Diabetic Volunteers Research Articles

Plasma Adiponectin and Leptin Levels, Body Composition, and Glucose Utilization in Adult Women With Wide Ranges of Age and Obesity

The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span. We studied 148 women aged 18-81 years with a BMI range of 17.2-44.3 kg/m(2). Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose utilization (M) was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol x m(-2) x min(-1)). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (<40, 40-59, and >or=60 years, respectively), as well as by glucose tolerance status. Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, VO(2max), and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P < 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and BMI, percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P < 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P < 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and VO(2max). The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat, insulin, and leptin levels in women. Adiponectin is positively associated with M across the age span in women.

A preliminary evaluation of a novel method to monitor a triple antioxidant combination (vitamins E, C and α-lipoic acid) in diabetic volunteers using in vitro methaemoglobin formation

Eight otherwise healthy diabetic volunteers took a daily antioxidant supplement consisting of vitamin E (200 IU), vitamin C (250 mg) and α-lipoic acid (90 mg) for a period of 6 weeks. Diabetic dapsone hydroxylamine-mediated methaemoglobin formation and resistance to erythrocytic thiol depletion was compared with age and sex-matched non-diabetic subjects. At time zero, methaemoglobin formation in the non-diabetic subjects was greater at all four time points compared with that of the diabetic subjects. Resistance to glutathione depletion was initially greater in non-diabetic compared with diabetic samples. Half-way through the study (3 weeks), there were no differences between the two groups in methaemoglobin formation and thiol depletion in the diabetic samples was now lower than the non-diabetic samples at 10 and 20 min. At 6 weeks, diabetic erythrocytic thiol levels remained greater than those of non-diabetics. HbA 1c values were significantly reduced in the diabetic subjects at 6 weeks compared with time zero values. At 10 weeks, 4 weeks after the end of supplementation, the diabetic HbA1 c values significantly increased to the point where they were not significantly different from the time zero values. Total antioxidant status measurement (TAS) indicated that diabetic plasma antioxidant capacity was significantly improved during antioxidant supplementation. Conversion of α-lipoic acid to dihydrolipoic acid (DHLA) in vivo led to potent interference in a standard fructosamine assay kit, negating its use in this study. This report suggests that triple antioxidant therapy in diabetic volunteers attenuates the in vitro experimental oxidative stress of methaemoglobin formation and reduces haemoglobin glycation in vivo.

Dissociation of augmented physiological, hormonal and cognitive responses to hypoglycaemia with sustained caffeine use

In patients with Type I diabetes and healthy volunteers, ingestion of modest amounts of caffeine augments the usual symptomatic and counter-regulatory responses to hypoglycaemia. The aim of the present study was to determine whether these are lost with sustained caffeine use, i.e. does tolerance develop? Eleven healthy caffeine consumers underwent two identical hyperinsulinaemic glucose clamp procedures. For 7 days prior to each clamp, subjects consumed a caffeine-free diet supplemented with 200mg of caffeine capsules twice daily (caffeine-replete) or placebo (caffeine-withdrawn). During each clamp, blood glucose was held for 80min at 4.5mmol/l and then 2.5mmol/l. At 85min, subjects were given a 200mg caffeine capsule. Measurements were taken of symptoms, plasma catecholamine, middle cerebral artery blood velocity (VMCA) and cognition. Following the acute caffeine challenge and during hypoglycaemia, VMCA fell only in the caffeine-withdrawn condition [-5.1 (-7.3, -3.0)cm/s compared with -1.9 (-4.0, +0.2) cm/s in caffeine-replete condition; P&lt;0.04; values are differences (95% confidence intervals)]. Plasma catecholamine levels and global cognitive performance were unaffected by caffeine status, whereas tests of executive intellectual function were better preserved during hypoglycaemia in the caffeine-replete condition (P&lt;0.05). The influence of caffeine on hypoglycaemic symptomatic awareness depended upon the duration of the hypoglycaemic stimulus. At onset, symptoms were more intense in caffeine-withdrawn state (P&lt;0.01); however, with increasing duration of hypoglycaemia, symptom intensity was greater in caffeine-replete condition (P&lt;0.05). Thus previous caffeine consumption influences the physiological and symptomatic responses to acute hypoglycaemia, but complete tolerance does not develop with sustained use.

Oral arginine has no acute effect on blood glucose concentrations or glucose production in type 2 diabetic volunteers

A 49-year old male with type 2 diabetes mellitus was given 3 grams (gm) of oral arginine per hour for 10-hours, the effects on plasma glucose, insulin, C-peptide and glucose concentrations were determined. Oral arginine administration decreased plasma glucose concentrations and glucose production by approximately 40% over an 8-hr study (5%/hr). Supplemental arginine is inexpensive and may provide physicians with an additional tool in the treatment of type 2 diabetes. Six obese volunteers with type 2 diabetes were studied to document the effects of oral arginine on fasting glucose concentration and glucose production rate (GPR). Patients were admitted to the General Clinical Research Center for a 3-day stay. Oral arginine was ingested at 3-gm per hour starting at 4 am until 2 pm on day 2 or day 3 (randomized to arginine or to no-arginine supplement). Oral arginine administration was well tolerated and failed to increase C-peptide or insulin concentrations over the 10-hr period of administration. Unlike what was documented in the first diabetic patient, the prospective administration of oral arginine failed to reduce glucose concentrations (9.9 ± 1.8 vs 10.3 ± 1.8 mM) or GPR (14.7 ± 1.5 vs 15.7 ± 2.3 μmol/kg/min; arginine vs no-arginine; NS). The fall in blood glucose over the 8-hour period was not significantly increased during oral arginine administration (3.3% vs 2.6% per hour, arginine vs no-arginine, NS). These data demonstrate that 3-gm per hour of oral arginine had no effect on GPR or fasting blood glucose concentration in obese type 2 diabetic volunteers.

Evaluation of the VIA-GLU Blood Glucose Monitor in Healthy and Diabetic Volunteers

Evaluation of the VIA-GLU Blood Glucose Monitor in Healthy and Diabetic Volunteers

Dislipidemia pós-prandial como achado precoce em indivíduos com baixo risco cardiovascular

OBJETIVO: correlacionar a hipertrigliceridemia pós-prandial com conhecidos fatores de risco para aterosclerose. MATERIAL E MÉTODOS: Foram estudados 47 pacientes não diabéticos (30 mulheres e 17 homens, idade: 40,5 ± 14,9 anos, IMC: 26,1 ± 5,4kg/m²) com trigliceridemia de jejum normal (&lt;200mg/dl). Triglicerídeos, HDL e colesterol total foram medidos nos tempos 0, 3 e 5 horas após ingestão de aproximadamente 70g de gordura (200g de creme de leite a 25% e 2 gemas), sendo então avaliados vários parâmetros. RESULTADOS: Pacientes com pico de triglicerídeos de 3 horas maior que o 2º quartil (164,8mg/dl), apesar de triglicerídeos de jejum normais, apresentaram maior IMC (28,1 ± 5,6 vs. 24,2 ± 4,5kg/m²; p= 0,008), maior circunferência abdominal (95,7 vs. 84,1cm; p= 0,001), maior relação cintura/qudril (0,92 vs. 0,86; p= 0,008), maior pressão diastólica (83,1 vs. 77,2mmHg; p= 0,02) e menor HDL (39,1 vs. 48,3mg/dl; p= 0,008). CONCLUSÕES: A hipertrigliceridemia pós-prandial se correlaciona com vários fatores de risco cardiovascular mesmo em pacientes normotrigliceridêmicos.

The effect of different vasoconstrictor containing local anaesthetic solutions on plasma glucose in normal and diabetic-volunteers

In this study, the change in plasma glucose half an hour after injection of different vasoconstrictors contained in local anaestheticsolution where measured both in normal and diabetic volunteers. Single cartridge contain (1.8) ml of plain (2%) Xylocain or that with (1:80000) concentration of a adrenaline or (3%) prilocain with (0.03) IU of felypressin injected at labial to left maxillary lateral incisor region. The result showed that half an hour after injection of a adrenaline containing solution, a very highly significant increase in plasma glucose noticed in both study groups from pre-injection base line value (p<0.001). Increase in plasma glucose in diabetic group were significantly greater than that in normal control group (p<0.05). Within diabetic volunteers, this increase were significantly greater in insulin dependent diabetic group than that in non insulin dependent volunteers. After injection of plain solution or that containing felypressin, reduction in plasma glucose noticed. In conclusion, adrenaline contained within local anaesthetic solution produce hyperglycemic effect even in dose of single dental cartridge. This response enhanced in diabetic patient in general with greater enhancement noticed in insulin dependent patient.

Beneficial role of amino acids in mitigating cytoskeletal actin glycation and improving F-actin content: in vitro.

The actin filaments present in circulating leukocytes facilitate their passage through microvenules and capillaries by helping in their deformability. Decreased deformability of granulocytes is now known to cause occlusion of the retinal microcapillaries leading to hypoxia and the subsequent development of diabetic retinopathy. Structural and functional loss of proteins, due to non-enzymatic glycation and glycoxidation, has been reported to cause diabetic pathogenesis. As amino acids have been earlier reported to have antidiabetic properties, the present study involves the investigation of the susceptibility of the cytoskeletal actin to glycation and its mitigation by free amino acids. This study also involves quantifying F-actin in cultured mononuclear cells obtained from diabetic and normal healthy volunteers and on the effect of glucose and free amino acids on F-actin content. Commercial non-muscle actin and actin immuno-pre-cipitated from granulocytes obtained from (a) normal healthy human volunteers and (b) patients with type 2 diabetes mellitus were subjected to glycation studies using [U] (14)C glucose. The effect of free amino acids, as antiglycating agents, was determined using various concentrations of lysine, arginine, alanine, aspartic acid and glutamic acid. F-actin content in cultured mononuclear cells was estimated by flow cytometry using fluorescein isothiocynate (FITC)-Phalloidin. Commercial actin at physiological conditions of pH and temperature was found to undergo non-enzymatic glycation. The extent of in vitro glycation was significantly low (P<0.001) in actin isolated from patients with type2 diabetes when compared to the non-diabetic group, suggesting an increased in vitro structural modification of actin in patients with diabetes. All the free amino acids tested were found to have varying degrees of antiglycating effect. The F-actin content in the intact mononuclear cells obtained from diabetic patients was found to be low when compared with normal healthy volunteers (P<0.001). Similarly the F-actin content was significantly low when the normal mononuclear cells were incubated with glucose. This effect was reversed upon the addition of free amino acids to the incubation mixture. Free amino acids can play a positive role in improving leukocyte deformability by mitigating cytoskeletal actin glycation and improving F-actin content.

Postabsorptive muscle protein metabolism in type 1 diabetic patients after pancreas transplantation.

Insulin was shown to induce protein anabolism in vivo mainly by inhibiting proteolysis. Heterotopic pancreas transplantation in type 1 diabetes mellitus is characterized by peripheral hyperinsulinemia due to systemic rather than portal insulin delivery. Therefore, we studied the postabsorptive muscle protein metabolism in type 1 diabetic patients with or without pancreas transplantation. The forearm balance technique was performed in 9 type 1 diabetic patients on exogenous insulin treatment, in 4 type 1 diabetic patients following successful pancreas transplantation and in 6 healthy volunteers. Labelled leucine and phenylalanine were infused to quantify whole-body and muscle protein synthesis, respectively. In the postabsorptive state, whole-body protein synthesis (leucine kinetics) was similar in pancreas-transplanted patients and controls. In contrast, muscle protein synthesis tended to be less negative in pancreas-transplanted patients with respect to type 1 diabetic patients and healthy volunteers. The present data suggest that recipients with peripheral insulin delivery and chronic hyperinsulinemia are characterized by a preferential stimulation of protein synthesis in muscle rather than in the splanchnic district. When insulin was infused acutely, while maintaining euglycemia, the whole-body and muscle protein synthesis rates were approximately halved in type 1 diabetic patients with and without pancreas transplantation. We conclude that pancreas transplantation is able to normalize basal and insulin-stimulated protein metabolism. Chronic hyperinsulinemia counteract steroid-induced protein degradation by means of a mild, but persistent stimulation of muscle protein synthesis.

CHANGES IN THE TEAR PROTEIN PATTERNS OF DIABETIC PATIENTS USING TWO-DIMENSIONAL ELECTROPHORESIS.

Four to five million Germans suffer from diabetes mellitus, and worldwide there are about 100 million people that suffer with the disease. In diabetic patients, dry eye and other ocular surface diseases occur more often than in healthy subjects. Very little is known about the alterations in tears caused by diabetes mellitus, or its influence on the pathogenesis of e.g., the dry eye disease. Recent studies from our group showed that there are differences in the one-dimensional electrophoretic tear protein separations between diabetic patients and healthy volunteers.1,2 The aim of this study is to analyze the tear protein patterns of patients suffering from diabetes (DIA) (Fig.l), and to compare them to the patterns of healthy subjects (CTRL) using two-dimensional electrophoretic techniques.

Use of in vitro methaemoglobin generation to study antioxidant status in the diabetic erythrocyte

Poor glycaemic control in diabetes and a combination of oxidative, metabolic, and carbonyl stresses are thought to lead to widespread non-enzymatic glycation and eventually to diabetic complications. Diabetic tissues can suffer both restriction in their supply of reducing power and excessive demand for reducing power. This contributes to compromised antioxidant status, particularly in the essential glutathione maintenance system. To study and ultimately correct deficiencies in diabetic glutathione maintenance, an experimental model would be desirable, which would provide in vitro a rapid, convenient, and dynamic reflection of the performance of diabetic GSH antioxidant capacity compared with that of non-diabetics. Xenobiotic-mediated in vitro methaemoglobin formation in erythrocytes drawn from diabetic volunteers is significantly lower than that in erythrocytes of non-diabetics. Aromatic hydroxylamine-mediated methaemoglobin formation is GSH-dependent and is indicative of the ability of an erythrocyte to maintain GSH levels during rapid thiol consumption. Although nitrite forms methaemoglobin through a complex GSH-independent pathway, it also reveals deficiencies in diabetic detoxification and antioxidant performance compared with non-diabetics. Together with efficient glycaemic monitoring, future therapy of diabetes may include trials of different antiglycation agents and antioxidant combinations. Equalization in vitro of diabetic methaemoglobin generation with that of age/sex-matched non-diabetic subjects might provide an early indication of diabetic antioxidant status improvement in these studies.

Chronic Consumption of Short-Chain Fructooligosaccharides Does Not Affect Basal Hepatic Glucose Production or Insulin Resistance in Type 2 Diabetics

Short-chain fructooligosaccharides (FOS) are prebiotics, which escape digestion in the small intestine and are fermented by the colonic microflora into short-chain fatty acids. Recently, we found that the daily consumption of 20 g FOS decreased basal hepatic glucose production in healthy subjects without any effect on insulin-stimulated glucose metabolism. In this study, we evaluated the effects of the chronic ingestion of FOS on plasma lipid and glucose concentrations, hepatic glucose production and insulin resistance in type 2 diabetics. Type 2 diabetic volunteers (n = 10; 6 men, 4 women) received either 20 g/d FOS or sucrose for 4 wk in a double-blind crossover design. FOS did not modify fasting plasma glucose and insulin concentrations or basal hepatic glucose production. The plasma glucose response to a fixed exogenous insulin bolus did not differ at the end of the two periods. Erythrocyte insulin binding also did not differ. Serum triacylglycerol, total and HDL cholesterol, free fatty acid, apolipoproteins A1 and B and lipoprotein (a) concentrations were not modified by the chronic ingestion of FOS. We conclude that 4 wk of 20 g/d of FOS had no effect on glucose and lipid metabolism in type 2 diabetics.

A long-term comparison between enalapril and captopril on insulin sensitivity in normotensive non-insulin dependent diabetic volunteers

There are conflicting reports about the effects of angiotensin converting enzyme inhibitors on insulin sensitivity and glycaemic control. In addition, the chronic effects of ACEI on insulin sensitivity in normotensive but insulin resistant individuals have been controversial. To determine the long-term effects of low-dose captopril or enalapril on insulin sensitivity and lipid parameters in normotensive non-insulin dependent diabetic volunteers. Twenty-eight normotensive non-insulin dependent diabetes mellitus subjects on diet alone or diet plus oral hypoglycaemic agents were randomized in a single-blind cross-over study to receive either captopril (12.5 mg daily) or enalapril (5 mg daily). Initially, captopril was compared with enalapril for 28 days with a 28-day washout period between drug regimens. For the long-term study, the subjects then remained on the second ACEI for a further 11 months. Insulin sensitivity was measured using the isoglycaemic hyperinsulinaemic clamp (insulin infusion rate 20 mIU/kg/min) at the start and completion of each part of the cross-over study and then at 3, 6 and 12 months of drug therapy. Fasting glucose, insulin, HbA1, lipids and lipoproteins were measured at the start of each clamp. No first or second order carry-over effects were demonstrated between the ACEIs. No differences were detected between enalapril and captopril on insulin sensitivity at any of the time points. Statistically significant hypotension was avoided, and at doses used the ACEIs did not modify any parameters of glycaemic control over the 12-month study period. There were no significant alterations in plasma cholesterol, triglycerides, HDL cholesterol or Apo A1 levels during the study. Long-term low-dose ACEIs (captopril/enalapril) do not modify insulin sensitivity, glycaemic control or lipids in normotensive non-insulin dependent diabetic subjects.

Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient

Diabetics would benefit greatly from a device capable of providing continuous noninvasive monitoring of their blood glucose levels. The optical scattering coefficient of tissue depends on the concentration of glucose in the extracellular fluid. A feasibility study was performed to evaluate the sensitivity of the tissue reduced scattering coefficient in response to step changes in the blood glucose levels of diabetic volunteers. Estimates of the scattering coefficient were based on measurements of the diffuse reflectance on the skin at distances of 1-10 mm from a point source. A correlation was observed between step changes in blood glucose concentration and tissue reduced scattering coefficient in 30 out of 41 subjects measured.

Glycaemic Response to Selected Cereal-based South Indian Meals in Non-insulin-dependent Diabetics

There is a lack of data on the glycaemic response of Indian foods, particularly that of South Indian foods. In South India the bulk comes from cereal-based carbohydrates. The glycaemic response of three different meals in 20 non-insulin-dependent diabetic volunteers was therefore assessed. Each meal was isocaloric and balanced. Each meal comprised 60% carbohydrate, 20% protein and 20% fat, varying only in the type of carbohydrate. The carbohydrate exchange in each meal (rice, wheat and ragi, which form important staple foods of South Indians) contributed 39% of the total calories of the meal. The wheat-based meal showed the lowest glycaemic response, followed by ragi. The results confirmed the important role played by wheat in diabetic diets because of its blood sugar-reducing properties.

Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro III: Effect of diabetes

The fate of dapsone hydroxylamine has been investigated in diabetic and normal human erythrocytes. In erythrocytes from four type 1 (insulin dependent) diabetic subjects, there was a significant decrease in dapsone hydroxylamine-mediated methaemoglobin formation compared with cells drawn from normal individuals (P < 0.01). However, the ability of the diabetic cells to detoxify the hydroxylamine to dapsone was not correspondingly reduced and was not different to normal cells. The initial rate of the accelerating effect of diethyl dithiocarbamate (DDC) on hydroxylamine-mediated methaemoglobin and dapsone formation was significantly reduced in diabetic compared with normal cells. There was no significant difference in hydroxylamine-dependent methaemoglobin formation between diabetic erythrocytes pretreated with either statil or sorbinil and untreated diabetic cells. Dapsone recovery in diabetic erythrocytes incubated with statil was not significantly different from statil-free incubations. However, in the presence of sorbinil, there was a marked reduction in dapsone formation at all four time points, ( P < 0.001 at 15 min). Mean measured levels of glutathione did not differ significantly between the normal (380 ± 30.9 mg/L; N = 8) and diabetic (349 ± 58.7 mg/L; N = 8) volunteers. In summary, although diabetic erythrocytes were less sensitive to the effect of dapsone hydroxylamine-mediated methaemoglobin formation in comparison with normal cells, glutathione-dependent hydroxylamine reduction to dapsone was unaffected.

An improved technique for the 2H/1H analysis of urines from diabetic volunteers.

The H2-H2O ambient-temperature equilibration technique for the determination of 2H/1H ratios in urinary waters from diabetic subjects provides improved accuracy over the conventional Zn reduction technique. The standard deviation, approximately 1-2%, is at least a factor of three better than that of the Zn reduction technique on urinary waters from diabetic volunteers. Experiments with pure water and solutions containing glucose, urea and albumen indicate that there is no measurable bias in the hydrogen equilibration technique.

Development of a Miniaturized Glucose Monitoring System by Combining a Needle-Type Glucose Sensor With Microdialysis Sampling Method: Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients

To develop a reliable and practical glucose monitoring system by combining a needle-type glucose sensor with a microdialysis sampling technique for long-term subcutaneous tissue glucose measurements. A microdialysis Cuprophan hollow-fiber probe (inner diameter, 0.20 mm; length, 15 mm) was perfused with isotonic saline solution (120 microliters/h) and glucose concentrations in the dialysate were measured by a needle-type glucose sensor extracorporeally. This system was tested both in vitro and in vivo. Subcutaneous tissue glucose concentrations were then monitored continuously in 5 healthy and 8 diabetic volunteers for 7 to 8 days. A hollow-fiber probe was inserted into the abdominal subcutaneous tissue. This monitoring system achieved excellent results in vitro. Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to > 27.8 mM glucose, with a time delay of 6.9 +/- 1.2 min associated with a rise in glucose and 8.8 +/- 1.6 min with a fall in the glucose level (means +/- SE). The overall correlation between subcutaneous tissue (Y) and blood (X) glucose concentration was Y = 1.08X + 0.19 (r = 0.99). The subcutaneous tissue glucose concentration could be monitored precisely for 4 days without any in vivo calibrations and for 7 days by introducing in vivo calibrations. Glycemic excursions could be monitored precisely in the subcutaneous tissue by this microdialysis sampling method with a needle-type glucose sensor in ambulatory diabetic patients.

Intensive Insulin Therapy and Weight Gain in IDDM

Intensive insulin therapy is frequently complicated by excessive weight gain. The purpose of this study was to determine the cause and composition of this weight gain. Therefore, changes in body composition, energy expenditure, glycosuria, and substrate kinetics were evaluated in patients with IDDM who transferred from conventional insulin therapy to intensive insulin therapy. Six adult patients with IDDM were studied on conventional insulin therapy and after 2 mo of intensive insulin therapy while maintaining constant caloric intake and were compared with a group of 6 matched nondiabetic volunteers. Body composition was determined by underwater weighing. Energy expenditure was measured during 24-h stays in a whole-room calorimeter. Whole-body turnover rates of glucose, glycerol, palmitate, and leucine were determined by isotope dilution methods. Intensive insulin therapy lowered the mean daily blood glucose concentration and HbA1 (14.8 +/- 1.6 to 7.7 +/- 0.6 mM and 12.9 +/- 0.9 to 9.6 +/- 0.6%, both P < 0.01) and almost eliminated glycosuria (428 +/- 116 to 39 +/- 22 mmol/day, P < 0.05). Body weight increased 2.6 +/- 0.8 kg with intensive insulin therapy (P < 0.05) as a result of an increase in fat mass (2.4 +/- 0.8 kg, P < 0.05). Daily energy expenditure decreased 5% (118 +/- 32 kcal/day) with intensive insulin therapy (P < 0.05). The rates of glucose, glycerol, free fatty acid, and leucine turnover, triglyceride/free fatty acid cycling, and nonoxidative glucose and protein disposal were reduced in the diabetic volunteers during intensive insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Metformin Increases Glucose Transporter Protein and Gene Expression in Human Fibroblasts

To investigate the effect of the antihyperglycemic drug metformin on glucose transporter protein and gene expression, skin fibroblasts obtained from normal and diabetic volunteers were grown in culture and incubated with metformin at various concentration for up to 16 days. Metforinin caused a dose and time dependent increase in GLUT1 number with a maximum at a concentration of 10 μg metformin given over 4 days. This was accompanied by an increase in GLUT1 mRNA, suggesting that metformin has a stimulating effect on glucose transporter gene expression. No significant difference was observed between cells obtained from type H diabetic patients and those from controls. We conclude that in human fibroblasts GLUT1 de novo synthesis is involved in the long term effect of metformin on glucose transport.