Objective The main objective is to evaluate the current diabetic retinopathy (DR) screening by optometrists under Risk Assessment and Management Programme (RAMP) in general outpatient clinics (GOPC), and to compare it to conventional screening by clinical examination. The secondary objective is to predict the prevalence of DR and maculopathy (DMac) in the study cohort, and identify risk factors especially the role of nephropathy. Methodology Ophthalmologist’s re-grading of the digital fundus photos previously screened by optometrists according to RAMP protocol was used as the gold standard to evaluate the current screening programme. Accuracy of optometrist screening was calculated by percentage of agreement and Kappa coefficient. Fundus photo grading by ophthalmologist and optometrist was compared to clinical examination findings in eye clinics. Sensitivities and specificities were calculated, and plotted on ROC curve for comparison of the two methods of screening. Prevalences of DR and DMac were estimated from the gold standard grading, and their correlation with other factors also screened by RAMP was identified using chi-square test and logistic regression. Results There was an overall over-grading of disease by optometrists. The overall inter-observer agreement in diagnosis was 81.2%, and the overall kappa coefficient was 0.65 (p<0.001), which reached substantial strength of agreement. Use of mydriatics reduced the percentage of ungradable photos by at least 4 times. The overall agreement of clinical examination with ophthalmologist-photo-grading was 69.2%, and that with optometrist was 60.9%, and the respective Kappa coefficients were 0.31 (p<0.001) and 0.25 (p<0.001). The areas under curve (AUC) on ROC curve were larger for optometrist photo screening (DR=0.85 and DMac=0.80) than clinical examination (DR=0.52 and DMac=0.54). The prevalences of DR and DMac were 19.4% and 3.3% respectively. Duration of DM was the only common significant predictor of referable DR and DMac by chi-square test. 15-year of disease significantly increased the risk of more advanced DR and DMac. Nephropathy was only significant for DR but not DMac. Moderate renal dysfunction as indicated by decreased excretory glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and presence of macroalbuminuria significantly worsened DR staging, by over 5 times (p=0.02). Family history of diabetes mellitus (DM), on the other hand, increased the risk of DMac only, by 5 times (p=0.01). Conclusion The current optometrists’ screening is reasonably valid and reliable, although there is room for improvement. None-the-less, the higher false-positive rates than false-negative rates for referable disease suggests that it is safer than otherwise. It is a better method than clinical examination. Duration of DM and presence of nephropathy, especially macroalbuminuria which predates decrease in eGFR, and family history of DM can predict more advanced DR and/or DMac development. / published_or_final_version / Public Health / Master / Master of Public Health

Introduktion: Sjuksköterskor idag står inför en växande patientgrupp med diabetes, som har svårläkta fotsår. Patienterna finns i alla vårdformer som primärvård, specialistvård och kommunal hälso- och sjukvård. För att patienten ska kunna upprätthålla en god livskvalitet och ett bra socialt liv krävs det en säker och snabb sårläkning. Syfte: Arbetets syfte var att beskriva vad som påverkar sårläkning hos patienter med diabetes och svårläkt fotsår, vid undertrycksbehandling. Metod: Denna litteraturstudie har utgått ifrån Polit och Becks (2012) niostegsmodell. Sökningarna har gjorts i CINAHL och PubMed. Kvalitetsgranskning gjordes som resulterade i tio kvantitativa vetenskapliga artiklar. Artiklarnas resultatdel analyserades och grupperades utifrån syftet och efter gemensamma områden.  Resultat: Resultatet i litteraturstudien delades in i två kategorier: sårstatus och behandlingstid. I resultatet framkom att undertrycksbehandling sågs som mer effektiv behandlingsmetod än konventionell fuktighetsbevarande sårbehandling. Volym och sårdjup minskade mer effektivt vid undertrycksbehandling än med konventionell fuktig sårbehandling. Slutsats: Litteraturstudien visar att undertrycksbehandling kan bidra till snabbare sårläkning hos diabetiker med svårläkt fotsår. Alla studier valde mätvärden som storlek, djup och typ av vävnad för att beskriva sårstatus. Behandlingstiden varierade i studierna. Det visade sig även att det vetenskapliga underlaget var begränsat.

No description available.

Diabetes causes early structural changes to the glomerular basement membrane (GBM), which alters its function and leads to loss of protein in urine. Formation of advanced glycation endproducts (AGEs) is one mechanism proposed to be responsible for the structural changes to the GBM. AGEs are thought to affect blood flow i.e. glomerular filtration rate (GFR) and vascular permeability which over time manifests as overt proteinuria. The gradual loss of minute amounts of protein (albumin) is referred to as microalbuminuria (MA). Microalbuminuria is a dynamic process, with patients regressing to normoalbuminuria more often than progressing to overt proteinuria. Microalbuminuria is not specific to patients with diabetic nephropathy (DN) and new markers specific to DN are being sought. A prospective study was undertaken at the Inkosi Albert Luthuli Central Hospital (IALCH) to evaluate the relationship of serum glycated albumin, urinary and serum components of capillary basement membrane and DN in South African Black and Indian patients with type 1 diabetes. The study was undertaken with sampling of blood and urine at baseline, 6-months, 1 year and 2-year follow-up. Serum glycated albumin, urinary type IV collagen and plasma fibronectin were measured at each visit. Since correlations could be performed only at each time point individually, generalised estimating equation (GEE) regression models were constructed in SPSS (15.0) with time specified as a factor in order to take account of relationships among variables over time. The results of this study showed that serum percentage glycated albumin (PGA), plasma fibronectin (FN) and urinary type IV collagen were not better predictors of incipient impaired renal function than MA. Although previous authors have variously reported serum GA, plasma FN and urinary type IV collagen to be predictive of impaired renal function, these studies were conducted mainly in patients with overt DN. The present study suggest that markers of overt renal dysfunction are not necessarily useful predictors of incipient DN. Differences in predictive relationships point to a different disease processes in the two ethnic groups. Of particular note was the lack of a predictive relationship of either fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c) with any of isotope GFR, estimated GFR and proteinuria in Black patients. The most significant finding of this study showed that combination of serum creatinine and MA provided broadest range of predictors of isotope GFR, estimated GFR and proteinuria. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Diabetic cardiomyopathy is defined as changes in the structure and function of the myocardium that occur in diabetic patients in the absence of other cardiovascular risk factors. Our laboratory has shown that conjugated linoleic acid (CLA - a naturally-occurring polyunsaturated fatty acid with multiple health benefits) prevents endothelin-1-induced myocyte hypertrophy in vitro, as well as cardiac hypertrophy in vivo using a rodent model of spontaneously hypertensive heart failure. These cardioprotective effects of CLA were mediated through activation of peroxisome proliferator activated receptors (PPAR isomers α and γ) and stimulation of diacylglycerol kinase ζ (DGKζ). Thus, the aims of this study were to (i) determine the effect of CLA on hyperglycemia-induced structural and functional abnormalities of cardiomyocytes, and (ii) assess the role of PPAR-γ and DGK. High glucose treatment induced hypertrophy of primary adult cardiomyocytes, as indicated by augmented cell size and protein synthesis compared to untreated cardiomyocytes. The hyperglycemia-induced hypertrophy was attenuated by pretreatment with CLA (30 µM). The ability of CLA to prevent hyperglycemia-induced hypertrophy was suppressed by GW9662 (1 µM) and R59022 (10 μM), pharmacological inhibitors of PPAR-γ and DGK, respectively. In addition to structural abnormalities, high glucose impaired contractile function of adult cardiomyocytes as measured by maximal velocity of shortening, maximal velocity of relengthening, and peak shortening. Hyperglycemia-induced contractile dysfunction was likewise prevented by pretreatment with CLA (30 µM). Collectively, these findings support the idea that hyperglycemia is an independent risk factor for the development of diabetic cardiomyopathy. Hypertrophy and contractile dysfunction elicited by high glucose were prevented by CLA. The antihypertrophic actions of CLA are mediated, at least in part, by activation of PPAR-γ and DGK.

No description available.

Diabetics often have elevated levels of serum lipids and cholesterol and increased risk of cardiovascular disease. Streptozotocin-induced diabetes was used to determine whether elevated serum cholesterol levels in diabetics are due to loss of control of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the committed step in cholesterol synthesis. Strain A/ST female mice were fed 10% corn oil diets, half with 2% cholesterol. Experimental groups were injected with 9.0 mg streptozotocin / 100g body weight. Diabetes was confirmed by weight loss, elevated blood sugars, and enlarged spleens. Reductase activity was assayed spectrophotometrically. Serum cholesterol levels were determined by gas liquid chromatography. Both diabetic and control mice fed cholesterol had elevated serum cholesterol levels and decreased reductase activities. These observations suggest that HMG CoA reductase is not the primary control point in the control of serum cholesterol levels in diabetic mice. The increase in serum cholesterol in the SI mice was not more than in the control group, suggesting that increased serum cholesterol is not a key factor in the control of coronary heart disease and related diseases in diabetics. The HMG CoA reductase activity was reduced in both SI and control mice fed 2% cholesterol, but not significantly, possibly due to a small sample size. Other substances that control serum cholesterol are all density classes of lipoproteins (high, intermediate, low, and very low) as well as the chylomicrons. / Department of Biology

Diabetic cardiomyopathy is defined as changes in the structure and function of the myocardium that occur in diabetic patients in the absence of other cardiovascular risk factors. Our laboratory has shown that conjugated linoleic acid (CLA - a naturally-occurring polyunsaturated fatty acid with multiple health benefits) prevents endothelin-1-induced myocyte hypertrophy in vitro, as well as cardiac hypertrophy in vivo using a rodent model of spontaneously hypertensive heart failure. These cardioprotective effects of CLA were mediated through activation of peroxisome proliferator activated receptors (PPAR isomers α and γ) and stimulation of diacylglycerol kinase ζ (DGKζ). Thus, the aims of this study were to (i) determine the effect of CLA on hyperglycemia-induced structural and functional abnormalities of cardiomyocytes, and (ii) assess the role of PPAR-γ and DGK. High glucose treatment induced hypertrophy of primary adult cardiomyocytes, as indicated by augmented cell size and protein synthesis compared to untreated cardiomyocytes. The hyperglycemia-induced hypertrophy was attenuated by pretreatment with CLA (30 µM). The ability of CLA to prevent hyperglycemia-induced hypertrophy was suppressed by GW9662 (1 µM) and R59022 (10 μM), pharmacological inhibitors of PPAR-γ and DGK, respectively. In addition to structural abnormalities, high glucose impaired contractile function of adult cardiomyocytes as measured by maximal velocity of shortening, maximal velocity of relengthening, and peak shortening. Hyperglycemia-induced contractile dysfunction was likewise prevented by pretreatment with CLA (30 µM). Collectively, these findings support the idea that hyperglycemia is an independent risk factor for the development of diabetic cardiomyopathy. Hypertrophy and contractile dysfunction elicited by high glucose were prevented by CLA. The antihypertrophic actions of CLA are mediated, at least in part, by activation of PPAR-γ and DGK.

Thromboxane receptor (TPr) activity is elevated in diabetes and contributes to complications of diabetic kidney disease (DKD). TPr blockade appears to have therapeutic potential. Several rodent models of DKD show attenuation of renal damage and proteinuria upon administration of the TPr antagonist, S18886. However, the cellular targets that underlie the injurious effects of TPr activation in DKD remain to be elucidated. A pilot study in our laboratory subjected a conditionally-immortalized mouse podocyte cell line to high glucose (25 mM D-glucose) and equibiaxial mechanical stretch (an in vitro simulator of increased glomerular capillary pressure associated with glomerular hyperfiltration in early diabetes). qRT-PCR revealed that exposure of podocytes to mechanical stretch (10% elongation) and high glucose for 6 hours yielded a 9-fold increase in TPr mRNA levels vs. controls (non-stretch, 5mM D-glucose + 25mM L-glucose) (p<0.05, n=5). We hypothesized that TPr expression and activity are increased in podocytes during the onset of DKD resulting in maladaptive effects on this key glomerular filtration barrier cell type. We showed that enhanced TPr signaling threatens podocytes viablility. Cultured podocytes treated with the TPr agonist, U-46619 (1 μM) for 24 hours are more vulnerable to apoptosis as quantified by Hoescht 33342 (20% cell death p<0.001, n=3) , TUNEL (30-fold increase, ns, n=3) and Annexin-V labeling (3-fold increase, p <0.001, n=3). To further support these in vitro findings, we developed a transgenic mouse with podocyte-specific overexpression of TPr. A construct consisting of a desensitization resistant mutant of the human TPr with both N- and C-terminal HA-epitope tags under the control of an 8.3 kb fragment of the immediate 5’ mouse NPHS1 promoter was cloned, isolated and injected into FVB/n oocytes that were implanted into pseudopregnant CD1 females. Founders were characterized for TPr transgene expression, and TPr transgene mRNA levels were detected by qRT-PCR. Our in vitro results suggest that increased TPr expression in podocytes of diabetic mice may contribute to filtration barrier damage and have important implications in the development and progression of DKD.

No description available.