Poobalan Naidoo

Dose-response relationships of sulfonylureas: will doubling the dose double the response?

type 2 diabetes mellitus is currently a global health problem. Although the armamentarium of oral hypoglycemic agents is continuously expanding, sulfonylureas (SUs) are still extensively used for the management of type 2 diabetes mellitus. However, despite decades of use, there is controversy as to the dosing of SUs. Despite many dose-response relationship studies indicating that SUs should be prescribed at lower doses, their dose recommendations remain unchanged. Moreover, studies have demonstrated that high doses of SUs may result in a deterioration of glycemic control and increased frequency of protracted hypoglycemic episodes. In view of the controversial dose-response relationship of SUs, it is suggested that the dose of SUs be titrated against glycemic parameters of blood glucose and glycated hemoglobin.

Effects of Gliclazide Dose Escalation on Postprandial Hyperglycemia in Type 2 Diabetes Mellitus: A Prospective, Open-Label, Case-Controlled, Dose-Escalation Study

OBJECTIVES The aims of this study were to determine the effects of increasing doses of gliclazide on postprandial glucose excursions after a standardized breakfast and lunch, and to clarify the relationship between gliclazide dose and glucose response. METHODS This prospective, open-label, case-controlled, dose-escalation study was conducted at the Addington Hospital Diabetes Clinic, eThekwini/Durban, KwaZulu-Natal, South Africa. Male and female patients aged ≥18 years with type 2 diabetes mellitus (DM) and postprandial hyperglycemia (2-hour postprandial blood glucose [PPBG2 h] level, ≥11.1 mmol/L [≥200 mg/dL]) and receiving an oral hypoglycemic agent were eligible. After a 1-week washout period during which patients were asked to discontinue treatment with all oral hypoglycemic agents, baseline glycemic measurements were performed (fasting blood glucose, PPBG2 h, 6-hour postprandial blood glucose [PPBG6 h], mean blood glucose [MBG], plasma insulin, fasting serum fructosamine, and glycosylated hemoglobin). All patients subsequently received 2 weeks of oral treatment with each of 3 doses of gliclazide: 40, 80, and 160 mg/d. Glycemic parameters were measured at the end of each dosing interval. Adverse-effect monitoring included direct reporting of untoward effects to the resident medical practitioner, clinical examination, monitoring of home blood glucose records, hematology, and liver and kidney function tests. Compliance was assessed using pill counts, examination of diary entries, and patient interview. RESULTS Thirty-three patients were screened; 14 entered the dose-escalation phase. Thirteen patients completed the study (7 women, 6 men; mean [SD] age, 52.0 [11.1] years); 1 was withdrawn because of poor compliance. Dose escalation from 40 to 80 mg/d was associated with a significant change only in MBG (mean [SD], 11.3 [4.2] vs 10.0 [3.9] mmol/L [203.6 (75.7) vs 180.1 (70.3) mg/dL]; P<0.001). Dose escalation from 80 to 160 mg/d was associated with a significant change only in PPBG6 h (9.5 [4.2] vs 10.3 [4.1] mmol/L [171.1 (75.7) vs 185.6 (73.9) mg/dL]; P=0.018). No other significant changes in glycemic parameters between doses were found throughout the treatment period. No adverse effects were reported. CONCLUSIONS In this small study of gliclazide dose escalation in patients with type 2 DM and postprandial hyperglycemia, gliclazide 80 mg/d was associated with a reduction in postprandial hyperglycemia. Dose escalation from 80 to 160 mg/d was not found to be associated with additional clinical benefit. Based on these results, we recommend that gliclazide dose escalation to the maximum dose recommended by the manufacturer be guided by measures of glycemia. All doses were well tolerated.

Non-referral of potential organ donors in South Africa: insights, challenges and ethical dilemmas

Traditionally, minimal potential organ donor referrals emanate from general medicine departments. We use a clinical vignette to draw attention to challenges related to referral of potential organ donors from general internal medicine departments. In addition, we provide potential solutions to overcome challenges and reflect on the ethical issues of non-referral of potential organ donors. It is hoped that this paper will increase the awareness of organ donation in the medical fraternity in Africa and thus mitigate critical shortages of organs for transplantation.