Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.
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PMID:Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes. 131 6

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration. 138 91

Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

The superoxide anion (O2-) production in polymorphonuclear leukocytes stimulated by phorbol myristate acetate in IDDM and non-insulin dependent diabetes mellitus (NIDDM) was determined by the method of Johnston et al, compared with that of each age matched controls. And the correlation between O2- production and hemoglobin (Hb) A1 and A1c value was investigated. The O2- production in IDDM was 24.4 +/- 7.4 (mean +/- SD, n mol per 4 X 10(5) cells) at 10 min. and 51.4 +/- 8.7 at 30 min., in NIDDM each 31.6 +/- 9.3, 60.2 +/- 14.4, and in controls each 40.5 +/- 4.2, 72.4 +/- 3.1. O2- production in IDDM was significantly lower than that in NIDDM (p less than 0.001 at 10 min. and p less than 0.01 30 min.) and controls (p less than 0.001 at 10 and 30 min.). O2- production at 10 and 30 min. possessed a negative correlation with Hba1 and A1c value (HbA1: p less than 0.01 at 10 min. p less than 0.05 at 30 min., HbA1c: p less than 0.01 at 10 and 30 min.). These findings suggest that impaired O2- production might be one of the factors accounting for depressed bactericidal activity of polymorphonuclear leukocytes in IDDM, and that a protracted hyperglycemia might shed some effect on O2- production.
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PMID:[Superoxide anion (O2-) production by polymorphonuclear leukocytes in insulin dependent diabetes mellitus (IDDM)]. 165 12

Several lines of evidence suggest that hypertension is a contributing factor to diabetic nephropathy, a major cause of mortality in diabetes mellitus patients. The present study tested the hypotheses (1) that insulin dependent diabetes (IDD) causes hypertension, and (2) that simultaneous hypertension and IDD causes greater renal damage than would be expected from the independent contributions of each disease. IDD was induced by injection of streptozotocin (STZ, 65 mg/kg i.p.) into male Wistar rats, causing severe hyperglycaemia within 4 days. Seven days after the STZ treatment, hypertension was initiated by subcutaneous implantation of deoxycorticosterone acetate and administration of 1% saline in the drinking water (DOCA-NaCl). IDD rats not receiving DOCA-NaCl displayed a small elevation of blood pressure one week after STZ treatment, but thereafter displayed significant hypotension. The IDD rats receiving DOCA-NaCl displayed elevated systolic arterial pressure throughout the study, but by the end of the experiment, their mean systolic arterial pressure was significantly lower than that of the rats treated with DOCA-NaCl alone. Only the IDD/DOCA-NaCl rats displayed significant signs of renal dysfunction, i.e. greatly increased proteinuria and morphological renal damage, including marked distension of distal tubules and occasional casts. No other group displayed these abnormalities.
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PMID:Effects of simultaneous diabetes and hypertension in an insulin dependent diabetic model. 176 11

Plasma membrane fluidity of polymorphonuclear leukocytes was investigated in 28 patients with insulin dependent diabetes mellitus and 30 healthy controls. Membrane fluidity was measured by steady-state fluorescence anisotropy of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) incorporated into the plasma membrane. The fluorescence anisotropy values in resting (unstimulated) polymorphonuclear leukocytes from diabetic subjects were significantly higher than those of controls (0.318 +/- 0.003 vs 0.287 +/- 0.003, P less than 0.001). The addition of the respiratory burst stimulus phorbol myristate acetate induced a stable increase in fluorescence anisotropy values in both groups. Fluorescence anisotropy values of stimulated polymorphonuclear leukocytes from the diabetic and control groups were not significantly different (P greater than 0.05). These data demonstrate a decrease in plasma membrane fluidity of resting polymorphonuclear leukocytes obtained from diabetic subjects. This finding could be in part explained by an increase in their basal respiratory burst activity.
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PMID:Alterations in membrane fluidity of diabetic polymorphonuclear leukocytes. 179 18

NIDDM and hypertension are both characterized by insulin resistance and/or hyperinsulinemia. In IDDM, factors associated with nephropathy produce hypertension. To avoid exacerbation of the metabolic condition, and to prevent further deterioration in glycemic control, treatment of hypertension in the diabetic patient should include the administration of medication with the fewest adverse effects on glucose homeostasis. If diuretics are to be used, it appears that loop diuretics may be preferable to the thiazides or potassium-sparing compounds. Among the remaining classes of antihypertensive drugs, ACE inhibitors may be the agents of choice because of their potential positive effects on insulin sensitivity and renal function, and their lack of severe adverse side-effects.
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PMID:Insulin sensitivity and blood lipids during antihypertensive treatment with special reference to ACE inhibition. 197 44

The pathophysiological connections between insulin resistance, hypertension and type 2 diabetes are discussed in this review article. Increased blood pressure levels are often found in type 2 diabetic patients long before the diabetes itself is diagnosed. By contrast, in type 1 diabetes hypertension is predominantly the consequence of diabetic glomerulopathy. Non-pharmacological strategies should be favoured in the treatment of hypertension in type 2 diabetic patients before specific pharmacological intervention is started. Antihypertensive treatment with beta-blocking agents and diuretics is criticized by many experts in the field of metabolic disorders, since these drugs induce a deterioration of glycaemic control and lipid metabolism in diabetic patients. Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking agents have no influence on metabolism, these drugs are recommended for the antihypertensive treatment of diabetic patients. Further studies should be undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective effect. Since most type 2 diabetic patients do not develop diabetic nephropathy, a possible nephroprotective effect of ACE inhibitors is only relevant to the antihypertensive treatment of type 1 diabetic patients.
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PMID:[Hypertension, insulin resistance and diabetes mellitus: pathophysiological interactions and therapeutic consequences]. 198 Jul 67

The respiratory burst of polymorphonuclear leukocytes was investigated in 24 children with insulin dependent diabetes mellitus and 24 healthy controls. This oxygen dependent, membrane associated process generates a number of toxic oxygen metabolites which are implicated in the pathogenesis of endothelial damage. The activity of polymorphonuclear leukocytes was studied in terms of luminol amplified chemiluminescence. It was found that the resting luminol amplified chemiluminescence activity of isolated polymorphonuclear leukocytes from diabetic children was significantly higher than that of controls (342,000 +/- 174,000 cpm vs. 165,000 +/- 82,000 cpm, p less than 0.01). The addition of respiratory burst inhibitors caused a significant reduction of basal chemiluminescence (greater than 80%). When the ratio of phorbol myristate acetate stimulated activity to basal activity was calculated and used as an activation index, it was found to be significantly reduced in diabetics relative to controls (4.29 +/- 2.46 vs. 8.34 +/- 3.21, p less than 0.01). These observations suggest that increased release of toxic oxygen metabolites from polymorphonuclear leukocytes in diabetic subjects may play a role in the development of diabetic angiopathies.
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PMID:Alterations of the respiratory burst of polymorphonuclear leukocytes from diabetic children. A chemiluminescence study. 216 90

The purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one-fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone.
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PMID:The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study. 219 80


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