Introduction South Asians with diabetes have more severe diabetic retinopathy (DR) and cardiovascular complications than white Caucasians. However, how big this gap is and the relation with the... Show moreIntroduction South Asians with diabetes have more severe diabetic retinopathy (DR) and cardiovascular complications than white Caucasians. However, how big this gap is and the relation with the severity of DR has not been studied. Here, we quantify the difference in time from diabetes diagnosis until a first non-fatal Major Adverse Cardiovascular Event (TUF MACE) in different DR groups in South Asians and Europeans. Methods 3831 adults with type 2 diabetes, 1358 South Asians and 2473 Europeans, treated in our diabetes clinic between 2006 and 2017 were included. Data on risk factors, diabetes duration, age of diagnosis and diabetes complications were collected from the diabetes-specific database and analysed using descriptive statistics and Cox regression. DR was graded in 3 categories, and non-fatal MACE was pre-specified. Results Prevalence of non-fatal MACE was the same when DR was absent, increased with increasing severity of DR in both ethnic groups, but was more frequent in South Asians with DR (mild: 50 vs. 42% and severe 62 vs. 46%. Classic risk factors only differed in relation to smoking habits, which were significantly lower in South Asians. After correction for classic risk factors and age at diabetes diagnosis TUF MACE was significantly shorter in South Asians, an effect also seen in the no-DR group (4.1 yrs. HR 1.5, 95% CI 1.3-1.8 and 7.4 yrs. earlier, HR 2.0, 95% CI 1.6-2.6 for no-DR and severe DR, respectively). Conclusions When adjusted for age at diabetes diagnosis, we show that time until first non-fatal MACE in South Asians is significantly shorter compared to Europeans and increases from no- to severe DR. Show less
BACKGROUND: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently... Show moreBACKGROUND: South Asians are more prone to develop atherosclerotic cardiovascular disease (ASCVD) compared with white Caucasians, which is not fully explained by classical risk factors. We recently reported that the presence of aggregation-prone low-density lipoprotein (LDL) in the circulation is associated with increased ASCVD mortality.OBJECTIVE: We hypothesized that LDL of South Asians is more prone to aggregate, which may be explained by differences in their LDL lipid composition.METHODS: In this cross-sectional hypothesis-generating study, LDL was isolated from plasma of healthy South Asians (n = 12) and age- and BMI-matched white Caucasians (n = 12), and its aggregation susceptibility and lipid composition were analyzed.RESULTS: LDL from South Asians was markedly more prone to aggregate compared with white Caucasians. Among all measured lipids, sphingomyelin 24:0 and triacylglycerol 56:8 showed the highest positive correlation with LDL aggregation. In addition, LDL from South Asians was enriched in arachidonic acid containing phosphatidylcholine 38:4 and had less phosphatidylcholines and cholesteryl esters containing monounsaturated fatty acids. Interestingly, body fat percentage, which was higher in South Asians (+26%), positively correlated with LDL aggregation and highly positively correlated with triacylglycerol 56:8, sphingomyelin 24:0, and total sphingomyelin.CONCLUSIONS: LDL aggregation susceptibility is higher in healthy young South Asians compared with white Caucasians. This may be partly explained by the higher body fat percentage of South Asians, leading to sphingomyelin enrichment of LDL. We anticipate that the presence of sphingomyelin-rich, aggregation -prone LDL particles in young South Asians may increase LDL accumulation in the arterial wall and thereby contribute to their increased risk of developing ASCVD later in life. (C) 2019 National Lipid Association. Published by Elsevier Inc. Show less
Conclusion: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of... Show moreConclusion: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. Show less
In 1551, the Swiss naturalist Konrad Gessner first described brown adipose tissue (BAT) as being __neither fat, nor flesh (nec pinguitudo, nec caro), but something in between__. Now, some 460 years... Show moreIn 1551, the Swiss naturalist Konrad Gessner first described brown adipose tissue (BAT) as being __neither fat, nor flesh (nec pinguitudo, nec caro), but something in between__. Now, some 460 years later, we know that Gessner had guessed the origin of brown adipocytes correctly. A unique property of the brown adipocyte is its capacity to dissipate energy stored in triglycerides (TG) as heat, which is mediated via the uncoupling protein UCP1. The recent discovery that active BAT is present in human adults meant the beginning of an exciting new area in metabolic research. BAT is currently regarded as a potential target to combat obesity and related diseases by inducing a sustained increase in energy expenditure. Interestingly, South Asians have lower energy expenditure, which may thus theoretically be caused by a reduction in BAT activity. The studies of which the results are described in this thesis were aimed at 1) gaining more insight into the physiology of BAT, 2) identifying novel tools and targets that may activate BAT, and 3) investigating the involvement of BAT in metabolism in humans with a focus on potential differences between South Asians and white Caucasians. Show less
This thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients.... Show moreThis thesis describes the pathophysiology of insulin resistance in the South Asian population and comprises studies on pharmacological and weight loss interventions in insulin resistant patients. Because of the increasing number of patients with obesity and T2DM, more research is needed to identify patients at risk of developing T2DM and to elucidate specific therapeutic targets to improve insulin resistance. For now, the prevention of overweight and obesity is the most essential step in the fight against the worldwide obesity and T2DM epidemic Show less
South Asians have a high incidence of diabetes and subsequent cardiovascular and renal complications. Increasing evidence points towards the involvement of the complement system. We found higher... Show moreSouth Asians have a high incidence of diabetes and subsequent cardiovascular and renal complications. Increasing evidence points towards the involvement of the complement system. We found higher levels of both complement C3( the central molecule in the complement cascade) and SC5b-9 (the effector phase of complement activation) in type 2 diabetic South Asians compared to Caucasians. However, neither C3 nor Sc5b-9 predicted cardiovascular events, though higher SC5b-9 levels were associated with renal damage. Mannose binding lectin (MBL, the recognition molecule of the lectin pathway) was studies. A low MBL genotype was associated with cardiovascular events, whiel a high serem MBL level was associated with progressive renal failure. Show less
