OSA and DIABETES MELLITUS

Richard S. Goodstein DO, FCCP

Haggin Pulmonary & Sleep Medicine

“ OSA is independently

associated with Insulin

Resistance”

AJRCCM : 2002 ; 165.670

Mary Ip et al

ADIPOCYTES

New Understanding of Adipocytes

Adipokines

Regulatory role in Insulin

sensitivity/ resistance

Regulatory role in systemic

inflammatory process

Immunologically active

Changing concept of an inert

adipocyte to that of an active

participant in metabolism is key

to our discussion !

ADIPOKINES

Leptin…pro-inflammatory

Adiponectin…anti-

inflammatory

LEPTIN

ADIPOCYTES

OBESITY IS PRO-INFLAMMATORY

STIMULATES

LEPTIN

STIMULATES TGF- beta

INCREASES

TNF/ IL-6

REDUCES

Ob- R

OBESITY

Obesity as Pro-Inflammatory

State

In obesity as adipocytes hypertrophy

Increase in “ activated (Th-1) “

macrophages

Increase in pro-inflammatory cytokines

Increase FFA

DM II / Fatty Liver/ Asthma / MetS

OBESITY IS SELF-PERPETUATING

OBESITY

REDUCES

Ob-R

INCREASES

INSULIN

INSULIN RESISTANCE

INHIBITS GH

REDUCES

IGF-1

INSULIN RESISTANCE

OBESITY FURTHER INHIBITED BY

OSA

ROLE OF INSULIN RESISTANCE

Insulin Resistance

Increased TG + FFA

Pro-inflammatory

INSULIN AND OBESITY

Pro-inflammatory

Insulin Insensitivity

INSULIN SENSITIVITY

FBS/ INSULIN DOSE

Metabolic Syndrome (MetS)

Metabolic Syndrome

Central Obesity

Insulin Resistance

Lipid Abnormalities

Hypertension

OSA

MetS : The Usual Suspects

Insulin Growth

Factor-1

GHRH-GH-

Somatostatin

Leptin

INSULIN GROWTH FACTOR -1

Protein hormone

Similar to Insulin

Helps cell growth

Inhibits apotosis

IGF-1 DEFICENCY

Decreased peripheral utilization of

glucose

Increased Insulin resistance

Increased hepatic gluconeogenesis

Increased adipose uptake

Central adiposity

Human Growth Hormone (HGH)

Leptin

Increased adiposity

Down regulates T regulator cells (Treg)

Increases Th-1 pro-inflammatory state

Increases Reactive Oxygen Species

(ROS)

Increases TGF-beta which increases ASM

and BHR . Increases Vascular SM and

PAH.

ALTERED GENOMICS and

DIABETES

TELOMERES

TELOMERES

TELOMERES and OSA

Uh..OK so what does this have

to do with Sleep Apnea ?

OBESITY and OSA

AUTONOMIC NEUROPATHY IN DM

ALTERED GENOMICS and

DIABETES

INDUCIBLE CELL DEATH (APOTOSIS)

OSA INHIBITS GH

OSA and IR

TREATMENT MAKES A DIFFERENCE

IS CPAP AN ADJUNCT THERAPY IN IDDM ??

CPAP in DM

Increases IGF-1

Increases GH

Reduces Ghrelin

Reduces Leptin

Normalizes Circadian Counter-

regulatory hormones

THUS ….?????

Adipose Deposition and Metabolic Syndrome

Increased risk of Met

Syndrome and Asthma

HOMEOSTATIC METABOLIC ASESSMENT (HOMA)

• AHI>5.

• Low SpO2

• CT90 (Time in which SpO2 < 90%)

THESE MARKERS WERE INDEPENDENT OF BMI AGE , GENDER , SMOKING AND ETOH CONSUMPTION.

Theorell-Haglow et al. Eur Respir J. 2008:31;1054-1060.

GLUCOSE INTOLERANCE

• Total Sleep Time < 7-8 hours

• Sleep fragmentation

• Decreased or absence of REM Sleep

I’M DONE !!