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Biomedical subjects

U Smith

Publications and source records attributed to U Smith.

At least 73 records · Page 4Linked to original sources
PubMed1996

Insulin action and age. European Group for the Study of Insulin Resistance (EGIR).

Evidence that age is associated with insulin resistance is discordant. We analyzed euglycemic insulin clamp (1 mU x min(-1) x kg(-1)) data collected at 20 centers throughout Europe from 1,146 men and women with normal glucose tolerance, ranging in age from 18 to 85 years. In the whole group, insulin action (as the M value) declined slightly with age (at a rate of 0.9 micromol x min(-1)-kg(-1) per decade of life, 95% CI = 0.4-1.3, P = 0.0002). When adjusted for BMI, this relationship was no longer statistically significant. The same result was obtained whether insulin action was expressed per kilogram of body weight or per kilogram of fat-free mass, expressed as the M:I ratio, or estimated from fasting plasma insulin concentrations. Subgroup analysis showed that a significant BMI-adjusted decrease in insulin action with age was present only in lean (BMI <25 kg/m2) women (a rate of 1.6 micromol x min(-1) x kg(-1) per decade, 95% CI = 0.6-2.5, P = 0.001), in whom percentage fat mass also increased with age (by 0.38% body weight per decade, P = 0.0007). Insulin action was positively associated with insulin suppression of circulating free fatty acids (FFAs) (+1.5 micromol x min(-1) x kg(-1) for each 10% increase in FFA suppression, P < 0.0001) in a multivariate model accounting for sex, BMI, age, and fasting FFA levels. Furthermore, insulin suppression of FFAs improved with age in men (2% per decade, P < 0.0001) but not in women. In the subgroup of lean women in whom insulin action declined with age, adding FFA suppression to a multiple regression equation canceled the association between age and insulin action. Thus, the small effect of age on insulin action could be adequately explained on the basis of age-related changes in body composition and substrate competition. We conclude that in healthy Europeans, age per se is not a significant cause of insulin resistance of glucose metabolism or lipolysis.

Adult↗
PubMed1996

Gastric emptying in type 2 diabetes: quick or slow?

Although it is now widely accepted that around one-half of patients with Type 1 diabetes have delayed gastric emptying of both solid and liquid meals, the situation with respect to patients with Type 2 diabetes is less clear cut. Recent reports in the literature suggest that gastric emptying, at least of liquids, is more rapid than normal for patients with "early' Type 2 diabetes, whereas patients with later stages of the disease may have delayed or normal emptying of solids. Given the large number of possible confounding factors, such as age, gender, and previous dietary history in this population, as well as the influences of hyperglycaemia and hyperinsulinaemia on gastric emptying, this area clearly requires further investigation under more stringent conditions.

Blood Glucose↗
PubMed1995

Hyperinsulinaemia impairs gastrointestinal motility and slows carbohydrate absorption.

Experimental euglycaemic hyperinsulinaemia (insulin levels 46 +/- 4 mU/l) impaired the post-absorptive gastrointestinal motility in healthy individuals; the effect being particularly pronounced in the upper gastrointestinal tract (stomach and proximal duodenum). The postprandial gastric emptying, measured with a standardized 99mTc labelled meal, was also significantly delayed (t50 increased by 38% or 32 min). This was combined with a slower carbohydrate absorption (delay in peak blood glucose level about 40 min). Furthermore, during experimental hyperinsulinaemia higher blood glucose levels were seen at 120 min than at 60 min after food ingestion. This was not seen in any subject in the control study where only 0.9% NaCl was infused. Blood levels of the motility-stimulating hormone, motilin, were significantly lower during experimental hyperinsulinaemia. Thus, experimental hyperinsulinaemia impairs the gastrointestinal motility in both the postabsorptive and postprandial states. This effect is combined with a delayed carbohydrate absorption. Hyperinsulinaemia per se may thus lead to alterations in carbohydrate absorption and can also contribute to the gastrointestinal disturbances in diabetes.

Acute Disease↗
PubMed1995

Microdialysis assessment of adipose tissue metabolism in post-absorptive obese NIDDM subjects.

Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with 133Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 +/- 0.7 mmol L-1) (mean +/- SEM) and nine obese non-diabetic subjects (glucose, 4.9 +/- 0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 +/- 110 vs. 876 +/- 59 mumol L-1 (P < 0.05) for lactate and 75 +/- 10 vs. 66 +/- 8 mumol L-1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 +/- 63 vs 1107 +/- 64 mumol L-1 and 314 +/- 28 vs. 311 +/- 17 mumol L-1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5 +/- 0.2 vs 2.4 +/- 0.3 mL 100 g-1 min-1) (P < 0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 +/- 0.4 vs 2.4 +/- 0.8 and 2.1 +/- 0.4 vs 3.1 +/- 0.5 mumol kg-1 min-1 in NIDDM and control subjects, respectively). Thus, in the post-absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Lipid intolerance in smokers.

OBJECTIVES: Smokers have recently been shown to be insulin resistant and to exhibit several characteristics of the insulin resistance syndrome (IRS). In this study, we assessed fasting and postprandial lipid levels in healthy, normolipidaemic, chronic smokers and a matched group of non-smoking individuals. DESIGN: A standardized mixed meal (containing 3.78 MJ and 51 g of fat) was given in the morning after an overnight fast. The smokers were either abstinent from tobacco for 48 h or were allowed to smoke freely, including being allowed to smoke six cigarettes during the study. SUBJECTS: Twenty-two middle-aged, healthy male subjects, nine habitual smokers and 13 non-smoking control subjects, were recruited to the study. The smokers had all been smoking at least 10 cigarettes per day for at least 10 years. RESULTS: The smokers exhibited a lipid intolerance in that their postprandial increase in triglyceride levels was more than 50% higher than in the non-smokers' group. This lipid intolerance could not be discerned in the postabsorptive state because the fasting triglyceride levels were the same in both groups, while the smokers had significantly lower high-density lipoprotein (HDL) cholesterol. The peak postprandial triglyceride level correlated closely and negatively with fasting HDL cholesterol, indicating an impaired lipolytic removal capacity in smokers. CONCLUSIONS: Healthy, normotriglyceridaemic smokers exhibit an abnormal postprandial lipid metabolism consistent with lipid intolerance. It is suggested that postprandial hyperlipidaemia is a characteristic trait of the insulin resistance syndrome and that the defect in lipid removal is related to the low HDL cholesterol in this syndrome. The insulin resistance syndrome is likely to be an important reason for the increased propensity for cardiovascular disease in smokers.

Eating↗
PubMed1995

Characterization of the insulin-antagonistic effect of growth hormone in insulin-dependent diabetes mellitus.

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.

Adult↗
PubMed1995

Effects of insulin and beta-adrenergic blockade on the migrating motor complex in humans.

BACKGROUND: Interdigestive small-intestinal motility is suppressed by hyperglycemia and also by hyperinsulinemia per se. Since hyperinsulinemia may increase sympathetic activity, the present study was undertaken to ascertain to what extent insulin affects phase III of the migrating motor complex (MMC) and MMC-related duodenal retroperistalsis and whether beta-adrenergic receptors may mediate the effects of insulin. METHODS: Fasting motility was studied in eight healthy volunteers on three occasions with an eight-lumen perfused pressure catheter, with closely spaced recording points in the proximal duodenum. On the control day 5-h antroduodenojejunal manometry was performed. On another study day euglycemic hyperinsulinemic clamping was performed for 2 h after an initial basal recording. On a 3rd day motility was recorded during propranolol infusion, combined with a period of euglycemic hyperinsulinemia. RESULTS: During hyperinsulinemia complete absence of phase III of the MMC in the gastric antrum was observed, whereas 55% of the MMC had a gastric phase-III component on the control day. The duration of phase III in the proximal duodenum was decreased during hyperinsulinemia compared with the control period (p < 0.05). This inhibitory effect of insulin on the activity front was not prevented by beta blockade. Under control conditions the proportion of retroperistaltic pressure waves in the proximal duodenum was 13 +/- 8% in early phase III, increasing in late phase III to 79 +/- 15% (p < 0.01). Duodenal phase III during hyperinsulinemia showed a similar increase in retroperistalsis, from 4 +/- 4% in early phase III to 67 +/- 21% in late phase III (p < 0.01). The corresponding proportions during beta blockade were 16 +/- 10% and 86 +/- 14%, respectively. CONCLUSIONS: Hyperinsulinemia per se abolishes antral phase III and makes the duodenal phase III shorter but does not interrupt the distinct pattern of retroperistalsis in late phase III. Beta-adrenergic receptors seem not to be important for these effects of insulin or for the retroperistalsis in duodenal phase III.

Adult↗
PubMed1994

The cGMP-inhibitable phosphodiesterase modulates glucose transport activation by insulin.

To assess the role of the cGMP-inhibitable phosphodiesterase (cGI-PDE) in the action of insulin on glucose transport, adipocytes from young, lean rats were preincubated for 20 min at 37 degrees C with and without OPC 3911, a specific inhibitor of cGI-PDE, and 3-O-methylglucose uptake was measured. Insulin-stimulated glucose transport was impaired by OPC 3911 (approximately 15%) and this impairment became more pronounced in the presence of the degradable cAMP-analogue 8-bromo-cAMP (approximately 45%). This analogue alone did not significantly decrease glucose transport. Furthermore, insulin sensitivity was impaired by the combination of OPC 3911 and 8-bromo-cAMP. Maximal insulin-stimulated glucose transport in adipocytes from aging, obese rats was affected similarly by OPC 3911 and 8-bromo-cAMP, suggesting that cGI-PDE activity is not markedly altered in this insulin-resistant state. In conclusion, cGI-PDE exerts a modulating effect on the stimulatory action of insulin on glucose transport. This effect is particularly pronounced when the cellular cAMP levels are elevated.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus. Effects of hyperglycaemia and insulin.

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.

Adult↗
PubMed1994

Carbohydrates, fat, and insulin action.

Insulin resistance is a common disorder and is seen in many conditions that are associated with increased risk for cardiovascular disease (eg, obesity, diabetes, hypertension, and cigarette smoking). The role of the diet, irrespective of degree of obesity, in modulating insulin sensitivity is uncertain. An extremely high carbohydrate-fat ratio improves insulin sensitivity whereas more moderate changes (40-60% carbohydrate) produce less convincing results. However, increased fasting concentrations of triglycerides and lower concentrations of high-density-lipoprotein (HDL) cholesterol have frequently been seen with these diets, together with lower concentrations of low-density-lipoprotein (LDL) cholesterol. High-carbohydrate diets based on foods with a low glycemic index combined with a high dietary fiber content should be evaluated. Such diets may produce the desired effects while they prevent unwanted increases in fasting triglyceride concentrations and lower HDL cholesterol.

Animals↗
PubMed1994

Metformin and metoprolol CR treatment in non-obese men.

OBJECTIVE: To study the effect of metformin and metoprolol CR on insulin sensitivity, blood lipids, fibrinolytic activity and blood pressure. DESIGN: A double-blind, placebo controlled, triple cross-over study with randomization to either metformin, 850 mg b.i.d., or metoprolol CR 100 mg o.d., or placebo for a period of 18 weeks. The glucose uptake was measured with the euglycaemic clamp technique after every 6 weeks' treatment period. Blood pressure and blood samples were taken every 3rd week. SUBJECTS: Eighteen non-obese men (53 +/- 6 years of age). RESULTS: Metformin decreased C-peptide (P < 0.02), FFA (P < 0.003), total and low-density lipoprotein cholesterol, tissue plasminogen activator antigen and the urinary potassium excretion (P < 0.05 for all), but not blood pressure compared to placebo. Metoprolol CR reduced diastolic blood pressure and pulse rate; fasting free fatty acids and the urinary potassium increased (P < 0.05 for all). No effect of metformin or metoprolol CR was seen on the glucose disposal rate, blood glucose, plasma insulin, triglycerides, high-density lipoprotein cholesterol, lipoprotein(a), uric acid or plasminogen activator inhibitor 1 activity or antigen. The glucose uptake was not particularly decreased in these subjects. CONCLUSION: The study shows that metformin has some favourable effects on metabolism and that metoprolol CR is fairly neutral in this regard. The lack of effect of metformin on glucose disposal rate and blood pressure can be explained by the fact that the individuals studied were neither insulin resistant nor hypertensive. The data does not preclude an antihypertensive effect by treating a concomitant insulin resistance.

Analysis of Variance↗
PubMed1994

The insulin resistance syndrome in smokers is related to smoking habits.

The relationship between smoking habits, insulin resistance, and related risk factors for cardiovascular disease was examined in 57 middle-aged male smokers whose degree of insulin resistance was quantified by using the euglycemic clamp technique. Smoking habits correlated with degree of insulin resistance and consequently with various manifestations of the insulin resistance syndrome including levels of insulin, high-density lipoprotein cholesterol, triglycerides, and plasminogen activator inhibitor-1 (PAI-1) activity. Smoking habits, independent of degree of insulin resistance, were also related to levels of total cholesterol and low-density lipoprotein cholesterol as well as triglycerides. Stepwise regression analyses considering the effects of age, lean body mass, body fat, body mass index, waist/hip ratio, and alcohol consumption showed that only smoking habits and percent body fat were independently related to degree of insulin resistance. This study shows that insulin resistance and the insulin resistance syndrome are important but not unique contributors to the strong risk profile for cardiovascular disease in middle-aged men who smoke.

Adult↗
PubMed1994

Lactate release from the subcutaneous tissue in lean and obese men.

Lactate concentration in the subcutaneous interstitial fluid and adipose tissue blood flow (ATBF, ml/100 g.min) were simultaneously measured with the microdialysis technique combined with 133Xe clearance in the abdominal and femoral subcutaneous adipose tissue in nine lean and nine obese men. The studies were performed both in the postabsorptive state and 2 h after an oral glucose load and the results compared to the lactate levels in arterialized venous plasma. After an overnight's fast, arterial lactate was 738 +/- 49 and 894 +/- 69 microM (mean +/- SE) (P < 0.05) in the lean and obese subjects, respectively. The interstitial lactate levels were significantly higher than blood lactate in both subject groups without any regional differences. Abdominal and femoral ATBF was 3.2 +/- 0.6 vs. 2.8 +/- 0.4 and 1.7 +/- 0.3 vs. 2.4 +/- 0.4 ml/100 g.min (P < 0.05) in lean and obese subjects, respectively. Mean apparent lactate release from the abdominal vs. femoral adipose tissue in the fasting state was 10.5 +/- 3.1 vs. 8.6 +/- 2.3 and 6.0 +/- 2.3 vs. 8.5 +/- 2.3 mumol/kg.min (NS) in lean and obese subjects, respectively. Both plasma and interstitial lactate levels increased significantly after an oral glucose load in both subject groups. However, apparent lactate release increased significantly only in the lean group. It is concluded that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state and that this is further enhanced in obese subjects due to their large adipose mass.

Abdomen↗
PubMed1994

Effects of hyperglycemia on interdigestive gastrointestinal motility in humans.

BACKGROUND: Gastrointestinal motility disorders are common in patients with diabetes mellitus. Recent studies indicate that hyperglycemia can affect gastric emptying and gastric motility in healthy subjects and diabetics. METHODS: The effect of acute hyperglycemia on gastrointestinal motility was studied with a manometric technique in healthy subjects. Seven individuals, four men and three women, 23-34 years old, were studied on 2 different days. On 1 of the days a 5-h registration was performed after an overnight fast. On another day and after an initial basal period, acute steady-state hyperglycemia was induced by intravenous glucose infusion for 90 min. Motility variables were evaluated in four segments: in the gastric antrum, the proximal duodenum, the distal duodenum, and the proximal jejunum. RESULTS: Fasting migrating motor complex rhythm including migration of phase III prevailed during hyperglycemia. Compared with euglycemia, the motility index in phase II was lower during hyperglycemia in all segments studied. In the antrum the difference was 62% (p < 0.01); in the proximal duodenum, 37% (p < 0.01); in the distal duodenum, 44% (p < 0.05); and in the jejunum, 58% (p < 0.01). During hyperglycemia the prevalence of propagated contractions in phase II was significantly lower than during euglycemia both in the antrum and the proximal duodenum. In the last part of phase III in proximal duodenum most individual contractions were propagated in orad direction compared with early phase III, and this difference persisted during hyperglycemia. The number of long clusters was significantly increased during hyperglycemia as compared with euglycemia: 2.0 +/- 0.6 per hour versus 0.4 +/- 0.14 (p < 0.01). In late phase II plasma levels of motilin and pancreatic polypeptide were significantly decreased during hyperglycemia. CONCLUSION: Hyperglycemia not only reduces the motility in the stomach but also inhibits motility in both the duodenum and the jejunum. The results show that acute hyperglycemia has an important impact on small-intestinal motility.

Adult↗