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Query: UMLS:C0011849 (diabetes)
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After reviewing the available data on drug-induced hyperkalemia, we conclude that the situation has not improved since Lawson quantitatively documented the substantial risks of potassium chloride over a decade ago (90). As discussed, the risk of developing hyperkalemia in hospital remains at least at the range of 1 to 2% and can reach 10%, depending on the definition used (Table 2). Potassium chloride supplements and potassium-sparing diuretics remain the major culprits but they have been joined by a host of new actors, e.g., salt substitutes, beta-blockers, converting enzyme inhibitors, nonsteroidal antiinflammatory agents, and heparin, among others. Readily identifiable risk factors (other than drugs) for developing hyperkalemia are well-known but seem to be consistently ignored, even in teaching hospitals. The presence of diabetes mellitus, renal insufficiency, hypoaldosteronism, and age greater than 60 years results in a substantial increase in the risk of hyperkalemia from the use of any of the drugs we have reviewed. If prevention of hyperkalemia is the goal, as it should be, the current widespread and indiscriminate use of potassium supplements and potassium-sparing diuretics will need to end. We remain intrigued by Burchell's prescient pronouncement of over a decade ago that "more lives have been lost than saved by potassium therapy" (28).
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PMID:Drug-induced hyperkalemia. 286 67

Hypertension in diabetic patients is more common than in controls, contributes substantially to their increased cardiovascular morbidity and mortality, and should be treated as accurately as diabetes mellitus itself. After appropriate exclusion of secondary forms, the first therapeutic step consists of reduction of overweight, salt intake, and smoking; the omission of interfering drugs; and adequate instruction. Step 2 has usually been the prescription of a diuretic drug, in spite of its known side effects on carbohydrate and lipid metabolism. A new possible alternative may be a calcium antagonist. Results in 10 hypertensive diabetic persons suggest that at a dose that normalizes blood pressure, neither carbohydrate nor lipid metabolism is altered, uric acid decreases, the exaggerated cardiovascular reactivity toward norepinephrine becomes normal, and the pressor dose for angiotensin II tends to rise. Body weight, blood volume, exchangeable sodium, as well as plasma and urinary sodium, potassium, and creatinine levels were unchanged. The third therapeutic step is the addition of a cardioselective beta blocker in a moderate dose. This avoids the disadvantages of beta 2-adrenergic blockade such as decreased insulin output, prolonged hypoglycemia, diminished glucagon secretion, and increased vasospasticity during hypoglycemic states, as well as aggravation of peripheral vascular disease. Alternatives are other sympatholytics with their known tendency to cause or increase orthostatic and sexual problems or, again, a calcium antagonist. In step 4, a hydralazine-type drug or prazosine is added. The fifth step, which adds minoxidil or captopril to the previous drugs, should only be taken after a specialist reevaluates the overall situation.
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PMID:Antihypertensive therapy in diabetic patients. 286 38

Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of greater than 9 yr [8 with albumin excretion rate less than 15 micrograms/min (group 1) and 7 with albumin excretion rate greater than 100 micrograms/min (group 2)] and in 8 normal subjects during amino acid infusion (33 mumol.kg-1.min-1, Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 mumol.kg-1.min-1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P less than .01; IDDM group 2: 6%, P less than .01) than in normal subjects (38%).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jan
PMID:Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects. 290 15

Weanling sand rats (Psammomys obesus) develop hyperinsulinemia or diabetes or both, if fed a standard laboratory diet without a supplement of fiber rich salt bush. The annuli fibrosi of hyperinsulinemic or diabetic animals, which are still hyperinsulinemic, show a slight but statistically significant increase in chondroitin sulfate and a lesser, statistically nonsignificant increase in keratan sulfate. Possible causes of these changes are discussed and the likelihood of a role of hyperinsulinism in their production is pointed out.
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PMID:Effects of hyperinsulinism and of diabetes on proteoglycans of the intervertebral disc in weanling sand rats. 309 15

We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7-10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes.
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PMID:Acute effect of calcium and insulin on hyperfiltration of early diabetes. 310 8

Permeability-surface area products (PA) were determined with a quantitative in vivo injection technique at the blood-nerve barrier of tibial nerve, and at the blood-brain barrier, in control and streptozotocin-induced diabetic rats. The PA product for [14C]mannitol at the blood-nerve barrier was increased by 100% in diabetic animals, 3.12 +/- 0.15 X 10(-5) ml X s-1 X g-1, compared with controls, 1.61 +/- 0.10 X 10(-5) ml X s-1 X g-1. In contrast, PA for [14C]mannitol at the blood-brain barrier was unaltered in the diabetic animals. Following intravenous injection, no leakage of microperoxidase across the perineurium or endoneurial vessels of diabetic rats could be demonstrated by morphological techniques. Nerve blood-space, as determined with intravenous [3H]inulin, and blood-nerve barrier surface area as determined by morphometric methods, did not differ in diabetic when compared to control animals. Thus, the calculated permeability coefficient for [14C]mannitol at the blood-nerve barrier was about 100% greater in diabetic nerve compared to control nerves. The increased permeability was accompanied by a 7% increase in nerve-water content and a 32% decrease in motor-nerve conduction velocity. The results demonstrate a specific vulnerability of nerve as compared to brain in an animal model of diabetes mellitus. Chronically altered permeability to small water-soluble molecules reduces the protective effect of salt impermeability at the blood-nerve barrier against nerve edema, and may be an important pathogenic mechanism in diabetic neuropathy.
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PMID:Altered blood-nerve barrier permeability to small molecules in experimental diabetes mellitus. 310 45

The effect of dietary salt on glycaemic responses to different test meals was investigated. Eight healthy male volunteers ate four test meals on consecutive mornings and in random order; the meals were 50 g carbohydrate taken as a 20% glucose solution or as boiled macaroni with and without supplementation with 6 g salt. In contrast with other reports, no significant differences in peak plasma glucose concentrations or areas under the plasma glucose curves could be established. These findings do not support a beneficial effect of salt restriction on glycaemic control in diabetes.
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PMID:Influence of salt on glycaemic response to carbohydrate loading. 310 2

Atherosclerosis and hypertension are, by far, the most common cardiovascular diseases affecting women, and both are influenced by diet. Atherosclerosis occurs more commonly in men than women; generally women are 10 to 15 years older than men when symptoms develop. The prevalence of hypertension is about equal in the two sexes, particularly in middle aged and older persons. These cardiovascular diseases are major causes of death and disability in this country. Atherosclerosis results in myocardial infarction, thrombotic strokes, and claudication. Hypertension, when severe, damages small blood vessels, causing kidney failure, hemorrhage, strokes, and heart failure; when the condition is mild to moderate, it produces atherosclerosis. Nutritional factors are of primary importance in both atherosclerosis and hypertension. Risk factors for atherosclerosis related to nutrition are hypercholesterolemia, hyperglycemia-diabetes, and for hypertension, obesity, high salt intake, and excessive use of alcohol. Of all these risk factors, obesity seems to be the most important because it is strongly linked to hypertension and diabetes. Dietary intake of saturated fat is a potent factor in determining the blood cholesterol level, and reducing intake often decreases the level, thus lessening the risk of atherosclerotic complications. Although high salt intake and excessive alcohol use produce hypertension in susceptible people, less is known about the frequency of this adverse effect than is known about obesity.
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PMID:Nutrition and cardiovascular diseases of women. 312 Feb 15

Interactions between type IV collagen and heparin were examined under equilibrium conditions with rotary shadowing, solid-phase binding assays, and affinity chromatography. With the technique of rotary shadowing and electron microscopy, heparin appeared as thin, short strands and bound to the following three sites: the NC1 domain, and in the helix, at 100 and 300 nm from the NC1 domain. By solid-phase binding assays the binding of [3H]heparin in solution to type IV collagen immobilized on a solid surface was found to be specific, since it was saturable and could be displaced by an excess of unlabeled heparin. Scatchard analysis indicated three classes of binding sites for heparin-type IV collagen interactions with dissociation constants of 3, 30, and 100 nM, respectively. Furthermore, by the solid-phase binding assays, the binding of tritiated heparin could be competed almost to the same extent by unlabeled heparin and chondroitin sulfate side chains. This finding indicates that chondroitin sulfate should also bind to type IV collagen. By affinity chromatography, [3H]heparin bound to a type IV collagen affinity column and was eluted with a linear salt gradient, with a profile exhibiting three distinct peaks at 0.18, 0.22, and 0.24 M KCl, respectively. This suggested that heparin-type IV collagen binding was of an electrostatic nature. Finally, the effect of the binding of heparin to type IV collagen on the process of self-assembly of this basement membrane glycoprotein was studied by turbidimetry and rotary shadowing. In turbidity experiments, the presence of heparin, even in small concentrations, drastically reduced maximal aggregation of type IV collagen which was prewarmed to 37 degrees C. By using the morphological approach of rotary shadowing, lateral associations and network formation by prewarmed type IV collagen were inhibited in the presence of heparin. Thus, the binding of heparin resulted in hindrance of assembly of type IV collagen, a process previously described for interactions between various glycosaminoglycans and interstitial collagens. Such regulation may influence the assembly of basement membranes and possibly modify functions. Furthermore, qualitative and quantitative changes of proteoglycans which occur in certain pathological conditions, such as diabetes mellitus, may alter molecular assembly and possibly permeability functions of several basement membranes.
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PMID:Heparin type IV collagen interactions: equilibrium binding and inhibition of type IV collagen self-assembly. 319 14

Polydimethylsiloxane (silicone) implants were subcutaneously placed in the back of diabetic and normal rats. After three months the rats were killed and the fibrous capsule around the implants was histologically and biochemically examined. A significant quantitative difference (p less than 0.001) was found in the thickness of the capsules, which were two to three times thicker in the diabetic animals. The biochemistry showed an increase of neutral salt-soluble collagen in the diabetic group; electrophoresis revealed only type I collagen in the diabetic and type I and III in the normal rats. From this experimental trial it seems that diabetes mellitus is another factor in formation of a thick capsule around silicone implants.
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PMID:Capsule around silicone implants in diabetic rats: histological and biochemical study. 327 8


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