ADA 2005
Close Concerns Blog
We’ve just arrived in San Diego today for the ADA. Fabuloso, that it is not in New Orleans or Orlando! San Diego – quick flight from San Francisco, the sun is shining, life is good ..
There are going to be over 12,000 people here and one can already tell. We attended a bunch of sessions today and everything was paaaaacked. Generally there hasn't been blowyouaway data but the tone is upbeat - new therapies out, new therapies on their way, excitement abounds. Here were some details from today ...:
• Comparison of Incidence of Topics for ADA Abstracts: Wow, so check these out. We compared keyword placement for last year versus this year. Of course keywords are just key-words, nothing more nothing less, but … metabolic syndrome has 208 placements this year in abstracts compared to 134 last year. Obesity now has 372, up from 299. And inhaled insulin rose 80% from 10 to 18!
Comparison of Incidence of Topics for ADA Abstracts
Keyword 2003 2004 2005
Continuous 89 139 109
GLP-1 59 59 68
DPP-IV & DPP-4 7 11 15
Analog & Analogue 40 56 46
Obesity 283 299 372
Metabolic Syndrome 98 134 208
Inhaled Insulin 11 10 18
Pramlintide 8 8 4
Rimonabant 0 0 3
Dual PPAR 3 5 21
• Excellent sessions to start the day – one on insulin pumps and diabetes, with Drs. Wolpert, Bode, Schade, and Buckingham. All the positives of pumps were discussed, with really the main negative being price. Dr. Bode said that as of 2004, 250,000 people in the US have pumps. One question examined focused on type 2 patients – some said as many as 50,000 (“ok, 35,000”) type 2 patients wore pumps – Dr. Bode felt this was very high estimate. I agree. Really, probably no one knows! We need IMS for pumps : >. This session was com-peting with multiple agent therapy for type 2 patients – Byetta looks good at 82 weeks, that’s for sure, in term of sustained (increased) A1C drop and reduced (further) weight.
• Metabolex’s metaglidasen is a novel TZD based on a single isomer of the compound halofenate, originally developed in the 1970s as a lipid-lowering agent. In original Phase III halofenate tri-als, Merck discovered that 50 type 2 diabetes patients who had accidentally been enrolled in the study saw lower blood glucose levels in addition to a reduction in lipid levels. Halofenate was never commercialized. BUT! In a recent randomized controlled trial in 217 type 2 diabe-tes patients whose blood glucose levels were not adequately controlled by insulin therapy, the addition of metaglidisen (MBX-102) 400 mg lowered A1C by 1.0%±0.15% (± SE) from base-line (p<0.05), which was 0.7% better than placebo (p<0.05). Lipid levels were unchanged ex-cept for a significant decrease in trigylceride levels with metaglidasen 400 mg (15% vs base-line, 38% vs placebo). Metaglidisen looks unique among TZDs because it does not cause weight gain or edema. Metaglidisen was well tolerated and had less weight gain (0.3 and 0.7 kg) than insulin alone (0.8 kg). Edema was detected in 11.0 and 5.8% on metaglidasen 200 and 400 mg, respectively, and in 16.2% on placebo. We learned some of this from Dr. Julio Rosenstock and some from the company – we’ll be staying tuned.
• At the International Pancreas and Islet Transplant Association session, we heard about biolu-minescence as a possible method of detecting transplanted islet cell viability in vivo. To date, luciferin (the enzyme that makes fireflies glow) has been used to detect islet cell health in vivo in mice. Today, Alvin Powers (Vanderbilt University) explained the many potential benefits and few risks of luciferin in greater detail. Unfortunately, Powers concluded, luciferin will never find application in humans because the sheer quantity of body tissues between the loca-tion of implanted islets, whether placed in the portal vein of the liver or elsewhere, will absorb too much of the light given off by luciferin before it can be measured externally. Mice are small enough that luciferin can easily be detected externally using certain imaging techniques (but not by the naked eye, which would actually be pretty funny – would they be firemice?).
• In the Medtronic MiniMed corporate sponsored symposium, Dorothea Deiss discussed the German outcomes from the GuardControl trial, intended to showcase the utility of real-time continuous glucose monitoring for improving glycemic control in young type 1 patients. In 90 days, the A1C of the control group stayed at 10% while the A1C of the Guardian RT users reduced from 10% to 8.9%. This session was very well done – very popular – the excitement about continuous is nonstop.
• Chronic inflammation associated with obesity-- IL-6 in specific--was a hot topic today. Dr. Robert Mooney from the University of Rochester pointed out that IL-6 levels are three to five times higher patients with insulin resistance and type 2 diabetes. He said that IL-6 is a “bad guy” in the context of obesity and insulin resistance. On the other hand, Dr. Bente Klarlund Pedersen accused TNF as being the driver behind metabolic syndrome and said that IL-6 is not to blame. The proof from her view: she infused TNF in a study subject (never in the U.S.?!?) and found that TNF induced insulin resistance, resulting in an inhibition of glu-cose uptake.
• IL-6 is the center of more confusion: Dr. Bente Klarlund Pedersen found that high levels of IL-6 are associated with physical inactivity, but acute exercise causes an increase in levels of IL-6. A paradox! Exercise enhances the transcription rate of the IL-6 gene in skeletal muscle.
• Said Dr. John N. Fain, in a sentence that captured our attention: “Human adipose tissue is like an endocrine tumor that is responsible for the hypertension and diabetes that accompanies obesity …” 45 minutes later, Dr. Bente Klarlund Pedersen added that skeletal muscle is also an endocrine organ, as it releases IL-6, which goes on to affect other parts of body. Who knew!
• Dr. Samuel Klein from Washington University in St. Louis spoke on the crisis of nonalcoholic fatty liver disease (NAFLD). Steatosis is prevalent in 85% of people with extreme obesity, and cirrhosis is also frighteningly prevalent in cases of extreme obesity. Dr. Klein said that NAFLD should be considered a part of metabolic syndrome. As far as treatment goes for obesity, liposuction is not an effective way to treat fatty liver disease and insulin resistance. He found that weight loss by dieting resulted in a decreased size of fat cells a decreased amount of fat in the liver and muscles. Weight loss by liposuction, however, resulted in a de-crease in the number of fat cells but not a decrease in the size of the fat cells or a decrease in the amount of fat in the lever or skeletal muscle. The therapeutic effects of gastric bypass surgery with respect to fatty liver disease are controversial, according to Dr. Klein.
• Dr. Meng Tan said that pioglitazone (Actos) lowers triglyceride levels more effectively than rosiglitazone (Avandia).
• Microcvascular complications and resulting nephropathy are generally indicative of larger car-diovascular dysfunction. Highly vascularized kidney is the canary in the coal mine said George L. Bakris, MD Considerations in the Management of Hypertension in Patients with Diabe-tes.
• Impaired Glucose Tolerance can create dramatic effects in endovascular function (Richard Ne-sto, MD Managing the Metabolic Syndrome: The Evidence and the Options).
More soon – over and out …
Your ADA team: Kelly L. Close, Melissa P. Ford, Kaitlin L. Gamson, Clair A. Glogowsky, and Olayinka A. Olowoyeye
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