Hormonal
In Type 1 Diabetes, hyperglucagonemia (excess glucagon) is the primary cause of hyperglycemia and catabolic symptoms, rather than insulin deficiency alone.
For Type 1 Diabetics, managing blood sugar requires addressing high glucagon levels, not just injecting more insulin. Current insulin monotherapy often fails to suppress glucagon without causing hypoglycemia elsewhere. Therapies that suppress glucagon (like somatostatin analogs or leptin) may offer better stability than insulin alone.
Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes.
Why this rating
Strong mechanistic evidence from animal models (Gcgr-null mice, dogs) and human clamp studies, though human clinical trials for long-term glucagon suppression are noted as lacking.
Source
Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover
Roger H. Unger et al. · Journal of Clinical Investigation · 2012
DOI 10.1172/jci60016
More from this paper
- Glucagon receptor blockade or suppression prevents the catabolic consequences of insulin deficiency (hyperglycemia, ketoacidosis) in animal models.Strong
- Somatostatin infusion suppresses hyperglucagonemia and markedly reduces hyperglycemia in Type 1 Diabetic humans, even when insulin is reduced or discontinued.Good
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