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Query: UMLS:C0011849 (diabetes)
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This letter briefly reports a case linking the appearance of overt diabetes mellitus to progestational therapy, and is intended as an addition to the literature associating insulin-dependent diabetes with progestational therapy. A 51-year-old white woman, who had undergone masectomy and prophylactic oophorectomy, had no history of glucose intolerance and was given Prednisolone (15 mg daily) postoophorectomy. Interval clinical evaluations of glucose levels were between 184 and 223 mg/dl during estrogen therapy. Tumor recurrence 12 years later forced withdrawal of estrogen therapy, and the patient was placed on trial therapy with megestrol acetate (40 mg, 4 times daily). 6 weeks after initiation of progestational therapy, the patient was admitted with a glucose level of 400 mg/dl and a 4+ acetone reading in her urine. Insulin therapy was instituted; megestrol acetate was withdrawn; but the diabetes was not reversed and insulin treatment continues. The author compares this case with others previously reported where medroxyprogesterone acetate was the progestational agent apparently causing irreversible diabetes mellitus.
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PMID:Letter: Medroxyprogesterone acetate and diabetes mellitus. 125 75

Blood serum activity of ACE, alfa2-macroglobulin as well as triglycerides concentration was determined in 90 patients with diabetes and in 40 healthy persons. Taking into account criteria established by WHO the patients with diabetes were divided into two groups. The first group consisted of 32 patients with diabetes of type I (juvenile one); the second group consisted of 58 patients with diabetes of type II (adult one). It was found that blood serum level of all tested parameters is statistically increased (p < or = 0.001) in comparison with control group. In patients with diabetes of type I the level of alfa2-macroglobulin and ACE was higher than in those with diabetes of type II. The serum contents of triglycerides in both groups of patients was comparable. No correlation between parameters determined in patients with diabetes was found.
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PMID:Blood serum angiotensin-converting enzyme, alfa2-macroglobulin and triglycerides in patients with diabetes. 128 70

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antihypertensive therapy in diabetic patients. 128 10

ACE inhibitors are used on a large scale basis in hypertensive diabetics, while the association between diabetes and hypertension is frequent and harmful. This is due to their excellent tolerance and efficacity. No specific advantage has been reported in their use regarding tolerance, i.e., they may not alter insulin sensitivity consistently. Conversely, ACE inhibitors may offer the specific advantage of protecting kidney function against diabetic microangiopathy, since their effects on glomerular haemodynamics seem independent from their hypotensive effect.
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PMID:[Converting enzyme inhibitors in diabetes]. 129 43

Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge is consistently observed. Studies using insulin glucose clamp techniques in combination with tracer glucose infusion and indirect calorimetry have demonstrated that the insulin resistance in hypertensive subjects is located in muscles and restricted to glycogen synthesis. The relations between hyperinsulinemia and blood pressure do not prove that the relationship is a causal one. However, at least four mechanisms may link hyperinsulinemia with hypertension: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport and proliferation of vascular smooth muscle cells. Diuretics and beta-blockers may enhance insulin resistance, which is not affected by calcium antagonists, but decreased by the ACE inhibitor captopril. Weight reduction and regular physical exercise can improve insulin sensitivity and decrease blood pressure values. These nonpharmacological interventions should be more strongly recommended to diabetic and nondiabetic hypertensive patients.
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PMID:Hyperinsulinemia, insulin resistance and essential hypertension. 130 12

1. The effect of administration of the angiotensin converting enzyme inhibitor (ACEI), lisinopril (Carace; 10-40 mg twice daily) and the calcium channel blocker, nifedipine (Adalat Retard; 20-40 mg twice daily) on ex vivo [45Ca2+] uptake by platelets from hypertensive diabetic (type 1 and 2) patients was investigated. 2. At the end of at least 3 months treatment, blood was collected prior to the patient taking the morning dose of medication and washed platelets prepared. [45Ca2+] uptake was monitored following the addition of adrenaline, isoprenaline and dibutyryl cAMP (dbcAMP), as well as in unstimulated (zero) platelets. 3. Both nifedipine and lisinopril significantly inhibited the ex vivo uptake of [45Ca2+] by platelets when this process was stimulated by adrenaline, isoprenaline and dibutyryl cAMP. Basal uptake was also inhibited in both groups. 4. These data consolidate the hypothesis that ACE inhibitors may possess calcium channel/calcium mobilisation blocking properties. Apart from its hypertensive action, lisinopril may also reduce platelet activity via modulation of calcium dynamics, thereby reducing the incidence of vascular complications associated with diabetes mellitus.
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PMID:Lisinopril and nifedipine administration inhibits the ex vivo uptake of [45Ca2+] by platelets from hypertensive diabetic patients. 131 54

The in vitro potency of neopterin (NP) as an antioxidant and its in vivo activity to suppress alloxan-induced diabetes were investigated. The reduced form of neopterin, 5,6,7,8-tetrahydroneopterin (NPH-4), showed an extremely high superoxide anion radical scavenging activity in two assay systems, i.e. xanthine/xanthine oxidase- and macrophage/phorbol myristate acetate (PMA)-reaction systems. NPH-4 also inhibited the oxidation of linoleic acid about as effectively as uric acid. Furthermore, NPH-4 and NP effectively suppressed alloxan-induced mouse diabetes. These results suggest that pteridines play an important role as endogenous antioxidants.
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PMID:Neopterin as an endogenous antioxidant. 131 24

We examined changes in guanosine triphosphate-dependent signal transduction mechanisms in the retina from the early stages of the streptozotocin-diabetic rat, a model for Type 1 (insulin-dependent) diabetes mellitus. Guanosine triphosphate binding, guanosine triphosphatase activity, and binding of (azido) guanosine triphosphate decreased significantly in the retina as early as 2 weeks after the induction of diabetes. The ability of guanosine triphosphate to inhibit forskolin-stimulatable adenyl cyclase was also abolished. These data suggest functional deterioration of G-proteins, especially Gi, in diabetic retina. Further studies using retinal rod outer segments revealed deterioration in light-sensitive, guanosine triphosphate-dependent functions of transducin in diabetic rats. Pertussis toxin-catalysed ADP ribosylation of the alpha subunit of transducin, a heterotrimeric G-protein of rod outer segments, was also reduced in diabetes. No functional effects were seen in purified subunits of transducin subjected to non-enzymatic glycation in vitro. On the other hand, incubation of non-diabetic rod outer segments with (12-0-tetradeconyl) phorbol-13-acetate, a protein kinase C agonist, in the presence of magnesium and adenosine triphosphate resulted in the reduction of guanosine triphosphate-binding and hydrolysis, thus indicating that protein kinase C may be involved in the regulation of these activities. The significance of these observations in the early visual abnormalities associated with diabetes is discussed.
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PMID:Functional alterations of G-proteins in diabetic rat retina: a possible explanation for the early visual abnormalities in diabetes mellitus. 132 50

The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.
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PMID:Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters. 132 74

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.
Diabetes Res Clin Pract 1992 Jun
PMID:Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus. 133 Apr 63


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