in six dogs and compared with that of normal animals. The grafts were able to prevent the diabetic ketosis that was observed in a control group after total pancreatectomy without following transplantation. — Systemic hyperglycaemia enhanced the insulin release from the transplanted pancreas, as measured by increased IRI levels after intravenous glucose administration. In contrast, the stimulation of insulin secretion by oral glucose loading was less than in normal dogs, while the glucose assimilation was also increased in transplanted animals.-It was speculated that the duodenum might be more susceptible to immunological damage than the pancreas, and that consequently an impairment of the resorption of glucose and of the production of intestinal factors controlling the secretion of insulin may result.-In the near future, pancreatico-duodenal transplantation does not appears to become a therapeutical alternative to the conventional treatment of diabetes mellitus in man.     

Blood sugar,serum insulin and serum free fatty acid responses to graded glucose pulses in hypothyroid dogs

Summary The actions of hypothyroidism on BS, serum IRI and circulating FFA profiles observed in response to single glucose pulses at three levels of stimulation (1.00, 0.66 and 0.33 g/kg body weight) in male dogs were studied. Hypothyroidism modified neither of the mean basal values of these variables. There were different mean BS responses for every time and dose with significant interaction between the two. The BS curves at different doses were not parallel. There was a different time effect for every dose of glucose, and normal and hypothyroid dogs did not differ in this respect. The mean serum IRI responses found in normal and hypothyroid dogs were different; the mean responses at different times also differed, and there were significant normality-time and dose-time interactions. If the hypothyroid dogs and the euthyroid controls received a particular dose of glucose, a significant time effect on the serum IRI level was observed. In the normal dogs receiving glucose dose 1.00, a significant serum IRI response between 5 and 25 min was observed; in the hypothyroid dogs receiving a similar treatment, the significant response lasted from 5 to 45 min. In the normal dogs receiving glucose dose 0.66, the response was significant only at 5 min, and the serum IRI levels were below baseline between 60 and 90 min, while in the hypothyroid dogs the IRI response lasted from 5 to 25 min. In both normal and hypothyroid dogs receiving the 0.33 dose, the responses were significant between 5 and 25 min. As for the mean serum FFA responses to glucose, they were different at every time, and a significant normality-time interaction was found. In the euthyroid controls, the response lasted from 5 to 60 min, while it was longer in the hypothyroid dogs, lasting from 5 min after glucose injection until the end of the test. Sponsored by theConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Established Investigator (CONICET), Argentina.     

Insulin levels during fasting and the glucose tolerance test and Homa's index predict subsequent development of hypertension

OBJECTIVE: To determine whether there is a longitudinal relationship between hypertension and hyperinsulinemia and to find the most useful parameter(s) for predicting the subsequent development of hypertension. SUBJECTS AND METHODS: The oral glucose (75 g) tolerance test (OGTT) was performed in 313 patients, who were divided into three groups according to glucose tolerance based on the WHO criteria: normal, borderline and diabetes mellitus. The fasting insulin (IRI) levels, sigmaIRI (the sum of the insulin levels 0, 30, 60 and 120 min after the OGTT), insulinogenic index and Homa's index, a candidate for the simple assessment of insulin sensitivity, of the normotensive and hypertensive subjects in each subgroup were compared. In addition, 145 normotensive subjects were followed up for over 3 years and observed for the development of hypertension. RESULTS: Hypertensive diabetic subjects had not only higher fasting IRI levels and sigmaIRI values, but they also had higher Homa's indices than normotensive diabetics. Normotensive subjects with normal glucose tolerance (n = 20) did not develop hypertension. However, 16 out of 94 patients with borderline glucose tolerance and five out of 31 diabetics became hypertensive. The incidence of hypertension in the group with fasting IRI > or = 15, sigmaIRI > or = 150 or Homa's index > or = 4 was between 5 and 9 times higher than that in the group with fasting IRI < 10, sigmaIRI < 100 or Homa's index < 2. This difference was still significant when multivariate analysis, including various factors such as age, body mass index (BMI) and sex, was performed. CONCLUSIONS: These results suggest that higher plasma IRI levels and/or insulin resistance are closely related to the pathogenesis of hypertension in patients with diabetes mellitus. Homa's index, fasting and sigmaIRI may be useful predictors of the subsequent development of hypertension.     

Somatotrophic diabetes: Insulin release responses to arginine and glucagon in dogs

Summary Growth hormone injected daily in 6 dogs for 6 days caused a 20-fold elevation in fasting serum immunoreactive insulin (IRI) without appreciable change in serum glucose in 1 day. In the somatotrophic diabetes that occurred after 2 days, the hyperinsulinaemia was maintained and the serum IRI/glucose (I/G) ratio declined from the early high level but remained elevated. During this treatment, in response to glucose infusion, the rise in serum IRI above the initially high fasting level was 16 times the normal. In response to glucagon, the rise in IRI was twice the normal and the rise in glucose was more prolonged, resulting in a decline in the I/G ratio. In response to arginine infusion, the rise in serum IRI was 8 times the normal and the rise in the I/G ratio was twice normal. Following a meal, the rise in serum IRI was 8 times the normal. Thus, with growth hormone treatment the insulin secretory responses to these stimulating factors were magnified over the already elevated fasting level of secretion. The insulin content of the pancreas was reduced to less than 10% of normal by growth hormone treatment for 6 days, due apparently to elevation of the rate of secretion over the rate of formation of insulin.     

Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice: relationships between recovery and hormone contents in transplants or host pancreas.

Recovery from diabetes was observed in streptozotocin-treated mice that received subcutaneous, isogeneic transplants of duct-ligated pancreas. Transplants excised from recovered hosts contained both immunoreactive insulin (IRI) and glucagon (IRG), indicating that both A and B cells capable of hormone storage were present. The IRI content in transplants, although only one sixth of that transplanted 6 wk earlier, was still 21/2 times greater than that in the host pancreas and was inversely related to the plasma glucose of the recipient during and after recovery. The IRI content in the transplant added to that in the host pancreas totaled 13% of the IRI found in the normal mouse pancreas, which sufficed for over-all recovery from diabetes but was insufficient to provide normal glucose tolerance and insulin response to a major glucose challenge. The abnormally high content of glucagon noted in the pancreas of hyperglycemic, sham transplanted mice was reduced by one-half in the pancreas of those transplanted mice returning to normal plasma glucose and insulin. Thus, the insulin content of the transplant was important to the recovery of isografted mice, but in addition, and perhaps as a consequence of recovery, there was a slight increase in the insulin storage capacity of the host pancreas and a marked reduction of glucagon compared to the content of these hormones in the pancreas of hyperglycemic, sham transplanted mice.     

Metabolic effects of enalapril in the treatment of essential hypertension.

In an open two-month study with an initial placebo period, the effect of enalapril on glucose tolerance, insulin (IRI) sensitivity and lipid profile was evaluated in 20 patients with mild to moderate essential hypertension. The following results were obtained: 1. Enalapril produced a favourable effect of blood pressure both in monotherapy and if combined with a diuretic. 2. Therapy did not lead to significant differences in blood glucose, IRI or IRI/glucose increase at 1 or 2 hours of oral glucose tolerance test either in patients with monotherapy or combination therapy, and with normal or disturbed glucose tolerance, respectively. 3. Serum lipids (total and HDL-cholesterol and triglycerides) did not change significantly in any group of patients.     

Studies in the diabetic mutant mouse: V. Glucose tolerance in mice homozygous and heterozygous for the diabetes (db) gene

Summary Mice homozygous and heterozygous for the diabetes (db) gene were studied to determine: 1. whether latent carbohydrate intolerance is present in young normoglycemic diabetic mutants (db/db); 2. whether normoglycemic food restricted diabetic mutants are carbohydrate intolerant; and 3. whether mice heterozygous for thedb gene (db/+) manifest abnormalities in glucose tolerance, serum IRI levels or body weights. Blood glucose levels were determined 0, 1/2, 1, 2 and 3 h following intraperitoneal administration of 2 mg glucose/g body weight. Normals (+/+) and diabetics (db/db) showed similar glucose tolerance curves during the first two weeks of life; however, both were markedly glucose intolerant compared to normal adult mice. At 3 weeks a small number of mutants had higher 3 h levels than any achieved in normal mice. By 4 weeks the average value for diabetics prior to glucose loading (0 time) was significantly (P < 0.02) elevated (db/db — 144 mg glucose/100 ml, +/+ = 124 mg glucose/100 ml). Although food restriction reduced blood glucose concentration at 0 time, persistence of carbohydrate intolerance was readily demonstrable following glucose loading. — Abnormalities in heterozygotes (db/+), 3 to 16 months of age, were primarily restricted to male mice, which showed moderate, but statistically significant elevations in blood glucose both at 0 time and following glucose administration. Forty percent of male heterozygotes had higher serum IRI levels than any observed in normal control males. Body weights of male heterozygotes were significantly greater (P<0.01) than those in agematched normals.USPHS Research Career Development Awardee, Grant K4-AM-7394.     

Ten-year follow-up of Japanese overweight subjects with impaired glucose tolerance: identification of a diabetes-prone subpopulation.

Ninety-four overweight subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were followed for 10 years. No one from the NGT group developed diabetes, however 32% of the IGT subjects did develop diabetes. Initial data of the IGT subjects who developed diabetes were significantly different from those who did not develop diabetes. Fasting, peak and/or sigma plasma glucose (PG), IRI and CPR at 180 minutes and CPR/IRI at 0 and 180 minutes were increased, and the peak time of PG was delayed; also the prevalence of a positive family history was higher, and the body weight heavier. Seventy-nine percent of IGT subjects with the initial sigma PG of greater than or equal to 40 mM or a positive family history developed diabetes whereas only 3% of those with sigma PG of less than 40 mM and a negative family history developed diabetes. Therefore, it might be considered that among the overweight adults with IGT, those with sigma PG of greater than or equal to 40 mM or a positive family history are diabetes prone and those with sigma PG of less than 40 mM and a negative family history are diabetes resistant.     

Diabetic type of the prednisolone-glucose test as the earliest latent stage of diabetes mellitus

Prednisolone-glucose tests (PGT) were done in 349 healthy persons and immunoreactive insulin (IRI) secretion in the time course of the glucose tolerance test (GTT) was studied in 48 persons. PGT of diabetic type was established in 33.3% of the persons with normal body mass and in 55.1% with excess body mass and GTT of boundary type. PGT of diabetic type is characterized by insulin secretion of diabetic type in response to glucose intake: the absence of the first peak of a rise of the IRI level and the second higher peak of the IRI level with a prolonged maintenance of IRI values up to the end of the test. The results suggest that PGT of diabetic type is an earlier stage of diabetes mellitus as compared to GTT of diabetic type. Therefore PGT can be used for distinguishing GTT of boundary type as one of the manifestations of diabetes mellitus and as a risk factor. Therapeutic antidiabetic measures are recommended to persons with PGT of diabetic type and prophylactic measures to persons with PGT of normal type.     

Glucose tolerance and insulin release in l-asparaginase treated rabbits

Male New Zealand White Rabbits were injected intravenously with either a single dose of 10,000 IU Escherichia colil-asparaginase/kg body weight containing 80 mg of d-mannitol/10,000 IU E. colil-asparaginase or 80 mg d-mannitol kg/body weight alone. Elevated fasting glucose (G) and elevated fasting immunoreactive insulin (IRI) levels were observed in the l-asparaginase treated rabbits at 1 wk. They peaked at 3 wk and declined thereafter. However, fasting G and IRI levels remained significantly elevated at the end of the study (9–15 wk after injection) compared to preinjection levels and levels of the controls. Glucose and IRI levels 0.5 hr post an intravenous glucose load (1 g/kg body weight) also became elevated post l-asparaginase and followed a time course similar to that of the fasting G and IRI levels. These 0.5-hr levels also remained significantly elevated at the end of the study. These data show that a single dose of 10,000 IU/kg body weight produces a hyperinsulinemic diabetes in New Zealand White Rabbits that appears to persist in a mild form for at least 9–15 wk.     

积雪草对2型糖尿病大鼠胰岛素抵抗影响的研究

目的：观察积雪草提取液对2型糖尿病大鼠胰岛素抵抗（IR）的影响。方法：尾静脉注射链脲佐菌素（STZ）并高糖高脂饲料喂养诱导2型糖尿病大鼠模型。随机分为积雪草低剂量组、积雪草高剂量组、二甲双胍组、模型组与正常组。观察体重、口服糖耐量试验（OGTT）、血甘油三酯（TG）、总胆固醇（TC）、空腹血清胰岛素（FINS）、胰岛素抵抗指数（IRI）（IRI=FINS×FPG/22.5）的改变。结果：①模型组大鼠体重明显增加（P〈0.01）,OGTT、TG、TC水平较正常对照组明显增高（P〈0.01）;②药物治疗后,积雪草组及二甲双胍组体重、血糖、血脂、IRI均明显降低（P〈0.01）;③积雪草高剂量组在降低血糖、血脂水平方面与二甲双胍组之间无明显的统计学差异（P〉0.05）,在降低IRI方面与二甲双胍组之间有明显的统计学差异（P〈0.01）。结论：2型糖尿病大鼠存在糖脂代谢紊乱及IR,积雪草可明显降低其血糖水平、减轻体重、降低血脂及IRI,其降低血糖、血脂水平的作用与二甲双胍相当,其降低IRI水平的作用优于二甲双胍。     

Pancreatic hormone secretion in patients with newly detected diabetes mellitus

The level of pancreatic hormones was studied in 10 healthy persons and in 40 patients with diabetes mellitus detected for the first time by GTT, their body mass being normal. For assessment of immunoreactive insulin (IRI), the level of proinsulin and biological activity of serum insulin were determined, and these indices were compared with glucose and C-peptide levels. The examinees' inhomogeneity was shown; on the basis of the findings obtained 2 groups were identified. A decrease in the levels of IRI, C-peptide and biological activity of serum insulin in the 1st group indicated a possibility of type I diabetes mellitus in such patients. Hyperinsulinemia, not correlating with glucose and C-peptide, a high percentage of proinsulin and low biological activity of serum insulin were noted in the 2nd group. The study permitted a differentiated approach to assessment of patients and a choice of therapeutic tactics.     

Glucagon and insulin secretion in potential diabetes

Summary Insulin and glucagon have been studied in 20 subjects (both of the subjects’ parents were diabetic or in case of only one diabetic parent, the other showed a first degree familiarity of diabetes): 10 showed normal glucose tolerance (‘true prediabetics’) and 10 impaired glucose tolerance (‘genetic chemical diabetes’). Mean insulin response to oral (100 g) and i.v. glucose load (200 mg/kg followed by 20 mg/kg/min for 60 min) and to arginine infusion (25 g in 30 min) was normal in the prediabetics and delayed and higher in the subjects with chemical diabetes as compared to the control group. Glucagon response to arginine was higher, but not significantly, in prediabetics and in subjects with chemical diabetes. In both of these groups glucagon suppression by glucose was not observed. The insulin/glucagon molar ratio was significantly reduced after glucose infusion in these two groups. No correlation was found between insulin and glucagon secretion after arginine or glucose. A possible alteration in the mechanism controlling glucagon secretion even in the earliest phases of diabetes is suggested. This work was supported in part by C.N.R. (Consiglio Nazionale delle Ricerche), Roma, grant # CT 76.01345.04.