Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Prescribing practices and clinical predictors of glucose-lowering therapy within the first year in people with newly diagnosed Type 2 diabetes.

AIM: To examine prescribing practices and predictors of glucose-lowering therapy within the first year following diagnosis of Type 2 diabetes mellitus in a clinical care setting. METHODS: We followed people enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort from outpatient hospital clinics and general practices throughout Denmark in 2010-2013. We used Poisson regression to compute age- and gender-adjusted risk ratios (RRs). RESULTS: Among 1158 new Type 2 diabetes mellitus patients, 302 (26%) did not receive glucose-lowering therapy within the first year, 723 (62%) received monotherapy [685 (95%) with metformin], and 133 (12%) received more than one drug. Predictors of receiving any vs. no therapy and combination vs. monotherapy were: age < 40 years [RR: 1.29 (95% CI: 1.16-1.44) and 3.60 (95% CI: 2.36-5.50)]; high Charlson Comorbidity Index [RRs: 1.20 (95% CI: 1.05-1.38) and 2.08 (95% CI: 1.16-3.72)]; central obesity [RRs: 1.23 (95% CI: 1.04-1.44) and 1.93 (95% CI: 0.76-4.94)]; fasting blood glucose of ≥ 7.5 mmol/l [RRs: 1.25 (95% CI: 1.10-1.42) and 1.94 (95% CI: 1.02-3.71)]; and HbA1c ≥ 59 mmol/mol (≥ 7.5%) [RR: 1.26 (95% CI: 1.20-1.32) and 2.86 (95% CI: 1.97-4.14)]. Weight gain ≥ 30 kg since age 20, lack of physical exercise and C-peptide of < 300 pmol/l also predicted therapy. CONCLUSIONS: Comorbidity, young age, central obesity and poor baseline glycaemic control are important predictors of therapy one year after Type 2 diabetes mellitus debut.

Safety and biological efficacy of an adeno-associated virus vector-cystic fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary sinus.

OBJECTIVE: The host immune response and low vector efficiency have been key impediments to effective cystic fibrosis transmembrane regulator (CFTR) gene transfer for cystic fibrosis (CF). An adeno-associated virus vector (AAV-CFTR) was used in a phase I dose-escalation study to transfer CFTR cDNA into respiratory epithelial cells of the maxillary sinus of 10 CF patients. STUDY DESIGN: A prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of AAV-CFTR was conducted. PATIENTS: Ten patients with previous bilateral maxillary antrostomies were treated. MAIN OUTCOME MEASURES: Safety, gene transfer as measured by semiquantitative polymerase chain reaction (PCR), and sinus transepithelial potential difference (TEPD) were measured. RESULTS: The highest level of gene transfer was observed in the range of 0.1-1 AAV-CFTR vector copy per cell in biopsy specimens obtained 2 weeks after treatment. When tested, persistence was observed in one patient for 41 days and in another for 10 weeks. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. Little or no inflammatory or immune responses were observed. CONCLUSION: AAV-CFTR administration to the maxillary sinus results in successful, dose-dependent gene transfer to the maxillary sinus and alterations in sinus TEPD suggestive of a functional effect, with little or no cytopathic or host immune response. Further study is warranted for AAV vectors as they may prove useful for CFTR gene transfer and other in vivo gene transfer therapies. A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF.

[The suicidal patient. 1. Occurrence and relevance of contact with a general practitioner prior to the suicidal actions]. / Den suicidale patient. 1. Hyppighed og relevans af kontakten til praktiserende laeger forud for suicidale handlinger.

A multipractice investigation was undertaken concerning suicidal behaviour. Sixty-six patients committed suicide and 227 attempted suicide. During the month prior to the suicidal actions, 2/3 of the patients had had contact with their general practitioners. Only very few had been in contact with a psychiatric department or with a practising psychiatrist during the same period. In a few cases, the general practitioner found that the most recent consultation was relevant in cases of patients who committed suicide. 28% of the patients who committed suicide and also were seen by their general practitioners within the last month suffered from serious somatic disease. Where the cases of attempted suicide were concerned, the general practitioners considered that 40% of the most recent consultations were relevant. In order to improve attention to suicidal signals, other forms of cooperation between the primary sector and hospitals, eg in the form of district psychiatric teams, are suggested.

[The suicidal patient. 2. Methods of suicide, diagnoses and social conditions]. / Den suicidale patient. 2. Selvmordsmetoder, diagnoser og sociale forhold.

By means of a multipractice investigation in which 347 general practitioners participated, 293 schemata were collected about patients who had undertaken suicidal acts. The material consists of 66 suicides and 227 attempted suicides. By and large, the sex and age distributions correspond to those in previous investigations. The number of attempted suicides in this investigation was only half of that anticipated. This may be due to lapse, seasonal variations, underrepresentation of urban practice etc. Strikingly many patients undertook acts in this material without having psychiatric diagnoses and the psychiatric diagnosis did not appear to play any part as regards whether the suicidal act lead to suicide. The methods employed appear otherwise to reflect development in society and pharmacotherapy. Where men were concerned, it appears that suicide is relatively most common among widowers, unemployed and early retirees while, where women were concerned, divorcees and early retirees were most frequently involved. Attempted suicide is most frequently carried out by unemployed men and by divorced and early retirees of both sexes. This investigation cannot indicate any definite occupational group which involves a risk as regards suicidal acts and economical factors appear only to play a part where attempted suicide is concerned.

Disease activity and serum proteins in ulcerative colitis. Immunochemical quantitation.

Nine different serum proteins from 50 patients suffering from ulcerative colitis were quantitated by means of Laurell's rocket-electrophoresis. The periods of study extended for up to five years. Twenty-six patients were seen at brief intervals from days up to two months; 18 patients were seen at intervals from two to six months. As surgical intervention was urgently required in six cases, few determinations were made in these patients. The disease was classified into five phases according to its clinical activity (as assessed by temperature, blood via the rectum, and number of episodes of diarrhoea). The phases are designated: active febrile; active afebrile; unstable; remission; and restitution. The concentrations of orosomucoid and haptoglobin were found to rise in parallel with intensified clinical activity, while the concentration of pre-albumin falls, thus making these proteins particularly useful for determining changes in the clinical status of the patients. The concentration of pre-albumin during the active phase was especially useful in cases where it was to be decided whether or not surgery was indicated. Concentrations of orosomucoid and IgG were not as useful as pre-albumin in these cases. In patients who escaped operation, the concentration of pre-albumin was seen to rise from low values up to normal before clinical improvement set in.