Elevated basal insulin secretion and normal dynamic insulin sensitivity in borderline hypertension.

BACKGROUND AND AIM: Borderline hypertension is often the initial stage of stabilized hypertension. This study aimed to provide insight on insulin behavior and its relationship with glucose metabolism by investigating insulin secretion and hepatic clearance in non-steady-state conditions in borderline hypertensive patients. METHODS AND RESULTS: We studied 15 patients (6 F, 9M, 44 +/- 2 yr, 78 +/- 2 kg, systolic pressure 155 +/- 10 mmHg, diastolic 93 +/- 5) and 15 comparable healthy controls. All underwent an intravenous glucose test, with minimal model analysis to measure insulin sensitivity S1, glucose effectiveness SG, insulin pre-hepatic release, hepatic extraction, and insulin appearance rate in the systemic circulation. Basal glucose (3.98 +/- 0.12 vs 3.94 +/- 0.11 mmol/L, hypertensive vs control subjects respectively), i.v. glucose tolerance factor KG (2.0 +/- 0.2 vs 2.2 +/- 0.1% min-1), SG (0.035 +/- 0.004 vs 0.032 +/- 0.007 min-1) and S1 [3.5 +/- 0.5 vs 3.8 +/- 0.3 10(4) min-1 (microU/mL)] were similar, both basal insulin and C-peptide exhibited a marked increase (87 +/- 8 vs 46 +/- 6 pmol/L, p = 0.0003; 637 +/- 62 vs 381 +/- 76 pmol/L, p < 0.03) demonstrating insulin resistance in basal conditions. Insulin secretion per unit volume was greater in patients, both at basal (43 +/- 5 vs 24 +/- 5 pmol/L/min, p = 0.01) and after stimulation (total hormone released = 18 +/- 2 vs 11 +/- 2 nmol/L in 4 h, p = 0.022). Post-hepatic insulin delivery was also elevated (basal = 11 +/- 1 vs 6 +/- 1 pmol/L/min, p < 0.002, total = 5 +/- 1 vs 3 +/- 0.3 nmol/L in 4 h, p = 0.02), while no difference was detected in hepatic extraction (66 +/- 4% vs 66 +/- 3). CONCLUSION: Borderline hypertensive patients display normal glucose tolerance with basal insulin resistance and normal dynamic insulin sensitivity. Peripheral hyperinsulinemia derives from the combination of normal hepatic extraction with an overproduction of hormone, mostly due to the basal component. Because borderline hypertension often degenerates into overt disease, our results point to a progression that leads to the well-known insulin resistance proper to sustained hypertension.

Beta-cell response and insulin hepatic extraction in noncirrhotic alcoholic patients soon after withdrawal.

A decreased tolerance to carbohydrates has been reported in several studies of liver diseases, whereas only a few investigations have been performed in chronic noncirrhotic alcoholic patients with and without alcohol abstinence. The aim of this study was to evaluate in detail the metabolic portrait of six noncirrhotic alcoholics during the early phase of alcohol withdrawal by quantifying the main processes involved in glucose disappearance. Data from frequently sampled intravenous glucose tolerance tests (FSIGTs) were analyzed by means of the minimal model (MINMOD) approach, which provided measurements of the (prehepatic) beta-cell secretion and of insulin degradation in the liver, along with indexes of insulin sensitivity and glucose effectiveness. Plasma insulin levels were lower in the patients (basal, 3.5 +/- 0.2 v 8.0 +/- 1.8 in matching controls, P < .05; area under the curve, 1.41 +/- 0.07 mU/mL in 240 minutes v 4.06 +/- 0.37, P < .001), and C-peptide concentrations were higher (basal, 107 +/- 3.5 v 36 +/- 9 ng/dL in controls, P < .05; area under the curve, 492 +/- 118 ng/mL in 240 minutes v 245 +/- 66, P = .05). The model analysis confirmed the absence of a decrease beta-cell release; in fact, in the alcoholics there was a basal secretion of 19 +/- 5 versus 9 +/- 2 pmol/L/min in controls (P < .05) and a total release of 9.5 +/- 1.8 nmol/L in 240 minutes versus 6.5 +/- 1.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in myotonic dystrophy.

The aim of the present study was to obtain a comprehensive picture of the rate of insulin secretion and of tissue sensitivity to the endogenous hormone in myotonic dystrophy patients (MyD). The minimal model approach was utilized for the analysis of frequently sampled intravenous glucose tolerance test data (FSIGT). This method provided the characteristic parameters: SI, insulin sensitivity index; SG fractional glucose disappearance independent of dynamic insulin; n, fractional insulin clearance; phi 1 and phi 2 first and second phase insulin delivery sensitivities to glucose stimulation. In MyD patients SI was reduced (p less than 0.01) by 71% to 1.4 +/- 0.3 x 10(-4) min-1/(microU/ml), whereas in controls it was 4.85 +/- 0.77; SG was within the normal range: 0.044 +/- 0.012 min-1 in MyD patients and 0.036 +/- 0.017 min-1 in controls; phi 1 increased in MyD patients (7.4 +/- 1.3 min (microU/ml)/(mg/dl) versus 4.1 +/- 1.2 in controls); phi 2 increased in MyD patients (126 +/- 47 x 10(4) min-2/(microU/ml)/(mg/dl) versus 17 +/- 6 in controls; p less than 0.05). MyD patients showed a normal tolerance with the glucose disappearance constant, KG within the normal range: 2.75 versus 2.62% min-1 in controls. In MyD patients insulin resistance was associated with a higher than normal insulin delivery for both secretory phases, although the second phase was responsible for releasing a greater amount of hormone. In conclusion MyD patients try to compensate for overall insulin resistance by a more marked pancreatic response.

[Melituric picture in a group of myasthenics]. / Il quadro meliturico in un gruppo di miastenici.

On the ground of preceding researches carried out about myodystrophias, the authors studied the melituric symptomatology in both a group of myasthenic patients and a group of control. The chromatographic analysis and the dosage of some urinary carbohydrates, showed that there are not statistically significant differences between the group of myasthenic patients and that of controls.

Influence of bromocriptine on glucose-3-H3 metabolism in vivo.

The dopaminergic agonist Bromocriptine has been perfused in vivo in normal Wistar rats to control its activity on Glucose-3-H3 metabolism. Bromocriptine shows a rapid influence on glucose production rate (Ra) and glucose utilization rate (Rd). Both rates increase, but since Bromocriptine effects on glucose production rate is more significant than the ones on glucose utilization, the final results is an increase in plasma glucose levels. Since glucose production rate in normal animals is practically equal to hepatic glucose output, the most logical explantation of Bromocriptine activity is the activation of glycogenosis with a rise of plasma glucose levels.

The effects of a load of phenilalanine on glucose metabolism.

The clinical and experimental hyperphenylalaninemic conditions seem associated with disorders of carbohydrates metabolism. Examples are the increased liver glucose turnover and the glycogen depletion under Phenylalanine load and the hyperexcretion of glucose in the urine of PKU children. We studied the effects of an acute load of Phenylalanine on Glucose-3-H3 kinetics and plasma glucose levels in adult male Wistar rats. The effects of the load were very slow and after 40 minutes we observed an increase in the rate of plasma glucose production (Ra), that in normal animals in an almost exclusive liver function. As result of this glucose production there was a modest increase in plasma glucose levels.

Mellituria screening in some metabolic diseases.

Mellituria was studied in 83 subjects: 25 normal adults and children and 58 patients with several metabolic diseases. In comparison to the controls, no significant differences were found in 9 patients with cystinuria and in 2 patients with Apert's syndrome. The large excretion of glucose was the only important pattern of the 11 patients with insulin-dependent diabetes. In 23 patients with porphyria cutanea tarda a statistically significant increase in the excretion of pentose was observed. In 16 children with the classical form of phenylketonuria, a significant hypoexcretion of glucose was found. This latter observation could be explained by the carbohydrate metabolic alterations described in experimental hyperphenylalaninemia.

[Effects of sodium salicylate on blood sugar]. / Effetti del salicilato di sodio sulla glicemia.

The effect of constant perfusion of sodium salicylate on blood glucose has been studied in anestethyzed normale Wistar rats. The sodium salicylate perfused at the rate of 0,148 mg/min for 30 minutes has not statistically significant effect on glycemia.

[Metabolism of glucose-3-H3 during perfusion of sodium salicylate]. / Il metabolismo del glucosio-3-H3 nel corso della perfusione di salicilato di sodio.

The effect of sodium salicylate perfused at constant rate for 30 minutes on Glucose-3-H3 kinetics has been studied in anestethyzed normal Wistar rats, controlling blood glucose levels, Ra and Rd. While blood glucose levels and Rd were not affected, the Ra values were influenced between the 20th and the 30th minute of salicylate perfusion.

[Free carbohydrates of the normal liver]. / Carboidrati liberi del fegato normale.

A separation of liver carbohydrates was carried by means of paper chromatography on deproteinized ethanolic extracts of frozen livers. The carbohydrates most frequently observed were Ribose, Xylose, Fructose, Glucose, Maltose, Maltotriose, Maltotetrose; isomaltose was found less frequently.

[The action of cyclic somatostatin on hypoglycemia due to prolonged fasting in normal animals]. / L'azione della somatostatina ciclica sulla ipoglicemia da prolungato nell'animale normale.

The authors have examined the action of cyclic Somatostatin on blood glucose levels in normal rats and in rats starved for 36 and 50 hours. The infusion of 0,235 gamma/min. of Somatostatin for thirty minutes in the normals induced a slight increase in blood glucose levels that was statistically non significative. Under the same condition, the cyclic Somatostatin increased, in a statistically significant way, the levels of plasma glucose in both starved groups of rats.

[Effect of cyclic somatostatin on ethanol-induced hypoglycemia]. / La somatostatina ciclica sulla ipoglicemia da etanolo.

The authors examined the activity of the cyclic Somatostatin on Ethanol hypoglycemia. While the peptide is capable of increasing the plasma glucose levels of hypoglicemia starved rats, it does not increase the levels of plasma glucose in normal rats under the action of ethanol perfusion.