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

Patients with non-insulin dependent diabetes mellitus and obesity show an elevated risk for development of arterial hypertension, while many non-obese, non-diabetic patients with essential hypertension display resistance to insulin-induced glucose disposal, accompanied by hyperinsulinaemia. This close association has lead some investigators to postulate that insulin resistance could be implicated in the pathogenesis of essential hypertension. Among the various factors considered as potential links between insulin resistance and high blood pressure, the sympathetic nervous system can be considered a prime candidate. In particular, our recent data in hypertensive patients have documented that the muscle sympathetic response evoked by insulin is about threefold greater than that observed in normal subjects. Such finding is well in agreement with previous observations in hypertensives obtained with experimental maneuvers and extends them by showing an abnormal sympathetic response to a physiological stimulus like insulin, so important in every day life. Recent data both from our and other laboratories have clearly established that an acute activation of sympathetic nervous system is able to antagonize insulin-mediated glucose uptake in the skeletal muscle, making very real the possibility that a primary defect in insulin sensitivity in hypertension may be further aggravated by the greater sympathetic response evoked by episodic stimuli, such as postprandial hyperinsulinaemia. However, while insulin evokes an increase in sympathetic nervous activity, at same time it is able to blunt the vasoconstrictive effects caused by the reflex sympathetic activation. Such vascular modulating effect of insulin is lost in essential hypertension, indicating that the resistance to insulin effect in this disease is not only present in skeletal muscle metabolism but it is also evident at the vascular level.
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PMID:The crosstalk between insulin and the sympathetic nervous system: possible implications in the pathogenesis of essential hypertension. 916 36

Several reports indicate higher endothelin-1 (ET-1) levels in patients with non insulin dependent diabetes mellitus (NIDDM), although this finding has not been confirmed by other studies. The discrepancy may be partially explained by the frequent coexistence in NIDDM patients of other pathologies, such as essential hypertension, and by the presence of diabetic vascular complications or renal failure, able, per se, to increase ET-1 circulating levels. This study aimed to evaluate the influence of arterial hypertension and/or of diabetic angiopathy on ET-1 circulating levels in a group of NIDDM patients. We measured ET-1 plasma concentrations in three groups of subjects: a) 22 NIDDM patients with or without hypertension and with or without vascular complications; b) 11 hypertensive patients; c) 14 age-matched healthy volunteers. Plasma ET-1 concentrations were significantly higher in NIDDM patients with angiopathy (7.3 +/- 0.7 pg/ml, mean +/- Standard Error; p < 0.001) than diabetics without angiopathy (4.4 +/- 0.53 pg/ml), hypertensive patients (4.7 +/- 0.85 pg/ml) and healthy subjects (3.1 +/- 0.19 pg/ml). This report indicates that increased plasma ET-1 levels in NIDDM patients may be ascribed only to those with vascular compliances, while hypertension, per se, does not affect ET-1 plasma levels in these patients.
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PMID:Vascular damage and not hypertension per se influences endothelin-1 plasma levels in patients with non insulin dependent diabetes mellitus. 927 Feb 91

The therapeutic advantage of the long acting ACE-inhibitor benazepril in a 12 weeks intervention period on 23 diabetic (3 IDDM, 20 NIDDM) patients with essential hypertension was studied. Participants-giving informed consent before beginning the study-on the base of repeated casual blood pressure measurements were divided into "slightly" (n = 8) and "moderately" (n = 15) hypertonic groups. Type of diabetes, time elapsed since its manifestation, actual antidiabetic therapy, period of existence of the hypertension (newly discovered vs known and treated for a time) were independent from the point of view of entering the study. Initial dose of benazepril was 5-10 mg/day depending on the blood pressure level, followed by a stepwise dose elevation according to the control investigations (at weeks 2, 4, 8 and 12 casual blood pressure control, at weeks 4 and 12 ambulantory blood pressure monitoring, ABPM as well) to a maximal daily dose of 20 mg. In the majority of patients benazepril was given in a morning single dose, in some cases because of a better tolerability divided into two parts. 20 patients received benazepril in monotherapy, 3 patients combined with other antihypertensive preparations. Parameters indicating severity of hypertension-hypertonic time index, hyperbaric impact-showed significant improvement already at week 4 when analysed in the total of patients and the moderately hypertonic group respectively. As a tendence the same was observed also in the slightly hypertonic group. No remarkable side effects, or alterations of the metabolic state and in the investigated laboratory parameters appeared. Based on these results benazepril is an effective choice in the treatment of diabetic hypertensive patients.
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PMID:[Experience with benazepril, a long-acting ACE inhibitor, in the management of diabetic hypertension]. 927 85

Hyperinsulinemia and insulin-resistance are metabolic disturbances associated with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance, overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in vivo) changes achieved by life style modifications or drug interventions require a reproducible technique. To evaluate the day-to-day intra-individual repeatability of SAI-in vivo, we determined the variation in the SI index (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11 subjects with a wide range of insulin-resistance. SI (first study) varied from 0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002). The average interday coefficient of variation was 20.9 +/- 13.9% and was similar in subjects with low or high SI values. We also measured SAI in vivo by assessing the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in 11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8 mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p = 0.0002). Our results suggest that the Mmins is a fairly reproducible procedure and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a fast-execution practice is necessary or cost restrictions are required.
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PMID:[Repeatability of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test]. 928 67

Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the "insulin resistance syndrome," according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well-established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.
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PMID:Endothelial dysfunction: cause of the insulin resistance syndrome. 928 92

Non-insulin-dependent diabetes mellitus, obesity, and essential hypertension are associated with hyperinsulinemia that results from insulin resistance and insulin has been reported to accelerate atherosclerosis. We studied the effects of insulin and insulin-like growth factor-1 (IGF-1) on the growth of porcine vascular smooth muscle cells and on the synthesis of extracellular matrix. The cells were cultured 3-8 changes of Dulbecco's modified Eagle's medium (DMEM) with 10% FCS. Subconfulent cells were put in wells 1 x 10(4) or 1 x 10(5) cells/well in DMEM with or without insulin or IGF-1. The number of cells was counted, and protein and DNA synthesis, expression of genes for collagen alpha1(1), and collagen synthesis were measured. Insulin (0, 16, and 160 nM) and IGF-1 (0, 1, 31, and 13.1 nM) increased number of cells by 50% and 40%, in a dose-dependent manner. Protein and DNA synthesis were also increased by insulin (3.8 and 3.0 times) and by IGF-1 (3.9 and 1.8 time). Collaged protein synthesis was increased 2.3-fold by IGF-1 at 13.1 nM, and insulin (16,000 nM) caused a 26.5-fold increase. Levels of collagen alpha1(1) mRNA were also increased by both insulin and IGF-1. These results suggest that insulin and IGF-1 can cause vascular hyperplasia associated with increased collagen synthesis, which indicates that insulin, IGF-1, or both may have an important role in vascular growth.
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PMID:[Effect of insulin and insulin-like growth factor-1 on vascular smooth muscle cells]. 938 74

Reduced ability or failure to stimulate cyclic adenosinemonophosphate (AMP) synthesis on a second addition of hormone 30 min after a first stimulation was taken as an indirect indication of the synthesis of the cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP). In diabetic rats, because of an increased possibility of restimulating cyclic AMP synthesis, the formation of cyclic PIP should be reduced. Additionally, severalfold increased basal cyclic AMP synthesis can be observed in diabetic hepatocytes in comparison with controls. Upon measuring cyclic PIP levels after hormonal stimulation in all organs of diabetic rats, it was found that stimulation of cyclic PIP synthesis by insulin decreased gradually in a time-dependent manner. Plasma membranes were prepared from diabetic Ksj db/db mice and from spontaneously hypertensive rats (SHR), and in a subsequent assay for cyclic PIP synthetase, an up to 60% decrease of enzyme activity was found. Cyclic PIP synthetase can be completely inhibited by preincubation with protein kinase A. It is most likely that this serine phosphorylation reaction by which the enzyme is inhibited also in vivo is a result of increased cyclic AMP levels. The addition of 10(-5)-10(-4) M sulfonylureas to the enzyme assay of liver plasma membrane causes full inhibition, and the addition of 10(-5)-10(-4) M biguanides, a two- to fourfold activation of the enzyme. Activation of cyclic PIP synthetase by biguanides can also be demonstrated in intact cells. It is a fast reaction and additive with respect to the activation by fluoride or guanylyl-imidodiphosphate (GMP-PNP), and it is most likely the effect with which the biguanides produce the correcting changes in metabolism. Furthermore, antihypertensive drugs like captopril, guanethidine, and dihydralazine also activate cyclic PIP synthetase. In contrast to the activation by the biguanides, this effect is not additive to the activation by fluoride. It appears that essential hypertension and type 2 diabetes are connected with or may be the result of a reduction in synthesis of the intracellular messenger cyclic PIP, whose synthesis is stimulated by hormones like insulin and noradrenaline (alpha-adrenergic action).
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PMID:Insulin resistance, a result of reduced synthesis of prostaglandylinositol cyclic phosphate, a mediator of insulin action? Regulation of cyclic PIP synthetase activity by oral antidiabetic and antihypertensive drugs. 945 69

It is commonly accepted that the tolerance to insulin and hyperglycemia of the patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some defect of insulin receptors or disturbances in the signaling pathway of the cell. This disease is often accompanied by hypertension. In this paper the high activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8 times higher than normal), of angiotensin-converting enzyme (ACE) (4 times greater than normal), and of leukocyte elastase (2.7 times higher than normal) were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity was coincident with rising of ACE activity, which may be the cause of the fast bradykinin inactivation and arising of hypertension. The treatment with ACE inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in patients' plasma which was accompanied with decreasing of the arterial pressure and some restoration of the carbohydrate metabolism indicators. The hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin from destruction and increased the glucose consumption by tissues. The high activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM patients' plasma and/or instability of plasmatic and granular membranes of leukocyte in conditions of hyperglycaemic plasma are probably the cause of endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the cause of injuring and decreasing of susceptibility of the cell receptors for insulin and bradykinin.
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PMID:[Possible participation of angiotensin-converting enzyme and leukocyte elastase in the pathogenesis of insulin-independent diabetes mellitus]. 963 24

The serum concentrations of digoxin-like immunoactivity (DLIA) were measured in 99 patients: 20 healthy volunteers (HV), 15 patients with insulin-dependent diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes mellitus without hypertension taking oral hypoglycemic (OHA) agents (NIDDM/-HT), 11 patients with NIDDM without hypertension taking insulin (NIDDM/-HT+INS), 12 NIDDM patients with hypertension taking OHA (NIDDM/+HT), nine NIDDM patients with hypertension taking insulin (NIDDM/+HT/+INS), 10 patients with essential hypertension with normal insulin levels (HT/-HI), and in eight patients with essential hypertension with hyperinsulinemia (HT/+HI). The numbers (%) of subjects with DLIA levels above the detection limit of the assay used (> 0.1 nmol/L) were, in the NIDDM/-HT group, 12/14 (85.7%) and in the NIDDM/+HT group, 9/12 (75%), significantly higher (P < .05) than in the HV (7/20; 35%), IDDM (3/15; 20%), and HT/-HI groups (2/10; 20%). The number and percentage of subjects with DLIA levels above the detection limit in the HT/+HI group was six of eight (75%), significantly (P < .05) higher than in the IDDM and HT/-HI groups, and tended to be higher than in the HV group (P < .055). Means and SD of serum DLIA levels (nmol/L) in the NIDDM/-EH (0.18/0.09) and NIDDM/+EH (0.19/0.15) groups were significantly higher (P < .05) than in the HV (0.09/0.07), IDDM (0.05/0.05), and EH/-HI (0.06/0.06) groups. DLIA levels in the HT/+HI group (0.15/0.12) were significantly higher (P < .05) than in the IDDM and HT/-HI groups. The percentage of DLIA levels above the detection limit, as well as the mean and SD of DLIA in the NIDDM group taking OHA, did not differ from those in subjects taking insulin. In all subjects studied (n = 99), DLIA correlated with C-peptide (r = 0.30; P < .01) and glomerular filtration (GF) (r = -0.21; P < .05). After exclusion of insulin-treated patients, DLIA correlated significantly with plasma glucose (PG; r = 0.25; P < .05), immunoreactive insulin (IRI; r = 0.41; P < .001), C-peptide (r = 0.27; P < .05), and GF (r = -0.26; P < .05) (n = 64). Correlation of DLIA with IRI (r = 0.33; P < .05; n = 38) also persisted after exclusion of patients taking insulin and those with DLIA levels below the detection limit. Similarly, DLIA also correlated with C-peptide (r = 0.64; P < .05) and IRI (r = 0.70; P < .05) in the subgroup of 10 patients with the highest levels of DLIA (> 0.25 nmol/L). None of the sera (n = 15) with different DLIA concentrations (0.0-0.38 nmol/L) exhibited K-pNPPase (Na+-K+-ATPase) inhibitory activity. In conclusion, this work demonstrated elevated serum DLIA in NIDDM and HT/+HI patients, and its correlation with IRI and GF. However, due to the fact that the chemical nature and biologic properties of DLIA are still a matter of debate, it is too early to speculate whether the elevation of DLIA is just a secondary result associated with HI and reduced GF, or whether it also has pathophysiologic consequences. Nevertheless, in both cases the elevated concentrations of substances with DLIA and their interference with antidigoxin antibodies may affect therapeutic monitoring of digitalization in NIDDM and HT/+HI patients. Also, the elevated DLIA could subclassify these patients. The significance of such subclassifications (pathophysiologic, therapeutic, or prognostic), however, will need further investigation.
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PMID:Endogenous digoxin-like immunoactivity in subjects with diabetes mellitus and hypertension. 965 25

Hypertension in pregnancy and gestational diabetes have in common a lack of universally accepted classification and nomenclature that hinders comparison of data between research groups and contributes to the lack of consensus in the literature on these conditions. The inter-relationship of hypertension and gestational diabetes can be considered from three viewpoints according to whether hypertension is present before, during, or after the pregnancy. The first question is whether hypertension predating pregnancy predisposes to gestational diabetes. Epidemiological evidence and physiological argument based on the common etiologic factor of insulin resistance would suggest that gestational diabetes should be more common in the presence of preexisting hypertension. The limited clinical data available support this hypothesis. There are three issues concerning the coexistence of hypertension and gestational diabetes: whether gestational diabetes predisposes to pregnancy-induced hypertension, whether pregnancy-induced hypertension predisposes to gestational diabetes and what effect the combination has on morbidity and mortality. A number of studies have investigated whether pregnancy-induced hypertension is more common in women with gestational diabetes, but no consensus has been reached. There is little direct clinical evidence on the reverse issue, but data are presented to suggest that pregnancy-induced hypertension may only predispose to gestational diabetes when its etiology is gestational hypertension and not preeclampsia. The issue of how the coexistence of pregnancy-induced hypertension and gestational diabetes affects maternal or neonatal morbidity and mortality is largely unanswered. The last question is whether gestational diabetes has any prognostic significance with regard to the future development of hypertension in the mother. It is well known that gestational diabetes predisposes to subsequent NIDDM and that NIDDM is associated with a high incidence of essential hypertension. Once again insulin resistance may be a unifying factor. However, there is no direct clinical evidence that gestational diabetes predisposes to future hypertension.
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PMID:Hypertension in women with gestational diabetes. 970 24


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