Associations between spirometric impairments and microvascular complications in type 2 diabetes: a cross-sectional study.

OBJECTIVE: Evidence shows that the conventional cardiometabolic risk factors do not fully explain the burden of microvascular complications in type 2 diabetes (T2D). One potential factor is the impact of pulmonary dysfunction on systemic microvascular injury. We assessed the associations between spirometric impairments and systemic microvascular complications in T2D. DESIGN: Cross-sectional study. SETTING: National Diabetes Management and Research Centre in Ghana. PARTICIPANTS: The study included 464 Ghanaians aged ≥35 years with established diagnosis of T2D without primary myocardial disease or previous/current heart failure. Participants were excluded if they had primary lung disease including asthma or chronic obstructive pulmonary disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The associations of spirometric measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio) with microvascular complications (nephropathy (albumin-creatinine ratio ≥3 mg/g), neuropathy (vibration perception threshold ≥25 V and/or Diabetic Neuropathy Symptom score >1) and retinopathy (based on retinal photography)) were assessed using multivariable logistic regression models with adjustments for age, sex, diabetes duration, glycated haemoglobin concentration, suboptimal blood pressure control, smoking pack years and body mass index. RESULTS: In age and sex-adjusted models, lower Z-score FEV1 was associated with higher odds of nephropathy (OR 1.55, 95% CI 1.19-2.02, p=0.001) and neuropathy (1.27 (1.01-1.65), 0.038) but not retinopathy (1.22 (0.87-1.70), 0.246). Similar observations were made for the associations of lower Z-score FVC with nephropathy (1.54 (1.19-2.01), 0.001), neuropathy (1.25 (1.01-1.54), 0.037) and retinopathy (1.19 (0.85-1.68), 0.318). In the fully adjusted model, the associations remained significant for only lower Z-score FEV1 with nephropathy (1.43 (1.09-1.87), 0.011) and neuropathy (1.34 (1.04-1.73), 0.024) and for lower Z-score FVC with nephropathy (1.45 (1.11-1.91), 0.007) and neuropathy (1.32 (1.03-1.69), 0.029). Lower Z-score FEV1/FVC ratio was not significantly associated with microvascular complications in age and sex and fully adjusted models. CONCLUSION: Our study shows positive but varying strengths of associations between pulmonary dysfunction and microvascular complications in different circulations. Future studies could explore the mechanisms linking pulmonary dysfunction to microvascular complications in T2D.

Macrovascular and renal microvascular complications in West Africans with intermediate hyperglycemia living in West Africa and Europe: The RODAM study.

Background: Metabolic conditions, including intermediate hyperglycemia (IH), affect migrants to a greater extent than the populations of origin. Evidence suggests that IH increases the risk of vascular complications, but it is unclear whether the differences in IH between the non-migrant and migrant populations translate to differences in vascular complications between the two populations. We compared the prevalence of macrovascular and renal microvascular complications among West Africans with IH living in West Africa and their migrant compatriots in Europe. Methods: Data from the multicenter Research on Obesity and Diabetes among African Migrants(RODAM) study were analyzed. Ghanaians with IH(524 non-migrant and 1439 migrants) were included. Logistic regression analyses were used to determine the associations between migrant status and macrovascular [coronary artery disease(CAD) and peripheral artery disease(PAD)] and renal microvascular[nephropathy] complications with adjustment for age, sex, socioeconomic status, smoking, systolic blood pressure, BMI, total cholesterol, HbA1c, C-reactive protein, and serum uric acid. Findings: The prevalence of microvascular/macrovascular complications was higher in non-migrants than in migrants(nephropathy 15.3vs.9.7%; PAD 3.1%vs.1.3%; and CAD 15.8% vs. 5.0%). The differences persisted in the fully adjusted model: nephropathy [odds ratio, 2.12; 95% CI(1.46-3.08); PAD, 4.44(1.87-10.51); CAD 2.35(1.64-3.37)]. Non-migrant females had higher odds of nephropathy[2.14(1.34-3.43)], PAD[7.47(2.38-23.40)] and CAD [2.10(1.34-3.27)] compared to migrant females. Non-migrant males had higher odds of nephropathy[2.54(1.30-4.97)] and CAD[2.85(1.48-5.50)], but not PAD[1.81(0.32-10.29)],than their migrant peers. Interpretation: Macrovascular and renal microvascular complications were more prevalent in non-migrants than in migrant West Africans with IH. Further studies are needed to identify factors that increase the risk to aid preventive/treatment strategies.

Associations between spirometric measures and exercise capacity in type 2 diabetes.

BACKGROUND: Physical exercise aids glycemic control and the prevention of diabetes-related complications. However, exercise beyond an individual's pulmonary functional capacity may be detrimental. To date, little is known about the relationship between pulmonary function and exercise capacity in people with type 2 diabetes (T2D). We investigated the relationship between pulmonary function and exercise capacity in T2D. METHODS: Spirometry and 6-min walk test (6MWT) were conducted for 263 systematically sampled adults with T2D without primary heart/lung disease. The primary measure of exercise capacity was the 6-min walk distance (6MWD); impaired exercise capacity was defined as 6MWD<400 m. Logistic regression analyses were used to assess the associations between spirometric measures and exercise capacity with adjustments for age, sex, height, body mass index, diabetes duration, glycated hemoglobin concentration, smoking, suboptimum blood pressure control, and total cholesterol concentration. RESULTS: Compared with individuals with normal spirometry, those with pulmonary restriction/obstruction had significantly lower 6MWD (404.67 m vs. 451.70),p < 0.001). The proportion of individuals with impaired exercise capacity was higher in individuals with impaired pulmonary function compared with those with normal pulmonary function (39.8% vs. 20.7%,p = 0.001). In the unadjusted models, decreasing Z-score FEV1 [odds ratio 1.40, 95% confidence interval (1.07-1.83),p = 0.013] and Z-score FVC [1.37 (1.06-1.76),0.016], but not Z-score FEV1/FVC ratio [1.00 (0.78-1.27),0.972] were significantly associated with impaired exercise capacity. In the fully adjusted model, the strength of association remained statistically significant for Z-score FEV1 [1.60 (1.06-2.41),0.025] but not Z-score FVC [1.48 (0.98-2.23),0.065]. CONCLUSIONS: Our study shows inverse associations between FEV1 and impaired exercise capacity in T2D, Future research could characterize optimal exercise levels based on a patient's FEV1.

Ethnic disparities in the association between low-grade inflammation biomarkers and chronic kidney disease: The HELIUS Cohort Study.

AIMS: Ethnic differences exist in the prevalence and progression of chronic kidney disease (CKD). However, underlying mechanisms remain unclear. It has been proposed that chronic low-grade inflammation plays an important role in CKD pathogenesis. In the current analysis, we study the association between systemic inflammatory biomarkers and CKD prevalence in different ethnic groups. METHODS: We examined cross-sectional associations between biomarkers of low-grade inflammation, including serum high-sensitive (hs)-CRP, fibrinogen, and D-dimer, and CKD prevalence in different ethnic groups residing in Amsterdam, the Netherlands. We included 5740 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan populations) aged 18 to 70 years of the Healthy Life in an Urban Setting study (HELIUS) cohort. RESULTS: In the fully adjusted models, adjusted for ethnicity-specific cut-off values, elevated fibrinogen [odds ratio 2.50 (95 % confidence interval 1.10-5.78)] and D-dimer [2.99 (1.28-7.00)] were significantly associated with CKD in Dutch. In South-Asian Surinamese, a significant association with elevated D-dimer [2.66 (1.32-5.37)] was found. CONCLUSIONS: Our study shows that there are both differences in biomarker levels and the association with CKD across ethnic groups. Future research to identify potential drivers of the differential associations and susceptibility of CKD among ethnic groups to reduce the CKD burden is necessary.

A Cross-Sectional Study of Ocular Changes in Children and Adolescents with Diabetes Mellitus in Selected Health Facilities in Ghana.

BACKGROUND: The main objective of the study was to determine the prevalence of diabetic retinopathy (DR), other diabetes-related ocular changes (e.g., cataracts, corneal ulceration), and non-diabetic ocular disease in Ghanaian children and adolescents. The second objective was to evaluate the relationship between these conditions and age at diagnosis, current age, diabetes mellitus (DM) duration, and participant's sex. METHODS: A cross-sectional study, undertaken by a multidisciplinary team, included a cohort of children and adolescents (4-19 years) with DM recruited from selected health facilities in Ghana, from March 2016 to September 2019, after written informed consent or assent. The cohort will be followed up for 3 years to determine the natural course of the ocular changes, reported later. Participants were examined for all microvascular and macrovascular complications, non-diabetic ocular disease, anthropometric measurements, laboratory characteristics and quality of life issues. Full ocular examination was also undertaken. Statistical Package for Social Sciences (SPSS Version 25.0) was used for the data analysis. Continuous and categorical variables were presented as mean and standard deviation (SD), median (interquartile range) and as percentages (%), respectively. T-test and Mann-Whitney U test were used in establishing associations. RESULTS: A total of 58 participants were recruited. DR was detected in only 1 out of 58 (1.7%) participants at baseline. Cataracts were the most common ocular finding, detected in 42 (72%) at baseline. Other anterior segment changes observed included blepharitis 46 (79.3%) and tear film instability 38 (65.5%). There was a significant positive association between duration of the DM and the risk of cataract (p = 0.027). Participants' age at diagnosis was significantly associated with the presence of prominent corneal nerves (p = 0.004). CONCLUSIONS: DR was uncommon in this cohort of young persons with DM in Ghana. Cataracts, blepharitis and refractive errors were ocular changes commonly observed. All young persons with diabetes should undergo regular eye examination in all clinics where follow-up care is provided.

Associations of Serum Uric Acid Levels With Macrovascular and Renal Microvascular Dysfunction Among Individuals From Sub-Saharan Africa.

Importance: Serum uric acid (SUA) level is associated with vascular dysfunction in Eurasian populations, but little is known about this association in individuals from sub-Saharan Africa, who have a high prevalence of both relatively high SUA levels and vascular dysfunction. Objectives: To assess the associations of SUA levels with macrovascular and kidney microvascular dysfunction in individuals of sub-Saharan African ancestry and evaluate potential factors that could mediate these associations. Design, Setting, and Participants: Cross-sectional analyses of baseline data from the multicenter Research on Obesity and Diabetes Among African Migrants study, conducted from 2012 to 2015, were performed from January to March 2021. The population included Ghanaian individuals living in Ghana and Europe. Exposure: Abnormal SUA levels. Main Outcomes and Measures: Logistic regression was used to examine the associations of SUA level quartiles with microvascular (albuminuria) and macrovascular (peripheral artery disease and coronary artery disease) dysfunction, with adjustments for age, sex, estimated glomerular filtration rate, site of residence, socioeconomic status, alcohol, smoking, diabetes, hypertension, waist-hip ratio, and total cholesterol level. Mediation analysis was performed to assess whether the association was via elevated blood pressure, hemoglobin A1c, and high-sensitivity C-reactive protein levels or via weight-hip ratio. The research questions were formulated after data collection. Results: A total of 4919 Ghanaian individuals (3047 [61.9%] women) aged 25-75 years (mean [SD], 46.26 [11.08] years) were included. There was a significant positive association between SUA quartiles and albuminuria, but not coronary artery disease or peripheral artery disease, after adjustment for covariates. After full adjustment, individuals in the fourth SUA quartile had higher odds of albuminuria (adjusted odds ratio [aOR], 1.54; 95% CI, 1.07-2.21), but not peripheral artery disease (aOR, 1.35; 95% CI, 0.87-2.08) or coronary artery disease (aOR, 1.09; 95% CI, 0.77-1.55), compared with individuals in the first quartile. After full adjustment, systolic and diastolic blood pressure significantly mediated the association between SUA concentrations and albuminuria, accounting for 19.4% of the total association for systolic and 17.2% for diastolic blood pressure; hemoglobin A1c, high-sensitivity C-reactive protein, and waist-hip ratio did not mediate this association. Conclusions and Relevance: In this cross-sectional study among a sub-Saharan African population, elevated SUA levels were significantly associated with kidney microvascular dysfunction and mediated partly through elevated blood pressure. These findings suggest that individuals from sub-Saharan Africa with elevated SUA levels may benefit from periodic screening for kidney microvascular dysfunction to aid early detection or treatment.

Inflammation and its associations with aortic stiffness, coronary artery disease and peripheral artery disease in different ethnic groups: The HELIUS Study.

BACKGROUND: evidence shows important ethnic differences in vascular dysfunction rates; however, the mechanisms driving these differences remain unclear. One potential factor is the ethnic differences in the role of inflammation in vascular injury. We tested the hypothesis that low-grade inflammation is unequally associated with vascular dysfunction in different ethnic groups. METHODS: we included 5698 participants (similar-sized Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccans) of the HELIUS study (the Netherlands) conducted between 2011 and 2015. Logistic regression was used to examine the associations of Z-score inflammatory biomarker concentration (high sensitivity C-reactive protein [hs-CRP], fibrinogen, and d-dimer) with vascular dysfunction (aortic stiffness, coronary artery disease [CAD], and peripheral artery disease [PAD]), with adjustments for age, sex, smoking (pack-years), BMI, hypertension, HbA1c, total cholesterol, and statin use. FINDINGS: in the fully adjusted models, higher Z-score hs-CRP was positively associated with CAD in Dutch [OR 1·63, (95% CI 1·21-2·18)] and PAD in South Asians [1·25(1·03-1·53)], respectively. Higher Z-score fibrinogen was positively associated with CAD in African Surinamese [1·28(1·03-1·59)] while higher Z-score d-dimer was positively associated with PAD in Moroccans [1·39(1·01-1·93)]. Higher Z-score hs-CRP [0·71(0·54-0·94)] and fibrinogen [0·75(0·58-0·97)] concentrations were negatively associated with PAD in African Surinamese. INTERPRETATION: our study shows that inflammatory biomarkers are unequally associated with vascular dysfunction in different ethnic groups. These observations provide opportunities for future studies aimed at assessing the predictive roles of inflammation on vascular disease in different ethnic groups.

Associations between macrovascular and renal microvascular dysfunction in type 2 diabetes and non-diabetes: the HELIUS study.

BACKGROUND: Although the associations between measures of macrovascular and microvascular dysfunctions are well characterized in diabetes, there is limited data on these associations in individuals without diabetes. We compared the associations between macrovascular dysfunction and renal microvascular dysfunction in individuals with type 2 diabetes (T2D) and without diabetes. METHODS: Cross-sectional analyses of baseline data from the multiethnic Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands), including 986 participants with T2D and 7680 participants without diabetes were done. Logistic regression analyses were used to examine the associations between macrovascular dysfunction [aortic stiffness, coronary artery disease (CAD), peripheral artery disease (PAD), and stroke] and renal microvascular dysfunction [albuminuria] with adjustments for age, sex, ethnicity, waist-to-hip ratio, systolic blood pressure, LDL-cholesterol, and smoking (and HbA1c and diabetes duration for the T2D group). RESULTS: In the fully adjusted models, aortic stiffness was associated with albuminuria in individuals with T2D [OR 2.55; 95% CI,1.30-4.98], but not without diabetes [0.96; 0.63-1.45]; stroke was associated with albuminuria in T2D [2.40;1.10-5.25], but not in non-diabetes [1.39;0.83-2.33]. In age-sex adjusted models, CAD was associated with albuminuria in T2D [1.65;1.09-2.50] and in non-diabetes [1.56;1.13-2.15]; the associations were no longer significant in the fully adjusted model. There were no associations between PAD and albuminuria in T2D and non-diabetes. CONCLUSIONS: Our study shows important differences in the associations between measures of macrovascular and renal microvascular dysfunction in T2D and non-diabetes. These findings provide opportunities for future research aimed at prevention and treatment strategies for individuals with vascular dysfunction.

Microvascular and macrovascular complications in type 2 diabetes in a multi-ethnic population based in Amsterdam. The HELIUS study.

OBJECTIVE: To assess ethnic differences in diabetes-related microvascular and macrovascular complication rates in a multi-ethnic population in the Netherlands. STUDY, DESIGN AND SETTING: Data from the HELIUS study comprising of 165 Dutch, 591 South-Asian Surinamese, 494 African Surinamese, 272 Ghanaian, 368 Turkish, and 444 Moroccan participants with diabetes were analyzed. Logistic regression was used to assess ethnic differences in microvascular (nephropathy) and macrovascular (coronary heart disease (CHD), peripheral artery disease (PAD) and stroke) complications, with adjustments for age, sex, education, and the conventional risk factors. RESULTS: In an age-sex adjusted model, ethnic minorities had higher odds of nephropathy than Dutch except for Ghanaians and African Surinamese. The difference remained statistically significant in South-Asian Surinamese (odds ratio: 2.29; 95% CI, 1.09-4.80), but not in the Turkish (1.01; 0.43-2.38) and Moroccan (1.56; 0.68-3.53) participants. The odds of CHD was higher in all ethnic minorities than in Dutch, with the odds ratios ranging from 2.73 (1.09-6.84) in Ghanaians to 6.65 (2.77-15.90) in Turkish in the fully-adjusted model. There were no ethnic differences in the odds of PAD and stroke. CONCLUSIONS: The findings suggest ethnic inequalities in macrovascular and microvascular complications in diabetes, with nephropathy and CHD being the most common complications affecting ethnic minorities.

Higher prevalence of peripheral arterial disease in Ghana compared to Ghanaian migrants in Europe: The RODAM study.

BACKGROUND: Evidence suggests that the burden of peripheral artery disease (PAD) is rising more rapidly than other forms of cardiovascular diseases in sub-Saharan Africa, but the extent to which they differ between rural and urban settings in Africa and upon migration to Europe is unknown. We assessed the burden of PAD among Ghanaians living in rural- and urban-Ghana and Ghanaian migrants living in three European countries. METHODS: Cross-sectional analyses of baseline data from the multicenter Research on Obesity and Diabetes among African Migrants (RODAM) study were done. Data from 5516 participants living in Europe (1487 Amsterdam, 546 Berlin, 1047 London) and Ghana [1419 urban and 1017 rural] aged 25-70years were included. PAD was defined as ankle brachial index≤0.90. Comparisons among sites were made using logistic regression analysis. RESULTS: The age-standardized prevalence of PAD was higher in Ghanaians living in rural [7.52%, 95% CI = 5.87-9.51] and urban [8.93%, 7.44-10.64] Ghana than for their compatriots living in Europe [5.70%, 4.35-7.35 for London; 3.94%, 2.96-5.14 for Amsterdam; and 0.44%, 0.05-1.58 for Berlin]. The differences persisted even after adjustment for age, sex, education and the conventional cardiovascular risk factors [adjusted odds ratio = 3.16, 95% CI = 2.16-4.61, p < .001 for rural-Ghana; and 2.93, 1.87-4.58, p < .00 for urban-Ghana, compared with Ghanaian migrants in Europe]. CONCLUSIONS: Our study shows that Ghanaians living in Ghana have higher prevalence of PAD than their migrant compatriots. Further work is needed to identify potential factors driving the high prevalence of PAD among non-migrant Ghanaians to assist interventions aimed at reducing PAD burden.