OSA and DIABETES MELLITUS Richard S. Goodstein DO, FCCP Haggin - PowerPoint PPT Presentation

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 OBESITY LEPTIN REDUCES STIMULATES Ob- R TGF- beta INCREASES TNF/ IL-6

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 INCREASES REDUCES INSULIN Ob-R

INSULIN RESISTANCE INHIBITS OBESITY FURTHER GH INHIBITED BY OSA REDUCES INSULIN RESISTANCE IGF-1

ROLE OF INSULIN RESISTANCE Insulin Resistance Increased TG + FFA Pro-inflammatory

INSULIN AND OBESITY Pro- Insulin inflammatory 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 !!