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CURATOR

I am an early career investigator from Nigeria. I trained as a Biochemist and specialize in Clinical Biochemistry and Molecular Biotechnology and study the influence of promising/ drug-able natural products on biological membranes in diseases such as diabetes and its complications.

I like active healthy living. I like gardening and swimming. I am also a Taichi and Reiki practitioner.

PINBOARD SUMMARY

I´m a postdoc fellow at the Laboratorio de Biofísica y Nanotecnología, IMMF-UNC-CONICET, Argentina

Antiretroviral drugs have greatly extended the life span of HIV-infected persons, but research suggests they are in high risk of developing diabetes (Nduka et al., 2017). A new tool to preserve vital cells for diabetes treatment can help people with both conditions.

In 10 seconds? Scientists can now save most pre-transplant ‘islet cells’ derived from donors that are vital to restore insulin production in Type 1 diabetes patients. This is important news for HIV positive people, who are on antiretroviral therapy (ART).

Why so? New research suggests HIV-infected patients on ART are at high risk of developing diabetes or prediabetes. Additionally, age, family history of diabetes, obesity and Hispanic or Black origins can increase the risk of the disease for them (Nansseu et al., 2018), just when breakthroughs in ART made it possible to live with the virus as long as healthy people.

Is there an explanation? The interplay between prediabetes/diabetes and antiretroviral drugs has been established, but more research is needed (Rucker et al., 2018). Scientists think the WHO recommendation of initiating ART soon after an HIV diagnosis regardless of the age of the patient, or the key indicator of their CD4 immune cell count could be an explanation (Maganga et al., 2015).

And how ‘islet cells’ come into play? Currently there is no cure for the various types of diabetes. However, in the case of Type 1, there is a way to save people from having to constantly check their insulin-levels and be exposed to complications with their eyes, kidneys and their nervous and cardio-vascular system. The method involves transplanting ‘islet cells’ from donors into patients, but there is a problem.

How the transplantation is done? It’s a keyhole surgery involving injecting the cells into the liver or between the muscles of patients, which usually results in quick improvement. Healthy islets cell then correctly regulate the blood sugar levels in patients’ pancreases.

So, what is the problem and the solution? The problem is that once the islet cells are harvested from the donor, they become extremely vulnerable and die easily in transport. The small number of donors makes it important to preserve these cells. Scientists have invented a miniscule ‘egg-box’ that protects these cell clusters from physical damage and supplies them with the required nutrients and oxygen.

So will this help all HIV-infected patients? Only the group with Type 1 diabetes. In the meantime researchers emphasise the importance of education campaigns. Diabetes patients need to check their HIV-status and HIV-infected people on ART need to make nutritional and other lifestyle changes to mitigate the possibility of developing diabetes (Ekrikpo et al., 2018).

15 ITEMS PINNED

Impact of Oxygen on Pancreatic Islet Survival.

Abstract: Pancreatic islet transplantation is a promising treatment option for individuals with type 1 diabetes; however, maintaining islet function after transplantation remains a large challenge. Multiple factors, including hypoxia associated events, trigger pretransplant and posttransplant loss of islet function. In fact, islets are easily damaged in hypoxic conditions before transplantation including the preparation steps of pancreas procurement, islet isolation, and culture. Furthermore, after transplantation, islets are also exposed to the hypoxic environment of the transplant site until they are vascularized and engrafted. Because islets are exposed to such drastic environmental changes, protective measures are important to maintain islet viability and function. Many studies have demonstrated that the prevention of hypoxia contributes to maintaining islet quality. In this review, we summarize the latest oxygen-related islet physiology, including computational simulation. Furthermore, we review recent advances in oxygen-associated treatment options used as part of the transplant process, including up-to-date oxygen generating biomaterials as well as a classical oxygen inhalation therapy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Pub.: 06 Apr '18, Pinned: 20 Apr '18

Improvement of islet function and survival by integration of perfluorodecalin into microcapsules in vivo and in vitro.

Abstract: Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained. Furthermore, the best islet function represented by glucose-stimulated insulin secretion was observed for the PFD-alginate capsules in hypoxic condition. For the in vivo study, the same number of naked islets and encapsulated islets (alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic mice. Non-fasting blood glucose levels and the area under the curve for glucose based on intraperitoneal glucose tolerance tests in the PFD-alginate group were lower than in the alginate group. The harvested islets stained positive for insulin in all groups, but the ratio of dead cell area was 4 times higher in the alginate group than in the PFD-alginate group. In conclusion, integration of PFD in alginate microcapsules improved islet function and survival by minimizing the hypoxic damage of islets after intraperitoneal transplantation.

Pub.: 14 Jan '18, Pinned: 20 Apr '18

Single-donor islet transplantation and long-term insulin independence in select patients with type 1 diabetes mellitus.

Abstract: Islet transplantation is a recognized treatment option for select patients with type I diabetes mellitus. However, islet infusions from multiple donors are often required to achieve insulin independence. Ideally, insulin independence would be achieved routinely with only a single donor. Identification of factors associated with insulin independence after single-donor islet transplantation may help to select recipient-donor combinations with the highest probability of success.Subjects undergoing islet transplantation at a single center (Edmonton, Canada) between March 1999 and August 2013 were included. Recipient, donor, and transplant characteristics were collected and compared between recipients who became insulin independent after one islet transplantation and those who did not.Thirty-one patients achieved insulin independence after a single-donor islet transplantation, and 149 did not. Long-term insulin-free survival was not different between the groups. Factors significantly associated with single-donor success included recipient age, insulin requirement at baseline, donor weight, donor body mass index, islet transplant mass, and peritransplant heparin and insulin administration. On multivariate analysis, pretransplantation daily insulin requirements, the use of peritransplantation heparin and insulin infusions, and islet transplant mass remained significant.We have identified clinically relevant differences defining the achievement of insulin independence after single-donor transplantation. Based on these differences, a preoperative insulin requirement of less than 0.6 U/kg per day and receiving more than 5,646 islet equivalents (IEQ)/kg have a sensitivity of 84% and 71% and specificity of 50% and 50%, respectively, for insulin independence after single-donor islet transplantation. With ideal patient selection, this finding could potentially increase single-donor transplantation success and may be especially relevant for presensitized subjects or those who may subsequently require renal replacement.

Pub.: 10 Jun '14, Pinned: 20 Apr '18

Risk factors for islet loss during culture prior to transplantation.

Abstract: Culturing islets can add great flexibility to a clinical islet transplant program. However, a reduction in the islet mass has been frequently observed during culture and its degree varies. The aim of this study was to identify the risk factors associated with a significant islet loss during culture. One-hundred and four islet preparations cultured in an attempt to use for transplantation constituted this study. After culture for 20 h (median), islet yield significantly decreased from 363 309 +/- 12 647 to 313 035 +/- 10 862 islet equivalent yield (IE) (mean +/- SE), accompanied by a reduction in packed tissue volume from 3.9 +/- 0.1 to 3.0 +/- 0.1 ml and islet index (IE/islet particle count) from 1.20 +/- 0.04 to 1.05 +/- 0.04. Culture did not markedly alter islet purity or percent of trapped islet. Morphology score and viability were significantly improved after culture. Of 104 islet preparations, 37 suffered a substantial islet loss (> 20%) over culture. Factors significantly associated with risk of islet loss identified by univariate analysis were longer cold ischemia time, two-layer method (TLM) preservation, lower islet purity, and higher islet index. Multivariate analysis revealed that independent predictors of islet loss were higher islet index and the use of TLM. This study provides novel information on the link between donor- isolation factors and islet loss during culture.

Pub.: 21 Jun '08, Pinned: 20 Apr '18

Lower Concentrations of Circulating Medium and Long Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.

Abstract: In HIV-negative individuals, a plasma metabolite profile characterized by higher levels of branched-chain amino acids (BCAA), aromatic amino acids, and C3/C5 acylcarnitines is associated with insulin resistance and increased risk of diabetes. We sought to characterize the metabolite profile accompanying insulin resistance in HIV-positive persons to assess whether the same or different bioenergetics pathways might be implicated. We performed an observational cohort study of 70 non-diabetic, HIV-positive individuals (50% with body mass index ≥ 30 kg/m2) on efavirenz, tenofovir, and emtricitabine with suppressed HIV-1 RNA levels (< 50 copies/mL) for at least 2 years and a CD4+ count over 350 cells/µL. We measured fasting insulin resistance using the homeostatic model assessment 2, plasma free fatty acids using gas chromatography, and amino acids, acylcarnitines, and organic acids using liquid chromatography/mass spectrometry. We assessed the relationship of plasma metabolites with insulin resistance using multivariable linear regression. The median age was 45 years, median CD4+ count was 701 cells/µL, and median hemoglobin A1c was 5.2%. Insulin resistance was associated with higher plasma C3 acylcarnitines (p=0.01), but not BCAA or C5 acylcarnitines. Insulin resistance was also associated with lower levels of C18, C16, C12, and C2 acylcarnitines (p≤0.03 for all), and lower C18 and C16 acylcarnitine:free fatty acid ratios (p=0.002, and p=0.03, respectively). Insulin resistance in HIV-positive persons is characterized by lower levels of plasma acylcarnitines, including the C2 product of complete fatty acid oxidation, suggesting impaired fatty acid uptake and/or oxidation is a central feature of glucose intolerance in this population.

Pub.: 03 Apr '18, Pinned: 19 Apr '18

Mortality and treatment response amongst HIV-infected patients 50 years and older accessing antiretroviral services in South Africa.

Abstract: Little is known about the clinical presentation and outcomes amongst older HIV infected populations accessing ART in sub-Saharan Africa. We compared mortality amongst HIV infected patients accessing ART that were <  50 years to those ≥50 years in Kwa-Zulu Natal, South Africa. We undertook a retrospective review of medical records of patients that accessed HIV services at the CAPRISA AIDS Treatment program (CAT) between June 2004 to December 2012 (N = 4003). HIV infected patients, 14 years or older were enrolled. All-cause mortality and treatment response to ART in those < 50 years to those ≥50 years were compared. A Kaplan-Meier curve and log-rank test were used to compare the cumulative probability of death between the two age groups with the primary endpoint being mortality. Statistical analysis was done using SAS (version 9.4.; SAS Institute Inc., Cary, NC, USA). Of 4003 individuals, 262 (6.5%) were ≥ 50 years (older group). The median age in those ≥50 years and <  50 year was 54.5 and 32.0 years, respectively. The younger group was mainly female (64.7%). There was no difference in mortality rate, between the older (6.9/100 person-years (py), 95% confidence interval (CI): 4.7-9.6) and younger group (5.3/100 py, 95% CI: 4.7-5.8) at 60 months (p = 0.137). In the multivariable model older patients had a significantly higher risk of death compared to younger patients. (hazard ratio (HR) 1.60, 95% CI: 1.08-2.39, p = 0.019).The rate of CD4+ cell count increase was higher in those < 50 years (β = 0.34, 95% CI: 0.19-0.50, p < 0.001) with no difference in viral suppression. The older group showed significantly higher prevalence of diabetes (6.3%) and hypertension (21.5%), p < 0.001. ART initiation in older HIV infected patients was associated with a higher mortality compared to those younger than 50 years. ART immunological response was less robust in older individuals. The increase in hypertension and diabetes among older patients suggests the need to restructure and integrate primary and specialized health care services into ART services.

Pub.: 11 Apr '18, Pinned: 19 Apr '18

Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults.

Abstract: Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

Pub.: 20 Aug '15, Pinned: 19 Apr '18

Incidence and risk factors for prediabetes and diabetes mellitus among HIV infected adults on antiretroviral therapy: systematic review and meta-analysis.

Abstract: To summarize evidence on the rates and drivers of progression from normoglycemia to prediabetes and/or diabetes mellitus (hereafter 'diabetes') in antiretroviral treatment (ART)-exposed HIV-infected people.We searched EMBASE, PubMed, Web of Science, and Global Index Medicus to identify articles published from 1 January 2000 to 30 April 2017. A random-effects model produced a summary estimate of the incidence across studies and heterogeneity was assessed using Cochrane's Q statistic.We included 44 studies, whose methodologic quality was high with only 10 (30%) medium-quality studies and none of low quality. There was substantial heterogeneity between studies in estimates of the incidence of diabetes and prediabetes. The pooled incidence rate of overt diabetes and prediabetes were 13.7 per 1,000 person-years of follow-up (95%CI: 13-20; I² = 98.1%) among 396,496 person-years and 125 per 1,000 person-years (95% CI: 0-123; I² = 99.4) among 1,532 person-years, respectively. The major risk factors for diabetes and prediabetes were aging, family history of diabetes, Black or Hispanic origin, overweight/obesity, central obesity, lipodystrophy/lipoatrophy, dyslipidaemia, metabolic syndrome, increased baseline fasting glycemia, and certain ART regimens.These data highlight the important and fast increasing burden of diabetes and prediabetes among the ART-exposed HIV-infected population. More research is needed to better capture the interplay between prediabetes/diabetes and ART in HIV-infected patients, considering the increasing number of ART-exposed patients subsequent to the World Health Organization's recommendation of initiating ART at HIV infection diagnosis regardless of CD4-count and age.

Pub.: 03 Feb '18, Pinned: 19 Apr '18

Is There Sufficient Evidence for a Causal Association between Antiretroviral Therapy and Diabetes in HIV-infected Patients? A Meta-analysis.

Abstract: The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes.We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference (MD) in FPG concentrations and odds ratios (OR) of diabetes and metabolic syndrome were pooled using random-effects meta-analyses.Data on 20,178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled MD: 4.66 mg/dl, 95% confidence interval [CI] 2.52 to 6.80, 24 studies) and the odds of diabetes (Pooled OR: 3.85, 95% CI 2.93 to 5.07, 10 studies) and metabolic syndrome (Pooled OR: 1.45, 95% CI 1.03 to 2.03, 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥ 18 months (Pooled MD: 4.97 mg/dl, 95% CI 3.10 to 6.84, 14 studies), but not in studies with mean ART duration < 18 months (Pooled MD: 4.40 mg/dl, 95% CI -0.59 to 9.38, 7 studies).ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.

Pub.: 25 Apr '17, Pinned: 19 Apr '18

Chronic kidney disease in the global adult HIV-infected population: A systematic review and meta-analysis.

Abstract: The widespread use of antiretroviral therapies (ART) has increased life expectancy in HIV patients, predisposing them to chronic non-communicable diseases including Chronic Kidney Disease (CKD). We performed a systematic review and meta-analysis (PROSPERO registration number CRD42016036246) to determine the global and regional prevalence of CKD in HIV patients. We searched PubMed, Web of Science, EBSCO and AJOL for articles published between January 1982 and May 2016. CKD was defined as estimated glomerular filtration rate (eGFR) <60ml/min using the MDRD, Cockcroft-Gault or CKD-EPI equations. Random effects model was used to combine prevalence estimates from across studies after variance stabilization via Freeman-Tukey transformation. Sixty-one eligible articles (n = 209,078 HIV patients) in 60 countries were selected. The overall CKD prevalence was 6.4% (95%CI 5.2-7.7%) with MDRD, 4.8% (95%CI 2.9-7.1%) with CKD-EPI and 12.3% (95%CI 8.4-16.7%) with Cockcroft-Gault; p = 0.003 for difference across estimators. Sub-group analysis identified differences in prevalence by WHO region with Africa having the highest MDRD-based prevalence at 7.9% (95%CI 5.2-11.1%). Within Africa, the pooled MDRD-based prevalence was highest in West Africa [14.6% (95%CI 9.9-20.0%)] and lowest in Southern Africa (3.2%, 95%CI 3.0-3.4%). The heterogeneity observed could be explained by WHO region, comorbid hypertension and diabetes mellitus, but not by gender, hepatitis B or C coinfection, CD4 count or antiretroviral status. CKD is common in HIV-infected people, particularly in Africa. HIV treatment programs need to intensify screening for CKD with added need to introduce global guidelines for CKD identification and treatment in HIV positive patients.

Pub.: 17 Apr '18, Pinned: 19 Apr '18