Fall In Fasting Blood Glucose Research Articles

Effects of Nigella Sativa on Type-2 Diabetes Mellitus: A Systematic Review.

Diabetes mellitus is one of the most prevalent metabolic disorders that affect people of all genders, ages, and races. Medicinal herbs have gained wide attention from researchers and have been considered to be a beneficial adjuvant agent to oral antidiabetic drugs because of their integrated effects. Concerning the various beneficial effects of Nigella sativa, this systematic review aims to provide comprehensive information on the effects of Nigella sativa on glucose and insulin profile status in humans. A computerized database search performed through Scopus and Medline via Ebscohost with the following set of keywords: Nigella Sativa OR black seed oil OR thymoquinone OR black cumin AND diabetes mellitus OR hyperglycemia OR blood glucose OR hemoglobin A1C had returned 875 relevant articles. A total of seven articles were retrieved for further assessment and underwent data extraction to be included in this review. Nigella sativa was shown to significantly improve laboratory parameters of hyperglycemia and diabetes control after treatment with a significant fall in fasting blood glucose, blood glucose level 2 h postprandial, glycated hemoglobin, and insulin resistance, and a rise in serum insulin. In conclusion, these findings suggested that Nigella sativa could be used as an adjuvant for oral antidiabetic drugs in diabetes control.

Evaluation of anti-diabetic activity of commercially available extracts of phyllanthus emblica in streptozocin induced diabetic rats

Phyllanthus emblica (syn. Emblica officinalis) or amla, is supposed to rejuvenate all the organ systems of the body, provide strength and wellness. It keeps us away from all the diseases by boosting our immune system. Besides, Phyllanthus emblica plant is reported to possess many pharmacological and clinical properties.Objective: To evaluate the anti- diabetic activity of commercially available extracts Phyllanthus emblica on high fat diet and low dose streptozocin induced diabetic rats.Materials and Methods: Diabetes was induced in albino rats using streptozocin 35 mg/kg i.p after giving high fat diet for 2 weeks. Animals with fasting blood glucose (FBG) above 200 mg/dl one week after injecting streptozocin were randomly divided into four groups of six rats each. Group 1- Diabetic rats, received only the distilled water (control),Group 2 - Diabetic rats, received Phyllanthus emblica crude extract (200 mg/kg/day)– Phyllanthus emblica Low dose (PEL), Group 3– Diabetic rats, received Phyllanthus emblica crude extract (400 mg/kg/day) – Phyllanthus emblica High dose (PEH), Group 4– Diabetic rats, received Glibenclamide (0.6 mg/kg/day) - Standard (S). All the animals received the respective drugs for six weeks. FBG was measured every 2 weeks till the end of sixth weeks by glucose-oxidase method.Results: Commercially available extracts Phyllanthus emblica showed significant fall in fasting blood glucose (P<0.001) from second week onwards in comparison to diabetic control group.Conclusion: The results suggest that commercially available extracts Phyllanthus emblica have significant hypoglycemic activity in diabetic model.

In vivo assessment of antidiabetic and antioxidative activity of natural phytochemical isolated from fruit-pulp of Eugenia jambolana in streptozotocin-induced diabetic rats

ABSTRACTObjectives: Eugenia jambolana (E. jambolana) is well known for its antidiabetic potential. The aim of the present study was to investigate the antidiabetic and antioxidative effect of an active compound (FIIc) isolated from fruit-pulp of E. jambolana in streptozotocin (45 mg/kg body weight)-induced diabetic rats.Methods: FIIc was isolated from the crude aqueous extract of fruit-pulp by ion-exchange column chromatography and high-performance column chromatography. Detailed UV, NMR, and IR spectra suggested that FIIc is α-hydroxy succinamic acid. FIIc was orally administered to diabetic rats at a dose of 10, 15, and 20 mg/kg body weight (mg/kg bwt.) to determine its effective dose. Thereafter, effective dose was administered to 8 weeks to determine its antidiabetic and antioxidative activity by estimation of glycemic index, lipid profile, key enzymes of carbohydrate metabolism, and oxidative stress parameters.Results: Administration of 15 mg/kg dose daily for 8 weeks led to significant (P < 0.001) fall in fasting blood glucose. Treatment with FIIc (15 mg/kg bwt.) showed significant improvement (P < 0.001) in all the biochemical parameters.Discussion: The results demonstrate that FIIc possesses significant antidiabetic and antioxidative activity.

Continuous Glucose Monitoring and Cognitive Performance in Type 2 Diabetes

Type 2 diabetes is associated with reductions in cognitive function that are associated with glycated hemoglobin (HbA1c) levels, but there is no information on whether cognition is related to postmeal glucose spikes. We explored the relationship of cognition to glucose levels measured by a continuous glucose monitoring system (CGMS) both before and after a weight loss diet. Forty-four white subjects with type 2 diabetes (59.0 ± 6.2 years old; body mass index, 32.8 ± 4.2 kg/m(2); HbA1c, 6.9 ± 1.0%) completed an 8-week energy-restricted (approximately 6-7 MJ, 30% deficit) diet. Cognitive functioning (short-term memory, working memory, speed of processing [inspection time], psychomotor speed, and executive function) was assessed during four practice sessions, baseline, and Week 8. Parallel glucose levels were attained using the CGMS in 27 subjects. Outcomes were assessed by fasting blood glucose (FBG), postprandial peak glucose (G(max)), time spent >12 mmol/L (T > 12), and 24-h area under the glucose curve (AUC(24)). Despite a fall in FBG of 0.65 mmol/L after 8 weeks, digits backward results correlated with FBG at both Week 0 and Week 8 (r = -0.43, P < 0.01 and r = -0.32, P < 0.01, respectively). Digits forward results correlated with FBG (r = -0.39, P < 0.01), G(max) (r = -0.46, P < 0.05), and AUC(24) (r = -0.50, P < 0.01) at Week 0 and FBG (r = -0.59, P < 0.001), G(max) (r = 0.37, P = 0.01), AUC(24) (r = -0.41, P < 0.01), and percentage weight loss (r = 0.31, P < 0.01) at Week 8. Cognitive function was not altered by weight loss, gender, baseline lipid levels, or premorbid intelligence levels (National Adult Reading Test). FBG, G(max,) and AUC(24) were related to cognitive function and an energy-restricted diet for 8 weeks did not alter this relationship.

Effect of germinated &amp;lt;i&amp;gt;Glycine max&amp;lt;/i&amp;gt; seeds on glycemic control in STZ+NAD induced type 2 diabetic models: a preliminary study

Objective: Glycine max (soybean) is a legume (Fabaceae) native to East Asia. Glycine max seeds are a powerful stimulant of immune system, used to decrease menopause symptoms, estrogen, treat certain types of cancers including that of the breast, lungs, prostate. It is also used for treating diabetes, liver and kidney disorders. The study aimed to investigate the effect of germinated Glycine max seeds on glycemic control in Streptozotocin (STZ) plus Nicotinamide (NAD) induced type 2 diabetic rats. Methods: The effect of Glycine max seed extract at the dose of 100, 200, 400 mg/kg b.w, respectively, germinated at different time intervals was investigated in STZ+NAD induced diabetic rats. The study was conducted for 21 days to investigate the effect of extract on blood biochemical parameters indicative of hyperglycemia; fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycosylated hemoglobin (GHb) and lipid profile, i.e. total cholesterol (TC), low and high density lipoprotein cholesterol (LDL-c and HDL-c) and triacylglycerol (triglycerides, TG) levels. Results: Aqueous extract (200 mg/kg b.w) of 12 h soaked and germinated Glycine max seeds produced significant reduction in FBG after 90 min (9.6%) and 3 h (15.6%) of administration. When the extract (200 mg/kg) was administered daily for three weeks to diabetic rats, significant fall in FBG (48.6%) and GHb (30.2%) was observed. Glucose tolerance was also found to be improved. Extract also showed significant hypolipidemic effect in diabetic rats as apparent from fall in TG, TC and LDL-c, and significant improvement on HDL-c. Conclusion: The results suggest that aqueous extract of 12 h germinated Glycine max seeds possess antihyperglycemic as well as hypolipidemic activity.

Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin–induced diabetic rats

Objective To evaluate the antihyperglycemic activity of ethyl acetate extract of Hypericum perforatum ( H. perforatum) in streptozotocin (STZ)–induced diabetic rats. Methods Acute toxicity and oral glucose tolerance test were performed in normal rats. Male albino rats were rendered diabetic by STZ (40 mg/kg, intraperitoneally). H. perforatum ethyl acetate extract was orally administered to diabetic rats at 50, 100 and 200 mg/kg doses for 15 days to determine the antihyperglycemic activity. Biochemical parameters were determined at the end of the treatment. Results H. perforatum ethyl acetate extract showed dose dependant fall in fasting blood glucose (FBG). After 30 min of extract administration, FBG was reduced significantly when compared with normal rats. H. perforatum ethyl acetate extract produced significant reduction in plasma glucose level, serum total cholesterol, triglycerides, glucose-6-phosphatase levels. Tissue glycogen content, HDL-cholesterol, glucose-6-phosphate dehydrogenase were significantly increased compared with diabetic control. No death or lethal effect was observed in the toxic study. Conclusions The results demonstrate that H. perforatum ethyl acetate extract possesses potent antihyperglycemic activity in STZ induced diabetic rats.

Antidiabetogenic action of Morus rubra L. leaf extract in streptozotocin-induced diabetic rats.

Researchers all over the world are exploring herbal supplements to control diabetes and its complications. This study evaluated the antidiabetic action of Morus rubra L. aqueous leaf extract through its effect on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-induced diabetic rats. The extract was orally administered to diabetic rats (100, 200 and 400 mg/kg body weight) daily for 21 days. Fasting blood glucose was measured on days 0, 7, 14 and 21. At the end of the experiment, blood samples were drawn to measure glucose tolerance, glycosylated haemoglobin, insulin, C-peptide and lipid parameters. Antioxidant enzymes (superoxide dismutase and catalase), reduced glutathione and lipid peroxides were determined in blood and liver tissue. Histopathological examination of pancreatic tissue was also performed. The extract showed a dose-dependent fall in fasting blood glucose. Treatment with 400 mg/kg extract produced a significant reduction in glycosylated haemoglobin with a concomitant elevation in plasma insulin and C-peptide levels. The altered serum lipids in diabetic rats were significantly restored following treatment with the extract. In erythrocytes, as well as liver, the activity of antioxidant enzymes and content of reduced glutathione were found to be significantly enhanced, while levels of serum and hepatic lipid peroxides were suppressed in extract-fed diabetic rats. Histopathological examination of pancreatic tissue revealed an increased number of islets and beta-cells in extract-treated diabetic rats. M. rubra aqueous leaf extract leads to control over hyperglycaemia and dyslipidaemia. The study also demonstrates its antioxidant nature, and hence it may be protective against diabetic complications.

Antidiabetogenic action of Morus rubra L. leaf extract in streptozotocin‐induced diabetic rats

Objectives Researchers all over the world are exploring herbal supplements to control diabetes and its complications. This study evaluated the antidiabetic action of Morus rubra L. aqueous leaf extract through its effect on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-induced diabetic rats. Methods The extract was orally administered to diabetic rats (100, 200 and 400 mg/kg body weight) daily for 21 days. Fasting blood glucose was measured on days 0, 7, 14 and 21. At the end of the experiment, blood samples were drawn to measure glucose tolerance, glycosylated haemoglobin, insulin, C-peptide and lipid parameters. Antioxidant enzymes (superoxide dismutase and catalase), reduced glutathione and lipid peroxides were determined in blood and liver tissue. Histopathological examination of pancreatic tissue was also performed. Key findings The extract showed a dose-dependent fall in fasting blood glucose. Treatment with 400 mg/kg extract produced a significant reduction in glycosylated haemoglobin with a concomitant elevation in plasma insulin and C-peptide levels. The altered serum lipids in diabetic rats were significantly restored following treatment with the extract. In erythrocytes, as well as liver, the activity of antioxidant enzymes and content of reduced glutathione were found to be significantly enhanced, while levels of serum and hepatic lipid peroxides were suppressed in extract-fed diabetic rats. Histopathological examination of pancreatic tissue revealed an increased number of islets and β-cells in extract-treated diabetic rats. Conclusions M. rubra aqueous leaf extract leads to control over hyperglycaemia and dyslipidaemia. The study also demonstrates its antioxidant nature, and hence it may be protective against diabetic complications.

Antidiabetic activity of Paspalum scrobiculatum Linn. in alloxan induced diabetic rats

Ethnopharmacological relevance Paspalum scrobiculatum Linn. (Poaceae) is traditionally used to treat diabetes mellitus. The grains of Paspalum scrobiculatum are having potential in the development of drug for diabetes due to their antidiabetic activity. Aim of the study To evaluate the antidiabetic activity of aqueous and ethanolic extracts of grains of Paspalum scrobiculatum Linn. (Poaceae) in alloxan induced diabetic rats. Materials and methods Aqueous and ethanolic extracts (250 and 500 mg/kg body weight), were administered orally to male Wistar albino rats. Alloxan monohydrate was used to induce diabetes mellitus. Total phenolic content was estimated in the extracts. The parameters studied included oral glucose tolerance test, fasting blood glucose, serum insulin and glycated haemoglobin levels, liver glycogen content, serum lipid profile, and changes in body weights. Results In oral glucose tolerance test, reduction of fasting blood glucose levels took place from 60 min of extract administration. The extracts produced a dose-dependent fall in fasting blood glucose (FBG). After 15 days of treatment with extracts the maximum reduction in FBG (35.14%) was observed in diabetic rats treated with ethanolic extract 500 mg/kg dose. A significant increase in serum insulin level was observed in the treated rats. Serum lipid levels were reversed towards near normal and a control in the loss of body weight was observed in treated rats as compared to diabetic control. The extract treatment also showed a significant increase in the liver glycogen and a significant decrease in glycated haemoglobin levels. The results demonstrate that Paspalum scrobiculatum possesses significant antidiabetic activity in diabetic rats. Conclusion The results suggest that Paspalum scrobiculatum has antidiabetic activity, thereby justifying its traditional claim and augmenting it into the present day systems of medicine.

Antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata L. leaves in experimental diabetes

Ethnopharmacological relevance Cassia auriculata L. (Caesalpiniaceae) is widely used from ancient period to treat diabetes mellitus. The leaves of Cassia auriculata are having potential in the development of drug for diabetes due to its antihyperglycemic and lipid-lowering activity. Aim of the study The present study was to evaluate antihyperglycemic and hypolipidemic activity of aqueous extract of Cassia auriculata leaves (CLEt) in streptozotocin (STZ)-induced mild diabetic (MD) and severe diabetic (SD) rats. Materials and methods Male Albino rats were rendered diabetic by STZ (45 mg/kg, intraperitoneally). CLEt was orally administered to MD and SD rats at 100, 200 and 400 mg/kg doses for 1 day to determine antihyperglycemic activity. The 400 mg/kg dose was administered daily for 3 weeks to assess glycemic control and hypolipidemic effect. Results CLEt showed dose dependant fall in fasting blood glucose (FBG). After 5 h of extract administration at 400 mg/kg dose, FBG was reduced by 13.9% and 17.4% in MD and SD rats respectively. After 3 weeks treatment, CLEt produced significant reduction in FBG and glycosylated haemoglobin (GHb) in both MD and SD rats. Serum lipid levels were reversed towards normal in extract fed MD and SD rats. Conclusions The results demonstrate that CLEt possesses potent antihyperglycemic and hypolipidemic activity in both MD and SD rats.

Antihyperglycemic effect of the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus

The oral antihyperglycemic effect of the water and ethanolic extracts of the fruit-pulp of Eugenia jambolana (EJ) was investigated in alloxan-induced diabetic with fasting blood glucose between 120 and 250 mg/dl as well as severely diabetic rabbits (fasting blood glucose above 250 mg/dl). Water extract was found to be more effective than the ethanolic extract in reducing fasting blood glucose and improving blood glucose in glucose tolerance test. Chromatographic purification of the water extract yielded not only two hypoglycaemic fractions (F-III more active than F-IV) but indicated the presence of hyperglycemic compounds (F-I and F-II) also in the water extract of Eugenia jambolana fruits. When administered as a single dose of 25 mg/kg of body weight; F-III could reduce fasting blood glucose from 174.0 ± 4.6 to 137.3 ± 5.4 mg/dl in diabetic (21% fall) and from 266.0 ± 5.4 to 202.2 ± 5.2 mg/dl in severely diabetic rabbits (24% fall). After treatment of diabetic and severely diabetic rabbits daily once with 25 mg/kg, body weight with F-III for 7 and 15 days, respectively, there was fall in fasting blood glucose (38% diabetic; 48% severely diabetic) and improvement in blood glucose during glucose tolerance test (48%) in diabetic rabbits. Further, there was increase in the plasma insulin levels in both diabetic (24.4%) and severely diabetic rabbits (26.3%). The in vitro studies with pancreatic islets showed that the insulin release was nearly two and half times more than that in untreated diabetic rabbits. The mechanism of action of FIII fraction appears to be both pancreatic by stimulating release of insulin and extra pancreatic by directly acting on the tissues.

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90 min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90 min. Ethanolic extract (100 mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90 min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance.

Should surgeons treat diabetes in severely obese people?

Many people enjoy the opportunity of eating more than they need with little requirement for physical exertion. In the USA the proportion of adults aged 20–74 years with a body mass index greater than 30 kg/m 2 Prescott-Clark P Primatesta P Health survey for England 1996. Stationery Office, London1996 Google Scholar has increased from 12-3% in 1976–80 to 22-5% in 1988–94. 1 Flegal KM Carroll MD Kuczmarski RJ Johnson CL Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord. 2000; 22: 39-47 Crossref Scopus (2537) Google Scholar In the UK this proportion rose from 6% to 16% in men and from 8% to 17-3% in women between 1980 and 1996. 2 Prescott-Clark P Primatesta P Health survey for England 1996. Stationery Office, London1996 Google Scholar Obesity predisposes to type 2 diabetes via insulin resistance, impaired glucose tolerance, and pancreatic [3-cell failure, 3 DeFronzo RA The Triumvirate: b-cell, muscle, liver, a collusion responsible for NIDDM. Diabetes. 1987; 37: 667-687 Crossref Google Scholar and largely explains the worldwide increase in this disease. 4 Hodge AM Zimmet P The epidemiology of obesity. Bailliere's Clin Endocrinol Metab. 1994; 8: 577-599 Summary Full Text PDF PubMed Scopus (88) Google Scholar As might be expected, if maintained, the potential benefits of weight loss are remarkable (panel). 5 Jung RT Obesity as a disease. Br Med Bull. 1997; 53: 307-321 Crossref PubMed Scopus (280) Google Scholar Weight loss of 10 kg can achieve greater reductions in HbA1c and fasting plasma glucose than treatment with Metformin, with similar reductions in diabetes-related deaths, and improved control of lipid and blood pressure without the need for additional drug treatment. 6 UK Prospective Diabetes Study (UKPDS) GroupEffect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352: 854-865 Summary Full Text Full Text PDF PubMed Scopus (7402) Google Scholar Weight loss should therefore be the main aim of treatment in overweight individuals with type 2 diabetes, but is rarely achieved. Indeed, weight gain is a major complication of treatment whether with sulphonylureas, insulin, or the thiazolidinediones. In the quest for normoglycaemia, drugs are used as surrogates for weight loss, which alone acts at the cause of the disease. Further weight gain is the price paid for short-term improvement in glucose concentrations. Tabled 1 Based on figure from reference 5 Mortality 20–25% fall in total mortality 30–40% fall in diabetes-related deaths 40–50% fall in obesity-related cancer deaths Blood pressure Fall of 10 mm Hg systolic Fall of 20 mm Hg diastolic Angina 91% reduction in symptoms 33% increase in exercise tolerance Lipids 10% fall in total cholesterol 15% fall in LDL cholesterol 30% fall in triglycerides 8% increase in HDL cholesterol Diabetes >50% reduction in risk of developing diabetes 30–50% fall in fasting blood glucose 15% fall in HbA1c Open table in a new tab

Preliminary studies on the hypoglycaemic effect ofAbroma augusta in alloxan diabetic rats

The hypoglycemic effect of the aqueous extract ofAbroma augusta (Family: Steculiceae) was studied in normal as well as alloxan diabetic rats. Treatement of diabetic rats with 4 ml (4gm dry weight) of agueous extract ofA. augusta for 16 weeks resulted in gradual but significant fall in fasting blood glucose and improvement in glucose tolerance. Serum total and LDL cholesterol and triacylglycerol which increased in diabetic rats showed improvement. These results show that the water extract ofA. augusta has both hypoglycemic and hypocholesterolemic effects.

Blood pressure and metabolic changes during dietary l-arginine supplementation in humans

Dietary l-arginine supplementation has been proposed to reverse endothelial dysfunction in such diverse pathophysiologic conditions as hypercholesterolemia, coronary heart disease, and some forms of animal hypertension. In particular, chronic oral administration of l-arginine prevented the blood pressure rise induced by sodium chloride loading in salt-sensitive rats. To investigate the effects of l-arginine–rich diets on blood pressure and metabolic and coagulation parameters we performed a single-blind, controlled, crossover dietary intervention in six healthy volunteers. The subjects (aged 39 ± 4 years, body mass index [BMI] 26 ± 1 kg/m 2, mean ± SEM) received, in random sequence, three different isocaloric diets, each for a period of 1 week (Diet 1: control; Diet 2: l-arginine enriched by natural foods; Diet 3: identical to Diet 1 plus oral l-arginine supplement). Sodium intake was set at a constant level (about 180 mmol/day) throughout the three study periods. A blood pressure decrease was observed with both l-arginine-rich diets (Diet 2 v 1, SBP: −6.2 mm Hg [95% CI: −0.5 to −11.8], DBP: −5.0 mm Hg [−2.8 to −7.2]; Diet 3 v 1, SBP: −6.2 mm Hg [−1.8 to −10.5], DBP: −6.8 mm Hg [−3.0 to −10.6]). A slight increase in creatinine clearance ( P = .07) and a fall in fasting blood glucose ( P = .008) occurred after Diet 3 and, to a lesser extent, after Diet 2. Serum total cholesterol ( P = .06) and triglyceride ( P = .009) decreased and HDL cholesterol increased ( P = .04) after Diet 2, but not after Diet 3. These results indicate that a moderate increase in l-arginine significantly lowered blood pressure and affected renal function and carbohydrate metabolism in healthy volunteers.

Fenfluramine Increases Insulin Action in Patients With NIDDM

These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently sampled intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a significant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 +/- 1.2 vs. 8.4 +/- 0.89 mM, mean +/- SE, P less than .01) with no significant fall in fasting serum insulin (20 +/- 2 vs. 24 +/- 3 microU/ml) or C-peptide (1.3 +/- 0.2 vs. 1.3 +/- 0.1 nM). During euglycemic-hyperinsulinemic (1 mU.kg-1.min-1) clamp studies there was a significant increase in insulin action from 12.7 +/- 2.3 to 17.3 +/- 1.8 min-1.10(3) microU.ml-1 (P less than .05), although clamp insulin levels were lower after fenfluramine treatment (136 +/- 14 vs. 96 +/- 9 microU/ml, P less than .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 +/- 1.5 vs. 20.1 +/- 2.1 ml.kg-1.min-1, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECTS OF INSULIN TREATMENT ON BODY FLUID VOLUMES AND PLASMA RENIN ACTIVITY IN DIABETES MELLITUS

The effects of insulin treatment on body fluid volumes and plasma renin activity were studied in 7 normotensive non-ketotic diabetic patients. Blood and urine samples were obtained for measurements of fasting blood glucose, daily excretion of urinary glucose, hematocrit, plasma renin activity and plasma aldosterone concentration on the control days of poor metabolic control and twice a week after starting the treatment with insulin. The dosage of insulin was increased by the levels of fasting blood glucose. Body fluid volumes were also measured on the control days and on the 14th day after starting the treatment ; plasma volume and extracellular fluid volume were determined by dilution of Evans blue and sodium thiocyanate, respectively.After starting the treatment, hematocrit decreased and both plasma volume and extracellular fluid volume increased significantly, accompanied by a fall in fasting blood glucose and daily excretion of urinary glucose. Plasma renin activity decreased significantly from 3.9 = 1.6 ng/ ml/hr on the control days to 0.7 ± 0.3 ng/ml/hr on the 14th day ; however, plasma aldosterone concentration did not change. The increase in body fluid volume may be attributable to a sodium-retaining effect of insulin on the kidney and a decrease in osmotic diuresis of urinary glucose. The increase in body fluid volumes may contribute to a fall in plasma renin activity. Further studies are needed to elucidate the reason why plasma aldosterone concentration did not alter.

Glycosylated serum albumin: an intermediate index of diabetic control.

Glycosylated hemoglobin (HbA1) is widely used as an index of glycemic control in diabetic patients. However, due to the long survival time of erythrocytes (120 days), it remains elevated for several weeks after improved control. Other plasma proteins are similarly glycosylated, and as glycosylated serum albumin (GSA) has a shorter half-life (20 days), it should detect glycemic changes earlier. Fasting blood glucose (FBG), GSA, and HbA1 were measured weekly in newly diagnosed diabetic patients (N = 12) for 8 wk after beginning treatment. After 4 wk, a similar fall in FBG and GSA levels, i.e., 72% and 58% respectively, was observed. In contrast, HbA1 fell significantly less (P less than 0.01), by only 39% of its initial value. By 8 wk there was no significant difference between the percentage reduction in the three indices of control. Therefore, GSA provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention and can be regarded as an intermediate index of diabetic control.

Insulin resistance in obese children

Insulin secretion and peripheral insulin sensitivity were studied in 19 grossly obese girls and 17 age-matched non-obese girls by means of the intravenous glucose tolerance test (IVGTT) and the simulated early insulin response test (SERT), respectively. The SERT measures the fall in fasting blood glucose after a short infusion of insulin, performed so as to simulate the early phase of insulin release to an acute stimulus (ERex). At the IVGTT, the obese girls showed significantly increased early insulin response (ERend) in comparison with the non-obese girls. In the SERT, the rise in plasma insulin caused a much smaller decrease in blood glucose in the obese girls than in the reference girls. The relationship between insulin sensitivity and insulin secretion of each subject was evaluated from the plot of the ERex/ERend ratio vs. blood glucose decrement. This showed tKat the hyperinsulinemia of the obese girls frequently did not match the degree of peripheral resistance. The results support the concept that hyper-function of the beta-cells is an effect secondary to the insulin resistance of peripheral tissues.

Plasma growth hormone response to insulin-induced hypoglycemia in diabetes mellitus.

Plasma human growth hormone (HGH) response to insulin-induced hypoglycemia was studied in patients with diabetes mellitus and age and sex matched normal subjects. The diabetics comprised two groups: (a) those with retinopathy, (b) those without retinopathy. Adequate hypoglycemia (50% or a greater fall in fasting blood glucose) was achieved by i.v. administration of insulin 0.1 U/kg body weight in normal subjects and 0.2 U/kg in diabetics. Mean fasting plasma HGH levels did not differ significantly between control subjects (1.39 ± 0.25 SEM, ng/ml), diabetics without retinopathy (1.55 ± 0.25) and diabetics with retinopathy (1.81 ± 0.6). There was a significant rise in plasma HGH, following insulin-induced hypoglycemia in all three groups. When mean Δ HGH or sum HGH value in different groups were compared, no significant difference was observed. However, mean HGH-hypoglycemia index (Δ HGH · 100/nadir blood glucose) was significantly lower in the two diabetic groups as compared to that obtained in control subjects, but it was identical in diabetics with or without retinopathy. In 32% of diabetic patients abnormal blood glucose and plasma HGH responses were observed.