Clinical significance and safety of combined treatment with chemotherapy and pulmonary rehabilitation regarding health-related quality of life and physical function in nontuberculous mycobacterial pulmonary disease

BackgroundIn the treatment of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD), pulmonary rehabilitation (PR) has been recommended as a non-pharmacological therapy. However, no study has validated the combination of chemotherapy and PR in this context. This study investigated the effect of chemotherapy and supervised PR on health-related quality of life (HRQoL) and physical function in NTM-PD patients.MethodsThis prospective cohort study included patients diagnosed with NTM-PD who had a planned hospitalization of at least 3 weeks for chemotherapy and PR. HRQoL (Leicester Cough Questionnaire [LCQ] and chronic obstructive pulmonary disease assessment test [CAT]), physical function (incremental shuttle walk distance [ISWD], quadriceps force), and C-reactive protein levels were assessed before and after treatment, and the corresponding data were analyzed in conjunction with clinical data. The adverse events of PR were also investigated.ResultsForty-two patients who met the study criteria were included in the analysis. After treatment, all LCQ item scores, total CAT score and sub-item scores related to respiratory symptoms, ISWD, quadriceps force, and C-reactive protein levels were found to have improved significantly. In the chronic cough with excessive sputum production (CCS) group, the proportions of responders who showed improvements in LCQ and CAT scores and ISWD greater than the corresponding minimal clinically important difference were significantly greater than those in the non-CCS group. No PR-related adverse events were reported.ConclusionsCombined treatment with chemotherapy and PR may improve HRQoL and physical function, and supervised PR can be provided safely.     

Association of longitudinal changes in quality of life with comorbidities and exacerbations in patients with severe asthma

BackgroundQuality of life (QoL) assessment is important in the management of severe asthma, and comorbidities and/or exacerbations may affect longitudinal QoL. However, there are few reports on the longitudinal assessment of QoL in patients with asthma over multiple years and its related factors. This study aimed to clarify the relationship of longitudinal changes in QoL with comorbidities and/or exacerbations during a prolonged observation period in patients with severe asthma.MethodsA total of 105 subjects who participated in the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) with a six-year follow-up were analyzed. QoL was assessed annually, using the Standardized Asthma Quality of Life Questionnaire, and the subjects were divided into three groups: (1) persistently good QoL, (2) persistently poor QoL, and (3) fluctuating QoL. Assessed comorbidities comprised depression, gastroesophageal reflux disease, and excessive daytime sleepiness (EDS), a key symptom of obstructive sleep apnea.ResultsOf 105 subjects with severe asthma, 53 (50%) were classified in the persistently good QoL group, 10 (10%) in the persistently poor QoL group, and 42 (40%) in the fluctuating QoL group. The persistently poor QoL group was associated with shorter time to hospitalization due to exacerbation and the presence of multiple comorbidities. In addition, the presence of EDS was an independent contributor to the fluctuating QoL group compared to the persistently good QoL group.ConclusionsThe presence of multiple comorbidities and hospitalization due to exacerbation contribute to longitudinal changes in QoL in patients with severe asthma.     

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study

BackgroundBronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM.MethodsThis retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort.ResultsIn total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score.ConclusionsBronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.     

Effects of home-based exercise training on functional outcomes and quality of life in patients with pulmonary hypertension: A randomized clinical trial

ObjectivesThe objective of this study was to assess the effects of home-based exercise training (HBET) on function and quality of life (QoL) in patients with pulmonary hypertension (PH).MethodsA prospective, nonblinded, randomized clinical trial was carried out on 84 medically stable patients with PH belonging to any functional class or etiology and of either sex. Patients were randomized to either standard care or HBET. Both groups also received education using the Pulmonary Hypertension Manual (PulHMan). Outcomes included functional capacity from 6-min walk distance (6MWD), QoL using the Medical Outcomes Survey Short Form – 36, functional class (FC), and right heart indices (right ventricular systolic pressure [RVSP] and tricuspid annular plane systolic excursion [TAPSE]) and were assessed at entry and after 12 weeks.ResultsHBET improved 6MWD by 48.5 m and 13 m in the experimental and control groups, respectively (p < 0.001). QoL showed statistical improvements after HBET between the groups for the physical and mental components and for the various subdomains (except body pain). Furthermore, FC improved by one grade with HBET (p < 0.001).ConclusionHBET program improved functional capacity, QoL, and FC in patients with PH.     

Is the Leicester Cough Questionnaire useful for nontuberculous mycobacterial lung disease?

BackgroundAlthough the incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide, there is no established standard of care leading to eradication. Therefore, research on health-related quality of life (HRQOL) is important for patients with NTM-LD. HRQOL is commonly evaluated using the St. George's Respiratory Questionnaire (SGRQ), developed for chronic obstructive pulmonary disease (COPD). However, NTM-LD differs from COPD in that few patients complain of dyspnea or wheezing, and cough and sputum are their main symptoms. The Leicester Cough Questionnaire (LCQ) is an HRQOL questionnaire dedicated to cough, but few studies have used it for NTM-LD. This study evaluated HRQOL in patients with NTM-LD using the SGRQ and LCQ and clarified the usefulness of the LCQ.MethodsInformation on age, height, weight, lung function, percent ideal body weight, laboratory data, radiological scores, exercise capacity, SGRQ, and LCQ were collected from the medical records of 81 patients. Correlations between SGRQ and LCQ domains were assessed using Spearman's rank correlation coefficients. Multivariate analysis was performed with SGRQ and LCQ total scores.ResultsStatistically significant correlations were observed between all domains, and the correlation between the total scores was ?0.67 (p < 0.01). Multivariate analysis with total scores as the dependent variable showed that the explanatory variables were lung function (p < 0.05) and radiological score (p < 0.05) in the SGRQ, and radiological score (p < 0.05) and C-reactive protein level (p < 0.05) in the LCQ.ConclusionThe LCQ, which evaluates an inflammatory response involved in the diagnosis of NTM-LD, may be useful to assess HRQOL in patients with NTM-LD.     

Gastroesophageal reflux-like symptoms are associated with hyposalivation and oropharyngeal problems in patients with asthma

BackgroundPrevious studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma.MethodsThis study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation.ResultsIn total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (<0.25 g/min). The patients with hyposalivation were significantly older (p < 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p < 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p < 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation.ConclusionsAge, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.     

Health-related quality of life of multidrug-resistant tuberculosis patients: A study of eastern Uttar Pradesh,India

IntroductionMuch attention has been given to the microbiological aspect, drug treatment, and clinical indicators of MDR-TB, but patients' QOL has remained a neglected area. In this study, we aimed to find the quality of MDRTB on various quality of life domains during the initiation of the MDR Treatment regimen.Materials & methodsA cross-sectional study was conducted over a period of 6 months at the Drug-Resistance Tuberculosis Management Centre (DR-TB Centre), of a tertiary care centre in the eastern Uttar pradesh, India. Patients with age >18 years diagnosed with MDR-TB (Multidrug resistance TB) were included in the study. The WHO QOL-BREF scale was used to assess the health-related quality of life of patients. Data were analyzed using SPSS version 21. The institutional ethical review committee approved the study, and consent was taken before the participation of patients.ResultsA total of 157 patients were included in the study & 45.85% were dissatisfied with their condition. Social domain of WHO QOL-BREF is having the lowest mean score (28.51 ± 15.4) while psychological has high mean values (39.92 ± 6.91). There was a significant difference in the physical health domain with respect to age (p-value 0.001). Similar differences have been seen in the psychological domain regarding patient sex (p-value 0.001), smoking and alcohol within the social domain, and loss of income in the environmental domain.ConclusionThe mean value of different domains of WHO QOL-BREF is low in MDR-TB patients, with social relation domain being the most affected.     

Low Mediterranean Diet scores are associated with reduced kidney function and health related quality of life but not other markers of cardiovascular risk in adults with diabetes and chronic kidney disease

Background and aimsHow Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes.Methods and resultsThis is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA_1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1–2 vs 3–5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA_1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01).ConclusionsLow MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.     

Lifetime risk of cardiovascular disease and life expectancy with and without cardiovascular disease according to changes in metabolic syndrome status

Background and aimsThe relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status.Methods and ResultsDynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan–Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%–41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%–42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%–45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%–30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years).ConclusionsRecovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.     

Pulmonary tuberculosis misdiagnosed as extensively drug-resistant tuberculosis due to selection of a nontuberculous mycobacterial colony from a preculture dish used for a drug-susceptibility test

Drug-susceptibility test (DST) is important for tuberculosis care; however, there are several pitfalls with the procedure. A 70-year-old woman was diagnosed with extensively drug-resistant tuberculosis based on the result of a DST using microdilution method. Because she had no history of medication for tuberculosis and the sputum acid-fast bacillus smear test turned negative during standard treatment, identification of the strain used for DST was performed. Consequently, the strain was found to be M. intracellulare. It was assumed that a colony of M. intracellulare that had existed in the preculture solid medium was selected and used for the DST.     

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy

Background and aimsNonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy.Methods and resultsAdult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017.Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs.ConclusionNAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.     

Health-related quality of life after adverse bleeding events associated with antithrombotic drug therapy – A systematic review

Little is known about the health-related quality of life (HRQOL) following adverse bleeding events associated with antithrombotic drug therapy. This systematic review assesses the HRQOL of patients who suffered a bleeding event related to antithrombotic drug use. A literature search was performed using PubMed, EMBASE, and the Cochrane Library from inception through June 16, 2017. Studies measuring HRQOL after a bleeding event related to antithrombotic drug therapy for primary or secondary prevention of a thromboembolic event were included. Four studies with a total of 13,209 patients met the inclusion criteria, and of them, 3,649 patients developed a bleeding event. Patients who were included received antithrombotic drugs because of acute myocardial infarction or atrial fibrillation. EQ-5D, SF-36, and GHP MOS-13 were used to measure HRQOL. The follow-up time ranged from 6 to 29 months. Patients who suffered a bleeding event reported worse HRQOL compared to those who did not (EQ-5D – average increase on all domains of 0.09, p-values ranging from <0.001 to 0.003; SF-36 – average decrease on all domains of 21.4, p < 0.001; and GHP MOS-13 score – decrease of 11.9 points, p < 0.05) and an increased health concern (13.4-point increase; p < 0.05). In conclusion, adverse bleeding events occurring because of the use of antithrombotic agents are associated with a clinically relevant lower HRQOL and hence deserve more attention as part of the shared decision-making process between patients and providers. These data should be valuable for facilitating more substantive care and risk discussions regarding potential changes in outcome and rehabilitation.     

Plasma phospholipid dysregulation in patients with cystathionine-β synthase deficiency

Background & aimsPatients with cystathionine β-synthase deficiency (CBSD) exhibit high circulating levels of homocysteine and enhanced lipid peroxidation. We have characterized the plasma lipidome in CBSD patients and related lipid abnormalities with reactions underlying enhanced homocysteine levels.Methods and resultsUsing an ultra-high-performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry method, plasma lipids were determined with an untargeted lipidomics approach in 11 CBSD patients and 11 matched healthy subjects (CTRL). Compared to CTRL, CBSD patients had a higher medium and long-chain polyunsaturated fatty acids (PUFA) content in phosphatidylethanolamine (PE) and lysophosphatidylethanolamine (LPE) species (p < 0.02), and depletion of phosphatidylcholine (PC; p = 0.02) and of lysophosphatidylcholine (LPC; p = 0.003) species containing docosahexaenoic acid (DHA), suggesting impaired phosphatidylethanolamine-N-methyltransferase (PEMT) activity. PEMT converts PE into PC using methyl group by S-adenosylmethionine (SAM) thus converted in S-adenosylhomocysteine (SAH). Whole blood SAM and SAH concentrations by liquid chromatography tandem mass spectrometry were 1.4-fold (p = 0.015) and 5.3-fold (p = 0.003) higher in CBSD patients than in CTRL. A positive correlation between SAM/SAH and PC/PE ratios (r = 0.520; p = 0.019) was found.ConclusionsA novel biochemical abnormality in CBSD patients consisting in depletion of PC and LPC species containing DHA and accumulation of PUFA in PE and LPE species is revealed by this lipidomic approach. Changes in plasma SAM and SAH concentrations are associated with such phospholipid dysregulation. Given the key role of DHA in thrombosis prevention, depletion of PC species containing DHA in CBSD patients provides a new direction to understand the poor cardiovascular outcome of patients with homocystinuria.     

Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure

BackgroundPolymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy.MethodsPatients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy.ResultsFourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P < 0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P < 0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P < 0.01 and P < 0.05), these levels did not change after treatment.ConclusionsPMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.     

Nutrition in adult patients with selected lysosomal storage diseases

Lysosomal storage disorders (LSDs) are a group of clinically heterogeneous disorders affecting the function of lysosomes and are characterized by an accumulation of undigested substrates within several cell types. In recent years there have been substantial advances in supportive care and drug treatment for some LSDs, leading to improved patient survival, as seen in Gaucher, Pompe and Fabry disease and some Mucopolysaccharidoses; however, many symptoms still persist. Thus it is now even more important to improve patients' quality of life and reduce symptoms and comorbidities. One potential way of achieving this goal is through adjunct nutritional therapy, which is challenging as patients may be overweight with associated consequences, or malnourished, or underweight. Furthermore, drugs used to treat LSDs can modify the metabolic status and needs of patients. There are currently not enough data to make specific dietary recommendations for individual LSDs; however, suggestions can be made for managing clinical manifestations of the diseases, as well as treatment-associated adverse events. The metabolic and nutritional status of adult patients must be regularly assessed and individualized dietary plans may be created to cater to a patient's specific needs. Damage to the autophagic process is a common feature in LSDs that is potentially sensitive to dietary manipulation and needs to be assessed in clinical studies.     

Incidence and natural history of gastric high-grade dysplasia in patients with familial adenomatous polyposis syndrome

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Exposure to Chinese famine in early life modifies the association between hyperglycaemia and cardiovascular disease

Background and aimsThe Great Leap Forward Famine during 1959–1961 was the world's largest famine, and its adverse long-term effects might be more apparent in the coming decade with ageing of the exposed populations. The aim of this study was to examine whether the Chinese Famine modified the effect of hyperglycaemia on cardiovascular disease (CVD).Methods and resultsWe used data of 4337 adults born between 1952 and 1964 collected from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) between hyperglycaemia and CVD. The prevalence of CVD showed significant difference among different famine exposure cohorts (P = 0.0156). After multivariable adjustment, the ORs (95% CIs) were as follows: 1.46 (0.94, 2.26) for late childhood, 1.76 (1.06, 2.90) for mid childhood, 1.40 (0.86, 2.27) for early childhood, 2.55 (1.30, 5.02) for the foetal cohort and 1.10 (0.63, 1.95) for the non-exposed cohort. There was a significant interaction between hyperglycaemia and famine exposure for CVD (P = 0.0374). In addition, the subgroup analyses showed that the effect of hyperglycaemia on CVD in the foetal exposure cohort was significantly higher than those in any of the other famine-exposed cohorts, especially in those who lived in rural areas (OR: 4.67, 95% CI: 1.70–12.84), those who lived in severe famine areas (OR: 5.01, 95% CI: 1.22–20.66) and those who were men (OR: 3.66, 95% CI: 1.01–13.33).ConclusionExposure to the Chinese Famine, especially during the foetal stage of life, aggravated the association between hyperglycaemia and CVD.