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Masquerading as Type 2 DM:

• LADALatent Autoimmune Diabetes of Adults

• T3c DM“other types” or pancreatogenic diabetes

Mary E. Steward, APRN-CNP, MS, MPH, CDEAssistant Professor, Internal MedicineOU School of Community Medicine, Tulsa, OK

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Speaker Disclosure

• I have no financial relationships or affiliations to disclose.

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Making the Diagnosis“IDDM” = obsolete term

• Age at presentation– 50% of T1DM may be

diagnosed >30 yrs.

• Body Habitus– 50% T1DM w/BMI >25– 25% T1DM +2 signs

Metabolic syndrome

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Types of Diabetes

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LADA• “Type 1.5”• Autoimmune DM progressing slowly

– May not need insulin for 6 mos-6 yrs.• 4-14% of people dx with DM

– 15-20% of people dx with T2DM• Do not initially require insulin at dx.• Share genetic features with T1 & T2• Family Hx is common, esp T1DM• BMI <35 typical, age 25-40 common

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LADA Labs• C-peptide (.8-3.1)

– low to normal in early disease– Low to undetectable, late– If high, use insulin sensitizer

• Autoantibodies: **GAD,** Islet cell, IA2 (islet tyrosine phosphatase 2/insulinoma assoc antigen), Insulin Autoantibody, Zn co-transporter A, freq positive for only 1.

• TIP: Check C-peptide first, if <1, get GAD

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LADA vs T2DM

• Better Metabolic profile: – Lower BMI– lower blood pressure– better lipids– fewer signs Metabolic Syndrome

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LADA vs T1DM

• Less aggressive Beta cell loss– May tolerate delayed insulin start

(not advised)

• Fewer multiple auto-antibodies– Higher GAD antibody titer =

• faster progression • more severe beta cell loss• quicker progression to insulin

• Risk for DKA is lower, increases with length of dx.

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Management of LADA

• Insulin primary, similar to T1DM, physiologic regimen, for islet cell preservation

– Augments beta-islet function– Reduces hyperglycemia– Decreases severity of insulitis– Suppresses auto reactive T-cells

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LSA Postprandial Pattern “stairstep”

Fasting Pattern “wave”

GLUCOSE PATTERNS

HIGHBaseline

HIGHExcursions from AM, Lability

Normal1-2 hrs.excursions

B L S

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Management of LADA cont.

Potential to preserve beta cell function• DPP4 inhibitors may improve beta cell

function, GLP-1 incretins• Metformin if insulin resistance or TZD

Avoid sulfonylureas—deplete endogenous reserve

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Screen for Autoimmune

• Increased risk other autoimmune– Esp. thyroid– More common

LADA>T2DM

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CV Risk

• Risk is lower than DM2 generallymonitor BPuse statinsexercisediet weight management

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Don’t be Fooled!

• Lower BMI <35• Age at onset 20-50• Less Family Hx DM• Less response to Lifestyle• Marked postprandial pattern• Insulin required within 3 yrs of

diagnosis?

–Think LADA

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65 yrs. CM BMI 26, wt 200# Dx DM2 2002

• Actos/glipizide/Januvia/Lantus 40units HSmetformin intolerance

• Neg FH DM• PMH: Htn, Chol., A. fib, Barrett’s• TSH wnl. • A1c 8.5%, despite careful food choices• +Periph neurop on foot exam

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Labs

• C-peptide 0.37 (.8-3.1)

• GAD 5.3+ (<5) - autoantibodies can diminish in longstanding disease

• Negative ICA <1:4, IA2 <0.8

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LADA

• Stop orals for DM2• Lower basal significantly (20 units)• Start low dose meal insulin

– insulin:carb ratio of 1:15 or 1:20• Many LADA may have had dramatic

response to meal analog insulin in past with hypo & reluctant to restart, be conservative

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33 yrs. CF, Dx DM2 2014BMI 27, Wt 178

• Metformin 1000 BID, Levemir 25 BID, Novolog 5 TID Premeal

• PMH: anxiety, substance abuse-cannabis, amphetamines, panic disorder, PTSD

• A1c 12.2% MPG 360• Office BS 135 fasting

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Lab

• C-peptide 0.62 (.8-3.1)

• Likely insulin omission & liquid carbs contributed to high A1c

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Lab/Dx• GAD 8 (<5)

LADA• Stop metformin • Zero calorie drinks• Rebalance insulin basal/bolus (@.6/kg = 50 units)

• Switch to once daily basal (Lantus, Basaglar, Tresiba, Toujeo)

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Masquerading as DM2 –T3c

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T3cDM Distribution

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T3c• >75% from chronic pancreatitis• 1-9% prevalence of DM patients, average of 4-

5% most populations• Typically >age 50• Deficient insulin production, reduced islet # & function

• Impaired pancreatic function– Inhibited glucose-stimulated insulin release

from pro-inflammatory cytokines– Hepatic & peripheral insulin resistance– Reduced incretin effect

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Pathophysiology – Incretins (5)

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Alcohol-associated Chronic Pancreatitis

• Cumulative presence of DM– 50 % at 10 yrs.– 83% at 25 yrs.

• Exocrine insufficiency usually pre-dates endocrine insufficiency

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Chronic Pancreatitis (CP)

• 50% endocrine insufficiency (75% T3c)

• 80% exocrine deficiency– Within 5 yrs. of diagnosis

• Repeated acute attacks cause cumulative tissue damage, collagen deposition, scar formation that blocks glandular structure & function

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Exocrine Dysfunction CP• Malabsorption

– Weight loss, muscle depletion– Diarrhea– Steatorrhea

• Digestive Enzyme replacement with meals

• Reduction of fat intake• Small, multiple meals throughout day• Fat soluble Vit D monitoring• High risk atraumatic fracture

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Additional Challenges CP

• Epigastric pain & use of opioids– ?pancreatic neuropathy, responsive to

TCA, gabapentin, pregabalin, SSRI• Alcohol & smoking cessation –

metabolic/exogenous toxins• T3c “pancreatogenic” diabetes more

likely w/surg. resection esp. distal pancreas, smoking, longer duration CP dx, pancreatic calcifications

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Labs T3c

• Normal to low C-peptide based on disease progression

• Negative Auto-antibodies• Normal insulin sensitivity• Low risk DKA early, higher as disease

progresses• Low serum levels lipid soluble

Vitamins D, E, K• Labile glucose swings

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Treatment T3c DM• A1c <8% - metformin (GI side

effects), reduces risk of pancreatic Ca (antineoplastic properties)

• Decreased hepatic insulin sensitivity, unsuppressed hepatic glucose output– Reduced pancreatic polypeptide

secretion alpha cells causing erratic glucose swings

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Treatment T3c DM cont.

• Insulin as next therapy• Caution risk hypo (SU, insulin),

loss of counterregulatory hormones, impaired nutrient absorption, low glycogen stores, exaggerated peripheral sensitivity to insulin, persistent alcohol intake, poor dietary intake due to pain, smoking, alcohol, postprandial symptom avoidance

• AVOID: Incretin-based therapies like GLP-1, DPP4 inhibitors; TZDs

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Treatment T3c DM cont.• Regular meal pattern with standardized

CHO intake, do not skip meals

• Small, frequent meals, rich in soluble fiber, low in fat, Vit D supplement

• Avoid alcohol & smoking• Enzyme replacement, stabilize postprandial BS/incretin

• Minimize high sugar food & fluids• Monitor glucose, test if symptoms of low

• Avoid sugar alcohols (sorbitol) laxative effect

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PMH

• Past or current pancreatic disease?• Alcohol history?

12 oz

1 oz

5 oz

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Microvascular Complications

• May be at greater risk– Regular dilated eye exam– Urine microalbumin– Neuropathy evaluations– Foot checks

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Risk/Complications

• Risk for pancreatic cancer– CP is 5% over 20 yrs.– DM2 over 2x standard population risk– T3cDM may be a “harbinger”

• Macrovascular complications less common

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43 yrs. HISP M. BMI 33, wt. 246 #

• PMH: hypothyroid, elev BP w/o dx Htn, pancreatitis, alcohol abuse, venous stasis

• FH: neg DM• Labs: A1c 10.4% MPG 293, office BS

164• Dx: DM2 Started on metformin ER

500mg, 2 tab BID.

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Lab

• C-peptide 0.5 (.8-3.1)

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Lab/Dx

• GAD Autoantibody <5 (<5)

DM T3c• Start insulin (A1c 10.4%), wt 246#,

Simple regimen to start Novolog Mix 70/30, 24 units BID, before largest 2 meals

• Continue metformin 2g/day (eGFR >45)

for antineoplastic & IR benefits

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37 yrs HISP M, Dx DM2 2005,BMI 44, wt. 350#

• Novolog 20 TID premeal, Lantus 35 BIDmetformin intolerant

• FH + DM2• Periph neurop, Bilat retinop, Necrobiosis

lipoidica, hx. DM foot ulcer, venous insufficiency

• 3/2018 Leukocytoclastic vasculitis• 12/2018 Acute pancreatitis/necrosis,

NAFLD, CT w/cirrhosis

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Lab

• Labs: A1c 11.8% MPG 314• Meds: Creon, methadone,

gabapentin . . .

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Dx DM2

• Pre-existing DM2• Complication of pancreatitis

• Further eval. liquid carbs, insulin omission, injection site hypertrophy, incidence hypoglycemia/how treated

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Don’t be Fooled!

• Pancreatitis/GI history– Weight loss, muscle depletion– Diarrhea– Steatorrhea– Epigastric pain, esp postprandial

• Age ~50• Alcohol & smoking history

–Think T3c

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Masquerading as Type 2 DM:

• LADALatent Autoimmune Diabetes of Adults

• T3c DM“other types” or pancreatogenic diabetes

Mary E. Steward, APRN-CNP, MS, MPH, CDEAssistant Professor, Internal MedicineOU School of Community Medicine, Tulsa, OK