Age dependence of endogenous galactose formation in Q188R homozygous galactosemic patients

The age dependence of endogenous galactose formation was investigated in Q188R homozygous galactosemic patients (n=18; 4-38 years) using the primed continuous infusion approach with D-[1-13C]galactose as a substrate. Studies were conducted under postabsorptive conditions (fasting >10h) and good metabolic control. In the patients, the release of galactose from endogenous sources into plasma (R(a)) decreased with age and ranged from 4.6 to 2.0 micromol/kg body weight per h. Galactitol and galactonate release rates paralleled the galactose R(a) but at a lower level. The mean relation of galactose, galactitol, and galactonate release was 10:5:1. Statistically, there was a highly significant (p<0.0001) inverse correlation between total galactose release (i.e., sum of R(a) plus galactitol and galactonate release) and age. The data (total galactose=y, age=t) were best fitted to the simple exponential model y=y(0)+axexp(-bt) by non-linear regression analysis. The parameter estimates were y(0)=3.0+/-0.2, a=6.5+/-0.4, and b=0.11+/-0.02. The value of y(0) provides an estimate of total galactose release in adult patients (i.e., approximately 13 mg/kg body weight per day), summation operator (y(0)+a) provides an estimate for galactosemic newborns (i.e., approximately 41 mg/kg body weight per day). The data show that significant amounts of endogenous galactose are formed in galactosemic patients with release rates being several fold higher in infants than in adults. The present findings can explain the persistently elevated galactose-1-phosphate levels in erythrocytes-and its age dependence-in galactosemic patients even when under strict dietary treatment.     

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized,double‐blind,parallel arm,placebo‐controlled trial

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow‐up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid–femoral pulse wave velocity (p = .002), left brachial–ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.     

Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

Evidence for current diagnostic criteria of diabetes mellitus

Diabetes mellitus is a non-communicable metabolic derangement afflicting several millions of individuals globally. It is associated with several micro and macrovascular complications and is also a leading cause of mortality. The unresolved issue is that of definition of the diagnostic threshold for diabetes. The World Health Organization and the American Diabetes Association (ADA) have laid down several diagnostic criteria for diagnosing diabetes and prediabetes based on the accumulating body of evidence.This review has attempted to analyse the scientific evidence supporting the justification of these differing criteria. The evidence for diagnosing diabetes is strong, and there is a concordance between the two professional bodies. The controversy arises when describing the normal lower limit of fasting plasma glucose (FPG) with little evidence favouring the reduction of the FPG by the ADA. Several studies have also shown the development of complications specific for diabetes in patients with prediabetes as defined by the current criteria though there is a significant overlap of such prevalence in individuals with normoglycemia. Large multinational longitudinal prospective studies involving subjects without diabetes and retinopathy at baseline will ideally help identify the threshold of glycemic measurements for future development of diabetes and its complications.