Cardiovascular risk reduction in older people with type 2 diabetes mellitus-a comprehensive narrative review.

Metabolic targets are controversial in older people with type 2 diabetes due to functional heterogeneity and morbidity burden. Tight blood pressure and metabolic control appears beneficial in fit individuals who are newly diagnosed with type 2 diabetes and have fewer comorbidities. The benefits of low blood pressure and tight metabolic control is attenuated with the development of comorbidities, especially frailty. Guidelines consider frail older people as one category and recommend relaxed targets. However, sarcopenic obese frail individuals may benefit from tight targets and intensification of therapy due to their unfavourable metabolic profile, accelerated diabetes trajectory and high cardiovascular risk. In addition, the early use of sodium glucose transporter-2 inhibitors and glucagon like peptide-1 receptor agonists may be beneficial in this frailty phenotype due to their cardio-renal protection, which is independent of glycaemic control, provided they are able to engage in resistance exercise training to avoid loss of muscle mass. In the anorexic malnourished frail individual, early use of insulin, due to its weight gain and anabolic properties, is appropriate. In this phenotype, targets should be relaxed with deintensification of therapy due to significant weight loss, decelerated diabetes trajectory and increased risk of medication side effects.

Spatial clustering in childhood diabetes: evidence of an environmental cause.

If environmental factors are important in the aetiology of insulin-dependent (Type 1) diabetes mellitus, primary schooling would be more likely to be shared by cases in an epidemic year compared with controls. We have examined a case control study, comparing primary schools attended. Cases were identified from an established register with known accurate ascertainment and compared with controls taken from a central register of all children and date of birth, sex, and race matched. Parents were asked to complete a structured questionnaire which included questions relating to the child's schooling. There were 187 cases with at least a first matched control. Thirty-two of the cases attended the same nursery or primary school as another case, 18 in the same academic year, compared with 12 controls attending the same school as another control (99% confidence interval (CI) for the difference between proportions 0.0572 - 0.107). Of these cases diagnosed in 1986, 9 attended the same school as another case. Spatial clustering occurs in Type 1 diabetes. This is further evidence of an environmental factor contributing to the genesis of the disease.

Human erythrocyte membrane fluidity and calcium pump activity in primary combined hyperlipidaemia.

1. Human erythrocyte membrane cholesterol, fluidity and basal and calmodulin-stimulated calcium pump (Ca(2+)-Mg(2+)-ATPase) activities were compared in 24 patients with primary combined hyperlipidaemia and 20 age-matched normolipidaemic control subjects. 2. There was no correlation between serum and membrane cholesterol. Despite the differences in serum cholesterol levels between the two groups, membrane cholesterol levels were similar. 3. 1,6-Diphenyl-1,3,5-hexatriene anisotropy was lower in the hyperlipidaemic group, suggesting increased fluidity in the hydrocarbon core of the phospholipid membrane bilayer. 4. Basal calcium pump activity was lower in the hyperlipidaemic group with increased membrane fluidity. 5. These results suggest that membrane adaptive mechanisms can maintain membrane cholesterol within a narrow range, that serum triacylglycerol is more important than serum cholesterol in determining membrane fluidity and that increased membrane fluidity reduces basal calcium pump activity.

Human red cell membrane fluidity and calcium pump activity in normolipidaemic type II diabetic subjects.

Red cell membrane cholesterol, 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[(4-trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) anisotropies and basal and calmodulin-stimulated calcium pump activities were compared in 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients and 20 normolipidaemic control subjects using the Mann-Whitney U-test. Serum cholesterol, membrane cholesterol, and membrane DPH and TMA-DPH anisotropies were similar in the two groups but both basal and calmodulin-stimulated calcium pump activities were reduced in the diabetic group: basal activity (median (inter-quartile range), mumol mg-1 h-1) 1.66 (1.18-1.97) vs 2.09 (1.90-2.50), p < 0.005 and calmodulin-stimulated activity 4.19 (3.07-5.48) vs 5.53 (4.70-6.88), p < 0.006. Although there were no correlations between glycaemic control and membrane anisotropy and between glycaemic control and calcium pump activity, the reduction in calcium pump activity is most likely due to a direct effect of diabetes on the calcium pump protein itself.

Chronic granulomatous disease--a case showing long-term survival.

The diagnosis of chronic granulomatous disease of childhood was made in a 10-year-old boy following episodes of recurrent cervical abscesses and ulcerative stomatitis since the age of 4 years. Nineteen years on, on antibiotic prophylaxis, he is now married and remains active although he has been hospitalized with serious complications on many occasions.

Colchicine therapy in Behçet's syndrome--a report of five cases.

Five patients with Behçet's syndrome of varying duration were treated with colchicine (500 micrograms b.i.d.). All improved clinically and one has remained clear for 1 year after cessation of therapy, although in one patient who had neurological symptoms, paraesthesiae have persisted throughout treatment.