Take Home Message
- Individuals with poor lifestyle and obesity are at higher risk of incident T2D nevertheless of their genetic risk.
- In children aged 6‐10, the unexpected 4.6% prevalence of prediabetes underlines the onset of prevention of diabetes at a young age and requirement for population‐based studies across all ages
- In patients with T1DM, there is strong correlation among geographic socio-economic status and readmission outcomes, but there is limited correlation
- In older people with T2DM, the cardiovascular morbidity and mortality risks have reduced significantly over the years however in younger people it remains unchanged.
- The child’s gluten intake at 18 months of age could elevate the risk of type 1 diabetes in the child but not the maternal intake in pregnancy.
- Dapagliflozin increases health-related quality of life and decreases death and hospitalisation, with and without diabetes, in patients with heart failure and reduced ejection fraction.
1. Obesity and unfavourable lifestyle increase type 2 diabetes‐risk independent of genetic predisposition
A new research was presented by Jakupovic H, on 16th September 2019 at 55 EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain. Type 2 diabetes (T2D) is an increasingly common disease that provides considerably to the global burden of disease. In the etiology of T2D, genetic predisposition, obesity, and unfavorable lifestyle have a key role.
The current strategy to inhibit T2D is emphasized by the encouragement of a healthy lifestyle. In high-risk subjects, weight loss exhibited delay in the onset of T2D by lifestyle interventions. But, the effects of lifestyle factors and obesity on T2D risk may differ among individuals depending on genetic variation. Therefore, in the development of T2D, it is essential to understand the interplay among genetic predisposition, obesity, and unfavorable lifestyle. The authors conducted a study to assess whether the effects of obesity and unfavorable lifestyle on T2D risk are independent of genetic predisposition. A casecohort sample of 9,556 men and women were assigned from the Danish prospective Diet, Cancer and Health cohort and Prenticeweighted Cox regression models were applied by them.
49.5% of the participants developed T2D during an average 12 years of follow-up. No current smoking, moderate alcohol consumption, regular physical activity, and a healthy diet were the healthy lifestyle factors shown a favorable lifestyle. An unfavorable lifestyle was explained as no or only one healthy lifestyle factor while the remaining participants were defined as having an intermediate lifestyle. A genetic risk score (GRS) determined genetic risk by incorporating 213 genetic loci vigorously correlated with T2D. The GRS was stratified into low (lowest 25%), intermediate (middle 50%) and high risk (top 25%) groups. The researchers found that T2D risk was reduced by adherence to a favorable lifestyle and normalweight independent of genetic predisposition (p>0.05 for GRS-lifestyle and GRS-obesity 2 interaction). Obesity (BMI ≥ 30 kg/m ) elevated T2D-risk by 5.8-fold (95% CI: 5.2-6.6) as compared to non-obese individuals, although the independent outcomes of high (vs. low) genetic risk and unfavorable (vs. favorable) lifestyle were relatively limited (HR=1.8, 95% CI 1.6-2.0; and HR=1.2, 95% 1.1-1.3, respectively). The authors concluded that Individuals with poor lifestyle and obesity are at higher risk of incident T2D nevertheless of their genetic risk.
2. Differences in prediabetes and diabetes associated co‐morbidities between men and women
A new research was presented by Ofenheimer th th A, on 16 September 2019 at 55 EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain. Gender and sex may affect co-morbidities correlated with prediabetes and diabetes based on biological and behavioural variation. The authors conducted a study to examine sex and gender differences in the prevalence of co-morbidities in patients with prediabetes and diabetes except assessing the prevalence of prediabetes and diabetes (by FPG and HbA1c levels).
11,014 patients aged 6-80 years were included in this observational, population-based cohort study. Analyses included blood samples, ankle-brachial index, ECG, dual energy X-ray absorptiometry scan, and an interviewer-administered questionnaire. Prediabetes and diabetes were explained by fasting plasma glucose levels (prediabetes: 100-125mg /dL , diabetes: ≥ 126mg/dL) and/or HbA1c (prediabetes: 5.7- <6.5%, diabetes: ≥6.5%) and/or glucose-lowering pharmacological therapy (prediabetes: no, diabetes: currently). For distribution comparisons of ordinal scaled parameters, T-tests for independent samples were used to analyse group differences in means, Chi-square test and Fisher’s exact test. 20.2% (male 23.6%; female 17.1%) was the prevalence of prediabetes and 5.4% for diabetes (male 7.3%; female 3.7%) over all ages. The authors found that the prevalence of prediabetes aligned from 4.8% up to 42.3% in women and from 4.4% (6-<10 years) up to 40.4% (70+ years) in men.
The authors said that co-morbidity profile mainly in those with prediabetes, was remarkably different among male and female participant: women more frequently suffered from arrhythmia, non-coronary artery disease, osteoporosis, elevated systemic inflammatory biomarkers, and depression, while men with prediabetes more frequently exhibited angina pectoris, myocardial infarction, and media sclerosis. The authors concluded that in children aged 6‐10, the unexpected 4.6% prevalence of prediabetes underlines the onset of prevention of diabetes at a young age and requirement for population‐based studies across all ages.
3. Deprivation associated with increased risk of death following hospital admission with type 2 diabetes
A new research was presented by Robbins T, on 18 th September 2019 at 55 th EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain shows that in patients with type 2 diabetes (T2D), where you live has an effect on how likely you are to die, and in patients with type 1 diabetes (T1D), how likely you are to be readmitted to hospital following hospital discharge. Diabetic patients are at elevated risk of negative consequences at hospital discharge nevertheless of admission reason. Generally socioeconomic factors operate poor outcomes in diabetes. The authors conducted a study with an innovative approach to analyse effect of socioeconomic factors on readmission and mortality to relate patient level health data to national geographic & census data.
A new researchers analysed retrospective data of all patients discharged with a diabetes diagnosis over 3-years, extracted from an electronic health record (EHR) of a large UK tertiary referral centre. 46,357 distinct discharges were included in data extraction. To postcode sector socioeconomic data which extracted from Office of National Statistics Census and Population Density datasets, data were matched at patient level. 19 socioeconomic variables were analysed including index of multiple deprivation, employment, ethnicity, activity levels, unpaid care, language, population and housing density. 28-day readmission and 180- day mortality were outcome measures. Outcomes estimated across pre-specified diabetes cohorts. Standardised effect sizes estimated for all statistically substantial variables and compared across patient cohorts and outcomes. National Institute of Health Research RDS apprised research strategy which supported patient public involvement.
The authors found that in the T2DM patient cohort, socioeconomic status was numerically substantially correlated with 14 of 19 socioeconomic variables in association to 180d mortality (p<0.05 Student’s T test). In comparison with the T1DM cohort, there was no statistically consequential correlation among mortality and socioeconomic variables. Language, ethnicity & index of multiple deprivation were associated with strongest effect sizes (Cohen’s D). Socioeconomic status was substantially correlated with only 1 of 19 variables for 28d readmission in T2DM patient cohorts as compared to 9 numerically significant variables in T1DM cohorts. Readmission for T1DM cohorts and effect sizes in association to socio-economic status was extreme and strongest for deprivation indices (Cohen’s D 0.29) and health related activity impairment (0.15). The authors added “This research is important to guide execution and analysis of interventions to increase effects at hospital discharge. Use of geographic postcode sector data can be readily included into EHR systems and future risk stratification models to permit personalised data-driven”. The authors concluded that in patients with T1DM, there is strong correlation among geographic socio-economic status and readmission outcomes, but there is limited correlation
4. UK study shows increasing proportion of younger adults with type 2 diabetes, with younger cases having a worse metabolic profile
A new research was presented by Koye D, on 18 th September 2019 at 55 th EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain exhibits that the proportion of younger adults being diagnosed with type 2 diabetes (T2D) has improved since the start of the century. The authors conducted a study to assess temporal pattern of young-onset T2DM, risk factor control, comorbidities and the risk of macrovascular disease (MVD) and all-cause mortality (ACM) in young people as compared to older people with T2DM.
From January 2000, 343,714 people diagnosed with T2DM were recognized by nationally representative UK primary care electronic medical records. A new researchers extracted data at diagnosis (Dx) of T2DM, on anthropometric, clinical and laboratory measures and comorbidities, and on MVD and ACM in median 7 years follow-up. From 2000 to 2017, the temporal trend in the proportion of people at Dx in the age groups 18-40, 41-50, 51-60, 61-70 and 71-80 were analysed. The temporal trend of rate / 1000 person years for MVD and ACM were analysed.
Overall 343,714 incident cases of T2DM were recognized, 11% and 16% were in the 18-40 and 41-50 years age groups respectively with mean age 53 years. Proportion of people in these age groups marginally increased from 9.5% to 12.5% and 14% to 17.5% respectively over 17 years. The authors found that the youngest group had substantially greater BMI (mean: 35 kg/m 2 , 69% obese) and LDL-C (74% with LDL-C ≥ 100 mg/dL) as compared to older people, 51% had SBP ≥ 130 mmHg, and 2 / 4 % had microvascular disease / MVD at determination. With mean (SD) HbA1c of 9.2 (2.1)% (73% with A1c ≥ 7.5%), the youngest people had continually higher HbA1c temporal trends with little reduction, while the HbA1c level at diagnosis has reduced over time in people aged ≥ 60 years. From around 2005 onwards, the temporal patterns of occurrence rates of MVD remained similar for all age groups. But, for people aged >60 years, the ACM rate reduced over time (by ~ 20% in 60-70 years group and ~ 30% in 70-80 years group), but remained unchanged in the 18-40, 41-50 and 51-60 years groups. “Young-onset diabetes has a more assertive phenotype as compared to older-onset diabetes. More intense strategies are needed to increase longer term cardiovascular and mortality effects in this population”. The authors concluded that the percentage of young-onset T2DM has increased from 2000 to 2017. Young people with T2DM have a greater cardiovascular risk factor burden. In older people with T2DM, the cardiovascular morbidity and mortality risks have reduced significantly over the years however in younger people it remains unchanged.
5. Child’s gluten intake during infancy, rather than mother’s during pregnancy, linked to increased risk of developing type 1 diabetes
A new research was presented by Lund-Blix NA, on 19 th September 2019 at 55 th EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain shows that a child’s intake of gluten is correlated with a 46% improved risk of developing type 1 diabetes for each extra 10g of gluten consumed at age 18 months. No studies have explored the association among risk of developing type 1 diabetes in childhood and the amount of gluten intake by both the mother during pregnancy and the child in early life. The authors conducted a study to assess the correlation among the maternal gluten intake during pregnancy, child’s gluten intake at age 18 months, and the risk of type 1 diabetes in the child in a Norwegian population-based nation-wide study.
A new researchers studied 86,306 children in the Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018. The outcome was clinical type 1 diabetes, discovered in a nation-wide childhood diabetes registry. Cox regression analysed hazard ratios for the exposures maternal gluten intake in pregnancy and child’s gluten intake at 18 months. The authors procured the amount (g/day) of gluten intake from a semi-quantitative food frequency questionnaire at week 22 of pregnancy and from a questionnaire completed by the guardian when the child was 18 months old. The authors found that 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years) during a mean follow-up of 12.3 years (range 0.7-16.0). In pregnant mothers, the average gluten intake was 13.6 grams/day, and 8.8 grams/day for the child at 18 months of age.
The authors found that Maternal gluten intake in mid-pregnancy was not correlated with the development of type 1 diabetes in the child (adjusted HR 1.02 (95% CI 0.73 to 1.43) per 10 grams/day increase in gluten intake). But, the child’s gluten intake at 18 months of age was correlated with an elevated risk of later developing type 1 diabetes (adjusted HR 1.46 (95% CI 1.06 to 2.01) per 10 grams/day increase in gluten intake). The authors concluded that the child’s gluten intake at 18 months of age could elevate the risk of type 1 diabetes in the child but not the maternal intake in pregnancy.
6. New research shows Dapagliflozin used to treat diabetes can also treat heart failure, in patients with and without diabetes (the DAPA-HF Study)
A new research was presented by McMurray JJV on 19 th September 2019 at 55 th EASD Annual Meeting 2019 in Fira de Barcelona, Barcelona, Spain shows that Dapagliflozin is definitely a treatment for heart failure and not just a drug for diabetes. Dapagliflozin has already been proved to decrease the risk of developing heart failure in patients with type 2 diabetes. The authors conducted a study to analyse whether the drug could also be used to treat patients with T2D in whom heart failure had already developed (established heart failure), and also heart failure in patients without type 2 diabetes. The researchers deliberated the trial (the DAPA-HF study) enlisted 4,744 patients from 20 countries with heart failure and reduced ejection fraction, of whom 45% had T2D, and 55% did not have T2D. Patients were randomized to either Dapagliflozin 10 mg once daily or matching placebo. The primary endpoint was a combination of a first episode of worsening heart failure (hospitalisation for heart failure or an urgent heart failure visit requiring intravenous therapy) or death from cardiovascular causes. The researchers found that the primary outcome arised in 386 of 2,373 patients (16.3%) in the Dapagliflozin group and in 502 of 2,371 patients (21.2%) in the placebo group across a median follow- up of 18.2 months, interpretating to a 26% decreased risk in the Dapagliflozin (HR 0.74; 95% CI 0.65–0.85; p<0.00001). The results were similar in the groups with T2D (HR 0.75 / 25% reduced risk) and without T2D (HR 0.73 / 27% reduced risk). The components of the primary outcome were also assessed separately by the researchers. A first episode of worsening heart failure was experienced by total 237 patients (10.0%) receiving Dapagliflozin and 326 patients (13.7%) receiving placebo, hence exhibiting a 30% decreased risk in the Dapagliflozin group (HR 0.70; 95% CI 0.59–0.83; p<0.00004). The Dapagliflozin group showed 18% lower risk in the cardiovascular death (227 (9.6%) vs. 273 (11.5%), resp.) (HR 0.82; 95% CI 0.69–0.98; p=0.03). All-cause mortality was decreased by 17% (HR 0.83, 95%CI 0.71-0.97; p=0.22). Symptoms were also increased as calculated by the Kansas City Cardiomyopathy Questionnaire (p<0.001). The authors further added “Adverse events rarely needed the discontinuation of treatment. There was no remarkable excess of any serious adverse event due to Dapagliflozin group. The clinical suggestions are potentially large – few drugs gain these results in heart failure and Dapagliflozin does even when added to excellent standard therapy.” The authors concluded that Dapagliflozin increases health-related quality of life and decreases death and hospitalisation, with and without diabetes, in patients with heart failure and reduced ejection fraction.
