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PubMed1993

[The computer support of hypoglycemic therapy in non-insulin-dependent diabetes mellitus].

Computer program designed by the authors and described in the article is realized as a reference system providing data on combinations of drugs used for diabetes mellitus. The system supplies information on hypoglycemic effects of representatives from each of three groups (insulins, sulfonamides, biguanides) administered both separately and in association with second drug selected by user. Interface of the system (drug menus and output windows) is friendly and demand no special training and operating skill. The program is written in C language and compiled as a single executable module for IBM-compatible personal computers.

Diabetes Mellitus, Type 2↗
PubMed1994

N4-(arylmethylene)-N1-[1-(1,2,5,6-tetrahydropyridyl)]-sulphanilamide derivatives as novel possible hypoglycemic agents.

Two series of sulphanilamide derivatives (Va-i and Vla-i), comprising both azomethine and arylsulphonamidotetrahydropyridine moieties, were especially synthesized to investigate the additive effect of such moieties on the pharmacological activity of the produced sulphonamides as possible therapeutic agents for producing hypoglycemia. Most of the hitherto prepared sulphanilamide derivatives, exhibited marked hypoglycemic activity. Structure-activity relationships were investigated and discussed, not only on the basis of lipophilic (pi) and/or electronic (sigma) characters of the aromatic substituent (R), but also in light of a steric effect in these molecules. The structure of the newly synthesized compounds was inferred from elemental and spectral analysis.

Animals↗
PubMed1993

[Does hypoglycemic treatment with gliclazide and gliquidone affect platelet function in type II diabetic patients?].

The estimation of the influence of gliclazide and gliquidone treatment on platelet function in type II diabetic patients was undertaken in the study. Aggregation parameters were assessed before and after the change of hypoglycemic therapy. Gliclazide was applied in the group I (11 patients, mean age 63.1 +/- 7.22 years, duration of diabetes 5.63 +/- 2.98 years), group II (19 patients, mean age 58.3 +/- 12.4 years, duration of diabetes 7.1 +/- 2.4) received gliquidone. The reference group consisted of 10 healthy volunteers (mean age 51.7 +/- 6.9). Aggregation parameters (threshold ADP concentration, intensity and velocity of the aggregation) were measured in examined groups of subjects. Metabolic control was estimated basing upon spectrophotometric measurement of fructosamine level. Significant increase in threshold ADP concentration (1.89 +/- 0.47 mumol/l before and 2.36 +/- 0.58 mumol/l after the treatment change p < 0.05) in group II was found. Threshold ADP concentration did not change significantly in group I (2.5 +/- 0.8 mumol/l before v 2.14 +/- 0.68 mumol/l after treatment). Significant decrease in the aggregation intensity was found in both groups (in group I 8.48 +/- 1.7 before v 6.39 +/- 2.17 after; in group II 7.35 +/- 1.73 before v 6.05 +/- 1.6 after 1 month treatment--both p < 0.05). The aggregation velocity did not change significantly (group I 61. +/- 11 before v 51.3 +/- 18.7 after, group II 63.2 +/- 14.8 and 62.8 +/- 13.7 respectively). Reference group values were ADP 2.7 +/- 0.16, intensity 6.22 +/- 0.53, velocity 63.2 +/- 2.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Synthesis and pharmacological evaluation of some novel 5-(pyrazol-3-yl)thiadiazole and oxadiazole derivatives as potential hypoglycemic agents.

Four series of 5-(pyrazol-3-yl)thiadiazole and oxadiazole derivatives (Va-c, VIa-c, VIIIa-c, IXa-c) have been synthesized from 5-arylazo-3-carbethoxy-4-methoxy-1-phenylpyrazole (Ia-c) with a view to investigate their pharmacological activity. The structure of the synthesized products was inferred from elemental and spectral data. The hypoglycemic effect, antimicrobial activity and toxicity of these potential chemotherapeutic agents were evaluated. Nineteen of these products were effective, when administered at an oral dose of 100 mg/kg body weight in inducing a marked reduction in blood glucose level.

Animals↗
PubMed1996

Efficacy of combination therapy with insulin and oral hypoglycemic agents in patients with type II diabetes during a 1-year period.

In this retrospective study, the authors assess the efficacy of combined insulin and oral hypoglycemic agents (OHAs) in controlling glycemic levels, as well as lipid levels and insulin requirements, in 48 patients with type II diabetes mellitus during a 1-year period. Thirty-two of these patients had secondary failure to an OHA (group 1). Sixteen patients (group 2) were taking high doses of insulin alone. Overall, 64.6% of all the patients responded to the combination therapy and insulin at 6 months. Response was defined as a decrease in hemoglobin A1c of more than 0.5%. At 12 months, 50% of these patients continued to respond to this regimen. No significant differences were seen in the patients' total cholesterol and triglyceride levels between responders and nonresponders in each group. After 1 year of combination OHA and insulin therapy, 50% of the patients showed a 21.4% reduction in their daily insulin dose.

Administration, Oral↗
PubMed1996

Mode of action of three structurally different hypoglycemic agents: a comparative study.

The mechanism of dose-dependent hypoglycemic effect, the margin of safety and ED50 of three structurally unrelated compounds, tolbutamide (TB), centpiperalone (CP) and a swerchirin-containing fraction (SWI) from the plant Swertia chirayita, were investigated in experimental models. After a single oral administration of TB, CP and SWI to groups of normal and streptozotocin (STZ)-induced mild and severe diabetic rats, the blood sugar lowering effect and ED50 of the agents were determined. Plasma Immuno Reactive Insulin (IRI) levels and the degree of islet beta cell degranulation were assayed using RIA and histochemical staining, respectively, in normal rats treated with the agents. The percent blood sugar lowering, increase in IRI levels and beta cell degranulation were highest in CP treated normal rats (69, 124 and 75%, respectively). In addition, CP was the only agent found active in STZ-induced severely diabetic rats (P < 0.01). In STZ-mild diabetic rats, however, TB was more effective than CP and SWI. By analysis of data using Anova method, it is concluded that CP is more effective than SWI (P < 0.01) and TB. However, SWI an impure natural product showed better blood sugar lowering than tolbutamide which is a drug in use.

Animals↗
PubMed1997

Increased complications in noninsulin-dependent diabetic patients treated with insulin versus oral hypoglycemic agents: a population study.

A cross-sectional population study was performed in a cohort of 890 non-insulin-dependent diabetes mellitus (NIDDM) patients residing in the greater Denver metropolitan region. Its purpose was to evaluate the relationship between insulin and oral hypoglycemic agents (OHAs) with regard to metabolic control and diabetic complications. The mean glycosylated hemoglobin for patients treated with insulin was 12.0 +/- 0.15% versus 11.4 +/- 0.14% (p < .03) for OHA. The difference in fasting blood sugar for the insulin-treated group (195.0 +/- 3.5 mg/dl) versus the OHA-treated group (194.0 +/- 2.9 mg/dl) was not statistically significant. Categorical increases in urinary albumin excretion were associated positively within insulin versus OHA therapy (p < .0001). Patients treated with insulin therapy had a higher frequency of peripheral vascular disease (insulin therapy, 14%; OHA therapy, 10%; p < .05); neuropathy (insulin therapy, 55%; OHA therapy, 37%; p < .0001); and retinopathy (insulin therapy, 71%; OHA therapy, 45%; p < .0001). The frequency of cardiovascular disease was equivalent in the two groups (17% versus 13%). In protocols correcting for diabetes duration, glycosylated hemoglobin, and gender in a multivariate model, the use of insulin still was related significantly to increases in urinary albumin excretion (p < .01), retinopathy (p < .0001), and neuropathy (p < .0008). In a subgroup of individuals with diabetes duration > 10 years (n = 211 for insulin treatment, n = 118 for OHA treatment), the frequency of neuropathy still was significantly higher in the insulin group (63% vs 49%; p < .016) as was retinopathy (85% vs 58%; p < .0001). Overt albuminuria also was more significant in the insulin-treated patients (p < .04). In summary, the NIDDM patients treated with insulin had more nephropathy, retinopathy, and neuropathy than did NIDDM patients treated with OHA, independent of duration of diabetes, fasting blood glucose, glycosylated hemoglobin, age, and blood pressure level. These results in NIDDM patients may be due to contributions from worse blood glucose control at an earlier stage in the patients' diabetes and/or the mitogenic, atherogenic, thrombogenic, and vascular permeability effects of insulin.

Administration, Oral↗
PubMed1997

Experimental animal studies on the hypoglycemic effects of a Copalchi extract.

The hypoglycemic effect of a Copalchi extract (Sucontral) was tested in 60 adult-male and female-Wistar rats in the present randomized, placebo-controlled, parallel-comparative animal study. A control group receiving only an Altromin standard chow was compared to treatment groups which received an Altromin chow enriched with Copalchi dry substance at 0.028% m/m or at 0.28% m/m. The study period was 30 days. The distinctly significant blood glucose lowering effect of the Copalchi extract could be demonstrated in both treatment groups. No significant difference in the antidiabetic effect was seen between the two concentrations. The onset of action of the Copalchi extract was observed between treatment day 1 and 3. A 20-25% decrease in the blood glucose concentration was achieved between the 7th and 15th day of treatment and remained at this level thereafter. This plateau was reached in the female rats already between treatment day 3 and 5. The parallel observed increase in the mean body weight was not striking and generally was the same between the test animals and the control animals.

Animals↗
PubMed1997

Hypoglycemic effect of Prunus amygdalus seeds in albino rabbits.

On administration of 2.5 g almond seed and its proportionate fractions, viz. 1.22 g defatted seed and 1.28 g oil to three groups of albino rabbits, they showed a definite hypoglycemic action during a two months study. The active factor seems to be a non oil fraction which is only partly soluble in ethyl ether.

Animals↗
PubMedDate not supplied

Prolonged hypoglycemic crisis associated with glyburide.

An elderly patient taking glyburide 5 mg/day for noninsulin-dependent diabetes mellitus was hospitalized because of severe hypoglycemia. Laboratory results indicated both renal and hepatic abnormalities were present at the time of admission. Despite infusion of 10% dextrose and supplemental boluses of 50% dextrose, the hypoglycemic crisis persisted for 3 days. After it resolved, the patient's diabetes was controlled by diet alone. The patient's age and the presence of hepatic and/or renal impairment must be taken in account in prescribing glyburide. Recognizing patients who may require dosage changes, and educating them on the signs and symptoms of hypoglycemia, may help prevent hospitalizations resulting from this complication associated with glyburide.

Aged↗
PubMed1998

Effects of insulin therapy on non-insulin-dependent diabetics with secondary oral hypoglycemic agent failure.

BACKGROUND: To search for the mechanisms of secondary oral hypoglycemic agent (OHA) failure in non-insulin-dependent diabetic (NIDD) and to identify the effects of insulin therapy on these patients, we observed their pancreatic beta-cell function and metabolic parameters. MATERIALS AND METHODS: The clinical characteristics and C-peptide responses to glucagon were analyzed in 37 NIDD with secondary OHA failure. All patients received insulin therapy and we measured their fasting plasma glucose (FPG), body mass index (BMI) and glycohemoglobin (HbA1C) levels at 3 months, their serum triglyceride and cholesterol levels at 6-12 months and performed glucagon tests at 0.5-29 months. RESULTS: Poor beta-cell function was observed in 11 (29.7%) patients (Group A) and fair beta-cell function in 26 (70.3%) patients (Group B). The mean age at diagnosis, the number of years since diagnosis of diabetes, FPG levels and HbA1C levels were similar in both groups. However, the patients in Group A had a lower average BMI (18.9 +/- 0.7 vs 22.1 +/- 0.6 kg/m2, p = 0.006) than those of Group B. After insulin therapy, the FPG levels (215 +/- 14 vs 282 +/- 12 mg/dL, p < 0.001) and HbA1C levels 9.2 +/- 0.5 vs 11.6 +/- 0.5%, p < 0.001) of both groups decreased but the BMI (23.1 +/- 0.7 vs 21.6 +/- 0.7 kg/m2, p < 0.001) increased significantly. However, the blood lipid levels and beta-cell function did not change. The beta-cell function was still poor in 5 out of 6 patients in Group A, but it was unchanged in all patients in Group B. CONCLUSION: About 1/3 of NIDD with secondary OHA failure are permanently insulin deficient and need long-term insulin treatment.

Administration, Oral↗
PubMed1996

Mouse embryonic cardiac metabolism under euglycemic and hypoglycemic conditions.

Children of mothers with insulin-dependent diabetic mothers (IDDM) have a 2-4 times higher incidence of congenital birth defects as compared to the general population, including cardiac abnormalities, of unknown etiology. Using rodent embryos to explore potential teratogenic factors of the altered IDDM metabolism, it has been shown that exposure to hypoglycemia in vitro results in a variety of defects, including cardiac malformations. Since pregnant diabetics experience frequent episodes of low blood glucose, it was hypothesized that hypoglycemia may play a role in the generation of heart abnormalities seen in children born to IDDM mothers. Several studies have indicated that during embryogenesis the heart is dependent on glucose for energy production such that under hypoglycemic conditions, insufficient amounts of ATP may be produced resulting in abnormalities. To test this hypothesis, cardiac ATP content was monitored in D10-D12 (plug day = D1) hearts. In addition, the contribution of glycolysis and the Krebs cycle to ATP production was monitored. D10 hearts exposed to euglycemic control conditions were found to be primarily dependent on glycolysis for ATP production from glucose before switching to the Krebs cycle and oxidative phosphorylation for energy production from this substrate on D11. Exposure to hypoglycemia did not alter the timing of this maturation process or deplete cardiac ATP content. However, cardiac lactate levels increased approximately twofold in the presence of hypoglycemia on d10. Since increased concentrations of lactate are harmful to many tissues and have been shown to be detrimental to the adult rat heart, lactic acidosis may explain the origin of cardiac defects produced by hypoglycemia, and not a deficiency of ATP.

Adenosine Triphosphate↗
PubMed2000

Hypoglycemic sensorimotor polyneuropathy associated with insulinoma.

Hypoglycemia-induced peripheral neuropathy due to insulinoma is unusual and, as far as we know, has previously been reported in only 34 patients. In this case report, we describe the clinical features, electrophysiological features, and pathological findings in a 37-year-old patient with polyneuropathy from repeated hypoglycemic episodes over a 9-year period that related to an insulinoma. The literature is discussed. The reported case is of special interest because the peripheral neuropathy led to the correct diagnosis.

Adult↗
PubMed1993

Hypoglycemic and insulin response to a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF-I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states.

Adult↗
PubMedDate not supplied

Glipizide: a second-generation sulfonylurea hypoglycemic agent. Pharmacology, pharmacokinetics and clinical use.

Glipizide is a second-generation sulfonylurea in which the substitutions on the arylsulfonylurea nucleus are large, relatively nonpolar groups. This chemical change increases the intrinsic hypoglycemic activity of the molecule 100-fold on a weight basis compared to first-generation agents. In addition, the pharmacokinetic properties, spectrum and severity of side effects and metabolism of this agent are somewhat different from those of first-generation sulfonylureas. The most important component of the antidiabetic action of glipizide is its effect in potentiating insulin action. Glipizide-mediated increases in nutrient-stimulated insulin secretion may contribute to its antidiabetic action. The drug is effective in controlling the blood glucose in patients with noninsulin-dependent diabetes mellitus. It is at least as effective as and probably more effective than first-generation sulfonylureas in controlling hyperglycemia in diabetes. Glipizide is relatively free of serious side effects and is contraindicated principally in patients with significant liver or kidney disease.

Animals↗
PubMed1986

Selective lesions of mesostriatal dopamine neurons ameliorate hypoglycemic damage in the caudate-putamen.

Unilateral 6-hydroxydopamine lesion of the mesostriatal dopaminergic system was found to ameliorate neuronal necrosis in the caudate-putamen following 30 min of insulin-induced hypoglycemic coma. We propose that increased release of dopamine in the striatum during hypoglycemia or in the recovery period potentiates a deleterious neuronal hyperexcitation, probably induced by excessive release of glutamate or related compounds, thereby aggravating neuronal necrosis.

Animals↗
PubMed1994

The influence of repeated spreading depression-induced calcium transients on neuronal viability in moderately hypoglycemic rats.

The calcium transients which are associated with spreading depression (SD) do not lead to neuronal necrosis, even if the SDs are repeated over hours. We have previously shown that a restriction of energy production by moderate hypoglycemia prolongs the calcium transients during SD. In the present experiments, we explored whether such prolonged transients lead to neuronal necrosis. To that end, SDs were elicited for 2 h by topical application of KCl in anesthetized rats at plasma glucose concentrations of 6, 3, and 2 mM. The animals were then allowed to recover, and they were studied histopathologically after 7 days. In two other groups, hypoglycemic coma of 5 min duration (defined in terms of the d.c. potential shift) was induced either without or with a preceding train of SDs. These animals were also evaluated with respect to histopathological alterations. SDs elicited for 2 h did not give rise to neuronal damage when elicited at plasma glucose concentration of 6 mM, and, of the animals maintained at 3 and 2 mM, only a few animals showed (mild) damage. In general, therefore, repeated SDs with calcium transients of normal or increased duration fail to induce neuronal damage. The results suggest that, if calcium transients are responsible for a gradual extension of the infarct into the penumbra zone of a focal ischemic lesion some additional pathophysiological factors must be present, such as overt energy failure, acidosis, or microvascular damage. A hypoglycemia-induced calcium transient of 5 min duration gave no or only moderate neuronal damage. However, if a series of SDS were elicited in the precoma period, the damage was exaggerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗