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19OL044a – Olson Center for Women’s Health Webinar Series:

Sugar High: A Review of Pre-Diabetes, Diabetes and Gestational Diabetes

The webinar will begin in a moment.• To receive Continuing Nursing Education contact hours, please review

the Program Announcement form.• Upon completion of the activity, continue to the same link you used to

register (https://app1.unmc.edu/cne/19Ol044a/evaluation.cfm), then click on the “Evaluation” tab

• After completing the Evaluation, your certificate will be available to print or save.

Sugar HighA review of pre-diabetes, diabetes and

gestational diabetes

Lisa Carter, PA-CNebraska Medicine Department of Diabetes, Endocrinology and Metabolism

Objectives

Differentiate between pre-diabetes, diabetes and gestational diabetes

Describe complications associated with pre-diabetes, diabetes and gestational diabetes

Compare treatment options for pre-diabetes, diabetes and gestational diabetes

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Definition

Diabetes mellitus is a group a metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both.

Normally:

InsulinGlucose Glucose

Classification of Diabetes

Type 15-10%

• Insulin deficiency due to beta cell destruction

• 95% autoimmune, 5% idiopathic

Type 2>90%

• Progressive loss of beta cell function on the background of insulin resistance

Gestational

• Diagnosed in 2nd or 3rd

trimester• Insulin

resistance mediated by placental hormone production

• Pancreatic function insufficient to overcome this resistance

Misc

• Monogenic diabetes syndromes

• Disease of the exocrine pancreas

• Drug or chemical induced diabetes

• Endocrin-opathies

Type 1 Diabetes (T1DM)

Glucose Insulin Glucose

Pathophysiology of T1DM

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Clinical Presentation of T1DM

Usually young

Rapid progression

Weakness, fatigue

Polyuria, polydipsia, polyphagia

Thin or losing weight

Diabetic Ketoacidosis

Diagnosis of T1DM

Plasma glucose ≥ 200, rather than A1c, should be used to diagnose the acute onset of Type 1 diabetes in individuals with symptoms of hyperglycemia

Differentiation between T1DM and T2DM Presence of antibodies Clinical presentation Family history Insulin and C-peptide levels

Treatment of T1DM

REQUIRE INSULIN TO LIVE Multiple daily injections

Continuous insulin infusion (pump)

Treatment of T1DM

Insulin dosing 0.4-1.0 units/kg/day = total daily insulin (basal +

bolus)

50% = basal insulin dose, 50% = prandial insulin dose

Rapid acting analogs reduced risk of hypoglycemia

Carb counting Allows a better match of prandial insulin dose to

carb intake

500/TDD of insulin = # of grams of carbohydrate covered by 1 unit of insulin

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Classification of Diabetes

Type 15-10%

• Insulin deficiency due to beta cell destruction

• 95% autoimmune, 5% idiopathic

Type 2>90%

• Progressive loss of beta cell function on the background of insulin resistance

Gestational

• Diagnosed in 2nd or 3rd

trimester• Insulin

resistance mediated by placental hormone production

• Pancreatic function insufficient to overcome this resistance

Misc

• Monogenic diabetes syndromes

• Disease of the exocrine pancreas

• Drug or chemical induced diabetes

• Endocrin-opathies

Type 2 Diabetes (T2DM)

Glucose Insulin Glucose

Clinical Presentation of T2DM

Adult-onset (though increasingly seen in childhood)

Overweight/Obese

Acanthosis nigricans

Asymptomatic

Blurred vision

Numbness, tingling or pain in feet

Recurrent infections

Risk Factors for T2DM

Risk Factors: Age 45 or older Have a first degree relative with T2DM Physically active < 3 days per week Overweight Metabolic syndrome History of gestational diabetes Women with polycystic ovarian syndrome African American, Hispanic/Latino American,

Native American, Alaska Native, Asian Pacific Islander

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Screening for T2DM

Who should be screened? Anyone with 2+ risk factors

Women with a history of GDM should be screened lifelong at least every 3 years

For all other people, screening should begin at age 45 and should be repeated at least every 3 years depending on results and risk factors

Pre-Diabetes

Pre-diabetes is characterized by glucose levels that do not meet the criteria for diabetes but are too high to be considered normal.

Treatment of Pre-Diabetes

Goal: prevent progression to diabetes

The Diabetes Prevention Program (DPP) 7% weight loss goal through healthy diet

150 minutes of moderate intensity physical activity per week

www.cdc.gov/diabetes/prevention/lifestyle-program

Metformin

Screen at least annually for T2DM

Treatment of T2DM

Diabetes self management education

Lifestyle modifications Healthy Diet

Exercise

Weight loss

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Efficacy Hypoglycemia Weight change

ASCVD CHF Progression of DKD

Dosing/use considerations

Additional considerations

Metformin High No Neutral(possible loss)

Potential benefit Neutral Neutral Contraindicated with eGFR < 30

GI side effectsPotential for B12 deficiency

SGLT-2 inhibitors Intermediate No Loss Benefit: Empagliflozin, Canagliflozin

Benefit: Empagliflozin, Canagliflozin

Benefit: Empagliflozin, Canagliflozin

Canagliflozin: not rec if eGFR < 45Dapagliflozin: not rec if eGFR <60Empagliflozin: contraindicated if eGFR < 30

Risk of amputation, bone fractures (Canagliflozin)DKA riskGU infection riskVolume depletion/hypotension

GLP-1 RA High No Loss Neutral: Lixisenatide, Exenatide extended release

Benefit: Liraglutide, Semaglutide

Neutral Benefit:Liraglutide, Semaglutide

Exenatide: Not indicated if eGFR < 30Lixisenatide: caution if eGFR < 30Increased risk of side effects in people with renal impairment

Risk of thyroid C-cell tumorsGI side effects riskInjection sitereactions riskPancreatitis risk

DPP-4 inhibitors Intermediate No Neutral Neutral Potential risk: saxagliptin, alogliptin

Neutral Renal dose adjustment required

Pancreatitis riskJoint pain

TZD High No Gain Potential benefit: Pioglitazone

Increased risk Neutral No dose adjustment required.Generally not recommended in renal impairment due to potential for fluid retention.

CHF risk (Pioglitazone, Rosiglitazone)Fluid retention riskBone fracture riskBladder cancer risk (Pioglitazone)

Sulfonylureas High Yes Gain Neutral Neutral Neutral Glyburide not recommended. Use caution to avoid hypoglycemia

FDA warning of risk of CV mortality with older medication (Tolbutamide)

Insulin Highest Yes Gain Neutral Neutral Neutral Lower doses requiredwith a decrease in eGFR

Injection site reactionsHypoglycemia risk

Glycemic Targets for Diabetes

A1c < 7% reduces risk of microvascular complications

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Complications of T1DM and T2DM

Chronic Complications

Macrovascular Complications

Cardiovascular disease People with diabetes are twice as likely to have heart

disease as people without diabetes – and at an earlier age.

Cerebrovascular disease People with diabetes are twice as likely to have a

stroke as people without diabetes – and at an earlier age.

Peripheral vascular disease Diabetes is the leading cause of lower limb

amputations in the U.S.

Estimated $37.3 billion in cardiovascular-related spending per year associated with diabetes.

Estimation of 10 year ASCVD risk http://tools.acc.org/ASCVD-Risk-Estimator-Plus

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Macrovascular Complications

Control individual modifiable cardiovascular risk factors Glucose control Hypertension Hyperlipidemia Smoking Cessation Weight management

Aspirin therapy For those with known ASCVD

Treat with anti-hyperglycemic medications that have cardiovascular benefit SGLT-2 inhibitors: Empagliflozin and Canagliflozin GLP-1 RA: Liraglutide, Semaglutide

Microvascular Complications:Retinopathy In 2005-2008, 4.2 million adults with

diabetes aged 40 years or older had diabetic retinopathy

Leading cause of adult-onset blindness in the U.S.

Screening: Annual eye exam Within 5 years of diagnosis of T1DM

At diagnosis of T2DM

Pre-pregnancy or in 1st trimester if pre-existing DM

Microvascular Complications: Retinopathy Non-proliferative retinopathy

Retinal capillaries leak proteins, lipids or red cells into the retina which causes Micro aneurysms, dot hemorrhages, exudates and retinal edema

Proliferative retinopathy Small vessel occlusion causes retinal

hypoxia which stimulates new vessel growth

Vision is usually normal until vitreous hemorrhage or retinal detachment occur

Microvascular Complications: Retinopathy

TreatmentGlycemic, blood pressure and

cholesterol control

Panretinal laser photocoagulation

Intravitreous injections of anti-vascular endothelial growth factor (anti-VEGF)

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Microvascular Complications:Nephropathy Leading cause of chronic kidney disease

in the U.S. Screening: Annual urine albumin-to-

creatinine ratio in T1DM ≥ 5 years everyone with T2DM everyone with co-morbid hypertension

Diagnosis Urine albumin-to-creatinine ratio > 30

μg/mg is abnormal 2+ abnormal readings over 3-6 months

Microvascular Complications: Nephropathy

Treatment Optimize glucose control

Consider SGLT-2 inhibitor or GLP-1 agonist shown to reduce progression of CKD

Control hypertension Treat with ACE inhibitor or ARB

(contraindicated in pregnancy)

Microvascular Complications: Neuropathy Autonomic Neuropathy

Cardiac autonomic neuropathy Resting tachycardia, orthostatic hypotension

Gastrointestinal neuropathy Gastroparesis, esophageal dysmotility, constipation, diarrhea,

fecal incontinence

Genitourinary neuropathy Sexual dysfunction, bladder dysfunction

Microvascular Complications: Neuropathy Peripheral Neuropathy

Commonly distal, symmetric polyneuropathy

Pain, burning and tingling sensation early on which may progress to numbness and loss of protective sensation.

Increases risk of wounds, infection and amputation

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Microvascular Complications:Peripheral Neuropathy More than half the amputations of feet and

legs in the U.S. are due to diabetes. Screening: Comprehensive foot exam at least

annually. If history of sensory loss, ulceration or amputation assess feet at every visit.

Evaluate skin integrity, assess for deformities, neurologic and vascular assessment

Microvascular Complications:Peripheral Neuropathy Treatment

Optimize glucose control

Gabapentin, Pregabalin, Duloxetine as initial treatment of neuropathic pain

Obtain ankle-brachial index/vascular studies for anyone with symptoms of claudication or decreased pedal pulses

Specialized therapeutic footwear for high risk patients

Podiatry referral for ongoing preventive care and surveillance in high risk individuals

Classification of Diabetes

Type 15-10%

• Insulin deficiency due to beta cell destruction

• 95% autoimmune, 5% idiopathic

Type 2>90%

• Progressive loss of beta cell function on the background of insulin resistance

Gestational

• Diagnosed in 2nd or 3rd

trimester• Insulin

resistance mediated by placental hormone production

• Pancreatic function insufficient to overcome this resistance

Misc

• Monogenic diabetes syndromes

• Disease of the exocrine pancreas

• Drug or chemical induced diabetes

• Endocrin-opathies

Pathophysiology of GDM

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Complications of GDM

Infant Macrosomia Shoulder dystocia and birth trauma Neonatal hypoglycemia, hyperbilirubinemia Stillbirth Risk of childhood and adult onset obesity and

diabetes

Mother Hypertension and Pre-eclampsia Higher rate of Cesarean section for large infant Risk of developing type 2 diabetes later in life

(estimated that 70% of women with GDM develop diabetes within 22-28 years after pregnancy)

Risk Factors for GDM

History of gestational diabetes in a previous pregnancy

Previous delivery of a child weighing 9 lbs or more

Overweight Physical inactivity Age > 25 years Polycystic ovarian syndrome African American, Hispanic/Latino American,

Native American, Alaska Native, Hawaiian Native or Pacific Islander

Family history of T2DM in a first degree relative

Screening and Diagnosis Treatment of GDM

Blood sugar testing 4 times daily for monitoring

Target blood sugars Fasting < 95 mg/dL

1 hour post prandial < 140 mg/dL

2 hour post prandial < 120 mg/dL

Lifestyle modifications Diet and exercise

Insulin Only medication that is FDA approved

for treatment of GDM

Does not cross the placenta

Metformin

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Surveillance and Delivery

Fetal surveillance with non-stress tests (NST)

Delivery Diet controlled GDM expectant

management until 40w6d

Well controlled with medication delivery 39w0d – 39w6d

Poorly controlled may deliver 37w0d –38w6d

Post Partum Management of GDM

Resume a normal diet

Test for prediabetes or diabetes at 4–12 weeks postpartum, using the 75-g oral glucose tolerance test

Women found to have pre-diabetes should receive intensive lifestyle interventions or Metformin to prevent diabetes.

Women should have lifelong screening for the development of pre-diabetes or diabetes at least every 3 years.

SummaryType 1 Diabetes Type 2 Diabetes Gestational Diabetes

Mechanism Insulin deficiency Insulin resistance + progressive insulin deficiency

Insulin resistance + relativeinsulin deficiency

Presentation Young, acute, polyuria and polydipsia

Adult, asymptomatic, symptoms of chronic complications

Pregnant, asymptomatic

Diagnosis Usually random BG > 200 with symptoms

Hemoglobin A1c, FBG, OGTT or random BG > 200 with symptoms

OGTT

Treatment Insulin Diet, exercise, oral medications,non-insulin injectable, insulin

Diet, exercise, insulin,Metformin

Complications Heart disease, cerebrovascular disease, peripheral vascular disease, retinopathy, nephropathy,

neuropathy

Infant: macrosomia, birth trauma, hypoglycemiaMother: Pre-eclampsia, c-sectionBoth: increased risk for diabetes

Other May be preventable if detected at pre-diabetes stage!

Reminder• Upon completion of the activity, continue to the same

link you used to register (https://app1.unmc.edu/cne/19Ol044a/evaluation.cfm), then click on the “Evaluation “ tab

• After completing the Evaluation, your certificate will be available to print or save.

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