Insulin analogues in the treatment of diabetes in pregnancy

Abstract

SUMMARYPregnancy affects both maternal and fetal metabolism, and even in non-diabetic women, it exerts a diabetogenic effect. Among pregnant women, 2% to 14% develop gestational diabetes. Pregnancy can also occur in women with preexisting diabetes, which may predispose the fetus to many alterations in organogenesis, restrict growth, and the mother, to some diabetes-related complications, such as retinopathy and nephropathy, or to acceleration of the course of these complications, if they are already present. Women with gestational diabetes generally start their treatment with diet and lifestyle changes; when these changes are not enough for optimal glycemic control, insulin therapy must then be considered. Women with type 2 diabetes using oral hypoglycemic agents are advised to change to insulin therapy. Those with preexisting type 1 diabetes should start intensive glycemic control. As basal insulin analogues have frequently been used off-label in pregnant women, there is a need to evaluate their safety and efficacy. The aim of this review is to report the use of both short-and long-acting insulin analogues during pregnancy and to enable clinicians, obstetricians, and endocrinologists to choose the best insulin treatment for their patients. Arq Bras Endocrinol Metab. 2012;56(7):405-14 Keywords Type 1 diabetes; type 2 diabetes; gestational diabetes; insulin analogues; insulin lispro; insulin aspart; insulin glulisine; insulin glargine; insulin detemir SUMÁRIO A gravidez afeta tanto o metabolismo materno quanto o fetal e, mesmo em mulheres não diabéticas, apresenta um efeito diabetogênico. Entre as mulheres grávidas, 2% a 14% desenvolvem o diabetes gestacional. A gravidez pode ocorrer também em mulheres já diabéticas, o que pode predispor o feto a muitas alterações na organogênese, restrição de crescimento e a mãe a algumas complicações relacionadas ao diabetes, tais como retinopatia e nefropatia, ou acelerar o curso dessas complicações se já estiverem presentes. Pacientes com diabetes gestacional geralmente iniciam seu tratamento com dieta e mudanças no estilo de vida; porém, quando essas medidas falham em atingir um controle glicêmico adequado, a insulinoterapia deve ser considerada. Pacientes com diabetes tipo 2 em uso de hipoglicemiantes orais são aconselhadas a iniciar o uso de insulina. Pacientes com diabetes tipo 1 preexistente devem iniciar um controle glicêmico estrito. Em função do fato de os análogos basais de insulina estarem sendo utilizados muito frequentemente off-label em pacientes grávidas, faz-se necessário avaliar sua segurança e eficácia nessa condição. O objetivo desta revisão é avaliar o uso de tais análogos, tanto de ação curta como prolongada, durante a gravidez, para possibilitar médicos clínicos, obstetras e endocrinologistas escolher o melhor regime terapêutico para suas pacientes. Arq Bras Endocrinol Metab. 2012;56(7):405-14 Descritores Diabetes tipo 1; diabetes tipo 2; diabetes

Use of Insulin Lispro Protamine Suspension in Pregnancy

“…In general, insulin analogs may reduce the risk of hypoglycemia and promote a more physiological glycemic profile than regular human insulin in pregnant women with T1D, T2D, or GDM [ 34 ]. However, there are a number of potential concerns associated with the use of these agents during pregnancy.…”

“…Although data from randomized controlled trials (RCTs) are limited, experience with insulin lispro and insulin aspart has generally indicated that these RAIAs produce similar outcomes to regular human insulin in pregnant women with T1D, T2D, or GDM [ 34 , 39 – 42 ]. These latter findings have led to the conclusion that there is no evidence of an adverse effect of these insulins on pregnancy or on the health of the fetus/newborn [ 34 , 36 , 37 , 41 , 43 , 44 ].…”

“…The long-acting insulin analogs (LAIAs) have potential benefits in the management of pregnancy in women with T1D because of their ability to mitigate the risk of nocturnal hypoglycemia and to provide and maintain the stringent glycemic targets needed in this population. A number of studies have shown that insulin glargine and insulin detemir are safe and promote good glycemic control during pregnancy [ 34 , 44 , 50 – 52 ], and both can be considered for use in pregnant women (Table 1 ) [ 53 , 54 ]. There is currently no clinical experience with insulin degludec in pregnant women, although animal studies have not revealed any embryotoxicity or teratogenicity differences between insulin degludec and regular human insulin [ 55 ].…”

“…Insulin lispro does not cross the placental barrier and is considered a useful treatment option for pregnant women with diabetes [ 34 ]. As discussed in the Pharmacology section, ILPS has the same binding properties as insulin lispro, and also has a stable and predictable pharmacological profile.…”

Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in gestational diabetes?

“…This pathology accounts for ~5% of pregnant women worldwide and it is associated with high risk of fetal perinatal alterations (e.g., macrosomia, insulin resistance) and higher incidence of diseases in the adulthood (e.g., GD, obesity, dyslipidemia, hypertension, metabolic syndrome) (Poston, 2010; Negrato et al, 2012). GD is associated with reduced maternal circulating T 4 levels in the first trimester of pregnancy.…”