UMLS:C0085580 - FACTA Search

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Query: UMLS:C0085580 (essential hypertension)
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Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.
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PMID:Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM. 151 93

Individual dietary regulation is still an important part of all forms of treatment of diabetes. In insulin dependent diabetes (IDDM) it is rational to advise the patient 1) to arrange his diet so that this results in a low glycaemic response, which implies a relatively high intake of dietary fibre and polysaccharides, 2) to distribute the food into 5-6 daily meals and 3) to consume a low-fat diet. This prevents too pronounced postprandial hyperglycaemia and hypoglycaemia between meals. Simultaneously, insulin sensitivity is increased and not only the insulin requirement but also peripheral hyperinsulinism tend to be reduced. Dietary regulation in IDDM is thus a compensation for the defective synchronization of variations in the plasma levels of glucose and insulin in the present day forms of insulin therapy. Nine out of ten diabetic patients are non-insulin dependent (NIDDM). The great majority are obese, 50% have essential hypertension and just as many have dyslipidaemia (raised serum triglyceride and reduced serum high density lipoprotein (HDL)-cholesterol). The condition is characterized pathophysiologically by insulin resistance in muscle, fat and liver tissue and delayed and frequently reduced glucose-stimulated secretion of insulin. The most important element in dietary regulation in NIDDM is, therefore, reduction of the energy content of the food with the object of achieving and maintaining reduction in weight. Even moderate reduction, in the majority of NIDDM patients, will have the effect that metabolism of carbohydrates and lipids becomes approximately normal on account of considerable increase in insulin sensitivity and to a lesser degree increased secretion of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dietary treatment of diabetes mellitus. Background and rationale for recommendations in the 1990's]. 141 88

Kidney disease is a primary cause of morbidity and mortality in diabetic patients. Factors that predetermine development of nephropathy remain unknown. Poor glycemic control, insulin requirement, duration of diabetes and family history of hypertension appear to be associated with an increased risk. Arterial hypertension, which is twice as common in diabetic patients as in the normal population, accelerates the progression of diabetic nephropathy. The pathophysiologic mechanisms responsible for hypertension appear to be different in IDDM and NIDDM. In IDDM, hypertension occurs usually as a consequence of diabetic renal disease. Conversely, the pathogenesis in NIDDM appears to be multifactorial. In either condition, aggressive blood pressure control is the single most important intervention proven to retard the progression of nephropathy. A stepped-care approach similar to that for essential hypertension with slight modifications is indicated in the treatment of the hypertensive diabetic patient with nephropathy. Nonpharmacological therapy, including dietary protein restriction, should be used as first step. Selection of the ideal antihypertensive must be based not only on efficacy but also on its side effect profile. Angiotensin converting enzyme inhibitors and calcium antagonists have a low incidence of side effects and do not induce metabolic disturbances. Therefore, they are the agents of choice for patients who do not respond to nonpharmacological therapy alone. Thiazide diuretics and beta-blockers should be used as first line therapy only for specific indications. Antihypertensive therapy combined with good glycemic control and dietary protein restriction constitute the standard of care for diabetic patients with hypertension and renal disease.
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PMID:Hypertension and kidney disease of diabetes mellitus. 176 55

An endogenous sodium pump inhibitor, or digitalis-like factor (DLF), has been postulated to mediate essential hypertension. It may also play a role in preeclampsia. However, studies of this factor in hypertensive pregnancy have not provided consistent findings. Part of this may be due to the absence of subclassification of pregnant women with pregnancy-induced hypertension (PIH) when assessing these parameters. In this study we explored serum DLF and digoxin-like immunoreactive factor (DLIF) in insulin-dependent diabetic (IDDM) women with normotensive pregnancies or PIH, comparing them to each other and to nondiabetic pregnant women. Our results demonstrated that nondiabetic women with preeclampsia (PE, PIH with proteinuria) had significantly increased serum DLF and DLIF compared to normotensive pregnant women (NL BP). Women with transient hypertension of pregnancy (THP, PIH without proteinuria) had intermediate values (DLF. NL BP: 3.3 +/- 0.6, THP: 4.8 +/- 1.1, PE: 7.6 +/- 1.3% inhibition [Na,K]-ATPase, P < .05 ANOVA; DLIF. NL BP: 0.22 +/- 0.02, THP: 0.28 +/- 0.03, PE: 0.35 +/- 0.02 ng digoxin equivalents/mL, P < .05 ANOVA). Pregnant normotensive IDDM women had significantly higher serum DLF and DLIF activity than their nondiabetic counterparts (DLF. non-IDDM NL BP: 3.3 +/- 0.6 v IDDM NL BP: 8.8 +/- 1.2% inhibition [Na,K]-ATPase, P = .0008; DLIF. non-IDDM NL BP: 0.22 +/- 0.02 v IDDM NL BP: 0.31 +/- 0.02 ng digoxin equivalents/mL, P = .005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Digitalis-like factor and digoxin-like immunoreactive factor in diabetic women with preeclampsia, transient hypertension of pregnancy, and normotensive pregnancy. 873 86

We investigated both sodium-lithium countertransport (Na-Li CT) and ouabain-sensitive sodium transport (Na pump) of erythrocytes in healthy subjects (group A), patients with non-insulin-dependent diabetes (NIDDM) without nephropathy (group B), patients in the proteinuric stage (group C), and those in the renal insufficiency stage (group D). Erythrocytes from all four groups had a similar initial water and ionic content and were loaded with similar degrees of Li and Na for efflux studies. There were no significant differences in erythrocyte Na-Li CT or Na pump among the four groups. However, the maximal rate of Na-Li CT was significantly higher in a group of subjects with essential hypertension when compared with groups A, B and C, consistent with the view that there is a genetic marker for essential hypertension. Ouabain-insensitive Na efflux (Na leak) of erythrocytes was found to be significantly higher in group D than in groups A or B. Also, a significant positive correlation existed between Na leak and urine protein levels of the subjects studied. Our results thus indicate that in contrast with insulin-dependent diabetic patients (IDDM) where an elevated Na-Li CT is observed, with diabetic nephropathy, Na-Li CT in NIDDM is apparently not associated with nephropathy; rather the ouabain-insensitive Na efflux appears to be correlated with the stages of nephropathy in NIDDM. The association suggests that the rate of ouabain-insensitive Na efflux may provide an index for assessing the degree of nephropathy in NIDDM patients.
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PMID:Abnormalities of sodium transport in non-insulin-dependent diabetes: association with renal disease. 810 99

Genotypic abnormalities of the renin-ANG system have been suggested as a risk factor for the development of diabetic nephropathy. Cleavage of angiotensinogen is the rate-limiting step in the activation of the renin-ANG system. The TT genotype of a polymorphism encoding threonine instead of methionine (M235T) has been associated not only with increased plasma angiotensinogen concentration but also with essential hypertension. In addition, a polymorphism in the angiotensinogen gene substituting methionine for threonine (T174M) has been associated with hypertension in nondiabetic populations. We studied the relationship between these polymorphisms in the angiotensinogen gene in IDDM patients with diabetic nephropathy (121 men, 74 women, age 40.9 +/- 10 years, diabetes duration 27 +/- 8 years). There was no difference in M235T genotype distribution between IDDM patients with diabetic nephropathy and those with normoalbuminuria: 73/97/25 (37/50/13%) vs. 67/95/23 (36/52/12%) had MM/MT/TT genotypes, respectively. No difference in distribution of T174M genotypes between nephropathic and normoalbuminuric IDDM patients was observed either: 148/44/1 (77/23/0.5%) vs. 141/42/2 (76/23/1%) had TT/TM/MM genotypes, respectively. In patients with nephropathy, systolic blood pressure was higher (161 +/- 22 mmHg [mean +/- SD]) in patients carrying TT genotype of the M235T angiotensinogen polymorphism as compared with patients with MM or MT genotypes (150 +/- 23 mmHg; P = 0.03). We conclude that neither the M235T nor the T174M polymorphism in the angiotensinogen gene contributes to genetic susceptibility to diabetic nephropathy in white IDDM patients, whereas the TT genotype of the M235T is associated with elevated blood pressure in patients with diabetic nephropathy.
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PMID:Angiotensinogen gene polymorphisms in IDDM patients with diabetic nephropathy. 859 44

Recent studies have suggested that an inherited predisposition to essential hypertension may increase susceptibility to nephropathy for patients with IDDM. Essential hypertension has been linked to the angiotensinogen (AGT) gene in genetic linkage studies in American and European populations. A molecular variant (M235T), which has a functional effect, has been described with highest plasma AGT levels being associated with the TT genotype. In a case-control study, we have evaluated the role of this functional genetic marker in patients with IDDM and nephropathy and in IDDM patients without nephropathy. We studied 195 IDDM patients, of whom 95 had established diabetic nephropathy; the remaining 100 patients, who had no evidence of microalbuminuria, served as control subjects. All patients were whites born in Northern Ireland. The point mutation in the AGT gene was analyzed using restriction typing. The background frequency of the M235T variant was assessed in 80 healthy blood donors, and the TT genotype was present in 9%. This genotype occurred in 8% of control IDDM patients without nephropathy and 19% of IDDM patients with nephropathy (P = 0.025). The odds ratio for diabetic nephropathy associated with the TT genotype was 2.7 (95% CI 1.04-7.52). There was no relationship between blood pressure and AGT genotypes in the control group. We cannot exclude the possibility that the observed association in the nephropathy group is due to an association between AGT genotype and hypertension. This evidence may help to explain the predisposition to diabetic nephropathy afforded by hypertension and merits further investigation.
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PMID:A molecular variant of angiotensinogen is associated with diabetic nephropathy in IDDM. 877 23

Increased erythrocyte (RBC) sodium-lithium (Na-Li) counter transport (CT) has been reported to be a genetic marker for essential hypertension (EHT). In addition, increased RBC Na-Li CT has been demonstrated in insulin-dependent diabetic (IDDM) patients with nephropathy, indicating that a predisposition to hypertension may cause renal damage and impaired renal function. Therefore, the present study was designed to determine RBC Na-Li CT in subjects with essential hypertension (EHT) and non-insulin-dependent diabetics (NIDDM) with or without hypertension (NIDDMHT or NIDDMNT), using the method of Canessa et al. with a slight modification by flame photometry and expressed as nmol Li/5 x 10(6) RBC/h. Na-Li CT in patients with EHT (0.159 +/- 0.051 (S.D.), n = 26) or NIDDMHT (0.168 +/0 0.083, n = 42) was higher than that in NIDDMNT patients (0.127 +/- 0.059, n = 27, P < 0.05). Among the NIDDMHT patients, those with clinical nephropathy had the same levels of Na-Li CT as those without nephropathy. When the NIDDM patients were divided into two groups with or without insulin treatment, the Na-Li CT in hypertensives was higher than that in normotensives, irrespective of whether or not they were on insulin therapy. Addition of insulin to RBCs in vitro did not augment the Na-Li CT activity. These results suggest that an increase of Na-Li CT may not be due to the stimulatory effect of endogenous or exogenous insulin, and reflect a genetic predisposition for hypertension, and hence diabetic nephropathy, not only in IDDM but also NIDDM patients.
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PMID:Elevated erythrocyte sodium-lithium counter-transport in hypertensive patients with non-insulin-dependent diabetes mellitus. 879

Hypertension is seen in approximately 85% of IDDM patients with diabetic nephropathy and blood pressure elevation is an early event in the development of this complication. In IDDM patients with clinical nephropathy, a positive correlation has been demonstrated between the blood pressure and the urinary albumin excretion and reduction of blood pressure reduces albuminuria as well as the rate of decline in glomerular filtration rate. Also extrarenal abnormalities such as retinopathy, cardiovascular diseases and signs of endothelial dysfunction, sometimes seen in non-diabetics with severe and/or prolonged hypertension, are frequently demonstrated in IDDM patients with clinical nephropathy. The aim of the present study was to provide circumstantial evidence for the thesis that hypertension in IDDM patients with nephropathy is secondary to the kidney involvement and not the cause of the kidney disease. Furthermore, by familial and physiological studies the review also aimed to contribute to the understanding of the pathogenesis of hypertension in patients with clinical nephropathy. Finally the question of optimal pharmacological antihypertensive treatment was discussed. It was demonstrated that in IDDM patients with elevated urinary albumin excretion above normal level the prevalence of hypertension is 60%, whereas in patients without signs of renal impairment hypertension is not more prevalent as in the age and sex-matched background population (about 4% in both groups). Based upon the observation, that some of these IDDM patients with hypertension but normal UAE were hypertensive for many years, we designated this group as IDDM patients with essential hypertension for further studies. In this group, we had the opportunity to study the association between blood pressure and the development of extrarenal complications in patients with IDDM. The group with essential hypertension and IDDM showed to have less retinopathy compared with diabetics with similar blood pressure but elevated UAE. In contrast to the hypertensive patients with nephropathy, a normal transcapillary escape rate of albumin and normal plasma levels of von Willebrand factor, of angiotensin-converting-enzyme and of inactive renin were demonstrated in the former group of patients. Thus, the extrarenal abnormalities found in IDDM patients with hypertension are more closely associated to the presence of albuminuria than to the elevation of blood pressure, indirectly supporting the hypothesis that hypertension per se is not the cause of these abnormalities in the IDDM patients with nephropathy. Furthermore, the present study does not disclose a genetic disposition to hypertension in IDDM patients with elevated UAE.
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PMID:Hypertension in insulin-dependent diabetes. 890 79

In subjects with essential hypertension, loss of the normal nocturnal dip in blood pressure is associated with a greater risk of developing end-organ complications. In subjects with diabetes, smoking carries a similar association. To assess whether these factors may have an aetiological and synergistic role in the vascular complications of diabetes, 24-hour blood pressure monitoring was performed in insulin-dependent diabetic (IDDM) patients with normal albumin excretion (n = 19) and microalbuminuria (n = 21) of comparable age and duration of diabetes, and with no evidence of autonomic neuropathy or hypertension. The potential influence of smoking was examined by subdividing the groups, depending on smoking status. Ten of the microalbuminuric group and 9 of the normoalbuminuric group were current smokers, the remaining patients never having smoked. There was a significant difference between mean (+/-SD) daytime vs nocturnal blood pressure in patients with normal albumin excretion (114 +/- 3/70 +/- 4 vs 102 +/- 3/62 +/- 3 mmHg; p < 0.001) and microalbuminuria (109 +/- 5/75 +/- 5 vs 101 +/- 3/65 +/- 4 mmHg; p < 0.001) but mean blood pressure values did not differ significantly between the groups. A similar fall in nocturnal blood pressure was found in smokers and non-smokers with and without microalbuminuria (p < 0.001), but there was no difference between the mean blood pressure values in the different subgroups. In conclusion, normotensive IDDM patients, who do not have autonomic neuropathy, retain a significant diurnal variation in blood pressure, irrespective of smoking habit or presence of microalbuminuria.
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PMID:Diurnal variation in blood pressure in insulin-dependent diabetic smokers and non-smokers with and without microalbuminuria. 911 82

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