Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood

Key Points

Question  What is the prevalence of complications of type 1 diabetes and type 2 diabetes among teenagers and young adults who had been diagnosed during childhood and adolescence?

Findings  In an observational study of 1746 patients with type 1 diabetes and 272 with type 2 diabetes with onset younger than 20 years, the prevalence of diabetic kidney disease, retinopathy, and peripheral neuropathy was significantly greater in patients with type 2 diabetes, even after adjustment for differences in hemoglobin A1clevel, body mass index, waist-height ratio, and mean arterial blood pressure.

Meaning  Among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence, the prevalence of complications was higher among those with type 2 diabetes compared with type 1 diabetes, but frequent in both groups.

Abstract

Importance  The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown.

Objective  To determine the prevalence of and risk factors for complications related to type 1 diabetes vs type 2 diabetes among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence.

Design, Setting, and Participants  Observational study from 2002 to 2015 in 5 US locations, including 2018 participants with type 1 and type 2 diabetes diagnosed at younger than 20 years, with single outcome measures between 2011 and 2015.

Exposures  Type 1 and type 2 diabetes and established risk factors (hemoglobin A1c level, body mass index, waist-height ratio, and mean arterial blood pressure).

Main Outcomes and Measures  Diabetic kidney disease, retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension.

Results  Of 2018 participants, 1746 had type 1 diabetes (mean age, 17.9 years [SD, 4.1]; 1327 non-Hispanic white [76.0%]; 867 female patients [49.7%]), and 272 had type 2 (mean age, 22.1 years [SD, 3.5]; 72 non-Hispanic white [26.5%]; 181 female patients [66.5%]). Mean diabetes duration was 7.9 years (both groups). Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence of diabetic kidney disease (19.9% vs 5.8%; absolute difference [AD], 14.0%; 95% CI, 9.1%-19.9%; P < .001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; P = .02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; P < .001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; P < .001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; P < .001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, –3.1% to 6.5; P = .62). After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease (odds ratio [OR], 2.58; 95% CI, 1.39-4.81; P=.003), retinopathy (OR, 2.24; 95% CI, 1.11-4.50; P = .02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; P = .001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; P = .80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; P = .55).

Conclusions and Relevance  Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1, but frequent in both groups. These findings support early monitoring of youth with diabetes for development of complications.

Advertisements

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function

BACKGROUND

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms.

METHODS

We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest.

RESULTS

Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27±0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used bronchodilators and 23% used inhaled glucocorticoids.

CONCLUSIONS

Although they do not meet the current criteria for COPD, symptomatic current or former smokers with preserved pulmonary function have exacerbations, activity limitation, and evidence of airway disease. They currently use a range of respiratory medications without any evidence base. (Funded by the National Heart, Lung, and Blood Institute and the Foundation for the National Institutes of Health; SPIROMICS ClinicalTrials.gov number, NCT01969344.)

N Engl J Med 2016; 374:1811-1821

A Multicenter Observational Study of Incretin-based Drugs and Heart Failure

BACKGROUND

There is concern that antidiabetic incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues, can increase the risk of heart failure. Ongoing clinical trials may not have large enough samples to effectively address this issue.

METHODS

We applied a common protocol in the analysis of multiple cohorts of patients with diabetes. We used health care data from four Canadian provinces, the United States, and the United Kingdom. With the use of a nested case–control analysis, we matched each patient who was hospitalized for heart failure with up to 20 controls from the same cohort; matching was based on sex, age, cohort-entry date, duration of treated diabetes, and follow-up time. Cohort-specific hazard ratios for hospitalization due to heart failure among patients receiving incretin-based drugs, as compared with those receiving oral antidiabetic-drug combinations, were estimated by means of conditional logistic regression and pooled across cohorts with the use of random-effects models.

RESULTS

The cohorts included a total of 1,499,650 patients, with 29,741 hospitalized for heart failure (incidence rate, 9.2 events per 1000 persons per year). The rate of hospitalization for heart failure did not increase with the use of incretin-based drugs as compared with oral antidiabetic-drug combinations among patients with a history of heart failure (hazard ratio, 0.86; 95% confidence interval [CI], 0.62 to 1.19) or among those without a history of heart failure (hazard ratio, 0.82; 95% CI, 0.67 to 1.00). The results were similar for DPP-4 inhibitors and GLP-1 analogues.

CONCLUSIONS

In this analysis of data from large cohorts of patients with diabetes, incretin-based drugs were not associated with an increased risk of hospitalization for heart failure, as compared with commonly used combinations of oral antidiabetic drugs. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number,NCT02456428.)

By Kristian B. Filion et al, N Engl J Med 2016; 374:1145-1154March 24, 2016

Primary prevention and risk factor reduction in coronary heart disease mortality among working aged men and women in eastern Finland over 40 years: population based observational study

Objective To estimate how much changes in the main risk factors of cardiovascular disease (smoking prevalence, serum cholesterol, and systolic blood pressure) can explain the reduction in coronary heart disease mortality observed among working aged men and women in eastern Finland.

Design Population based observational study.

Setting Eastern Finland.

Participants 34 525 men and women aged 30-59 years who participated in the national FINRISK studies between 1972 and 2012.

Interventions Change in main cardiovascular risk factors through population based primary prevention.

Main outcome measures Predicted and observed age standardised mortality due to coronary heart disease. Predicted change was estimated with a logistic regression model using risk factor data collected in nine consecutive, population based, risk factor surveys conducted every five years since 1972. Data on observed mortality were obtained from the National Causes of Death Register.

Results During the 40 year study period, levels of the three major cardiovascular risk factors decreased except for a small increase in serum cholesterol levels between 2007 and 2012. From years 1969-1972 to 2012, coronary heart disease mortality decreased by 82% (from 643 to 118 deaths per 100 000 people) and 84% (114 to 17) among men and women aged 35-64 years, respectively. During the first 10 years of the study, changes in these three target risk factors contributed to nearly all of the observed mortality reduction. Since the mid-1980s, the observed reduction in mortality has been larger than predicted. In the last 10 years of the study, about two thirds (69% in men and 66% in women) of the reduction could be explained by changes in the three main risk factors, and the remaining third by other factors.

Conclusion Reductions in disease burden and mortality due to coronary heart disease can be achieved through the use of population based primary prevention programmes. Secondary prevention among high risk individuals and treatment of acute events of coronary heart disease could confer additional benefit.

By Pekka Jousilahti et al, BMJ 2016;352:i721

Association Between Hospitalization With Community-Acquired Laboratory Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination

Importance Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection.

Objective To assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia.

Design, Setting, and Participants The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community acquired pneumonia conducted from January 2010 through June 2012 at 4 US sites. In this case-control study, we used EPIC data from patients 6 months or older with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (case) and influenza-negative (control) patients with pneumonia, controlling for demographics, comorbidities, season, study site, and timing of disease onset. Vaccine effectiveness was estimated as (1−adjusted odds ratio)×100%. Exposure Influenza vaccination, verified through record review.

Main Outcomes and Measures Influenza pneumonia, confirmed by real-time reversetranscription polymerase chain reaction performed on nasal/oropharyngeal swabs. Results Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%) with influenza-associated pneumonia and 766 of 2605 controls (29%) with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI, 0.28-0.68; estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%).

Conclusions and Relevance Among children and adults hospitalized with community acquired pneumonia, those with laboratory-confirmed influenza-associated pneumonia, compared with those with pneumonia not associated with influenza, had lower odds of having received influenza vaccination.

Association Between Hospitalization With Community-Acquired Laboratory Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination by Carlos G. Grijalva, et al. JAMA. 2015;314(14):1488-1497

Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial

Objective To examine the effect of the bivalent human papillomavirus (HPV) vaccine on
miscarriage.
Design Observational long term follow-up of a randomized, double blinded trial combined
with an independent unvaccinated population based cohort.
Setting Single center study in Costa Rica.
Participants 7466 women in the trial and 2836 women in the unvaccinated cohort enrolled
at the end of the randomized trial and in parallel with the observational trial component.
Intervention Women in the trial were assigned to receive three doses of bivalent HPV
vaccine (n=3727) or the control hepatitis A vaccine (n=3739). Crossover bivalent HPV
vaccination occurred in the hepatitis A vaccine arm at the end of the trial. Women in the
unvaccinated cohort received (n=2836) no vaccination.
Main outcome measure Risk of miscarriage, defined by the US Centers for Disease
Control and Prevention as fetal loss within 20 weeks of gestation, in pregnancies exposed
to bivalent HPV vaccination in less than 90 days and any time from vaccination compared
with pregnancies exposed to hepatitis A vaccine and pregnancies in the unvaccinated
cohort.
Results Of 3394 pregnancies conceived at any time since bivalent HPV vaccination, 381
pregnancies were conceived less than 90 days from vaccination. Unexposed pregnancies
comprised 2507 pregnancies conceived after hepatitis A vaccination and 720 conceived in
the unvaccinated cohort. Miscarriages occurred in 451 (13.3%) of all exposed pregnancies,
in 50 (13.1%) of the pregnancies conceived less than 90 days from bivalent HPV
vaccination, and in 414 (12.8%) of the unexposed pregnancies, of which 316 (12.6%) were
in the hepatitis A vaccine group and 98 (13.6%) in the unvaccinated cohort. The relative risk
of miscarriage for pregnancies conceived less than 90 days from vaccination compared with
all unexposed pregnancies was 1.02 (95% confidence interval 0.78 to 1.34, one sided
P=0.436) in unadjusted analyses. Results were similar after adjusting for age at vaccination
(relative risk 1.15, one sided P=0.17), age at conception (1.03, P=0.422), and calendar year
(1.06, P=0.358), and in stratified analyses. Among pregnancies conceived at any time from
bivalent HPV vaccination, exposure was not associated with an increased risk of
miscarriage overall or in subgroups, except for miscarriages at weeks 13-20 of gestation
(relative risk 1.35, 95% confidence interval 1.02 to 1.77, one sided P=0.017).
Conclusions There is no evidence that bivalent HPV vaccination affects the risk of
miscarriage for pregnancies conceived less than 90 days from vaccination. The increased
risk estimate for miscarriages in a subgroup of pregnancies conceived any time after
vaccination may be an artifact of a thorough set of sensitivity analyses, but since a genuine association cannot totally be ruled out, this signal should nevertheless be explored further in existing and future studies.

Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial by Orestis A Panagiotou, et al. on behalf  of the Costa Rica HPV Vaccine Trial (CVT) Group
BMJ2015; 351 (Published 07 September 2015)

Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study

Objective To examine the association between warfarin treatment and longitudinal outcomes after ischemic stroke in patients with atrial fibrillation in community practice.

Design Observational study.

Setting Hospitals (n=1487) participating in the Get With The Guidelines (GWTG)-Stroke program in the United States, from 2009 to 2011.

Participants 12,552 warfarin naive atrial fibrillation patients admitted to hospital for ischemic stroke and treated with warfarin compared with no oral anticoagulant at discharge, linked to Medicare claims for longitudinal outcomes.

Main outcome measures Major adverse cardiovascular events (MACE) and home time, a patient centered outcomes measure defined as the total number of days free from institutional care after discharge. A propensity score inverse probability weighting method was used to account for all differences in observed characteristics between treatment groups.

Results Among 12,552 survivors of stroke, 11,039 (88%) were treated with warfarin at discharge. Warfarin treated patients were slightly younger and less likely to have a history of previous stroke or coronary artery disease but had similar severity of stroke as measured by the National Institutes of Health Stroke Scale. Relative to those not treated, patients treated with warfarin had more days at home (as opposed to institutional care) during the two years after discharge (adjusted home time difference 47.6 days, 99% confidence interval 26.9 to 68.2). Patients discharged on warfarin treatment also had a reduced risk of MACE (adjusted hazard ratio 0.87, 99% confidence interval 0.78 to 0.98), all cause mortality (0.72, 0.63 to 0.84), and recurrent ischemic stroke (0.63, 0.48 to 0.83). These differences were consistent among clinically relevant subgroups by age, sex, stroke severity, and history of previous coronary artery disease and stroke.

Conclusions Among ischemic stroke patients with atrial fibrillation, warfarin treatment was associated with improved long term clinical outcomes and more days at home.

Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study by Ying Xian, et al. BMJ 2015; 351 :h3786