Practice Update: Endocrinology | Volume 1. Number 2. 2016

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EXPERT COMMENTARY Findings consistent withmany prior studies By Dr Camille Powe I n this large cohort study using

Association of maternal overweight and obesity with risk of pre-eclampsia in women with diabetes Diabetologia Take-home message • In this population-based cohort study in Sweden, researchers investigated the association of maternal overweight (BMI, 25–29.9 kg/m 2 ) and obesity (>30 kg/m 2 ) with pre-eclampsia in women with diabetes. Pre- eclampsia was more likely in women with type 1 and type 2 diabetes (OR, 5.74 and 2.11, respectively) compared with women without diabetes. Maternal overweight and obe- sity increased the risk of pre- eclampsia in women without diabetes (OR, 1.69 and 3.22 for overweight and obesity) and women with type 1 diabe- tes (OR, 1.17 and 1.48) but not in women with type 2 diabetes (OR, 0.84 and 1.23). • Maternal overweight and obe- sity increased the likelihood of pre-eclampsia in women without diabetes and women with type 1 diabetes but not in women with type 2 diabetes. In order to reduce the risk of pre-eclampsia, women should strive for a normal weight pre-pregnancy. AIMS/HYPOTHESIS Women with type 1 or type 2 diabetes are at increased risk of pre-eclampsia. Overweight and obesity are associated with an increased risk of pre-eclampsia in women without diabetes. The aim of the study was to investigate the impact of maternal overweight and obesity on the risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. METHODS In a population-based co- hort study including singleton births in Sweden, we estimated the risk of pre-eclampsia among women with type 1 diabetes (n =7062) and type 2 diabetes (n=  886), and investigated whether maternal overweight (BMI 25–29.9 kg/m 2 ) and obesity (BMI ≥30.0 kg/m 2 ) modified the risk. Logistic regression analyses were used to estimate crude and adjusted ORs with 95% CIs, using women without diabetes as the reference group (n  =  1,509,525). RESULTS Compared with women without diabetes, the adjusted ORs for pre-eclampsia in women with type 1 and type 2 diabetes were 5.74 (95% CI 5.31, 6.20) and 2.11 (95% CI 1.65, 2.70), respectively. The corresponding risks of pre- eclampsia combined with preterm birth were even higher. Risks of pre- eclampsia increased with maternal overweight (BMI 25–29.9 kg/m 2 ) and obesity (BMI ≥30.0 kg/m 2 ), fore- most in women without diabetes, to a lesser extent in women with type 1 diabetes but not in women with type 2 diabetes. CONCLUSIONS/INTERPRETATION Maternal overweight and obesity increased risks of pre-eclampsia in women with type 1 diabetes but not in women with type 2 diabetes. Even so, considering associations between maternal BMI and over- all maternal and offspring risk, all women (with and without diabetes) should aim for a normal weight be- fore pregnancy. Maternal overweight and obe- sity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. Diabetologia 2016 Jul 01;[Epub ahead of print], Persson M, Cnattingius S, Wikström AK, et al.

mechanisms by which diabetes and obesity increase preeclampsia risk in pregnant women are likely to be simi- lar to the non-pregnant state, where both conditions are associated with hypertension and proteinuria (the cardinal signs of preeclampsia). Randomised trials in women with milder degrees of glucose intolerance (gestational diabetes) demonstrate that glycaemic control reduces preec- lampsia risk. This study suggests that reducing pre-pregnancy body weight may further reduce preeclampsia risk

preeclampsia risk (5-fold), while type 2 diabetes carried a 2-fold increased risk, compared with to women without diabetes. Early preg- nancy overweight or obesity further increased the risk of preeclampsia in type 1, but not type 2 diabetes. It is important to note that 82% of women with type 2 diabetes studied were overweight or obese, thus the lack of an effect of early pregnancy BMI on preeclampsia in this group does not negate overweight/obesity as a preeclampsia risk factor. The

in women with type 1 diabetes. Al- though no association was observed between early pregnancy body mass index and preeclampsia in women with type 2 diabetes, accumulated evidence suggests that reduction of body weight prior to pregnancy in type 2 diabetes leads to improved glycae- mic control – this itself is expected to reduce the risk of preeclampsia. Dr Camille Powe is Endocrinology Fellow at Massachusetts General Hospital.

whole-population registry data from Sweden, investigators examined the risk of preeclampsia associated with diabetes and ex- cess body weight. Consistent with many prior studies, the authors find that type 1 diabetes, type 2 diabetes, and overweight/obesity are strong independent risk factors for preeclampsia. In this study, type 1 diabetes conferred the highest increase in

ADVERTORIAL

Maintaining healthy weight and glycaemic control in adolescents with type 1 diabetes: Does insulin choice matter?

Insulin omission and weight in adolescents: ISPAD recommendations Deliberate insulin omission is acknowledged in the ISPAD Clinical Practice Consensus Guidelines as a common weight control strategy in type 1 diabetes. 1 The guidelines recommend regular monitoring of adolescents to identify weight loss or inappropriate weight gain early and recommend that deliberate insulin omission should be considered as a cause in any adolescent experiencing weight loss, and in those with high HbA 1c , irrespective of weight. 1 Deliberate insulin omission should be considered as a cause in any adolescent experiencing weight loss and in those with high HbA 1c , irrespective of weight – ISPAD 2014 1 Weight effects of Levemir ® in type 1 diabetes clinical studies Two parallel-group, randomised controlled trials have examined weight changes in children and adolescents treated with Levemir ® or NPH. 11,12 In each study, a significant difference in weight outcome was observed between treatment groups, with less increase in Body Mass Index (BMI) 12 and closer-to-normal weights 11 reported with Levemir ® versus NPH. Results from paediatric studies are complemented by a body of clinical evidence in adults with type 1 diabetes. In adults, significantly less weight gain has been consistently reported with Levemir ® versus NPH across several parallel-group, randomised controlled trials (p<0.05). 3–10 Insulin choice in adolescence Unwanted weight gain in type 1 diabetes may affect treatment adherence and glycaemic control, which in turn promotes the development of diabetes complications. 13,14 Given these things, Levemir ® may have an important role to play in the treatment of young patients with type 1 diabetes. 2

At every age, children with type 1 diabetes are heavier than their peers without diabetes. 1 While it had previously been assumed that weight gain was an inevitable consequence of insulin therapy, a large body of evidence indicates that Levemir ® (insulin detemir) has weight-sparing effects. 2–12 These weight-sparing effects were examined in a recent review. 2

It had previously been assumed that weight gain was an inevitable consequence of insulin therapy – Russell-Jones et al , 2015 2

The 2015 review concluded that weight-sparing with Levemir ® is likely due to a combination of processes, each influenced directly or indirectly by CNS-mediated reduced energy intake. 2 Of the hypotheses presented, three were able to account for both short-term and long-term weight-sparing effects. 2 Food intake hypothesis Reduced caloric intake during Levemir ® treatment has been consistently observed in animal and human studies. 2 Central nervous system (CNS) hypothesis Levemir ® may enter the brain and directly affect the CNS or may influence the CNS indirectly via peripheral activity. Insulin activity within the brain is associated with increased satiety and improved weight control. 2 Hepatoselective hypothesis Compared with NPH, Levemir ® has a greater effect on the liver and less of an effect on the peripheral tissues. This may lead to a suppression of hepatic glucose output and less peripheral lipogenesis. 2 Weight control behaviours in adolescents with type 1 diabetes A recently-published, 14-year follow up study of 126 girls with type 1 diabetes observed that behaviours aimed at weight loss are persistent and recurrent during adolescence and early adulthood. 13 Among 71 individuals assessed at final follow up, the most commonly reported behaviours were dieting (33.8%), insulin omission for weight loss (26.8%), excessive exercise for weight control (25.4%) and self-induced vomiting (8.5%). 13

My type of treatment 15 For PBS information refer to the Primary advertisement. Please review the Product Information before prescribing. The Product Information is available on page 5 of this journal, or can be accessed at www.novonordisk.com.au. References: 1. Smart CE et al. Pediatr Diabetes 2014;15(Suppl 20):135–53. 2. Russell-Jones D et al. Diabetes Obes Metab 2015;17(10):919–27. 3. Bartley PC et al. Diabet Med 2008;25(4):442–9. 4. De Leeuw I et al. Diabetes Obes Metab 2005;7(1):73–82. 5. Hermansen K et al. Diabetologia 2004;47(4):622–9. 6. Home P et al. Diabetes Care 2004;27(5):1081–7. 7. Pieber TR et al. Diabet Med 2005;22(7):850–7. 8. Russell-Jones D et al. Clin Ther 2004;26(5):724–36. 9. Standl E et al. Diabetes Technol Ther 2004;6(5):579–88. 10. Vague P et al. Diabetes Care 2003;26(3):590–6. 11. Thalange N et al. Diabet Med 2013;30(2):216–25. 12. Robertson KJ et al. Diabet Med 2007;24(1):27–34. 13. Colton PA et al. Diabetes Care 2015;38(7):1212–7. 14. Cameron FJ et al. Pediatr Diabetes 2014;15 Suppl 20:245–56. 15. Levemir ® Approved Product Information (Oct 2013) Novo Nordisk Pharmaceuticals Pty Ltd. ABN 40 002 879 996. Level 3, 21 Solent Circuit, Baulkham Hills, NSW 2153. NovoCare ® Customer Care Centre (Australia) 1800 668 626. www.novonordisk.com.au. ® Registered trademark of Novo Nordisk A/S. U/LM/0516/0104c. INK2592-09_CEN. July 2016.

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