[Diabetes and pregnancy--internal medicine aspects: expectations and facts].
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Biomedical subjects
Publications and source records attributed to H Mehnert.
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The effects of indapamide on diabetic patients with micro-albuminuria were evaluated in a multicentre study to assess the advantages of this compound in long-term renal protection. Thirty-two hypertensive diabetic patients (10 males, 22 females, aged 46-84 years) were given indapamide at 2.5 mg/day for a 2-month period. There was a significant fall in systolic blood pressure (174 +/- 18 to 148 +/- 12 mmHg, P less than 0.001) and diastolic blood pressure (95 +/- 13 to 85 +/- 8 mmHg, P less than 0.001) and in the albumin excretion rate (median, 40.8 to 18.9 mg/l; P less than 0.05). Blood glucose, glycosylated haemoglobin, electrolytes, creatinine and serum lipids remained unchanged. There was a small but significant correlation between changes in systolic blood pressure and changes in albuminuria (r = 0.04, P less than 0.05). Thus, the effect of indapamide on albumin excretion cannot be explained by a decrease in the intraglomerular perfusion pressure alone. Indapamide, therefore, might be of potential interest in the long-term renal protection of the diabetic patient with elevated blood pressure values and/or micro-albuminuria.
The effect of standardized isometric forearm work on circulating and local kinin concentrations was investigated in 12 healthy volunteers using the forearm catheter technique. Radioimmunological kinin determination in arterial blood and in the venous effluent of forearm muscle tissue was performed using a modification of Shimamoto's technique of blood sampling and kinin extraction. Under basal conditions, there was no arterio-venous difference of kinins. Throughout the whole experiment, arterial--reflecting systemically circulating--kinins did not change. In muscle venous blood, immunoreactive kinins were not significantly elevated during work, whereas a marked increase was detected in the recovery period (5.0 +/- 0.6 vs. 10.2 +/- 2.0 pmol/l; p less than 0.01). The data demonstrate, that kinins are locally generated in calculated amounts (32.7 +/- 8.4 fmol/(100 g x min) that are known to be sufficient to induce local vasodilatory and metabolic effects at the site of muscle contraction, but below the threshold for systemic cardiovascular actions.
Flow cytometry was recently introduced for the detection of antibodies in human serum to a cultured insulin-secreting rat insulinoma cell line (RINm5F) to investigate humoral immune reactivity in newly diagnosed type I (insulin-dependent) diabetic patients. Fifty-three patients were observed for 6-20 mo after clinical onset of diabetes with a reported duration of symptoms of less than 6 wk. Human anti-RINm5F antibodies were detected in 28%, human anti-islet cell antibodies in 62%, and anti-insulin autoantibodies in 36% of patients before initiation of insulin therapy. Occurrence of human anti-RINm5F antibodies at this stage was correlated with human anti-insulin autoantibodies rather than with the formation of anti-islet cell antibodies. Incidence of anti-RINm5F antibodies in individuals with duration of diabetes greater than 6 wk was 38%, whereas human anti-islet cell antibodies and anti-insulin antibodies became detectable in 72 and 61% of the patients, respectively. These findings are in line with previous reports of immunoprecipitation by human diabetic serums of a 64,000-Mr antigenic structure in freshly prepared rat islet cells. The results suggest a reactivity of distinct classes of antibodies in serums of patients with type I diabetes to disparate antigens on human islet cells and cloned rat insulinoma cells and, moreover, reactivity to insulin as the secreted product. Further characterization of the reacting RINm5F antigens and prospective studies in subjects at risk for diabetes are required to validate the application of RIN cells to the investigation of immune mechanisms involved in the pathogenesis of human type I diabetes.
For total parenteral nutrition in diabetes, the same relation between carbohydrates, fat and protein of 50, 30-35 and 15-20% of total calories as in regular oral feeding has to be taken. For carbohydrates, a 2:1:1 mixture of fructose, glucose and xylitol should be used, since this is to a lesser extent blood glucose level raising as glucose alone and the dose-dependent side effects of the sugar substitutes are negligible. If insulin is infused intravenously, it is important that the carbohydrates are given simultaneously, in order to prevent deleterious hypoglycemnia. Mixtures of MCT and LCT are to be preferred towards pure LCT-emulsions, since the faster elimination of MCT/LCT-solutions may be of clinical relevance in diabetics type II, who frequently have a disturbed lipid metabolism. For protein, the normal amino acid pattern can be used, special solutions are not necessary.
The effects of the highly beta 1-selective beta-blocker betaxolol (Kerlone) on carbohydrate and lipid metabolism in type II diabetic subjects were compared in a cross over study with those of a diuretic (xipamide-triamterene combination, Neotri). Betaxolol significantly lowered blood pressure with a tendency to better efficacy than the diuretic. The betaxolol-induced decrease in heart rate could be a contributing factor in attenuating the progression of atherosclerosis. No significant alterations were observed in postprandial blood glucose, glycosylated haemoglobin and 24-h urinary glucose excretion. The lack of noticeable influence on the carbohydrate metabolism during 4-week therapy is presumably related to the high beta 1-selectivity of betaxolol. Considering that diabetic hypertensive patients are at high risk for atherosclerosis it appears also favourable that betaxolol did not increase triglyceride levels and even decreased total cholesterol. The protective effect of beta-Blockers has been well established in the secondary and primary prevention of cardiovascular diseases. Especially diabetic patients might be expected to benefit from this therapy, if given preferably as beta 1-selective blocker that impairs carbohydrate and lipid metabolism in lesser extent.
The influence of intra-arterial (i.a.) prostaglandin E1 (PGE1) on the metabolism of amino acids, glucose and free fatty acids in healthy volunteers was determined by means of the forearm technique. The continuous increase of perfusion from baseline 2.9 +/- 0.1 ml/100 g x min to 5.4 +/- 1.5 after 60 minutes of PGE1 infusion, indicates an increase of basal glucose utilisation from 0.51 +/- 0.11 to 2.5 +/- 0.36 mumol/100 g x min via and additional raised glucose extraction rate. Furthermore, PGE1 resulted in a cessation of the basal muscular glycerol production and led to a change from a basal production of free fatty acids to a net absorption into the muscle. This change from an oxidation of free fatty acids to glucose results in an improved energetic gain of 0.72 mol ATP/mol 02. Baseline values showed a release of most amino acids which, after PGE1 decreased significantly or even changed to an intake. The overall balance of all amino acids changed from baseline -27.9 (i.e. release) to +33.2 nmol/100 x min (i.e. intake). This indicates an inhibition of muscular proteolyses and/or a stimulation of protein synthesis under i.a. PGE1. This additional metabolic effect of PGE1 might be an explanation as to why agents with purely vasodilating actions did not prove therapeutically effective in the treatment of peripheral arterial disease in the past.
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In type 2 diabetes with "secondary failure of sulfonylurea therapy" good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia. 16 type 2 diabetics with "secondary failure" were treated either with insulin alone (group A; n = 8) or with 3.5 mg b.i.d. glibenclamide plus small amounts of intermediate insulin (group B; n = 8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years. Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14 +/- 2 IU (means +/- SEM) after one month and 19 +/- 2 IU after two years in group B. In contrast 30 +/- 3 IU and 43 +/- 5 IU respectively were needed in group A (p less than 0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6 +/- 3.7 vs. 18.6 +/- 1.6 mcU/ml; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
In order to study left ventricular function digitized M-mode-echocardiograms were analyzed. 34 patients with insulin-dependent diabetes mellitus (mean age 37.8 years, mean diabetes history 21.5 years) were compared with 35 healthy individuals (mean age 40.9 years). Only patients with negative exercise-ECG, normal 2-D-echocardiogram and normal systemic arterial blood pressure were enclosed. In diabetics the time-constant Te of free wall endocardial retraction was significantly prolonged (76.8 +/- 21.2 ms versus 64.0 +/- 7.9 ms in normals, p less than 0.005), the dimension change during early diastole (dD DS-ERF) was significantly reduced (54.5 +/- 13.1% versus 69.8 +/- 9% in normals, p less than 0.001) and the dimension change during atrial contraction phase (dD ACP) was significantly enlarged (23.4 +/- 14.4% versus 14.3 +/- 6.4% in normals, p less than 0.001). These data suggest that impaired left ventricular diastolic function can be found in patients with long standing insulin-dependent diabetes mellitus.
The effectiveness of combined insulin and glibenclamide was compared with that of insulin alone in a multicenter double-blind trial of secondary sulphonylurea failures. Protocols of 176 patients at 26 centers were available, but only 68 could ultimately be included in the analysis. Combined insulin and glibenclamide (Euglucon N) had been taken by 37 patients, combined insulin and placebo by 31. The final criterion, postprandial one-hour blood sugar level of less than or equal to 220 mg/100 ml after 24 weeks, was attained by nearly 75% of patients in both groups. Fasting blood sugar and postprandial one-hour blood sugar as well as HbA1 did not differ during the entire test period of 24 weeks. Mean daily insulin dose was 20 IU in the insulin/glibenclamide group, 35 IU in the insulin/placebo group. This increased the number of second evening insulin injections by 50% in the insulin/placebo group compared with the insulin/glibenclamide group. The frequency of mild hypoglycemia was similar in the two groups. The results indicate that combined insulin/glibenclamide, given over a period of six months to patients with secondary sulphonylurea failure, provided metabolic results as good as those with insulin alone. The required insulin dosage was thus reduced by more than a third.
Using the forearm technique, muscular ketone body metabolism was investigated in 12 healthy volunteers during an i.v. infusion of lipid emulsions containing long chain triglycerides (LCT) or a mixture of medium- and long chain triglycerides (MCT/LCT). During the basal period, arterial concentrations and muscular extraction of beta-hydroxybutyrate and acetoacetate were linearly correlated as expected. This relationship was abolished during the infusion of both lipid emulsions. In addition, fractional extraction rates of ketone bodies were reduced. These changes were most probably mediated by elevated levels of free fatty acids and triglycerides as well.
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We carried out sonographic examination of 160 type I diabetics measuring the renal volume, the parenchyma/renal pelvis index and the brightness of the parenchyma. Creatinine and beta-2-microglobulin in the serum, creatinine clearance and albumin excretion by urine were determined as functional parameters. In contrast to existing results, we were unable to find significant changes in kidney size or function in newly diagnosed diabetics (duration of diabetes up to 6 months). Both the parenchyma/renal pelvis index and the kidney parenchyma were unchanged compared to control persons of the same age. It was only if diabetes lasted from 6 months to 5 years, that the renal volume was 19% larger (192 +/- 37 cm3/1.73 m2) than that of recently diagnosed patients (p less than 0.01). The index had increased by 15%, whereas the creatinine clearance had increased by 18% to 121 +/- 27 ml/min as a result of increased perfusion. The renal volume decreased continuously over a five-year period of duration of diabetes. Initially, microalbuminuria became manifest, followed some time later by a decrease in creatinine clearance and a corresponding increase in creatinine and beta-2-microglobulin in serum. No change in parenchyma brightness was noted. Diabetics with moderate renal insufficiency (creatinine 1.2 to 2 mg/dl) compared to diabetics without insufficiency developed larger kidneys (207 cm3/1.73 m2; p less than 0.01). Only in case of severe insufficiency (creatinine greater than 2 mg/dl) did the kidneys did shrink significantly (121 cm3/1,73 m2, n = 8, p less than 0.01). The temporary enlargement of the kidneys could be a prognostically unfavourable sign pointing towards a developing diabetic nephropathy.
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