Search PubMed⌕ Search

Biomedical subjects

L C Groop

Publications and source records attributed to L C Groop.

At least 55 records · Page 3Linked to original sources
PubMed1995

Insulin resistance and abnormal albumin excretion in non-diabetic first-degree relatives of patients with NIDDM.

Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes mellitus. To establish whether microalbuminuria in non-diabetic subjects as well is associated with insulin resistance and associated abnormalities in glucose and lipid metabolism, oral glucose tolerance tests were performed with measurement of urinary albumin excretion rate, lipids and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp technique. Abnormal albumin excretion rate (AER), defined as AER 15-200 micrograms/min, was associated with higher systolic blood pressure (p < 0.05), higher fasting glucose values (p < 0.05), lower HDL-cholesterol (p < 0.05) and lower apolipoprotein A-I (p < 0.05) concentrations than observed in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal albumin excretion rate (38.0 +/- 2.8 vs 47.3 +/- 2.4 mumol.kg lean body mass-1.min-1; p = 0.028). This difference was almost completely accounted for by a reduction in non-oxidative glucose metabolism (17.7 +/- 1.9 vs 27.4 +/- 2.7 mumol.kg lean body mass-1.min-1; p = 0.010), which correlated inversely with the AER (r = -0.543; p = 0.013). These results suggest that in non-diabetic individuals genetically predisposed to NIDDM, abnormal AER is associated with insulin resistance and abnormalities in glucose and lipid metabolism.

Albuminuria↗
PubMed1995

Determinants of insulin-stimulated skeletal muscle glycogen metabolism in man.

To examine factors which influence skeletal muscle glycogen synthesis in man, we related insulin sensitivity measured by euglycaemic insulin clamp in 43 healthy males to muscle glycogen synthase (GS) activity, GS protein content (Western blot), glycogen concentrations and fibre composition. Insulin increased muscle glycogen content (P < 0.05) and the change in glycogen content correlated with the GS protein content (r = 0.90, P = 0.01). GS protein concentration correlated inversely with age (r = -0.69, P = 0.04). Non-oxidative glucose disposal was inversely related to per cent type 2B fibres (r = -0.52, P < 0.05). The influence of age on these relationships was separately studied in young (n = 12, age = 26 +/- 2 years) and elderly (n = 15, age = 56 +/- 2 years) males. Insulin increased GS activity significantly only in young subjects (from 17.8 +/- 3.0 to 25.3 +/- 3.2 nmol mg protein-1 min-1; P = 0.015). GS activity and non-oxidative glucose disposal correlated in young (r = 0.69, P = 0.01) but not in the elderly (r = 0.064, P = 0.82) males, and this relationship was not influenced by the degree of obesity. In conclusion, muscle fibre type and GS activity are both determinants of muscle glycogen metabolism in healthy, normoglycaemic males. The close relationship between non-oxidative glucose metabolism and GS activity in young males is altered in ageing.

Adult↗
PubMed1995

Isolation and characterization of the human muscle glycogen synthase gene.

Impaired glycogen synthase (GS) activity in skeletal muscle has been considered to be an inherited trait in patients with non-insulin-dependent diabetes mellitus (NIDDM). We therefore isolated the human muscle GS gene from genomic libraries and determined the genomic structure. The entire coding region, the 5'-flanking region, and the exon-intron boundaries were sequenced. The gene consists of 16 exons spanning approximately 27 kb of DNA and exists as a single copy in the human genome. The negatively charged parts with all known phosphorylation sites were coded by the first and the last exon. A single transcription initiation site was located 167 nucleotides upstream of the initiation codon. All of the exons and the putative promoter region were analyzed by single-strand conformation polymorphism in 30 insulin-resistant Finnish NIDDM patients, and three polymorphic sites were found. A missense mutation Gly464/Ser in exon 11 was found in 2 of 228 NIDDM patients screened but in 0 of 154 control subjects. These two patients were characterized further by severe insulin resistance and premature arteriosclerosis. The characterization of the genomic structure of the human muscle GS gene will facilitate studies of its role in the development of insulin resistance and NIDDM.

Adult↗
PubMed1995

GAD antibodies in NIDDM. Ten-year follow-up from the diagnosis.

OBJECTIVE: To study the frequency of antibodies to glutamic acid decarboxylase (GAD) and islet cell antibodies (ICAs) and their predictive value with respect to the development of insulin deficiency in 133 newly diagnosed middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 126 control subjects and to study the persistence of GAD antibodies in diabetic patients during the follow-up. RESEARCH DESIGN AND METHODS: The study participants consisted of a well-characterized group of 133 middle-aged newly diagnosed patients with NIDDM and 126 control subjects. The follow-up examinations were performed 5 and 10 years after the baseline. The development of absolute and relative insulin deficiency was based on a stimulated C-peptide level that was undetectable or < 0.70 nmol/l, respectively. GAD antibodies were measured retrospectively from stored samples. RESULTS: The overall prevalence of GAD antibody and ICA positivity at the time of diagnosis was 9.0 and 3.8% in diabetic patients and 1.6 and 0% in the control population, respectively. During the 10-year follow-up, 3 (2.3%) and 10 (7.5%) of the diabetic patients developed absolute and relative insulin deficiency, respectively. Of these, two (67%) and six (60%) had been GAD antibody-positive at the time of diagnosis. The sensitivity and specificity of the GAD antibody to predict absolute or relative insulin deficiency were 67 vs. 94% and 60 vs. 95%, while corresponding figures for ICA were 33 vs. 97% and 20 vs. 98%, respectively. The negative predictive value of GAD antibody testing was higher than positive predictive value (97 vs. 50%). During the follow-up, low-grade GAD antibody positivity showed an evanescent nature, whereas the high levels were quite persistent. CONCLUSIONS: In an unselected population of newly diagnosed NIDDM patients, the prevalence of latent autoimmune diabetes in adults was < 10%. While GAD antibody and ICA measured at the time of diagnosis of NIDDM are equally specific predictors of subsequent insulin dependency, the GAD antibody may have a higher sensitivity. Therefore, measurements of GAD antibody may aid the clinician in the choice of treatment of these patients.

Autoantibodies↗
PubMed1994

Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group.

OBJECTIVES: To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers. PATIENTS: Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. INTERVENTION: The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day. MEASUREMENTS: Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months. RESULTS: Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups. CONCLUSIONS: Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.

Adolescent↗
PubMed1994

Effect of insulin on GLUT-4 mRNA and protein concentrations in skeletal muscle of patients with NIDDM and their first-degree relatives.

We examined whether insulin resistance, i.e. impaired insulin stimulated glucose uptake in NIDDM patients and their first-degree relatives is associated with alterations in the effect of insulin on the expression of the GLUT-4 gene in skeletal muscle in vivo. Levels of GLUT-4 mRNA and protein were measured in muscle biopsies taken before and after a euglycaemic insulin clamp from 14 NIDDM patients, 13 of their first-degree relatives and 17 control subjects. Insulin stimulated glucose uptake was decreased in the diabetic subjects (19.8 +/- 3.0 mumol.kg LBM-1.min-1, both p < 0.001) compared with control subjects (44.1 +/- 2.5 mumol.kg LBM-1.min-1) and relatives (39.9 +/- 3.3 mumol.kg LBM-1.min-1). Basal GLUT-4 mRNA levels were significantly higher in diabetic subjects and relatives compared to control subjects (99 +/- 8 and 108 +/- 9 pg/micrograms RNA vs 68 +/- 5 pg/micrograms RNA; both p < 0.01). Insulin increased GLUT-4 mRNA levels in all control subjects (from 68 +/- 5 to 92 +/- 6 pg/micrograms RNA; p < 0.0001), but not in the diabetic patients (from 99 +/- 8 to 90 +/- 8 pg/micrograms RNA, NS), or their relatives (from 94 +/- 9 to 101 +/- 11 pg/micrograms RNA, NS). In the relatives, individual basal GLUT-4 mRNA concentrations varied between 55 and 137 pg/micrograms RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1994

Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle.

We assessed insulin effects on plasma free fatty acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and body mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs. 20.4 +/- 3.5% in young, P < 0.05), by performing sequential euglycemic clamps at five insulin doses (0.6, 1.5, 3, 6, and 15 pmol.min-1.kg-1) in combination with indirect calorimetry and [1-14C]palmitate plus [3-3H]glucose infusion. At baseline, plasma FFA concentration, turnover infusion. At baseline, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were all increased in the elderly (897 +/- 107 vs. 412 +/- 50 mumol/l and 11.2 +/- 1.4 vs. 5.14 +/- 0.86, 3.45 +/- 0.65 vs. 1.37 +/- 0.25, and 4.63 +/- 0.72 vs. 3.01 +/- 0.33 mumol.min-1.kg-1 lean body mass, P < 0.05 for all comparisons), whereas glucose turnover was similar as a result of decreased glucose oxidation (8.2 +/- 1.4 vs. 13 +/- 1.9 mumol.min-1.kg-1 lean body mass, P < 0.05) and increased glucose storage (6.6 +/- 1.4 vs. 1.7 +/- 1.3 mmol.min-1.kg-1 lean body mass, P < 0.05). At all insulin infusions, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were higher in the elderly than in the younger group (P < 0.05). However, if normalized per fat mass, all FFA and lipid metabolic fluxes, both in the postabsorptive state and during hyperinsulinemia, were comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

What is the benefit of increasing the sulfonylurea dose?

OBJECTIVE: To study the clinical benefit of increasing the dose of the sulfonylurea, glipizide, from 10 to 40 mg per day. DESIGN: A placebo-controlled, double-blind, cross-over study. SETTING: An outpatient clinic at the Helsinki University Hospital, Finland. PATIENTS: Twenty-three patients with noninsulin-dependent diabetes mellitus. METHODS: Patients were given glipizide in three different dose schedules for 3 months each: 10 mg in the morning or 10 mg or 20 mg in the morning and the evening. Glycemic control was followed by HbA1c measurements and blood glucose monitoring at home. Beta cell function was assessed by measuring insulin responses to a test meal. RESULTS: Mean home-monitored blood glucose was 12.4 mmol/L during placebo treatment, and it was 9.6, 9.2, and 8.9 mmol/L after treatment with glipizide, 10, 20, or 40 mg, respectively. The levels of blood glucose and HbA1c differed after all treatment groups from placebo (P < 0.001) but not among themselves. The insulin response to a test meal was greatest after 10 mg of glipizide and weakest after 40 mg/d (P = 0.02 compared with the 10-mg dose). All treatments stimulated insulin secretion more than placebo (P < 0.001). CONCLUSIONS: Increasing the glipizide dose to more than 10 mg once daily produces little or no benefit and may reduce beta-cell function.

Aged↗
PubMed1993

Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus.

BACKGROUND: The storage of glucose as glycogen in skeletal muscle is frequently impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their nondiabetic relatives. Despite an intensive search for candidate genes associated with NIDDM, no data have been available on the gene coding for the key enzyme of this pathway, glycogen synthase. METHODS AND RESULTS: Using a human complementary DNA probe, the restriction enzyme Xbal, and Southern blot analysis, we identified two polymorphic alleles, A1 and A2, in the glycogen synthase gene. The gene was localized to chromosome 19. The A1A2 or A2A2 genotype was found in 30 percent of 107 patients with NIDDM but in only 8 percent of 164 nondiabetic subjects without a family history of NIDDM (P < 0.001). The diabetic patients with the A2 allele had a stronger family history of NIDDM (P = 0.019), a higher prevalence of hypertension (P = 0.008), and a more severe defect in insulin-stimulated glucose storage (P = 0.001) than the diabetic patients with the A1 allele. The concentration of the glycogen synthase protein in biopsy specimens of skeletal muscle from the patients with the A2 allele was normal, however, suggesting that expression of the gene was unaltered. The Xbal polymorphism was due to a change of a single base in an intron. CONCLUSIONS: The Xbal polymorphism of the glycogen synthase gene identifies a subgroup of patients with NIDDM characterized by a strong family history of NIDDM, a high prevalence of hypertension, and marked insulin resistance.

Alleles↗
PubMed1993

Human hexokinase II: localization of the polymorphic gene to chromosome 2.

Type 2 (non-insulin-dependent) diabetes mellitus is characterized by decreased levels of glucose 6-phosphate in skeletal muscle. It has been suggested that the lower concentrations of glucose 6-phosphate contribute to the defect in glucose metabolism noted in muscle tissue of subjects with Type 2 diabetes or subjects at increased risk of developing Type 2 diabetes. Lower levels of glucose 6-phosphate could be due to a defect in glucose uptake, or phosphorylation, or both. Hexokinase II is the isozyme of hexokinase that is expressed in skeletal muscle and is responsible for catalysing the phosphorylation of glucose in this tissue. The recent demonstration that mutations in another member of this family of glucose phosphorylating enzymes, glucokinase, can lead to the development of Type 2 diabetes prompted us to begin to examine the possible role of hexokinase II in the development of this genetically heterogeneous disorder. As a first step, we have cloned the human hexokinase II gene (HK2) and mapped it to human chromosome 2, band p13.1, by fluorescence in situ hybridization to metaphase chromosomes. In addition, we have identified and characterized a simple tandem repeat DNA polymorphism in HK2 and used this DNA polymorphism to localize this gene within the genetic linkage map of chromosome 2.

Alleles↗
PubMed1993

Insulin action and substrate competition.

An increased supply of FFAs for oxidation leads to a reduced rate of glucose oxidation and interferes with the inhibitory action of insulin on hepatic glucose production. Available evidence indicates that in humans skeletal muscle is a site for such substrate competition, which involves both pyruvate oxidation and glycogen synthesis. The insulin resistance of obesity is thought to be mostly of metabolic origin, and fully reversible. A reduction in FFA supply by weight reduction can, however, reverse this defect. The insulin resistance associated with NIDDM is thought to be primary, with a strong genetic basis, and partially irreversible. Patients with NIDDM are unable to increase their glucose oxidation normally in response to insulin to meet the energy demands of the body. Increased oxidation of lipids represents a compensatory phenomenon to meet these demands. Therapeutic use of the glucose-FFA cycle to lower blood glucose levels has yielded conflicting results. Studies are in progress to develop agents that inhibit gluconeogenesis by interfering with FFA oxidation. Nicotinic acid derivatives seem to enhance glycogen synthesis acutely by activating glycogen synthetase. Whether these or similar agents can be used to restore impaired glycogen synthesis, the most characteristic genetic defect in NIDDM, cannot be answered until the effect has been proven in chronic studies. The existence of substrate competition between amino acids and glucose, and an intrinsic hypoaminoacidaemic property of amino acids, makes it possible to expand the Randel cycle into a glucose-FFA-amino acid cycle, which integrates control of substrate disposition at the whole body level.

Animals↗
PubMed1993

Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.

UNLABELLED: We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). IN CONCLUSION: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.

Adult↗
PubMed1993

Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease.

The classification of adults with diabetes mellitus can be invalidated by patients who initially present as NIDDM but who later become frankly insulin dependent. In some of these, the pathogenesis could be similar to that in IDDM, namely autoimmune destruction of the pancreatic beta-cells. We studied 102 patients > 35 yr of age at diabetes onset who had initially been nonketotic and non-insulin-dependent for > or = 6 mo. They were classified according to glucagon-stimulated C-peptide levels into an insulin-deficient group (n = 33) and a non-insulin-deficient group (n = 69). We measured antibodies to GAD, islet cell cytoplasm, thyroid antigens, and gastric parietal cells in both groups. Anti-GAD was significantly higher in the insulin deficient group, 76% (25 of 33), than in the non-insulin deficient group, 12% (8 of 69), and this difference was substantially greater than that shown for ICAs. Thus, in a proportion of adults who present with NIDDM, a slowly evolving autoimmune insulitis can be revealed by testing for anti-GAD. This could have important connotations not only for early intervention, but also for the correct classification of diabetes.

Adult↗
PubMed1993

The relationship between early insulin release and glucose tolerance in healthy subjects.

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Therefore insulin and C-peptide responses to oral glucose were measured in healthy subjects with and without a single dose of oral and intravenous glipizide. The intravenous glipizide administration caused a marked early insulin response, whereas oral glipizide administration resulted in greater total and peak insulin concentration. Oral glipizide did not reduce plasma glucose until 45 min of the glucose load. In contrast, enhancement of the early insulin response with intravenous glipizide almost completely prevented postprandial glucose rise. In conclusion, early insulin release is a major factor determining oral glucose tolerance in healthy subjects.

Adult↗
PubMed1992

Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration.

OBJECTIVE: To investigate the predictive value of microalbuminuria (albumin excretion rate 30-300 mg/24 h) as a risk factor for overt diabetic nephropathy in patients with longstanding insulin dependent diabetes. DESIGN: 10 year follow up of patients with normoalbuminuria (albumin excretion rate < 30 mg/24 h), microalbuminuria (30-300 mg/24 h), and macroalbuminuria (> 300 mg/24 h) based on two out of three timed overnight urine samples. SETTING: Outpatient clinic of Helsinki University Hospital. SUBJECTS: 72 consecutive patients who had had insulin dependent diabetes for over 15 years. MAIN OUTCOME MEASURES: Urinary albumin excretion rate, mortality, and prevalence of diabetic complications after 10 years. RESULTS: 56 patients were re-examined at 10 year follow up, 10 had died, five were lost to follow up, and one was excluded because of non-diabetic kidney disease. At initial screening 22 patients had macroalbuminuria, 18 had microalbuminuria, and 26 had normal albumin excretion. Only five (28%, 95% confidence interval 10% to 54%) of the microalbuminuric patients developed macroalbuminuria during the 10 year follow up and none developed end stage renal failure. Two (8%, 1% to 25%) normoalbuminuric patients developed macroalbuminuria and four (15%, 4% to 35%) became microalbuminuric. Seven (32%, 14% to 55%) of the macroalbuminuric patients developed end stage renal failure and six (27%, 11% to 50%) died of cardiovascular complications. CONCLUSION: Microalbuminuria is not a good predictor of progression to overt nephropathy in patients with longstanding insulin dependent diabetes.

Adult↗
PubMed1992

Insulin resistance in type 2 (non-insulin-dependent) diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle.

To study whether insulin resistance in Type 2 (non-insulin-dependent) diabetes mellitus is due to a defect in the expression of the insulin-responsive glucose transporter gene (GLUT-4) in human skeletal muscle, we measured the level of GLUT-4 mRNA and (in some of the subjects) its protein in muscle biopsies taken from 14 insulin-resistant patients with Type 2 diabetes, 10 first-degree relatives of the diabetic patients and 12 insulin-sensitive control subjects. Insulin sensitivity was measured with a + 45 mU.m2(-1).min-1 euglycaemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. GLUT-4 mRNA was measured using a human GLUT-4 cDNA probe and GLUT-4 protein with a polyclonal antibody specific for the 15 amino acid carboxy-terminal peptide. Both Type 2 diabetic patients and their relatives showed impaired stimulation of total-body glucose disposal by insulin compared with control subjects (29.5 +/- 2.1 and 34.0 +/- 4.8 vs 57.9 +/- 3.1 mumol.kg lean body mass-1.min-1; p less than 0.01). This impairment in glucose disposal was primarily accounted for by a reduction in insulin-stimulated storage of glucose as glycogen (13.0 +/- 2.4 and 15.6 +/- 3.9 vs 36.9 +/- 2.2 mumol.kg lean body mass-1.min-1; p less than 0.01). The levels of GLUT-4 mRNA expressed both per microgram of total RNA and per microgram DNA, were higher in the diabetic patients compared with the control subjects (116 +/- 25 vs 53 +/- 10 pg/microgram RNA and 177 +/- 35 vs 112 +/- 29 pg/microgram DNA; p less than 0.05, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗