Vincent W. Wong

Saliva and bloodspot cortisol: novel sampling methods to assess hydrocortisone replacement therapy in hypoadrenal patients

background  In patients with hypoadrenalism, it is often difficult to assess the optimal dose of glucocorticoid replacement. Serial serum cortisol measurements for a cortisol day curve are sometimes used, but this has low acceptability for patients. In this study, we evaluate the reliability of saliva and capillary bloodspot cortisol as alternative methods in assessing cortisol profiles in hypoadrenal patients on hydrocortisone replacement.

Gestational diabetes mellitus: Who requires insulin therapy?

Background:  The prevalence of gestational diabetes mellitus (GDM) is increasing in Australia. Management of GDM has taken up a significant share of the workload of diabetes services in public hospitals, especially in managing women who require insulin therapy.

Gestational diabetes mellitus in five ethnic groups: a comparison of their clinical characteristics

Diabet. Med. 29, 366–371 (2012)

Impact of Improved Glycemic Control on Cardiac Function in Type 2 Diabetes Mellitus.

Background—Patients with type 2 diabetes mellitus are at risk of heart failure. Specific therapeutic interventions for diabetic heart disease are still elusive. We aimed to examine the impact of improved glycemic control on left ventricular (LV) function in these patients. Methods and Results—A total of 105 subjects with type 2 diabetes mellitus (aged 54±10 years) and poor glycemic control received optimization of treatment for blood glucose, blood pressure, and cholesterol to recommended targets for 12 months. LV systolic and diastolic function, measured by LV global longitudinal strain (GLS) and septal e′ velocities, were compared before and after optimization. At baseline, patients had impaired LV systolic (GLS −14.9±3.2%) and diastolic function (e′ 6.2±1.7 cm/s). After 12 months, glycated hemoglobin (HbA1c) decreased from 10.3±2.4% to 8.3±2.0%, which was associated with significant relative improvement in GLS of 21% and septal e′ of 24%. There was a progressively greater improvement in GLS as patients achieved a lower final HbA1c. Patients achieving an HbA1c of <7.0% had the largest improvement. The 15 patients whose HbA1c worsened experienced a decline in GLS. Patients who improved their HbA1c by ≥1.0% had a significantly higher relative improvement in e′ than those who did not (32% versus 8%; P=0.003). Baseline GLS, decrease in body mass index, and treatment with metformin were additional independent predictors of GLS improvement. Conclusions—Improvements in glycemic control over a 12-month period led to improvements in LV systolic and diastolic function. This may have long-term prognostic implications.

High-dose insulin in experimental myocardial infarction in rabbits: protection against effects of hyperglycaemia

INTRODUCTION Hyperglycaemia at the time of acute myocardial infarction (AMI) is a predictor of survival and is associated with increased mortality and morbidity in patients with or without diabetes mellitus. On the other hand, insulin has been shown to reduce myocardial injury in experimental studies but its benefits have not been confirmed in clinical studies. METHODS The isolated perfused heart model was used to examine the direct effect of incremental doses of insulin and varying degrees of hyperglycaemia on infarct size and cardiomyocyte apoptosis in rabbit hearts. The rabbit hearts were subjected to 30-min ischaemia and 2.5-h reperfusion. RESULTS Insulin, given alone just before reperfusion, dramatically reduced infarct size in a dose-dependent manner (75-300 μU/ml) during experimental myocardial infarction (46%±2% to 10.9%±3%, P<.001). Acutely elevated glucose levels (33 mmol/L) induced a significantly greater infarct size and cardiomyocyte apoptosis compared to hearts subjected to normal glucose levels. On the other hand, high-dose insulin (300 μU/ml) given 5 min before reperfusion attenuated the extent of infarction and reduced apoptosis in hearts that were exposed to high glucose levels. CONCLUSION Acutely elevated levels of glucose induced larger infarct area during ischaemia-reperfusion, and this is mediated through proapoptotic pathways. Insulin, when given just before reperfusion, confers cardioprotection in a dose-dependent manner and reverses the detrimental effect of acute hyperglycaemia. High-dose insulin as well as maintaining normoglycaemia remain important factors that improve outcomes following myocardial infarction.

High cortisol levels in hyperglycaemic myocardial infarct patients signify stress hyperglycaemia and predict subsequent normalization of glucose tolerance

Context  It is unclear if people who develop stress hyperglycaemia have underlying abnormal glucose metabolism, an exaggerated hormonal response to stress, or both. Similarly, it is unknown whether stress hyperglycaemia predicts future glucose intolerance.

Hyperglycaemia following glucose challenge test during pregnancy: When can a screening test become diagnostic?

OBJECTIVE The 50g-glucose challenge test (GCT) is commonly used for screening of gestational diabetes (GDM) in low risk pregnant women. If elevated, glucose tolerance test is performed to confirm the diagnosis. In this study, we evaluated whether GCT alone is sufficient to diagnose GDM when the GCT result is very elevated. RESEARCH DESIGN AND METHODS Using a database of 62877 pregnancies over 10 years, the positive predictive value (PPV) of GCT for GDM was assessed using different GCT cut-off values. RESULTS At a glucose cut-off value of 11 mmol/l, the PPV for GDM was 85.3%, based on the subsequent GTT. This increased to 95.3% when the cut-off was 12 mmol/l. Furthermore, the PPV was consistently higher when GCT was performed in the morning. CONCLUSION We concluded that the diagnosis of GDM can be made when the glucose level following GCT is very elevated, and GTT need not to be performed for confirmation of GDM. The timing of GCT also affected PPV for GDM, and has implications on the diagnostic value of the test.

Mini Review: Changes in the Incidence of and Progression to Proliferative and Sight-Threatening Diabetic Retinopathy Over the Last 30 Years

ABSTRACT Purpose: Diabetic retinopathy is a leading cause of blindness worldwide. The last 3 decades have seen major improvements in glycemic and blood pressure control as well as the introduction of national screening programs, and we sought to determine if rates of proliferative diabetic retinopathy have changed as a result. Methods: We conducted a systematic review to determine whether the incidence and progression rates of proliferative diabetic retinopathy and sight-threatening retinopathy have changed, focusing on large population-based studies with objective assessment of diabetic retinopathy. Results: Comparisons across different studies is problematic due to different baseline retinopathy severity, different reported outcomes and different follow-up periods, but within these constraints certain trends could be identified. This review provides evidence that the incidence and progression of these conditions has reduced by approximately 2–3 fold over the last 3 decades. Conclusion: These results have implications for current diabetic retinopathy screening guidelines and has identified future areas where research could be improved.

Adopting the new World Health Organization diagnostic criteria for gestational diabetes: How the prevalence changes in a high-risk region in Australia

AIMS In this study, we assessed changes in prevalence of gestational diabetes mellitus (GDM) in a region with diverse cultural backgrounds in Australia under the new World Health Organization (WHO) diagnostic criteria, with reference to the womans ethnicity, age and pre-pregnant body mass index (BMI). METHODS We recorded results of all 75-gram oral glucose tolerance tests (OGTTs) performed on pregnant women between February and December 2015 together with their demographic details, and determined the prevalence of GDM based on the old Australian Diabetes in Pregnancy Society (ADIPS) and the new WHO criteria respectively. RESULTS Over that period, 2140 OGTTs were performed in 1725 pregnant women. The prevalence of GDM was 14.8% (255/1725 women) under old ADIPS criteria, but went up to 29.6% (510/1725) when using WHO criteria. An increase in prevalence was observed in all ethnic groups. Women from East/South-East Asia had the lowest increment (from 19.2 to 22.3%) while those from South Asia had the highest (from 22.0 to 44.4%). Prevalence of GDM was 45.9% amongst women with BMI>30kg/m2. For women from South Asia with BMI>30kg/m2, 70.0% would have GDM. Birth outcomes were similar between women who would have GDM under WHO but not the old ADIPS criteria (untreated), and those who were treated for GDM under old criteria. CONCLUSION In parts of Australia, adoption of WHO diagnostic criteria could result in doubling of the prevalence of GDM, depending on the womens demographic characteristics. Women from South Asia or those with obesity should be targeted for pre-pregnant lifestyle intervention.

Left ventricular diastolic reserve in patients with type 2 diabetes mellitus.

Aims Diastolic reserve is the ability of left ventricular filling pressures to remain normal with exercise. Impaired diastolic reserve may be an early sign of diabetic cardiomyopathy. We aimed to determine whether diastolic reserve differs in type 2 diabetes (DM) compared with non-DM, and to identify clinical, anthropological, metabolic and resting echocardiographic correlates of impaired diastolic reserve in patients with DM. Methods and results 237 patients (aged 53±11 years, 133 DM, ejection fraction 68±9%) underwent rest and exercise echocardiography. Mitral E and septal e′ were measured at rest, immediately post, and 10 min into recovery. Analysis of covariance (ANCOVA) and binary regression with continuous outcomes were used to model e′ and E/e′ changes with exercise to identify impaired diastolic reserve defined as post-exercise E/e′ ≥15. After adjusting for baseline differences, patients with DM immediately post-exercise had a lower septal e′, a lower Δe′ (1.2 vs 2.3 cm/s, p=0.006) and a higher Δ septal E/e′ (1.7 vs 0.08, p<0.001) than patients without DM. In patients with normal resting E/e′ of ≤8 (n=130), DM had a significantly higher post-exercise septal E/e′ and a higher Δseptal E/e′ (2.63 vs 0.50, p<0.001). E/e′ in patients with DM remained significantly elevated up to 10 min post-exercise. Hypertension, longer duration of insulin therapy, poorer glycaemic control, worse renal function, larger left atrial volume and lower septal e′ were independent correlates of impaired diastolic reserve in patients with DM. Conclusions Patients with DM have impaired diastolic reserve manifest as a blunted e′ response with exercise, persisting into recovery. Clinical, anthropometric, metabolic and echocardiographic correlates of impaired diastolic reserve in patients with DM were identified. An impaired LV diastolic reserve may be the underlying pathophysiological mechanism in patients with DM with unexplained exertional dyspnoea and may allow earlier detection of DM cardiomyopathy.