A tale of two sisters - delayed diagnosis of genetic hyperinsulinaemic hypoglycaemia.

Summary: Congenital hyperinsulinism is the leading cause of persistent hypoglycaemia in infants and children; however, it is uncommon to be diagnosed in adulthood. We describe the cases of two sisters who presented with hyperinsulinaemic hypoglycaemia aged 47 and 57 years old, who were subsequently diagnosed with compound heterozygous likely pathogenic variants in the ABCC8 gene, a known cause of monogenic congenital hyperinsulinism. We discuss the typical presenting features, investigation findings, and treatment strategies for patients with this condition. Learning Points: Congenital hyperinsulinism is a rare cause of hyperinsulinaemic hypoglycaemia diagnosed in adulthood. Clinical presentation is similar to an insulinoma, and imaging modalities may assist in differentiation. There are minimal medical therapies currently available for patients non-responsive to diazoxide (such as those with ABCC8 and KCNJ11 variants). Continuous glucose monitoring can be helpful in giving patients autonomy in managing their disease, as well as relieving anxiety and fear associated with hypoglycaemia.

Non-invasive measures of tissue autofluorescence are increased in Type 1 diabetes complications and correlate with a non-invasive measure of vascular dysfunction.

OBJECTIVE: To determine if ocular and skin autofluorescence, reflecting advanced glycation end-products, and vascular stiffness correlate in non-diabetic and Type 1 diabetic subjects and if levels differ by diabetes status. RESEARCH DESIGN AND METHODS: Patients with Type 1 diabetes (n = 69, 19 with and 50 without vascular complications) and 60 subjects without diabetes (control) had ocular and skin autofluorescence and pulse-wave analysis performed in the fasted state. Correlations between measures within groups used the Pearson or Spearman correlation-coefficient and measures between groups were compared by ANOVA. RESULTS: Lens and skin autofluorescence correlated in control (r = 0.58, P = 0.0001) and in Type 1 diabetes (r = 0.53, P = 0.001). Corneal autofluorescence correlated with lens (r = 0.53, r = 0.52, P = 0.0001) and skin autofluorescence (r = 0.34, P = 0.01 and r = 0.49, P = 0.00001) in control and Type 1 diabetes respectively. In Type 1 diabetes, small and large artery elasticity correlated inversely and systemic vascular resistance correlated positively with skin autofluorescence (all P = 0.001), and with lens and corneal autofluorescence (all P < 0.03). In Type 1 diabetes tissue advanced glycation end-products correlated with C-reactive protein and inversely with the estimated glucose disposal rate and with circulating advanced glycation end-product levels. Relative to non-diabetic subjects, lens, corneal and skin fluorescence were increased (all P < 0.001) and small artery elasticity was decreased in diabetes (P = 0.04). Lens, corneal and skin autofluorescence were greater (all P = 0.0001) in patients with Type 1 diabetes with complications compared to those without complications, but small artery elasticity did not differ significantly. CONCLUSIONS: Ocular and skin autofluorescence and vascular stiffness correlate in non-diabetic and Type 1 diabetes subjects and are increased in Type 1 diabetes. Tissue advanced glycation end-products correlate with vascular risk factors, including circulating advanced glycation end-products.

Effects of oestrogen and progesterone on age-related changes in arteries of postmenopausal women.

1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima-medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with oestrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90 postmenopausal women taking HRT and 91 not taking HRT participated in the study. The groups were similar for age, body mass index, numbers of smokers, physical activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was reduced and high-density lipoprotein-cholesterol was increased in the HRT group compared with the non-HRT group; low-density lipoprotein-cholesterol, triglyceride and lipoprotein (a) values were similar in these two groups. Results for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was significantly greater in men than in women and was related to age; SAC was higher in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group showed increased carotid stiffness compared with the HRT-E group. 6. There is an apparent protective effect of long-term oestrogen therapy on carotid IMT and age-related changes in arterial stiffness. Progestin does not alter the IMT effects but may adversely influence arterial stiffness.