RESUMEN
Ever since the discovery of insulin a century ago, relentless attempts have been made to develop insulins that closely mimic the timeaction- profile of human physiologic insulin. The early basal insulins like neutral protamine Hagedorn (NPH), were intermediate-acting, with high risk of hypoglycemia. These primary limitations led to attempts at developing improved basal insulins with a longer duration of action. After several attempts at prolonging insulin action using phenol and structural modifications of the insulin hexamer, insulin glargine was developed in 1988. The superior and unique pharmacological properties, longer duration of action, and significantly lowered risk of hypoglycemia enabled insulin glargine to be distinguished from NPH as a better basal insulin, providing holistic glycemic control. The present review highlights the circumstances that led to the search of truly basal insulins, focusing on the journey of insulin glargine 100 U/mL (Gla-100).
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Glucemia , Humanos , Hipoglucemiantes , Insulina , Insulina Glargina , Insulina de Acción ProlongadaRESUMEN
BACKGROUND AND AIMS: Diabetes in tropical chronic pancreatitis (TCP), also known as fibrocalculous pancreatic diabetes (FCPD), is frequently seen at diagnosis. The aim of the present study was to determine the natural history of endocrine failure in TCP subjects without diabetes at baseline. METHODS: Of 73 TCP subjects without diabetes according to World Health Organization (WHO) criteria at baseline who were seen at an out-patient center, 54 (74.0%) underwent periodic oral glucose tolerance tests on follow up. Another 54 sex-matched, non-diabetic subjects without chronic pancreatitis served as controls. Baseline demographic and clinical characteristics were noted. RESULTS: After a median follow up of 5.0 years in TCP subjects and 7.0 years in controls, 27 of 54 TCP subjects (50%) developed diabetes compared with 14 of 54 controls (25.9%). Of the TCP subjects, those who developed diabetes on follow up were older (31 +/- 12 vs 23 +/- 11 years; P = 0.013), had a higher body mass index (21.7 +/- 4.4 vs 18.2 +/- 3.5 kg/m2; P = 0.004), higher 2 h post-load plasma glucose (8.8 +/- 1.9 vs 6.7 +/- 1.4 mmol/L; P < 0.001) and lower fecal chymotrypsin (2.1 +/- 1.2 vs 4.3 +/- 2.5 U/g; P < 0.001) at baseline compared with those who did not develop diabetes. The median time for the development of diabetes after diagnosis of TCP was 9.6 years (compared with 14.4 years among controls). Only 2 of 13 TCP subjects (15.4%) who had undergone surgical interventions during the normal glucose tolerance phase developed diabetes during follow up. CONCLUSIONS: In TCP, there is progressive deterioration of endocrine pancreatic function, with development of diabetes in 50% of patients upon follow up, suggesting that FCPD is merely a later stage in the course of TCP. Early surgery may prevent the development of diabetes in TCP subjects.