The regulation of glucose-induced insulin secretion by Pre-stimulus glucose level and tolbutamide in normal man

Summary The relationship between the pre-stimulus glucose level and immunoreactive insulin responses to a glucose challenge (20-g IV) was studied in normal subjects. When the steady-state pre-stimulus glucose concentration was lowered by a 0.33 mU· kg^-1· min^-1 insulin infusion or raised by a 900mg/ min glucose infusion, no effect on first phase insulin secretion (mean 3–5 min insulin level) was observed. In contrast, the second phase response (10–60 min insulin area after glucose pulse) to intravenous glucose fell during insulin infusion and increased during the glucose infusion. Overall, a linear relationship was found between the change of pre-stimulus glucose level from the control to that during the insulin or glucose infusion and the change in second phase response (r=0.65, n = 14, p<0.02). The effect of tolbutamide infusion (7 mg·m^-2· min^-1) when compared with saline control was to increase both first phase (+54 ±13 mU/1, n=8, p <0.001, mean±SEM) and second phase (+972±256mU · mur^-1 · 1^-1, P<0.01) insulinsecretion. It is concluded that the first phase response to a glucose pulse is independent of the steady-state pre-stimulus glucose concentration and is directly enhanced by tolbutamide; in contrast, second phase is related to both the steady-state pre-stimulus glucose level and tolbutamide. These findings suggest that changes in basal or pre-stimulus plasma glucose during therapy with sulphonylurea drugs may be expected to influence the second phase insulin responses to glucose challenge.     

Characterisation of the effect of intravenous infusion of glucose and tolbutamide on the insulin delivery rate in man

Summary Serum insulin response to a single bolus of IV glucose or tolbutamide was measured in eight healthy subjects. Insulin disappearance rate was assessed by deconvolution from the serum insulin levels, using the measured insulin disappearance rate. The mean rate constant of insulin disappearance was 0.238±0.005 min^–1 (mean±SEM). Basal insulin delivery rate was 8.0 to 9.0 mU/min and the delivery rate following glucose injection (0.5 g/kg body weight) showed a biphasic response, whereas that after tolbutamide injection (15.6 mg/kg body weight), a monophasic response. After glucose injection, 1.7±0.3 U of insulin was delivered during the first phase (0–10 min) and 5.6±1.6 U during the second phase (11–60 min). After tolbutamide injection, 1.5±0.3 U of insulin was delivered during the first 10 min. Between 11 and 40 min, 1.6±0.5 U of insulin was delivered. The results thus confirm and also quantitate biphasic insulin secretion after a bolus of glucose with a monophasic response after tolbutamide. The method is suitable for studies of the insulin secretogogues in man.     

The response of serum glucose,free fatty acid and immunoreactive insulin to oral glucose and intravenous tolbutamide in normal,potentially diabetic and diabetic subjects

Summary Glucose, free fatty acids and immunoreactive insulin levels were measured in 323 normal, potentially diabetic and diabetic subjects after an oral glucose load and an intravenous injection of tolbutamide. The results indicate that, in potentially diabetic and diabetic subjects, the insulinogenic response to glucose lasted longer than in normal subjects. It is suggested that this phenomenon be due to the loss of cell sensitivity to the recently demonstrated inhibitory feedback induced by insulin itself. The insulinogenic response to tolbutamide and the FFA response to tolbutamide and insulin did not help in differentiating prediabetic from normal subjects. No consistent relationship was found between body weight and serum insulin response to glucose.This work was aided by Grant No. AM 06034 from the National Institutes of Health and by a Grant from the Upjohn Company.     

Insulinopenia in impaired glucose tolerance preservation of insulin response to i.v. arginine and tolbutamide

Summary Immunoreactive insulin (IRI) response to successive i.v. injections of glucose (0.3 g/kg), arginine (5 g) and tolbutamide (20 mg/kg) was measured in 11 non-obese patients with mild glucose intolerance and 11 control subjects. In 3 of the patients the IRI response to i.v. arginine and subsequent i.v. glucose was also measured. The mean peak IRI level following glucose was grossly diminished in the patients compared to controls but peak IRI levels following arginine and tolbutamide were similar in the two groups. Administering arginine prior to glucose in the 3 patients tested resulted in a lowering of the IRI response to arginine but no increase in the IRI response to glucose. The decreased IRI response to i.v. glucose associated with an adequate response to i.v. arginine and tolbutamide in these patients suggests a failure of the B-cell sensor mechanism for glucose and may provide a physiological explanation for the recognized value of restricting carbohydrate relative to protein in the treatment of this condition. Any defect in the sensor mechanism for arginine appears quantitatively much less severe than that to glucose. Presented in part at British Diabetic Association Meeting, Cardiff, 1977.     

The behaviour of the serum insulin level in non obese adult diabetics after intravenous glucose,tolbutamide and glucagon

Summary The serum insulin and blood glucose levels after the i.v. administration of three secretion stimuli, namely glucose, tolbutamide and glucagon, were investigated in 10 normal weight patients with maturity-onset diabetes and compared with the levels in a control group. The insulin values were lower in the diabetics than in the normals after each of the three stimuli. Glucose was the most potent in normals and the least potent in diabetics. The behaviour of the serum insulin level after glucose was not uniform in the diabetics; in some patients the rise was either delayed or diphasic. It may be assumed that in maturity-onset diabetes of normal body weight the biosynthesis and release of insulin are impaired by some influence exerted by the main factor, i.e. the glucose metabolism within the -cells of the Langerhans islets.

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Zusammenfassung Bei 10 normal-gewichtigen Patienten mit Alters-Diabetes wurde das Verhalten der Insulinaemie und des Blutzuckers nach i.v. Verabreichung von 3 die Insulinsekretion anregenden Substanzen untersucht: Glukose, Tolbutamid, Glukagon. Die Resultate wurden mit denjenigen der Kontroll-gruppe verglichen. Die Insulinwerte nach der Verabreichung der 3 die Sekretion stimulierenden Substanzen waren bei den Diabetikern niedriger als bei den Normalpersonen. Die Glukose erwies sich als der kraeftigste Reiz bei Nicht-Diabetikern und der schwächste bei den Diabetikern. Das Verhalten der Insulinaemie nach Verabreichung von Glukose war bei den Diabetikern nicht gleichmaessig: bei einer Anzahl von Faellen war das Ansteigen der Insulinaemie verspaetet oder zeitigte ein biphasisches Verhalten. Man darf annehmen, dass die Patienten mit Diabetes des Erwachsenenalters und Normalgewicht eine Veraenderung der Biosynthese und der Insulinfreisetzung unter dem Einfluss des Hauptfaktors, d.h. des Glukosestoffwechsels innerhalb der -Zellen der Langerhans'schen Inseln aufweisen.

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Resumen En 10 enfermos de diabetes madura, de peso normal, se ha estudiado el comportamiento de la insulinemia y de la glicemia después de haberles suministrado i.v. tres substancias estimulantes de la secreción insulínica: glucosa, tolbutamida y glicogón. Los resultados han sido comparados con los que se han obtenido en el grupo de control. Los valores insulínicos observados tras el suministro de las tres substancias estimulantes de la secreción han resultado más bajos en los individuos diabéticos que en los sanos. La glucosa ha resultado el estimulante más poderoso en la secreción de individuos normales y el más débil en los diabéticos. El comportamiento de la insulinemia tras suministro de glucosa no ha sido uniforme en los enfermos de diabetes: en una parte de ellos el aumento de la insulinemia se presentaba retrasado o con una marcha difásica. Se puede suponer que los enfermos con diabetes de la madurez y de peso normal presenten una alteración de la biosíntesis y de la liberación de insulina bajo la influencia del factor principal, es decir, del metabolismo de la glucosa dentro de las células de las islas de Langerhans.

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Resume Les AA. ont étudié 10 sujets avec diabète de la maturité, de poids normal, de point de vue de l'insulinemie et de la glycémie après administration i.v. de trois substances stimulantes la sécretion insulinique: glucose, tolbutamide et glucagone. Les résultats étaient comparés avec ceux obténus dans le groupe de contrôle. Les valeurs insulinémiques observés après l'administration des trois substances stimulates la sécretion étaient inferieurs chez les diabétiques vis à vis aux valeurs observés chez les sujets normaux. Le glucose est resulté le stimulus le plus éfficace sur la sécretion chez les sujets normaux et le moins éfficace chez les diabétiques. Le comportément de l'insulinemie après administration de glucose n'était pas uniforme chez les sujets diabétiques: dans une partie de ceux-ci l'augmentation de l'insulinemie était retardée ou démontrait une allure diphasique. On peut envisager que le sujets avec diabète de la maturité et de poids normal présentent une altération de la biosynthèse et de la libération de insuline sous l'influence du facteur principal c'est à dire du métabolisme du glucose dans les cellules beta des îles de Langerhans.

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Riassunto In 10 pazienti affetti da diabete maturo, di peso normale, è stato studiato il comportamento dell'insulinemia e della glicemia in seguito alla somministrazione i.v. di tre sostanze stimolanti la secrezione insulinica: glucosio, tolbutamide e glucagone. I risultati sono stati confrontati con quelli ottenuti nel gruppo di controllo. I valori insulinici osservati dopo la somministrazione delle tre sostanze stimolanti la secrezione sono risultati inferiori nei diabetici che nei soggetti sani. Il glucosio è risultato il più potente stimolo sulla secrezione nei soggetti normali ed il meno potente nei diabetici. Il comportamento dell'insulinemia dopo somministrazione di glucosio non è stato uniforme nei pazienti diabetici: in una parte dei casi l'aumento dell'insulinemia era ritardato od aveva andamento difasico. Si può supporre che i pazienti con diabete della maturità e di peso normale presentino un'alterazione della biosintesi e della liberazione di insulina sotto l'influenza del fattore principale, cioè del metabolismo del glucosio entro le cellule delle isole di Langerhans.

     

Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations

BACKGROUND: Earlier prospective studies have identified insulin action and secretion as predictors of T2DM in populations with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) (2-h OGTT < 7.8 and 7.8-11 mmol/L, respectively). Fasting plasma glucose (FPG), an additional and recently modified (normal <5.6 mmol/L) diagnostic criterion is associated with insulin secretion. We wanted to establish whether insulin secretion persists as an independent predictor of T2DM in individuals with no clinical evidence of impaired glucose regulation based on FPG and 2-h plasma glucose concentrations. METHODS: Insulin action (M, euglycemic-hyperinsulinemic clamp), insulin secretion (acute insulin response (AIR), IVGTT), and adiposity (%Fat, DXA or densitometry) were compared at baseline in 358 Pima Indians (232M/126F, 18-44 years old) with normal glucose regulation of whom 61 (35M/26F) developed diabetes (DIAB) during a median follow-up time of 7.6 years. RESULTS: In proportional-hazard analysis, % Fat (HR = 1.52, p = 0.03), M (HR = 0.51, p = 0.04) and AIR (HR = 0.64, p = 0.003) predicted the development of diabetes after adjustment for age and sex. In regression analysis adjusting for age, sex, %Fat and M at baseline, the non-diabetic group (NON-DM) had a higher AIR (p = 0.0002) than the DIAB group; the positive association of AIR with adiposity observed in the NON-DM group was absent in the DIAB group. Cumulative incidence rates (12y) for diabetes were highest (48%) in subjects with both M and AIR below the population median and lowest (11%) in subjects with both M and AIR above the population median. CONCLUSION: AIR can predict diabetes prior to the current clinical indicators of impaired glucose regulation.     

Effects of feeding and fasting on the insulin secretory response to glucose and sulfonylureas in intact rats and isolated perfused rat pancreas

Summary In intact rats 16 h of fasting reduced the plasma insulin response to i.v. stimulation with either glucose, tolbutamide or glibenclamide by 50–80 %, without affecting the extractable insulin content of the pancreas. In subsequent studies with the isolated perfused rat pancreas two distinct patterns of insulin release could be discerned during the secondary phase. In thefed state, glucose 1.5 mg/ml induced a more or less constant elevation of the insulin secretion rate over 30 min (type I). At glucose concentrations of 2 and 3 mg/ml the release pattern was characterized by progressively increasing secretion rates (type II pattern). Infusion of tolbutamide (0.2 mg/ml) lowered the threshold for glucose stimulation and induced both patterns of secretion at lower glucose concentrations.Fasting for 24 h caused a 70–80 % inhibition of insulin secretion per 30 min at glucose levels of 1.5 and 2 mg/ml. Decreased glucose sensitivity was indicated by a shift to the right of the entire dose-response curve for glucose and by reduced inhibition (30 %) at a glucose level of 3 mg/ml. The effect of tolbutamide was also strongly diminished. The percent inhibition of the response to tolbutamide at different levels of glucose showed a pattern of inhibition similar to that observed with glucose alone. These findings suggest that the glucose-dependent release mechanism is highly sensitive to relatively short periods of fasting.Presented in part at the Sixth Annual Meeting of the European Association for the Study of Diabetes, Warsaw, September 1970.Supported by a grant from the Netherlands Organization for the Advancement of Pure Research (Z.W.O.).     

Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1alpha mutation carriers.

AIMS: Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity. The present study was undertaken to compare the plasma insulin responses to glucose and tolbutamide in HNF-1alpha mutation carriers with those of healthy control subjects. METHODS: Seven mutation carriers; three normoglycaemic, two with impaired glucose tolerance, and two with newly detected diabetes, underwent an oral glucose tolerance test and a tolbutamide-modified intravenous glucose tolerance test with measurements of plasma insulin. Twenty-two healthy subjects served as controls. RESULTS: The plasma insulin response to intravenous glucose was reduced in the HNF-1alpha mutation carriers compared to the control subjects, with an area under the curve (median (interquartile range)) of 812 min pmol/l (421, 1647) and 1933 min pmol/l (1521, 2908), respectively (P = 0.03). In striking contrast, the plasma insulin response to tolbutamide was preserved, with an area under the curve of 2109 min pmol/l (1126, 3172) and 2250 min pmol/l (1614, 3276) in the mutation carriers and control subjects, respectively. CONCLUSIONS: HNF-1alpha mutation carriers are characterized by preserved tolbutamide-induced insulin secretion. Compared to healthy subjects, our MODY3 individuals did not show any increased serum insulin response to tolbutamide, suggesting that HNF-1alpha mutation carriers are not characterized by sulphonylurea hypersensitivity.     

基础及早期胰岛素分泌对2型糖尿病患者血糖水平的贡献

目的　探讨 2型糖尿病人群基础及早期胰岛素分泌对血糖水平的贡献。方法　 2型糖尿病患者 81例 ,测定标准餐试验 0、3 0、60、12 0min血浆葡萄糖及真胰岛素水平。计算胰岛素敏感性指数 (ISI)和早期胰岛素分泌 (ΔI3 0 /ΔG3 0 ) ,以评估机体胰岛素敏感性 ,以多因素回归方法评估早期及基础胰岛素分泌对2型糖尿病人群血糖变化的贡献。结果　多因素回归分析显示 ,ISI和ΔI3 0 /ΔG3 0 对血糖变化的贡献几乎相等。在标准餐试验各时点胰岛素值中 ,空腹及 60min血浆真胰岛素水平对血糖水平的变化起主要作用 ;空腹胰岛素对血糖曲线下面积的作用强于ΔI3 0 /ΔG3 0 的作用。结论　基础及早期胰岛素分泌对血糖水平的变化都有重要影响     

Derivation of a quantitative measure of insulin sensitivity from the intravenous tolbutamide test using the minimal model of glucose dynamics

Summary Using the decay phase of the glucose response during an intravenous tolbutamide test, a minimal model of glucose dynamics was used to calculate a value for an index of insulin sensitivity. This index describes the efficiency of insulin in accelerating the instantaneous rate of glucose disposal, and provides a measure of insulin resistance. The validity of estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test have been assessed with reference to estimates of this index derived from the intravenous glucose tolerance test for which the model was originally designed. There were three studies: (A) estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test in a group of normal, healthy men and women were compared with results obtained in a comparable group of subjects using the intravenous glucose tolerance test. The two methods gave estimates of the index of insulin sensitivity that were identical; (B) A group of patients taking methandienone, an anabolic steroid previously shown to cause marked insulin resistance, were tested whilst taking the steroid and either before, or at least two months after treatment. Each patient was tested by both intravenous tolbutamide test and intravenous glucose tolerance test on both occasions. Estimates of the index of insulin sensitivity from intravenous glucose tolerance or intravenous tolbutamide procedures both on and off treatment were significantly correlated (off treatment: r _s ,= 0.71, n=9, p<0.05; on treatment: r _s =0.69, n=9, p<0.05); (C) A group of patients undergoing investigations for suspected disturbances in carbohydrate metabolism was studied, each patient having had both an intravenous tolbutamide and intravenous glucose tolerance test. The group studied included patients in whom a degree of insulin resistance would be expected. Estimates of the index of insulin sensitivity from the two methods were closely correlated (r _s =0.95, n=25, p<0.001). This strong, identical correlation obtained between the intravenous glucose tolerance and intravenous tolbutamide tolerance estimates of index of insulin sensitivity in studies B and C over a wide range of values [intravenous tolbutamide tolerance test: 0.11–1.07 min^–1U^–1 1; intravenous glucose tolerance test: 0.12-1.06 min^–1U^–11]. This suggests that the intravenous tolbutamide estimates of index of insulin sensitivity are closely comparable to those derived from intravenous glucose tolerance test over a broad range of insulin sensitivities. We suggest that the use of intravenous tolbutamide to induce a dynamic change in insulin-glucose relationships, and mathematical modelling of those dynamics, can provide a valuable, quantitative measure of insulin sensitivity in a variety of clinical situations.     

The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed Type II diabetes: the Insulin Resistance Atherosclerosis Study

Abstract Aims/hypothesis. Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. Methods. We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. Results. Insulin sensitivity correlated inversely with fasting insulin (r _s = –0.42) and intact proinsulin (r _s = –0.32) (p < 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r _s = 0.23) and inversely with the intact proinsulin:insulin ratio (r _s = –0.29, p < 0.001). Fasting glucose correlated positively with intact proinsulin (r _s = 0.34) and the intact proinsulin:insulin ratio (r _s = 0.24, p < 0.001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p < 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. Conclusion/interpretation. Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects. [Diabetologia (1999) 42: 1060–1066] Received: 25 February 1999 and in revised form: 12 April 1999     

Regulation of energy metabolism in pancreatic islets by glucose and tolbutamide

Summary The kinetics of insulin secretion and oxygen uptake in response to D-glucose and tolbutamide were compared in mouse pancreatic islets. In addition, the role of decreased ATP as a driving force for secretagogue-induced oxygen consumption was examined. D-glucose (10–30 mmol/1) triggered a biphasic insulin release which always coincided with a monophasic increase in islet oxygen uptake. In the presence of D-glucose (5–30 mmol/1), tolbutamide (3–500 g,mol/1) consistently elicited an initial peak of insulin secretion which was followed by a continued decline. Tolbutamide-induced secretory profiles were accompanied by similar respiratory profiles. Oxygen consumption per ng of insulin released during the test phase was higher after elevation of the glucose concentration than after addition of tolbutamide. In conjunction with 5 or 10 mmol/l D-glucose, but not with 15 or 30 mmol/1 D-glucose, tolbutamide (30–100 mol/1) lowered islet ATP content significantly (p < 0.02). Phosphocreatine was not found in isolated islets, although they contained substantial creatine kinase activity. It is concluded that the driving force for Tobutamide-induced oxygen uptake is a decrease in the phosphorylation potential caused by the work load imposed by stimulation of the secretion process. However, a major proportion of the respiratory response to glucose also results from enhancement of biosynthesis.     

The effect of mixing human soluble and human crystalline zinc-suspension insulin: plasma insulin and blood glucose profiles after subcutaneous injection

The effect of mixing human soluble insulin with two newly developed formulations of human crystalline zinc-suspension insulin was studied in two groups of 8 normal and 6 diabetic subjects. Mixing Human Actrapid with Human Ultratard and Humulin-S with Humulin-Zn, for 60 s before subcutaneous injection, significantly blunted the rise in free insulin levels (p less than 0.05) and the onset of action of the short-acting insulins (p less than 0.01). The loss of solubility that occurs on mixing these insulins, with the consequent loss of the rapid acting component, may diminish their therapeutic usefulness in the control of post-prandial blood glucose.     

Ultrastructure of β-cells during the dynamic response to glucose and tolbutamide in vitro

Summary Ultrastructural changes in cells of the isolated perfused rat pancreas were observed during the dynamic response to glucose and tolbutamide. Evidence of granule secretion into the extracellular space by emiocytosis was noted during the first 60 sec of glucose stimulation, but not thereafter nor at any time during tolbutamide stimulation. Packaging of granules within the Golgi apparatus was apparent after 60 min of glucose injection, but not in the case of tolbutamide. These findings support the concept that glucose initially stimulates the release of a small labile pool of preformed insulin, while continued administration stimulates Golgi packaging activity and the provision of additional insulin for the secretory process. High tolbutamide alone, in contrast increases the Golgi complex, coated vesicles, multivesicular bodies and cytosegresomes. Thus it may stimulate packaging without insulin provision, or alternatively, increase lysosomal degradative processes.Supported in part by U.S. Public Health Service Grants AM 11182 and AM 01410.     

大米不同烹调方法对健康人餐后血糖和胰岛素分泌的影响

动值[(19.7±6.8)mU/L]明显低于大米粥[(27.6±13.1)mU/L,P<0.05]和葡萄糖[(29.9±12.2)mU/L,P<0.05].结论 健康人进食等量大米煮成的大米粥餐后血糖波动比进食大米饭更大,早期胰岛素分泌增加,餐后胰岛素波动增大.     

Evidence for specific binding of tolbutamide to the plasma membrane of the pancreatic B-cells

Summary The uptake of³H-labelled tolbutamide by microdissected pancreatic islets from obese-hyperglycemic mice has been studied. Tolbutamide is taken up in excess of the extracellular space of the islets. The uptake is saturable with a maximum uptake of about 3 mmoles/kg dry weight and a half-maximum at a 2 mM concentration in the medium. Albumin and glibenclamide depress the islet uptake of tolbutamide. The data support the view that tolbutamide stimulates insulin release by specific binding to the plasma membrane of the B-cells. Traduzione a cura di G.U.     

Dexamethasone treatment fails to increase arginine-induced insulin release in healthy subjects with low insulin response

Summary We have compared insulin responses to L-arginine before and during dexamethasone treatment in healthy subjects, previously classified as subjects with either high or low insulin response according to a standardized glucose infusion test. Arginine stimulation was administered as a 150 mg/kg bolus followed by 10 mg·kg^–1·min^–1 to six subjects with high insulin response and to seven subjects with low insulin response. Before dexamethasone treatment the incremental insulin level during 0–10 min of arginine was higher in subjects with high (36.5±6.8 U/ml) than in subjects with low response (14.5±2.3 U/ml), p<0.01 for difference. Dexamethasone treatment (6 mg/day for 60 h) markedly enhanced the insulin response to arginine in subjects with high response (+99% 0–30 min) but failed to affect the subjects with low response (+4% 0–30 min). The C-peptide response to arginine exhibited similar differences between groups. Decreased responsiveness to arginine in subjects with low insulin response, especially during dexamethasone treatment, suggests a Beta-cell capacity defect although a decreased potentiating-sensing effect of glucose cannot be completely ruled out.     

The relationships between thyroid-stimulating hormone level and insulin resistance,glucose effectiveness,first- and second-phase insulin secretion in Chinese populations

Increased insulin resistance (IR); decreased glucose effectiveness (GE); and both first-and second phase of insulin secretion (FPIS, SPIS) have always been important factors for the development of type 2 diabetes. Therefore, in this study, we evaluated the relationships between thyroid-stimulating hormone (TSH) and these 4 factors in adult Chinese.We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured with the equations built by our group.

• IR = log (1.439 + 0.018 × sex - 0.003 × age + 0.029 × BMI - 0.001 × SBP + 0.006 × DBP + 0.049 × TG - 0.046 × HDLC - 0.0116 × FPG) × 10 ^3.333
• FPIS = 10 [1.477 - 0.119 × FPG + 0.079 × BMI - 0.523 × HDLC]
• SPIS = 10 [-2.4 - 0.088 × FPG + 0.072 × BMI]
• GE = (29.196 - 0.103 × age - 2.722 × TG - 0.592 × FPG) ×10 ⁻³

The t test was performed to evaluate the differences between normal and diabetic groups. To evaluate the differences of the mean values of the 4 groups, from the highest to the lowest levels of TSH, we used a one-way analysis of variance.Age, high density lipoprotein-cholesterol and GE were higher in women. On the other hand, body mass index, blood pressure, low density lipoprotein-cholesterol, triglyceride, FPIS, SPIS and IR were higher in men. TSH was positively related to IR, FPIS, and SPIS and negatively related to GE. According to the r values, the tightest relationship was between TSH and IR, followed by GE, FPIS and SPIS.In conclusion, our data showed that IR, FPIS, and SPIS were positively related to the TSH level in middle-aged Chinese, whereas GE was negatively related. In both genders, IR had the tightest association followed by GE, FPIS, and SPIS.     

Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects

AIM: To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. METHODS: A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. RESULTS: Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. CONCLUSIONS: A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased.