Endocrine Abstracts

Alzheimer’s disease (AD) is a neurodegenerative disease that manifests itself in the gradual loss of cognitive and behavioral functions. In humans, glucagon is processed in pancreatic alpha cells located next to insulin-secreting beta cells, suggesting a local interaction. Glucagon is also produced in the intestinal L-cells and in small amounts in the hypothalamus. The main function of glucagon is to counteract the effects of insulin and thus maintain balanced blood glucose level. In addition, glucagon also has the same neuroprotective effect as insulin on lowering glutamate in the central nervous system in diabetic rats, although both hormones have the opposite effect on glucose levels. Glucagon reduces glutamate in the central nervous system, reduces neuronal cell damage and improves neurological scores in mice. This study focused on glucagon levels in non-diabetic women with AD compared to controls, as well as on the changes of glucagon levels after five years in controls.

Methods

We evaluated the fasting metabolic parameters and glucose tolerance in 70 controls (median of age 68.2 years) and 41 women with AD (median age 74.7 years), both groups without type 2 diabetes. A group of 37 controls was re-evaluated after 5 years. The data were processed by GLM ANOVA (Statgraphics 18 × 64).

Results

Women with AD and controls had a similar body composition (median BMI [kg/m²]: 25.7 (22.6, 29.4) vs . 27.7 (24.3, 30.2); P = 0.13), insulin resistance (median HOMA R: 1.74 (1.44, 2.74) vs . 2.05 (1.4, 3.67), P = 0.91) and insulin secretion (median HOMA F: 114 (79.8, 173) vs . 103 (78.8, 149), P = 0.1). Women with AD and controls had the same fasting glucose (median glucose [mmol/l]: 5.1 (4.8, 5.3) vs 5.3 (5, 5.8); P = 0.06), but women with AD had lower levels of glycated hemoglobin (median HbA1c [%]: 37 (35.3, 38.8) vs . 38 (37, 40.3); P < 0.01). Compared to controls, women with AD had significantly higher glucagon levels (median glucagon [pmol/l]: 51.1 (46.1, 57.3) vs . 41.5 (38.8, 46.5); P < 0.001). Long-term follow-up (5 years) of controls showed a decrease in glucagon levels with increasing age (P < 0.001).

Conclusion

Glucagon levels in women with AD are not associated with glucose tolerance or diabetes. Patients with AD have the same fasting blood glucose as controls, and even lower glycated hemoglobin (a long-term indicator of glucose metabolism). Women with AD could be resistant to glucagon, or it is a consequence of the brain’s protective mechanism. The grants: NV 18-01-00399, MH CZ-DRO (EU 00023761).