Treatment Of Glucose Intolerance Research Articles

Comparative analysis of the drugs efficacy for carbohydrate metabolism early disorders (prediabetes) treatment: A review

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.

Antidiabetic actions of GPR55 agonist Abn-CBD and sitagliptin in obese-diabetic high fat fed mice

GPR55 has been recognized as a novel anti-diabetic target exerting positive effects on beta cell function and mass. This study evaluated the metabolic actions and therapeutic efficacy of GPR55 agonist abnormal cannabidiol (Abn-CBD) administered alone and in combination with sitagliptin in diet-induced obese-diabetic mice.Chronic effects of 21-day oral administration of Abn-CBD (0.1 µmol/kg BW) monotherapy and in combination with sitagliptin (50 mg/kg BW) were assessed in obese-diabetic HFF mice (n = 8). Assessments of plasma glucose, circulating insulin, DPP-IV activity, CRP, amylase, lipids, body weight and food intake were undertaken. Glucose tolerance, insulin sensitivity, DEXA scanning and islet morphology analysis were performed at 21-days.Sitagliptin, Abn-CBD alone and in combination with sitagliptin attenuated plasma glucose by 37–53 % (p < 0.01 – p < 0.001) and enhanced circulating insulin concentrations by 23–31 % (p < 0.001). Abn-CBD alone and with sitagliptin reduced bodyweight by 9–10 % (p < 0.05). After 21-days, Abn-CBD in combination with sitagliptin (44 %; p < 0.01) improved glucose tolerance, whilst enhancing insulin sensitivity by 79 % (p < 0.01). Abn-CBD increased islet area (86 %; p < 0.05), beta cell mass (p < 0.05) and beta cell proliferation (164 %; p < 0.001), whilst in combination with sitagliptin islet area was decreased (50 %; p < 0.01). Abn-CBD alone, in combination with sitagliptin or sitagliptin alone decreased triglycerides by 34–65 % (p < 0.001) and total cholesterol concentrations by 15–25 % (p < 0.001). In addition, Abn-CBD in combination with sitagliptin reduced fat mass by 19 % (p < 0.05) and reduced CRP concentrations (39 %; p < 0.05).These findings advocate Abn-CBD monotherapy and in combination with sitagliptin as a novel and effective approach for bodyweight control and the treatment of glucose intolerance and dyslipidaemia in type-2-diabetes.

Secretion of GLP-1 but not GIP is potently stimulated by luminal d-Allulose (d-Psicose) in rats

Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. d-Allulose (allulose), also known as d-psicose, is a C-3 isomer of d-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0.5–2.0 g/kg body weight) elevated plasma GLP-1 levels for more than 2 h in a dose-dependent manner. The effects of allulose on GLP-1 secretion were higher than that of dextrin, fructose, or glucose. In addition, oral allulose increased total and active GLP-1, but not glucose-dependent insulinotropic polypeptide (GIP), levels in the portal vein. In anesthetized rats equipped with a portal catheter, luminal (duodenum and ileum) administration of allulose increased portal GLP-1 levels, indicating the luminal effect of allulose. Allulose-induced GLP-1 secretion was abolished in the presence of xanthohumol (a glucose/fructose transport inhibitor), but not in the presence of inhibitors of the sodium-dependent glucose cotransporter 1 or the sweet taste receptor. These results demonstrate a potent and lasting effect of orally administered allulose on GLP-1 secretion in rats, without affecting GIP secretion. The potent and selective GLP-1-releasing effect of allulose holds promise for the prevention and treatment of glucose intolerance through promoting endogenous GLP-1 secretion.

Endoscopic Bariatric and Metabolic Therapies: New and Emerging Technologies

Endoscopic bariatric and metabolic therapies (EBMT) are a new addition to the treatment arsenal for obesity. These include devices that are placed or removed via flexible endoscopy, and procedures that utilize instruments that require flexible endoscopy for the indications of weight loss or treatment of glucose intolerance (from pre-diabetes to diabetes). The EBMTs are generally divided into gastric and small bowel categories, and although individual EBMTs may have unique mechanisms of action, similar themes in proposed mechanism of action are seen in the gastric and small bowel EBMTs, respectively. In this review we will describe the therapies approved for use in the United States or currently in the process of obtaining approval for use in the United States. We will discuss potential mechanisms of action and examine safety and efficacy data.

Role of the M3 muscarinic acetylcholine receptor in β‐cell function and glucose homeostasis

The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose-stimulated insulin secretion from pancreatic beta-cells. Studies with isolated islets prepared from whole body M(3) muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M(3) muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M(3) receptors only in pancreatic beta-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M(3) receptors in pancreatic beta-cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet-induced glucose intolerance and hyperglycaemia. These findings indicate that beta-cell M(3) muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through beta-cell M(3) muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.

STUDIES OF PREVALENCE OF GLUCOSE INTOLERANCE IN CYSTIC FIBROSIS PATIENTS: EXPERIENCE WITH THE USE OF INSULIN

The prevalence and treatment of glucose intolerance were evaluated in 18 cystic fibrosis patients.

Relationship of fetal macrosomia to a 75g glucose challenge test in nondiabetic pregnant women.

We determined in nondiabetic women, the relationship of plasma glucose values obtained 2 hours after a 75 g oral glucose challenge test (GCT) at 16-20 weeks' gestation, with the incidence of macrosomia in term deliveries (37-41 weeks' gestation). From 1988-1990, in a systematic screening programme data collected prospectively from 1,331 women were analysed retrospectively. Women with gestational diabetes or impaired glucose tolerance (n = 53) were excluded. The rest (n = 1,278) had no evidence of glucose intolerance including 1,215 women with normal plasma glucose by GCT (< 7.8 mmol/L 2 hours after 75 g oral glucose load) and 63 women with abnormal GCT but not abnormal value at a glucose tolerance test. The GCT values were divided into 5 groups: Group A (< 4.5 mmol/L), B (4.5-5.5 mmol/L), C (5.6-6.6 mmol/L), D (6.7-7.7 mmol/L) and E (> 7.8 mmol/L). The variables studied were age, parity, gestational age at delivery and incidence of macrosomia. Using > 4 kg birth-weight as the definition of macrosomia, the incidence increased from 1.2% to 9.5% with increasing plasma glucose values in the GCT from Group A (> 4.5 mmol/L) to E (> 7.8 mmol/L). Similar trends of increasing incidences from 7.2% to 15.8% and 2.9% to 9.5% were noted when 90th and 95th birth-weight percentiles, respectively were used as definitions of macrosomia. The test of linear trend in this association was significant (p < 0.01). These results were not influenced by parity or gestational age at delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term Treatment of Glucose Intolerance in Middle-aged Subjects by Diet, Exercise and Sulfonylurea

In a screening survey of women and men 47-54 years old for detection of glucose intolerance (GI), with 75 g oral glucose tolerance tests (OGTT), 25 subjects with GI were randomly selected for a therapeutic trial for normalization of the GI. A control group of 18 GI subjects was chosen randomly from the same health survey and given no treatment for 5-10 months; no significant changes in OGTT variables, body mass index, blood pressure or blood lipids were found in this group during follow-up. The treatment group was given advice concerning a low-sucrose, low-fat, high-fiber and energy-restricted (when overweight) diet and also concerning exercise - single-handed (16 subjects) or in an exercise group (9 subjects). The GI improved in the 25 treated subjects after 6 months of this therapy. Thus the total area under the glucose curve and the 1-h and the 2-h glucose values had decreased, the mean 2-h glucose value was restored to normal (less than 7.0 mmol X l-1) and 48% of the treated subjects had a normal 2-h glucose value. Body mass index, systolic blood pressure, serum cholesterol and serum triglycerides were also reduced at the follow-up. The 6-month result was similar in the subgroup of nine GI subjects who followed the dietary advice and exercised in a group for at least one hour per week during at least three months. Physical working capacity was increased, although non-significantly. Glipizide, 1.25 mg daily, was added at breakfast to ten GI-subjects who still had pathological 2-h glucose values after 6 months of dietary and exercise treatment. After a further 6 months of treatment of these 10 subjects, the total glucose area and the 2-h glucose value were reduced, while the mean 2-h glucose value had not required the normal level. Body mass index was unchanged. Another four subjects in this subgroup now showed a normal 2-h glucose value. In conclusion, the 2-h glucose value was restored to normal in totally 64% of all treated GI subjects after short-term treatment with a diet, exercise and, in some cases, added glipizide.

Effect of long term bromocriptine treatment on glucose intolerance in acromegaly.

Blood glucose, plasma GH, insulin and glucagon levels during oral glucose tolerance test before and after treatment with bromocriptine (5-20 mg daily for 2-9 months) were investigated in eleven acromegalic patients with glucose intolerance. Nine out of 11 patients showed improvement or normalization in glucose tolerance after bromocriptine therapy. Basal levels of plasma GH were markedly decreased in 7 of 11 patients treated, although the improved glucose tolerance was not always associated with a drop of basal plasma GH levels. In contrast, basal plasma glucagon level showed a distinct fall in all the patients whose glucose tolerance was improved, but unchanged in whom glucose tolerance was not ameliorated. The mean values of plasma GH and glucagon after oral glucose load were significantly lower during bromocriptine therapy than those before the treatment, respectively. Basal levels of plasma insulin and its response to glucose load did not change after bromocriptine treatment. Bromocriptine thus appears to be a good alternative in the treatment of glucose intolerance in acromegalic patients and the improvement of glucose tolerance by bromocriptine may be related to the reduction in plasma glucagon levels. The possibility, however, is not excluded that a decrease by bromocriptine in the total daily GH secretion is a cause of the improved glucose tolerance.