Elisabeth Bernroider

Hepatic glucose metabolism in humans: its role in health and disease

The liver is mainly responsible for maintaining normal concentrations of blood glucose by its ability to store glucose as glycogen and to produce glucose from glycogen breakdown or gluconeogenic precursors. During the last decade, new techniques have made it possible to gain further insight into the turnover of hepatic glucose and glycogen in humans. Hepatic glycogen varies from approximately 200 to approximately 450 mM between overnight fasted and postprandial conditions. Patients with type-1 diabetes (T1DM), type 2 diabetes (T2DM) or partial agenesis of the pancreas exhibit increased endogenous glucose production and synthesize only 25-45% of hepatic glycogen compared with non-diabetic humans. This defect can be partly restored in T1DM by combined long- and short-term optimized treatment with insulin. In T2DM, increased gluconeogenesis was identified as the main cause of elevated glucose production and fasting hyperglycaemia. These patients also exhibit augmented intracellular lipid accumulation which could hint at a link between deranged glucose and lipid metabolism in insulin-resistant states.

Cerebral glutamate metabolism during hypoglycaemia in healthy and type 1 diabetic humans

Background  The mechanisms responsible for the progressive failure of hypoglycaemia counterregulation in long‐standing type 1 diabetes are poorly understood. Increased brain glucose uptake during hypoglycaemia or alterations of brain energy metabolism could effect glucose sensing by the brain and thus contribute to hypoglycaemia‐associated autonomic failure.

Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes.

Objectives: The aim of this study was to examine hormonal counterregulation during insulin-induced hypoglycemia in type-1 diabetic patients during long-term near normoglycemic insulin therapy and intensive clinical care. Methods: Type-1 diabetic patients (age 35.3 ± 2 years, body mass index 22.8 ± 1 kg·m–2, mean diabetes duration 13.6 (11–17 years), mean HbA1c during the last year 6.6 ± 0.1%) and nondiabetic subjects were studied during (0–120 min) and after (120–240 min) hypoglycemic (3.05 mmol/l) hyperinsulinemic (∼330 pmol/l) clamp tests. Results: During hypoglycemia peak plasma concentrations of glucagon (199 ± 16 vs. 155 ± 11 ng/l, p < 0.05), epinephrine (4,514 ± 644 vs. 1,676 ± 513 pmol/l, p < 0.001), norepinephrine (2.21 ± 0.14 vs. 1.35 ± 0.19 nmol/l, p < 0.01) and cortisol (532 ± 44 vs. 334 ± 61 nmol/l) were reduced in the diabetic patients. Plasma lactate did not change from baseline values (0.51 ± 0.06 mmol/l) in diabetic but doubled in healthy subjects (1.13 ± 0.111 mmol/l, p < 0.001 vs. control). During the posthypoglycemic recovery period plasma concentrations of free fatty acids were higher in diabetic patients at 240 min (1.34 ± 0.12 vs. 2.01 ± 0.23 mmol/l, p < 0.05). Conclusion: Despite long-term near physiologic insulin substitution and the low incidence of hypoglycemia, hormonal hypoglycemia counterregulation was impaired in type-1 diabetic patients after a diabetes duration of more than 10 years.