Diabetes and The Gastrointestinal Tract

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Diabetes and The Gastrointestinal Tract
Jeffrey I. Brown, M.D. Knoxville Gastrointestinal
Specialists
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Diabetes and the Gastrointestinal Tract

• Defintions
• Epidemiology
• Diagnosis
• Metabolic Syndrome
• Organ Involvement
• Treatment
• Pharmacology
• Surgery

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ENDOCRINE CELLS of the GI
TRACT
Alpha cells ? glucagon Beta cells ?
insulin Delta cells ? somatostatin G cells ?
gastrin I cells ? CCK (cholecystokinin) K cells ?
GIP (glucose dependent insulinotropic
peptide) L cells ? GLP-1 (glucagon like
peptide-1) S cells ? secretin
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Diabetes - derivation
Diabetes pass through Diarrhea flow
through Mellitus honey Insipid without taste
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Diabetes- Epidemiology (USA)
- 26 million diabetics (8.3) - undiagnosed in
27 - 79 million pre-diabetics - 1 in 3 US
adults with diabetes a/o metabolic syndrome -
increased risk Blacks, Hispanics, Native
Americans
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Diabetes - Classification
Type I - immune mediated - one million
Americans - insulin virtually absent -
requires insulin treatment Type II - insulin
resistance - beta cell failure - defect
in compensatory insulin secretion -
genetic/environmental causes
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Diabetes Classification (cont.)
Gestational Other - corticosteroids -
glucagonoma - somatostatinoma -
hemochromatosis - pancreatitis - etc.
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Somatostatinoma Triad

• Gallstones
• Diabetes
• - Diarrhea/Steatorrhea

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Diabetes- Diagnosis ADA Criteria

• Hemoglobin A1C 6.5
• FPG 126 mg/dl
• 2 hour PG 200 mg/dl during OGTT
• In patient with classic symptoms and random PG
  200 mg/dl

Criteria 1 3 confirmed by repeat testing
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Diabetes - diagnosis Hemoglobin A1C (Hb A1C)

• - Revised diagnostic criteria (2010)
• Hb A1C 6.5
• correlates with mean glucose concentration
• correlates with diabetic complications
• convenient
• less sensitive than plasma glucose measurements

? fewer individuals diagnosed with
diabetes
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Diabetes Drug Therapy
Sulfonylureas (Glyburide, Glipizide) Biguanid
es (Metformin) Thiazolidinediones
(Avandia, Actos) Alpha glucosidase
inhibitors GLP-1 receptor agonists DPP-4
inhibitors others
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Diabetes Drug Therapy Metformin
Primary action on liver First line therapy for
type 2 diabetes Avoid in those with liver or
kidney problems No weight gain GI side effects
(20) nausea/vomiting, diarrhea, pain
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Diabetes Drug Therapy Thiazolidinediones
(TZDs)

• Insulin sensitizing agents
• Reverses insulin resistance
• Consistently lowers glucose levels
• Associated with weight gain, edema, anemia
• Increases Adiponectin levels

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ADIPONECTIN

• an Adipoctyokine
• produced only in adipose tissue
• Insulin sensitizing
• anti-atherogenic
• low levels in the obese and type 2 diabetics

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THAIZOLIDINEDIONES

• TROGLITAZONE (REZULIN)
• - hepatotoxicity
• ROSIGLITAZONE (AVANDIA)
• - cardiovascular risk
• PIOGLITAZONE (ACTOS)
• - bladder cancer?

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TZDs role in treating other conditions

• NON-ALCOHOLIC FATTY LIVER DISEASE
• POLYCYSTIC OVARY SYNDROME
• LIPODYSTROPHY (HIV)

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INCRETIN HORMONES
GLUCAGON LIKE PEPTIDE-1 (GLP-1) GLUCOSE
DEPENDENT INSULINOTROPIC PEPTIDE (GIP)
- increases food (glucose) induced insulin
secretion - decreases glucagon secretion -
rapid degradation by DPP-4 (dipeptidyl peptidase
4)
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INCRETIN THERAPY
EXENATIDE (BYETTA) GLP-1 agonist Saliva of
Gila Monster T ½ ? 2.4 hours Nausea/weight
loss Pancreatitis/pancreatic cancer?
LIRAGLUTIDE (VICTOZA) GLP-1 analog T ½ ? 12
hours Nausea/vomiting/diarrhea Pancreatitis
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DIPETIDYL PEPTIDASE-4 INHIBITORS (DPP-4
INHIBITORS)
SITAGLIPTIN (JANUVIA) SAXAGLIPTIN
(ONGLYZA) LINAGLIPTIN (TRADJENTA)
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METABOLIC SYNDROME

• Group of risk factors that indicate increased
  risk for
• type 2 diabetes
• - premature cardiovascular disease

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METABOLIC SYNDROME
3 of 5 criteria

• Central (truncal) obesity waist circumference
  gt 40 (men)
• 
  gt 35 (women)
• Glucose 100 mg/dl
• - Blood pressure 130 mm Hg sys./ 85 mm Hg
  dias.
• serum triglycerides gt 150 mg/dl
• HDL cholesterol lt 40 mg/dl (men)
• lt 50 mg/dl
  (women)

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• BODY MASS INDEX (BMI)
• A proxy for human body fat
• body weight (Kg) divided by height (m) squared

• underweight lt 18.5
• normal 18.5
  25.0
• overweight 25.0
  30.0
• obese 30.0
  35.0 (Class I)
• severe obesity 35.0
  40.0 (Class II)
• extreme morbid obesity 40.0 50.0
  (Class III)
• super morbid obesity 50.0 60.0
• super-super morbid obesity gt 60.0

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BARIATRIC SURGERY

• Definition any surgical treatment for obesity
• markedly reduces co-morbidities
• consider if BMI gt 40.0
• gt 35.0 with
  co-morbid conditions
• types of surgery - restrictive
• -
  malabsorptive
• - both

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BARIATRIC SURGERY
HEALTH BENEFITS

• DIABETES REVERSED (90)
• HYPERLIPIDEMIA CORRECTED (70)
• HYPERTENSION RELIEVED (70)
• FATTY LIVER RESOLVES (90)
• SLEEP APNEA MARKEDLY IMPROVED
• GERD SYMPTOMS RELIEVED
• BACK/JOINT PAIN IMPROVED
• OVERALL REDUCTION IN MORTALITY 89 !

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DIABETES GI TRACT INVOLVEMENT
- ESOPHAGUS - STOMACH - SMALL/LARGE BOWEL -
LIVER/BILIARY - PANCREAS
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ESOPHAGUS
Abnormal Motility associated with diabetic
neuropathy (75) Usually asymptomatic GERD more
common Prone to Candida infection
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STOMACH
Gastritis/Gastric Atrophy more common Association
with Pernicious Anemia Reduced acid
secretion Decreased incidence of ulcer disease
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STOMACH - GASTROPARESIS

• seen in upto 60
• symptoms include nausea, vomiting, pain,
  bloating, early satiety
• occurs in those with longstanding disease
  (autonomic neuropathy)
• worsened by hyperglycemia (poor diabetic
  control)

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GASTROPARESIS - TREATMENT

• ANTIEMETICS
• DIET MODIFICATION
• smaller/liquid meals
• j tube feedings
• TPN
• MEDICATIONS
• metoclopramide
• erythromycin
• domperidone
• - GASTRIC ELECTRICAL STIMULATION (GES)

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GASTRIC ELECTRICAL STIMULATION
ENTERRA SYSTEM pulse generator/electrodes
place surgically GES A) gastric pacing -
improves gastric emptying B) neurostimulation
- controls nausea/vomiting
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GASTRIC ELECTRICAL STIMULATION - 10 YEAR DATA

• Greater Symptom Reduction
• Improved Gastric Emptying ? normalized in 23
• Decreased Hb A1C levels ? translates to fewer
  complications
• Significant Weight Gain
• Reduction in Hospitalization Days
• Reduced Medication Usage (for gastroparesis)

McCallum, et al, Clin. Gastro Hep. 9(4)314-319
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DIABETES SMALL
INTESTINE/COLORECTUM
DIABETIC DIARRHEA NEUROPATHY RELATED
BACTERIAL OVERGROWTH CELIAC
DISEASE MEDICATION RELATED
CONSTIPATION - 20 FECAL INCONTINENCE
DECREASED SPHINCTER TONE BLUNTED RECTAL
SENSATION COLON CANCER ? obesity related
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DIABETES LIVER/BILIARY
HIGHER INCIDENCE OF ACUTE HEPATITIS B
1.4 vs 0.7 per 100,000 patients GALLSTONES
MORE FREQUENT (2X) lithogenic
bile hypomotility
prophylactic cholecystectomy? STEATOSIS in upto
80
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DIABETES - NONALCOHOLIC FATTY LIVER DISEASE
(NAFLD)
Most common form of liver disease in USA (6-30
million) Spectrum of disease -
simple steatosis - steatohepatitis
(NASH) - cirrhosis ? develops in 20
of NASH patients Risk Factors female
diabetes
obesity
hyperlipidemia cryptogenic cirrhosis ? 70
obese/50 diabetic!!
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NAFLD - TREATMENT

• slow/gradual weight loss
• control diabetes/hyperlipidemia
• pharmacologic treatment TZDs, others
• surgery
• bariatric - improvement in 90
• liver transplant

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DIABETES - PANCREAS
Acute pancreatitis more common in type 1 diabetes
(2X) Diabetes - risk factor for pancreatic
cancer New onset diabetes ? can be early sign of
pancreatic cancer Chronic pancreatitis exocrine
? endocrine insufficiency.
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CONCLUSION
Epidemic of Diabetes Obesity Hemoglobin A1C
used for diagnosis of diabetes ( 6.5) BMI
definition and use in classification of
obesity Gut hormone manipulation in treatment
(incretin hormones) Benefits of GES and Bariatric
Surgery