Glucokinase activating mutation causing hypoglycaemia diagnosed late in adult who fasts for Ramadhan

Summary Activating mutation of glucokinase gene (GCK) causes resetting of insulin inhibition at a lower glucose threshold causing hyperinsulinaemic hypoglycaemia (GCK-HH). This is the first reported case who tolerated years of regular fasting during Ramadhan, presenting only with seizure and syncope now. We describe a case with GCK gene variant p.T65I diagnosed in a 51-year-old woman with hypoglycaemia unawareness even at glucose level of 1.6 mmol/L. Insulin and C-peptide levels during hypoglycaemia were suggestive of hyperinsulinism, but at a day after intravenous glucagon, hypoglycaemia occurred with low insulin and C-peptide levels, pointing against insulinoma as the underlying aetiology. Imaging studies of the pancreas and calcium arterial stimulation venous sampling were unremarkable. A review of old medical records revealed asymptomatic hypoglycaemia years ago. Genetic testing confirmed activating mutation of GCK. Hypoglycaemia was successfully controlled with a somatostatin analogue. This case highlights the importance of consideration of genetic causes of hypoglycaemia in adulthood, especially when imaging is uninformative. Learning points Consider genetic causes of endogenous hyperinsulinism hypoglycaemia in adulthood, especially when imaging is uninformative. Late presentation of activating mutation of GCK can occur because of hypoglycaemia unawareness. Long-acting somatostatin analogue may be useful for the treatment of activating mutation of GCK causing hypoglycaemia. Depending on the glucose level when the blood was taken, and the threshold of glucose-stimulated insulin release (GSIR), the serum insulin and C-peptide levels may be raised (hyperinsulinaemic) or low (hypoinsulinaemic) in patients with activating mutation of GCK. Glucagon may be useful to hasten the process of unmasking the low insulin level during hypoglycaemia below the GSIR level of which insulin released is suppressed.

Islet Transplantation in Type 1 Diabetes Mellitus With Hypoglycaemic Unawareness

The primary indications for ICT in T1DM are glycaemic lability and hypoglycaemia unawareness. ICT is an effective, minimally invasive treatment for stabilising glycaemic control, correcting hypoglycaemia unawareness and improving quality of life even when exogenous insulin-independence is not fully achieved. However, the majority of patients require two islet transplants. The need for lifelong immunosuppression, in combination with the limited availability of donor pancreases, currently limits the wider application of ICT, particularly in the treatment of children newly diagnosed with T1DM. New technologies, including macro- and micro-encapsulation, xenotransplantation and stem cell-derived b cells offer hope for the future of b cell replacement. Yet, until then, a continued focus on optimising donor pancreases, improving the islet isolation procedure, use of novel immunosuppression, and understanding the mechanisms behind graft loss is required.

Prevalence of hypoglycaemia in a random population after Roux-en-Y gastric bypass after a meal test

Objective Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. Design This is a cross-sectional study of patients 4 years after primary RYGB. Methods From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L. Results The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001). Conclusion In a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.