Prevalence, patterns and associated risk factors for dyslipidaemia among individuals attending the diabetes clinic at a tertiary hospital in Central Malawi.

BACKGROUND: Dyslipidaemia among individuals with diabetes is a significant modifiable risk factor for atherosclerotic cardiovascular diseases (ASCVDs). ASCVDs are a major cause of mortality and morbidity globally, especially in people with diabetes. In Malawi, limited data exist on the prevalence and biochemical characteristics of diabetic dyslipidaemia. This study investigated the prevalence and biochemical characteristics of dyslipidaemia in individuals attending the diabetes clinic at Kamuzu Central Hospital, the largest tertiary referral hospital in Central Malawi. METHODS: Using a cross-sectional design, sociodemographic, medical and anthropometric data were collected from 391 adult participants who were enrolled in the study. Blood samples were analysed for glycosylated haemoglobin (HBA1c) and fasting lipid profiles. The prevalence of dyslipidaemia was calculated, and the biochemical characteristics of the dyslipidaemia were defined. The associations between dyslipidaemia and risk factors such as sociodemographic characteristics, obesity, and HBA1c levels were evaluated using logistic regression analysis. RESULTS: Prevalence of dyslipidaemia was observed in 71% of the participants, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality among the study participants. None of the participants were receiving any lipid-lowering therapy. On bivariate analysis, dyslipidemia was positively associated with female sex [OR 1.65 (95% CI 1.05- 2.58); p = 0.09], age ≥ 30 years [OR 3.60 (95% CI 1.17-7.68); p = 0.001] and overweight and obesity [OR 2.11 (95% CI 1.33-3.34); p = 0.002]. On multivariate analysis, being overweight or obese was an independent predictor of dyslipidaemia [AOR 1.8;(95% CI 1.15- 3.37); p = 0.04]. CONCLUSION: Dyslipidaemia was highly prevalent among individuals with diabetes in this study, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality. Overweight and obesity were also highly prevalent and positively predicted dyslipidaemia. This study highlights the importance of appropriately addressing dyslipidaemia, overweight and obesity among individuals with diabetes in Malawi and other similar settings in Africa as one of the significant ways of reducing the risk of ASCVDs among this population.

Prevalence, patterns and associated risk factors for dyslipidaemia among individuals attending the diabetes clinic at a tertiary hospital in Central Malawi.

Background: Dyslipidaemia among individuals with diabetes is a significant modifiable risk factor for atherosclerotic cardiovascular diseases (ASCVDs). ASCVDs are a major cause of mortality and morbidity globally, especially in people with diabetes. In Malawi, limited data exist on the prevalence and biochemical characteristics of diabetic dyslipidaemia. This study investigated the prevalence and biochemical characteristics of dyslipidaemia in individuals attending the diabetes clinic at Kamuzu Central Hospital, the largest tertiary referral hospital in Central Malawi. Methods: Using a cross-sectional design, sociodemographic, medical and anthropometric data were collected from 391 adult participants who were enrolled in the study. Blood samples were analysed for glycosylated haemoglobin (HBA1c) and fasting lipid profiles. The prevalence of dyslipidaemia was calculated, and the biochemical characteristics of the dyslipidaemia were defined. The associations between dyslipidaemia and risk factors such as sociodemographic characteristics, obesity, and HBA1c levels were evaluated using logistic regression analysis. Results: Prevalence of dyslipidaemia was observed in 71% of the participants, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality among the study participants. On bivariate analysis, dyslipidemia was positively associated with female sex [OR 1.65 (95% CI 1.05-2.58); p = 0.09], age ≥ 30 years [OR 3.60 (95% CI 1.17-7.68); p = 0.001] and overweight and obesity [OR 2.11 (95% CI 1.33-3.34); p = 0.002]. On multivariate analysis, being overweight or obese was an independent predictor of dyslipidaemia [AOR 1.8 ;( 95% CI 1.15-3.37); p = 0.04]. Conclusion: Dyslipidaemia was highly prevalent among individuals with diabetes in this study, and elevated low-density lipoprotein cholesterol was the most frequent lipid abnormality. Overweight and obesity were also highly prevalent and positively predicted dyslipidaemia. This study highlights the importance of appropriately addressing dyslipidaemia, overweight and obesity among individuals with diabetes in Malawi and other similar settings in Africa as one of the significant ways of reducing the risk of ASCVDs among this population.

Estimation of Pediatric Dosage of Antimalarial Drugs, Using Pharmacokinetic and Physiological Approach.

Most of the individuals who die of malaria in sub-Saharan Africa are children. It is, therefore, important for this age group to have access to the right treatment and correct dose. Artemether-lumefantrine is one of the fixed dose combination therapies that was approved by the World Health Organization to treat malaria. However, the current recommended dose has been reported to cause underexposure or overexposure in some children. The aim of this article was, therefore, to estimate the doses that can mimic adult exposure. The availability of more and reliable pharmacokinetic data is essential to accurately estimate appropriate dosage regimens. The doses in this study were estimated using the physiological information from children and some pharmacokinetic data from adults due to the lack of pediatric pharmacokinetic data in the literature. Depending on the approach that was used to calculate the dose, the results showed that some children were underexposed, and others were overexposed. This can lead to treatment failure, toxicity, and even death. Therefore, when designing a dosage regimen, it is important to know and include the distinctions in physiology at various phases of development that influence the pharmacokinetics of various drugs in order to estimate the dose in young children. The physiology at each time point during the growth of a child may influence how the drug is absorbed, gets distributed, metabolized, and eliminated. From the results, there is a very clear need to conduct a clinical study to further verify if the suggested (i.e., 0.34 mg/kg for artemether and 6 mg/kg for lumefantrine) doses could be clinically efficacious.

High prevalence of dyslipidaemia among persons with diabetes mellitus and hypertension at a tertiary hospital in Blantyre, Malawi.

BACKGROUND: Dyslipidaemia drives the process of atherosclerosis, and hence a significant modifiable risk factor complicating hypertension and diabetes. In Malawi, the prevalence, screening and management of dyslipidaemia among persons with diabetes mellitus have not been reported. This study aimed to investigate the prevalence, biochemical characteristics, screening and management practices for dyslipidaemia among persons with diabetes mellitus, hypertension, and diabetes mellitus and hypertension comorbidity at Queen Elizabeth Central hospital in Blantyre, Malawi. METHODS: This was a cross-sectional study conducted in 2021. A total of 256 adult participants (diabetes mellitus = 100); hypertension = 100; both conditions = 56) were included. Medical data and anthropometric measurements were recorded. Blood samples were analysed for HbA1C and serum lipids. Associated risk factors for dyslipidaemia were also assessed. RESULTS: Dyslipidaemia was prevalent in 58%, 55%, and 70% of participants with diabetes mellitus, hypertension, and both conditions. Low-density lipoprotein cholesterol (LDL-C) dyslipidaemia was the most common in all participant groups. Participants with both diabetes and hypertension had 2.4 times (95% CI 1.2-4.6) increased risk of LDL-C dyslipidaemia than those with diabetes alone (p < 0.02). Being overweight or obese and age over 30 years were risk factors for dyslipidaemia in participants with diabetes mellitus alone (OR 1.3 (95% CI 1.1-1.6), p < 0.04, and OR 2.2 (95% CI 1.2-4.7) (p < 0.01), respectively. Overweight and obesity predicted LDL-C dyslipidaemia in hypertensive patients (OR 3.5 (95% CI 1.2-9.9) p < 0.001). Poorly controlled hypertension and the use of beta-blockers and thiazide diuretics predicted dyslipidaemia among patients with both diabetes mellitus and hypertension (OR 6.50 CI 1.45-29.19; and OR 5.20 CI 1.16-23.36 respectively). None of the participants had a lipogram performed before the study or were on lipid-lowering therapy. CONCLUSIONS: Dyslipidaemia with LDL-C derangement was highly prevalent, especially in individuals with both diabetes mellitus and hypertension, and there was absent use of lipid-lowering therapy. Screening and managing dyslipidaemia should be reinforced to reduce the risk of cardiovascular complications in this population at increased risk.

Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal.

The prolonged, postweaning fast of northern elephant seal (Mirounga angustirostris) pups is characterized by a reliance on lipid metabolism and reversible, fasting-induced insulin resistance, providing a unique model to examine the effects of insulin on lipid metabolism. We have previously shown that acute insulin infusion induced a shift in fatty acid metabolism dependent on fasting duration. This study complements the previous study by examining the effects of fasting duration and insulin infusion on circulating levels of oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids. Northern elephant seal pups were studied at two postweaning periods (n = 5/period): early fasting (1-2 wk postweaning; 127 ± 1 kg) and late fasting (6-7 wk postweaning; 93 ± 4 kg). Different cohorts of pups were weighed, sedated, and infused with 65 mU/kg of insulin. Plasma was collected prior to infusion (T0) and at 10, 30, 60, and 120 min postinfusion. A profile of ∼80 oxylipins was analyzed by UPLC-ESI-MS/MS. Nine oxylipins changed between early and late fasting and eight were altered in response to insulin infusion. Fasting decreased prostaglandin F2α (PGF2α) and increased 14,15-dihydroxyicosatrienoic acid (14,15-DiHETrE), 20-hydroxyeicosatetraenoic acid (20-HETE), and 4-hydroxy-docosahexaenoic acid (4-HDoHE) (P < 0.03) in T0 samples, whereas insulin infusion resulted in an inverse change in area-under-the-curve (AUC) levels in these same metabolites (P < 0.05). In addition, 12-12-hydroperoxyeicosatetraenoic acid (HpETE) and 12-HETE decreased with fasting and insulin infusion, respectively (P < 0.04). The oxylipins altered during fasting and in response to insulin infusion may contribute to the manifestation of insulin resistance and participate in the metabolic regulation of associated cellular processes.

Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes.

Zn2+ is an essential regulator of coagulation and is released from activated platelets. In plasma, the free Zn2+ concentration is fine-tuned through buffering by human serum albumin (HSA). Importantly, the ability of HSA to bind/buffer Zn2+ is compromised by co-transported non-esterified fatty acids (NEFAs). Given the role of Zn2+ in blood clot formation, we hypothesise that Zn2+ displacement from HSA by NEFAs in certain conditions (such as type 2 diabetes mellitus, T2DM) impacts on the cellular and protein arms of coagulation. To test this hypothesis, we assessed the extent to which increasing concentrations of a range of medium- and long-chain NEFAs reduced Zn2+-binding ability of HSA. Amongst the NEFAs tested, palmitate (16 : 0) and stearate (18 : 0) were the most effective at suppressing zinc-binding, whilst the mono-unsaturated palmitoleate (16 : 1c9) was markedly less effective. Assessment of platelet aggregation and fibrin clotting parameters in purified systems and in pooled plasma suggested that the HSA-mediated impact of the model NEFA myristate on zinc speciation intensified the effects of Zn2+ alone. The effects of elevated Zn2+ alone on fibrin clot density and fibre thickness in a purified protein system were mirrored in samples from T2DM patients, who have derranged NEFA metabolism. Crucially, T2DM individuals had increased total plasma NEFAs compared to controls, with the concentrations of key saturated (myristate, palmitate, stearate) and mono-unsaturated (oleate, cis-vaccenate) NEFAs positively correlating with clot density. Collectively, these data strongly support the concept that elevated NEFA levels contribute to altered coagulation in T2DM through dysregulation of plasma zinc speciation.

The Capacity of the Fecal Microbiota From Malawian Infants to Ferment Resistant Starch.

In Low and Middle-Income Countries (LMIC), weaning is associated with environmentally acquired and inflammation-associated enteric disorders. Dietary intake of high amylose maize starch (HAMS) can promote commensal fermentative bacteria and drive the production of short chain fatty acids (SCFAs). By stabilizing commensal gut microbiology, and stimulating the production of anti-inflammatory metabolites, HAMS supplementation might therefore influence enteric health. However, the extent to which the gut microbiota of LMIC infants are capable of fermenting HAMS is unclear. We assessed the capacity of the fecal microbiota from pre-weaning and weaning Malawian infants to ferment HAMS and produce SCFAs using an in vitro fermentation model. Fecal microbiota from both pre-weaning and weaning infants were able to ferment HAMS, as indicated by an increase in bacterial load and total SCFA concentration, and a reduction in pH. All of these changes were more substantial in the weaning group. Acetate production was observed with both pre-weaning and weaning groups, while propionate production was only observed in the weaning group. HAMS fermentation resulted in significant alterations to the fecal microbial community in the weaning group, with significant increases in levels of Prevotella, Veillonella, and Collinsella associated with propionate production. In conclusion, fecal microbiota from Malawian infants before and during weaning has the capacity to produce acetate through HAMS fermentation, with propionate biosynthetic capability appearing only at weaning. Our results suggest that HAMS supplementation might provide benefit to infants during weaning.

Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding.

Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin. Albumin binds most metal ions and harbours four primary metal binding sites: site A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous efforts to clarify the identity of IMA and the causes for its reduced cobalt-binding capacity were focused on the NTS site, but the degree of N-terminal modification could not be correlated to the presence of ischemia. More recent work suggested that Co2+ ions as used in the ACB assay bind preferentially to site B, then to site A, and finally to the NTS. This insight paved the way for a new consistent molecular basis of the ACB assay: albumin is also the main plasma carrier for free fatty acids (FFAs), and binding of a fatty acid to the high-affinity site FA2 results in conformational changes in albumin which prevent metal binding at site A and partially at site B. Thus, this review advances the hypothesis that high IMA levels in myocardial ischemia and many other conditions originate from high plasma FFA levels hampering the binding of Co2+ to sites A and/or B. This is supported by biophysical studies and the co-association of a range of pathological conditions with positive ACB assays and high plasma FFA levels.