Assessment of putative risk factors in the development of Diabetic Retinopathy in Wales

The aim of this thesis was to assess the relationships between glycaemic exposure and β-cell function with prevalence, incidence and progression of diabetic retinopathy (DR) over 5 years in newly-diagnosed treatment-naïve subjects with type2 diabetes mellitus (T2DM). At diagnosis, we studied 544 subjects and demonstrated DR was independently associated with fasting and postprandial hyperglycaemia and reduced fasting β-cell function during standardized meal and intravenous glucose challenge. The insulin-independent component of glucose tolerance (SG) was also impaired and independently associated with presence of DR at diagnosis. We followed up 233 subjects over 5 years and established independent association between chronic glycaemic exposure (HbA1c,/fasting/ postprandial hyperglycaemia) at diagnosis and incident DR during this period. We also demonstrated that fasting and postprandial β-cell responsiveness to nutrient challenge along with SG at baseline was independently associated with development of DR over 5 years. There was no difference in glycaemic status between those with or without DR at 5 years highlighting the relevance of early history of glycaemic exposure in our subjects to future incidence of DR. Finally, in 45 T2DM subjects with DR at diagnosis, fasting, postprandial glucose and HbA1c along with fasting, postprandial β-cell responsiveness at diagnosis were all independently associated with DR progression. Thus, this study has indicated that hyperglycaemia resulting from pancreatic β-cell deficiency contributes to the risk of development and progression of DR. The data emphasises the need for earlier diagnosis of T2DM and cautious normalization of glycaemia to eliminate glucotoxicity on the already impaired β-cell function. The evidence indicates the potential value of supporting β-cell function aiming to achieve near-normal glycaemia and thus preventing the onset and progression of DR in subjects with T2DM

Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function

Purpose: The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. Methods: A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). Results: A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. Principal Conclusions: In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemi

Light-emitting devices based on Evans blue under alternating-current and direct-current modes: different charge injection mechanisms

Light-emitting devices (LEDs) have been fabricated with a blend of evans blue dye and poly(methylmethacrylate) (PMMA) insulating material. Luminance has been observed under both direct-current (DC) and alternating-current (AC) modes. Different charge injection and operation mechanisms have been shown to be applicable under DC and AC biases. From the current-voltage characteristics under DC voltage, Fowler-Nordheim (FN) tunnelling mechanism and Richardson-Schottky thermionic emission have been found to be applicable in forward and reverse bias directions, respectively. In general, luminance has been observed only in the forward bias direction. Under AC voltage, there has been accumulated hole-assisted electron injection, which has resulted in luminance in both bias directions for all molar concentrations of evans blue, and particularly higher luminance level in the reverse-biased half-cycle. Moderately high-frequency (40 kHz) electroluminescence (EL) has been obtained from these devices

Incidence of diabetic retinopathy in newly diagnosed subjects with type 2 diabetes mellitus over 5 years: Contribution of B-cell function

Aims Identifying and modulating risk factors is essential to prevent visual impairment due to diabetic retinopathy (DR). This study examines incident DR with metabolic and hormonal factors in newly-diagnosed, treatment naïve, individuals with Type2 Diabetes Mellitus (T2DM), over a 5 year period from diagnosis. Methods 233 T2DM subjects underwent serial DR screening using digital photography and standardised Meal Tolerance Tests at diagnosis and after 1, 2 and 5 years. Subjects (179) with no DR throughout the 5-year study period were compared with those who developed DR (54). Results Of 233 subjects, 54(23.2%) developed DR by 5 years, background DR in 50(93%) and exudative maculopathy in 4(7%) individuals. Of these subjects, 12(22%) developed DR after 1 year, 15(28%) after 2 years and 27(50%) after 5 years. At baseline, those with DR at 5 years had higher HbA1c (p = 0.017), higher fasting plasma glucose (PG) (p = 0.031) and postprandial PG (p = 0.009). They were associated with reduced basal β-cell secretory function (M0) (p = 0.025), lower (p = 0.000) postprandial β-cell responsiveness (M1) and β-cell function (HOMA-B) (p = 0.044). Conclusions There is an independent association between glycaemic control and β-cell dysfunction at the time of diagnosis of T2DM, with incident DR over a follow-up period of 5 years

Use of day 1 early morning cortisol to predict the need for glucocorticoid replacement after pituitary surgery

Background. Assessment of adrenal reserve in patients who have undergone pituitary surgery is crucial. However, there is no clear consensus with regards to the type and timing of the test that should be used in the immediate post-operative period. Recently, there has been increased interest in measuring post-operative cortisol levels. We present our data utilising day 1 post-operative early morning cortisol as a tool to assess adrenal reserve in steroid-naive patients. Methods. A retrospective analysis of endoscopic pituitary surgery undertaken over a 2-year period. 82 patients underwent 84 surgeries in total. Patients who were already on glucocorticoids pre-operatively and patients with Cushing's disease, pituitary apoplexy and those without follow-up data were excluded, leaving a study group of 44 patients with 45 operations. A 9am day 1 post-operative cortisol value of > 400 nmol/L was taken as an indicator of adequate adrenal reserve. All the patients were reassessed at 6 weeks with a standard short synacthen test (SST) using 250 micrograms of intravenous synacthen. Results. 22 out of 45 patients had a cortisol value of > 400 nmol/L on day 1 post-operatively and were discharged without glucocorticoid supplementation. Of these, only 2 patients subsequently failed the SST when reassessed at 6–8 weeks. The remaining 23 patients had a cortisol value of < 400 nmol/L on day 1 post-operatively and were discharged on hydrocortisone 10 mg twice daily. At 6–8 weeks, nine continued to show suboptimal stimulated cortisol levels whereas the remaining fourteen patients showed adequate adrenal reserve. The 9 am cortisol value had high specificity (81.8%) and positive predictive value (90.9%) for integrity of the HPA axis. Sensitivity was 58.8% and negative predictive value was 39.1%. Conclusion. A day 1 post-operative early morning cortisol is a useful tool to predict adrenal reserve post-pituitary surgery, enabling clinicians to avoid unnecessary blanket glucocorticoid replacement

Ethnic differences in the prevalence of diabetic retinopathy in persons with diabetes when first presenting at a diabetes clinic in South Africa

OBJECTIVE To describe the prevalence and associated risk factors for diabetic retinopathy (DR) within a multiethnic population at presentation to a diabetes clinic in South Africa. RESEARCH DESIGN AND METHODS Retinal photography was conducted using a nonmydriatic digital camera without mydriasis and graded by one of three senior graders. Logistic regression analyses were used to assess the association between any DR, referable DR, and clinical risk factors. RESULTS A total of 1,537 persons with type 1 and 3,978 with type 2 diabetes were included. Prevalence of any DR in type 1 diabetes was 35.2% (background DR 26% and referable DR 9.2%) and in type 2 diabetes was 20.5% (14.1 and 6.4%, respectively). In type 1 diabetes, there was an increased risk of any DR in Asian Indians, whereas the risk of referable DR was increased for indigenous Africans compared with Caucasians. In type 2 diabetes, the risk was increased for all non-Caucasians compared with Caucasians. Longer duration of diabetes and elevated HbA(1c) were independently associated with any and referable DR in both type 1 and type 2 diabetes, with the addition of hypertension and smoking in type 1 diabetes when adjusted for age at diagnosis of diabetes, sex, and ethnicity. CONCLUSIONS The prevalence of DR in this population from South Africa was similar to that reported globally; however, ethnic differences were observed. Increasing duration of diabetes and poor glycemic control were the strongest risk factors associated with any and referable DR in both type 1 and type 2 diabetes

Diabetic retinopathy in newly diagnosed subjects with type 2 diabetes mellitus: contribution of β-Cell function

Purpose: The association of hyperglycemia and diabetic retinopathy (DR) in established type 2 diabetes mellitus (T2DM) subjects is well accepted. However, the association between β-cell responsiveness and insulin sensitivity leading to fasting and postprandial hyperglycemia with DR in newly diagnosed treatment-naïve T2DM subjects remain unreported. Methods: A total of 544 newly diagnosed treatment-naïve T2DM subjects were screened for DR (digital photography) and underwent a standardized meal tolerance test. Serial plasma glucose and insulin levels were measured, and fasting (M0) and postprandial β-cell responsiveness calculated Calculating Pancreatic Response Program along with homeostasis model assessment-β cell function (HOMA-B) and HOMA-Insulin Sensitivity. A subgroup of 201 subjects also underwent a frequently sampled IV glucose tolerance test and the acute insulin response to glucose, insulin sensitivity, and glucose effectiveness (SG) estimated (MINMOD model). Results: A total of 16.5% (90) subjects had DR at diagnosis. Subjects with DR had significantly reduced M0, HOMA-B and SG leading to higher fasting and postprandial (2 hour) glucose and significantly lower fasting and postprandial (2 hour) insulin. Factors independently associated with DR in multivariate logistic regression analysis were M0, HOMA-B, and SG with fasting and postprandial (2 hour) glucose and insulin. There was no statistical difference in glycated hemoglobin, systolic blood pressure, acute insulin response to glucose, and insulin sensitivity between those with or without DR. Principal Conclusions: In this cohort of newly diagnosed T2DM subjects, DR is associated with reduced β-cell responsiveness, resulting from β-cell failure rather than insulin resistance, leading to fasting and postprandial hyperglycemia and hypoinsulinemi

Prevalence of diabetic retinopathy within a national diabetic retinopathy screening service

Aims Determine the prevalence and severity of diabetic retinopathy (DR) and risk factors in a large community based screening programme, in order to accurately estimate the future burden of this specific and debilitating complication of diabetes. Methods A cross-sectional analysis of 91 393 persons with diabetes, 5003 type 1 diabetes and 86 390 type 2 diabetes, at their first screening by the community based National Diabetic Retinopathy Screening Service for Wales from 2005 to 2009. Image capture used 2×45° digital images per eye following mydriasis, classified by qualified retinal graders with final grading based on the worst eye. Results The prevalence of any DR and sight-threatening DR in those with type 1 diabetes was 56.0% and 11.2%, respectively, and in type 2 diabetes was 30.3% and 2.9%, respectively. The presence of DR, non-sight-threatening and sight-threatening, was strongly associated with increasing duration of diabetes for either type 1 or type 2 diabetes and also associated with insulin therapy in those with type 2 diabetes. Conclusions Prevalence of DR within the largest reported community-based, quality assured, DR screening programme, was higher in persons with type 1 diabetes; however, the major burden is represented by type 2 diabetes which is 94% of the screened population