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Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.

Abstract. Patients with a hereditary myopathy with paroxysmal myoglobinuria were studied in the chronic state of the disease. They were characterized by muscle contractions of fairly normal strength and quite good endurance in exercise with small muscle groups, but a poor physical performance in exercise of some duration with large muscle groups. Several facts indicate that it was not muscular weakness, but the circulatory capacity that was a main factor limiting the physical working capacity in exercise of some duration with large muscle groups. The oxygen uptake was largely normal in relation to the work performed. However, even light exercise on a bicycle ergometer caused tachycardia (approaching maximum heart rate), a high cardiac output (approaching, for the size of the individual, maximum values in the normal range) and an abundant blood flow through the exercising legs. Thus, there were no signs of insufficient heart function, but the utilization of the oxygen of the blood in the exercising limbs was low. The concentration of lactate, and particularly of pyruvate, in the blood, and the lactate and pyruvate production increased more than in the controls for the slight work performed. During exercise the lactate/pyruvate ratio decreased and the calculated “excess of lactate” was negative, while it increased in normal subjects. After exercise the excess lactate was higher in the patients than in the controls. This indicates an abnormal muscle metabolism, probably a decreased capacity for pyruvate oxidation. It is suggested that a metabolic disturbance caused an abnormally large production of metabolites in the working muscles, resulting in muscular vessel dilatation by a local humoral effect. The muscles acted almost like a‐v shunts and, as a consequence, the patients had a hyperkinetic circulation, i.e. a low O2 uptake in relation to cardiac output, a low a‐v O2 difference for mixed venous blood and for the venous blood of the exercising limbs.

The rheological behavior of blood and its components under physiologic and pathophysiologic conditions is reviewed, with a focus on the type and extent of pathohemorheological changes in surgical patients during hospitalization and thereafter, as well as their clinical consequences with regard to thromboembolic complications. During the operation and the postoperative period various hemorheological and hemostasiological alterations acquire clinical significance: 1. hyperreagibility of platelets with increased aggregation and adhesion tendency 2. changes in fibrinogen, albumin, and globulin concentrations, which affect viscosity and red cell aggregation 3. impairment of red cell deformability 4. increase in clotting factors 5. disturbance of fibrinolysis characterized by diminution of plasmatic plasmin and increase in antiplasmin activity In addition, anesthetic techniques have also been shown to affect hemorheological and hemostasiological parameters. The complex pattern of pathohemorheological and hemostasiological changes shows that thromboembolism in the course of surgical interventions is provoked by multifactorial disorders. Thrombosis prevention should, therefore, counteract both hemorheological and hemostasiological disturbances. Since pathohemorheological and pathohemostasiological changes are already detectable before, and increase during operation, preventive measures should start before the surgical intervention to obtain maximum benefit. Therapeutic possibilities for the avoidance of these multifactorial disturbances are discussed with particular reference to pentoxifylline, which satisfies the complex requirements of a hemorheologically and hemostasiologically active therapeutic agent.

Recently we reported the association of severe insulin resistance and congenital fibre type disproportion myopathy (CFTDM) in two brothers from a Danish family [1]. It has now been shown that the insulin resistance and possibly the myopathy in the two brothers is associated with compound heterozygous mutations of the insulin receptor gene [2]. The allele inherited from their father, who is less insulin resistant and has no CFTDM [1], has a missense mutation that changes Arg 1174 ®Gln. The allele inherited from their mother, who is less insulin resistant than the patients and her husband [1], carries a point mutation at the last base pair in exon 17 (position 3396). This G to A change affects the ±1 donor splice site of exon 17, resulting in a mixture of two mRNAs from that allele. The abnormal skipping of exon 17 (exon 17± variant) shifts the amino acid reading frame and creates a stop codon 36 amino acids after the end of the sequence encoded by exon 16 and this leads to a truncated receptor missing the entire tyrosine kinase domain. In the exon 17 + variant, the point mutation is silent and should result in a normally transcribed insulin receptor. Diabetologia (1999) Summary We studied insulin receptor kinase activation in two brothers with congenital muscle fibre type disproportion myopathy and compound heterozygous mutations of the insulin receptor gene, their parents, and their unaffected brother. In the father who has a heterozygote Arg 1174 ®Gln mutation, in situ activation of the receptor kinase in skeletal muscle was reduced about 70 %. Selection of only those receptors that bound to anti-phosphotyrosine antibody showed that these receptors had normal kinase activity and that the reduction in overall kinase activity was due to the inability of about 70 % of the receptors to become insulin-dependently activated. The mother carries a point mutation at the last base pair in exon 17 which, due to abnormal alternative splicing, could lead to normally transcribed receptor or truncated receptor lacking the kinase region. Kinase activation was normal in the mother's skeletal muscle, suggesting that virtually no truncated receptor was expressed. Receptor kinase activity was, however, reduced by 95 and 91 % in the compound heterozygous brothers. This suggests that the mother's mutated allele contributes little to the generation of functional receptor protein and that the receptors in the mother's skeletal muscle are transcribed almost exclusively from the non-mutated allele. The mutation in exon 17 could lead to reduced transcription or rapid degradation of a predominantly transcribed truncated gene product or both. [Diabetologia (1999) Abbreviations: CFTDM, congenital fibre type disproportion myopathy; aPY, anti-phosphotyrosine antibody; aIR, anti-insulin receptor antibody; IRS-1, insulin receptor substrate-1; GLU4:TYR1, Polymer with a 4:1 ratio of glutamic acid and tyrosine, used as insulin receptor substrate; IGF-1, insulin-like growth factor-1.