RESUMEN
OBJECTIVE: This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Primary care records in England (n = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA1c ≥7% [53 mmol/mol]) and insulin requirement. RESULTS: We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38-2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47-1.82]; P < 0.001). The 559 cases of diabetes following pancreatic disease were mostly classified by clinicians as type 2 diabetes (87.8%) and uncommonly as diabetes of the exocrine pancreas (2.7%). Diabetes following pancreatic disease was diagnosed at a median age of 59 years and BMI of 29.2 kg/m2. Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3-2.2]; P < 0.001) compared with type 2 diabetes. Insulin use within 5 years was 4.1% (3.8-4.4) with type 2 diabetes, 20.9% (14.6-28.9) with diabetes following acute pancreatitis, and 45.8% (34.2-57.9) with diabetes following chronic pancreatic disease. CONCLUSIONS: Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.
Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Páncreas Exocrino/fisiopatología , Pancreatitis/epidemiología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Índice de Masa Corporal , Enfermedad Crónica , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inglaterra , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Hiperglucemia/tratamiento farmacológico , Incidencia , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Obesity is a growing epidemic, and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs that aim to cause effective weight loss with minimal side effects. Both glucagon and GLP-1 reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. We hypothesized that the combination of both peptides, administered at doses that are individually subanorectic, would reduce appetite, while GLP-1 would protect against the hyperglycemic effect of glucagon. In this double-blind crossover study, subanorectic doses of each peptide alone, both peptides in combination, or placebo was infused into 13 human volunteers for 120 min. An ad libitum meal was provided after 90 min, and calorie intake determined. Resting energy expenditure was measured by indirect calorimetry at baseline and during infusion. Glucagon or GLP-1, given individually at subanorectic doses, did not significantly reduce food intake. Coinfusion at the same doses led to a significant reduction in food intake of 13%. Furthermore, the addition of GLP-1 protected against glucagon-induced hyperglycemia, and an increase in energy expenditure of 53 kcal/day was seen on coinfusion. These observations support the concept of GLP-1 and glucagon dual agonism as a possible treatment for obesity and diabetes.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Péptido 1 Similar al Glucagón/farmacología , Glucagón/farmacología , Adulto , Estudios Cruzados , Glucagón/administración & dosificación , Péptido 1 Similar al Glucagón/administración & dosificación , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/prevención & control , Masculino , Adulto JovenRESUMEN
Glucagon and glucagon-like peptide (GLP)-1 are the primary products of proglucagon processing from the pancreas and gut, respectively. Giving dual agonists with glucagon and GLP-1 activity to diabetic, obese mice causes enhanced weight loss and improves glucose tolerance by reduction of food intake and by increase in energy expenditure (EE). We aimed to observe the effect of a combination of glucagon and GLP-1 on resting EE and glycemia in healthy human volunteers. In a randomized, double-blinded crossover study, 10 overweight or obese volunteers without diabetes received placebo infusion, GLP-1 alone, glucagon alone, and GLP-1 plus glucagon simultaneously. Resting EE--measured using indirect calorimetry--was not affected by GLP-1 infusion but rose significantly with glucagon alone and to a similar degree with glucagon and GLP-1 together. Glucagon infusion was accompanied by a rise in plasma glucose levels, but addition of GLP-1 to glucagon rapidly reduced this excursion, due to a synergistic insulinotropic effect. The data indicate that drugs with glucagon and GLP-1 agonist activity may represent a useful treatment for type 2 diabetes and obesity. Long-term studies are required to demonstrate that this combination will reduce weight and improve glycemia in patients.