A follow-up of 1475 Type 1 (insulin-dependent) diabetic patients diagnosed before 1953 (815 males, 660 females) and before the age of 31 years was conducted. All patients were seen at the Steno Memorial Hospital and were referred from all parts of Denmark; 91 (6%) could not be traced. The rest (94%) were followed until death or for at least 25 years; 249 (17%) were followed for greater than 40 years. Clinical diabetic nephropathy developed in 531 (41%) of the 1303 patients in whom sufficient information was available regarding proteinuria. Other causes of proteinuria were found in 3%, and 57% did not develop persistent proteinuria. The prevalence of diabetic nephropathy was 21% after 20-25 years of diabetes duration followed by a decline to 10% after 40 years. Two incidence peaks of the onset of proteinuria were seen, one after 16 and another after 32 years duration of diabetes and was low after 35 years duration. The cumulative incidence was 45% after 40 years of diabetes. A male preponderance was seen among patients with nephropathy. A significant difference in the pattern of annual incidence rates of diabetic nephropathy was seen, when groups with onset of diabetes before 1933, between 1933-1942, and 1943-1952, respectively, were compared. An association between daily insulin requirement and nephropathy incidence was found. Patients with nephropathy had a much poorer survival than those without proteinuria; 40 years after onset of diabetes, only 10% of patients who developed nephropathy were alive, whereas greater than 70% of patients who did not develop nephropathy survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten years of study has resulted in considerable but fragmented knowledge about regional cerebral blood flow in migraine with aura (classic migraine). In the present study, the number of repeatedly studied patients (n = 63) was large enough to determine statistically significant sequences of events and statistically significant spatial relations. The first observable event was a decrease of regional cerebral blood flow posteriorly in one cerebral hemisphere. Further development of this pathological process was accompanied by the aura symptoms. Thereafter headache occurred while regional cerebral blood flow remained decreased. During the headache phase, regional cerebral blood flow gradually changed from abnormally low to abnormally high without apparent change in headache. In some patients headache disappeared while regional cerebral blood flow remained increased. Although regional cerebral blood flow reduction and aura symptoms in the great majority of patients were unilateral, one-third had bilateral headache. Unilateral headache usually localized to the side on which regional cerebral blood flow was reduced and from which the aura symptoms originated (i.e., aura symptoms were perceived to occur contralaterally but presumably originated in the hypoperfused hemisphere). Our results suggest a simple model for migraine attacks: A pathological disturbance in one cerebral hemisphere causes the aura symptoms and after a time delay, it also causes the headache by stimulating local vascular nociceptors. Bilateral headache caused by a unilateral cerebral disturbance may be explained by recent neuroanatomical and neurophysiological findings.

In healthy individuals, the incretin hormone glucagon-like peptide 1 (GLP1) potentiates insulin release and suppresses glucagon secretion in response to the ingestion of nutrients. GLP1 also delays gastric emptying and increases satiety. In patients with type 2 diabetes mellitus (T2DM), supraphysiological doses of GLP1 normalize the endogenous insulin response during a hyperglycaemic clamp. Owing to the short plasma half-life of native GLP1, several GLP1 receptor agonists (GLP1RAs) with longer half-lives have been developed for the treatment of T2DM. These compounds vary in chemical structure, pharmacokinetics and size, which results in different clinical effects on hyperglycaemia and body weight loss; these variations might also explain the difference in cardiovascular effect observed in large-scale cardiovascular outcome trials, in which certain GLP1RAs were shown to have a positive effect on cardiovascular outcomes. Owing to their metabolic effects, GLP1RAs are also considered for the treatment of several other lifestyle-induced conditions, such as obesity, prediabetes and liver disease. This Review provides insights into the physiology of GLP1 and its involvement in the pathophysiology of T2DM and an overview of the currently available and emerging GLP1RAs. Furthermore, we review the results from the currently available large-scale cardiovascular outcome trials and the use of GLP1RAs for other indications.