Evidence-based treatment of hyperglycaemia with incretin therapies in patients with type 2 diabetes and advanced chronic kidney disease

Type 2 diabetes is the leading cause of chronic kidney disease (CKD). The prevalence of CKD is growing in parallel with the rising number of patients with type 2 diabetes globally. At present, the optimal approach to glycaemic control in patients with type 2 diabetes and advanced CKD (categories 4 and 5) remains uncertain, as these patients were largely excluded from clinical trials of glucose-lowering therapies. Nonetheless, clinical trial data are available for the use of incretin therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, for patients with type 2 diabetes and advanced CKD. This review discusses the role of incretin therapies in the management of these patients. Because the presence of advanced CKD in patients with type 2 diabetes is associated with a markedly elevated risk of cardiovascular disease (CVD), treatment strategies must include the reduction of both CKD and CVD risks because death, particularly from cardiovascular causes, is more probable than progression to end-stage kidney disease. The management of hyperglycaemia is essential for good diabetes care even in advanced CKD. Current evidence supports an individualized approach to glycaemic management in patients with type 2 diabetes and advanced CKD, taking account of the needs of each patient, including the presence of co-morbidities and concomitant therapies. Although additional studies are needed to establish optimal strategies for glycaemic control in patients with type 2 diabetes and advanced CKD, treatment regimens with currently available pharmacotherapy can be individually tailored to meet the needs of this growing patient population.     

Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions,biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research.

Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.

Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.

Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.

Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses.     

The effect of acute hyperglycaemia on QTc duration in healthy man

Aims/hypothesis. Prolongation of heart rate-adjusted QT (QTc) is associated with an increased risk of coronary heart disease and sudden death. The objective of this study was to investigate whether acute increases of plasma glucose concentrations in healthy subjects could influence QTc and QTc dispersion. Methods. Plasma glucose concentrations were quickly raised to 15 mmol/l in 20 healthy subjects (10 men/10 women) and maintained for 2 h. On another occasion, and in random order, all subjects underwent the same hyperglycaemic clamp as above and an infusion of the somatostatin analogue octreotide (25 μg as iv bolus followed by a 0.5 g/min infusion) to block the release of endogenous insulin. Results. Systolic and diastolic blood pressures, heart rate and plasma catecholamine concentrations showed significant increases (p < 0.05) starting after 60 min of hyperglycaemia. QTc, QTc dispersion and PR interval also showed significant increments at 120 min of the hyperglycaemic clamp. The infusion of octreotide did not influence QTc duration, QTc dispersion, PR interval and the haemodynamic effects of acute hyperglycaemia. Conclusion/interpretation. The results show that acute hyperglycaemia produces significant increments of QTc and QTc dispersion in normal subjects. In this context, endogenously released insulin during acute hyperglycaemia seems to play a minor part. [Diabetologia (2000) 43: 571–575] Received: 12 October 1999 and in revised form: 24 January 2000     

Effect of short-term hyperglycaemia on haemodynamics in type 1 diabetic patients

OBJECTIVES: Mechanisms underlying glucose-mediated development and progression of diabetic complications are incompletely understood. We tested the impact of short-term hyperglycaemia on systemic blood pressure and regulatory hormones in type 1 diabetic patients. DESIGN AND METHODS: We included 18 patients [13 men, mean (SEM) diabetes duration 10 (1) years] without signs of autonomic neuropathy or renal complications in a randomized single-blinded cross-over trial using insulin-glucose clamp technique. Patients were clamped for 90 min to blood glucose of 5 mmol L(-1) (euglycaemia) and 15 mmol L(-1) (hyperglycaemia) in random order. Blood pressure was measured noninvasively every 5 min (Takeda TM2421 device). Regulatory hormones were determined at the end of each clamp period. RESULTS: Systolic blood pressure increased [mean (95% CI)] 3 (1, 5) mmHg during hyperglycaemia from 123 (SEM 2) during euglycaemia, P=0.01. Diastolic blood pressure remained unchanged at 78 (2) mmHg. Hyperglycaemia reduced plasma concentrations of: renin [14 (4, 23)%, P=0.02], angiotensin II [17 (8, 25)%, P<0.01] and adrenaline [20 (10, 29)%, P<0.01]. Plasma concentration of atrial natriuretic peptide increased by 11 (6, 17) pg mL(-1) (P<0.01) from 43 (2) pg mL(-1). We calculated a median (range) increase in extracellular volume and plasma volume (PV) of 2.6 (0.7-5.3)% and 5.0 (-4.7 to 8.6)%, respectively. CONCLUSIONS: In type 1 diabetic patients without signs of autonomic neuropathy short-term hyperglycaemia induced a modest increase in systolic blood pressure and suppression of the renin-angiotensin system, possibly caused by PV expansion because of fluid shift from intra- to extracellular compartment.     

Perioperative evaluation of glycaemic status in neck dissection: a retrospective analysis at a single hospital centre

Diabetes mellitus is generally considered a risk factor for impaired wound healing. This study aimed to evaluate the glycaemic status of patients undergoing neck dissection and describe its impact on postoperative outcomes, especially wound healing. A retrospective analysis was performed of the preoperative, intraoperative, and postoperative glycaemic data obtained from the medical charts of 60 adult patients who had undergone 64 neck dissections. Nine of the 64 procedures were performed in diabetic patients (14.1%). The average glucose values were: preoperative 5.99 ± 1.25 mmol/l, intraoperative 8.90 ± 2.62 mmol/l, and postoperative 10.01 ± 2.49 mmol/l. All registered preoperative hyperglycaemia cases (eight cases) were diabetic. Postoperative insulin therapy was done in 14 procedures (21.9%). Wound healing complications were found in five patients (7.8%); there was no wound infection. There was no association of wound healing complications with preoperative diabetic status (P = 1.000), preoperative glucose control (P = 1.000), preoperative (P = 0.469), intraoperative (P = 0.248), and postoperative (P = 0.158) glucose values, or with postoperative glucose control (P = 0.577). These data do not support the association of stress-induced hyperglycaemia or diabetes mellitus with postoperative wound healing problems in neck dissection.