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PubMed2000

Long-term dietary treatment with increased amounts of fiber-rich low-glycemic index natural foods improves blood glucose control and reduces the number of hypoglycemic events in type 1 diabetic patients.

OBJECTIVE: To evaluate in type 1 diabetic patients 1) the long-term feasibility of a high-fiber (HF) diet composed exclusively of natural foodstuffs and 2) the efficacy of this diet in relation to blood glucose control and incidence of hypoglycemic episodes. RESEARCH DESIGN AND METHODS: The study was randomized with parallel groups. Participants were part of a larger multicenter study on the effects of acarbose on glucose control in diabetes. A total of 63 type 1 diabetic patients, age 28 +/- 9 years, BMI 24 +/- 0.6 kg/m2, after a 4-week run-in period on their habitual diet, were randomized to either an HF (n = 32) or a low-fiber (LF) diet (n = 31) for 24 weeks. The two diets, composed exclusively of natural foodstuffs, were weight-maintaining and, aside from their fiber content, were similar for all nutrients. At the end of the run-in period and the dietary treatment, fasting blood samples for the measurement of plasma cholesterol, HDL cholesterol, triglyceride, and HbA(1c) were collected. A daily glycemic profile was performed on a day in which the participants had consumed a standard menu representative of their treatment diet (HF or LF). RESULTS: Of the 63 study subjects, 29 in the HF group (91%) and 25 in the LF group (81%) completed the study Compared with the LF diet, the HF diet after 24 weeks decreased both mean daily blood glucose concentrations (P < 0.05) and number of hypoglycemic events (P < 0.01). When compliance to diet was taken into account, 83% of the subjects on the HF diet and 88% on the LF diet were compliant. In this subgroup, compared with the LF diet, the HF diet significantly reduced mean daily blood glucose concentrations (P < 0.001), HbA(1c) (P < 0.05), and number of hypoglycemic events (P < 0.01). CONCLUSIONS: In type 1 diabetic patients, an HF diet is feasible in the long term and, compared with an LF diet, improves glycemic control and reduces the number of hypoglycemic events.

Adult↗
PubMedDate not supplied

[Hypoglycemic activity of the insulin-heparin complex and conditions for its appearance].

In animals with experimentally induced stable hyperglycemia attended by heparin deficiency in the blood, the insulin-heparin complex (the ratio of heparin and insulin in the complex was 1:4.7) produces a stronger hypoglycemic effect than that of an equivalent dose of insulin. A simple mixture of insulin and heparin (in the same ratio) causes an equally strong hypoglycemic effect. In animals with experimentally induced stable hyperglycemia without attendant heparin deficiency in the blood the hyperglycemic effect of the insulin-heparin complex and the mixture of these preparations does not differ from that of an equivalent dose of insulin. The results of the study bear evidence that intensification of the hypoglycemic effect in administration of insulin with heparin is due to the existence of hypoheparinemia, and confirm the concept that for adequate manifestation of the hypoglycemic effect of insulin a sufficient concentration of heparin is necessary.

Animals↗
PubMed1984

Glyburide (DiaBeta): a new second-generation hypoglycemic agent.

Glyburide is an improved drug for the management of non-insulin-dependent diabetes mellitus (NIDDM). It is at least as effective as the first-generation oral hypoglycemics and is effective in doses that are considerably less than those needed with first-generation sulfonyl-ureas. While its mode of action is similar to that of other agents, glyburide has the unique feature of prolonged activity despite a short half-life and short duration in the body. Side effects are minimal, and toxic reactions have not been reported. While hypoglycemic episodes can occur, as with any blood glucose-lowering agent, they can be prevented by being alert to patients who may be more sensitive to oral agents. Unlike older sulfonylureas, about 50% of glyburide is excreted through the feces. In 14 years of worldwide experience, glyburide has rarely shown disulfiram-like effects and has not shown antidiuretic effects. While glyburide produces an insulin release response to glucose that parallels a normal physiological response, it appears to also decrease resistance to insulin and sensitize the receptors while utilizing the patient's available endogenous insulin. There are two major metabolites, but they are inert and are rapidly excreted, having no hypoglycemic effect. Considering the safety of glyburide and the large worldwide population that uses this agent, it is expected that this new second-generation hypoglycemic agent will greatly increase the therapeutic spectrum for NIDDM. Not only is it possible for more patients with diabetes to be treated, but many already being treated orally can achieve better regulation with this effective new oral agent.

Animals↗
PubMedDate not supplied

Pancuronium effect on the neuromuscular function of hypoglycemic rats.

An expected response in a hypoglycemic patient to a muscle relaxant formed the basis for the research presented in this study. There was no information available in the accessible literature and references gave no data on this subject. But because perioperative hypoglycemia is not unusual, we scheduled this experimental work. Four groups of 6 white adult Wistar albino rats were used in the study. Group A was the normoglycemia control group, with blood glucose levels of 80-120 mg/dl. Groups B, C and D were made hypoglycemic by i.v. injection of insulin 1 IU/100 g b.w. Blood glucose levels were reduced to 50% of the control values in hypoglycemic animals, which were sacrificed 40 min later. Phrenic nerve-hemidiaphragm preparations were placed in a 100 ml bath containing Paradelis-Zaimis solution, 37 degrees C, pH 7.2, aerated with O2/CO2:95/5%. After stabilization and recording of neuromuscular activity, pancuronium bromide was administered in doses of 1.5 x 10(-9) M in groups A and B, 3 x 10(-9) M in group D. Statistical analysis between A-B, A-C, A-D groups was done with Student's paired t test. Results showed that under hypoglycemic conditions the amount of pancuronium bromide needed for complete neuromuscular blockade was 2.5-fold greater than that needed in normoglycemic conditions. These findings suggest that the integrity of the neuromuscular junction is altered during hypoglycemia.

Animals↗
PubMed1981

Effect of antacids on activity of oral hypoglycemics.

The effect of some antacids on the dissolution and hypoglycemic activity of acetohexamide, tolazamide, and tolbutamide tablets was investigated, as was the adsorption of the three drugs onto the antacids. The dissolution rates of the three drugs in the presence of magnesium oxide, aluminum hydroxide, magnesium carbonate, and calcium carbonate increased (0.5-1 hr) and then plateaued or decreased (1-3 hr). Magnesium trisilicate directly suppressed the dissolution of the three drugs. The antacids reduced the hypoglycemic activity of tolbutamide in the following order:magnesium trisilicate greater than magnesium oxide greater than aluminum hydroxide greater than magnesium carbonate greater than calcium carbonate. The same order occurred for the first three antacids with acetohexamide and tolazamide. Decreased hypoglycemic activity of the drugs may have been due to their adsorption to the coadministered antacids.

Adsorption↗
PubMedDate not supplied

Hypoglycemic treatments and the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations.

The fibrinolytic system was investigated in 115 patients with maturity-onset diabetes mellitus in good metabolic control and without thromboembolic manifestations. The patients were divided into 7 groups according to the hypoglycemic therapy: diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin. Our results indicate that in maturity-onset diabetes both fibrinolytic activity and inhibitors of fibrinolysis are increased. The enhanced fibrinolytic activity was not affected by different hypoglycemic drugs, whereas the main antiplasmins showed wide variations in the different treatment groups. In particular, a significant reduction of alpha 2M was observed in patients on glibenclamide therapy. In conclusion, our study showed that the high fibrinolytic state seems to be a constant element in diabetes, and that the different behaviors of the fibrinolytic system, reported by various authors in patients taking different hypoglycemic drugs, could be explained by the wide range of plasmin inhibitor levels observed in these conditions.

Aged↗
PubMedDate not supplied

Assisting effects of lithium on hypoglycemic treatment in patients with diabetes.

In this article, we report the assisting effect of lithium on hypoglycemic treatment in patients with diabetes. Thirty-eight diabetic patients, 15 male and 23 female, aged 20-70 yr, 33 noninsulin-dependent diabetes mellitus (NIDDM) patients, and 5 insulin-dependent diabetes mellitus (IDDM) patients, were recruited in this study. Fasting and 1-h postprandial blood glucose (BG) profiles were undertaken from three groups of patients with diabetes before and after short-term of treatment of lithium carbonate. Group I was treated with diet only, Group II with oral hypoglycemic agents (OHA), and Group III with insulin. The fasting blood glucose (FBG) level and 1-h postprandial blood glucose (1-h PBG) level before and after treatment of lithium were: Group I: FBG: 7.67 +/- 0.48 vs 7.13 +/- 0.82; 1-h PBG 15.13 +/- 0.88 vs 10.33 +/- 0.96; Group II: FBG: 8.84 +/- 0.67 vs 6.04 +/- 0.57; 1-h PBG: 12.33 +/- 0.72 vs 9.95 +/- 0.82; Group III: FBG: 10.87 +/- 0.83 vs 6.83 +/- 0.79; 1-h PBG: 12.45 +/- 0.93 vs 9.17 +/- 1.00 mmol/L, respectively. The FBG and PBG of all three groups decreased significantly after lithium treatment, except the FBG in Group I. These data suggest that combined with other therapy, lithium could improve glucose metabolism in most patients with diabetes. Our results suggest that lithium has an assisting hypoglycemic effect on antidiabetic treatment.

Adult↗
PubMed2004

Reduction of cardiovascular morbidity and mortality in type 2 diabetes. A rational approach to hypoglycemic therapy.

Type 2 diabetes mellitus is the single most important risk factor for the development of coronary artery disease. Unfortunately, the traditional therapeutic strategies for the treatment of hyperglycemia have proven to be ineffective in preventing cardiovascular complications. In recent years the number of available hypoglycemic agents has increased and considerable progress has been made regarding the comprehension of the pathophysiology of diabetes and its vascular complications. In the present article we firstly present benefits and risks of intensive vs standard hypoglycemic intervention, and the pros and cons of therapy targeted to postprandial hyperglycemia. Secondly, we discuss the cardiovascular effects of sulfonylurea agents and insulin, focusing on the role of intensive insulin treatment in the context of acute coronary syndromes. Thirdly, we review the epidemiological, clinical and experimental evidence linking insulin resistance and cardiovascular disease. Finally, we present the rationale and the role of metformin and thiazolidinedionetherapy in the prevention of cardiovascular complications. We conclude that the optimal use of the full spectrum of hypoglycemic agents has the potential to play a key role in the prevention of diabetes-related macrovascular complications.

Blood Glucose↗
PubMed1976

Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics.

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.

Administration, Oral↗
PubMed1992

Hypoglycemic activities of MTP-3631, a novel thiopyranopyrimidine derivative.

MTP-3631 is a novel thiopyranopyrimidine derivative structurally different from any existent hypoglycemic agents. MTP-3631 markedly decreased basal blood glucose and improved glucose intolerance in genetically diabetic C57BL/6J ob/ob mice, which was not affected by tolbutamide. MTP-3631 also caused hypoglycemic effects in normal rats, but no change was observed in plasma insulin level. Unlike buformin, MTP-3631 did not change plasma lactate level in ob/ob mice. These results suggest that the hypoglycemic mechanism of MTP-3631 may be essentially different from those of sulfonylureas and biguanides.

Animals↗
PubMed1991

Possibility of ideal blood glucose control by a new oral hypoglycemic agent, N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166), and its stimulatory effect on insulin secretion in animals.

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) revealed a new mode of hypoglycemic action with a more rapid onset and a shorter duration of action than the sulfonylureas (SUs). Hypoglycemic mechanisms and glycemic control benefits were demonstrated in laboratory animals. The stimulatory effect of A-4166 on insulin release, in fasting dogs with a cannula into the portal vein, was more rapid than that of tolbutamide after oral administration. A-4166 stopped the stimulation of insulin secretion very quickly, whereas tolbutamide maintained an elevation in plasma insulin levels for at least 6 hours. In the case of A-4166, a counter-regulatory glucagon response was observed during recovery from hypoglycemia, but it was significantly inhibited by tolbutamide. Hyperglycemia induced by glucose loading was rapidly inhibited by A-4166 in normal rats, in genetically diabetic KK mice and in STZ-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. Also, repeated administration of A-4166 for 2 weeks enhanced insulin secretion in the same manner as a single administration in normal rats. In conclusion, A-4166 is a new type of oral hypoglycemic agent, having a rapid and short-term insulin secretory effect and no suppressive effect on the hypoglycemia-induced glucagon response. Oral therapy with A-4166 would be beneficial in supplementing endogenous insulin secretion and would exert ideal glycemic control in NIDDM patients.

Animals↗
PubMed1991

Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus.

Salvia fruticosa Mill. has a folk reputation in the eastern Mediterranean region as a hypoglycemic agent. In order to confirm this claim, a 10% infusion of its leaves was tested, at an oral dose of 0.250 g/kg b.w.t., on normoglycemic rabbits and in rabbits made hyperglycemic by alloxan administration. This oral dose caused a statistically significant reduction in blood glucose levels in alloxanhyperglycemic rabbits, but not in normoglycemic animals, only after repeated administrations of the infusion (once a day for 7 consecutive days). Instead, the hypoglycemic effect was evoked by single oral doses of infusion in both normoglycemic and alloxanhyperglycemic rabbits orally loaded with glucose. However, in these animals S. fruticosa infusion did not modify plasma insulin levels. Moreover, the hypoglycemic effect of the drug was not evoked in rabbits which received the glucose load intravenously. These data strongly suggest that S. fruticosa treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose.

Administration, Oral↗
PubMed2004

Hypoglycemic potential of nateglinide versus glyburide in patients with type 2 diabetes mellitus.

Antidiabetic agents that augment insulin secretion can cause hypoglycemia. With the current trend toward early and aggressive treatment of patients with type 2 diabetes, the hypoglycemic potential of insulinotropic agents is of concern. This study aimed to compare the propensity of the "glinide," nateglinide, and the sulfonylurea (SU), glyburide, to elicit hypoglycemia in type 2 diabetic patients with moderately elevated fasting plasma glucose (FPG). Hyperglycemic clamps (target plasma glucose = 11.1 mmol/L) were initiated, and 30 minutes later patients received a single oral dose of nateglinide (120 mg, n = 15) or glyburide (10 mg, n = 12) in a double-blind fashion. At the end of the 2-hour clamp when the glucose infusion was terminated, plasma glucose and insulin levels were measured for 4 additional hours. The minimum plasma glucose level achieved after terminating the glucose infusion (glucose nadir) was used as an index of hypoglycemic potential. The mean (+/-SEM) glucose nadir was significantly lower in patients given glyburide (3.3 +/- 0.2 mmol/L) versus nateglinide (4.4 +/- 0.3 mmol/L, P = .025). Confirmed hypoglycemia (plasma glucose < or = 2.8 mmol/L) occurred in 2 of 12 patients given glyburide and in none of those given nateglinide. Plasma insulin levels were significantly higher from 100 to 240 minutes after clamp termination in patients given glyburide versus nateglinide. Nateglinide has less hypoglycemic potential than glyburide, suggesting that nateglinide may be a more appropriate insulinotropic agent for patients with moderate fasting hyperglycemia, such as elderly patients and those with comorbid cardiac ischemia.

Adult↗
PubMed1995

Conformational analysis of non-sulfonylurea hypoglycemic agents of the meglitinide family.

Non-sulfonylurea hypoglycemic agents of the meglitinide family such as S3075, repaglinide, KAD-1229, and A-4166, were found to display a comparable U-shaped conformation by molecular modelling, with hydrophobic cycles placed at the extremity of each branch and a peptidic bond placed at the bottom of the U. A comparable conformation was observed with the hypoglycemic sulfonylureas glibenclamide and glimepiride. A different conformation with a greater distance between the hydrophobic cycles at the extremity of each branch was found, however, with the biologically inactive enantiomers of A-4166 and repaglinide and the poorly efficient insulinotropic agent meglitinide. The identification of a common conformation of these hypoglycemic agents may help in the design of highly active compounds and provide an imprint of their postulated target receptor on the pancreatic B-cell plasma membrane.

Benzamides↗
PubMed2001

Absence of exacerbation of myocardial stunning in anesthetized dogs treated with KAD-1229, a novel hypoglycemic agent.

The effect of (+)-momocalcium bis[(2S,3a,7a-cis)-alpha-benzylhexahydro-gamma-oxo-2-isoindolinebutyrate]dihydrate (KAD-1229), a novel hypoglycemic agent with a chemical structure different from that of the sulfonylureas, on myocardial stunning was assessed in anesthetized dogs by comparison with that of glibenclamide, a sulfonylurea. Even though their hypoglycemic effects were of similar magnitude, glibenclamide (1 mg/kg, i.v.), but not KAD-1229, exacerbated the myocardial stunning induced by occlusion/reperfusion of the descending coronary artery. In a receptor-binding experiment, unlabeled glibenclamide completely inhibited [(3)H]glibenclamide binding to the myocardium, but KAD-1229 did not. These results suggest that the difference in binding properties of KAD-1229 and glibenclamide toward cardiac sulfonylurea receptors is one of the causes of their different effects on myocardial stunning. It is likely that KAD-1229 is highly specific for pancreatic sulfonylurea receptors and is speculated to be a safer hypoglycemic agent than, at least, glibenclamide.

ATP-Binding Cassette Transporters↗
PubMed2000

(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity.

We investigated the mechanism of the hypoglycemic effect of (R)-4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzene-sulfonamide [(R)-acetoxyhexamide; (R)-ACX], a new sulfonylurea compound. (R)-ACX potently stimulated the release of insulin from cultured pancreatic beta-cells (HIT T15 cells), established from hamster islet cells SV40-transformed. When (R)-ACX was orally administered to fasted rats, it decreased the plasma glucose level in a dose-dependent manner. The hypoglycemic effect of (R)-ACX was quick and short lasting, as compared to that of acetohexamide and glibenclamide. The quick and short-lasting hypoglycemic effect of (R)-ACX was thought likely to result from rapid absorption of (R)-ACX and rapid elimination of (R)-ACX and its metabolite, (R)-hydroxyhexamide. Furthermore, (R)-ACX was found to suppress the increase of blood glucose level due to starch loading in fasted mice. (R)-ACX may be useful in the control of postprandial hyperglycemia to patients with non-insulin-dependent diabetic mellitus.

Acetohexamide↗
PubMed2001

Hypoglycemic effect of S(-)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide.

A short-lasting hypoglycemic effect was observed when S(-)-hydroxyhexamide (S-HH), a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide (R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of R-HH to rabbits, in spite of their inability to oxidize R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both S-HH and R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic beta-cells). These results provide further evidence that both R-HH and S-HH exhibit a significant hypoglycemic effect.

Acetohexamide↗
PubMed2000

Hypoglycemic effect of extracts and fractions from Psacalium decompositum in healthy and alloxan-diabetic mice.

The hypoglycemic effect of the hexane, methanol and water extracts obtained from roots of Psacalium decompositum (Asteraceae) was investigated in fasting healthy mice. Only the water extract significantly reduced blood glucose in a dose-dependent manner in normal mice after intraperitoneal administration (P<0.05). This water extract was macerated with methanol obtaining a precipitate (WMP fraction), and it was studied in healthy and alloxan-diabetic mice. The WMP fraction showed significant hypoglycemic activity in healthy and mild diabetic mice, but the administration of this fraction to animals with severe diabetes did not cause any significant decrease in blood glucose levels. Two polysaccharide components isolated from WMP fraction showed hypoglycemic effect when tested in healthy mice.

Animals↗