Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.
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PMID:Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients. 305 47

This study was designed to quantitate glucose and FFA disposal by muscle tissue in patients with type II diabetes and to investigate the relationship between FFA metabolism and insulin resistance. The forearm perfusion technique was used in six normal subjects and two groups of normal weight diabetic patients, i.e. untreated (n = 8) and insulin-treated (n = 6). The latter received 2 weeks of intensive insulin therapy before the study. Plasma insulin levels were raised acutely [950-1110 pmol/L) (130-150 microU/mL)], while the blood glucose concentration was clamped at its basal value [4.9 +/- 0.1 (+/- SE) mmol/L in the normal subjects, 5.7 +/- 0.5 in the insulin-treated diabetic patients, and 5.5 +/- 0.3 in the untreated diabetic patients] by a variable glucose infusion. During the control period, arterial FFA concentrations were similar in the three groups, and they decreased to a comparable extent (less than 0.1 mmol/L) in response to insulin infusion. During the control period, the mean forearm FFA uptake was 2.5 +/- 0.5 mumol/L.min in the normal subjects, 2.9 +/- 0.5 in the insulin-treated patients, and 2.1 +/- 0.5 in the untreated diabetic patients. During the insulin infusion, FFA uptake was profoundly suppressed to similar levels in the normal subjects (0.9 +/- 0.1 mumol/L.min), the insulin-treated diabetic patients (1.1 +/- 0.3), and the untreated diabetic patients (0.9 +/- 0.1; P less than 0.001). Forearm glucose uptake was similar in the three groups during the control period. It increased during the insulin infusion, but the response in both diabetic groups was less than that in the normal subjects. The total amounts of glucose taken up by the forearm during the study period were 5.2 +/- 0.7, 2.6 +/- 0.5, and 2.1 +/- 0.6 mmol/L.min in the normal subjects, the insulin-treated diabetic patients, and the untreated diabetic patients, respectively (P less than 0.01). We conclude that 1) insulin-mediated glucose uptake by forearm skeletal muscle is markedly impaired in type II diabetes and improves only marginally after 2 weeks of intensive insulin therapy; 2) in contrast, no appreciable abnormality in forearm FFA metabolism is demonstrable in insulin-treated type II diabetic patients; and 3) FFA do not contribute to the insulin-treated skeletal muscle insulin resistance that occurs in patients with type II diabetes mellitus.
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PMID:Quantitation of forearm glucose and free fatty acid (FFA) disposal in normal subjects and type II diabetic patients: evidence against an essential role for FFA in the pathogenesis of insulin resistance. 305 49

This study analyzed eating attitudes and plasma glucose, insulin, unesterified fatty acid (FFA), human growth hormone (GH), and cortisol responses to an oral (100 g) glucose load in 26 female anorexia nervosa patients at an 8-year outcome evaluation in comparison to 14 age-matched female control subjects. Recovered patients who were of normal body weight and had cyclical menstruation (n = 19) showed glucose tolerance curves and insulin, cortisol, and GH responses that were indistinguishable from those of normal subjects, although patients tended to be more diet-conscious than controls and showed elevated fasting FFA levels. Two of 19 recovered patients met criteria for impaired glucose tolerance. Nonrecovered patients (n = 7) showed abnormal eating attitudes at an average underweight of 20% with persistent amenorrhea or oligomenorrhea. They had high fasting FFA plasma levels, significantly greater than normal rises in plasma glucose, a significant delay in serum insulin secretion, higher mean glucose levels before and after controlling for amount of exercise, and paradoxical release of GH. One of seven patients met criteria for diabetes mellitus and two of seven had impaired glucose tolerance. The findings suggest that fasting plasma FFA levels may reflect patients' eating and exercise habits more accurately than their verbal or written reports.
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PMID:Eating attitudes and glucose tolerance in anorexia nervosa patients at 8-year followup compared to control subjects. 305 85

Recent research has shown the marked differences in association with disease between obesity localized to the abdominal respectively to the gluteal-femoral regions. In this review systematic analyses were performed of the associations between obesity (body mass index, BMI) or abdominal obesity (increased waist-over-hip circumference ratio, WHR) on the one hand, and a number of disease end points, and their risk factors, as well as other factors on the other, WHR was associated with cardiovascular disease, premature death, stroke, non-insulin-dependent diabetes mellitus and female carcinomas. In contrast, BMI tended to be negatively correlated to cardiovascular disease, premature death, and stroke, but positively to diabetes. The established risk factors for these end points were found to correlate to WHR, while this was often not the case with BMI. BMI was positively correlated only to insulin, triglycerides and blood pressure. Together with diabetes mellitus, this seems to constitute a metabolic group of conditions which are thus associated with BMI. Androgens (in women), and perhaps cortisol, seem to be positively, and progesterone negatively correlated to WHR. The WHR was also positively associated with sick leave, several psychological maladjustments, psychosomatic and psychiatric disease. Attempts were made to interpret these findings. In a first alternative an elevation of FFA concentration, produced from abdominal adipose tissue, was considered to be the trigger factor for the pathologic aberrations associated with abdominal distribution of body fat. When obesity is added, the metabolic aberrations may be exaggerated. In a second alternative adrenal cortex hyperactivity was tested as the cause. When combined with the FFA hypothesis, this might explain many but not all of the findings. It seems possible to produce an almost identical syndrome in primates by defined experimental stress. Women with high WHR were found to have a number of symptoms of poor coping to stress. It was therefore suggested that part of the background to this syndrome might be a hypothalamic arousal syndrome developing with stress. It was concluded that obesity and abdominal distribution of adipose tissue constitute two separate entities with different pathogenesis, clinical consequences and probably treatment.
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PMID:The associations between obesity, adipose tissue distribution and disease. 329 56

The effect of variations in glucose tolerance on insulin's ability to regulate glucose uptake and plasma glucose and FFA concentrations was assessed in 22 obese individuals [8 with normal glucose tolerance, 7 with impaired glucose tolerance (IGT), and 7 with noninsulin-dependent diabetes mellitus (NIDDM)]. Patients with IGT had ambient insulin levels that were higher than normal, associated with elevated postprandial glucose levels and a marked reduction in insulin-stimulated glucose uptake. On the other hand, plasma FFA levels were relatively normal in IGT, possibly because of the hyperinsulinemia. Patients with NIDDM were also hyperinsulinemic, with insulin levels throughout the day that were approximately twice normal. Hyperinsulinemia in patients with NIDDM was associated with a significant decline in insulin-stimulated glucose uptake as well as with significant increases in both ambient plasma glucose and FFA concentrations. Thus, and in contrast to patients with IGT, plasma FFA metabolism in NIDDM was grossly abnormal, despite the concomitant hyperinsulinemia. These data indicate that insulin resistance in obese individuals varies as a function of degree of glucose tolerance, and insulin resistance in patients with NIDDM involves defects in the regulation of both plasma glucose and FFA metabolism.
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PMID:Effect of differences in glucose tolerance on insulin's ability to regulate carbohydrate and free fatty acid metabolism in obese individuals. 351 28

Plasma glucose, insulin, FFA, glucagon, and GH concentrations were measured over an 8-h period in normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM). Meals were consumed at 0800 h (20% of daily calories) and noon (40% of daily calories), and measurements were made hourly from 0800-1600 h. Day-long plasma glucose, insulin, and FFA concentrations were higher than normal (by two-way analysis of variance) in patients with NIDDM, whether obese or nonobese. In addition, day-long plasma glucagon concentrations were also higher than normal (by two-way analysis of variance) in both nonobese and obese patients with NIDDM. Furthermore, direct relationships were found between the total plasma glucagon response from 0800-1600 h and total plasma glucose (r = 0.57; P less than 0.001) and FFA (r = 0.30; P less than 0.06) responses. In contrast, plasma GH levels were not increased in patients with NIDDM. These data demonstrate that ambient plasma concentrations of both glucose and FFA are higher in patients with NIDDM, despite the fact that coexisting plasma insulin levels are equal to or higher than normal. The higher day-long plasma glucagon levels in patients with NIDDM may contribute to their higher plasma glucose and FFA concentrations.
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PMID:Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. 353 80

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.
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PMID:Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes. 354 67

The study deals with the subject of exercise in diabetic patients, with particular emphasis on acute physical stress in type--I and type--II diabetics. The principal task was to define metabolic changes as they occur in the diabetic subjected to acute stress induced by exercise, in comparison with non-diabetics; metabolic changes during prolonged stress as well as during the period of rest; and finally, to propose, on the basis of authors' experimental results and detailed literature research, appropriate rules of procedure for prescriptive exercise for the individual patient. There were 120 subjects divided into 8 groups. Using primarily a bicycle ergometer, the members of the individual groups were subjected to physical stress of various intensity and duration. A detailed analysis of each subject's metabolic response was performed, involving an assessment of 35 physiological and biochemical parameters, with main focus on determining biochemical changes. The study results are presented in detail both with respect to the metabolic response to a given stress in individual groups and comparatively for individual parameters with regard to specific stress rates and groups. Significant differences were found in the metabolic responses concerning the following parameters: acid-base balance, potassium, triglycerols, glucose, cholesterol, FFA, free glycerol, lactate, uric acid. On the basis of the results of experimental measurements, the following algorithm has been designed for prescribing exercise to diabetics: appropriate motivation; determination of the type of exercise; determination of the intensity of exercise; determination of the duration of exercise; respecting related contraindications and complications. A conclusion has been made that provided all possible risks and contraindications as well as prescription guidelines are respected, exercise is to be considered one of the basic principles of diabetes management.
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PMID:Diabetes mellitus and exercise. 367 32

The ability of insulin to stimulate tissue glucose uptake and lower plasma FFA concentrations was quantified in 12 individuals with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM), further subdivided into obese and nonobese subjects. Measurements were made during 5-h glucose clamp studies, carried out at plasma insulin concentrations of about 10 microU/ml (0-150 min) and about 60 microU/ml (150-300 min). Differences between the patient groups were compared by two-way analysis of variance. The ability of insulin to either suppress plasma FFA concentrations or stimulate glucose uptake was significantly reduced (P less than 0.001) in patients with NIDDM, and this was true of both the obese and nonobese groups. The defect in the ability of insulin to suppress plasma FFA concentrations in patients with NIDDM was more apparent at the lower insulin concentration, whereas resistance to insulin-stimulated glucose uptake in NIDDM was more dramatic at the high insulin concentration. Finally, a significant correlation (r = -0.67; P less than 0.001) between insulin-stimulated glucose uptake and plasma FFA concentration was found in the entire group. These data emphasize the fact that patients with NIDDM are resistant to multiple actions of insulin, and that the magnitudes of the defect in insulin suppression of plasma FFA levels and stimulation of tissue glucose uptake are roughly comparable.
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PMID:Resistance to insulin suppression of plasma free fatty acid concentrations and insulin stimulation of glucose uptake in noninsulin-dependent diabetes mellitus. 378 31

Circulating triglyceride is cleared by a combination of hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL). Although LPL has been extensively studied in diabetes, the effect of insulinization on H-TGL activity has not been well characterized. To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized). Plasma glucose, measured at the start of the studies, was 88 +/- 10 mg/100 mL (mean +/- SD) in the normal control dogs, 434 +/- 31 mL in pancreatectomized dogs in poor diabetic control, and 87 +/- 16 in good diabetic control. Peak (five minutes) postheparin plasma H-TGL activity was increased in dogs in poor diabetic control (212 +/- 43 nmol FFA/min/mL) v the normal control dogs (135 +/- 21 nmol FFA/min/mL, P less than 0.02). When the dogs were in good diabetic control, the peak H-TGL (202 +/- 40 nmol FFA/min/mL) was also significantly increased compared with the level in normal dogs, while the sum of five and 45 minute postheparin H-TGL levels for the dogs in good diabetic control was less than when they were in poor diabetic control (P less than 0.01). Thus, insulin-deficient diabetes in dogs increases H-TGL, and short-term improvement of glycemic control with insulin partially corrects this increase.
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PMID:Hepatic triglyceride lipase in diabetic dogs. 388 96


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