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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of continuous subcutaneous insulin infusion (CSII) by portable pump (Microjet MC2, Miles) and conventional optimized insulin therapy (OCT) on metabolic control were compared in a group of five insulin-dependent diabetic patients. A group of seven normal volunteers was examined as control. CSII treatment consisted of a basal insulin infusion and three boluses of 60 min, starting 30 min before each main meal. OCT was characterized by three daily s.c. insulin injections: regular insulin before breakfast and lunch, regular plus lente before dinner. Two protocols of study were performed. In the first one the metabolic (blood glucose, NEFA, 3-beta-OH-butyrate) and hormonal (free insulin, pancreatic glucagon, cortisol, growth hormone) profiles were examined in the hospital with the patients connected to a "blood glucose monitor," after 45 days of OCT and CSII treatment, respectively. In the course of CSII treatment, a better blood glucose profile was observed than during OCT (OCT: MBG = 162 +/- 18 mg/dl, M = 43 +/- 11, MAGE = 151 +/- 26 mg/dl. CSII: MBG = 133 +/- 8 mg/dl, M = 29 +/- 5, MAGE = 138 +/- 19 mg/dl: P less than 0.05), although the indices remained higher than in normal subjects (MBG = 85 +/- 3 mg/dl, M = 0.98 +/- 0.18, MAGE = 49 +/- 3.6 mg/dl). CSII treatment was also associated with an improvement of NEFA and 3-beta-OH-butyrate profiles. Plasma "free" insulin (IRI) ranged between 18.2 +/- 5.4 and 32 +/- 5.5 microU/ml during CSII. Plasma glucagon (IRG) concentration after overnight fast was 195 +/- 65 pg/ml and 220 +/- 55 pg/ml during OCT and CSII treatment, respectively, with minor changes throughout the day. (ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Care
PMID:Continuous subcutaneous insulin infusion treatment in insulin-dependent diabetic patients: a comparison with conventional optimized treatment in a long-term study. 718 33

Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it to their glucose tolerance, insulin resistance, and muscle insulin sensitivity as measured by insulin activation of glycogen synthase, an insulin-regulated enzyme that is rate-limiting for insulin action in muscle. Both muscle TG content and intracellular lipid determined by Oil red O staining of muscle fibers were negatively associated with glycogen synthase activation (r = .43, P = .03 and r = -.47, P = .02, respectively). In addition, intracellular lipid correlated with features of the insulin resistance syndrome, including an increased waist to hip ratio (r = .47, P = .01) and fasting nonesterified fatty acids ([NEFA] r = .44, P = .04). These data demonstrate that increased muscle TG stores are associated with decreased insulin-stimulated glycogen synthase activity. Intracellular fat may underlie a major part of the insulin resistance in normal subjects, as well as type II diabetics.
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PMID:Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. 876 49

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

Type II (non-insulin-dependent) diabetes mellitus is a metabolically heterogeneous condition, and is invariably preceded by impaired glucose tolerance (IGT). We examined whether metabolic heterogeneity is a feature of IGT. Three subject groups were studied: IGT subjects with two or more living non-insulin-dependent diabetic relatives (IGTWF, n = 17), and IGT subjects (IGTWOF, n = 17) and subjects with normal glucose tolerance (NGT, n = 25) without a family history of diabetes. Glucose tolerance, glucose (KITTG) and nonesterified fatty acid (KITTNEF) insulin sensitivity, and first-phase insulin secretion (FPIS) were assessed by oral glucose tolerance (OGTT), insulin tolerance (ITT), and intravenous glucose tolerance (IVGTT) tests, respectively. Comparison of groups was made by ANOVA and t test. The three groups were matched for age, gender, body mass index (BMI), and waist to hip ratio (WHR). IGTWOF and IGTWF subjects had comparable 2-hour plasma glucose levels on OGTT, and insulin secretion and KITTG were decreased to comparable degrees. However, in comparison to IGTWF subjects, IGTWOF subjects had increased fasting serum triglyceride (geometric mean, 1.8 [range, 0.8 to 4.5] v 1.1 [0.4 to 2.5] mmol. L-1, P = .02) and 2-hour plasma nonesterified fatty acid ([NEFA] mean +/- SD, 0.12 +/- 0.07 v 0.08 +/- 0.03 mmol.L-1, P < .02) levels and decreased KITTNEF values (4.0 [1.7 to 8.9] v 6.2 [2.8 to 12.1]%.min-1, P < .02). Thus, the two IGT groups had comparable changes in glucose metabolism, but IGTWOF subjects had additional abnormalities of lipid metabolism. In conclusion, metabolic heterogeneity is a feature of IGT, and this may reflect underlying etiological heterogeneity.
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PMID:Metabolic heterogeneity in impaired glucose tolerance. 925 74

The mechanisms underlying the associations between abnormal glucose tolerance and myocardial infarction are poorly understood. It has often been suggested that an increased plasma insulin concentration is causally linked to many of the metabolic abnormalities that are associated with abnormal glucose tolerance, although this suggestion remains controversial. Recently it has been proposed that proinsulin and proinsulin-like molecules may also be involved in the atherogenic process. Both hyperinsulinaemia and insulin resistance are associated with fasting hypertriglyceridaemia and both increased VLDL production and increased plasma triglyceride concentrations commonly occur in association with abnormal glucose tolerance and atheromatous vascular disease. In order to study the effects of insulin, proinsulin and proinsulin-like molecules on hepatic triglyceride secretion we have undertaken experiments in vitro using the liver cell line HepG2. In conjunction with these in vitro experiments we have also studied, in vivo, the associations between insulin, proinsulin, proinsulin-like molecules and plasma triglyceride concentrations in subjects with both normal and abnormal glucose tolerance. Our results in vitro show that proinsulin and proinsulin-like molecules have similar and not different effects to insulin but are less biologically active. In vivo, our results show that concentrations of insulin, proinsulin and proinsulin-like molecules per se are not an important determinant of plasma triglyceride concentrations. Both abnormal NEFA suppression during an oral glucose tolerance test and increased central adiposity are closely linked to poor glucose tolerance and are the most important determinants of plasma triglyceride concentrations. Taken together these results suggest that it is not insulin nor proinsulin concentrations per se that are causally linked to hypertriglyceridaemia. We suggest that abnormal NEFA suppression plays an important part in the increase in risk of vascular disease associated with insulin resistance.
Exp Clin Endocrinol Diabetes 1997
PMID:The role of insulin and proinsulin in the regulation of triglyceride metabolism. 928 40

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74

Decreased insulin sensitivity is associated with diabetes mellitus, ischemic heart disease, and hypertension, both independently and in association as what is called the metabolic syndrome. Although the negative effects of obesity, sedentary lifestyles, and high-fat diets on insulin sensitivity are well established, the influence of type and quantity of dietary carbohydrate is more controversial. This study aimed to assess the acute (24 h) effects of a high-sucrose compared with a high-starch diet on insulin sensitivity and to identify changes in blood metabolites that might lead to altered insulin sensitivity. Eight healthy adults consumed high-sucrose or high-starch diets (50% of dietary energy) in a randomized, crossover trial. Insulin sensitivity was assessed by a short insulin tolerance test the following morning. No differences were detected in insulin sensitivity, either for glucose metabolism [Kitt(glucose) (the rate constant for the decline in blood glucose concentrations) for sucrose diet = 3.86%/min, for starch diet = 3.72%/min; pooled SEM = 0.23] or for lipid metabolism [Kitt(NEFA) (the rate constant for the decline in blood fatty acid concentrations) for sucrose diet = 12.9%/min, for starch diet = 11.4%/min; pooled SEM = 1.18]. Profiles for blood glucose and serum insulin concentrations revealed higher peaks and lower troughs with the high-sucrose diet whereas area under the curve for glucose was higher with the high-starch diet (6780 +/- 245 mmol x L/min) than with the high-sucrose diet (6290 +/- 283 mmol x L/min) (P < 0.001). Plasma fatty acid concentrations showed a late postprandial rise with the sucrose-rich diet relative to the starch-rich diet, which was mirrored with a fractionally later peak in triacylglycerol concentrations.
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PMID:Acute effects on insulin sensitivity and diurnal metabolic profiles of a high-sucrose compared with a high-starch diet. 1007 50

The preferential channeling of different fuels to fat and changes in the transcription profile of adipose tissue and skeletal muscle are poorly understood processes involved in the pathogenesis of obesity and insulin resistance. Carbohydrate and lipid metabolism may play relevant roles in this context. Freely moving lean Zucker rats received 3- and 24-h infusions of Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, or saline plus heparin, to evaluate how an increase in free fatty acids (nonesterified fatty acid [NEFA]) modulates fat tissue and skeletal muscle gene expression and thus influences fuel partitioning. Glucose uptake was determined in various tissues at the end of the infusion period by means of the 2-deoxy-[1-3H]-D-glucose technique after a euglycemic-hyperinsulinemic clamp: high NEFA levels markedly decreased insulin-mediated glucose uptake in red fiber-type muscles but enhanced glucose utilization in visceral fat. Using reverse transcriptase-polymerase chain reaction and Northern blotting analyses, the mRNA expression of fatty acid translocase (FAT)/CD36, GLUT4, tumor necrosis factor (TNF)-alpha, peroxisome proliferator-activated receptor (PPAR)-gamma, leptin, uncoupling protein (UCP)-2, and UCP-3 was investigated in different fat depots and skeletal muscles before and after the study infusions. GLUT4 mRNA levels significantly decreased (by approximately 25%) in red fiber-type muscle (soleus) and increased (by approximately 45%) in visceral adipose tissue. Furthermore, there were marked increases in FAT/CD36, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 mRNA levels in the visceral fat and muscle of the treated animals in comparison with those measured in the saline-treated animals. These data suggest that the in vivo gene expression of FAT/CD36, GLUT4, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 in visceral fat and red fiber-type muscle are differently regulated by circulating lipids and that selective insulin resistance seems to favor, at least in part, a prevention of fat accumulation in tissues not primarily destined for fat storage, thus contributing to increased adiposity and the development of a prediabetic syndrome.
Diabetes 2001 Mar
PMID:Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats. 1124 80

The aim of this study was to compare the metabolic effects of a single equimolar subcutaneous injection of hepatic directed vesicle-insulin (HDV-insulin) and regular insulin on glucose levels and intermediary metabolism during a 75-g oral glucose tolerance test (OGTT). Nine Type 1 diabetic patients underwent two experiments separated by 4 weeks. Each experimental protocol consisted of an identical evening meal followed by overnight euglycemic control achieved by a continuous low-dose insulin infusion. The next morning a subcutaneous injection (0.1 U/kg) of HDV-insulin or regular insulin was administered 30 min before a 75-g OGTT. The overnight basal insulin infusion was maintained unaltered throughout the 150-min OGTT. Plasma glucose, glucoregulatory hormones (insulin, glucagon, cortisol), and intermediary metabolites (lactate, alanine, glycerol, NEFA, beta-hydroxybutyrate) were measured to assess the metabolic effects of the two insulin preparations. Compared to regular insulin, an equivalent subcutaneous dose of HDV-insulin significantly lowered glucose levels during OGTT (mean reduction 2.2+/-0.4 mmol/l; P<.005). Plasma levels of insulin and glucagon were equivalent during both series of experiments. Blood lactate, glycerol and plasma NEFA levels were not different during OGTT indicating similar peripheral action of the insulins. beta-Hydroxybutyrate levels were significantly reduced (P<.05) following HDV-insulin supporting a preferential hepatic action of the preparation. We conclude that HDV-insulin can significantly lower plasma glucose excursions compared to an equivalent dose of regular insulin during an OGTT in Type 1 diabetic patients. The metabolic profile of equivalent peripheral insulin, glucagon and glycerol levels but reduced beta-hydroxybutyrate values support a hepatospecific effect of HDV-insulin.
J Diabetes Complications
PMID:The effects of HDV-insulin on carbohydrate metabolism in Type 1 diabetic patients. 1152 95

The insulin-like growth factor (IGF) system, comprising insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and their binding proteins (IGFBPs), is linked to cell growth, the development of cardiovascular disease, and several cancers. Little is known about its epidemiology. The authors studied relations of the IGF system to anthropometric and metabolic variables in three population-based ethnic groups in Manchester, England, in 1994-1998 with differing disease risks: African Caribbean (n = 193), Pakistani (n = 130), and local Europeans(n = 142). Standardized anthropometry, glucose tolerance tests, and serum assays were performed. Body mass indices (BMIs) were high in all groups. IGF-I levels were highest in normoglycemic African Caribbeans and declined with age (r = -0.28). IGF-II levels were greatest in Europeans. IGFBP-1 concentrations increased with age in Pakistanis (r = 0.20) and Europeans (r = 0.29), but not in African Caribbeans (r = 0.06), and were inversely related to BMI (r = -0.37). Age- and sex-adjusted IGFBP-1 was inversely related to fasting insulin and proinsulin in all groups; participants with newly detected diabetes were relatively insulinopenic but had higher IGFBP-1 concentrations. Nonesterified (free) fatty acid (NEFA) concentrations increased with declining glucose tolerance. In multiple regression analysis, IGFBP-1 was independently and negatively related to fasting insulin, BMI, and African-Caribbean compared with European ethnicity but positively related to age, fasting glucose, and NEFA. IGF-I was inversely related only to age, NEFA, and Pakistani ethnicity. IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples.
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PMID:Epidemiology of the insulin-like growth factor system in three ethnic groups. 1154 55


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