UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary results of a three-year prospective, double-blind, placebo-controlled trial in non-insulin-dependent diabetic (NIDDM) patients show that an anti-hypertensive regimen, which includes the ACE inhibitor enalapril, preserves renal function to a greater extent than therapy with antihypertensive agents excluding ACE inhibitors (J Am Soc Nephrol 3:335, 1992). The influence of baseline urinary albumin excretion on the renal protective effects of enalapril treatment in these subjects was the objective of this further analysis. Adequate data were available in 121 patients of the 165 hypertensive NIDDM individuals studied [baseline glomerular filtration rate (GFR) 30 to 100 ml/min/1.73 m2]. Twenty-four hour urinary excretion of albumin (UAE), protein, urea nitrogen, creatinine and isotopically determined GFR were measured at baseline and six month intervals. Glycemic control and blood pressure regulation were assessed every three months. The rate of loss of GFR was significantly greater in patients with overt proteinuria at baseline (UAE > 300 mg/24 hr) as compared to patients with baseline sub-clinical proteinuria (UAE < or = 300 mg/24 hr). Antihypertensive treatment with enalapril preserved GFR significantly better (P < 0.01) in the patients with sub-clinical proteinuria at baseline (UAE < or = 300 mg/24 hr) than other antihypertensive treatments which excluded the ACE inhibitor. Furthermore, only 7% of the enalapril-treated group progressed to clinical albuminuria compared to 21% of control treated patients. Although the enalapril-treated group had a lower mean blood pressure during the maintenance period, no correlation between blood pressure (systolic, diastolic or mean arterial) and rate of change of GFR was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal protective effects of enalapril in hypertensive NIDDM: role of baseline albuminuria. 815 85

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.
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PMID:Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. 817 Sep 65

Alterations in the connective tissue of the arterial wall have been suggested to play a role in the development of macrovascular disease in diabetes mellitus. The present study deals with changes in the content of GAG in aortic tunica media in human diabetes by separately analysing normal areas and areas with fibrous plaques. The thoracic aorta from 15 diabetic patients (7 with IDDM, 8 with NIDDM), and 30 sex- and age-matched non-diabetic subjects were collected at autopsy. Tunica intima was removed and GAG were isolated from the dried defatted and pulverized tunica media. GAG were quantified by uronic acid analysis and characterized by electrophoresis on cellulose acetate. Results showed that IDDM patients had a relative and absolute increase in hyaluronic acid in normal tunica media compared to non-diabetic subjects. There was a significant positive correlation between hyaluronic acid content of normal tunica media and duration of diabetes, but not between hyaluronic acid content and age. When tunica media from plaque areas was compared to normal areas the same pattern was evident in diabetic patients as in non-diabetic patients--significantly increased proportion of dermatan sulphate and reduced hyaluronic acid. The data agree with the notion that the arterial wall is subject to different pathological processes in diabetes, one of classical atherosclerosis with changes in GAG similar to non-diabetic subjects, and the other seen in areas without plaques with dissimilar alterations in GAG. These data therefore support the concept of the presence of a macrovascular disease in diabetes different from atherosclerosis.
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PMID:Glycosaminoglycans in the human aorta in diabetes mellitus: a study of tunica media from areas with and without atherosclerotic plaque. 817 43

The present study compared the effect on insulin sensitivity of ACE inhibitors with a sulphydryl group (captopril) or those without a sulphydryl group (delapril and enalapril) during the hyperinsulinaemic euglycaemic clamp test in both animal and clinical experiments. A possible contribution of bradykinin to the improvement of insulin sensitivity by ACE-inhibition was also studied. In healthy control and depancreatized dog experiments, administration of captopril either intravenously (3.0 mmol.kg-1) or orally (5.0 mmol.kg-1) increased insulin sensitivity indices and plasma bradykinin concentrations. In comparison, intravenous administration of an active metabolite of delapril (3.0 mmol.kg-1) and oral administration of either delapril or enalapril (5.0 mmol.kg-1) showed slight, but not significant increases in insulin sensitivity indices and plasma bradykinin concentrations. Infusion of a bradykinin antagonist (N-alpha-adamantane-acetyl-D-Arg-[Hyp3,Thi5,8,D-Phe7]-b bradykinin) (0.5 nmol.kg-1 x min-1) abolished the effect of captopril on insulin sensitivity. Furthermore, intravenous administration of bradykinin (0.1 nmol.kg-1 x min-1) increased insulin sensitivity indices. In clinical experiments, insulin sensitivity indices decreased in the following order: normotensive healthy subjects, hypertensive non-diabetic patients, normotensive NIDDM patients and hypertensive NIDDM patients. In these four groups, oral administration of captopril (2.0 mmol.kg-1) significantly increased insulin sensitivity indices, and a concomitant increase in plasma bradykinin concentrations was observed. By contrast, oral administration of enalapril or delapril showed slight, but not significant effects on insulin sensitivity indices and plasma bradykinin concentrations. From these studies, it is concluded that ACE inhibitors with a sulphydryl group have more potent action on the improvement in insulin sensitivity than those without a sulphydryl group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect on insulin sensitivity of angiotensin converting enzyme inhibitors with or without a sulphydryl group: bradykinin may improve insulin resistance in dogs and humans. 817 45

The plasma membrane enzyme (Ca2+ + Mg2+)-adenosine triphosphatase [(Ca2+ + Mg2+)-ATPase] is hormonally regulated, and may participate in Ca2+ signaling by removing excess Ca2+ from the cell. Insulin increases ATPase activity in kidney cortical basolateral membranes (BLM) from normal rats, but fails to do so in membranes from insulin-resistant non-insulin-dependent diabetic (NIDDM) rats. To investigate mechanisms of insulin regulation of ATPase and to evaluate whether the loss of this regulation in diabetes is hormone-specific and depends on blood glucose levels, (Ca2+ + Mg2+)-ATPase function and its hormonal regulation were studied in kidney BLM from rats with mild and severe NIDDM. Km values for ATP and Ca2+ affinity of the ATPase were similar in diabetic and control rats, but the maximal velocity (Vmax) of the enzyme was higher in diabetic groups. Insulin, the protein kinase C (PKC) stimulator 12-0-tetradecanoylphorbol 13-acetate (TPA), parathyroid hormone (PTH), and cyclic adenosine monophosphate (cAMP) all increased the ATPase activity in BLM from controls by increasing the enzyme's affinity for Ca2+. A protein kinase A (PKA) inhibitor (H8 in low concentrations) abolished cAMP and PTH effects, but not those of insulin, whereas the PKC inhibitors (sphingosine and high concentrations of H8) did abolish the effects of insulin. Stimulations of ATPase activity by insulin and by PTH and cAMP were additive. Insulin and TPA lost their stimulatory effects on ATPase in BLM from rats with either mild or severe NIDDM, but PTH and cAMP maintained their stimulatory effects in these membranes. The data show [1] (Ca2+ + Mg2+)-ATPase activity is increased in NIDDM, and a hormone-specific loss of insulin stimulation of ATPase occurs; (2) these defects are not dependent on the level of glycemia; and (3) the stimulatory effects of insulin on the ATPase may be mediated in part via PKC. We suggest that the hormone-specific defect in insulin regulation of ATPase seen in the NIDDM rats may contribute to their insulin resistance.
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PMID:Hormone-specific defect in insulin regulation of (Ca2+ + Mg2+)-adenosine triphosphatase activity in kidney membranes from streptozocin non-insulin-dependent diabetic rats. 817 49

We determined whether overnight inhibition of lipolysis by a long-acting nicotinic acid derivative (acipimox) decreases gluconeogenesis from lactate in NIDDM patients. For this purpose, 250 mg of acipimox or placebo was administered in a double-blind crossover study at 2400, 0400, and 0800 to 8 NIDDM patients (54 +/- 4 yr of age, body mass index 29.5 +/- 1.3 kg/m2, fasting plasma glucose 11 +/- 1 mM). The next morning, total hepatic glucose production (glucose Ra) and gluconeogenesis from lactate were determined using primed, continuous infusions of [3-3H]glucose and [U-14C]acetate. Glucose and lipid oxidation rates were measured using indirect calorimetry. Mean overnight serum free fatty acid concentrations averaged 242 +/- 8 microM after acipimox and 721 +/- 30 microM after placebo (P < 0.001). Inhibition of lipolysis decreased lipid oxidation from 33 +/- 3 to 22 +/- 2 J.kg-1 x min-1 (P < 0.001) and increased carbohydrate oxidation from 15 +/- 3 to 23 +/- 2 mumol.kg-1.min-1 (P < 0.005). Gluconeogenesis from lactate decreased by approximately 40%, from 6.2 +/- 0.6 to 3.8 +/- 0.5 mumol.kg-1 x min-1 (P < 0.005); lactate oxidation increased from 5.6 +/- 0.8 to 7.9 +/- 1.1 mumol.kg-1 x min-1 (P < 0.005), with no change in plasma lactate concentrations or total lactate Rd. Fasting plasma glucose concentrations were comparable at 2400 (10.0 +/- 1.1 vs. 10.6 +/- 1.3 mM, acipimox vs. placebo) and between 0900 and 1000 (10.6 +/- 1.3 and 11.3 +/- 1.3 mM, respectively). Also, total glucose production rates remained unchanged (14.0 +/- 1.2 vs. 14.9 +/- 1.3 mol.kg-1 x min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM. 824 14

To measure the rate of gluconeogenesis in humans directly, one must administer and determine the specific activity or the enrichment in an intermediate in the gluconeogenic process and in the glucose formed, thus obtaining the fraction of the glucose formed by gluconeogenesis. By a separate determination of the rate of hepatic glucose production, the rate of gluconeogenesis can then be calculated. The closer the intermediate is to glucose-6-P, the more complete will be the measurement of the rate. Thus, if the intermediate is below the level of the triose phosphates, gluconeogenesis from glycerol will not be included in the estimate. Estimates of rates of gluconeogenesis from estimates of PEP enrichment or specific activity require a measure of the extent of exchange of label at the level of oxaloacetate. By using 14C or 13C labeled CO2 as the intermediate and estimating the relative rates of the reactions of the tricarboxylic acid cycle relative to gluconeogenesis from the distribution of 14C from [3-14]lactate in glutamine from the glutamine conjugate of phenylacetate, the enrichment or specific activity of PEP has been estimated. Correction must be made for the incorporation into the glutamine of 14CO2 formed from the [3-14C]lactate. Data support the validity of this approach toward estimating gluconeogenesis in NIDDM, but the approach is complex, time consuming and with uncertainties. Estimates that have been made using [2-14C] acetate are invalid because of the extensive metabolism of [2-14C]acetate in other than liver. Other approaches have promise, but technical problems may exist in their use and other problems, such as hepatic zonation and exchange reactions, may compromise their application.
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PMID:Estimating gluconeogenic rates in NIDDM. 824 84

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79

Non-insulin-dependent or type 2 diabetes is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action; these defects are worsened by the developing hyperglycaemia. Diabetes is an independent risk factor for the development of cardiovascular disease. In addition to hypertension, which is encountered in almost 50% of patients, lipid abnormalities, comprising elevations of both LDL-cholesterol and VLDL-triglycerides, as well as decreases in the levels of HDL-cholesterol, contribute to the high prevalence of vascular disease. Elevated levels of serum lipoprotein(a) may add to this increased risk. Considering the apparent clustering of risk factors such as poor metabolic control, obesity, hypertension and dyslipidaemia, the attainment of optimal blood glucose control forms only one of the aims of treatment to prevent the neurological and vascular complications, which severely affect the quality of life. Dietary advice comprises the adoption of healthy eating habits and reducing the intake of refined sugars and saturated fat. The long-term metabolic effects of intensive dietary therapy, however, have been disappointing. This necessitates early pharmacological treatment in a considerable number of patients. With mild hyperglycaemia, the metabolic effects of sulphonylurea and insulin treatment were comparable, but insulin is superior to sulphonylurea in patients who are more hyperglycaemic (fasting blood glucose > 11 mmol/l). In addition to its effects on blood glucose control, insulin therapy favourably affects dyslipidaemia. Treatment can be safely instituted on an outpatient basis, and hypoglycaemic side-effects are infrequent. Combination therapy of insulin and sulphonylurea results in similar metabolic improvement when compared with insulin treatment alone, but with a lower dose of insulin and the need for only one injection in two-thirds of patients. Drugs such as ACE inhibitors, which have no metabolic side-effects, have become the therapy of choice when treating hypertension in diabetic patients.
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PMID:Type 2 diabetes mellitus. Aspects of complications and treatment. 830 99

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.
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PMID:Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy. 836 Jul 96

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