Cinnamon: Possible Therapy for Gestational Diabetes

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CinnamonPossible Therapy for Gestational
Diabetes

• Marguerite Lisa Bartholomew, M.D.
• Mentor Mary Hardy, M.D.
• UCLA K30 Program

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Background

• Diabetes complicates 2-5 of all US pregnancies.
• 90 of cases are purely gestational
  hyperglycemia begins at approx 24 wks and
  resolves after delivery.
• High risk populations (Polynesian,Native
  American, obese women etc) 10 incidence of
  GDM.
• GDM is like type II DM (insulin resistance and
  relative lack in insulin action)-not a loss of
  pancreatic function.
• Obesity is now an epidemic in the US

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Obesity Trends Among U.S. AdultsBRFSS, 1991,
1996, 2003
(BMI ?30, or about 30 lbs overweight for 54
person)
1996
2003
No Data
lt10
10-14
15-19
20-24
? 25
Source Behavioral Risk Factor Surveillance
System, CDC.
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Diabetes During Pregnancy

• Untreated or poorly treated diabetes can have
  detrimental effects on the fetus (malformation,
  stillbirth, macrosomia, hyperbillirubinemia,
  neonatal hypoglycemia, birth injury, delayed
  pulmonary maturity etc).
• Optimum control of blood glucose reduces and can
  remove the risks for the fetus.
• Standard of care for women with diabetes during
  pregnancy is limited to diet, exercise, insulin,
  and more recently, glyburide
• Alternative treatments are sorely needed.

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Botanicals as an Alternative

• Cinnamomum cassia (cinnamon) has demonstrated
  hypoglycemic properties in vitro and in vivo.
• Could serve as a primary treatment, adjunct to
  traditional treatment, or preventative treatment.
  

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Hypothesis

• Cinnamomum cassia could be used safely and
  efficaciously for the treatment of diabetes
  during pregnancy

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Observation 1

• Cinnamon has been shown to have insulin-enhancing
  and antioxidant properties in vitro
• Khan A et al. Bio Trace Element Res 24183-188,
  1990
• Bailey CJ et al. Diabetes Care 12553-564, 1989
• Broadhurst et al. J Acric Food Chem. 2000
  Mar48(3)849-52)
• Anderson RA et al. J Agric Food Chem.2004. Jan
  1452(1)65-70

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Observation 2

• Extracts of cinnamon (water soluble polyphenol
  polymers specifically A type doubly linked
  procyanidin oligomers of the catechins /
  epicatechins) activate insulin receptors
• More specifically methylhydroxychalone polymer
  (MHCP)
• Imparl-Radosevich J et al. Regulation of the
  PTP-1 and insulin receptor kinase by fractions
  from cinnamon implications for cinnamon
  regulation of insulin signaling. Horm Res. 1998
  Sep50(3)177-82

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Observation 3

• Cinnamomum cassia in 1,3,and 6 grams/day doses
  decreased fasting serum glucose by 18-29 (vs
  placebo) in 60 non-pregnant subjects with type II
  DM without untoward side effects.
• Khan A et al. Cinnamon improves glucose and
  lipids of people with type II diabetes. Diabetes
  Care 263215-3218, 2003

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Observation 4

• There have no adverse events reported to the FDA
  concerning dry cinnamon.
• It is on the FDAs Generally Regarded as Safe
  list (GRAS) in amounts limited to use as a spice
  or nutritional supplement.
• Sources recommend limiting cinnamaldehyde dose to
  0.7 mg/kg/day
• Herbal texts recommend 1.0-5.0 grams per day
• Code of Federal Regulations Title 21, vol 3, chap
  1, part 182. FDA GRAS. 4/2003
• McGuffin M et al. Botanical Handbook of Safety.
  1997p.31.

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Observation 5

• Dry cinnamon has no known teratogenic or
  embryocidal effect in humans in doses commonly
  found in food.
• Recommendations to restrict cinnamon in pregnancy
  are often made without concrete evidence.
• It is unknown to what extent cinnamon metabolites
  may cross animal or human placentas.

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Cinnamomum cassia (family Lauraceae)

• Synonym cinnamomum aromaticum or chinese cinnamon
• Cap-T-Cin is commercially available (Natures
  Dawn)
• Dried cassia bark from Indonesia
• 600 mg caps

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Major concernCinnamaldehyde

• The minimum fatal dose reported for humans is
  0.5-5 grams / kg (National Library of Med
  Hazardous Substance Database. 2004)
• or 1oz-1 pint of cinnamon oil / 70kg person
• Most reports indicate mucosal irritation/erosion/a
  llergic reactions from cinnamon oil, not dry
  cinnamon
• Extremely high doses (940 mg/kg/day) have been
  associated with high mortality rates in
  non-gravid rats. (Herbert CD et al. 1994)
• There is conflicting data concerning effect on
  high doses given to pregnant rodents (1 showed no
  effect, one showed decreased skeletal
  ossification and renal abnormalities).

Hardin BD et al. 1987, Mantovani A et al 1989
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Preliminary data

• One capsule (600 mg) of Cap-T-Cin contains 19.8
  mg of cinnamaldehyde or 33 mg/1 gram.
• To follow guidelines for limiting cinnamaldehyde,
  a 70kg person should not exceed 50 mg/day of
  cinnamaldehyde or 1.5 grams of Cap-T-Cin per day.

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Specific Aims

• Assess the acute and chronic toxicity of
  cinnamomum cassia in rats.
• Assess the effects of cinnamomum cassia on the
  offspring of diabetic and nondiabetic pregnant
  rats
• Assess the placental transfer of cinnamaldehyde
  and polyphenolic polymers in a human placental
  model (recirculating single cotyledon model)
• Randomized placebo controlled trial of cinnamomum
  cassia for the treatment of gestational diabetes

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Interim Plan

• Get more preliminary data in a different
  direction (reduce toxicity concerns).
• Remove the cinnamaldehyde from the Cap-T-Cin
  with extraction processes.
• Pilot study with cinnamaldehyde free cinnamon
  (CFC).
• Randomize 20 pts to CFC or placebo.
• Outcome measure fasting and postprandial
  glucose, hemoglobin AIC etc.