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

The present prospective one-year randomized study was conducted to compare soluble human insulin, with a new rapid-acting human insulin analogue, lispro, with respect to postprandial glucose excursions, frequency of hypoglycaemic episodes, glucose control, and long-term safety in 39 subjects (20 females, 19 males) with Type 1 diabetes. The duration of diabetes, gender distribution, and age were similar in the two groups. The total number of hypoglycaemic episodes was significantly less (p < 0.04, Wilcoxon rank sum test) in subjects receiving insulin lispro compared with regular human insulin over the 12-month period. The 2-h postprandial glucose excursion at 1 year was also significantly less (p < 0.05, ANOVA) in the group treated with insulin lispro. The reductions in the total number of hypoglycaemic episodes and in the postprandial glucose excursion with use of insulin lispro may be beneficial for the long-term management of subjects with Type 1 diabetes. However, the greatest benefit identified by the subjects receiving insulin lispro was the greater convenience of the rapid-acting analogue.
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PMID:Pre-meal insulin analogue insulin lispro vs Humulin R insulin treatment in young subjects with type 1 diabetes. 874 12

The hypothesis that the prevalence of cardiovascular risk factors in people with diabetes is inversely related to socio-economic status was tested. Demographic and biochemical data were collected on 1246 patients, aged 20-69 years, attending a hospital diabetes clinic. This is estimated to represent between 71% and 78% of all people of this age with a diagnosis of diabetes in the health authority. In total, 296 people were classified as Type 1 (insulin-dependent) diabetic patients (age of onset < 31, now on insulin). Using data from the 1991 census a deprivation score was ascribed to each individual according to their area (enumeration district) of residence. The total study population was ranked by deprivation score and divided into quintiles. The relationships between means and quintiles of deprivation were assessed by ANOVA for linear trend, and between proportions and quintiles of deprivation by the chi-squared test for trend. In Type 1 diabetes increasing quintiles of deprivation were significantly related to mean serum cholesterol (p < 0.01) and proportion smoking (p < 0.01), and in Type 2 (non-insulin-dependent) diabetes to mean body mass index (p < 0.001), proportion smoking (p < 0.001), and proportion with proteinuria (p < 0.05). The need for health measures to prevent cardiovascular disease in people with diabetes is greatest in deprived areas.
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PMID:The relationships between cardiovascular risk factors and socio-economic status in people with diabetes. 874 16

Plasminogen activator inhibitor-1 (PAI-1) is related to insulin resistance and several components of the insulin resistance syndrome, and PAI-1 levels are elevated in subjects with non-insulin-dependent diabetes mellitus. Many Pima Indians are obese, insulin-resistant, and hyperinsulinemic, and they have high rates of diabetes but a low risk of ischemic heart disease. In contrast to whites and Asians, PAI-1 activity is similar between nondiabetic and diabetic Pima Indians. We therefore examined the association of PAI-1 with hepatic and peripheral insulin action measured using the hyperinsulinemic-euglycemic clamp. To investigate if insulin per se has any effect on PAI-1 in vivo, we also assessed the effects of endogenous (during a 75-g oral glucose load) and exogenous (during hyperinsulinemic clamp) insulin on PAI-1 antigen. Twenty-one (14 men and seven women; mean age, 26.3 +/- 4.8 years) Pima Indians underwent a 75-g oral glucose tolerance test (OGTT) and a sequential hyperinsulinemic-euglycemic clamp. Peripheral insulin action was measured as absolute glucose uptake (M value) and normalized to estimated metabolic body size (EMBS). Hepatic insulin action was measured as percent suppression of basal hepatic glucose output during hyperinsulinemia. PAI-1 antigen was determined using a two-site enzyme-linked immunosorbent assay that detects only free PAI-1. PAI-1 antigen concentrations were significantly related to body mass index ([BMI] rs = .54, P = .012), waist (rs=.52, P=.016) and thigh (rs=.63, P=.002) circumference, and fasting plasma insulin concentration (rs=.59, P=.004). PAI-1 antigen concentrations were not significantly associated with peripheral glucose uptake (M value) during either low-dose (rs= -.01, P=NS) or high-dose (rs= -.11, P=NS) insulin infusion. PAI-1 antigen was negatively correlated with basal hepatic glucose output (rs= -.57, P=.013) and percent suppression of hepatic glucose output during hyperinsulinemia (rs= -.69, P=.005). However, this relationship was largely due to the confounding effects of BMI, waist and thigh girth, fasting insulin, and 2-hour postload glucose concentrations, and was not significant when controlled for these variables (partial rs= -.30, P=NS). There was no significant relationship of PAI-1 antigen concentration with glucose storage or glucose oxidation. Despite a threefold increase in plasma insulin concentrations during the OGTT, there were no significant changes in PAI-1 antigen concentrations (median, 57, 61, 55, and 44 ng/mL at 0, 60, 120, and 180 minutes, respectively; P=NS by ANOVA). During the hyperinsulinemic clamp, mean plasma insulin concentrations at the end of low-dose (240 pmol/m2/min) and high-dose (2,400 pmol/m2/min) infusions were 1,005 and 14,230 pmol/L, respectively. However, PAI-1 antigen concentrations at the end of low-dose and high-dose insulin infusions were similar to those at baseline (median, 63, 43, and 58 ng/mL, respectively; P=NS by ANOVA). PAI-1 antigen in Pima Indians is related to several components of the insulin resistance syndrome. However, direct measurement of insulin resistance indicates that hepatic but not peripheral insulin resistance is related to PAI-1 antigen. Neither endogenous nor exogenous hyperinsulinemia for short periods had any significant effect on PAI-1 antigen concentrations. Short-term hyperinsulinemia is unlikely to be an important regulator of PAI-1 in Pima Indians. The relationship of PAI-1 antigen to hepatic insulin resistance is largely dependent on the relationship of PAI-1 to indices of obesity and fasting insulin concentrations.
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PMID:Relationship of hepatic and peripheral insulin resistance with plasminogen activator inhibitor-1 in Pima Indians. 884 79

Despite the establishment of heterotopic, whole cadaveric, pancreas-kidney transplantation as an effective form of therapy for type I diabetes with chronic renal insufficiency, uncertainty remains regarding the potentially deleterious effects of severe peripheral hyperinsulinemia and long-term immunosuppressive therapy on insulin sensitivity (SI) and, subsequently, on beta-cell function and maintenance of euglycemia over years. To examine the alterations in SI that may occur over time and their impact on glucose homeostasis, beta-cell function, SI, and glucose effectiveness (SG) were measured using the frequently sampled iv glucose tolerance test (FSIGTT) and minimal model method in 39 glucose-tolerant type I diabetic pancreas-kidney transplant recipients in a cross-sectional manner at 3, 6, 12, 24, 36, and 48 months post transplantation. Mean basal and poststimulation (oral glucose tolerance test and FSIGTT) serum glucose responses were similar among the groups from 3-48 months. Plasma insulin response during the FSIGTT was higher (P < 0.001, repeated measures ANOVA) at 6 months vs. 12-48 months. Incremental integrated areas under the curve for 1st phase, glucose-stimulated, tolbutamide-stimulated, and total insulin responses tended to be higher (P = NS) at 6 months. Glucose disappearance rate constant, kG, did not differ significantly from 3-48 months. Mean +/- SE S1 in the pancreas-kidney recipients was 4.25 +/- 1.6 x 10(-4) min-1/microU.mL-1 at 3 months (group 1, n = 7) (vs. 7.9 +/- 0.9 x 10(-4) normal reference), decreased to 2.95 +/- 0.6 at 6 months (group 2, n = 11), improved to baseline values of 4.6 +/- 1.0 at 12 months (group 3, n = 10), and normalized at 24 months (group 4, n = 6) to 7.5 +/- 1.7 (P = 0.008). The normalisation in SI was sustained at 36 months (group 5, n = 3, 8.0 +/- 3.7, P = 0.03), and up to 48 months (group 6, n = 5, 6.1 +/- 1.6, P = 0.04) in the type I diabetic pancrease allograft recipients. Corresponding SG tended to increase but did not differ significantly from 3 (1.69 +/- 0.2 x 10(-2)/min), 6 (2.33 +/- 0.39), 12 (1.9 +/- 0.2), 24 (1.9 +/- 0.4), 36 (1.98 +/- 0.15), and 48 months (2.27 +/- 0.3). Hepatic insulin extraction did not differ among the groups. SI correlated significantly with prednisone dose (r = -0.45, P = 0.002). In summary, after successful whole cadaveric, heterotopic, pancreas-kidney transplantation in type I diabetic recipients: 1) euglycemia remains relatively stable over 48 months; 2) SI is diminished early after transplantation (3-6 months), possibly caused by the effects of initially high doses of prednisone and hyperinsulinemia. However, this is compensated by a normal SG and by hyperinsulinemia to maintain euglycemia; 3) SI improves by 12 months and normalizes from 24-48 months, after transplantation, despite hyperinsulinemia and long-term immunosuppressive therapy. The time-dependent decrease in poststimulation insulin response after successful pancreas-kidney transplantation in type I diabetic recipients, therefore, is not caused by gradual beta-cell decline but rather is a response to normalization of SI. However, longitudinal studies pre-and post pancreas transplantation over an extended period of time will be necessary to confirm the present findings.
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PMID:Normalization of insulin sensitivity and glucose homeostasis in type I diabetic pancreas transplant recipients: a 48-month cross-sectional study--a clinical research center study. 885 94

Severe post-transplant obesity has previously been shown to have a negative impact on graft survival following kidney transplantation. It also contributes to late patient mortality and is associated with hypertension, diabetes and hyperlipidemia. We undertook Roux-en-Y gastric bypass (GBP) in three morbidly obese (200-260% ideal body weight) (IBW) patients 6-8 yr following kidney transplantation. Roux-en-Y gastrojejunostomy to a 30 ml stapled gastric pouch was created with the jejunojejunostomy (both loops) 80-120 cm from the ligament of Treitz. By 12 months post-GBP, weight loss plateaued at 100-150% IBW. Both patients that had developed post-transplant diabetes mellitus (PTDM) had complete resolution within 9 months following GBP. On average the patients required 3 less hypertension (HTN) medications after GBP; 2 of the 3 patients are now normotensive off medication. Improvements in hyperlipidemia were also shown. The absolute cyclosporine (CsA) requirement (mg/d) increased by approximately 33% (p = NS), and there was also a significant increase in the weight adjusted CsA requirement from 1.8 to 3.5 mg/kg/d (p = 0.02, ANOVA) following GBP in order to maintain similar TDX trough CsA levels. GBP offers significant reduction in weight, HTN, PTDM and hyperlipidemia in morbidly obese kidney transplant recipients. However, CsA dose requirements may increase after GBP as a consequence of the defunctionalized intestine.
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PMID:Gastric bypass in morbidly obese kidney transplant recipients. 893 Apr 54

Based on animal experiments it has been proposed that antihypertensive agents may differentially influence albuminuria through their divergent effects on glomerular haemodynamics or glomerular sieving properties and may beneficially influence the progression of diabetic nephropathy even without an effect on blood pressure. However, to date this hypothesis has not been tested in normotensive patients with diabetic nephropathy. The main aim of this study was therefore to investigate the effects of the administration of two antihypertensive agents on albuminuria during rest and exercise. The study consisted of 3 x 3 randomised, cross-over periods with five days double blind administration of enalapril (E: 2.5 mg bid), nitrendipine (N: 5 mg bid) and placebo (P) on 18 Type 1 normotensive (blood pressure < 140/90 mmHg) diabetic patients with incipient diabetic nephropathy (albuminuria 30-300 mg/24 h, normal glomerular filtration rate, diabetes duration > 6 years and presence of diabetic reinopathy. The aim of this study was to investigate the effect of enalapril and nitrendipine on blood pressure values and albuminuria during exercise challenge (bicycle ergometry: 20 min at 75 W and 20 min at 100 W) in comparison to the placebo. Albumin excretion rates during pre-exercise rest (mean +/- SD; E: 6.2 +/- 6.0; N: 7.1 +/- 8.0; P: 7.7 +/- 7.0 mg/mmol creatinine) and during exercise (E: 8.7 +/- 9.4; N: 8.2 +/- 8.2; P: 11.1 +/- 11.4 mg/mmol creatinine) were comparable between the drugs and not significantly different after administration of placebo. Blood pressure values were significantly different between the medications (systolic blood pressure: p = 0.0269; diastolic blood pressure: p = 0.0021, ANOVA for repeated measurements). There were no significant correlations between blood pressure values and albuminuria at any time. In normotensive patients with incipient diabetic nephropathy low-dose administration of enalapril, nitrendipine and placebo does not result in clear cut differences in albuminuria.
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PMID:Effects of enalapril and nitrendipine on exercise albuminuria in normotensive type I diabetic patients with incipient nephropathy. 893 14

The aim of the present study was to identify whether monocytic TNF alpha secretion patterns could serve as a potential phenotypic discriminator for periodontal disease susceptibility within insulin-dependent diabetes mellitus (IDDM) patients. In 32 IDDM individuals the lipopolysaccharide (LPS) stimulated monocytic TNF alpha secretion dose-response characteristics were analyzed and related to two different periodontal status categories. Diabetics were divided into group A (gingivitis or mild periodontal disease) and group B (moderate to severe periodontal disease). In addition, 17 non-diabetic individuals with various degrees of periodontal disease served as control patients. Diabetics as a group had a significantly higher monocytic TNF alpha production in response to increasing Porphyromonas gingivalis A 7436 lipopolysaccharide concentrations (0, 0.003, 0.03, 0.3 and 3.0 micrograms/ml) as compared to non-diabetic patients with gingivitis or adult periodontitis (p < 0.05). A significant difference in the dose response was also noted in the level of TNF alpha secreted as a function of P. gingivalis LPS concentrations between group A and B diabetics, as determined by two-way repeated measurements ANOVA (p < 0.05). Furthermore, there was no significant difference in the mean HbA1C between the two diabetic groups, and the TNF alpha level was not significantly associated with the HbA1C level within diabetic patients. These data suggest that the diabetic state results in an upregulated monocytic TNF alpha secretion phenotype (4.6-fold increase) which, in the presence of Gram-negative bacterial challenge, is associated with a more severe periodontal disease expression. In addition, approximately 40% (10 of 24) IDDM periodontitis patients in group B demonstrated a 62-fold elevation in TNF alpha secretion relative to non-diabetic gingivitis or periodontitis patients and a 13.5-fold increase relative to IDDM group A (gingivitis or mild periodontitis) patients.
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PMID:Monocytic TNF alpha secretion patterns in IDDM patients with periodontal diseases. 904 92

Current knowledge of the regulatory mechanisms of leptin synthesis and release is limited. To elucidate the role of short-term hyperinsulinaemia and hypoglycaemia on circulating levels of leptin, 7 healthy lean men underwent a 360-min hyperinsulinaemic (insulin infusion rate: 1.5 mU/kg/min) clamp in two conditions: (i) during 360 min of euglycaemia and (ii) during 120 min of euglycaemia followed by 240 min of graded hypoglycaemia (nadir 2.9 +/- 0.1 mmol/l). During hyperinsulinaemic euglycaemia, serum leptin levels were initially stable and then rose gradually after 180 min to a peak value of 147 +/- 7% of baseline (ANOVA, p < 0.01). During the hypoglycaemic clamp, the leptin profile differed from that of euglycaemic conditions (p < 0.01) since the increase was postponed and reduced. In both clamp studies, leptin dynamics contrasted with the changes in a control study performed in 7 other men whose serum leptin fell significantly (p < 0.05) to 77 +/- 4% of baseline values during a 360-min fast (following overnight fasting). It is concluded that hyperinsulinaemia for more than 3 h increases circulating levels of leptin in lean males, whereas hyperinsulinaemia with concomitant hypoglycaemia leads to transient suppression. The exact nature of the underlying mechanisms, e.g. changes in levels of insulin, glucose, various substrates, glucose turnover and/or counterregulatory hormones, remains to be determined.
Diabetes Metab 1997 Feb
PMID:Effects of hyperinsulinaemia and hypoglycaemia on circulating leptin levels in healthy lean males. 905 71

We measured the capacity of human plasma to induce cholesterol efflux from Fu5AH rat hepatoma cells in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Plasma from men with both NIDDM and CAD (n = 47) had the lowest efflux capacity (17.3 +/- 3.6%) whereas healthy control subjects with neither diabetes nor CAD (n = 25) had the highest capacity (19.8 +/- 3.4%). The groups with CAD but no diabetes (n = 44) and with NIDDM but no CAD (n = 35) had intermediate efflux values (18.5 +/- 3.8 and 18.5 +/- 3.9%, respectively). In a 2 x 2 factorial ANOVA, the differences were significant with respect to the presence of CAD (P = 0.038) and NIDDM (P = 0.041), with no interaction between the factors. The concentration of HDL particles containing apolipoprotein (apo) A-I but no apo A-II (LpA-I) was not related to efflux capacity in univariate or multivariate analyses. A multivariate regression analysis showed that when controlled for the presence of NIDDM and CAD, the concentration of particles containing both apo A-I and apo A-II (LpA-I:A-II) and plasma phospholipid transfer protein activity were both positively, independently, and significantly (P < 0.001) related to cholesterol efflux capacity.
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PMID:Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein. 912 15

In this article, we report on a nonobese C57BL/6 (B6) mouse model of NIDDM named Akita mouse, characterized by early age onset and autosomal dominant mode of inheritance. At 7 weeks of age, the mean morning blood glucose levels (mmol/l) under ad libitum feeding conditions were significantly higher (P < 0.01, analysis of variance [ANOVA]) in diabetic mice than in unaffected mice: 27.3 +/- 5.3 for diabetic males (n = 50) and 9.3 +/- 1.2 for unaffected males (n = 50); 13.6 +/- 3.8 for diabetic females (n = 50) and 8.7 +/- 1.1 for unaffected females (n = 50), while corresponding immunoreactive insulin levels in plasma were significantly lower in diabetic mice than in unaffected mice. In vitro insulin secretion was also impaired, even at 4 weeks of age. The 50% survival time for male diabetic mice (305 days) was significantly shorter than that of unaffected counterpart mice but not for diabetic females. Obesity did not occur in diabetic mice. Histological examinations of the pancreas in diabetic mice, from 4 to 35 weeks of age, revealed decreases in the numbers of active beta-cells without insulitis. Morphometry demonstrated specific decreases in immunologically detectable insulin density in islets in diabetic mice, even at 4 weeks of age, without changes of relative islet areas. By linkage analysis, a single locus was identified on the basis of 178 N2 mice [(B6 x C3H/He)F1 x B6 and (B6 x C3H/He)F1 x C3H/He]. This locus, which we named Mody4, was mapped to chromosome 7 in a region 2-8 cM distal to D7Mit189 (logarithm of odds [LOD] score = 15.6 and 10.3).
Diabetes 1997 May
PMID:A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. 913 60


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