Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning,Afternoon, and Evening

Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes.     

Diurnal Variation in Response to Intravenous Glucose

Intravenous glucose tolerance tests (25 g) were performed in the morning and afternoon on 13 apparently normal persons. The individual K values (rate of decline of blood sugar) were all higher in the morning tests, and the mean values were significantly higher in the morning. Fasting blood sugar levels were slightly lower in the afternoon. There was no difference between the fasting morning and afternoon plasma insulin levels, but the levels after glucose were lower in the afternoon. Growth hormone levels were low at all times in non-apprehensive subjects and unaffected by glucose. The results suggest that the impaired afternoon intravenous glucose tolerance, like oral glucose tolerance, is associated with impaired insulin release and insulin resistance.     

Diurnal Variation of Oral Glucose Tolerance: a Possible Pointer to the Evolution of Diabetes Mellitus

Possible diurnal variation in the blood sugar response to oral glucose was studied by comparing, in the same individuals, the results of oral glucose tolerance tests performed in the morning and the afternoon. In a group of normal individuals the blood sugar levels were significantly higher in the afternoon. In hyperglycaemic individuals the diurnal variation decreased as the blood sugar levels reached during the morning test increased, so that in a group of grossly hyperglycaemic men the mean morning and afternoon tests were almost identical. The causes of this diurnal variation are not known.     

Metabolic Response to Oral Glucose in Healthy South African White,Indian, and African Subjects

The response of serum insulin, growth hormone, plasma free fatty acids, triglycerides, and blood glucose to an oral glucose load was investigated in healthy White, African, and Indian subjects. Serum cholesterol, uric acid, platelet adhesiveness, and urine insulin clearance were also measured. Each racial group responded differently. Most striking were the differences between Africans and Whites; despite similar mean blood glucose values at all times during the test, the Africans had lower serum insulin levels, a lower urine insulin clearance, a much greater rise of growth hormone, a more definite and prolonged suppression of free fatty acid release, lower serum cholesterol and uric acid levels, and a trend towards lower plasma triglyceride values.The Indians tended to resemble Whites rather than Africans with respect to their insulin, growth hormone, cholesterol, and triglyceride levels. Their glucose tolerance was decreased compared with that of the other two groups, but suppression of their free fatty acids was enhanced. Platelet adhesiveness was similar in all three groups.The reasons for these differences are unknown, but must be related to genetic and environmental differences among the three races.     

Further Observations on the Diurnal Variation in Oral Glucose Tolerance

Diurnal variation in oral glucose tolerance was studied in 122 male volunteers aged 40 yearsand over who participated in a screening health examination. In those with screening blood sugar levels exceeding 110 mg./100 ml. the degree of diurnal variation was least in those with the highest morning glycaemia; the latter also tended to have lower afternoon fasting bloodsugar levels.In a group of 40 control subjects, afternoon glucose tolerance tests yielded significantly higher post-glucose blood sugar levels. The degree of diurnal variation was significantly and inversely related to the degree of obesity.     

Insulin and non-esterified fatty acids. Acute regulators of lipogenesis in perfused rat liver.

Livers from fed rats were perfused with whole rat blood and infused with oleate to maintain constant concentrations of serum non-esterified fatty acids over a wide physiological range. Infusion of insulin opposed the antilipogenic effects of increasing concentrations of serum non-esterified fatty acids. Secretion of very-low-density-lipoprotein triacylglycerols was directly proportional to the concentration of serum non-esterified fatty acids and was increased by insulin. The secretion of newly-synthesized fatty acids in very-low-density-lipoprotein triacylglycerols decreased with increasing concentrations of serum non-esterified fatty acid. Insulin opposed this change. Cholesterol biosynthesis was unaffected by alterations in concentration of serum non-esterified fatty acid but was increased by insulin. Equilibrium concentrations of perfusate lactate and glucose were increased by serum non-esterified fatty acids but steady-state rates of hepatic glucose output and lactate uptake were unchanged. Insulin decreased perfusate glucose concentrations and abolished the increase in its concentration that resulted from increases in non-esterified fatty acid concentrations.     

Insulin responsiveness of sheep, ponies, miniature pigs and camels: results of hyperinsulinemic clamps using porcine insulin

It had been suggested that marked species differences in glucose tolerance tests were due to differences in insulin resistance. To compare insulin responsiveness, euglycemic hyperinsulinemic clamps were carried out in sheep, ponies, miniature pigs and camels. Porcine insulin was infused as primed-continuous infusions for 2 h (6 mU x kg(-1) x min(-1)). The steady state glucose infusion rates in the pigs, sheep, ponies and camels were 96.0, 18.6, 7.1 and 6.1 micromol x kg(-1) x min(-1), respectively. The maximal plasma insulin concentrations during the insulin infusions were 2,700 microU x ml(-1) in the camels, 1,400 microU x ml(-1) in the sheep and ponies and 600 microU x ml(-1) in the pigs. The rate of insulin removal from plasma was lowest in the camels as compared to the sheep, ponies and pigs (0.019, 0.038, 0.035 and 0.070 min(-1), respectively). In all species the concentrations of plasma non-esterified fatty acids dropped significantly 10-30 min after the start of the insulin infusion. However, the rates of non-esterified fatty acid reduction were higher in the pigs and sheep than in the camels and ponies. Results confirm a considerably higher insulin responsiveness in the pigs as compared to the sheep. The ponies and camels were found to be even more insulin-resistant than the sheep.     

Plasma glucose, insulin and free fatty acids in infants with congenital heart disease.

The effect of congestive cardiac failure, hypoxia and hypoglycaemia on glucose tolerance and insulin secretion were studied in selected groups of infants with congenital heart disease. Fasting blood glucose level was significantly decreased in patients with congestive heart failure and in cyanotic infants without congestive heart failure. In the former it seemed to be correlated with the degree of malnutrition, while in cyanotic infants it was independent of the nutritional state. Plasma insulin levels were reduced in infants, with congestive cardiac failure, although their glucose tolerance test and free fatty acid concentrations were normal. It is suggested that the decreased plasma insulin concentration was a consequence of adaptation to reduced requirements. Glucose tolerance and insulin secretion were not affected by hypoxia or hypoglycaemia.     

Hormonal and Metabolic Studies in Pheochromocytoma

One patient with benign and another with malignant pheochromocytoma have been studied in an attempt to elucidate the effect of increased catecholamines on the response of blood sugar, unesterified fatty acids, insulin and growth hormone to a glucose load. The presence of increased catecholamines in both patients appeared to produce increased fasting plasma unesterified fatty acid levels, carbohydrate intolerance and an unusual plasma growth hormone response to glucose. There was no interference with the normal decrease in plasma unesterified fatty acids after glucose ingestion. The malignant tumour, but not the benign one, was associated with low plasma insulin levels.After removal of the benign tumour the fasting unesterified fatty acid levels became normal. In addition, following glucose ingestion there appeared to be a more normal plasma insulin and growth hormone response and improved glucose tolerance. After removal of the primary malignant tumour it is noteworthy that the distant metastases secreted abnormal amounts of both adrenaline and noradrenaline.     

Endogenous opiate modulators of insulin secretion in the obese

The effects of endogenous opiates on insulin response to oral glucose load were studied in obese subjects and in lean healthy volunteers. None of these having a family diabetes. After 3 days on an 1,800 cal./m2, 40% carbohydrate diet all subjects underwent two standard 75 g oral glucose tolerance tests (OGTT), one of which was accompanied by an i. v. administration of 10 mg of, an antagonist of opiates, the naloxone. In one group of obese impaired oral glucose tolerance test occurred. All obese, but not the lean healthy volunteers, showed: 1) increased basal plasma insulin levels, 2) higher insulin response to OGTT, 3) a decrease in insulin response to OGTT after naloxone administration, with significant differences at 60 min (p less than 0.01) and 90 min (p less than 0.025). In none of the subjects significant differences were observed in blood glucose levels after OGTT plus naloxone administration. These data suggest that increased endogenous opiates may affect insulin response to glucose in obese with impaired or normal oral glucose tolerance test. At present there seems to be no satisfactory explanation for unchanged blood glucose levels during OGTT with and without naloxone despite a decrease in insulin secretion in the obese patients.     

Insulin and Non-esterified Fatty Acid Metabolism in Asymptomatic Diabetics and Atherosclerotic Subjects

Glucose, insulin and non-esterified fatty acid (NEFA) metabolism was studied in 18 patients (mean age 49) with ischemic heart disease (IHD) who did not have any concurrent disorder known to affect glucose tolerance.Significant hyperglycemia and hyperinsulinemia were observed in the IHD patients after oral glucose. The serum NEFA declined to a lower level in IHD patients than in normal subjects who received glucose.In response to hypoglycemia following the oral administration of sodium tolbutamide the serum NEFA in IHD patients rose to a higher level in the rebound phase than in normal subjects. This rise was preceded by a sharp decline in the concentration of circulating insulin.In 72% of the patients (IHD sub-group) the blood glucose values after oral glucose satisfied the criteria for the diagnosis of diabetes mellitus. The metabolic changes following oral glucose in the IHD sub-group and in asymptomatic diabetics (AD), free of clinical atherosclerosis and with similar impairment in glucose tolerance, were compared. Despite insignificantly lower insulin concentrations, the AD showed a significantly lesser fall in circulating NEFA than did the patients in the IHD sub-group. After oral sodium tolbutamide the IHD sub-group patients showed a greater insulin response and a greater rebound increase in circulating NEFA than did the AD.These differences in response to oral glucose and to sodium tolbutamide suggest that the pathogenesis of the impaired glucose tolerance in IHD may be different from that responsible for abnormal carbohydrate tolerance in asymptomatic diabetics without evident atherosclerosis. The abnormalities demonstrated in glucose, insulin and NEFA metabolism may play a role in the genesis of the hyperlipoproteinemia and atherosclerosis of IHD. One possible mechanism leading to hyperlipoproteinemia in ischemic heart disease compatible with the data is discussed.     

Assessing Impaired Glucose Tolerance and Insulin Resistance in Polycystic Ovarian Syndrome with A Muffin Test: An Alternative to the Glucose Tolerance Test

ObjectiveTo determine the sensitivity of a high-glucose load in a meal as an alternative to the standard oral glucose tolerance test (OGTT) in detecting impaired glucose tolerance and insulin resistance in women with polycystic ovarian syndrome (PCOS) and the relationship of body composition to insulin resistance in the PCOS cohort.MethodsIn this prospective, single-center study, women with PCOS who were being followed up as outpatients were recruited. The study was performed between November 2007 and March 2008. All participants underwent OGTT before study enrollment. Participants were given a meal including carbohydrates, fat, and protein. Glucose and insulin levels were measured every 30 minutes for 2 hours after completing the meal. Body composition was measured by dual-energy x-ray absorptiometry.ResultsThirteen of the 15 participants completed the meal tolerance test and the body composition study. Four of 13 participants (31%) had abnormal glucose tolerance with the meal test compared with 2 of 8 participants (25%) who completed the OGTT. Those who had insulin resistance on OGTT were detected with the meal test. The 2-hour insulin levels following the meal were 38% higher than with the OGTT. Of 10 participants with insulin resistance, 9 had a total body fat mass greater than the 90th percentile, whereas 1 of 3 participants (33%) with normal body composition was insulin resistant.ConclusionAdministration of oral glucose load via a meal is an effective alternative to the OGTT in diagnosing impaired glucose tolerance and insulin resistance and may be more sensitive, without the adverse effects of the oral glucose load in the OGTT. PCOS is an independent risk factor for impaired glucose tolerance and insulin resistance, regardless of body composition. (Endocr Pract. 2010;16:810-817)     

Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse

The mechanisms that are responsible for the extension of lifespan in the mouse with targeted disruption (knockout [KO]) of the growth hormone (GH) receptor/binding protein (GHR-KO) are unknown. However, in the long-living Ames dwarf mouse, blood glucose and body core temperature (Tco) are consistently lower than in normal mice. In addition, insulin levels are reduced and corticosterone levels are elevated in male dwarfs. These functional alterations, similar to those seen in animals under caloric restriction, have not been proven to be causally related to the extension of lifespan, but they do provide some insight into what traits may be necessary for long life. Therefore, to investigate which of these parameters are similarly affected in two genetically unrelated, yet similarly long-living mouse models, we measured Tco, thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and insulin, in addition to morning and afternoon levels of glucose and corticosterone, in young adult male and/or female GHR-KO mice and their normal siblings. Tco in GHR-KO mice was numerically reduced throughout the 24-hr period; however, these differences were only significant 4 hr prior to lights-off (14:00 hr), immediately after lights-off (18:00 hr), and during the 3 hr preceding lights on (03:00 to 06:00 hr). GHR-KO mice had significantly reduced levels of T3 and T4, while the ratio of these hormones was similar to that in normal mice. Insulin levels in GHR-KO mice were lower than in normal mice; levels in male GHR-KO mice were below the detectable limits of the assay used. Glucose levels in GHR-KO mice (male and females) were lower than in normal mice in measurements taken in both morning and afternoon; however, these differences arose from consistent reductions in males, as morning glucose levels in GHR-KO females were similar to those of normal mice. Corticosterone levels measured in blood plasma collected under basal (nonstressed) conditions showed sex-related alterations. Basal corticosterone levels in female GHR-KO mice were similar to normal females, while those in male GHR-KO mice were higher than in normal males in the afternoon. Corticosterone levels in stressed GHR-KO females were similar to those measured in stressed normal females. These data show that the long-living GHR-KO mouse shares a reduction in glucose, insulin, thyroid hormones, and Tco with the Ames dwarf mouse. Reductions in these parameters may be important to the underlying mechanisms of delayed aging in these animals.     

Postnatal pancreatic islet β cell function and insulin sensitivity at different stages of lifetime in rats born with intrauterine growth retardation

Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and insulin sensitivity, we established the IUGR model by maternal nutrition restriction during mid- to late-gestation. Glucose tolerance test and insulin tolerance test (ITT) in vivo and glucose stimulated insulin secretion (GSIS) test in vitro were performed at different stages in IUGR and normal groups. Body weight, pancreas weight and pancreas/body weight of IUGR rats were much lower than those in normal group before 3 weeks of age. While the growth of IUGR rats accelerated after 3 weeks, pancreas weight and pancreas/body weight remained lower till 15 weeks of age. In the newborns, the fasting glucose and insulin levels of IUGR rats were both lower than those of controls, whereas glucose levels at 120 and 180 min after glucose load were significantly higher in IUGR group. Between 3 and 15 weeks of age, both the fasting glucose and insulin levels were elevated and the glucose tolerance was impaired with time in IUGR rats. At age 15 weeks, the area under curve of insulin (AUCi) after glucose load in IUGR rats elevated markedly. Meanwhile, the stimulating index of islets in IUGR group during GSIS test at age 15 weeks was significantly lower than that of controls. ITT showed no significant difference in two groups before 7 weeks of age. However, in 15-week-old IUGR rats, there was a markedly blunted glycemic response to insulin load compared with normal group. These findings demonstrate that IUGR rats had both impaired pancreatic development and deteriorated glucose tolerance and insulin sensitivity, which would be the internal causes why they were prone to develop type 2 diabetes.     

Influence of oral contraceptives on changes of the carbohydrate metabolism

Serum glucose and serum insulin levels were measured during oral glucose tolerance tests in 100 women, 20-39 years of age, who used the OC (oral contraceptive) preparation Stediril and in a control group of 96 women of the same age group. Significantly lower fasting serum glucose levels were observed after 6 months of OC use. Significant decreases in glucose tolerance were observed among OC users who had taken OCs for longer than 6 months. The blood glucose levels were elevated significantly in this group 60 and 120 minutes after the beginning of the test. No correlation could be found between age and changes in glucose tolerance. No significant differences in fasting serum insulin levels were found in either group. A significant increase in serum insulin levels was observed among women who had used OCs longer than 6 months; this increase was apparent only 120 minutes after the beginning of the test. These changes in glucose tolerance were found to be reversible. Glucose tolerance tests should be preformed once a year on OC users, more often if an abnormality in glucose metabolism, e.g. latent diabetes, is present.     

Carbohydrate- and lipid-enriched meals acutely disrupt glycemic homeostasis by inducing transient insulin resistance in rats

Chronic intake of high-carbohydrate or high-lipid diets is a well-known insulin resistance inducer. This study investigates the immediate effect (1-6 h) of a carbohydrate- or lipid-enriched meal on insulin sensitivity. Fasted rats were refed with standard, carbohydrate-enriched (C), or lipid-enriched (L) meal. Plasma insulin, glucose, and non-esterified fatty acids (NEFA) were measured at 1, 2, 4, and 6 h of refeeding. The glucose-insulin index showed that either carbohydrates or lipids decreased insulin sensitivity at 2 h of refeeding. At this time point, insulin tolerance tests (ITTs) and glucose tolerance tests (GTTs) detected insulin resistance in C rats, while GTT confirmed it in L rats. Reduced glycogen and phosphorylated AKT and GSK3 content revealed hepatic insulin resistance in C rats. Reduced glucose uptake in skeletal muscle subjected to the fatty acid concentration that mimics the high NEFA level of L rats suggests insulin resistance in these animals is mainly in muscle. In conclusion, carbohydrate- or lipid-enriched meals acutely disrupt glycemic homeostasis, inducing a transient insulin resistance, which seems to involve liver and skeletal muscle, respectively. Thus, the insulin resistance observed when those types of diets are chronically consumed may be an evolution of repeated episodes of this transient insulin resistance.     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

阿司匹林增加胰岛素抵抗大鼠胰岛素敏感性的实验研究

目的　观察阿司匹林对高脂饮食大鼠胰岛素敏感性的影响。方法　灌服阿司匹林前后采用腹腔注射胰岛素耐量试验 (IITT)观察大鼠胰岛素的敏感性 ,并测定空服胰岛素、血糖和血脂等。结果　高脂饮食 4月、阿司匹林治疗 4周后 ,IITT发现高脂组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著高于正常对照组 (P <0 0 5或P <0 0 1 ) ;而阿司匹林治疗组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著低于高脂组 (P <0 0 5或P <0 0 1 ) ,与正常对照组差异无显著性。结论　大剂量阿司匹林有增加胰岛素敏感性和改善脂代谢紊乱的作用     

Intravenous glucose tolerance,insulin, glucose,and free fatty acid levels after myocardial infarction

Glucose tolerance tests performed on 12 patients within 15 hours of myocardial infarction and repeated two to four weeks later showed failure of insulin secretion, hyperglycaemia, glucose intolerance, and high free fatty acid levels. More pronounced changes were found in patients with cardiogenic shock. These findings suggest that the therapeutic use of potassium, glucose, and insulin should be re-evaluated.     

Metabolic effects of low-dose incremental insulin infusion in diabetic man

An incremental insulin infusion technique to assess insulin action at physiological circulating levels in diabetic man is described. Insulin was infused during sequential one hour periods at rates of 0.01, 0.05 and 0.10 u/kg/h. Serum free insulin concentrations had reached a plateau by the second 30 minutes of each infusion period. Blood glucose concentrations fell at a similar rate during the two lower rates of insulin infusion, but the fall was significantly greater with the highest insulin infusion. Glucose production and utilisation were measured isotopically using a 3-3H glucose infusion technique. Glucose production was inhibited with the lowest insulin infusion rate and a marked increase in glucose metabolic clearance rate occurred with the highest insulin infusion. Key intermediary metabolites were measured and blood glycerol, total ketone bodies, and plasma non-esterified fatty acids fell with the lowest insulin infusion rate. It is concluded that this technique allows identification of the effect of insulin upon different metabolic processes.