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Our aim is to alleviate human suffering related to diabetes and its complications among those least able to withstand the burden of the disease. From 2002 to March 2017, the World Diabetes Foundation provided USD 130 million in funding to 511 projects in 115 countries.<br>For every dollar spent, the Foundation raises approximately 2 dollars in cash or as in-kind donations from other sources.<br>The total value of the WDF project portfolio reached USD 377 million, excluding WDF’s own advocacy and strategic platforms.
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Objectives • Discuss the safety of continuing pre-pregnancy medications • Decide when antihyperglycemic medication is required during pregnancy • Determine what antihyperglycemic medication to use • Discuss initial dosing and adjustment of dose • Discuss insulin administration, storage
Lipids and Blood pressure • Statins must be stopped • Preferably prior to pregnancy or • As soon as pregnancy determined • ACE inhibitors and ARBs (angiotensin II receptor blockers) must be stopped • Preferably prior to pregnancy or • As soon as pregnancy determined ACEI/ ARBs may cause renal failure in the fetus CDA, 2013 Kitzmiller, Block et al, 2008
Replacements • Dyslipidemia • Reduction of saturated fat intake, no trans fat intake, cholesterol intake < 200mg/day • Weight control • Physical activity • Hypertension • Reduce salt intake • Calcium channel blockers, labetalol, hydralazine and methyldopa. CDA, 2013
Triglycerides • Triglycerides may double by 20 weeks • Cholesterol, LDL and HDL may increase 10-20% • Initiate treatment if triglycerides over 1000mg/dl • Intensive glycemic control • Fish oil supplement Fibrates and niacin are best avoided during pregnancy Goldenberg, Benderly, Goldbourt, 2008 Kitzmiller, Block et al, 2008
Insulin • Indicated when target blood glucose levels not attained with diet and physical activity after 2 weeks • Human insulin should be used – less transfer of insulin antibodies • Rapid acting insulin analogues (lispro and aspart) have been shown to be safe in pregnancy • Improve postprandial levels • Lower risk of postprandial hypoglycemia • Fetal outcomes the same with human insulin (soluble) or rapid acting analogues
Insulin • Long acting insulin analogues • detemir has been approved for use in pregnancy • glargine has not yet been approved • Few studies on safety of long acting analogues in pregnancy • Usual recommendation is to use NPH or detemir as basal insulin • Premix insulins are an alternative but lack the flexibility of a basal bolus regimen
Starting insulin in GDM • If fasting high – start NPH or detemir at bedtime • If postprandial high – start soluble or rapid acting before meal. • Start with 4 units • Titrate 1-2 units/every 2 days until targets are reached • Educate • Administration • Storage • Hypoglycemia
Insulin Syringe • Correct syringe must be used for the strength of the insulin • if using 100u/1 ml insulin then must have a 100u/1ml syringe, • if using 40u/1ml insulin must have a 40u/1ml syringe. • Usually disposable – intended for 1 use only • Insulin pens are convenient alternatives to syringes but are more expensive • Easier to teach • Fewer mistakes with dosages
Insulin Practicalities Insulin practicalities • Storage • One month at room temperature once the vial has been opened or kept in fridge • Must never be frozen • Store away from source of heat • If refrigerator not available, store in clay pot • May be damaged by direct sunlight or vigorous shaking • Pre-drawn syringes can be kept for one month in fridge (provided power supply reliable)
Precautions Precautions • Insulin strength may vary (U40, U100) • Ensure the syringe matches the strength! • Clear insulins • Long acting insulin analogues • Regular/soluble insulin • Rapid acting insulin analogues • Cloudy insulin (should not be used if clumps do not dissolve on mixing • NPH or N • Premixed insulin • Identify and differentiate insulin type
Glucose lowering medications • Sulfonylurea – glibenclamide (glyburide) • Minimal transfer across the placenta • Not associated with neonatal hypoglycemia • Must be balanced with meals and snacks to prevent hypoglycemia • Higher incidence of pre-eclampsia • Good control achieved…but Jacobson et al . 2005
However… • Latest evidence suggests: • glibenclamide is associated with worse outcomes compared to insulin and metformin • Need more studies in this area Hence glibenclamide is not recommended in the routine management of GDM Feig, Moses, 2011 Balsells et al, 2015
Glucose lowering medications • Metformin • Does cross the placenta • Does not appear to have adverse effects on the fetus • May be used in polycystic ovarian syndrome to improve fertility and decrease spontaneous abortion rate
Metforminvs Insulin (MiG Trial) • Neonatal complications did not vary between the 2 subject groups. • Less severe hypoglycemia in the infants of mothers on metformin. • Women on metformin gained less weight • Preterm birth was more common in the metformin group, but there was no increase in other complications. • 76% of women who used metformin were more likely to say they would use metformin in a subsequent pregnancy than were women on insulin (27.2%). • 46.3% of women on metformin had to be on supplemental insulin as well. The conclusion of this study was that metformin was a safe option for GDM, and it was more agreeable to the patient. Rowan Hague Gao et al. 2008
However… • What is the effect on the babies? • Unknown as to whether the use of metformin during pregnancy is • Beneficial • Neutral • Deleterious • Need more studies in this area Metformin is therefore not recommended as a first line therapy for GDM Feig, Moses, 2011
Other oral agents • There is insufficient data on the use of other antidiabetic agents such as • meglitinides, • alpha glucosidase inhibitors, • thiazolidinediones, • GLP-1 agonists and DPP-4 inhibitors • The use of these agents in pregnancy cannot be recommended
Final word on oral agents • If a woman is on oral agents when diagnosed with GDM • Discontinue them • Start diet and exercise plan • Monitor blood glucose • Start insulin
References • Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical practice guidelines for the prevention and management of diabetes in Canada; Diabetes and pregnancy. Can J of Diabetes. 2013;37(suppl 1):S168-183. • Feig DS, Moses RG. Metformin during pregnancy. Diabetes Care. 2011;34:2329 • Goldenberg I, Benderly M, Goldbourt U. Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag. 2008 February;4(1):131–141. • Jacobson et al - Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization, American Journal of Obstetrics and Gynecology 2005 • Kitzmiller JL, Block JM, Catalano PM, et al. Managing preexisting diabetes for pregnancy: Summary of evidence and consensus recommendations for care. Diabetes Care. 2008;31(5):1060-1079. • Rowan JA, Hague WM, Gao W. et al. Metformin versus Insulin for the Treatment of Gestational Diabetes. NEJM 2008;358:2003-15