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

To study the effects of CSII on insulin action and intermediary metabolism, seven type 1 diabetic patients (duration 17 +/- 4 (SEM) years), underwent sequential euglycemic clamps 1/4, 6 and 12 months after changing from conventional insulin treatment to continuous subcutaneous insulin infusion (CSII); seven healthy subjects served as controls. For at least 14 h before the study, blood glucose was maintained between 4-10 mmol/l in the patients by intravenous insulin infusion, to avoid negatively biased clamp measures. A metabolite profile was taken in the basal state and during euglycemic hyperinsulinemia. At 1/4 month insulin sensitivity was decreased in the patients (ED50 82 +/- 14 vs 52 +/- 4 mU/l in controls, P less than 0.02), whereas insulin responsiveness was normal. During the course of one year, no change towards control values was found for insulin-stimulated glucose disposal. Concomitantly, HbA1 did not change either, and remained elevated (1/4 month 11.1 +/- 0.7%, 12 months 10.0 +/- 0.9% vs 6.5 +/- 0.3% in controls, P less than 0.01). Regarding basal intermediary metabolism, triglycerides became significantly improved (1/4 month 1.32 +/- 0.13 mmol/l, 12 months 0.70 +/- 0.05 mmol/l, P less than 0.05, vs 0.70 +/- 0.08 mmol/l in controls). The acetoacetate/3-OH-butyric acid ratio increased from 0.10 at 3 to 0.26 at 12 months, which was similar to controls. The absolute levels of acetoacetate and 3-OH-butyric acid remained elevated 2-3 fold. For other basal metabolite levels no systematic trend for improvement was found for 1/4 to 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1991 Apr
PMID:Glucose disposal and intermediary metabolism during one year of continuous subcutaneous insulin infusion (CSII). 185 35

Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension. In these conditions an increased cardiovascular reactivity to noradrenaline (NA) and angiotensin II (AII) can be observed. Using the euglycemic clamp technique, we determined the cardiovascular reactivity to graded infusions of NA and AII in nine healthy males before (Bas), and 1 and 6 h after infusion of insulin (50 mU/kg per h) was started. On separate days control experiments were carried out to control for any circadian variation. Insulin led to a decrease of the amount of circulating NA necessary to increase the diastolic blood pressure (DBP) 20 mmHg (actual experiment [mean +/- SEM]: Bas, 23.1 +/- 5.0; 1 h, 14.8 +/- 3.0; and 6 h, 12.3 +/- 3.1; and control experiment: Bas, 20.7 +/- 5.0; 1 h, 18.6 +/- 3.5; and 6 h, 17.3 +/- 3.3 nmol/liter; Bas vs. 1 and 6 h: P less than 0.05). Although the amount of NA infused to raise DBP 20 mmHg showed a similar decline after 1 h of insulin infusion, no such change from baseline could be observed at 6 h. This appeared to be due to an increase in NA clearance with more prolonged insulin infusion. Insulin exerted no effect on the amount of AII infused to increase DBP 20 mmHg (actual experiment: Bas, 27.6 +/- 6.4; 1 h, 28.8 +/- 10.0; and 6 h, 21.2 +/- 5.3; and control experiment: Bas, 33.6 +/- 5.7; 1 h, 34.2 +/- 6.1; and 6 h, 23.4 +/- 4.7 ng/kg/min; NS). We did observe a circadian variation in AII reactivity. Whether the increase in cardiovascular responsiveness to NA after administration of insulin contributes to the elevation in blood pressure frequently observed in patients with insulin resistance remains to be proven.
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PMID:Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II. 186 61

Ninety-six patients with insulin-dependent diabetes mellitus (IDDM) and non-proliferative retinopathy were randomized to intensified conventional treatment (ICT) (n = 44) or regular treatment (RT) (n = 52), and followed up for 5 years. HbA1c decreased from 9.5 +/- 0.2% (mean value +/- SEM) to 7.2 +/- 0.1% in the ICT group, and from 9.4 +/- 0.2% to 8.7 +/- 0.1% in the RT group (difference between the groups, P less than 0.001). Retinopathy increased in both groups (P less than 0.001), but after 5 years it was worse in the RT group (P less than 0.05). The urinary albumin excretion rate was higher in the RT group than in the ICT group after 5 years (239.9 +/- 129.7 micrograms min-1 vs. 46.0 +/- 26.1 micrograms min-1, P less than 0.05). Eight RT patients developed manifest nephropathy, compared with none in the ICT group (P less than 0.01). After 5 years the conduction velocities of the sural (P less than 0.05), peroneal (P less than 0.01) and tibial (P less than 0.001) nerves were lower in the RT group. The respiratory sinus arrhythmia was 12.1 +/- 1.2 beats min-1 in the RT group and 16.7 +/- 1.4 beats min-1 in the ICT group at the end of the study (P less than 0.01). The increases in retinopathy (P less than 0.01), nephropathy (P less than 0.01) and neuropathy (P less than 0.001) were all related to the mean HbA1c value during the study. Smoking habits only influenced the progression of retinopathy (P less than 0.05). Serious hypoglycaemia occurred in 34 ICT patients and 29 RT patients (242 and 98 episodes, respectively) (P less than 0.05). Whereas weight was stable in the RT group, the body mass index increased by 5.8% in the ICT group (P less than 0.01). In conclusion, microvascular complications of diabetes were retarded by intensified conventional insulin treatment. However, such treatment increased the frequency of serious hypoglycaemia, and led to an increase in body weight.
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PMID:Intensified conventional insulin treatment retards the microvascular complications of insulin-dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years. 186 59

To evaluate the potential of utilizing porcine islet tissue as an alternative to human islet tissue for transplantation, we developed a method for the isolation of large amounts of highly purified porcine islets, and assessed the in vitro and in vivo function of the isolated islets after 1, 4, and 7 days of culture. The pancreatic duct of the splenic lobe was cannulated and distended by injection of Hanks' balanced salt solution containing 1.5 mg/ml collagenase. The pancreas was then processed by a modification of the automated digestion-filtration method developed in this laboratory, and with purification accomplished by Euro-Ficoll gradients (dialyzed Ficoll in Eurocollins solution), consisting of two layers of 1.108 and 1.091 g/cm3 density, topped with a layer of HBSS. The postpurification yield was 5203 +/- 645 (mean +/- SEM) islets per gram of pancreas with a number of islet equivalents (IE) per gram pancreas (islet equivalence: 150-microns-sized islets) of 3551 +/- 305, and a volume of 6.27 +/- 1.7 mm3 islet tissue per gram of pancreas. The islet purity exceeded 90%. Overnight-cultured, perifused porcine islets released 53.1 +/- 8.2 pM insulin/200 IE at 3.3 mM glucose, and 114.9 +/- 25.4 pM insulin/200 IE at 16.7 mM glucose (P less than 0.001 vs. basal output). When theophylline was added, insulin secretion increased to 264.2 +/- 63.2 pM/200 IE (P less than 0.001 vs. basal secretion and P less than 0.005 vs. secretion at 16.7 mM glucose). After 4 days of culture, the islets still responded to secretagogues. The functional integrity of the isolated islets was confirmed by reversal of diabetes in aL3T4 antibody-treated C57B/B6 diabetic mice: normoglycemia was promptly restored by transplanting 1000 overnight- or 7-day-cultured (24 degrees C) islets under the kidney capsule. These results suggest that continued improvements of porcine islet isolation and culture could permit the use of porcine islets in immunoalteration and immunoisolation studies that may lead to eventual human transplantation.
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PMID:Automated large-scale isolation, in vitro function and xenotransplantation of porcine islets of Langerhans. 187 91

To define the kinetic mechanisms of insulin resistance (IR) in insulin-dependent diabetes (IDDM), we studied seven control (C) and five IDDM (glycohemoglobin, 14 +/- 2+) men matched for age (36 +/- 2 vs. 37 +/- 3 yr), lean body mass (59 +/- 2 vs. 58 +/- 3 kg), and leg volume (mean +/- SEM, 10.4 +/- 0.3 vs. 9.8 +/- 0.5 L). Maximal capacity (Vmax) and affinity (Km) for glucose uptake in whole body (WBGU) and leg skeletal muscle (LGU) were measured during a 120 mU/m2.min insulin infusion, and blood glucose was clamped at about 4, 7, 12, and 21 mmol/L. LGU = femoral arterio-venous glucose difference (FAVGD) X leg blood flow (LBF). Compared to C, IDDMs had about 35% lower rates of WBGU at all glucose levels (P less than 0.01). The FAVGD (millimoles per L) in C vs. IDDM was 1.23 +/- 0.05 vs. 1.06 +/- 0.09, 2.44 +/- 0.11 vs. 2.24 +/- 0.16, 2.91 +/- 0.18 vs. 2.91 +/- 0.30, and 3.27 +/- 0.12 vs. 3.35 +/- 0.4 (P = NS at each glucose). LBF (decaliters per min) was reduced in IDDM vs. C [2.8 +/- 0.5 vs. 4.3 +/- 0.4 (P less than 0.05), 3.1 +/- 0.4 vs. 5.1 +/- 0.7 (P less than 0.05), 2.7 +/- 0.2 vs. 6.3 +/- 0.8 (P less than 0.01), and 3.1 +/- 0.7 vs. 6.5 +/- 0.8 (P less than 0.01) at each glucose level]. Kinetic analysis revealed that 1) the Vmax for WBGU and LGU were reduced in IDDM vs. C (P less than 0.05), and 2) the Vmax for skeletal muscle glucose extraction (FAVGD) was identical in C and IDDM (3.6 mmol/L). The Km values for WBGU, LGU, and glucose extraction were not different in C and IDDM (approximately 6 mmol/L). Thus, in IDDM 1) decreased glucose uptake is due to reduced skeletal muscle glucose uptake; 2) muscle glucose extraction is normal, but blood flow is reduced; and thus, 3) in IDDM, IR is due to reduced glucose and insulin delivery (blood flow) to skeletal muscle. This represents a novel mechanism for in vivo IR.
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PMID:Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow. 187 38

We compared the effects of dietary treatment (D) and diet plus glibenclamide (DPG), for 3 weeks, on glycemia, insulin secretion and action in 2 groups of non-obese patients with NIDDM matched for fasting plasma glucose level. Fasting glycemia decreased in both groups with greater reductions after DPG (n = 7, 10.0 +/- 0.6 to 6.3 + 0.3 mmol/l, M +/- SEM, P less than 0.02) than after D (n = 7, 10.1 +/- 0.8 to 8.7 +/- 0.7 mmol/l, M +/- SEM, P less than 0.02). The magnitude of day-time elevation of plasma glucose over the fasting level, however, was reduced only after DPG. DPG but not D improved the plasma insulin response to glucose ingestion and in vivo insulin action measured by insulin tolerance test with unaltered erythrocyte 125I-insulin binding. This might indicate potentiation of insulin action at post-receptor binding steps. Improvements in in vivo insulin action and in insulin secretion after DPG closely correlated with decrease in fasting glycemia and reduction in the day-time elevation of plasma glucose levels, respectively. In conclusion, diet improved glycemic control in non-obese patients with NIDDM mainly by reducing fasting glycemia, although the mechanism remains unknown. Glibenclamide added to the diet further decreased fasting glycemia by improving in vivo insulin action and reduced the magnitude of day-time elevation of plasma glucose by enhancing endogenous insulin secretion.
Diabetes Res Clin Pract 1991 Feb
PMID:Comparative effects of diet or glibenclamide on insulin secretion and action in non-obese NIDDM. 190 11

Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/- 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reproducibility of insulin sensitivity measured by the minimal model method. 191 59

In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = -0.23, (95% confidence interval, -0.38 - -0.07) p less than 0.007 for male subjects and r = -0.24, (-0.37 - -0.11) p less than 0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = -0.33, (-0.45 - -0.20) p less than 0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (+/- SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 +/- 1.1 cm vs 176.9 +/- 1.3 cm in control subjects, p = 0.02. In the female subjects (n = 39) mean (+/- SEM) height was 159.4 +/- 1.0 cm vs 162.4 +/- 1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Height and glucose tolerance in adult subjects. 164 51

Our pilot study compared the short-term glycemic effects of a traditional "sucrose free" diet (Suc-Free, 2% total calories from sucrose) to a sucrose-containing diet (Suc-Con, 10% total calories from sucrose) in a clinical research center. Both weighed diets were isocaloric and included 50% carbohydrate, 30% fat, and 20% protein in three meals and three snacks; glucose, fructose, and dietary fiber were identical. Sucrose isocalorically replaced complex carbohydrate at each meal and for the afternoon snack. Ten children (7 to 12 years of age; mean total hemoglobin A1 level 8.9 +/- 0.3%) were randomly assigned, in a crossover design, to one of the two orders (Suc-Free followed by Suc-Con or Suc-Con followed by Suc-Free) for consecutive 2-day diet periods; insulin doses remained constant. Preprandial and postprandial blood glucose levels were measured for each meal and snack (18 measurements per day). To account for baseline differences, we calculated the change in blood glucose levels from baseline to 30 minutes and 1 hour for each meal and snack (mean +/- SEM). No differences were detected between diets. Total area under the glucose response curve (levels measured hourly from 8 AM to 9:30 PM in milligrams per deciliter) was not significantly different for the two diets (Suc-Free 3672 +/- 240; Suc-Con 3574 +/- 285; p = 0.74). No difference in 24-hour urinary glucose levels (measured in grams per day) was detected between the two diets (Suc-Free 35.6 +/- 7.5; Suc-Con 34.5 +/- 7.5; p = 0.84). Incidences of hyperglycemia that required supplemental short-acting insulin and of mild hypoglycemia were similar for both diet periods. Thus, in a controlled setting and during a short study period, children with insulin-dependent diabetes mellitus had a similar glycemic response to diets with and without a moderate amount of sucrose.
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PMID:Glycemic response to sucrose-containing mixed meals in diets of children of with insulin-dependent diabetes mellitus. 191 89

Low plasma high density lipoprotein (HDL) cholesterol concentration is a risk factor for coronary heart disease (CHD) and is frequently associated with high triglyceride concentration. Both of these abnormalities have been related to insulin resistance as estimated by plasma insulin concentrations and to measures of obesity, regional adiposity, and physical fitness. To determine which of these variables (fasting plasma insulin, obesity as measured by body mass index [BMI], or regional adiposity as measured by waist to hip ratio [WHR]) best identifies men with low HDL cholesterol and high triglyceride concentrations, we divided 83 men, aged 50-65 years, who were free of CHD or diabetes, into tertiles based on BMI, WHR, or fasting plasma insulin concentration. Only for plasma insulin tertiles were there statistically significant differences in HDL cholesterol (tertile 1, mean +/- SEM, 1.34 +/- 0.08 mmol/l; 2, 1.16 +/- 0.05 mmol/l; 3, 1.10 +/- 0.06 mmol/l; p less than 0.03) and triglyceride (tertile 1, 1.05 +/- 0.08 mmol/l; 2, 1.48 +/- 0.12 mmol/l; 3, 1.82 +/- 0.17 mmol/l; p less than 0.005) concentrations. In forward stepwise regressions with HDL cholesterol and triglyceride as dependent variables, fasting insulin concentration but not BMI, WHR, or maximal oxygen uptake (VO2max), a measure of physical fitness, predicted HDL cholesterol (R2 = 0.07, p less than 0.02) and triglyceride (R2 = 0.20, p less than 0.001) concentrations. The data suggest that plasma insulin concentration is an important predictor of HDL cholesterol and triglyceride concentrations independent of BMI, WHR, or VO2max.
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PMID:Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men. 193 67


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