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What is the relationship between obstructive sleep apnea and type 2 diabetes?

What is the relationship between obstructive sleep apnea and type 2 diabetes?. W. Jerome Alonso, MD A.W.A.K.E Meeting August 5, 2009 Redwood City, CA. Overview. Definition of Type 2 Diabetes Mellitus Significance of the condition Development and disease progression

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What is the relationship between obstructive sleep apnea and type 2 diabetes?

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  1. What is the relationship between obstructive sleep apnea and type 2 diabetes? W. Jerome Alonso, MD A.W.A.K.E Meeting August 5, 2009 Redwood City, CA

  2. Overview • Definition of Type 2 Diabetes Mellitus • Significance of the condition • Development and disease progression • Current associations between type 2 diabetes and obstructive sleep apnea • Possible mechanisms behind the interaction • Further investigations

  3. What is type 2 diabetes? “In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin.” – American Diabetic Association

  4. Significance • Common condition with approximately 15 million diabetics over the age of 18 in 2000; accounting for 7.3% of the population1from 4.9% in 1990 • Microvascular and macrovascular complications • Diabetic nephropathy, retinopathy, neuropathy • Coronary artery disease, cerebrovascular disease, and peripheral vascular disease • Individuals with type 2 diabetes without a prior MI (mean age 58) were at the same risk for MI (20 and 19 percent, respectively) and coronary mortality (15 versus 16 percent) as patients without diabetes who had a prior MI (mean age 56)2 The JournClin Invest. Sept 1999;104:787-794.

  5. Disease progression of Type 2 Diabetes Mellitus • Risk Factors • Genetic • Obesity (truncal) • Age • OSA? Insulin dependence Impaired glucose tolerance Impaired fasting glucose Insulin Resistance Hyperinsulinemic state Activation of pancreatic beta cells Impaired insulin secretion Overt Diabetes Prediabetes

  6. Spectrum of glycemic regulation

  7. Current Criteria for the Diagnosis of Diabetes (2009 Standards of Medical Care in Diabetes) ● Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h ● Symptoms of hyperglycemia and a casual (random) plasma glucose 200 mg/dl (11.1 mmol/l). Casual (random) is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, and unexplained weight loss. ● 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test (OGTT). The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. Diabetes Care. Vol. 32. Suppl 1. Jan 2009

  8. What’s the relationship with obstructive sleep apnea?

  9. Wisconsin Sleep Cohort • 1387 subjects; population based • Ages 30 – 60 yrs; primarily caucasian • 14.7% of those with AHI≥15 with diabetes vs 2.8% of those with AHI<5 • 2.3 fold likelihood of physician diagnosed diabetes with a AHI of ≥15 in comparison to having an AHI <5 after adjusting for age, sex and body habitus • 1.62 fold likelihood of developing diabetes mellitus within 4 yrs Am J RespirCrit Care Med Vol 172. pp 1590-1595

  10. Sleep Heart Health Study • 6441 subjects; population based; multicenter • 209 non-overweight with OSA; 1036 overweight/obese with OSA; 470 diabetics; 2656 with fasting glucose levels • diabetes was not significantly associated with SRB when adjusted for age, sex, BMI, race and neck circumference. • SRB was associated with a 1.3 fold likelihood of IFG, 1.2 for IGT, 1.4 for IFG and IGT and 1.7 for occult diabetes. • the severity of sleep-disordered breathing and frequency of arousals were independently associated with the degree of insulin resistance • degree of sleep-related hypoxemia was strongly associated with insulin resistance and glucose intolerance Diabetes Care. Vol. 26 (3); Mar 2003. Am J Epidemiol 2004; 160:521-530. Am J RespirCrit Care Med. Vol 172:1590-1595. 2005

  11. Principles and Practice of Sleep Medicine, 4thed

  12. Interventional Case-series • Harsh, Igor et al. • Improvement in insulin resistance with CPAP use after 2 days that persisted for 3 months non-diabetics. Larger improvement in non-obese. (n=31) • Improvement in insulin resistance in diabetics after 3 months. No improvement in HbA1c. • Maintenance of insulin resistance in non-diabetics after 2.6 years. Only 3 of 7 with insulin resistance during initial study had persistence of insulin resistance. Respiration 2004;71;252-259 Am J RespirCrit Care 2004; 169. pp 156-162 Med SciMonit, 2008; 14(3): CR117-121

  13. Double-blind Randomized Control trial • West, Sophie et al. • 42 men; type 2 diabetes; newly diagnosed OSA • Auto-titrating CPAP versus sham CPAP • HbA1c and HOMA measurements prior to and after CPAP for 3 months • No significant improvements in glycemic control or insulin resistance despite improvements in Epworth and MWT data • Average usage of 3.6 hours of CPAP per night Thorax 2007;62;969-974

  14. What do we do now? Thorax 2007;62;969-974

  15. Future directions • Repeat RCT with improved compliance +/- a titration study • Studies on individuals with prediabetes and prevention of overt diabetes • Effects of therapy on medication requirements and beta cell conservation

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